Unfinished Blog-Post: A Post-Mortem for Lombardi et al. 2009 - The Addendum

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

Unfinished Blog-Post: A Post-Mortem for Lombardi et al. 2009 - Unanswered Questions

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

Unfinished Blog-Post: To Pull A Gallo

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

BTW: It is this post I most regred not finishing – it is mainly missing one table in the middle, listing some parallels between the story of "Fictional Gallo" and those who brought us the XMRV fraud. However the so inclined readers might be able to find parallels by themselves.

Komaroff is an Idiot

I have to revise the high opinion I had of Anthony Komaroff. He jumbles all kind of definitions together and muddies the waters (when he should know better):

… What is fatigue? It's a sensation of sleepiness, muscle weakness, or a feeling that you don't have the energy to do something - either physical or mental. It's the brain that experiences fatigue; that means there are certain chemical changes in the brain that lead to fatigue - even though those chemical changes may be triggered by many different illnesses. …

Komaroff, what the heck????

No, no, no. Fatigue is not "sleepiness". Sleepiness is the urge to sleep – and you can be fatigued without being sleepy. Somnolence is "sleepiness". "Tiredeness" is maybe a combination of fatigue and "sleepiness". But one can be very well fatigued without being tired. Being chronicly "sleepy" and being chronicly "fatigued" are two different symptoms! Were you find one, it is not unusual to find the other, but they a separate sensations.

And fatigue is not the feeling of "muscle weakness". Yes, fatigue and the feeling of "muscle weakness" can go together (e.g. after doing way do much physical work) – but one can be very well fatigued without having the feeling of "muscle weakness".

Yes, one could say fatigue is the feeling that one is "lacking energy".

But for crying out loud, what is the problem with saying:
Fatigue is the feeling of EXHAUSTION.

Or you could bloody well say:
Fatigue is having the urge to rest.

And no, no, no. Fatigue (like for example the feeling of pain) is not simply "chemical changes in the brain". Both pain and fatigue are signals of the physical state of your body – if pain is the gauge of the engine temperature, then fatigue is the gauge of the petrol tank. If pain tells you "Mate, if you keep doing that, something is going end up on the fritz pretty soon", then fatigue tells you "Mate, you are running on reserve, take a rest and replenish your energy or you'll end up with power". Pain is (usually) alleviated by stopping the action that causes the pain, and fatigue is (usually) alleviated by resting. The cause is (usually) not in the brain, it is only registered in the brain.

Words fail me how someone like Komaroff, who is so seemingly methodical, can be so confused with elementary definitions of the diseases he deals with. And I find it shocking that he spreads this confusion.

PS: It is however interesting that he mentions both mental and physical fatigue, but alas, he does it not in a way that is helpful.

The Great Chronic Lyme Mirage – Advocates Gone Wild

Bullying Borrelia: When the Culture of Science is Under Attack
(Full Text PDF)

Paul G. Auwaerter, MD, and (by invitation) Michael T. Melia, MD

Abstract
Although Lyme disease responds to short courses of antibiotics, tick-borne Borrelia burgdorferi has been advanced by some as a frequent explanation for medically unexplained symptoms such as continual fatigue, musculoskeletal pains, and subjective neurocognitive dysfunction.

Often called “chronic Lyme disease” by adherents of this philosophy, it is loosely defined, and practitioners liberally prescribe nostrums, including prolonged antimicrobial therapies, in a belief that this eradicates suspected infection.

Perhaps due to the lack of supportive data, proponents of this theory have developed their own meetings, literature, activist groups, and substantial internet activities to advance their views.

Forces motivating this movement are explored, as are tactics used to advance non-scientific ideas that have included legal action and garnering legislative endorsement.

While neither logical nor evidence-based, “chronic Lyme disease” harnesses corrosive energies that taint modern medicine and society.

…

We know it all too well from ME/CFS: A minority of quack-doctors are proposing valid sounding theories with regards disease mechanisms – which goes hand in hand with cures they claim to have – and some patients and relatives are more than happy to advocate in their name. And when one calls out their lack of evidence, and the likelihood that the supposed cure does in many (if not most) cases harm, one is branded as an enemy. To hell with those malicious patient advocates and malicious patient activists, and to hell with these "LLMD" quack doctors.

And yes, people who supposedly have "Chronic Lyme" are ill with an (in all likelihood) organic disease. But no, it is not "Chronic Lyme" and in most cases it isn't even Post Lyme.

The Great Chronic Lyme Mirage – Herx Edition

Halperin / ALDF:

… Early work indicated that patients with acute, active early Lyme disease, as indicated by the presence of an erythema migrans (EM) skin lesion (when large numbers of spirochaetes are presumably present), sometimes exhibited a Jarisch–Herxheimer-like reaction within 24 h after initiation of treatment (Weber et al., 1988; Maloy et al., 1998).

This led to the notion that any worsening of symptoms during treatment constituted ‘Herxing’, regardless of the duration of symptoms or treatment at the time of the worsening.

The logical in-consistency of postulating that treatment-resistant disease was due to a small number of undetectable bacteria, while at the same time concluding that symptoms arising or worsening during antibiotic therapy were due to the release of large amounts of pharmacologically active bacterial products, was either discounted or never considered.

However, this then completed the very tidy but circular conceptual model.

If patients improved, even transiently, after treatment, this validated the diagnosis and justified further treatment; the possibility of a placebo effect or natural fluctuation in symptom severity was either never considered or completely rejected.

If patients worsened, this was considered to be due to a Jarisch–Herxheimer reaction, similarly validating the diagnosis.

If there were no response to therapy, this validated the assumption that this infection is highly resistant to standard antimicrobial therapy. …

The more I see of these "LLMD" quacks, the more I am sure that "Chronic Lyme" is a quack diagnosis.

The people who are misdiagnosed with "Chronic Lyme" have a disease, no question – and in most if not all cases it is an organic disease – but I am rather sure that it is not a active/persistent/latent ("chronic") lyme infection.

At the same time I believe that a very very small number of people who are misdiagnosed with "Chronic Lyme" might have "Post Lyme", where the bug is gone but the organic damage stays, same as there are Postviral Fatigue Syndromes and other postviral CFS-like diseases.

However, I am certain that no "LLMD" quack would be able to differentiate Post Lyme from Post Mono. These LLMDs see a patient and can only diagnose "Chronic Lyme", it seems …

As Tom Waits once sang:

LLMD always try so hard to look like real doctors
They couldn't catch a cold,
baby don't waste what's left of your health

So unless you have an acute infection and take short term antibiotics for it (for a couple of weeks) stay the hell away from antibiotics if they are given long-term, especially when they give you a long time supposed "Herx" reaction – because a "long-time Herx reaction" is not Herxheimer (due to Lyme "die off"), but the side-effects of antibiotics that are destroying your health.

Judy Mikovits: Unemployed and Bankrupt

And here I was thinking that Karma does not exist… – silly me.

So if we are lucky Dr. Mikovits will no longer be able to take advantage of a vulnerable patient population – one can dream.

Pity however that Lombardi and Ruscetti don't have the same luck as Saint Judy.

The Great Chronic Lyme Mirage

I found some interesting comments by Phillip J. Baker (who seems to be associated with the American Lyme Disease Foundation) underneath an otherwise not recommendable article & discussion (or rather an article & discussion which can only be recommendable as a negative example for the display of confirmation biases and cognitive dissonances).

Especially this comment by Phillip J. Baker struck a chord with me:

Believe what you will, Phyllis, but you are wrong. Ceftiofur and ceftriaxone are chemically different in structure. Embers et al. have provided no assurances in their work that they have similar PK and PD properties, let alone the same MIC. It is incumbent upon them to provide such data, as well as to show that therapeutic regimen used was adequate to clear the huge inoculum that was used to produce a disseminated infection. Obviously, their experimental design did not mimic the Klempner study, which is what Mario was initially funded to do. Why he chose to use ceftiofur is for him to explain, not me. As I said before, ceftiofur has not been approved by the FDA for use in humans and there are no published data showing that it is effective for treating borreliosis in animals, let alone humans. There is one report showing that it is not effective for treating borreliosis in ponies.

Phillip J. Baker
on February 24, 2012 at 1:52 pm

http://lymedisease.org/news/lymepolicywonk/lymepolicywonk-was-this-important-lyme-study-hidden-for-12-years.html#comment-3798

He goes on to notice in another comment:

I must say that I find it strange that the term ceftriaxone is used throughout the Embers et al. paper, and it is only in the first paragraph on page 9 that it is first mentioned that ceftiofur was actually used. I find that very strange indeed.

So to claim that Lyme is still active despite anti-biotics, Embers et al. have to pull these two tricks:

1. Use a "huge inoculum" to intruduce an amount of pathogens not encountered in the wild, causing an "massive disseminated infection" not encountered in the wild.
2. Use an antibiotic that (most likely) is not effective in clearing the pathogen (let alone in this massive disseminated infection) – and hide that as good as you can.

What Phillip J. Baker describes are the tactics of quacks.

No wonder anybody with at least a couple of working brain cells left*, who looks into the matter comes to the conclusion that "Chronic Lyme" is a BS quack diagnosis.

And just for the record: I do think that these patients have an organic disease, which severely affects their lives – however there is no evidence** that this disease is Lyme. There are many many diseases that can cripple your live, and possibly some of which are yet of unknown.

* As to so called "Lyme Literate Medical Doctors" ("LLMD"):
They do not seem to have any working brain cells left. My (purely anecdotal and not evidence based) advise is to stay away from medical doctors who have no working brain cells. LLMD? Just say no. Choose a doctor instead with working brain cells, this is usually better for your health.

** As to any non-standard tests used to detect "Chronic Lyme": I can offer you an even more reliable Lyme test! I will match any price, just give me a call!

John Maddox and "Self-"Correcting Science

There is one nice angle about John Maddox and his "courage to stand up science": In the mid- to end-eighties he launched an "investigation" into the Gallo/Montagnier/HIV disaster. When Gallo told Maddox things that shed serious doubt on Gallo's version of events, Maddox choose not to publish his findings.

While John Maddox choose not to pursue any leads he had, Abraham Karpas continued to turn up unpleasant facts about Gallo's research. And he would write them to Nature (I guess to "correct science"), where Maddox resided. And what courage did Maddox have? Karpas described it as "writing for Nature's wastebasket".  His research into Gallo's research ended up being published in the New Scientist and Scientific American, but not in Nature.
(John Crewdson, "Science Fictions", page 340)

So much for Maddox's "courage to stand up for science".

And so much for science being "self-correcting". It seems to me that personal biases and the mechanisms of the academic institutions strongly obstruct any corrections.

This whole "self-correcting science" meme seems like something told to little children, so they stop asking annoying questions.

(In Crewdson's book at the beginning of chapter 17 there is a nice side story involving Margot O'Toole turning up troubling "inconstancies" in the work of David Baltimore, after being a postdoc on one of his studies. His answer? Not to worry, these problems don't matter and the scientific process was "self-correcting" anyway – so she should let the matter rest.)

Gallo a Quack?

Well, who knew that? It seems like Gallo was quite a quack. In 1990 he claimed to have a cure for Kaposi's Sarcoma, when all he had was some experiments with mice (Crewdson, page 354-355).

Any other scientist doing such a thing would qualify as quack, so should we make an excuse for him?

Understanding Simon Wessely and his Paternalistic Counter-Enlightenment

Attention conservation notice: I will try to outline my impressions of what Simon Wessely's position on ME/CFS is – in order to understand the reason why his (and his peer's) practice is so insidious.

(Apologies for the amount of Wessely related content lately, but it seems that if there is nothing else ME/CFS-related to write about, one can always find a ME/CFS-quack to take apart.)

First to illustrate his position, some quotes from Simon Wessely's and Sharpe's work "Chronic Fatigue and Neurasthenia: A Review" (courtesy of a comment by ErnRoberts on the "noodlemaz" blog):

Our hypothesis is that fatigue syndromes are universal, but that culture is important in understanding the transition from symptoms to disability.

Where there is considerable concern around concepts such as immune dysfunction, viral persistence, and environmental toxicity (irrespective of the true prevalence of all of these factors), there may be a greater likelihood of symptom persistence and severe disability. …

Poor outcome in CFS is predicted by longer illness duration, more severe symptoms, older age, depression, and lack of social support, and also by a strong belief in physical causes.

Severely disabled patients attending specialist clinics have a particularly poor prognosis. 

… a reduction in the belief that activity is damaging is associated with recovery during rehabilitative therapy, suggesting that it may be a critical psychological target for effective rehabilitation …

“Patients’ beliefs about their illness and associated coping behaviour will be influenced by the information received from others.

A striking social aspect of CFS is the high level of activity of patient support and advocacy organizations, mainly over the Internet.

Studies from the United Kingdom have reported that patients who are members of a support group have a poorer outcome, despite similar illness duration and disability, and a poorer response to rehabilitation.

It is unknown whether this reflects self-selection into such groups or the effect of the group on patients’ beliefs, coping, and willingness to engage in rehabilitation.

Other factors include the experience of repeated questioning of the legitimacy of one’s illness by doctors and others, which probably serves to drive some patients to join advocacy organizations.

Perhaps unsurprisingly, in fibromyalgia, the acquisition of a disability pension is also associated with a worse prognosis. … 

Whatever the biological aspects of CFS, cognitive-behavioural models assume that the symptoms and disability are perpetuated, at least in part, by psychological, behavioural, and social factors.

Biological factors are assumed [Hear, hear! A true scientist who tries to falsify his theories!] to be either only partially responsible for the illness or largely reversible.

So I take it that Wessely believes that people with ME/CFS have a "false" believe that they have a bodily disease, and a "false" perception of "normal" bodily sensations. Furthermore he believes it is this "false" believe that is the only thing wrong* (which can be shown to be wrong).

Now, it seems his believe is that this "false illness perception" is what actually cause patients to stay ill – the worse the "perception", the worse the prognosis of getting better.** (Here Simon Wessely seems to have the made classic correlation/causation error, and putting the cart before the horse – why he can't do simple 2-day exercise challenges, à la Dr. Snell, which would falsify his theory, that can remain anybody's guess.)

Alas, it is not mainly this wrong premise about "false illness believes" that is primarily insidious, but the paternalistic practice that follows from this.

There is some controversy about whether giving patients a diagnosis of CFS is helpful or harmful.

There are those who feel that a diagnosis enables patients to both conceptualize their illness and communicate about it with others.

Others are concerned about the potentially harmful effect of a diagnosis, arguing that it medicalizes and pathologizes symptoms in a way that can exacerbate social and occupational disability.

The Management [sic] Plan

This should be explained [sic] to the patients as following from the formulation, focusing on illness perpetuating factors and consisting of elements aiming to

(a) relieve symptoms such as depression, pain, and sleep disturbance with agents such as antidepressants,

(b) assist the patients efforts at coping by stabilizing activity and retraining the body to function effectively (graded exercise, CBT), and

(c) assist the patients in managing the social and financial aspects of their illness and where possible remaining in or returning to employment (problem solving)

Patients seen in specialist settings in Western cultures with the label of CFS or its equivalents are often resistant to psychological labels and/or explanations.***

Simon Wessely does not seem to believe that an patient of his is accessible to rational dialogue, he even deems it harmful. Someone with a humanistic and enlightened perspective would talk to a patient, try to explain the disease model and get what I would call "rational buy-in" – instead, it seems Simon Wessely believes that ME/CFS patients need to be sucker-punched into a (disguised) mental illness diagnosis and a therapy they are not meant to understand (and could not give their informed consent to, obviously).

I feel that Simon Wessely believes it is wrong, wrong, wrong to tell the patient the truth – that must be the reason why there is such a disconnect between what says to the unwashed masses when he speaks to the public (and therefore to "his" patients) and what he tells to his peers.

The "Management [sic] Plan" seems to be one big fat lie, as the targets that are stated towards the patient ("relieve symptoms … with antidepressants", "assist … at coping" and "assist in managing the social and financial aspects of their illness") differ substantially from the "false illness believes" that are the root cause according to Simon Wessely.

And obviously selling a therapy to which people can not give informed consent – by the very rationale of the therapy – is usually something that does not jibe well with the medical authorities (or at least I assume so in any modern post-feudal nation). One more reason why Simon Wessely does good (at least good in his interest) to keep his intentions muddy and unclear to outsiders, and his practices effectively hidden from scrutiny.

Simon Wessely, an truly idealistic paragon of the Counter-Enlightenment – quick, someone make him a Baron or something for his fight against the unwashed masses!

________

* As to his claim that

“The bulk of evidence indicates that there are no proven pathologic or biochemical abnormalities of muscle or muscle metabolism, either at rest or with exercise, other than those associated with deconditioning”.

I refer you to the following lectures: Christopher Snell 2012, Alan Light 2011 and Alan Light 2007, all of which show pathological changes in a majority of tested ME/CFS patients during an exercise challenge – changes that can not be explained by false illness believes, deconditioning or sedentary behavior. But apparently a properly designed exercise challenge is rocket surgery and beyond the reach of even our very talented Simon Wessely.

** Especially the statements that "severely disabled patients attending specialist clinics have a particularly poor prognosis" and that "the acquisition of a disability pension is also associated with a worse prognosis" are truly awful statements, laying blame on specialists taking patients seriously and the approval of the disability pension. Anybody who has tried (in any country) to apply for such a pension knows that one is put under quite some scrutiny, and one has to be quite diseased to be approved (the very few fraudulent cases non-withstanding) – that those that passed such scrutiny have worse prognosis is apparently an unexpected surprise for Simon Wessely and prove in his cart-before-the-horse-world that the approval does the harm.

*** Could it just be, that patients might have good reason to reject the psycho-pathologization by Simon Wessely and his peers? And maybe even have rational cause to be angry at being psycho-pathologized in the face of a bodily disease (cf. Snell and Light)? I would even go so far and argue that if the practice of Simon Wessely does not make you angry, that you might be a bit lacking in your thinking department. What a perverted world, where those who praise Simon Wessely are seen as mature and intelligent.

Kentucky Fried Cardiovascular Research

The Scientist: A Decade of Misconduct

A senior cardiovascular disease and diabetes researcher at the University of Kentucky has been found guilty of falsifying data over the past 10 years.

Federal investigators have censured a former University of Kentucky (UK) senior biomedical researcher for serial scientific misconduct over a 10-year period, including the falsification of data in grant applications, progress reports, and published papers. The US Office of Research Integrity (ORI) announced the findings last week (November 20) with a notice in the Federal Register.

A joint investigation carried out over the course of 2 years by the ORI and the UK found that Eric Smart, who studied the molecular mechanisms behind cardiovascular diseases and diabetes, had falsified or fabricated a total of 45 figures—mostly images of Western blots, a technique used to identify proteins—in seven grant applications, three progress reports, and 10 published papers, some of which were cited more than 100 times, according to Thomson Scientific’s Web of Knowledge. The notice says that Smart also reported experimental data from knockout mice that did not exist.

“This is surprising and disappointing news to me,” said Philippe Frank of Thomas Jefferson University in Philadelphia. “Dr. Smart's papers were highly cited in the specific caveolae/cardiovascular research field.” William Sessa of the Yale University School of Medicine told The Scientist by email that he was “shocked at the extent of misconduct,” and that the reporting of data for knockout mice that did not exist in grant applications “is very problematic indeed.” But, he added, “since I do not know what aspects of the figures were incorrect or misrepresented, it is difficult to assess the impact on the field.”
…

Retration Watch has this to report:

Specifically, ORI finds that Respondent:

Falsely reported in Figure 14 and associated text in NIH grant applications R01 HL07897601 and -01A1 that experiments were performed to determine if endothelial-specific caveolin-1 null mice were protected from saturated fatty acid-induced atherosclerosis, when these mutant mice did not exist in the laboratory at the time; Dr. Smart also falsely reported the use of these mice in related progress reports R01 HL078976-02, -03, and -04 and in three (3) additional NIH grant applications: Figure 11 in R01 HL088150-01, Figure 11 in U54 CA116853, and Figure 9 in DK063025-01A2

So nothing to see here.

Continue to avoid saturated fat, and take your statins – as the good doctor said.

And while some people may actually and genuinely be surprised (and may actually and genuinely believe that saturated fat is the nutritional anti-christ), I am not the the slightest bit surprised that one needs to fake studies to come to the faulty paradigm which is en vogue now for decades in cardiovascular research. I guess if you work with a faulty paradigm, there is no other way but to fake results to uphold that faulty paradigm.

Mikovits: It's a retrovirus!!!! No, it's a genetic mutation!!!

So the very excellent Dr. Mikovits ("It's a retrovirus and it's gonna get everyone and your dog unless you test yourself and your loved ones!!!!") has stopped pushing worthless yet expensive XMRV tests with FUD on gullible (and desperate for answers) ME/CFS patients.

Instead, the fine Dr. Mikovits is now pushing genetic tests (for MTHFR, I take it) on gullible (and desperate for answers) ME/CFS patients – though thankfully the fear factor is much lower than it was with "HGRV is gonna get you and your loved ones!!!".

So the good Dr. Mikovits, who claimed until this very year that there is some huge government conspiracy – which included almost all known (retro)virologists – to hide the existence of extraterestrial life an retrovirus ("HGRV") that would torment all, all, all ME/CFS sufferers, so that very same Dr. Mikovits has made an 180 degree turn and seems to be claiming it is all in the genes, no virus needed – huh.

The words "lying", "fear-mongering" and "cunt" come to my mind – which is highly unfair to the excellent Dr. Mikovits, as I must admitt.

Cervantes on the Medical-Pharmaceutical-Industry

Cervantes on the Medical-Pharmaceutical-Industry:

The Senate finance committee has found that [the Medtronic corporation] paid -- get this, it's not a typo or an extra zero -- hundreds of millions of dollars to doctors to pretend to be the authors of articles they drafted, edited and approved praising its product InFuse. Senator Max Baucus says, "Medical journal articles should convey an accurate picture of the risks and benefits of drugs and medical devices, but patients are at serious risk when companies distort the facts the way Medtronic has." Indeed. The editors of Spine Journal weigh in: "If surgeons had known that the lead authors of the 13 original studies on InFuse had received payments ranging from $1.7 million to $64 million [sic!] from Medtronic and that its marketing employees were co-authors and co-editors, would they have been as eager to use InFuse on their patients?"

That's all well and good but BMJ fails to name the names of those "physicians." They are all cruising along with high powered appointments and continuing to publish.

Oh my

Oh my, not something specific to medical sciences:

… I know of people that have given a purportedly crippled software to a collegue to sabotage his project. I’ve been violently attacked verbally for having dared talking with my supervisor of a project I was collaborating with, because she feared that I wanted to “steal” her credit. I’ve seen more than once people “helped” during a project, only to find all credit for their work taken by the nice and smiling people who scammed them by “helping” them. There are endless horror stories like that. Everywhere.
…

The ones I’ve seen thriving in Cambridge, apart from geniuses (there are a few), are the guys who cling to a simple ecological tenet: Find your niche, where you are indispensable, and keep it in your claws at all costs. This means basically that these people do always the same thing, over and over again, simply because it’s the lowest-risk option. I could have done the same (I was pretty skilled during my Ph.D. in a quite obscure but interesting biophysics experimental technique) but I thought that doing science properly was also about learning and broadening your expertise. How wrong I was.

You can imagine yourself what does it mean also for research in general: Nobody takes risks anymore. Nobody young jumps and tries totally new things, because it’s almost surely a noble way to suicide your career.
…

Science is human – and some humans behave badly

Ed Yong discusses human science:

Over the last year, I’ve written several pieces about problems in psychology – namely, an overwhelming skew towards positive results, a lack of replications to check if they are correct, and a disturbing number of cases of misconduct. But of course, psychology is not alone here. These problems are pervasive in science, and it’s important to discuss them.

Publish shoddy study in PNAS, dupe patients, get access to NIH-funds!

CFS Advisory Committee, October 3-4, 2012:
… Dr. Susan Maier (NIH) reported that several new members were added to the Trans-NIH ME/CFS Working Group, including Dr. Harvey Alter. It’s very good news that Dr. Alter is staying involved in CFS despite the end of XMRV. …
(via CO-CURE maillist)

Oh isn't it simply great news that our beloved Harvey Alter, after pushing the shoddy Lo/Alter/XMRV study into PNAS, gets money from the NIH to continue his fabulous work? Dandy, indeed. Simply splendid. A great scientific addition, indeed.

In that spirit, I nominate Marc Hauser, Scott Reuben and Diederik Stapel as new members for the Trans-NIH ME/CFS Working Group – with such outstanding scientists we will know for sure how the NIH-money will be accounted for!

Doctors without Science

Seth Roberts at his best:

Extremely Disappointing Facts About Doctors

The gist of Unaccountable: What Hospitals Won’t Tell You … by Mart Makary, a med school professor at Johns Hopkins, is that doctors have failed to regulate themselves. Nobody else regulates them, so they are unaccountable. In many ways, Makary shows, bad behavior (e.g., unnecessary treatment, understating the risks of treatment) is common. Hospitals hide how bad things are. Makary mostly discusses surgeons — he’s a surgeon — but gives plenty of reasons to think other specialties are no better.

The book is one horror story after another. At one point, Makary quit medical school. He was disgusted and appalled by seeing doctors — his teachers — push an old woman to consent to an operation she didn’t want and didn’t need. She refused, again and again, but the doctors kept pushing. Makary objected. He was ignored. Finally she agreed. The operation killed her.

I know Peter Attia as a co-founder, with Gary Taubes, of the recently formed Nutritional Science Initiative. Makary met him when Attia did a surgery residency at John Hopkins Hospital. Attia had seen a doctor about back pain and had been told he needed surgery. They operated on the wrong side, causing damage that prevents Attia, an excellent athlete, from playing most sports. Eventually Attia left medicine. He felt “modern medicine was too frequently dishonest with patients, at times understating risks and overtreating patients as a matter of reflex” — “as a matter of reflex” meaning “as a matter of course”, i.e., usually. And Johns Hopkins Hospital is one of the better hospitals in America. “Almost everyone I talk to has a story about a friend or a family member who was hurt, disfigured, or killed by a medical mistake,” writes Makary. He has six such stories, including his grandfather and his brother. His grandfather died from unnecessary surgery.

…

Another "Oldies, but Goodies" episode

Thanks to RRM for bringing this to the attention of us all.

Patrick Moore
March 6, 2011, 9:05 pm

Occam’s Razor of Virology: When you find a virus that causes disease, the disease should be easier to understand and not harder.

If you have to come up with more explanations for the virus than you would without it, then you are wrong (e.g., XMRV infection is not a HERV and is restricted to a rare form of prostate cancer and CFS–diseases which share no apparent common features. Somehow, these prostate cancer and CFS patients have a common exposure to this virus as a risk factor despite there being no common epidemiologic patterns. Although XMRV is clearly a murine ERV, people with exposure to mice are not at noticeable risk for prostate cancer or CFS).

It makes more sense that XMRV is a murine ERV that jumped to a human prostate cancer cell line decades ago when it was passaged through a nude mouse as a xenograft (a common practice) as elegantly shown by the Hue et al Retrovirology article. It has since been detected as an intermittent PCR contaminant.

My advice, above all else, is to test samples blindly and randomly. If you have PCR contamination, your results will be “biased toward the mean” of no significant relationship. This is the easiest and least costly confirmation possible. When your postulated virus-disease relationship survives this stringent test, then you possibly have something. Then, the science begins. Randomized and blinded testing has saved me, on multiple occasions, from appearing to be a bigger idiot than my natural talents for idiocy allow.

For what it is worth, when the CFS-XMRV paper was first published, we had severe concerns about its methodology and conclusions, which was published in F1000 (subscription required so it is reprinted below). I think it it is still valid:

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.
Lombardi VC, Ruscetti FW, …, Silverman RH, Mikovits JA
Science 2009 Oct 23 326(5952):585 -9 [abstract on PubMed] [full text]
DOI: 10.1126/science.1179052 PMID: 19815723
Competing interests: None declared

Comments

The discovery of the cause of chronic fatigue syndrome would be an extraordinary finding. Rather than providing extraordinary proof, this manuscript has flaws that leave the reader unsure of knowing precisely what was measured.

To detect the xenotropic murine leukemia-like virus (XMRV), the authors used nested-PCR on non-randomized and non-blinded samples, a recipe for uncontrolled PCR contamination. This technique re-amplifies previously cycled products and is inherently prone to intermittent false positivity that has occurred in our lab and many others (e.g. {1} and {2} on which I am the author). This is a concern in light of post-publication claims that XMRV detection rates among chronic fatigue syndrome (CFS) patients have climbed from 67% to 95%, and XMRV tests are now being sold and advertised on the internet at http://www.redlabsusa.com.

Southern blotting, which would allay this suspicion, was not done. Other results in the study also lack support. Flow cytometry and immunostaining with murine leukemia virus (MLV) antibodies were used to directly detect viral proteins in patient cells (see Figure 2A of the paper). The CFS peripheral blood cells have robust monotonic staining rather than the bimodal peaks that are expected from a mixture of infected and uninfected populations of peripheral blood cells. It is not certain whether this level of viremia for an exogenous retrovirus is medically possible. It may, perhaps, be possible but it seems improbable and is a pattern more consistent with a cross-reactive endogenous retroviral antigen.

To confirm this finding, CFS peripheral blood cells (without negative controls in Figure 2B) were immunoblotted using cross-reactive spleen focus-forming virus (SFFV) and MLV antibodies. XMRV gp70 and p30 proteins are found at higher levels in 2 out of 5 CFS peripheral blood samples (1150 and 1221) than in the positive control — HCD-57 cells directly infected with SFFV — a very remarkable result. Repetition with negative control samples (see Figure 2C of the paper) has the higher molecular weight bands cut from the photograph, thus we cannot interpret potential positivity for p30 gag precursor proteins among the control samples (see CFS samples 1199 and 1220 in Figure 2B).

Finally, the positive control HCD-57 cell lane in Figure 2C lane 8 has a completely different banding pattern from the very same control in Figure 2B lane 7 for the p30 gag protein. The elementary issue of whether the authors are measuring XMRV has to be clarified. The fundamental basis for the CFS case and control samples is also not defined at an appropriate level. The samples (supplementary online material) were “selected for this study from patients fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome (S1) and the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) and presenting with severe disability”. These are two separate definitions, the latter published in the “Journal of Chronic Fatigue Syndrome” (which is no longer in print). It is unclear how the samples were selected from these two criteria. No references or cut-offs are given for tests used to clinically define the CFS patients as cases so we are unable to interpret the essential basis for the study. In addition, no description is given to indicate that controls were tested in the same manner as CFS patients; in fact, there is no description for negative control samples at all. For a disease whose diagnosis is controversial, a clear statement of where and how the cases and controls were selected is a critical first step.

"XMRV has never replicated outside of the laboratory setting."

XMRV has never replicated outside of the laboratory setting.

The association of XMRV with prostate cancer has now been thoroughly refuted.

So Silvermann does the right thing and tells us that there isn't XMRV in prostate cancer either – so this case is closed as well.

XMRV was from the beginning an dead end – no matter how much misinformation Mikovits and her acolytes have spread, with daily changing sock-puppets. Don't expect an apology from Mikovits, or Gerwyn/V99 and his army of sockpuppets, for chasing the ME/CFS community down an dead end.

The one thing that remains lacking is an truthful explanation by Mikovits and Ruscetti as to their "amazing" lab-results – what has been presented so far in the way of explanations remains inadequate.