Jan 08 2013
Rituximab for Chronic Fatigue Syndrome: Jumping the Gun
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179 Responses to “Rituximab for Chronic Fatigue Syndrome: Jumping the Gun”
I read Kogelnik’s name once every while, but I don’t really know much about him – so I can’t asses him very well. And I don’t know enough (yet) about Fluge and Mella to say whether they and their research can be trusted. So I will refrain from commenting one way or the other about them.
(Unlike XMRV, with Mikovits, Lombardi and Ruscetti, who are as far as I know frauds.)
But when I read this, I had to say something.
“In my opinion, what he is doing is not based on acceptable evidence and is not ethical. He is indulging in irresponsible, uncontrolled experimentation.”
The sad fact is that not only will do doctors do experimentation when faced with an disease of unknown etiology, unknown pathology and unknown treatment options, but *people* with ME/CFS *will* try irresponsible and uncontrolled experiments themselves and seek any “help” they can get. From vitamins in high doses, to herbs that have unknown side effects and dangers, “detox”&”chelation” regimes that massively harm, to long term antibiotics that do harm as well.
(Not to mention “expert” clinics who will gladly take $$$ for a two day check-up, but leave patients empty handed – these people will after such an experience gladly go to quacks who offer anything that looks like a solution.)
And while I agree that Rituximab might be problematic (for the reasons you stated), I think it is more responsible to give desperate patients access to this drug now, instead of accepting that they will experiment with worse things – and that, they will.
And if your aim is to reach (and warn) patients who would consider going to Rituximab: I think you will fail.
The question that needs to be asked: Does Kogelnik work with specialists who have knowledge and experience with the drug? If no, this is a major red flag and something that can be communicated to people with ME/CFS. If he does, I don’t think you have a case.
And just to clarify: with “expert” clinics I mean the big names, not some “Open Medicine Institute”.
Mrs Hall, I am the blogger and RN you are mentioning on this blog opinion.
With all due respect, i don’t think that you understand anything, nor that you ever met a patient with ME. I invite you to live in our shoes for a while and see for yourself.
Rituximab by itself is very safe, not only it is used for cancer, it is also used for other rheumatologic applications, like lupus and RA. Then the questions comes to, why me, a patient who got sick with EBV, never recovered, barely able to walk 50 meters and do my groceries, would be left behind and does not deserve a trial of Rituxan, considering they would give it to patient with joint destructions?
It always revolves around the fact that patient swith ME are never worthy of research. Govern,ents don’t think we are worthy of research and clinical trial grants, and researchers do not want to get in the field of ME, staying inthe safe areas of HIV and Cancercwhere they are sure to secure grants.
Patients have been neglected for over a quarter century. i know somewho got ill intheir teens, are now in theor thirties and are too sick to live ontheir own, and have never finished their schooling, held a job or marry and have children.
I am very very comfortable with Rituxan flowing in my veins, because it gives me hope. I have been monitored properly and furthermore, despite all of my B-cells gone, my CBC cannot be more normal, which means my body can handle at least some infections, but I am also watching for the possibility of infection becauseof my getting rid of the B-ells.
If it was to be done all over again, I would take that chance, because there are no other options that are acceptable at the moment for me, and I know other patients would do it too if given a chance, because the life we are living is a living death.
Patients face the stigma of this dam disease dayin and day out and we all want out of this nightmare. i applaud the work of Dr Kogelnik for organizing a stateofthe art biobank/research and hopefully official clinicaltrial when fundingcomes, and yes us patients will have to fund that too.
So please, don’t bash my blog, and don’t bash the work of Dr Kogelnik, and perhaps spend time in our shoes, or lend a hand through research and collaborativework.
KatiRituximabtourist.
Just one more thing: I took a look at the Open Medicine Institute and the “OMI-MERIT Initiative Signators”. While some names are not or not well known to me, the names I know are manly solid researchers: Especially Lucinda Bateman, Nancy Klimas, Kathleen and Alan Light, Chris Snell and Staci Stevens know what they are doing. Well, Ila Singh and Jose Montoya might be overselling their research, but none of them is a quack, and none is a fraud AFAIK. And none of the household quacks and idiots of ME/CFS research (that I know of, at least) are included in the list.
So take that for what its worth, but I think the Open Medicine Institute is most definitely *not* a “den of quacks”. (Kogelnik and some of the other OMI-MERIT names may or may not be sub-par, however.)
“Rituximab by itself is very safe,”
wrong: http://www.drugs.com/sfx/rituximab-side-effects.html
“It always revolves around the fact that patient swith ME are never worthy of research. Govern,ents don’t think we are worthy of research and clinical trial grants, and researchers do not want to get in the field of ME, staying inthe safe areas of HIV and Cancercwhere they are sure to secure grants.”
wrong:
Open trials for key word “Chronic Fatigue”: http://clinicaltrials.gov/ct2/results?term=chronic+fatigue&recr=Open
Open trials for keyword “Myalgic Encephalitis”: http://clinicaltrials.gov/ct2/results?term=myalgic+encephalitis&recr=Open
And that’s filtering out the trials that have been completed or being run and no longer recruiting
“Patients face the stigma of this dam disease dayin and day out and we all want out of this nightmare. i applaud the work of Dr Kogelnik for organizing a stateofthe art biobank/research and hopefully official clinicaltrial when fundingcomes, and yes us patients will have to fund that too.”
If his research is so state-of-the-art, why can’t he register a clinical trial like all the others? Also, (Forgive my naivete, I don’t have first hand knowledge of research/clinical trial funding, etc) is it normal for the cohort of a clinical trial to provide the funding for that trial? That doesn’t seem right. Shouldn’t the cohort be compensated BY the trial for their participation?
I don’t remember other posts on SBM focusing quite so much and so critically on one patient.
At this point, I do not think that it would be appropriate for anyone to be making money out of treatments for CFS outside of registered trials with genuinely informed consent, but it does seem that there is little funding for research and a lot of patients desperate to try something which will allow them to regain their health.
I think that this lack of funding is behind ‘what they were thinking’ with Mella and Fluge’s uncontrolled study. From what I understand, they are working to get funding for a blinded multi-centre RCT, but the cost of doing this research properly is very high.
May I suggest a different explanation. CFS is a diagnosis of exclusion, only when a doctor has ruled out all determinable causes of fatigue they can think of is a patient given the diagnosis. In some cases the doctor has doubtless missed some subtle or difficult to determine cause. The result is that the pool of CFS patients is very heterogeneous, which makes it hard to conduct any research. I am sure years from now, they will find out that some subsets of CFS patients actually had a previously diagnosed physiological condition, and henceforth they will be removed from the pool. I am also sure that in some patients, the fatigue is purely psychogenic. Determining which is which is extremely difficult. In the mean time, like the XMRV fiasco, doctors, researchers and desperate patients are jumping the gun and jumping to conclusions regarding etiology and treatments. The unfortunate fact is, there are simply no good, evidence-based treatments that are effective for all CFS patients, and the graded exercise therapy and cognitive behavioural therapy options currently offered are objectionable to many patients, I’m sure with good reason.
Do not mistake “we do not have an explanation or a cure” for “we don’t care” or (in this case) “let me take your money”. You are receiving and paying for this treatment on the basis of hope. While this is understandable, because doubtless you are desperate, it is not the same thing as proof. Pointing out the flaws in Kogelnik’s “research” and treatment is necessary to determine whether it holds genuine potential as a treatment, or is merely an expensive way to benefit from the placebo effect.
@TheDave:
No. That is not normal and at best highly dubiously ethical and almost always unethical. At its most simplistic, a clinical trial must try and prove that the potential benefit to the individual will outweigh the potential risks to get IRB approval. There are numerous variations and provisos for allowing research in cases where this cannot be met but there are reasonable expectations that the generalizable knowledge will be of great use to future patients. Since this latter criteria is harder to meet it requires more scrutiny. But in any event, there is always the assumption of harm with the knowledge that it may be greater than feasibly anticipated a priori. As such, the added burden of cost to the participant would be very easily considered to tip the balance of harm in the wrong direction and is easy pickin’s for an IRB to say no.
That said, mitigating factors such as limited funding can be use to justify small burdens of expense and time (like not reimbursing for transportation costs to trial sites) but this must be a carefully explicit part of the patient consent. In an ideal world, any and all costs possibly associated with a trial would be covered by the trial itself. This is a small part of why Burzynski is so incredibly unethical.
@Nybgrus: “That said, mitigating factors such as limited funding can be use to justify small burdens of expense and time (like not reimbursing for transportation costs to trial sites) but this must be a carefully explicit part of the patient consent.”
Kati, after a lot of trouble, got refund for the medicine from The Genentech Foundation, but the Norwegian patients (and, I suppose, the other overseas patients) are paying 8000$ per treatment, plus travel expenses. And travelling from Norway to US isn’t exactly cheap. Several of these poor souls have taken up private loans to finance this. One of them has spent something like 45,000$ till now, and is no better. She’s just even more exhausted after four trips to US. I don’t think this is ok.
Kogelnik is absolutely no Burzynski, but I can’t understand how he can stomach running a “study” that costs the patients half a fortune. And I can absolutely not understand why he doesn’t register his research. For one thing, he’ll have trouble getting his research published when he hasn’t got approval from the ethical board. Ethical rules aren’t just red tape, they are there to protect patients. If he’s a serious scientist, he should know, and he shouldn’t neglect them.
@Kati, Rituximab is not “very safe”. It can have very serious side effects, especially long term, and nobody knows the long term side effects (after years, that is). And you don’t give it to just anyone with rheumatological conditions. And when you do, you follow them very closely and monitor their immune function.
RA and lupus are very serious diseases, lupus can even be lethal, so there’s sometimes good reason to give immunosuppressive drugs. But Rituximab isn’t the first choice, even though it’s well documented for some rheumatological diseases. You first try other drugs that aren’t that risky and have been on the market longer.
If Rituximab turns out to really work for certain groups of ME/CFS patients, they will naturally “deserve” them. But it’s still early days, we simply don’t know enough yet, though the Norwegian results are promising.
What these patients really deserve is that all research, and treatment they are offered, is scientifically and ethically sound, and that noone, whether doctor or quack, experiments with them.
Excuse my sometimes clumsy English,
Pernille Nylehn
Norway
I suppose I’m one of those “poor souls” except I live in San Francisco. Open Medicine charges me less than $300 per infusion. The real money goes for the rituximab itself, which is a separate expense. No one is getting rich here, except Evil Big Pharma.
And yes, I *do* deserve scientifically and ethically sound treatment, thank you very much. Got some? Think I should refuse the only option around–oh, I forgot about the fermented antler velvet, the Venezuelan equine encephalitis vaccine, and the placental extract referred to in the clinical trials–because it’s not on the strait and narrow path of EBM? (BTW, the Norwegian trials did not get funded.)
There are some people here riding *very* high horses. Presumably through the halls of academe, and nowhere near me.
Yours in pathos, ignorance, and victimization,
Irene Fuerst
Pernille has it pretty much spot on.
Slow/minimal research is annoying, upsetting and frustrating. However, jumping at any hint of a possible treatment is a waste of time and money. Pouring money into DMARDs, ARVs, chemotherapeutic agents etc. is dangerous and counterproductive.
Science takes time. I understand the frustration and pain, but spending money I don’t have on “treatments” that aren’t, isn’t an option.
My two main diagnoses are massively neglected. Both are potentially fatal (one is always fatal without treatment) , both have caused me permanent disability (spinal cord damage, blindness, hearing impairment, constant pain, etc), and neither are researched anywhere near the level that CFS/ME is.
With the first disease, it’s too rare to attract any attention. There’s only one foundation studying it (US-based), and doctors are largely ignorant of the disease and how to manage it (One drug is available. If that doesn’t work neurosurgery is needed)
The second disease is pretty common, but only in the elderly. Anyone else who develops it is usually left to get horribly ill before receiving a diagnosis. Ironically they’re often diagnosed with CFS or fibromyalgia when doctors neglect to perform the single simple diagnostic text.
Treatment is simple, but the favoured regimen was designed for pensioners, in a “one size fits all” fashion. Sadly, it hasn’t really been revised in the decades since its inception, and. rarely works sufficiently in anyone under sixty. Those who can pay for private treatment, or import the treatment and self-treat, can live relatively normal lives.
Again, in the UK, there is one advocacy group trying to change how the condition is treated. They’ve had to raise money to pay for research into treatment and management.
Neither disease is “sexy” or controversial enough to warrant media interest, scientific and research interest, or public interest. Mentioning either gets blank stares, or shrugs. So I understand the feelings of total powerlessness and desperation. However, attacking researchers who are trying to shed light on either issue is not an option, even if the hypothesis is unpalatable. A study investigating a very contentious, upsetting theory in one of my conditions ended up disproving a “fact” of what triggered the onset of symptoms. It changed the course of research and patient management after decades of set practice.
Ultimately, all research is good research if it contributes to the knowledge base about a given condition. The damage is already done in my case, but I know future patients won’t have to suffer in the same way. I’ll happily engage in anything I’m able to, although now I’m limited to surveys only until I can leave the house. I’ll do that to help future ‘Mes’, so that they can stay productive and remain symptom-free.
However, charging patients thousands to take dangerous treatments, with the added “bonus” of costly and exhausting international travel, with the endpoint being neutral or even harmful, is not research. It’s unethical, Burzynski-lite experimentation. Where’s the documentation? The accountability? What if someone dies or is maimed, who picks up the tab?
This isn’t the way to go about things. All it does is empower the quacks and charlatans
Lessons need to be learned from the disgraceful XMRV debacle..
[...] Rituximab for Chronic Fatigue Syndrome: Jumping the Gun !! [...]
Indeed. He won’t be able to publish in a reputable journal if he doesn’t register his trial with ClinicalTrials.gov and if it doesn’t have ethical approval from an accepted IRB. I’m not aware of any reputable peer-reviewed journals that don’t require these two things before it will publish clinical trials. Again, it’s to protect patients by making it harder for investigators to disseminate their results if they’re not funded by the federal government or working for an academic university that receives federal funding and can thus get around the Common Rule. So, even if he were doing research worth publishing, the best he could do would be to self-publish the way quacks do or to publish in a bottom-feeding journal that doesn’t subscribe to standards that reputable biomedical journals subscribe to.
My conclusion? Kogelnik is a “brave maverick doctor” who has so deluded himself into thinking that he’s doing so much good, that he’s discovered something so astoundingly awesome, that it leads him to believe that the regular rules don’t apply to him and that he can prove he’s right without going through normal clinical trial channels.
This fits in with the Open Medicine Institute’s overall vibe, if you will. OMI is flush with venture capitalist cash, incorporated as a public benefits corporation, and does not need the money of any one patient.
A read through their website notes that it is chock-full-o’ catch phrases of the 21st century digital marketing kind, but basically it’s the same 19th century and onward venture capitalist scheme: toss a lot of money at obscure problems, expect novel solutions (that are patentable) and sit back for that 50x return which should occur in a year or so.
Dor Kogelnik is probably very enthusiastic about whatever it is he has found and is likely being encouraged in his “maverick” thinking by the board, advisors and management of OMI. It would be better for the public at large if less lucrative for OMI if the good doctor sat back and played by the rules that will make his discoveries applicable to the world.
^(Excuse my not policing the blasted auto-correct: that should be Dr. Kogelnik, not “dor.”)
I once admired the skeptical community, being something of a science junkie. But you are losing me by equating my doctor to that mephitic scoundrel Burzynski. I thought y’all were above ad hominem attacks and so on. Sorry, Gorski, I used to think you were my kind of guy.
No one is being lured by expensive false promises. AFAIK Open Medicine is not trolling for patients. I realize that rituximab isn’t aspirin (although, come to think of it, aspirin has its dangers) and that I may not get any benefit. If I were in a clinical trial I might not get any benefit, either, and I don’t see how off-label use of a drug is denying other patients something. This is the kind of logic behind the Defense of Marriage Act: let’s stop people we don’t like from doing something we get to do.
To reiterate: I pay less than $300 per infusion to Open Medicine. The large amounts of cash being cited go directly into the money-grubbing pockets of Evil Big Pharma.
I’ve had five infusions so far. I can’t say I’m much better. I can’t say I’m much worse, either. I have no regrets.
I’m pretty much housebound, can’t do much, in constant pain, all that fun stuff. So what I supposed to do? Listen to my betters and suffer in compliant silence? What have you done for me lately?
@Quill:
I think OMI’s web site sucks, too, but no one asked my opinion. I know nothing about VC funding. Do tell. You seem to know something the rest of us don’t.
You are paying $300 for the privilege of being involved in an scientifically useless clinical trial of one, for a treatment that has minimal prior probability, uncertain benefits and definite, recognized risks.
No, but the fact that there are few treatment options for CFS does not mean this option works. The fact that patients are undertaking uncontrolled, scientifically questionable, low-n trials presents several problems. First is the cost, money which could be better used in other ways (irrespective of if it’s an individual’s funds or government research dollars). Second is the way the trials will muddy the scientific process. Third is the way these uncontrolled observations and anecdotes will be circulated on the internet. Fourth is the hope it provides. While real hope is a good thing, false hope is not. If rituximab has no effect on CFS, individuals who undertake treatment and circulate their allegedly positive results on the internet are responsible for encouraging already vulnerable patients to experience more risks with placebo-only benefits.
GED and CBT have research support, but many patients find them objectionable because of the stigma and implications attached. This is a shame on many levels and for a variety of reasons.
It’s less that, than it is the consequences of your action. If rituximab is genuinely effective, your actions will almost certainly delay its acceptance. If rituximab is ineffective, your blog is encouraging desperate patients to undertake expensive and risky treatment. It is truly unfortunate that the etiology of CFS is not understood, even more unfortunate that the treatment options are less than ideal. That doesn’t mean rituximab is an effective treatment and it doesn’t mean these scientifically useless and expensive trials are risk-free or ethically unproblematic.
You appear to be misinterpreting valid scientific concerns over an extremely problematic treatment with condescension. Science attempts to arrive at correct solutions through rigorous criticism that divorces facts from emotions. It is unfortunate that CFS has no confirmed cause or easy treatment. It is unfortunate that CFS patients feel stigmatized. That doesn’t mean these criticisms are scientifically invalid, nor does it mean rituximab is effective.
I could do without the sarcastic martyrdom.
“you are losing me by equating my doctor to that mephitic scoundrel Burzynski.”
I can’t see where anyone has equated Kogelnik to Burzynski. I specifically said he is no Burzynski, and other commenters have echoed that.
Elburto did say “charging patients thousands to take dangerous treatments, with the added “bonus” of costly and exhausting international travel, with the endpoint being neutral or even harmful, is not research. It’s unethical, Burzynski-lite experimentation.”
That’s undeniably true. Kogelnik is doing some things that can be compared to some of the things Burzynski does, but that doesn’t “equate” him just as walking on two legs does not equate humans to chickens.
irenef remarked:
No special knowledge on my part.
http://en.wikipedia.org/wiki/Venture_capital
@WilliamLawrenceUtridge:
What blog? I don’t have a blog. I’m not encouraging anyone to do anything. Up until now only a few people have even known that I have received rituximab.
I was never under the impression I was in any kind of clinical trial. I am receiving an off-label treatment. My blood samples are being saved and I have given permission for them to be shared.
And I think my sarcasm pales in comparison to equating Drs. Kogelnik and Burzynski.
Assuming your doctor is honestly motivated by laudable concern for his patients and not the apparent profit motive imputed upon Burzynski, that does not discount the fact that he is conducting scientifically flawed trials that will not really help the CFS patient community. Perhaps you should talk to him about the importance of a proper clinical trial – if rituximab is genuinely effective, he is restricting its use to only those who can afford it, and a trip to his clinic. If it’s not, he’s exposing you and other patients to risks for no benefits.
Um…it kinda is. Perhaps not “false” promises, but certainly “unproven”.
Aspirin has recognized, proven benefits that are extremely well validated. The same can not be said for rituximab. If someone tried using aspirin to treat CFS, charging $600 per treatment for the privilege, you would see similar criticisms.
It denies the opportunity to test the hypothesis in a meaningful way, thus the ability to deliver the treatment to large numbers of patient if effective, or protect patients from unnecessary risks if not effective.
The Defense of Marriage Act is a social and political issue, where the scientific process has little involvement and the health consequences are tangential at best. Off-label use of rituximab is a medical and thus scientific issue. The logic is, providing people with false hope and exposing them to risks with no proven benefits, is inherently bad. A properly-controlled clinical trial would address this – risks are real but are offset by the ability to determine if there are benefits.
There is an opportunity cost for this use of money, editors and commentors here are indifferent to who gets the money, the objection is that resources are being used for benefits that may be illusory.
If you had been part of a clinical trial, you could have helped determine whether this is a viable treatment or not.
@Quill:
So Open Medicine is accused, on someone’s sayso, of bleeding patients’ wallets with false promises, but when I point out that I pay them what’s basically chump change, you claim they are flush with VC funds and don’t really need my money. So am I being used for some nefarious purpose? My cells are going to be patented, no doubt. What evidence do you have?
@irenef,
It’s reassuring to know you were not under the misapprehension that you were enrolled in a clinical trial, as blogger Kati apparently was.
Question: would you rather do what you have done or would you rather you had been given the option of enrolling in a randomized trial with a 50/50 chance that you would be assigned to a placebo control group but with the understanding that the knowledge gained would help determine once and for all if the drug was really effective?
irenef, you are combing, conflating and mixing up comments and including me in a group I am not a part of. I shouldn’t step in this, but:
“So Open Medicine is accused, on someone’s sayso, of bleeding patients’ wallets with false promises,…”
Hyperbole at best and I don’t see them accused of this on this blog.
“…but when I point out that I pay them what’s basically chump change…”
If three hundred dollars is “chump change” to you then bravo for your affluence.
“…you claim they are flush with VC funds and don’t really need my money…”
They do not. It is a matter of public record for OMI that they are quite well funded.
“…So am I being used for some nefarious purpose?…”
I have no idea but I suspect not, as do the medical commentators here. They are pointing out that your doctor is likely overly enthusiastic and isn’t following protocols in the field of medical research. He is passionate but unless he follows the rules he will not persuade.
“My cells are going to be patented, no doubt.”
Eh? I’ve no idea what you mean by that. Any patentable process or drug would be the goal of OMI, not attempting to patent a person’s individual cells, which as far as I know isn’t legal.
“…What evidence do you have?”
Evidence that you aren’t reading closely here and as stated in the start of this reply are confusing a lot of issues.
@WilliamLawrenceUtridge
I am not part of a trial. I have never told anyone I was part of a trial. No one told me I was going to be in a trial. I tried to get into one but didn’t meet the qualifications. Open Medicine has not claimed–to me, anyway–to be enrolling patients for a clinical trial.
My doctor is not conducting a clinical trial. He is offering an off-label treatment that presents risks to a seriously disabled group of patients.
There is no clinical trial.
@Quill:
Please point me to the public records that detail OMI’s funding. I would like that information..
And I do believe that human cell lines are patentable, just like rose bushes, and that this has gone to the supreme court. The human being involved does not need to be compensated. I do not have references offhand but I can get the details if it interests you.
@ Harriet Hall:
I’d go for the RCT. That’s a no-brainer.
Yes. That is the problem.
I suppose we’re all agreed, then: There is no clinical trial.
How dull the day has become. Someone, please, argue with me. This is the most fun I’ve had in months. Really.
@Quill:
Moore v. Regents of the University of California. Went before the California Supreme Court in 1990. From Wikipedia:
“Moore v. Regents of the University of California (51 Cal. 3d 120; 271 Cal. Rptr. 146; 793 P.2d 479) was a landmark Supreme Court of California decision filed on July 9, 1990 which dealt with the issue of property rights in one’s own body parts. John Moore underwent treatment for hairy cell leukemia at the UCLA Medical Center under the supervision of Dr. David W. Golde. Moore’s cancer was later developed into a cell line that was commercialized. The California Supreme Court ruled that Moore had no right to any share of the profits realized from the commercialization of anything developed from his discarded body parts.”
There’s more, of course. Quite controversial.
How about “No”?
I’m a woman with a wife. That does not endanger lives, waste time, give anyone false hope, mislead people, or cost
anyone money.
However, being denied the right to wed causes serious harm to same-sex couples. The US considerably privileges heterosexual couples WRT property ownership, healthcare, hospital visitation, having/adopting/fostering children, financial matters, and so on.
By all means, throw your money away on a non-treatment that’s potentially dangerous and apparently not helping you, go for it! I only wish I could come by that amount of money and then part with it so easily as mere “chump change”
But don’t compare legitimate scientific criticism of research-that-isn’t with the systematic abuse and denial of basic human rights of an entire class of people, because it doesn’t help your case.
Oh, and the whole “Evil Big Pharma” thing? Sort of disproves your whole “I was a super skeptic till you said mean things about CFSers using rituximab” schtick.
No doubt this topic will end up at 150+ comments of word salad and conspiracy theories, as CFS articles are prone to do.
Ah well, it’s a vibrant start to the SBM New Year, if nothing else. I can use my pharma-shill minion money (Draconi$ LizarDollar$) to spring for some popcorn.
“But don’t compare legitimate scientific criticism of research-that-isn’t with the systematic abuse and denial of basic human rights of an entire class of people, because it doesn’t help your case.”
elburto, I was getting ’round to mentioning that, so thank you kindly for beating me to it.
“No doubt this topic will end up at 150+ comments of word salad and conspiracy theories, as CFS articles are prone to do.”
One can hope.
But seriously, you get enough pharma-shill money for popcorn? I’m impressed! I only got enough for a postage stamp.
And irenef, since you’ve just demonstrated you can do online research, kindly go to it for the answers to the questions asked to me unless you want me to send you my rate sheet for such work. ($300 ain’t “chump change” for me although I’ll be the first to admit to being a chump.)
I don’t want to tire you out.
This kind of holier than tho, you’re not living up to medical gold standards so stop what you’re doing approach is common and is incredibly naive. We met up with the same attitude at the FDA hearing for Ampligen when the some members of the panel blithely said well, Hemispherx just do another trial, ignoring that there is no money to do a big trial.
The blogger simply wants evidence that B-cells issues contribute to ME/CFS. Is the blogger aware that the NOrwegian research council recently turned down funding for another Rituximab trial? Or that the NIH currently provides all of $6 million dollars a year for CFS funding. Where does the blogger expect the evidence to come from. Would the blogger suggest that sick patients simply wait another 10 years or so in the off chance that funding will improve? (Its gone down substantially in the last 10 years)
Dr. Kogelnik and other doctors are doing what they can for very sick patients who don’t have recourse to clinical trials for drugs for chronic fatigue syndrome because, for the most part, there aren’t any…because there isn’t interest and there certainly isn’t any money. They are doing the best they can with what they haveand people with ME/CFS are lucky they are around.
I find this statement incredibly ironic “he is missing out on the real race to understand and treat patients diagnosed with CFS/ME/CFIDS.” Please tell me where the real race is because when I look through the research and the funding…I don’t really see much a race going on.
Thank you Dr. Hall, for bringing this questionabletreatment to our attention. My 23 yr old granddaughter has recently been diagnosed with RA (and has psoriasis since aged 9) and my 38 yr old son also has RA. They are both just beginning treatment and understand that not everything works for all patients. Should they have difficulty and this stuff comes to the attention of any of us, I am glad I’ll be ready to sort things out–being the family matriarch (or busybody–depends on who you ask). At least this problem came from the other side of the family–there’s enough on my side already.
@Irene
I think the people here all mean well when they reply to you, and I think they are factually correct. Having said that, I don’t think being correct is enough and that they are not responding with enough compassion to your condition or point-of-view. You seem basically well-informed, so I hope you will look through what can seem insensitive from some commenters and make good (rational) decisions going forward.
@elburto:
My logic: As my choice of medical treatment doesn’t affect anyone else, a gay couple’s marriage does not affect anyone else. I was/patients like me were being criticized for a rather personal choice that was interpreted as being bad for other patients, as gay marriage is asserted to be a threat to society/Western Civilization/whatever.
“Chump change” with respect to what 1) quacks like Burzynski charge, 2) what most medical procedures lasting several hours cost, and 3) the amounts being bandied about by people who didn’t know what they were talking about, who assumed that because the treatment is expensive Open Medicine was pocketing unconscionable profits.
Evil Big Pharma=sarcasm. That’s why I used the caps. My husband has pharma clients. I don’t especially like them, but are putting a bit of food on the table.
I don’t think I’ve supplied any word salad, conspiracy theories, or death threats. I could tell the boyos to come on over–I know the rocks they live under–but I’d prefer to keep things entre nous.
@Quill:
So you make an assertion about Open Medicine’s funding but then refuse to document it, because I called $258 chump change and know something about intellectual property rights?
Touchy, aren’t we.
Then your logic is flawed as neither statement is true. Your choices do affect others, and such choices can be measured. For instance, how much of other people’s time (here and elsewhere) was taken up with your decision to go for such treatment? What else would you have spent that reoccurring $300 on? How many others know of what you do and have decisions altered or influenced by it? And gay marriage does affect many people, from changing public discourse to time and effort spent in legislatures, litigation, and lives able to be bound in legal union. It even affect heterosexual marriages in many ways, such as when such couples start to think about what makes a marriage especially in terms of commitment.*
We are all interconnected on this little rock in space and much more alike than different.
The thing here is that these choices can and should be made with the best available evidence, conscientiously and hopefully with an eye to benefitting other people. In the first case, by choosing to take part in what is apparently an unethical practice, you may be influencing others to do the same. That being said, I can’t fault you and only wish you the very best, mindful of what Janet has posted, and knowing I would be sorely tempted to do the same thing. I sincerely hope you not only get relief from your suffering but also complete remission. I just hope you do it in a way that won’t lead you or others to false hopes based on questionable practices.
*(Just in case my words seem too salad, I view gay marriage as an overwhelmingly positive thing and a basic human right.)
@irenef: you assumptions about that which you know not are not very precious.
WLU, would you please explain to me how this would be the case? How would the actions of one physician doing their own in-house trials delay the acceptance or proper testing and trials of that drug by others elsewhere?
@WLU, in any case, I have to say you seem to have the risks associated with this whole patient/doctor test-this, try-that thing down cold. I’m rather impressed.
I spent about an hour yesterday begging my doctor to just try something for some pain relief. I can’t tolerate most medications and have already tried the usuals. This article couldn’t have been more timely since we were discussing DMARDS. I’ll hold off without anything for a while longer, and so I walked away without a prescription. It’s rough not having any effective treatment, especially for disabling symptoms. I completely understand where irenef and Kati are coming from, but I hope they set a cut-off point, otherwise it’s too easy to be misled into trying one unproven treatment after another, chasing rainbows, expensive ones at that.
@Janet, I’m of the impression that Dr. Hall meant this treatment as being questionable for use with CFS patients. It is accepted treatment for those with RA.
@Janet and Sialis,
Yes, as I mentioned, Rituximab is an FDA approved treatment for RA and several other conditions. Nothing I wrote can be construed as a reason to be suspicious of its use for RA.
I have no problem whatsoever with patients trying experimental treatments when they are out of other options and are informed of the risks. I fully empathize with patients who are desperate for relief.
It may seem cruel to ask for controlled studies before treatment, but it is kindest in the long run. When multiple anecdotes of improvement circulate, it becomes just that much harder to accept later results of well-controlled trials. Stories trump science in our psychology. Jumping the gun muddies the waters. If patients had no access to these treatments outside of clinical trials, the pressure of public opinion might lead to funding.
@William Lawrence Utridge:
Quitter…watch Monty Python much?
Except for a nasty headache and an unpleasant jetlagged/wired/underslept feeling with a touch of tremulous hypoglycemia–possibly because I forgot last night’s meds–I am doing okay today.
@Janet:
Thanks for your kind words. I hope the kids do okay.
The only reason I’m here is that I think the regular posters are essentially honest if perhaps overconfident, but not really nasty. The big danger in skepticism is being overly skeptical–thinking you know more than you really do. I would hesitate before making the kinds of assumptions some of these people make.
@Quill:
Re: people’s time. I don’t know. I discussed the decision with my husband. He bills very high, but for me … special. I have paid Open Medicine for their time. The commenters here? I don’t know. I don’t think they are looking for compensation. I’m a slow writer. I can’t extrapolate very well from me to them.
The recurring $300–let’s call it $1500 for the sake of argument. It would have gone to paying off bills.
Very few people know me or know of my treatment. I am not a blogger, I don’t get too involved with online forums.
I’m not going to get into gay marriage anymore. I used it metaphorically and you are choosing to use it literally.
You say you would be tempted to do the same? I think many people would. You can’t be risk averse and do this. Or, to put it another way, life has to really suck.
Confession: I have been feeling better, off and on, since I had my last infusion a month ago. I just am not comfortable making any kind of statement to the world at large, because I am not sure it it will last. And the improvement is modest right now. Really, laughably modest.
I had no intention of jumping into this fray but I feel I must.
Forgive me if I make some mistakes due to lack of information. I did re-read Dr. Hall’s post just to make sure I got the point of what she was trying to say.
Firstly, in the case of Irenef, I tend to agree with her. She is absolutely within her rights to seek any treatment she wishes for any condition, and Dr. Kogelnik is perfectly within his rights to prescribe and provide her any treatment so long as it is under fully informed consent. From what Irenef is saying, she seems to be clear that this is a purely off-label and experimental use of a drug not at all in conjunction with any clinical trial. At base, neither party seems to be violating any rules, laws, or ethical standards.
I do not think the same can be said about Kati. Regardless of Dr. Kogelnik’s intent, it at least seems as if she is under the impression that this is some sort of study. The understanding of the treatment is fundamentally different between the two persons. Since it is the physician’s onus to ensure the patient has proper understanding in order to fulfill the requirements of informed consent, it is his responsibility to rectify this misunderstanding. Whether this is an actionable level of misinformation is not something I can determine.
All that said, it seems as if Dr. Kogelnik is potentially misleading Kati at least, if not Irenef. Part of this could be the very fact that Open Medicine is stated as being a research consortium of sorts and this could lend the false impression or it could be an intentional impression for false means. Regardless, is the the onus of Dr. Kogelnik to ensure that the research mission of OM is not misconstrued in his off label treatments of patients. If he is running a non-registered and not fully informed clinical trial of any kind, this is a serious violation, even if he has no intention of publishing his findings. And it seems, from what Dr. Hall has presented, that some degree of this appears to be the case. This may not apply at all to Irenef, but as long as it applies to at least one person it is of serious concern.
As for why doing such “research” would likely delay the acceptance of ritux for CFS if it were a legit treatment – it is simple: it would become a black sheep and much harder to study by legitimate groups because of perceptions of guilt by association. It wouldn’t necessarily be fair but it would reflect reality. The lone maverick doc thing just doesn’t help in the long run.
In the case of Irenef, I can see no such rationale. And this is coming from a “staunch card carrying skeptic firmly against CAM.” In the case of fully informed consent Irenef has every right to utilize her resources – regardless of who thinks they may or may not be “chump change” – for whatever means she wishes. Such is a free society. Sure, we could argue that resources are much better spent elsewhere and I think we would be scientifically correct. But unlike some commenters here think of me, I am not in the game of forcing everyone to my standard of scientific evaluation. If she wanted to try fermented antler velvet also her choice. Both avenues would be a waste of resources, but they are hers to waste.
Now from the scientific standpoint there is no rationale for administering ritux for CFS. There can’t be since we don’t have good clinical data to support it and we (obviously) don’t know the pathophysiology of CFS in order to employ Bradfrod-Hill criteria for scientific plausibility. So on this level I would simply advise Irenef that if she wouldn’t be willing to waste her money and time on fermented antler velvet she shouldn’t be willing to waste it on ritux treatments. If she understands this but still wants to anyways, I would implore her to be vigilant of her progress and set an a priori cut off point where she is comfortable saying it doesn’t work for her.
From a medical ethics standpoint however, I don’t think Dr. Kogelnik has a leg to stand on. Off-label use doesn’t mean “make up whatever you want.” There should be scientific rationale for the off-label use and the amount of evidence available simply cannot meet muster for that. If it did, the standard would be so low as to be meaningless. But that is an issue to take up with his employer (if any) and the state medical board.
On the allegations of pseudo-trial running, that is a much larger issue and should be the focus of this discussion – not bashing Irenef for making an informed decision that we disagree with. Regardless of whether we are right about our scientific opinion on the matter. I didn’t want to enter the discussion because I don’t have the time, energy, or desire to do the legwork on taking a serious stance as to whether Dr. Hall’s allegations regarding the pseudo-trial running are accurate. I also trust her integrity and ability and believe that if she thinks this is the case, she has good reason to. But I am not about to jump in and add my own voice without having done my own work on it.
But when I see the commenters here bashing someone who is clearly rational and informed, albeit making a decidedly poor decision from a scientific standpoint, it saddens me a bit and I felt the need to speak up. You guys aren’t clinicians so I suppose it isn’t fair for me to hold you up to the same standard, but at least a standard of decency should apply. Of course, it is a free.. um.. internet… so you may of course do as you please. But I believe it is counterproductive.
I’ll close by saying to Irenef – despite the unnecessary bashing, they are right in principle at least. There really is no scientific rationale to justify taking the ritux for your condition. I also absolutely believe your condition is real, but that we simply do not know the etiology of it. There are distinct dangers with taking ritux (and aspirin too – I wouldn’t recommend taking that either). And there is also the danger of confirmation bias if your condition improves – we simply would have no idea what caused the improvement. I absolutely appreciate your consternation and the debilitation your condition causes. I would simply implore you to save your money, resources, and energy since in cases where we genuinely don’t know – like this one – all the evidence shows us doing nothing is usually better than doing something. If you still wish to pursue the treatment knowing full well the complete lack of scientific rationale for it, so be it. I would merely ask that you be kind enough not to make it a point to tout the ritux as a cure for CFS if your condition improves because nobody could possibly know that to be the case.
@Quill:
“you assumptions about that which you know not are not very precious.”
Sorry? I don’t get that.
Seems Dr. Hall and I posted at the same time.
I agree with her concerns about anecdote – if a number of these off label trials lead to a few people having improvements and attributing it (rightly or wrongly, we simply cannot know) to the ritux, then a legitimate trial showing no effect would be much harder to convince people with. Hence my beseech at the end of my post.
That said, Dr. Kogelnik should be held accountable by his peers for what I can only see as irrational and irresponsible off-label use, regardless of the level of informed consent of his patients.
@nybgrus
Here, here. Thank you.
The rituximab treatment was based on serendipitous results from Norway. I think Dr. Hall mentioned that.
There is a rationale for the treatment having to do with dysfunctional signaling between natural killer and B cells. I don’t think it’s necessary to go into it now, but let’s just say there’s more to it than the healing qualities of fermented antler velvet.
I have several years of frozen blood samples sitting in a university lab, so if I do improve there’s at least the potential for someone to see what they can find in before and after samples.
I have no intention of touting ritux as a cure. I am no kind of evangelist.
A responsible journalist–I know I’m not talking to a newsroom, but there are points of comparison, as this is a public forum that wishes to assume a mantle of scientific impartiality–would never publish accusations of irresponsible behavior without contacting the person or corporate entity being accused. No one here has bothered to do this, which brings into question the impartiality of at least the practitioners of science-based medicine and dilutes any claims to authoritative knowledge.
@irenef:
The serendipitous results are not sufficient scientific rationale.
I do not know enough about dysfunctional signaling between NK and B cells, especially in the context of CFS to comment, though to my knowledge such a pathophysiological link has not been documented.
As far as I know, while the rationale for ritux is undoubtedly more than that of fermented antler velvet, it is still not enough to warrant its use and for all practical and clinical applications the two can be considered equivalent. For research purposes, that is a different story.
You seem educated enough on the topic and if you have sources I would be interested to read them (regard the NK/B cell/CFS interaction). If anyone else does I welcome that as well.
The years of frozen blood samples could prove to be a useful hypothesis generator in the future. Hopefully that pans out.
As I said, I have not reviewed the primary source data of Dr. Hall to further expound on it myself, but I trust her integrity enough to say that she is likely correct in her assertions of research impropriety and that she hedged her discussion of the matter adequately. For the purpose of calling to light potential research ethics violations and cautioning that the use of ritux for CFS is entirely premature and off-label use is unfounded, I do believe she has enough data to say that. If the veracity of her data is in question that is another story entirely, though as I said I certainly trust her ability and integrity on the matter. I am also absolutely certain that if more information comes to light that explains the data differently she would be the first the admit so and retract her comments. But as it stands, it seems research ethics violations may well be in play and regardless, ritux for CFS as off-label use is scientifically unfounded (with the unlikely exception of strong prior probability based on references I don’t know to exist on the pathophysiology of CFS).
@nybgrus:
Right now I’m not healthy enough to leave the house. The only resource I have is PubMed, so all I could provide would be what’s there. I’m not really sure I’m up to a literature search, either, so I’m not willing to make a commitment to that. I also don’t know how up to date their indexing is.
I also don’t know why I, as a patient, should be expected to know the pathophysiology of my diagnosis.
No one here knows much about the pathophysiology of CFS. Even coming from a self-confessed position of ignorance you still feel qualified to criticize someone else’s therapeutic choices.
I am willing to play the role of guinea pig and have told my doctors as much.
If y’all wanted to help instead of kibbitz, you’d write a grant proposal, get funded, and do some actual work. It’s actually an interesting disorder. An unequivocal, practical diagnostic test would be a good start.
@nybgrus:
Look at what Nancy Klimas has done.
Here’s a start:
Brain Behav Immun. 2010 Oct;24(7):1209-17. doi: 10.1016/j.bbi.2010.04.012. Epub 2010 May 4.
A formal analysis of cytokine networks in chronic fatigue syndrome.
Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA.
Irene – Where did nybgrus imply that you should know?
Nybgrus – nobody was “bashing Irene”
Dr Hall had written about some seriously shady “research”, and that was being discussed. Then, straight out of the gate, Irene posts:
Nobody said she (whoever she is) or anyone else didn’t deserve treatment.
Huh? Until that point people had been discussing the doctor who was apparently misleading patients. Nobody said “People with CFS are pathetic ignorant victims”
That initial comment is followed by more concern over this “pilot study” and the necessity of registering trials.
Irene comes back with allegations of ad hom attacks against her doctor, criticism of Dr Gorski, and comparing Dr Hall’s criticism of Kogelnik to laws denying gay couples of their human rights. Signed off with more passive-aggressiveness;
It’s like she’s either picking out keywords and commenting on them, regardless of their context, or having a conversation that we can only see one side of. Who said that CFS patients should be denied treatment, should never complain, that they were inferior?
Back to Irene – like I said, I understand your frustration, but research takes time. Some people will never live to see a miracle cure for their illness. However, railing at any skepticism or criticism is counterproductive.
I mean, after the car-crash that was XMRV (which is still being touted as gospel truth by some) are you surprised that people are urging caution?
Anger and frustration are natural. I’ve spent almost an exact year in this bed. I was moved off it once to facilitate a mattress flip. I stayed in my sling the entire time, then was lowered back down. I’ve seen nobody but my wife, my doctor and my district nurse team in that year.
I’ve been too ill to attend hospital appointments, I’ve had to miss funerals (including a parent), my best friend’s wedding, new babies, birthdays, Christmas, etc. Add the unrelenting pain that gave morphine such a huge kick up the ar$e that I might as well have been taking Skittles, and it’s been a hell of a year.
One year in exactly the same spot, without leaving the room. I’ve got frustration, confusion, disappointment, and every other negative emotion, in spades. Like I said earlier, my two main disabling health problems have no exciting new research, no studies.
Condition #1 is officially a rare disease, with only one US foundation dedicated to research.
Condition #2 has only one advocacy group in the UK that cannot convince the establishment that one size does not fit all patients. They are entirely member (ie. patient) funded. A recent EU-wide symposium revealed that woo and sCAM are trying to gain ground, and causing demonstrable harm to condition #2 patients.
So I’m alarmed, and concerned that nobody will ever gain ground in furthering knowledge of these problems, as they’re not ‘sexy’ or exciting enough to matter to researchers, let alone gather funding.
However, jumping on board such dangerous “treatments” as MMS, or wasting time and money on nonsense such as homeopathy, acupuncture, Rife etc. is just pointless. That’s especially true given that the time and money could be spent productively on assisting those who are trying to set up case studies of varying treatment regimens.
So my choices are nonexistent. But I’m hopeful that things will improve in the future for others, that genetic research could yield a cure, that. transplants might work, that using stem cells may be an option. That the mechanism behind #1 is found, studied, and reversed.
Until then, I just have to bide my time, and that doesn’t involve having a google alert for #1 or #2, or shouting down criticism or scrutiny, or spending my online time on the solitary websites for #1 and #2, reinforcing my negativity, and jumping at shadows of false hope.
I’d quickly lose the last traces of my sanity if I lived like that, as I’ve seen in others. I’m also not going to demand that commenters on SBM either propose their own hypotheses and compete for grants, or shut up altogether. I thought you Americans loved your free speech?
I have to take every day as it comes. I have to be grateful that I have a bed to lie in, and a wife to love and care for me, and a smartphone. There are too many 35 year olds who simply aren’t that lucky. That’s why I get annoyed at people who profit from misery, and exploit the vulnerable and desperate, because life’s bad enough as it is, without deliberate harm being added to bad luck.
@irenef:
I apologize if you perceived my writing as an expectation that you should know the pathophys of your condition. Based on your specific comment about NK/B cell interaction it sounded like you did not that you should. I was merely asking that if you did, could you share some references you had handy. I do not expect you to do a lit review.
My contention is that it is not just those here who don’t know about the pathophys of CFS… nobody does. It was a topic we discussed in medical school and that was the extent of the discussion – that it is a diagnosis of exclusion.
Therefore, the statement of ignorance justifies my stance that there cannot be rationale for off-label use of a drug. Without a decent amount of clinical data or at least an understanding of the actual pathophys of the disease, how can one make a rational decision about therapy?
In other words, it is not my ignorance making claims, I am claiming the ignorance of medical science. If there is evidence to the contrary I am quite open to it.
The last bit is also unfair. We each have our lives, jobs, studies, and expertises. I do sepsis and comparative effectiveness research – I can’t just suddenly change gears and do CFS research. But what I can do is comment on the scientific aspects of treatments of diseases and caution people against using treatments with no way to know the likelihood of success. History has shown us that in cases where we don’t have an understanding of something, doing anything is usually worse than doing nothing. That is all I am advocating. I can fully understand the frustration and desire to do something. As such I cannot fault you or anyone else for doing that something, regardless of whether I think it is scientifically justified or not. But what I can do is state the case of science, so that others who may – upon further information – change their thoughts on pursuing a course of action. If you recognize that there is no grander utility beyond maybe helping yourself (and nobody else, due to the nature of the therapeutic regimen you are doing) whilse acknowledging that it is at best a long shot and at least as likely to harm as help (and much more likely to harm) and you still wish to pursue this treatment, that is absolutely your right and I respect it.
But it is still my right to discuss the lack of scientific rationale and to critique a colleague of mine as acting unethically simply based on that fact alone.
@elburto:
First off, I am genuinely curious as to condition 1 and 2. I’ll take you at face value that you have these conditions regardless of whether you name them or not, but I am genuinely curious.
Also, people did begin to bash Irene. Whether it was expected, reasonable, or justified is a separate question. I personally feel as a (aspiring) clinician that I should hold myself to a higher standard and take the short end of the stick in such situations in refraining from the bash. I also clearly stated that others here aren’t and I can’t hold them to my standard, but that I felt in this situation it was counterproductive. This is not a creationist or Joe Mercola we are dealing with.
For that reason both here and in practice I accept a higher amount of “abuse” from patients since I acknowledge that in their shoes I would be very hard pressed not to act differently. It is not an excuse for the behavior, but an acknowledgement of empathy. I am certainly not perfect at this, and anyone here can track down my failures of the past, and I will certainly fail in the future. But whenever I can, I try and live up to the ideals I strive for in this regard.
I’m reminded of my mother (an RN) commenting about a particular hospitalist and saying she could never understand why he let patients abuse him so (verbally yelling at him and calling him a shitty doctor). He said that it was his burden to accept their abuse in order to work past it and achieve his goal of improving their health and their life. At the time this did not resonate with me as it does now. But learning more and actually caring for patients myself has made that lesson stick. I’m not a burger flipper who can tell off a patron who yells at me for neglecting to remove the pickles from her hamburger. I’m literally dealing with the single most important and valuable thing someone has – their life and their health. If I demand a uniform and rigorous standard from my colleagues, I’d be quite hypocritical to not to so myself… anonymously on the internet or not.
elburto, man, — wow! No words can do justice to that.
(Not meaning to respect the disability of our CFS visitors any less, or their right to pursue treatments at their own expense and risk, and, to a considerable degree, according to their own judgment.)
Nobody anywhere knows much about the pathophysiology of CFS. It is entirely possible the condition is neurological or even purely psychological. I know patients object to the possibility, I know they find it insulting, but the reality is CFS is a diagnosis of exclusion. It is not known if there is “one” CFS, multiple potentially separable subtypes, or multiple completely different types that get lumped together. Nobody knows, and the insults, harassment and condemnation both experienced by and made by CFS patients doesn’t help.
Yes, for very good reasons listed repeatedly above. If nothing else, the fact that publicly discussing your treatment has tremendous potential to delay research is a reason to take down your blog and remain silent about it on message boards.
Absolute agreement there. However, chances are it would merely result in shrinking the pool of CFS patients as those who can get diagnosed are no longer given the diagnosis of CFS and called something else instead. The central symptom of CFS is fatigue, which is nonspecific and extraordinarily common. An unfortunate reality.
I can certainly see the problems related to patients trying a treatment like Rituximab at this point, even with informed consent. But given the way in which CFS patients have been routinely treated by many medical staff, it seems very strange to focus upon the use of Rituximab as an example of poor medical practice.
Many patients have been treated as if their symptoms were a result of depression, or a fear of exercise, or just deconditioning, without informed consent and based upon even weaker evidence than that which currently supports the use of Rituximab as a treatment for CFS.
If we were to compare the problems with the Rituximab study to the problems found with the PACE trial, the largest and most expensive investigation of biopsychosocial interventions for CFS, run by the psychiatrists who developed these interventions:
Rituximab trail showed no significant result at what had been determined to be the primary end point in it’s protocol. PACE still has not released what had been determined to be it’s primary outcome measures, and completely abandoned most of the outcome measures laid out in it’s protocol, while refusing Freedom of Information requests for this data, eg: http://www.whatdotheyknow.com/request/pace_trial_recovery_rates_and_po
In the blinded Rituximab trial patients were not questioned about whether they thought they recieving active or placebo treatment. PACE was entirely and necessarily unblinded. Evidence from subjective questionnaire scores did not correlate well with data from more objective outcome measures, like the walking test or number of patients on disability benefits, but it was jsut subjective questionnaire score used to promote efficacy.
We have not identified a testable mechanism to explain the value of Rituximab as a treatment. In the editorial which accompanied PACE it was explained that while the models seem to be wrong, the (minor) improvements in subjective questionnaire scores are enough to justify these approaches. The models which underpinned CBT and GET as treatments for CFS have been tested, and found lacking.
There is a danger that patients with CFS could try Rituximab before there is good evidence of efficacy, despite the researchers involved saying that we should wait for more evidence and RCTs. The researchers from PACE have been saying that all patients with CFS should try their treatments, and that the only reason some patients do not want to devote more resources to them is anti-psychiatry or a fear of the stigma of mental health.
It seems that the promotion of psychosocial treatments for CFS is less ethical and more widespread. It would be wonderful if the high standards of care promoted above were a normal part of how CFS is treated, but at the moment it is not, and it seems strange to focus upon the use of Rituximab as an area of concern.
[...] Dette foregår på nettsiden “Science-Based Medicine”. Bloggposten heter “Rituximab for Chroinic Fatigue Syndrome: Jumping the Gun”. [...]
Dr. Hall certainly wasn’t. That was part of the focus. The other part was the implications of the information found regarding the research and ethics of OM.
Also, it makes perfect sense to point out that ritux is not reasonable to use for CFS outside a properly conducted study. In fact if I were sitting on the IRB to approve such a trial I would be extremely reticent because ritux is serious drug with serious side effects and from what I know currently there is not enough scientific data to justify the potential harm to study subjects to meet ethical standards. No matter how you slice it the discussion is reasonable.
And this isn’t the only discussion of CFS that has been had here at this site.
That is a misunderstanding. CFS is, by definition, a diagnosis of exclusion. That means that in order to diagnose it we must rule out all those other conditions you listed. Often this means trying the treatment for each one. If it doesn’t work we rule out the Dx. It is absolutely not correct to called that “without informed consent” since the patient is informed that the provisional (i.e. most likely) Dx is [X] but it could be other things and treated for that knowing they would move down the differential diagnosis until CFS is reached at the bottom. It is the only way to scientifically do it.
Considering that it is likely at least a subset of what gets callsed CFS is psychosocial in nature and everything we know would indicate that psychosocial outlook would influence the symptoms of CFS regardless of the underlying cause, it hardly seems unethical to treat it psychosocially. Unfortunately the stigma of such treatments remains, and indeed the medical field would do better to actively reduce that stigma, but the fact remains it is not only ethical but probably the best treatment we actually do have, especially considering there is no better one elucidated.
Many patients are wary of graded exercise therapy (GET) and cognitive behaviour therapy (CBT) involving the scheduling of increased activity or exercise, due to the adverse events that have been associated with the therapies. See, for example:
Kindlon T. Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Bulletin of the IACFS/ME. 2011;19(2):59-111
@WilliamLawrenceUtridge:
“…the insults, harassment and condemnation both experienced by and made by CFS patients doesn’t help.”
Except for a single post by another patient, I think I am the only CFS patient here. I have not consciously insulted, harrassed, or condemned anyone. I have not labeled anyone or implied that anyone is unethical, irresponsible, pathetic, passive-aggressive, or a host of highly inflammatory terms that have appeared in this discussion.
“If nothing else, the fact that publicly discussing your treatment has tremendous potential to delay research is a reason to take down your blog and remain silent about it on message boards.”
I don’t have a blog. My discussions here are far greater than anywhere else. I don’t see how anything I’ve said has the remotest influence on research. Attempting to silence someone because you disagree with their personal medical decisions is moving to a place I’d rather not go.
” The central symptom of CFS is fatigue, which is nonspecific and extraordinarily common.”
No, fatigue is not the central symptom of CFS, and the use of “chronic fatigue syndrome” as the name of the condition is misleading for that reason. The term is way too broad and non-specific and leads to confusion.
@ nybgrus
I do not see what it is that you think I have misunderstood.
I was describing models of CFS which have been used to justify the treatment of patients, not alternative diagnoses. Also, the cognitive aspects of some of the psychosocial approaches taken to CFS (which should be seen as only experimental) make it difficult for informed consent to be given. If a ‘treatment’ involves encouraging a patient to believe that their illness is “real but reversible by his or her own efforts”, then genuinely informed consent requires that a patient first be informed how likely it is that these cognitions are true, which would rather undermine the treatment. Perhaps this is why those researchers promoting and making money out of these interventions are so keen to avoid releasing data from publicly funded trials in the manner laid out in their published protocol: http://www.whatdotheyknow.com/request/pace_trial_recovery_rates_and_po
“everything we know would indicate that psychosocial outlook would influence the symptoms of CFS regardless of the underlying cause, it hardly seems unethical to treat it psychosocially.”
What does this really mean? All human behaviour and experience is heavily affected by psychosocial factors. The difficulties still faced by African-Americans will be affected by psychosocial factors – but medicalising the cognitions and behaviours of all African-Americans because of this would still be recognised as poor practice, and the unreasonable views of African-Americans such an approach would require and promote would be recognised as a cost ‘treatment’. Considering that medicalising and treating the cognitions and behaviour of all CFS patients seems to lead to only small improvements in subjective questionnaire scores in unblinded trials run by advocates, the unmeasured social costs to patients of such an approach is quite likely to outweigh any real benefits – social costs cannot be dismissed as mere ‘stigma’ by those wanting money for the psychosocial benefits that they bring to patients. If we are to hold those making money from the psychosocial treatment of CFS to the same standards those using Rituximab for CFS are being held to, then many of them seem much more deserving of criticism.
“many of them seem much more deserving of criticism.”
If we tried to measure who deserves the most criticism and only write about those, we wouldn’t get much done.
Som update about the Norwegian research: Fluge and Mella’s application to the Norwegian research board for 9 million NOK (about 2 million dollars) funding for their RCT was turned down (… along with 400 other good applicants, so this is hardly discrimination against ME-patients). But the Norwegian Secretary of health has given then 4 million NOK, and there’s an ongoing crowdfunding project, so they will probably be able to start their RCT.
@Irene: Kogelnik has said several times, e.g. to a Norwegian newspaper, that he has a project. He sometimes calls it a pilot study, sometimes a case-by-case study. He has also said, or implied, that he is collaborating with Fluge and Mella about it. According to you there’s no project but off-label treatment. It’s all rather confusing.
Perhaps someone could ask Kogelnik to comment? Harriet Hall, I suppose you’ve tried asking him?
About IreneF, I think many of you are confusing her with Kati, whose blog Hall quotes in her article. Irene has tried to say several times she doesn’t have a blog, but several people here keep criticising her for what she allegedly writes in her blog.
What about believing what se says, and checking your facts?
Regards
Pernille Nylehn
Norway
I’ve interacted with CFS patients here and on wikipedia. In both cases I have been called stupid, insensitive and biased. I am pretty sure I know why the CFS patients react the way they do – their suffering is trivialized – but that doesn’t mean their claims are valid or mine are invalid.
Then clearly my comments do not apply to you, and you are welcome to consider them as abstract observations aimed at no particular individual.
I would never try to silence someone because of their personal medical decisions. However, I will object to shoddy science, poor reasoning and decisions that have real-life consequences. I’m not arguing or advocating for blogs being shut down by some sort of ham-fisted state action. I’m merely pointing out that if someone tries rtuximab and ends up dead, comatose or permanently injured, some of the blame goes towards those who publicize their unscientific trials and create false hope for desperate patients.
From PubMed Health: “Chronic fatigue syndrome refers to severe, continued tiredness that is not relieved by rest and is not directly caused by other medical conditions.”
From the CDC: “Chronic fatigue syndrome, or CFS, is a debilitating and complex disorder characterized by profound fatigue that is not improved by bed rest and that may be worsened by physical or mental activity.”
From the 2011 ICC: “Marked, rapid physical and/or cognitive fatigability”
From cfids.org: “CFS is characterized by incapacitating fatigue (experienced as profound exhaustion and extremely poor stamina)”
From MEFMAaction: “The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level and is usually made worse by exercise”
There are other parts to the definitions, but clearly fatigue is at least one core symptom. I doubt that if someone had all the symptoms except fatigue you would be diagnosed with CFS, ME or CFIDS. I’m delighted to see the ICC’s 2011 publication has identified “profound dysregulation of the central nervous system and immune system, dysfunction of cellular energy metabolism and ion transport and cardiovascular abnormalities” and hope it represents real and meaningful results, not just pandering. I was particularly intrigued to see a 2009 citation that appeared to indicate objective measures of mitochondria dysfunction in 71 patients. Then I noticed they recommended dietary supplements and detoxification and lost interest. Then I clicked on the lead author’s website and despaired. If nothing else, were her arguments factually correct it would indicate that a subset of CFS patients were not actually CFS patients, they had nutritional deficiencies – once again indicating that CFS is a wastebasket diagnosis including people with conditions that are undiagnosed, not people with a hitherto-unrecognized condition.
I wanted to ask Kogelnik to explain what he is doing, but I was unable to find a email address. I would appreciate it if one of his patients would ask him to comment here.
Unsurprisingly, it looks like Dr. Myhill has yet to find a form of quackery or logical fallacy she doesn’t like:
http://drmyhill.co.uk/wiki/Detoxification
That website deserves a heapin’ helpin’ of insolence. Respectful, of course.
And IreneF, when I said “poor souls”, I was talking about the Norwegian patients who travel to USA and pay 8000 dollars per treatment at OMI. I think some of them has managed to get funding, but most of them don’t. One of them has spent 200,000 NOK so far, which equals about 40,000 dollars. That’s rather a lot of money, don’t you think? And most patients with ME aren’t well off, but living on welfare money from the state, or supported by relatives.
There are also several British patients coming to OMI for treatment, I suppose they pay the same price, plus travel expenses.
I think there are some good points being made here once you sift out the misinformation.
* I think venture philanthropy has been confused with venture capitalism.
* XMRV was science working the way it is supposed to work and scientists whose work is not replicated are not automatically frauds they are mistaken. Happens all the time in science – just ask John Ioannidis.
* Big Pharma is a regulated business that should probably be more closely regulated. If you don’t like “evil” artificial interventions then don’t take them. It’s pretty simple really. At least in the United States, no one can force a treatment you don’t want on you.
* There seems to be some confusion between what is appropriate for an individual vs how science is done. The decision between a physician and a patient to use a drug off-label, as pointed out, is not illegal or necessarily unethical. However, decisions about whether a drug is appropriate for entire populations must be based on clinical trials not individual (N=1) successes or failures. That requires significant sums of money regardless of how it is obtained and no matter what the treatment or the disease.
* Regarding ME and CFS, there are multiple definitions (both clinical and research) that define very different populations. The broader and less specific the definition the more likely it is to draw in people who are not ill or patients who have other diseases. Currently definitions range from the least specific (White et al 1991) to the most specific (Carruthers et al 2011).
For example, GET and CBT apparently do help a modest number of people (about 15% over standard care for GET), but the evidence base is very narrow and it is premature to extrapolate to patient groups who have not yet been specifically tested and are defined very differently from the original group tested. In the case of GET this would be patients with post exertional exhaustion lasting 24-hours or longer, unrelieved by rest and upon minimal exertion.
The gold standard for making comparisons across groups of patients identified by varying case definitions would be studies with completely separate cohorts by definition, not one large sample with embedded subgroups.
It is quite possible that ME and CFS are multiple discrete entities under an umbrella term. If so, the answer is may be subgrouping – not trying to make treatments one size fits all. Different forms of arthritis for example have very different causes and treatments as does hepatitis.
@Geo – I don’t know if you’ve had a chance to read any of James Coyne’s posts on this blog – if not check them out. He is quite outspoken/skeptical of some claims of benefits from psychological interventions and how those claims are published. He does focus primarily on cancer, though, so it’s not a perfect fit. But I don’t think it’s too outlandish to wonder if reputable journals are publishing questionable studies about the benefits of some psychological interventions in cancer survival rates, that there may also be questionable studies published in popular psychological interventions and CFS.
Personally I’d love to see an article on that topic – but I’m a big fan of skeptical psychologists like Scott Lilienfeld, Jean Mercer and Coyne. Not because I’m against psychology, but there is alot of bad psychology, bad therapists and bad advice out there. Things could be so much better with more skepticism applied.
I’m willing to bet shiny money that if you did a series of careful studies on those who respond to those two interventions, they would have significantly different characteristics from the overall average. It’s a wastebasket, hopefully it’ll turn into a recycling bin.
Assuming everyone else’s recylcing program involves separating out paper, plastic, mental and compostables.
@ H Hall:
“If we tried to measure who deserves the most criticism and only write about those, we wouldn’t get much done.”
That’s true.
@ KAL:
“For example, GET and CBT apparently do help a modest number of people (about 15% over standard care for GET), but the evidence base is very narrow and it is premature to extrapolate to patient groups who have not yet been specifically tested and are defined very differently from the original group tested.”
It’s also important to note that those figures (assuming that they are from PACE, which it looks like they are) are for quite an undemanding criteria for clinically significance – much less stringent than the criteria which had been laid out in the trial’s protocol. Secondary data from the trial, like the failure to improve the amount of paid employment those in treatment groups were able to do, could indicate that the subjective questionnaire scores used as primary outcomes are not be entirely reliable. Evidence from earlier trials of CBT for CFS have shown that it leads to patients answering questionnaires more positively, but not being able to increase their objectively measured levels of activity. That has not stopped those providing these treatments from claiming that PACE showed a recovery rate of 30-40% for CBT and GET. If homeopaths had behaved similarly with an unblinded trial of their treatments, I do not think that many people would be impressed.
@ mousethatroared:
I agree. Unfortunately I think that people are less likely to spend time upon a critical analysis of the evidence surrounding psychological interventions for CFS because of the uncertainty and controversy that surrounds CFS itself. Discussions very often descend to uninteresting observations about the fact that it’s possible for emotional problems to cause physical symptoms, the danger of dualism, or that patients are so ungrateful for the psychosocial research being done on them because of their unreasonable views about mental health matters. Also, almost all of the work around psychosocial aspects of CFS is done by those with an interest in justifying psychosocial interventions. Data is very often presented in misleading ways, so it takes a lot of work to be able to consider: ‘Do we really know what we’re doing here? Are we doing more good than harm?’
When there is so much uncertainty, and so little good quality research, it’s very easy for people to just assume that they can trust those who are making money as experts in this area.
This page has contact info. for Open Medicine Inst./Dr. Andreas Kogelnik:
http://openmedicineinstitute.org/contact-us/
@irenef,
I found that page but it only offers contact information for the Institute, not Dr. Kogelnik’s e-mail address. Since you are his patient, why don’t you contact him yourself and make him aware of my article and ask him to respond in the comments?
@Harriet Hall:
You can reach Dr. Kogelnik using that e-mail address. I cc-ed him a link to your post yesterday. He’s aware of what’s going on.
Here’s another link:
http://openmedicineinstitute.org/research-initiatives/mecfs-merit/
BTW, you and your colleagues have managed to silence Kati. I don’t think it was because of your superior and impartial reasoning, but through intimidation. Is that what you wanted? Do you feel like you struck a blow for rationality?
There has been little discussion of your failure to contact *anyone associated with Dr. Kogelnik* before posting your criticisms. I don’t see much difference between your methods and AM radio “news”.
“There has been little discussion of your failure to contact *anyone associated with Dr. Kogelnik* before posting your criticisms.”
In the world of science, we have no obligation or custom to contact researchers before we critique their research. Perhaps you think Dr. Gorski should have contacted Dr. Oz or Dr. Burzynski before he wrote criticisms of them; I don’t. Their record and their spoken and written words speak for themselves. Now that I know Dr. Kogelnik is aware of my article, I eagerly await his explanation of what Kati reported and of what Pernille tells us he has told reporters in Norway. If he was mis-quoted, he can set the record straight.
This is a form of ad hominen, essentially saying you are free to ignore our substantive points because we are mean. However, the criticisms were presented calmly, with civility, and no name-calling. Perhaps you can call attention to the flaws in our “superior and impartial reasoning” rather than trying to shame us into silence for hurting someone’s feelings.
Well-intentioned false hope is still false hope. Thinking happy thoughts does nothing to cure any disease. Shoddy science helps nobody over the long term, but it’s great at wasting scarce resources – both money and patients.
Please feel free to respond to matters of substance instead of continuing with your current approach.
Complaining that a blogger didn’t contact the subject of her blog post is a common trope used by supporters of doctors who are doing dubious science to attack critics of such doctors. It’s a trope rooted in the thinking of journalists, not scientists. In journalism, in any controversy or scandal it’s obligatory to get a quote from the person at whom the criticism is being leveled. Kogelnik’s words and actions as described in the public record, including irenef’s blog, combined with Kogelnik’s website, are more than enough material for a scientific critique, either in a blog or in a scientific article.
On the other hand, last year I did contact the Burzynski Clinic for comment about Marc Stephens’ harassment of skeptical bloggers who were criticizing Burzynski, but I did it more to see if I could get a response. I didn’t really expect one. Unfortunately, that means that Dr. Burzynski and his PR flack now have my university e-mail address, because I used that address to prove that I was an academic and not just some schmo off the street.
@Harriet Hall:
We are not in the world of peer review. This is not a scientific journal. It is a public forum about medicine.
How can Dr. Kogelnik bear responsibililty for what his patient says in a blog? I don’t see how he could provide an explanation for what she “reports”, or what someone else claims he said to people–who may or may not be professional journalists–in a foreign country.
No wonder science-based medicine is ignored by people who could benefit by a little critical thinking. You have convinced me that you are more invested in making points with each other than in discourse with the world at large.
@Gorski:
This is at least the third time I’ve said this: I don’t have a blog. I never had a blog. I’m not going to have a blog. Move along.
@WilliamLawrenceUtridge:
No, I haven’t ignored your points, I’ve argued them. As far as Kati goes–the patient who had a blog–she didn’t go black because of any substantive points. You failed to convince her that she is pursuing false hope.
@irenef,
Dr. Kogelnik is not responsible for what a patient says in a blog, but he is responsible for correcting the record if he discovers that he has been misquoted or misrepresented. He is also responsible for communicating accurate information to his patients and correcting any misunderstandings when he becomes aware of them.
@Harriet Hall, David Gorski, et al:
I think you are preaching to the choir. You have failed to convince anyone beyond people who I think are regulars here of your arguments. You have failed to convince me of anything but your failure to communicate effectively with people with whom you disagree, which I believe is something you want to do.
I am pre-disposed to agree with you. I have lurked, off and on, for a couple of years. I’m not completely ignorant. Yet you have alienated me, you have done the same to at least one other person, and some people here have expressed support for my position. What has this accomplished for you or anyone else?
Providers do tell patients that their symptoms are due to “fear of exercise”, or depression, as well as a host of other incredibly unethical and disproven pseudo-psychological diagnoses. It seems that most providers will readily prescribe an antidepressant or antipsychotic even to treat symptoms of muscle spasms, pain, tremors and dizziness just because they have no definitive test results that point to a confirmed disease. Too many doctors require a test result that says “The patient has Disease #5″. When a definitive test result is lacking, then the patient goes untreated, except for the offering of psychiatric medications, rather than attempt a careful trial treatment approach as described by nybgus. It seems to me that perhaps too many patients are incorrectly categorized as having CFS, or FMS simply because the physician doesn’t know what else to do.
I don’t see where anyone has called you names, or stated that you were ignorant. nybgrus made a few comments like the one shown below, but it is clearly about the concept in the statement, and not intended as a personal attack or insult. I think the misunderstanding here lies more with the fact that people here have different levels of communication and language skills – basic comments like the one below are being misunderstood.
I find that nybgrus, WLU, Dr. Hall and others have been patient in explaining their points. I tend to give people the benefit of the doubt and consider that many may not have the communication skills and experience to engage in these types of discussions without misunderstanding some things. It has been a real learning tool for me to read and comment here. It takes practice, like most things, people need to learn how to disagree and express their viewpoints in the best possible manner. It can be difficult for patients to read how doctors talk about their condition.
It’s reinforced to me that it is counterproductive for one to turn defensive and make comments like this: “How dull the day has become. Someone, please, argue with me. This is the most fun I’ve had in months. Really.”. As far as nybgrus’ comments go, they should be written up in a textbook for physicians to study on how to communicate with patients. I’m at a loss as to how anyone could object to those statements, other than due to being ill and irritable and desperate for effective treatment, all of which I can completely empathize 100%.
Other than confusion surrounding the owner of that blog, I see no other failure to communicate effectively. Effective communication doesn’t necessarily mean being successful at changing someone’s mind. That takes two, and both parties need to be open to it. Although, I think it is challenging for anyone new at reading information discussed in this manner to understand and relate.
@Irene, I’m curious as to what you consider as being the central symptom of CFS if it is not fatigue. Would you share that with us please?
@elburto, when you mention Rife, MMS, and homeopathy, it causes me to wonder if you have been diagnosed with Lyme disease.
Sure, there are lazy and/or bad practitioners. But that is not how we are trained nor what we should do.
Tough call to be so sweeping. There are many cases where it is evidence based and justified to administer such treatments, especially in attempting to make a diagnosis of exclusion, but even alone.
This is true. And at my institution we have conferences and in-services regularly and many of them address these sorts of concerns directly.
I’m genuinely flattered, thank you. I strive for excellence in communication, especially with my patients, and have a long way to go. But it is always nice to hear some positive encouragement, so thank you.
Which is precisely why I don’t take such comments personally. I’ve been ill, injured, and post-op without narcotics (I’m allergic). It isn’t fun and it is very, very hard to keep ones words and thoughts in check no matter how hard you try. The additional motivation is that in any case, responding in kind does absolutely no good for anyone involved.
LOL. Yeah, that one was pretty glaring. But it happens. I re-read comments a lot, especially my own, to make sure I understand and also learn for the future. I once read that Ben Franklin was a terrible writer and so he set out to get better. He wrote and wrote and spent countless hours reading and re-reading his writing, critiquing it and learning from it. Ever since then I re-read my own comments at least once almost always (after I post them I mean, to learn from them after responses come in). Sometimes I am in a hurry or typing fast, but nobody is perfect.
@Sialis:
When I first got sick, I had flu-like symptoms that would come and go. A neighbor thought I might have CFS, but I pointed out I felt sick, not tired. My symptoms have changed since then, and fatigue is a major problem, but it is one of many.
Secondly, there’s no good definition of fatigue. I used to swim, and I’d be pretty beat after, say, 40 laps, but it wasn’t what I experience now.
My symptoms now and in the past include:
Muscle pain
Sinus headache, congestion, occasional infections
Sore throat
Tachycardia
Orthostatic hypotension
Weakness
Feverish sensations
Light-headedness
Hives
Striated nails
Depressions in my tongue
Mouth sores
Glazed, red eyes
Circadian disruption
Hypoglycemia
Cognitive dysfunction/inability to concentrate/”brain fog”
Memory problems
Tremulousness/shakiness
I probably have postural orthostatic tachycardia syndrome (POTS) and delayed sleep phase syndrome.
My blood work shows antibodies to several infections that seem to be common among CFS patients: EBV, HHV-6, parvo B-19, Mycoplasma pneumoniae, and perhaps something else. I also have low NK cell function. I have wondered whether there’s a relationship between the higher-than-expected antibody production to this group of pathogens and the inactive NK cells. Not an infection but a consequence of an immunological dysfunction.
@sialis:
I like to argue with people who are worth arguing with and who have something important to say. I don’t get to do it much. And I will concede a certain degree of snarkiness.
I am not complaining about people calling me names. I don’t think I’ve misunderstood anyone. What I’m trying to express is more fundamental. What is the purpose of this blog? Are you, collectively, committed to changing people’s minds about choices in medical treatment? Do you think because you play by certain rules–that you seem to make up as you go along–you are winning the game?
I love science. It’s one of the most fun things in the world. But I don’t think you’re doing a good job.
@IreneF, if you don’t mind my asking: You pay 300$ per treatment. But who’s paying for your medicine? It costs 6000$ per dose. Do you also get refund from Genentech foundation?
Regards,
Pernille Nylehn
“I like to argue with people who are worth arguing with and who have something important to say. I don’t get to do it much. And I will concede a certain degree of snarkiness.”
If you knew your true worth, you could talk with anyone. If you knew the worth of others, you would know everyone has something important to say. If you ever allow yourself to discover what you -really- want to say, you will have limitless opportunities to say it. And if you had true self confidence, you would not need to hide and sneak behind elided lies, aka snark. Or so I’ve been told.
@PernilleN:
I don’t want to discuss my financial arrangements any further.
@IreneF: Ok!
@geo “Discussions very often descend to uninteresting observations about the fact that it’s possible for emotional problems to cause physical symptoms, the danger of dualism, or that patients are so ungrateful for the psychosocial research being done on them because of their unreasonable views about mental health matters. ”
Yup, those discussions are not my favorite, either.
And it’s hard to find a blog that focuses on real nuanced discussions on skepticism in clinical psychology, a shame.
I’m not a scientist or a physician and I have done even better than a damn good job considering where I was at just a few years ago. In fact I have done such a damn good job that to most people the progress is unfathomable. In fact most people would not even believe me when speaking of the progress at first, but I’m building trust and support – and I’m doing that by not insulting and demeaning those who have the intelligence, training and experience to either possibly help me in the future by educating me a bit, or at least continue to offer emotional support and good will, and I intend to pass that along to others as best I can. I all too fully appreciate the dangers in the treatments, irrational off-label prescribing, bogus studies and treatment trials as described on this blog and others like it.
This is so true, it seems rather apparent to me now that progress on any disease can be sabotaged by the very patients, and some of the physicians who are treating it.
If cognitive psychology has taught us anything, you’re probably more interested in maintaining a pre-existing world view than you are challenging it through new evidence. The reason science took tens of thousands of years to develop is because it is strongly counter to this self-confirmation bias, and instead uses empirical results as its main measurement tool. That’s also the reason that it has completely transformed the world, including medicine, in a little over three hundred years (a little over a century if you consider medicine, most of the early scientific work in medicine involved disproving previously held beliefs, it took a long time to start developing novel, effective treatments).
This is the reason why medicine uses experts (doctors) to channel treatments, because regular people are not up to the task. Even doctors, with years of training, still fall prey to cognitive biases on a regular basis. We are, after all, just monkeys with more wrinkles in their brains.
@irenef: Are you still fatigued, persistently, and this is not relieved by rest? If so, it seems like you may still have the core symptom of CFS. If you are not fatigued, I wonder if you would be diagnosed with something other than CFS. Again, an imperfect wastebasket diagnosis.
The real test is whether these markers are different from non-CFS controls. You always need a control group, otherwise all you can say is “X is Y”, which tells you nothing (unless you are attempting to establish a baseline).
Changing minds is extremely difficult to do, humans are self-justifying animals. Try reading Mistakes were Made (but not by me) by Carol Tavris and some other guy, it does a great job of this. Particularly when one is strongly invested in a position, it is very difficult to get them to change that position. It is an intractable problem common to nearly any non-empirical system of thought, be it CAM, CFS, off-label trials, politics and the like. Very rarely will any criticism reach or change the mind of the committed believer, I hope my comments will be read by fence-sitters who are more likely to change their minds because they haven’t committed to a position yet and are thus open to logic and evidence.
By endorsing a series of uncontrolled n=1 trials, you are not really supporting the idea that you understand science. How do you define it? And how do you reconcile your definition with thinking n=1 trials are a good thing?
@Quill
Heh, clearly I do not know the worth of others, because there are many people I know who have nothing important to say
@WilliamLawrenceUtridge:
Yes, I have post-exertional malaise. Sorry for not listing it.
“By endorsing a series of uncontrolled n=1 trials, you are not really supporting the idea that you understand science. How do you define it? And how do you reconcile your definition with thinking n=1 trials are a good thing?”
I am doing no such thing. We’ve been through this before. There is no trial. I never said there was a trial. (I don’t have a blog, either.). I am receiving an off-label medication. I have explained some of my decision-making process and my rationale for doing what I am doing. I am not endorsing anything.
Another patient, an RN, who had a blog, used terminology that may have been imprecise in the context of clinical trials. I don’t know much about nursing education, so I don’t know whether she could be expected to understand the niceties of scientific vocabulary. She was relating her personal experiences to the world at large, and trying to get funding and better treatment for CFS patients. Now this advocate has gone dark.
Someone else is worried because a CFS patient in Norway is flying to California for treatment. This may reflect more on Norwegian attitudes than anything else, since the the physicians who first used ritux on CFS patients issued an apology about their country’s previous attitude and treatment of this group.
“The real test is whether these markers are different from non-CFS controls. You always need a control group, otherwise all you can say is “X is Y”, which tells you nothing (unless you are attempting to establish a baseline).”
Yes. Exactly so. My own personal musings. It is something that struck me as odd.
Re: changing people’s minds. It’s hard work. Repeating something over and over doesn’t usually do it.
Irenef: “I love science. It’s one of the most fun things in the world. But I don’t think you’re doing a good job.”
WLU:By endorsing a series of uncontrolled n=1 trials, you are not really supporting the idea that you understand science. How do you define it? And how do you reconcile your definition with thinking n=1 trials are a good thing?
I haven’t followed this in great detail, but is Irenef actually saying that, or merely defending herself against attacks (or possibly perceived attacks) on her personal decision to try out this treatment under the terms that were available to her at the time? She should not be under attack for that — she has told Harriet that she would gladly have entered herself into a placebo-controlled trial if that option was on offer.
It is true that the consequent uncontrolled observations are likely to be highly misleading with this condition, but clinical research is hardly her responsibility.
Is this not a clash of different perspectives, both of which are largely valid? There can be unfortunate consequences from that clash, for both sides, depending upon which viewpoint prevails, but some things cannot be helped while personal freedoms are respected.
Irenef’s perspective is exactly that of the the typical CAM user. Unmet medical need + something that might help = considerable use of “unapproved” medical treatments . It happens whether we like it or not. “Science” as it relates to clinical research has scant relevance.
Your equation is incomplete, as it is missing at least two variables. Try this instead:
“Unmet medical need/desire” + something of marginal or nonexistent plausibility promoted as helping + [brave maverick doctor or charlatan] – proper informed consent = considerable use of [unproven or disproven] treatments
There, fixed that for ya. No need to thank me.
@pmoran:
While being compared to “the typical CAM user” is a little wince-inducing, you have got most of it in a nutshell.
By taking off-label medication, particularly for a condition with an unknown etiology or pathophysiology, you are in fact undertaking an n=1 trial, with subjective endpoints. You are taking rituximab, which has an uknown effect on CFS, and seeing if you feel better. It’s a very poorly designed n=1 trial since it lacks demonstrated prior probability (a failing of the unknown etiology of CFS) and no empirical or objective way of determining if it is successful or whether the effects are due to placebo. Essentially every patient taking medication is invovled in a similar trial since responses to medications can only be predicted at an aggregate level, not an individual level. But with an existing evidence base, at least there is reason to expect some success.
It’s not merely odd, it’s bad science. The kind that answers no questions, can not answer any question, but can (and often is) used by practitioners or (more often) sales people to flog a product or treatment. Often quacks will undertake such trials to co-opt the social capital of science and paint a thin veneer evidence that justifies their practices and can be used in publications. I would wonder what happens to your blood work results, and how it is used. If you are comfortable in saying so, I would be curious to know why you had the bloodwork done, and what your doctor said about it.
Yes, but sometimes if you keep hammering a point home, eventually the person will come to understand it. If nothing else, it can emphasize the importance of the point. Sometimes people will think about it after the fact and come to understand a point they did not understand before. I also recommend a lot of books, because skeptical thinking requires considerable knowledge and awareness of specific facts and reasoning – why to use a control group, why to use objective endpoints, how the human mind can fool itself, and so forth.
@David Gorski:
Is it so necessary for you to be insulting? It’s not helping your case.
If you know something about the pathophysiology of CFS that indicates that ritux is implausible or marginally plausible as a treatment, please share it.
Also, if you have any substantive evidence that Dr. Kogelnik is “a brave maverick doctor” (your link implied a comparison with Andrew Wakefield) or a charlatan, please share that, too. The Open Medicine website’s use of buzzwords that you don’t like doesn’t count. It’s not directed at you.
I don’t know why you think any of Dr. Kogelnik’s patient’s haven’t given informed consent.
@IreneF says:
“Someone else is worried because a CFS patient in Norway is flying to California for treatment. This may reflect more on Norwegian attitudes than anything else”
That’s me. But you left out a rather important point in my worries: These patients are paying 8000$ per treatment, plus travel and lodging. One of them has spent more than 40,000$ so far.
That worries me. Perhaps it’s a Norwegian attitude to be worried – no, angry – when very sick patients are charged that kind of money for taking part in a so called study (yes, they are told they are) with a treatment that is in practice experimental. If that’s a typical Norwegian attitude, I can’t say I’m sorry about being Norwegian.
As for the Norwegian doctors who discovered that Rituximab may be useful for some ME patients: They have said very clearly that the drug should not be used outside clinical studies. In other words: Kogelnik is doing exactly what these two very serious and dedicated doctors ask us not to. If you should pay heed to any Norwegian’s attitude, I think it should be to the only two people who have actually done proper research into Rituximab for CFS/ME. They are also oncologists, and have many years of experience with Rituximab (does Kogelnik have that kind of experience?).
I must say Kogelnik has a lot of nerve going against their advice. I’m sure he means well and wants to help, but what he is doing is still wrong. And even though he has he the patients’ informed consent, he is still the doctor, and he is responsible for what he is doing. And he will be to blame if something goes wrong. Rituximab is a potent drug that can have very serious side effects. And we don’t know yet if CFS/ME patients will have different, or more serious, side effects than other patients. That’s one of the many things we need to find out from properly performed clinical trials.
Regards
Pernille Nylehn
Norway
Irenef seems to understand what she is doing, and I did not “attack” her for her decision. I have no problem with patients trying experimental treatments with informed consent, and I understand the desperation. My problem is not with the patients but with doctors who encourage experimental treatments outside of clinical trials, especially when the rationale for the treatment is shaky, when the treatment is dangerous, and when the patients think they are in a clinical trial. I have tried to explain why I think that is short-sighted and only tends to delay proper research and the acceptance of its conclusions. Arguably, doctors who refuse to treat patients outside of clinical trials are acting in the ultimate best interest of all patients.
At least one of Dr. Kogelnik’s patients believed she was participating in a pilot study, and in this interview http://www.youtube.com/watch?v=08Qul7E-xv8 Dr. 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.
And please note that no one can say that Ritux is implausible in terms of the pathophysiology of CFS, because we don’t understand that pathophysiology. But in my opinion, the quality and amount of evidence available so far for Ritux is not a plausible justification for treating patients.
You have it backwards. The burden of evidence is on the person making the claim; i.e., Dr. Kogelnik. It is not on the scientist (and I am a surgeon-scientist with a lab and everything) questioning the claim. Consequently, the correct version of your statement is: If Dr. Kogelnik has compelling preclinical evidence supporting his hypothesis that rituximab is likely to be an effective therapy for CFS, then he should first share it with his scientific and medical colleagues by publishing it in the peer reviewed literature—and he should do it before conducting N of 1 trials (which is, as WLU just pointed out, exactly what he is doing) or using it off-label.
It’s very simple. Unless Dr. Kogelnik has compelling preclinical evidence of the efficacy of rituximab against CFS, then as part of the informed consent process he would ethically be obligated to tell potential subjects that he has no evidence that this would work and that there is currently no known plausible biological mechanism through which it could work. Consequently, he would be ethically obligated to tell patients that the potential for harm is far higher than any potential for benefit, and even in that case his behavior would still be dubious at best.
“Informed consent” doesn’t mean that it’s OK for a doctor to do anything to patients, as long as he asks consent and is very blunt and negative about the risks and benefits. I could tell a patient with a migraine that amputating his leg “might” help his migraine but has all the risks and downsides of an amputation, and even if the patient said yes it wouldn’t absolve me of having practiced bad medicine and behaved unethically. Now, using rituximab to treat CFS might not be as implausible as the example I just gave, but the same principle applies because we know so little about CFS that it is impossible even to estimate the plausibility. When we don’t know, the conservative and safe default is to assume it’s implausible until there is some good positive evidence to support its plausibility. Dr. Kogelnik appears not to have anything even close to that sort of evidence.
“Unmet medical need/desire” + something of marginal or nonexistent plausibility promoted as helping + [brave maverick doctor or charlatan] – proper informed consent = considerable use of [unproven or disproven] treatments
Commendable effort, David!
However, among other things, you don’t need the ongoing presence of a “[brave maverick doctor or charlatan]“. The vast majority of CAM use is enabled or triggered by either personal testimonial or the advice of laymen or other sufferers.
Line up all the quacks and shoot them, as per our oft-time mutual inclinations
, and patients and enthusiastic amateurs would simply carry on, sifting through medical history, the writings of Hulda Clark, Pauling, Revici, Gerson and whomever, and also the published medical literature for treatments to try out.
Very often also it is mainstream research, or a misreading of it, that stirs up “CAM” use. What doesn’t affect cancer in tissue culture, for example? Look at all those positive studies of glucosamine. It also requires some scientific gymnastics and niceties to completely dispose of the “positive” studies for treatment programs based upon acupuncture. Who can blame patients with difficult problems like chronic pain for wanting to try out methods that at least at first sight our own research seems to support?
See this, for example –
http://archinte.jamanetwork.com/article.aspx?articleid=1357513
“the same principle applies because we know so little about CFS that it is impossible even to estimate the plausibility. When we don’t know, the conservative and safe default is to assume it’s implausible until there is some good positive evidence to support its plausibility.”
Doesn’t that mean that no doctors would be allowed to provide ‘treatment’ for CFS outside of trials?
If this approach had been taken over the last 25 years, I think that we would now be in a much better place.
@mousethatroared:
“Yup, those discussions are not my favorite, either.
And it’s hard to find a blog that focuses on real nuanced discussions on skepticism in clinical psychology, a shame.”
Unfortunately, checking citations, trawling through data and explaining why certain statistical tricks are misleading doesn’t seem to make for the sort of easy reading people want for blogs. I’m guilty here too, as while I respect and read Coyne’s posts, I really don’t give them the attention and follow-up reading that they deserve. For something like CFS, where it’s harder to meaningfully measure outcomes, there’s little high quality research, and already a lot of animosity and distrust, it’s even less likely people would be willing to do this sort of work.
If you know anything about the pathophysiology of CFS, please share it! I was under the impression that there is still no well-accepted, well-validated etiology or pathophyisiology of CFS. How can we assume rituximab has any prior probability when you don’t know the cause? It’s like hypothesizing about the architecture of the alien civilizations on Alpha Centauri Bb. Certainly, given evidence supporting CBT and GET (problematic though it is) gives more prior plausibility to antidepressants than rituximab. CFS payments may find this objectionable, but science is about generating correct knowledge, not preserving feelings.
The comparison to Wakefield, whose motivation was probably in part greed, might not be apt – but there are also doctors motivated by a sincere desire to help patients that pushes them down the path of pathological science. Buzzwords are indeed part and parcel of actively fraudulent doctors as well since they can’t explain their treatments to their peers with real science and evidence.
@PernilleN:
Yes, it’s too bad that rituximab costs so much and that airfare is so expensive. People here travel to foreign countries for medical care, too, and it costs money.
In this country we have a tradition of allowing people to make their own decisions about how to run their lives.
As far as Fluge and Mella–the Norwegian researchers–they are signatories to the Open Medicine Institute’s research initiative:
http://openmedicineinstitute.org/research-initiatives/mecfs-merit/
I was never led to believe there was a close relationship, other than that they are in contact. I would assume they know OMI is treating patients with ritux. But I don’t see how they have any rights to contol its usage.
“I must say Kogelnik has a lot of nerve going against their advice. I’m sure he means well and wants to help, but what he is doing is still wrong.”
I think you have a lot of nerve by making these accusations. I’m sure you mean well and want to help, but what you are doing is still wrong.
Pernille reported that Fluge and Mella “have said very clearly that the drug should not be used outside clinical studies. ”
Of course they don’t “have any rights to control its usage” and no one ever suggested that they do. A bit of an over-reaction on your part, don’t you think? They did have the right to offer their advice, based on their interpretation of the evidence from their own studies. Kogelnik is going against that advice. Pernille offered her opinion that what he is doing is wrong. I agree. That’s what I said even before I was aware of Fluge and Mella’s specific advice.
I don’t think that indicates she “has a lot of nerve to make these accusations.” Now you have offered your opinion that Pernille’s offering her opinion is wrong. What are we to make of that?
@WilliamLawrenceUtridge:
I’ve already given a quite brief explanation of the rationale for the use of ritux and a citation about its pathophysiology. I realize this is in no way adequate but I’m really not the person to ask. It takes me a long time to respond and I have some other things to do. I’m lucky that I have the energy and focus to do anything.
I also suffer from major depressive disorder. Is there a well-accepted, well-documented etiology for that? I’ve taken a gamut of drugs running from Ativan to Zyprexa, including lithium, and received ECT. What about an explanation of how those things work? My treatment was essentially a series of throws to see what would stick, until something finally did. It took decades. Does anyone know about the long-term consequences of those drugs?
CBT? Don’t make me laugh.
In truth, all this fuss over unknown dangers and unknown effects and about physician responsibility and informed consent leaves me a little cold. The real world is quite a bit messier.
@irenef, May I ask, do you have a history of trauma, emotional or physical, either a single extreme incident or sustained abuse or neglect over a length of time?
@Harriet Hall:
Your objection to the interview revolves around a single clause involving semantic niceties that would not be meaningful to most people who watch the video. Dr. K also urges caution and says that the drugs are not to be used lightly.
I think Pernille is unduly concerned about what *other* people do and how they spend their own money. People have a tendency to do things we don’t like, but there are limits to the degree to which we can legitimately interfere, and I think both you and Pernille are wrong in making accusations of unethical and irresponsible behavior for which you have little more than hearsay evidence.
If the evidence we have is hearsay and is wrong, Dr. Kogelnik is welcome to join the comment thread and set the record straight. Apart from the apparent miscommunication (whether his fault or the fault of others), it now seems abundantly clear that he is treating patients outside clinical trials. That is not illegal and there is room for a difference of opinion. I doubt if a medical board would classify it as unethical, but I have explained why in my opinion I consider it not to be in the best interests of all patients in the long run.
Without the brave maverick doctor or quack, the patient has no way to get the unproven medicine.
@irenef, Did your doctor, Dr. K tell you that the Norwegian doctors who discovered that Rituximab may be useful for some ME patients also make it very clear to you that they said the drug should not be used outside of clinical trials, and did Dr. K explain in detail why this should be?
If he didn’t, then he is experimenting on you without providing you all of the relevant information so you can make an informed decision. He is misleading you. Lots of maverick doctors seem to misrepresent the initial research findings of others in this way – it gets patients in their offices who are desperate and willing to pay for expensive ‘cutting-edge’ treatments. Treatments, which have shown little evidence of efficacy and pose great risk to the patient, and mostly serve to line the pockets of the doctors and gain publicity for their practices among the ill and the desperate, thus bringing in more patients. In my opinion, it is the very definition of unethical and irresponsible medical care.
It’s certainly skirting the edge of unethical behavior and possibly going over.
@Sialis:
No, no history of trauma, abuse, or neglect.
Children raised in bad circumstances seem to have poorer outcomes overall, but I don’t think there’s any direct link to CFS, despite what the CDC has claimed. I don’t it was a good study.
But let’s not open that particular can of worms.
I just happen to have both MDD and CFS. The double whammy.
Do you think that most patients merely wake up one day and decide on their own to write a testimonial without any encouragement from the physician, their staff or their attorneys? Those testimonials serve to both advertise and gain protection for the doctor. I sincerely doubt that they are all whim decisions, letters of support written without any other hidden agenda. Certainly not in my experience.
@irenef, there was an announcement made by the FDA recently that they are changing the dosage guidelines for Ambien when used by women. They are now recommending half the dosage, as too many women apparently have slower metabolism of the drug. It is causing them to be over-medicated the next day. Sometimes doctors overlook the fact that the medications they prescribe could be causing some of their patients disabling symptoms. It seems to me that providers sometimes focus on what else is happening to a patient, rather than consider that their care, or lack thereof, could be the source of the problem.
@Sialis:
I don’t get the CAM quote. It didn’t come from me.
Are you insinuating that someone else is putting words into my mouth? You are wrong.
But I suppose I should be complimented in a way, because that means you think li’l old me couldn’t possibly have sufficient mental horsepower to say what I’ve said.
Ambien? I don’t take Ambien. I’ve experienced side effects from a drug that were overlooked by my physician. It was one of the reasons that I quit going to him.
Maybe I don’t have sufficient mental horsepower, because I feel like you’re expressing a concern that I’m not grasping.
@ David Gorski
“Without the brave maverick doctor or quack, the patient has no way to get the unproven medicine.”
This is absolutely not true. Rituximab may be pretty hard, or even impossible, to acquire and administer if a patient decides to self-medicate. However, many other drugs (antidepressant, anti(retro)virals, PDE-5 inhibitors, performance enhancing drugs etc. etc.) are easily obtainable through overseas pharmacies.
I just read a paper* about a 15 year old patient with anti-NMDA receptor encephalitis being treated with rituximab. There are couple more of these case reports and in this condition there are also no published and/or registred (pilot) trials. Is this also considered unethical and if not, why not?
* http://ajp.psychiatryonline.org/article.aspx?articleid=1555615
A decent chunk of the practice questions for my next round of board exams focuses on this issue. They set up a scenario in which something is wrong with the patient and ask you what the next best investigation is. The answer is “check for drug interactions or side effects.” From my perspective in studying for the boards, this seems to be harped on quite a lot actually. They don’t care that you know specifically which drug it is or what the interactions or side effects are, just that you should be looking for them. I think this is very good, since any idiot with a smart phone can pull up epocrates to check the interactions and side effects. But you need to think to take the phone out of your pocket in the first place.
@irenef: That quote was from someone other than you. I should have put their name in my comment. My other point, though not well made, was that sometimes patient’s symptoms are a result of their medical interventions, either the medications they are prescribed, or other medical treatments. I think those things are too readily dismissed by some physicians, perhaps especially those with larger egos. My assumption is that oftentimes those with chronic illness are on multiple medications. This in itself would pose a greater risk of drug interactions and more risk of side effects and adverse reactions. I don’t want to ask you what medications you are taking and I certainly wouldn’t expect you to post that online, nor am I licensed to offer an opinion on them. A lot of the symptoms you listed could be caused or exacerbated by various medications. I just urge you to examine them carefully and perhaps get a second opinion from a physician who is not associated with your current one – what about nybgrus? He sounds like a keeper to me. Get some sleep, dear.
@nybgrus, I think there’s more to it than remembering to look things up on epocrates, although that is indeed a good start. Look it up in front of the patient so they know that you care. It seems that sometimes the problem resides with the physician being able to admit that their patient, the one they are medicating is indeed experiencing an adverse reaction to the medications they prescribed. Some physicians sometimes have difficulty recognizing and/or admitting to their own prescribing errors, and seem under an outright gag order when it comes to speaking negatively about what another physician may be doing to a shared patient. Patients should be told straight up, “Your doc is a quack, and it’s specifically because of this and that”, instead they are likely told “You may want to think about getting another opinion sometime.” I also think some physicians have a hard time admitting to their mistakes, and as a result they take little action to correct them, mostly because they fear looking stupid or possibly being sued for the medical mistake.
@sialis:
Thank you for your concern. Drug interactions and side effects are something I think about because I’ve experienced them.
Nybgrus sounds like a nice fellow, reasonably intelligent, too. (I think he’s male, isn’t he?). I wonder if he wants to live in San Francisco.
I’ll be awake for another five or six hours. The night is young.
“The vast majority of CAM use is enabled or triggered by either personal testimonial or the advice of laymen or other sufferers.”
Do you think that most patients merely wake up one day and decide on their own to write a testimonial without any encouragement from the physician, their staff or their attorneys?
Yes. For all I know some of those on promotional web sites may have been solicited, but there are plenty of others on blogs, mailing lists and newsgroups.
Of course. I didn’t mean my comment to completely describe the situation.
And the whole “admitting errors” with patients is a big thing. Part of the ethics talk I will be giving to the new 3rd Year students as part of their orientation. I’ve been tasked with chatting about the new medical ethics resource and research project the hospital is doing and to encourage students to participate. I think it is a good idea, and I think we should always admit our error and admit when we don’t know something. This is an intentional and concerted effort on the part of both undergraduate and graduate medical education with mandatory training in systems models, ethics, and professional practice. Unfortunately there will always be those who blow it off or think it is stupid. But I think those are a fading minority and the culture shift of open communication and teamwork is well underway, which will put a lot of pressure on those of my colleagues who aren’t as considerate in these regards.
I can also speak anecdotally that many in my med school, and particularly the friends I keep, are very like minded. We plan on making our student society reflect these ideals which includes academic rigor as well.
I am a he. And thank you for the kind words.
San Fran is a possibility, though less likely. Not as much aerospace industry there for my significant other to pursue her career. Southern California is our long term goal, but Harvard/MIT is also on the radar for us.
We may also stay where we are for a bit as well.
Hopefully you will get some rest. I am off to bed shortly myself.
Harriet Hall said
“It has certainly not been established that CFS
symptoms can be attributed to B cell abnormalities ”
Have you read this paper, Altered fictional B-cell subset populations in patients with CFS compared to healthy controls
A.S.Bradley
B.Ford
A.S.Bansal
http://onlinelibrary. wiley.com/doi/10.1111/cei.12043/abstract
I don’t have institutional access to that journal so all I could read is the abstract, however this does not establish that CFS can be attributed to B cell abnormalities.
The study was small (33 CFS and 24 health controls) and noted a few differences in B cell sub population proportions between the two groups. The authors themselves do not know know the significany (i.e. if there was literature to support a tentative hypothesis as to what this means or why, they probably would have mentioned it).
It is a curious hypothesis generating study but nothing more. Larger studies need to be done to verify the findings of this one. It does not justify the experimentation of ritux with CFS in any manner (from a purely scientific prior plausibility standard) let alone as off label use.
You can contribute toward the larger studies that everyone agrees are essential:
http://openmedicineinstitute.org/foundation/mission/
I’m pretty sure there is no evidence that Lyme disease is a neuro-immune disease (save the already well described neurological sequelae such as Bell’s palsy). This seems suspicious of the “chronic Lyme” syndrome which has been discussed here at SBM numerous times.
@nybgrus:
Beats me. I know very little about Lyme. We were discussing CFS.
@irenef:
It was a critique in that chronic Lyme is a “brave maverick doctor” diagnosis that has no supporting evidence and plenty against it. The inclusion in the list on the mission statement of OMI is a red flag in my skeptical mind.
@nybgrus:
You could be right. As I mentioned before, I don’t care for the website. It hasn’t been up very long. Further discussion of it just seems like a tangential discussion that would yield more heat than light.
@irenef:
Indeed. A red flag doesn’t mean anything by itself. Smoke usually means fire but not always. But in context of the post here, it seems relevant.
From the paper
“‘Over the last decade we have observed an elevated prevalence of persistent fatigue in our patients with primary antibody deficiency and speculated on subtle B cell dysfunction.”
Importantly, Rituximab does not simply deplete CD20+ cells (B-cells) but has many mechanisms, including down regulating CD40L and GR80 on B -cells, decreasing CD4 effactor cells ,reducing NK cell numbers and activation, including macrophage maturation and reducig TNF alptha secretion and increasing the suppressive function of T regulatory cells [11]. However, the onset of B -B-cell depletion did correlate with reduction in symptoms and with the expected appropriate lag phase.
So it might be more involved than simply depleting B-cells, though that seems to be,an important aspect.
“Defective antibody class switching and antibody production would result in recurrent infection as seen in primary immunodeficiency states; however a milder defect may lead to inappropriate immune response and possibly autoimmunity”.
Suggesting that autoimmunity may be a milder result on a spectrum that also includes immune deficiency.
“Thus CFS patients may have some unusual, unrecognized autoimmune disease, or it is possible that CFS patients are unable to control lymphotrophic viral infection due to some defect of B-cell memory or T-cell dysfunction”.
Also talks about auto-reactions B-cells usually getting destroyed when they are made and speculate the we might have a problem with that destructive process
B cells can become either follicular B cells or marginal zone B-cells. Follicular B-cells might become plasmablasts of memory B cells, but the marginal zone B-cells always become plasmablasts
“One explanation for reduced plasmablasts in the CFS cohort is that increased numbers of transitional B-cells and naive B-cells may overwhelm the B-cell maturation process, which may consequently become suboptimal. Alternatively T-cell help provided by cytokines may not support naive B cells to develop into plasmablasts”.
They are interested in studying the B-cells before and after Rituximab use, to see how that alters B cell populations
. They are also interested in whether severe patients have more extreme results since they were just studying moderate cases where some immune symptoms were only intermittent.
“In conclusion we have observed patients with moderate CFS to have increased proportion of transitional and naive B-cells and reduced
plasmablasts. The precise basis for these findings is unclear and our work does not allow clarification of whether these changes are cause of the CFS symptoms or the result of patient inactivity
, sleep disturbance or raised stress, therapeutic response to Rituximab suggests that B-cells are some how involved in the pathogenesis or perpetuation of CFS symptoms”
“The precise basis for these findings is unclear and our work does not allow clarification of whether these changes are cause of the CFS symptoms or the result of patient inactivity, sleep disturbance or raised stress…”
Our point exactly! The research “does not establish that CFS can be attributed to B cell abnormalities.”
Dear Harriet
It is in fact quite common for doctors who specialize in treating ME/CFS patients to take an experimental approach.
This is because it is the unfortunate case that most scientists find research into ME/CFS just plain boring and unsexy, and as a consequence, the whole field is underfunded and neglected. So to an extent, this shifts the task of ME/CFS research and experimentation to clinicians.
Very few scientists ever dedicate their careers to studying ME/CFS. Even my own primary care doctor intimated to me that “nobody in the medical profession seems at all interested in ME/CFS”. I am an ME/CFS patient myself, incidentally.
Perhaps you might consider writing a new article specifically examining why scientists on the whole find research into ME/CFS boring, and why so few talented minds go into this field. This is the crux of the problem ; it is why there are no real treatment advancements for this life-robbing disease.
I actually had an idea about writing a booklet summarizing the fascinating mental and neurological aspects of ME/CFS, written in such a way as to demonstrate that ME/CFS is a deeply intriguing phenomenon.
My idea is that if you present the fascinating facets of ME/CFS in a way that engages the imagination of scientists, you might start getting more talented researchers dedicating their energies into unravelling the mysteries of ME/CFS.
Just a few of the fascinating facets of ME/CFS are as follows:
One particularly intriguing phenomenon is the significant overall lowering of consciousness and dulling of awareness you experience as a patient with ME/CFS. This reduced consciousness is called cognitive dysfunction, or more colloquially, “brain fog”. Brain fog makes you do all sorts of funny things. One ME/CFS patient I know actually forgot her own name when she was asked for it, due to brain fog, and had to get her husband to tell her what it was! Why does this brain fog occur in ME/CFS? Nobody really knows. Too few people have investigated it.
As a postgraduate, I actually studied cognitive science before I developed ME/CFS (from a respiratory virus), and during my studies I was particularly interested in the nature of consciousness. It seems to me that a disease like ME/CFS, in which there is a dulling or weakening in consciousness, might be a useful area of study for furthering the understanding of the phenomenon of consciousness.
Another intriguing symptomatic aspect of ME/CFS is the loss of the ability of the brain to filter out irrelevant or repetitive stimuli. In a normal healthy person, if for example they hear a car alarm go off down their street, at first this new noise rouses their consciousness attention, but then they soon forget about it, and after a few minutes, it does not really enter consciousness anymore. The technical name for this filtering out of repetitive stimuli is called habituation. Habituation acts to filter out repetitive stimuli, in order to prevent overloading of consciousness awareness with irrelevant information. In ME/CFS, repetitive noises such as car alarms can be extremely aggravating, because the brain is no longer able to properly habituate to repetitive noises, and so the noise is not filtered out, and thus deeply impacts into consciousness, becoming highly unpleasant an intrusive. Why does this happen in ME/CFS? Nobody really knows.
I also find it fascinating that language skills are significantly hit in ME/CFS patients. People with ME/CFS often develop “tip-of-the-tongue” word recall problems, grammatical problems, decreased spelling abilities, loss of vocabulary, and so forth. Why is language affected in this way? Nobody really knows.
And of course a defining characteristic of ME/CFS is the intriguing phenomenon where physical or mental exercise will quickly and dramatically worsen all ME/CFS symptoms. Why does this happen? Nobody really knows.
So in fact ME/CFS presents a fascinating array of strange symptoms. I cannot really understand why talented medical researchers choose not dedicate their careers to studying ME/CFS.
Perhaps you will take up my challenge of writing an article that tries to throw more light on why this is the case.
“I cannot really understand why talented medical researchers choose not dedicate their careers to studying ME/CFS.”
I can. It’s a controversial area, there is no test for CFS, it’s difficult to pin down who has it and what to study, there are more promising ways to spend research time and money, it’s perceived as a career-buster, discussion of CFS is overrun with emotion, etc. etc. Some medical researchers “have” dedicated their careers to studying CFS, with disappointing results. Edward Shorter’s book “From Paralysis to Fatigue” and “Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome” by Hillary Johnson shed a lot of light on the subject. The history of medicine is full of diseases with changing names that all involve “a fascinating array of strange symptoms,” and many of those symptom complexes have come and gone according to societal perceptions (“fads”). It would probably make more sense to study that spectrum, in the light of history, rather than just what is currently designated CFS. My personal guess is that we will eventually learn that a few patients with an objective disease are being lumped together with a lot of people who have somatoform disorders and psychological problems. Until that can be sorted out, research just adds to the confusion.
HH “My personal guess is that we will eventually learn that a few patients with an objective disease are being lumped together with a lot of people who have somatoform disorders and psychological problems. Until that can be sorted out, research just adds to the confusion.”
How can you sort it out without research?
As to cognitive dysfunction or “brain fog” – This is also a feature in some diseases and processes, Thyroid disease, Lupus and other systemic autoimmune diseases, menopause, anxiety and depression are the one’s I know off the top of my head. From my reading (which is limited to a laymen’s understanding) it doesn’t seem well understood in any of these cases. Bummer.
@ Yikes, I must read more thoroughly. Thanks for the note way up there that Retuximab is an accepted RA treatment. I read this blog early in the morning at the start of the coffee ritual and I’m not sure my brain is fully awake.
“How can you sort it out without research?”
First you need to do the necessary research to find out if CFS really exists as a definable entity. Current research jumps the gun, accepts the diagnosis, and goes on from there.
“brain fog” is undefined. Anyone who doesn’t feel well or is depressed can experience it. Tests for cognitive dysfunction are problematic because they are effort-dependent. If you aren’t motivated to try as hard, you don’t test as well. And many CFS patients are defensive and want to prove they are objectively sick. Not to say it can’t be studied, but studies will require very careful methodology to rule out all the confounders.
@IreneF wrote: “I think Pernille is unduly concerned about what *other* people do and how they spend their own money.”
One of the reasons SBM exists, is that many people spend a lot of money for useless and/or dangerous treatments, whether the treatments are provided by well-meaning CAM practitioners, doctors, nurses or not-so-well-meaning charlatans. The doctors who write this blog are concerned both about misrepresentation and misinformation of medicine and science, and about sick people who buy into useless and/or dangerous treatments.
Do you also think their concern is “undue”?
Re Fluge and Mellas advice (which they have said publicly, I don’t know what they’ve said to Kogelnik, if anything), and the fact that Kogelnik goes against that advice … what kind of accusation have I made? I said he has a lot of nerve, and that I think what he’s doing is wrong. That’s an opinion, not an accusation.
I thought people in your country believe in freedom of speech?
About people here having opinions based on hearsay: If OMI were open about their research and practice, and it was possible to find information on their website, we didn’t need to speculate. But they don’t. There’s no information about ongoing projects or treatments, they haven’t registered their projects in clinicaltrials.gov so we could see their protocols, and the information given in the Youtube videos is at best vague. I must confess I haven’t seen all of them, I want to read about research project, not watch them on TV. But judging from what other people say, there’s not much specific information to be found there.
Regards
Pernille Nylehn
Dr. Hall and others, given the absence of effective treatments and definitive diagnostic tests, and while more defined medical studies are on-going, what are your thoughts on having diagnostic and treatment centers that are organized in a roundtable fashion where the patient would meet with specialists from several different fields simultaneously for their initial evaluation and periodic follow-ups? One physician in the group would be assigned as the primary care provider, and oversee their treatments, but otherwise, the patient would be seen by a panel of appropriate specialists. For example, a patient with chronic, disabling symptoms diagnosed as CFS or FMS might have diagnostic/treatment interviews with a panel consisting of a neurologist, rheumatologist, infectious disease, pain management, allergy/immunologist, physical therapist, psychologist, and pharmacologist, with one of them being assigned as the primary care provider.
In my experience, despite their training and experience, many physicians do indeed overlook or misdiagnose various symptoms. They do indeed dismiss valid symptoms of disease or effects of medications as mental health problems. I feel this is especially true for female patients, unfortunately, but I could be biased with this thought. The misdiagnoses and oversights are understandable in many cases, as physicians are only human and they’re likely overworked, short on time and unable to devote enough follow-up time as is needed for the more time/resource-consuming, chronically ill patient.
I’ve too often seen where a classic symptom(s) is overlooked by what should have been the appropriate expert, and is instead realized much later by the patient or another physician of another area of expertise. It seems to me it would be helpful if everyone were in the same room at the same time and looking at the same things (the patient and a complete set of records and films). The physicians would all hear the same description of the symptoms from the patient, they could each ask questions and all hear the responses, and thus engage in meaningful roundtable discussion of the possible causes and treatments.
In the above scenario, if various specialists requested testing or other assessments, those tests could be ordered by the primary care provider, who would distribute the results to each panel member for review prior to the next roundtable follow-up appointment. It seems to me that better communication amongst providers would eliminate a lot of miscommunication, misdiagnoses, unnecessary testing, and careless and unnecessary prescribing, which all too often happens, in my experience.
Sialis – I’m not sure if you are aware of this, but your suggestion is similar to the Cleft Clinic model recommended for all children with Cleft Lip and Palate. My son has an annual appointment were he is examined by the Plastic Surgeon, Audiology, Pediatric Neuropsychologist , Speech Therapy, Nutrition Expert (I always forget the title), Reps from Maxillofacial Surgery, dentistry and orthodontics. The team has a group of patients for each clinic day and then goes through all the records in the afternoon and hashes out all the recommendations so that the applicable specialists are in agreement. It’s great. I will say that there is not alot of unnecessary prescribing for CLCP (that I know of) but clearly unnecessary or poorly timed surgery, therapies or dental/orthodontics are concerns that this model deals with. So maybe there is enough similarity to use that plan as a model.
As an aside, we don’t get a round table discussion with the Cleft Clinic, but we do get a report after the clinic with the recommendations from the team, signed off on by the whole team.
@sialis,
A multidisciplinary team is ideal for many conditions, especially chronic pain; but applying the concept to CFS might be problematic. It would serve to rule out other diagnoses, pick up on other conditions that could be treated, etc. But it might result in unnecessary tests being ordered (each specialist would have his favorite things to pursue) and it might increase the patient’s conviction that something is objectively wrong that is still being missed. There is something to be said for a single physician to gain the patient’s trust, do reasonable rule-out tests and when nothing is found, reassure the patient and enlist the patient’s cooperation in useful therapies like exercise and psychotherapy. With the present state of medical knowledge, instead of going on a wild goose chase for an elusive explanation, it probably makes more sense to accept that we just don’t know and to concentrate on helping the patient live with the illness and build strengths to cope and improve quality of life. While keeping an open mind, of course.
This is actually a common situation in primary care. For a patient with irritable bowel syndrome (IBS), I might tell him we couldn’t find anything structurally wrong with his bowel, but bowel functioning that is within the normal range seems to sometimes cause distressing symptoms for some people who are unusually sensitive or reactive. I might tell him we had done all the reasonable tests to rule out serious life-threatening causes and any further testing would be only likely to do more harm than good (for instance, we could do exploratory surgery and look around in his abdomen, but that is risky, unpleasant, and very unlikely to change our plan of management). I might praise the coping skills he was already using. I might tell him medical science couldn’t cure his problem, but it could do a lot to help him live with it. I could offer him understanding, sympathy, and support. And I would stress that we would be constantly monitoring new research and would quickly respond if any new symptoms developed (or changes in old symptoms) that might mean the situation had changed and that further testing was now indicated.
I’ve written a couple of articles on related subjects:
http://www.sciencebasedmedicine.org/index.php/not-treating-a-neglected-option/
http://www.sciencebasedmedicine.org/index.php/overdiagnosis/
Science-Based Medicine » Rituximab for Chronic Fatigue Syndrome: Jumping the Gun
Quoting Harriet: “It’s a controversial area, there is no test for CFS, it’s difficult to pin down who has it and what to study, there are more promising ways to spend research time and money, it’s perceived as a career-buster, discussion of CFS is overrun with emotion, etc.”
Yes, this is all true, and I can see how these background circumstances of ME/CFS could discourage the average scientist, or a scientist who sees his profession not as a vocation, but merely as a job. However for a scientist with idealism and talent, that should not be an insurmountable problem. Brilliant minds are often more motivated by intense scientific curiosity of their chosen area, rather than career realpolitik. I still suspect that the main reason researchers avoid ME/CFS is that many find the field boring, for some reason or another.
Though given that you do appreciate the difficulties of attracting anyone to work in the ME/CFS research field Harriet, shouldn’t your views on experimental clinicians like Dr Andreas Kogelnik be little less critical? Or even to a degree understandingly supportive? In ME/CFS, there are often no other avenues of treatment research outside the efforts made by these ME/CFS clinicians. Imperfect I know, but it is all there is.
Quoting Harriet: “My personal guess is that we will eventually learn that a few patients with an objective disease are being lumped together with a lot of people who have somatoform disorders and psychological problems. Until that can be sorted out, research just adds to the confusion.”
You talk of somatoform disorders as if they were an evidenced-based, scientific concept. Perhaps your skills in identifying scientific fallacies and logically flawed concepts is not quite up to scratch?
The flawed foundations of the somatoform disorder concept are based on the idea that if you cannot find a physical cause for a disease, then the disease may be somatoform. Yet there is no way to positively prove that a disease is somatoform; or even prove that somatoform disorders exist at all. So as a concept, it fails on the verifiability requirements of science. In fact, in principle any currently unexplained illness could be classed as somatoform, by the flawed axioms of somatoform disorders. Diabetes, for example, could have be considered somatoform before its physical causes were found.
In my view, there is not all that much difference between the somatoform disorder concept of disease, and the Medieval concept of malevolent spirits causing disease. Indeed, the efforts of Simon Wessely trying to convince the us that diseases like ME/CFS, irritable bowel syndrome and interstitial cystitis are all somatoform are more akin to pre-scientific Medieval evangelizing than 21st century critical thinking.
Quoting Harriet: “First you need to do the necessary research to find out if CFS really exists as a definable entity.”
Well what about depression and schizophrenia? Do we also need to find out if these exist as a definable entities before we do anything to alleviate the misery and suffering of these conditions? There are certainly no accurate objective tests for these conditions, just as there aren’t (yet) for ME/CFS, but that should not stall research into treatment.
Making ME/CFS into a more precisely definable entity would only take all researchers adopting the same inclusion criteria. The strict and precise “Canadian consensus definition” of ME/CFS has been favored by the more neurologically included researchers. However, the more sloppy “Oxford definition” (so sloppy in fact that it tends to select depressed people, as well as those with ME/CFS) is often favored by psychologists. This sloppiness of definition why a lot of the ME/CFS research performed by psychologists is flawed.
Quoting Mousethatroared: “As to cognitive dysfunction or “brain fog” – This is also a feature in some diseases and processes, Thyroid disease, Lupus and other systemic autoimmune diseases, menopause, anxiety and depression are the one’s I know off the top of my head.”
Very true, and that makes brain fog all the more intriguing. It might well be that the biochemistry of brain fog is the same in all these diseases, in which case, studying one disease may help understand brain fog in all.
In particular, the fact that brain fog in hypothyroidism is cured simply by giving the patient T4 (and sometimes also T3) thyroid hormone replacement means that the conditions under which this brain fog arises are very clearly defined — and this clear-cut case should help uncover the biochemical mechanism of brain fog, if some researcher took interest in it.
I don’t think it’s fair to compare CFS to depression and schizophrenia. They have been recognized for centuries and their manifestations have not changed. CFS may be something new… or it may be an old condition dressed up in new clothes.
It’s really illuminating to read the two books I listed above. There is a long history of classifying unexplained symptoms as everything from a “wandering womb” (hysteria) to “neurasthenia.” At different times in history, patients have manifested paralysis, fits, and other behaviors that were expected and accepted in their society. It wasn’t acceptable to say “I’m too fatigued to function” but it was acceptable to suffer from paralysis or to collapse with bizarre stereotypical fits. As customs changed, the paralyses and fits fell out of fashion and we don’t see them any more. It is abundantly clear that they did not have a definable underlying pathology.
Hip – “In particular, the fact that brain fog in hypothyroidism is cured simply by giving the patient T4 (and sometimes also T3) thyroid hormone replacement means that the conditions under which this brain fog arises are very clearly defined”
Yes, it’s often presented to me by doctors as clearly defined, but then you have studies like this –
http://www.medscape.com/viewarticle/760417_2
@Hip – sorry, this would have been the better link.
http://online.liebertpub.com/doi/abs/10.1089/thy.2010.0191
Quoting Harriet: “There is a long history of classifying unexplained symptoms as everything from a “wandering womb” (hysteria) to “neurasthenia.” At different times in history, patients have manifested paralysis, fits, and other behaviors that were expected and accepted in their society. It wasn’t acceptable to say “I’m too fatigued to function” but it was acceptable to suffer from paralysis or to collapse with bizarre stereotypical fits. As customs changed, the paralyses and fits fell out of fashion and we don’t see them any more. It is abundantly clear that they did not have a definable underlying pathology.”
The altering array of symptoms manifested in neurasthenia and ME/CFS-like illnesses throughout history is interesting, and these changes do require an explanation. Though the explanation offered by certain psychologists — that manifested ME/CFS symptoms change according to the social customs and fashions of the era — seem absurd and untenable. After all, we do not see the physical symptoms of any other disease vary according to expected and accepted customs.
I think the very idea that disease symptoms are culturally conditioned reflects the unfortunate tendency of certain schools of psychology to concoct over-embellished explanations for phenomena, with scant regard to the scientific method, which requires that explanatory theories be testable.
There is a simpler and more plausible explanation for this variation in ME/CFS symptomatology over history, which is as follows.
As is well-known, there is considerable evidence suggesting that ME/CFS has an infectious etiology, at least in part.
Certain subsets of ME/CFS actually have a proven infectious cause: Chlamydia pneumoniae, Coxiella burnetii and parvovirus B19 infections are all proven — and largely treatable — forms of ME/CFS. So we know for sure that infectious pathogens can be a cause of ME/CFS symptoms.
Outside of these proven infectious causes, the majority of cases of ME/CFS are of unproven etiology. However, these unproven etiology cases are often noted to follow an acute infection of some sort, which suggests that the cause may also be infectious. Indeed, one virus that for many decades has been associated with these unproven etiology ME/CFS cases is enterovirus. Recent work by Dr John Chia has show that in 82% of unproven etiology ME/CFS cases, patients have enterovirus protein in their tissue biopsies, compared to just 20% in healthy controls.
As you are undoubtedly aware, in the Enterovirus genus itself, there are dozens of different enteroviruses, each causing different symptoms, with some non-polio enteroviruses capable of causing transient paralysis. The other interesting and pertinent thing about enteroviruses is that they tend to appear in epidemics: a given enterovirus will remain in circulation for some years, and then disappear again for many years. (Not all viruses behave like this; EBV for example never follows this epidemic behavior.)
So in my opinion, the most likely explanation for the variations in ME/CFS symptoms over the centuries is simply that in different eras, you get different infectious pathogens appearing in epidemics, and the precise symptoms of ME/CFS will depend on the particular pathogen or pathogens causing ME/CFS in each era.
In eras when paralysis formed part of the typical ME/CFS symptoms, I suggest this was because at that time, ME/CFS was being triggered by an epidemic of a virus that was capable of causing paralysis. The alternative idea that paralysis was precipitated merely by cultural expectations seems absurd to me. Transient paralysis sometimes occurs in ME/CFS even today (but it is rare), a fact which supports the argument that paralysis is not a symptom determined by the behavioral fashions of an era, but depends on which particular virus you catch, and of course how your body responds to that virus.
Conditions like depression and schizophrenia have been linked to infectious agents as well, sure, but they are not generally observed to manifest after a trigger infection as ME/CFS often does. By comparison, ME/CFS etiology has a much stronger link to infectious agents, and so you might expect that the nature of this disease will depend much more upon the particular infectious agents in circulation in each era. Depression and schizophrenia are probably more genetically determined, and this is the likely reason that their manifestations do not change much over time.
I’m not familiar with all the nuances of symptoms which would warrant a diagnosis of CFS/ME or FMS, so it is rather difficult and likely inappropriate for me to offer an opinion as to the best type of treatment approach. I do believe that a multidisciplinary team approach, at least for diagnostic purposes, would be best for patients with medically unexplained symptoms, especially those which are significantly impacting their quality of life by either being disabling and/or progressing.
Doctors aren’t perfect, and the practice of medicine is not always suitable to a cookie cutter approach. It seems that with the more complex, unexplained illnesses a single primary care provider arrangement may not always be best suited to the patient’s needs. Although I wouldn’t necessarily consider them as quacks, there are a lot of primary care and other physicians who seem to hold opinions which are not evidence-based, or are perhaps older approaches that have long since been disproved. Just as patients may be easily duped into believing that acupuncture or NAET, or various untested herbs may offer significant relief, so do too many physicians. Others seem to fear treating any symptoms when they don’t know the specific cause. This leaves those patients suffering and with little treatment options. It is no surprise to me that many turn to alternative providers out of sheer desperation for some relief of symptoms.
I do feel that patients with unexplained symptoms are too frequently dropped into the CFS/FMS category. Illnesses with objective and observable yet non-specific symptoms are being dismissed into this CFS/FMS category. Furthermore, I think certain SBM physicians, including nybgrus, are perceptive enough to understand how easily patients may indeed be duped (sounds so much better than being made a fool) by certain types of providers, especially those who are relentless in advertising their treatments with misleading information. Patients should be better educated as to the placebo effects as is being discussed here on SBM, but so should physicians. I doubt that most patients understand why they may be feeling a bit better, or think that they feel better, after certain treatments such as acupuncture. It seems too many physicians are either unwilling or unable to explain such effects to their patients. I don’t know why. Uneducated people desperate for relief are most easily fooled. It is unfortunate that there are so many practitioners ready and willing to pounce on such needs and misrepresent the cause, effects and benefits of relatively useless treatments.
In any case, I am of the impression, and quite possibly an incorrect one, that CFS/FMS are not progressive illnesses, nor do they effect specific body parts consistently and significantly more than others, such as the lymph nodes and salivary glands of the head, neck and under the collar bone, or the intercostal cartilage. On the contrary, CFS and FMS seem like they cause more wide-spread pain of basically equal proportions throughout the body, although the focus of pain may vary from day to day. I could be completely wrong, as I am certainly not a specialist in this area, but those types of conditions are also being diagnosed as CFS/FMS. Patients with symptoms such as these should not automatically be dumped into the CFS/FM category.
@Harrit Hall:
“The history of medicine is full of diseases with changing names that all involve “a fascinating array of strange symptoms,” and many of those symptom complexes have come and gone according to societal perceptions (“fads”). It would probably make more sense to study that spectrum, in the light of history, rather than just what is currently designated CFS. My personal guess is that we will eventually learn that a few patients with an objective disease are being lumped together with a lot of people who have somatoform disorders and psychological problems. Until that can be sorted out, research just adds to the confusion.”
Historical fads are interesting, but it’s difficult to diagnose people after they are dead and gone. Vocabulary changes, too; “soldier’s heart” is nowadays called PTSD. (I always wondered what Dostoyevsky meant by “brain fever”.) Perhaps all those Victorian neurasthenics really did suffer from CFS; maybe some of them had pernicious anemia, MS, or chronic low-level infections.
The somatoform disorders have case definitions that differ from case definitions of CFS. So do psychological problems.
“. . . research just adds to the confusion.”
What you are implying is that CFS is not a “real” disease because there is no diagnostic test for it. Do I really need to remind people that absence of evidence is not evidence of absence? It seems as if your underlying objection to medical treatment of CFS patients is that we are not really sick.
And how could research add to the confusion?
Women in the 19th century had bizarre fits and paralyses and strange behaviors that bore no resemblance to anything reported by CFS patients, and that have gone out of fashion and no longer occur. Other well-described patients in history manifested the same nonspecific symptoms as CFS patients, and there have been many different names and explanations for those symptom complexes. Trying to study “neurasthenia” or “hysteria” were not productive avenues of research. I am not implying that CFS is not a real disease or that patients are not really sick, I’m just pointing out that once-popular diagnoses have vanished, and others have been re-categorized, so we need to be very careful to define what is being studied. I think most of us would agree that at least some CFS patients are misdiagnosed. Research adds to the confusion when multiple poorly defined conditions are lumped together and research looks at the lump rather than the components.
Incidentally, Da Costa’s “soldier’s heart” was very different from PTSD. See http://en.wikipedia.org/wiki/Da_Costa%27s_syndrome and http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001923/
There is some overlap of symptoms, but not enough to confuse the two diagnoses.
There is a germ of an idea in your objection, that people who have psychologically-based diseases are not really sick, that CFS must have a biological cause, and that if it doesn’t it’s somehow less worthy for respect and treatment. I agree that society in general is not very good at treating, dealing with or understanding mental illness or psychological suffering. I agree it is hard for psychogenic conditions to get respect, despite how profoundly miserable they can make sufferers. I can see why CFS patients object to any psychological attributions for their condition.
That does not mean that CFS has a biological cause for all patients. There is a very good case to be made that CFS has, for some patients, a purely psychological cause. Again, with a wastebasket diagnosis, it’s nigh-impossible to tell.
I’ve only just now read through in detail the last few comments. The first thing I’d like to clear up:
Firstly, thank you for the kind words. But more importantly, I am not a physician. I am currently in my 4th (last) year of medical school and will graduate as a physician this year. I will still have my residency training and then fellowship after. I apologize if I unintentionally gave the false impression that I am already a physician, let alone a trained one. I use terms such as “my patients” or “our patients” since I do, in fact, see patients and help manage their care in the course of my rotations. I also feel like they really are “our patients” since I am indeed soon to be a physician and I fully believe in the teamwork model of patient care.
I also agree with Dr. Hall and WLU – psychiatric/psychological illness has an unfair and unreasonable stigma surrounding it. Those with psych disorder/disease are truly suffering just as much as someone with organic disease. I believe that at least a big part of this stigma comes from the religious notion of a mind-brain duality with a soul being the seat of free will and cognition. Thus if it is “in your head” it is somehow not only divorced from your physical self but also changeable at your whim, thanks to the fact that you have free will. Both notions (duality and free will) make no sense in the modern neuroscientific era. But the stigma persists.
Lumping together a number of different conditions with different underlying etiologies but similar manifestations is indeed counterproductive. I have argued here that depression is an excellent example of this. If one looks at the various treatments for depression, how well they work (and don’t work), how much crossover there is, and the evidence for improvement from doing nothing in certain cases, the only reasonable conclusion is that the entity we call “depression” has a number of differing etiologies. The fact that this is the case, but it is all researched as one entity based on the neurotransmitter hypothesis has lead to a slew of attacks against psychiatry in general and anti-depressant medications in specific since, as we know, each drug only seems to help about 60% of people. This is also likened to the efficacy from talk therapy which becomes called a placebo and thus justifies attacks on neuropharmacotherapy. I have argued before that talk therapy is not placebo, but I won’t get into exactly why now. The reality is that the most reasonable explanation is at least 2-4 underlying etiologies all manifesting as “depression” getting lumped together. We simply don’t have the technological sophistication nor the detailed understanding to have a higher resolution of the underlying etiologies to target treatment better. So we must do trial and error. Which leads to disparaging comments and often patient despair since after the 2nd or 3rd failed attempt they feel we don’t know what we are doing (which is actually partially true).
That doesn’t mean we shouldn’t study depression or CFS/ME. It just means that we should learn our lesson and first focus on a more rigorous definition and diagnostic criteria before attempting to do clinical trials to treat, since otherwise we are inevitably lumping together disparate underlying etiologies and that will dilute our ability to actually determine what treatments work for specific subsets of CFS/ME. We may find a fantastically useful treatment for a particular subset, but because we have lumped in a different one with a different etiology, the results could look borderline or even negative. We then discard the attempted treatment (or it becomes maligned by some and overused by others like anti-depressants) at great disservice to that subset of CFS/ME patients.
It also leads to so many different causes fighting to be the cause of CFS/ME. Like the virus induced hypotheses. I have no doubt that is actually a subset. How big a subset? How to treat? Prognosis? Completely obfuscated by the catch-all nature of the diagnosis. The same goes for psychogenic etiologies, etc.
I believe this is what Dr. Hall has been saying. It sucks, to be sure. But such is the nature of science and the slow, but steady, progress it entails.
Nonspecific symptoms are ubiquitous. It’s called “being human.” See http://skepticalmothering.com/2013/01/16/do-you-have-forers-disease/ That’s why it’s so difficult to study diagnoses that depend largely on such symptoms.
“Non-specific” was a poor choice of words on my part. What is the proper term to describe a specific recurring symptom which is not indicative of a particular or specific disease process – Such as these transverse nail ridges, and given that they are not caused by nail bed trauma or diabetes. http://en.wikipedia.org/wiki/Beau%27s_lines
http://dermatlas.med.jhmi.edu/image/Beau_Line_1_040130
@nybgrus- You comment that 60% of people appear to be helped with anti-depressants and
“That doesn’t mean we shouldn’t study depression or CFS/ME. It just means that we should learn our lesson and first focus on a more rigorous definition and diagnostic criteria before attempting to do clinical trials to treat, since otherwise we are inevitably lumping together disparate underlying etiologies and that will dilute our ability to actually determine what treatments work for specific subsets of CFS/ME. ”
Is there evidence out there that any of the currently approved anti-depressants work on 60% of patients? The studies I have read indicate that the percentages are much lower; therefore using the current crop of anti-depressants on patients is potentially unethical since the side effects will usually outweigh the null positive effects. And despite the lack of rigorous definitions for depression, recent studies on ketamine have been showing incredible promise. As far as I have read, this is primarily based on patient self-reports. Because major depression is considered such a dangerous disease, researchers have been prepared to try different treatments and then figure out the mode of action. Early evidence indicates that NMDA receptors are much closer to the root of some (likely most) cases of depression than serotonin receptors.
Should researchers not try different drugs on depression because we aren’t good at breaking down subsets and root causes?
IANAD, but that’s my understanding of “non-specific” exactly – the symptom is not specific to any particular disease. It doesn’t mean “inexactly specified” in this context.
So “fatigue” is an exact symptom. But it is characteristic of many different conditions, so it is still “non-specific.”
I’m sure Dr. Hall will correct me if I am wrong.
“Ubiquitous” is defined as found everywhere or constantly encountered. I would consider fatigue, low back pain, headache, muscle soreness, etc., as ubiquitous. This particular non-specific symptom of transverse nail lines is not so common as to be found everywhere. It is not a common finding in general, and certainly most physicians do not easily or readily recognize it in my experience.
One would of course have to consider such symptoms in conjunction with the patient’s other symptoms. Transverse ridges, granuloma annulare, muscle tremors and spasms and fasciculations, ‘burning’ sensation of all salivary glands and lymph nodes throughout the head, neck and under the collar bone, plus severe intercostal and ‘neck’ pain, and biopsy diagnosed significant small-fiber neuropathy. In combination, are these symptoms considered ubiquitous, non-specific and “being human”? Moreso, and if so, would and should they be considered as deserving no treatment, not even palliative care? And what care, if any?
@Scott,
““fatigue” is an exact symptom”
Not really. I would call it both non-specific and inexactly specified. It depends on self-reporting, varies with patient perception of whether it is severe enough to report, and is really pretty nebulous.
Compare to nausea and vomiting. Vomiting is an exact symptom: emesis can be witnessed and measured. Nausea? We have to rely on the patient’s report of how he feels. What may be minor queasiness to one person, easy to disregard and not worth complaining about, might be reported as significant nausea by another person. And the self-reporting of one patient may change from moment to moment depending on distraction, emotional state, and other factors.
It is interesting that in the Wikipedia articleof the above mentioned Da Costa’s syndrome, it says that Da Costa noted that this condition often developed and persisted after an initial bout of fever or diarrhea.
Now, the occurrence of fever or diarrhea tends to indicate that an individual has contracted an infection. Since in recent years, diseases of unknown etiology are being increasingly linked to infectious agents, one might read Da Costa’s observations as a clue that Da Costa’s syndrome was in fact precipitated by a chronic infection, rather than a somatoform disorder.
To me, designating a disease as a somatoform disorder is the ultimate wastebasket and waste of time etiological description.
Scott,
““fatigue” is an exact symptom”
Harriet Hall – Not really. I would call it both non-specific and inexactly specified. It depends on self-reporting, varies with patient perception of whether it is severe enough to report, and is really pretty nebulous.”
Yeah – I can think of several kinds of sensations of “fatigue” or tiredness
There’s – I’m falling asleep in the middle of dinner tiredness
There’s – I have the flu and just moving feels like too much effort tiredness.
There’s – I just don’t have any pep for the last couple months.
There’s when I lift or carry things that normally don’t take any effort I get tired and have to rest.
There’s the high gravity day where everything seems like more effort, but which feels distinctly different than the other effort related tiredness.
Then there’s that sort of fatigue where you feel like you are just emotionally battling the events of the day and have had enough.
Just when I think that I can really connect one particular kind of fatigue to a cause, say – lack of pep to hypothyroid – things stop lining up. Maybe the TSH testing thyroid levels was normal, but the chest sounds wheezy. It’s a pain in the rear.
Unfortunately the body doesn’t seem polite enough to send unique signals for every ailment.
One might be tempted to call that a design flaw.
Along the lines of Dr. Novella’s post about why people turn to alternative treatments, I think when people have exact symptoms, but which are not indicative of any particular disease process, and those people are left without any treatment or pallative care while the symptoms progress, they will continue to search for answers. If they are readily dismissed as having a somatoform disorder, or told that the source of their symptoms is unknown, then they will continue to research and search for a cure or at least pallative care.
Uneducated patients (any many medical providers) who don’t recognize the deceptive advertising for certain alternative treatments, like those promoting acupuncture to treat disease, could most easily be lured into a bogus series of treatments. I find this especially true when one is given misinformation about other well-known conditions by medical experts. If the patient knows an expert is incorrect in their statements about something, they may rationalize that the same expert might be misinformed or uninformed about other things. So the patient keeps searching…
nybgrus
“One might be tempted to call that a design flaw.”
I keep sending letters to the management, but they haven’t responded yet. Poor customer service, I say.
There is a very interesting article just published on Cort Johnson’s new ME/CFS website, on the subject that fatigue may not be the most important symptom in ME/CFS, and that other symptoms such as sensory gating dysfunction may better characterize ME/CFS.
See here:
NOT FATIGUE AFTER ALL? NEW MODEL SUGGESTS OTHER SYMPTOMS BETTER EXPLAIN CHRONIC FATIGUE SYNDROME
I’ve often wondered if there is even anyone in the office.
nybrgus Ha! I was originally trying to make a joke about how my brain or nervous system isn’t running things as well as I’d like…rather than any intelligent design reference.
So, if I’m talking about my brain/nervous system, I’m pretty sure the “management” is in the office, they just generally ignore my calls. If we’re making religious references…I haven’t the slightest.
You gotta watch me, I tend to anthropomorphizes everything. Evolution, my nervous system, god(s), the freeway system…all occassionally conceived as sentient entities whose sole purpose is to inconvenience me.
@Nybgrus: ” Those with psych disorder/disease are truly suffering just as much as someone with organic disease.”
Are you saying the brain is not an organ?
@WilliamLawrenceUtridgeon
“That does not mean that CFS has a biological cause for all patients. There is a very good case to be made that CFS has, for some patients, a purely psychological cause.”
Are you saying psychology is not biology?
I’m sure neither of you mean to say that mind and body are completely different entities, but I do wish we could start using different words when we talk about psychological disease. It is just as much biological as hepatitis or the flu. The brain, the mind, emotions, thoughts, are biology, the brain is actually the most important organ. There’s no such thing as a purely somatic disease. There’s no such thing as a purely psychiatric disease. Human beings don’t consist of a brain linked to a body, we are one organism with many many intertwined systems. More and more research the past years has shown how closely linked “mind” and “body” are, to the point where distinguishing between them is impossible, and without meaning.
But as Nybgrus says, the stigma persists, and many patients are furious at the notion that they may also have psychological issues. They think that means we think they are crazy, or stupid, or hypochondriacs, and “not really sick”. I understand why they react that way, but it’s saddening. We (both doctors and the public) should know better by now.
And perhaps the most saddening thing: When people so vehemently protest at the notion that they might have “something” psychological, what does that say about our attitudes towards people with “real” psychiatric disease?
Regards,
Pernille Nylehn
The best, and I think determinative diagnostic test for CFS is post exertional malaise. You do an exercise to exhaustion on an ergometer where you can measure the work output and also O2 consumption and CO2 production, so you know when there is O2 debt and the real lactate threshold.
This easily distinguishes between people who are weak from detraining and from those who are weak from CFS. But people with CFS will be incapacitated for days, so it is not a test to be done lightly.
@daedalus2u: What if the patient has COPD? They wont be invalid for days after the test, of course, but they will probably have O2 debt and lowered lactate thershold.
@PernilleN:
You are absolutely correct. And I do believe your comment to me was indeed tongue in cheek. However, if you look through my history of posts here you will find that I (often fiercely) advocate for the realization that psychiatric disease is exactly that – organic disease. Unfortunately the language persists and is actually particularly entrenched in medicine. I agree that it should change and I think it will… eventually. But in all honesty probably not in my career and maybe not even in my lifetime.
Another aspect that I frequently comment on – both here and in my professional and personal life – is the notion of “talk therapy.” It is often used as a “placebo” and thus studies comparing “talk therapy” to pharmaceuticals can show equivalency and give fuel to the notion that neuropharmaceuticals (NPs for shorthand purposes here) are ineffective compared to placebo. Even in cases where active NPs are compared to a sugar pill, there is still actually no real “placebo.” When the organ of concern is the brain, we must realize that doing anything whether it be talking to the patient or giving them a sugar pill or even just giving them a hug is an active intervention that changes the neural cytoarchitecture of the person in question. We have good data demonstrating neural plasticity is extremely robust and that changes can and do happen on timescales as short as minutes with things like Hebbian learning cementing in those changes. This is, IMHO, the most parsimonious explanation as to why mild to moderate depression (for example) seems to have a fair bit of equivalence between NPs and “talk therapy” and even placebo, but severe depression is much more refractory and NPs show a greater response (and why CAMs such as St. John’s Wort seem to have effect for mild depression). The same with schizophrenia and pretty much any psychiatric disease. Just doing something has an actual and direct effect on the affected organ. The same cannot be said for kidney disease, for example. This muddies the waters and the old notions of “it’s all in your head” make people blind to these facts and their ramifications (that and religion, but I won’t go there).
The varying underlying etiologies of phsyciatric disease which we do not have the resolution to discern at this time plus the direct effects of literally any sensory input in changing the neural cytoarchitecture and neurotransmitter release and receptors with the fact that we are our neural cytoarchitecture explain (once again, IMHO – I am not an expert in these things at all) many of the “anomalies” we find in the data and should absolutely obviate the stigma associated with psychiatric disease.
We’ll get there on day. Such is the awesome power of the slow lumbering beast we call science.
As for D2u’s lactate/oxygen idea…. well, last night was the induction ceremony and celebration for the newly minted Year 3 students as they start their clinical work so my brain is very slow this morning and I simply can’t comment. Nor can I write as cogently as I normally do, as clearly evinced above.
Here is an article on CFS and post-exertional malaise.
http://www.cfids.org/cfidslink/2010/080402.asp
I don’t know about COPD. I think that someone can have both COPD and CFS simultaneously, but which would dominate is likely to be idiosyncratic.
Post-exertional malaise occurs in the muscles. COPD starts out as more of a lung thing, but eventually everything else gets involved too. Once the muscles get involved, then it is CFS too. If supplemental oxygen doesn’t improve exercise performance, then the lungs are not the limiting factor. This is the case in CFS and it does become the case in COPD.
The point of doing the O2/lactate threshold is to ensure that equivalent states of O2 debt are reached in the muscle. The post-exertional malaise is (I think) due to destruction of mitochondria and their very slow replacement.
@daedalus2u: I agree with most of ypour reasoning, but I’m not so sure about this one:
“COPD starts out as more of a lung thing, but eventually everything else gets involved too. Once the muscles get involved, then it is CFS too.”
I don’t think it’s wise to muddy the waters even more by defining serious COPD as a form of CFS. Especially since CFS is more than fatigue and post-exertional malaise. People with grave COPD tire easily, of course, since they hardly ever get enough oxygen, but they don’t have all the other symptoms og CFS. And, even more important, they respond well to exercise and physiotherapy, which ME/CFS-patients usually don’t, unless the exercise is very very light.
@Nybgrus: I do know your stance on mind-body, so it was probably unfair to pick on you, since your remark was obviously a slip of the tongue. But I picked on you anyway, to demonstrate how even the most conscientous tend to be trapped by language and traditional thinking.
As for “anything we do to a person changes their does something to their mind”, making psychiatric treatment difficult to evaluate: I think you are exaggerating a bit. Of course everything we do to a person – a chat, a hug etc – does something to his neural pathways. But it is still perfectly possible to distinguish between placebo effect and treatment effect. After all, hugging and chatting are hardly systematic interventions, while therapy is – be it psychotherapy, CBT or whatever.
Regards,
Pernille Nylehn
I think that when COPD progresses to cachexia, then it is like the other disorders that have progressed to cachexia, chronic heart failure, chronic kidney failure, chronic liver failure, and Alzheimer’s.
Those tissue compartments are all high metabolic organs. If mitochondria biogenesis becomes compromised, then patients become hypermetabolic as the existing mitochondria get pushed to higher potentials where there is more “slip” (less ATP per molecule of O2). Metabolism isn’t doing more, it is doing less, but doing it with ATP that is generated less efficiently.
Mitochondria wear out over time (few months), and if they are not replaced, eventually they fail and the tissue compartment with too many failed mitochondria fails too. That can happen quickly during sepsis where it causes multiple organ failure. What does it look like if the failure is more gradual? I think it looks like the chronic degenerative diseases of each particular organ. The high metabolic rate organs are more susceptible to this type of failure, so we have specific names for them.
As all of them get worse, eventually they start looking more and more similar and with vascular effects. When you start getting ectopic fat is when things are really bad. Visceral fat is not that bad, liver fat is worse (but still pretty common), but ectopic fat in the heart or kidney is a lot worse.
I see post-exertional malaise in CFS as the acute failure of too many mitochondria in muscle.
I have no problem with your reasoning about mitochondria etc. But you still can’t say CFS is the same, or somilar, to grave heart- or lung disease. Even you mean only the post-exertional malaise – COPD patients aren’t incapacitated for days after exercise, even when they are cachectic. They get better and better with exercise, even if it’s strenuous. I’ve tried rehabilitating both heart/lung patients and CFS patients, and there’s a vast difference.
Regards
Pernille Nylehn
Indeed. Not so much a slip of the tongue, but a necessity of communication within the current nomenclature of medicine. Trapped indeed – there is no particularly good way to express the notions without long explanations; explanations which most people don’t care to hear about and many would not accept at face value since it is counter to their “intuition” on the topic. As I said, I think this is changing, albeit slowly, and will eventually be the way psychiatry moves forward. At base, good psychiatry is a scientific discipline and they are making good strides in a positive direction. Anyways, I’ll quit now lest I start pontificating too much and extrapolating beyond reason. I’m certain you and others here get the gist of what I am trying to say.
Perhaps I am. But don’t you think it is a reasonable thought that those who have depression would be benefitted merely by having more attention paid to them and “something to do” every day as part of simply being in a trial? Just having others to converse with, care about their problems, and take pains to ensure ethical standards are met is certainly helpful and in some cases of mild depression with a specific etiology amenable to it can be curative. This, I think, is uncontroversial. My only contention is that these factors are not placebo effects – they are active interventions since they all actually actively and directly influence the pathological organ – the brain.
So when people – critics especially – look at studies and see not much difference between an active pharmaceutical treatment arm and the placebo pill arm of a trial, they are actually comparing 2 active treatments to 1 active treatment. Furthermore, my contention is that depression as an entity is difficult to define precisely, is obviously a continuum, and (my biggest leap, though obviously I think it is justified) that the same disease state has multiple etiologies that we simply cannot distinguish. In at least some of these etiologies and especially along the lower end of the severity continuum we would expect to find that 1 active treatment (the “placebo”) is clinically significant and the 2nd (drugs) doesn’t actually add much to the treatment (in other words, it is overkill). Thus, the clinical outcomes between the two groups doesn’t appear as large and those who merely look at that on face value conclude that drugs don’t have benefit (or at least not much) to patients since “placebo” works very well and has a large clinical effect size.
Since we randomize after the diagnosis is made, I am arguing that any given series can have an unkown number of depressive patients in either arm of the trial who will respond favorably to the “placebo” treatment (which I am further arguing is actually an active treatment) and thus explains the heterogeneity of studies and the varying response rates in different arms of different trials that we see.
And yes, structured CBT would likely be more effective but perhaps not much more than the aggregate of “placebo” effects in studies. What it certainly would be is more consistently effective. But we have good data to demonstrate that the precise method of “talk therapy” is significantly less important than how well the patient gets on with the practitioner. This, to me, fits in with the fact the neurobiology is complicated and thus different “styles” will fit different people better and be more able to effect change in the neurophysiology of the patient in question.
So systematic interventions are necessary to invent and study so that we can have a baseline of standardization and understanding but we see that because we are complex and variation in neurobiology is much more than in the rest of our biology, small non-sytematic things like hugging and chatting can be extremely profound in some, neutral in others, and in some even be detrimental. But all active treatments which can and do easily confound studies.
There are issues with calling treatments “active” or “placebo”, without knowing the mechanism(s) by which they have effects.
The definition of “placebo” that I like, is an effective treatment that has positive therapeutic effects mediated not through pharmacology, surgery, or other direct, physical effects.
A treatment that has no therapeutic effects is an ineffective treatment, no matter what its treatment modality. A treatment that does have positive therapeutic effects is an effective treatment, no matter what its treatment modality.
Placebos can have positive treatment effects. Distinguishing the placebo-mediated therapeutic effects from the pharmacologically-mediated therapeutic effects is important for clinical trials to compare treatments, it is not so important in treating patients in the absence of a clinical trial.
If the definition of a non-placebo hinges on it being systematic and ritualized (as in psychotherapy), then acupuncture is no less systematic and ritualized. An ineffective pharmacological treatment can have positive treatment effects through the placebo effect.
I’m somewhat offended by the links to ClinicalTrials.gov provided by The Dave that weren’t even searched correctly. Try using “quotes” around phrases next time. There’s even an example at the website right next to the search box.
Here are some more informing statistics from ClinicalTrials.gov
Myalgic Encephalomyelitis
23 studies found for: “myalgic encephalomyelitis” | Open Studies
23 studies found for: “chronic fatigue syndrome” | Open Studies
The above studies overlap
Prevalence:
0.2% – 0.7% (0.45% avg) https://www.mja.com.au/journal/2002/176/9/chronic-fatigue-syndrome
0.015% – 0.2% (0.1075% avg) http://www.biomedcentral.com/1741-7015/9/91
0.007% (7:100,000) – 3% (3000:100,000) (1.5035% avg) http://en.wikipedia.org/wiki/Chronic_fatigue_syndrome
Overall average 0.687%
Studies per sufferer: 23 / 0.687 = 33.47889374090247
If I had just taken the prevalence statistics from wikipedia like the other disease, the result would be even worse.
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Crohns
217 studies found for: crohns | Open Studies
0.029% (29:100,000) – 0.199% (199:100,000) (avg 0.2445%) http://en.wikipedia.org/wiki/Crohn's_disease
Studies per sufferer: 217 / 0.2445 = 887.5255623721881
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Multiple sclerosis
0.00002% (2:100,000) – 0.15% (avg 0.07501%) http://en.wikipedia.org/wiki/Multiple_sclerosis
299 studies found for: “Multiple sclerosis” | Open Studies
Studies per sufferer: 299 / 0.07501 = 3986.135181975737
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Systemic lupus erythematosus
0.04% (40:100,000) – 0.159% (159:100,000) (avg 0.0995%) http://en.wikipedia.org/wiki/Systemic_lupus_erythematosus#Epidemiology
125 studies found for: ” Systemic lupus erythematosus” | Open Studies
Studies per sufferer: 125 / 0.0995 = 1256.281407035176
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Schizophrenia
0.3% – 0.7% (avg 0.5%) http://en.wikipedia.org/wiki/Schizophrenia#Epidemiology
605 studies found for: Schizophrenia | Open Studies
Studies per sufferer: 605 / 0.5 = 1210
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I would be much easier to live with a disease knowing that all that can be done is being done, but that plainly isn’t so. I’m sure you could continue going through many more diseases and you would find the this disease comes out far worse off the whole way through.
What I wonder sometimes is whether patients diagnosed with CFS/ME or FMS really suffer from genetic conditions or other illnesses instead. Mitochondrial diseases are ones that I often consider. In my experience, patients are not routinely tested for any genetic or environmentally triggered hard to diagnose or rare diseases unless perhaps their symptoms are profoundly visible or imminently life-threatening. It is relatively easy after a few years of complaining to physicians to find one willing to test for more common illnesses, like Sjogren’s, Lupus, and Scleroderma, but any further testing is generally refused. If it doesn’t show up in the basic blood work, the patient is refused care, and many are indeed generally given a psychiatric diagnosis of some kind, especially women. I know this is an area of much disagreement between physicians and patients, and I only speak from the patient perspective.