IGeneX's Robert Giguere about their Lyme tests

After the wonderful world of lies fraud story-telling by Mikovits/Lombardi/WPI/VIPdx and their worthless wonderful XMRV test, I am very very very skeptical about any tests, especially when I read that the lab "uses additional markers for Lyme under which some people test positive who have been negative" and Giguere's presentation style reminds me more than a little about the way my dear friend Mikovits throws sand in patients eyes – for me this is reminiscent of the XMRV rip off disaster. So take take the following presentation with lots and lots of grains of salt:

IGeneX, Inc. - Lyme testing discussion
Robert O. Giguere, director of sales for IGeneX, Inc., explains Lyme disease testing at a talk in Fishkill early this month. The Palo Alto, Calif., company uses additional markers for Lyme under which some people test positive who have been negative.

One more thing, his anthropomorphic descriptions – like the Lyme bug as "smart" and that it tries to "evade" the immune system – seem more like woo than like science.

[UPDATE] I could not find anything published by the good Robert Giguere (and I haven't seen any references to anything published so far in the video), so everything he tells seems to be secret knowledge only passed on orally – this is a major red flag for me since Mikovotis the non-publisher (with her colorful and fact-pacted talks). And what's lovely is the "hides in tissue" fear-mongering we have seen with Mikovits. 50% of tests are positive, "If you get a positive result, you have active infection", "no false positives but false negatives" (keep testing until you are positive), same fear-mongering as we have seen with Mikovits. They use PCR in strange ways (50 cycles), Mikovits used PCR in strange ways (nested).

[UPDATE] If anybody can show the world a published study demonstrating sensitivity and specificity (false negatives and false positives) of these tests, then that would be fabulous.

Seth Roberts on Tonsils, Tonsillectomies, Polio and the Immune System

Seth Roberts on Tonsils, Tonsillectomies, Polio and the Immune System:

…
Around 1900, America started to have frequent polio epidemics. Starting in 1916, they happened every summer, which came to be called "polio season". Over the years, they got worse. In 1951, thousands of children died, and tens of thousands were crippled. … As both tonsillectomies and polio increased, a horrifying correlation emerged: Children who'd had a tonsillectomy were more likely to get a certain type of polio (infection of the bulbar region of the brain stem) than children who had not had a tonsillectomy. This became common knowledge. Polio Pointers said "don't have mouth or throat operations during a polio outbreak." In 1954, the American Journal of Public Health ran an editorial summarizing the link between tonsillectomy and polio. The main evidence was that within a group of children with polio, the ones with bulbar polio were about three times more likely to have had their tonsils removed than the ones with spinal polio (infection of the spinal cord). This resembles some of the first evidence connecting smoking and lung cancer: Hospital patients with lung cancer were much more likely to be heavy smokers than hospital patients with other diseases. Although Polio Pointers implied that tonsillectomies were unsafe only "during a polio outbreak," this was false. The data implied they were always unsafe: "This higher proportion of bulbar cases in tonsillectomized persons occurs at all ages regardless of the time elapsed since operation," said the editorial. A 1957 paper about the tonsillectomy/polio association cited 19 studies that had observed it. "The association is generally regarded as an underlying causal relationship," said the paper, meaning that the usual explanation was that tonsillectomy increased risk of bulbar polio. The paper found more evidence for this explanation. Researchers considered other explanations for the polio/tonsillectomy association (for example, are tonsillectomies more common among rich children? among sickly children? ) but failed to find supporting evidence. The tonsillectomy/polio connection is probably why tonsillectomies became less popular starting in the 1950s. They declined from extremely common (the most common of any operation) to very common (the most common operation done on children).

By 1960, the tonsillectomy/polio association was firmly established, but its explanation was a mystery. If it reflected cause and effect, why would tonsils protect against infection? Around this time, work by James Gowans and others started to answer this question by figuring out that lymphocytes are the main cells of our immune system. They detect bacteria and viruses and make antibodies against them. T cells, B cells, and natural killer (NK) cells -- all lymphocytes. In one experiment, Gowans and his co-workers drained the lymphocytes from rats. The rats lost the ability to make antibodies. When the researchers put the lymphocytes back into the rats, they regained the ability to make antibodies. That's just an example. Our understanding of what lymphocytes do comes from thousands of experiments.

When the function of lymphocytes became clear, the lymphatic system made much more sense. Lymph washes germs out of tissue and into lymph nodes, where lymphocytes detect and try to kill them. The high density of lymphocytes in the nodes ensures that germs will bump into them and be detected. When lymphocytes detect more germs than usual, they multiply and the nodes enlarge. Tonsils … like lymph nodes are full of lymphocytes. Their shape and placement causes them to sample the bacteria in your mouth, so they protect you against the bacteria in your mouth. Tonsils become swollen and sore during infections because the number of lymphocytes inside has increased -- the lymphocytes are fighting off the infection. These facts about the immune system and the lymphatic system, including the function of lymphocytes, are part of high school biology. …

Removal of your tonsils is removal of part of your immune system. Our understanding of the immune system implies that removal of tonsils reduces ability to fight off infection. We cannot say exactly what tonsils do, just as we cannot say exactly what many parts of the brain do, but our general understanding of the immune system (based on thousands of experiments) implies that removal of any part of it is very dangerous, just as our general understanding of the brain (based on thousands of experiments) implies that removal of any part of it is very dangerous. When a child gets a sore throat, it suggests that his immune system is not doing a good job fighting off infections; a better-functioning system would have killed the germs sooner. Cutting off part of the body that fights infections because of too many infections makes as much sense as getting rid of fire houses because of too many fires. If your outcome measure is narrow, you may conclude that damaging a vital organ is beneficial. For example, prefrontal lobotomies were once claimed to be a a good thing (some people became less disruptive). In rare cases, the benefits of removing part of a vital organ may outweigh the risks. If I were in intractable pain, I might agree to have part of my brain removed. But not because of six sore throats.
…

And BTW,  people with adeno- and tonsillectomies seem to have increased risk of obesity and of heart-attacks, among others – hmmm.

If you search tonsillectomy/adverse effects on PubMed, you will get more than 1000 references. There is no sign in the [Cochrane] review that the authors did that search or any other search for bad effects of tonsillectomies. If the authors had looked at the PubMed articles published before their review (about 900), they would have learned that the risks of tonsillectomy include polio, weight gain, vomiting (many articles), taste distortion (here, here, here), Hodgkin's disease (here, here, here, here, here, but here is evidence that disputes the association), Creutzfeld-Jacob disease (e.g., here, here), inflammatory bowel disease and Crohn's disease, rheumatoid arthritis, severe spine infection, neck infection (here, here), speech problems (here, here), hearing loss, ear pain, visual loss (here, here), depression, several other serious problems, and immunological abnormalities (e.g., here, here, here). They would have learned that tonsillectomy "is associated with a relatively high risk of postoperative complications" and that "the actual post-tonsillectomy haemorrhage rate is much higher than that recorded in hospital statistics." (The Cochrane Review says this risk is "small".) They would have learned, if they didn't already know, that "the tonsils have a large immune function."

HIV unimpressed by Stress Management – Proponents of Behavioral Interventions "surprised" by this

Stress Management Interventions for HIV+ Adults: A Meta-Analysis of Randomized Controlled Trials, 1989 to 2006

Lori A. J. Scott-Sheldon
Center for Health and Behavior, Syracuse University

Seth C. Kalichman
Center for Health, Intervention, and Prevention

Michael P. Carey and Robyn L. Fielder
Center for Health and Behavior, Syracuse University

Abstract
Objective:

Numerous studies document that stress accelerates disease processes in a variety of diseases including HIV. As a result, investigators have developed and evaluated interventions to reduce stress as a means to improve health among persons living with HIV. Therefore, the current meta-analysis examines the impact of stress-management interventions at improving psychological, immunological, hormonal, and other behavioral health outcomes among HIV+ adults.

Design

This meta-analytic review integrated the results of 35 randomized controlled trials examining the efficacy of 46 separate stress-management interventions for HIV+ adults (N = 3,077).

Main Outcome Measures

Effect sizes were calculated for stress processes (coping and social support), psychological/psychosocial (anxiety, depression, distress, and quality of life), immunological (CD4+ counts and viral load), hormonal (cortisol, dehydroepiandrosterone sulfate [DHEA-S], cortisol/DHEA-S ratio, and testosterone) and other behavioral health outcomes (fatigue).

Results

Compared to controls, stress-management interventions reduce anxiety, depression, distress, and fatigue and improve quality of life (d+s = 0.16 to 0.38). Stress-management interventions do not appear to improve CD4+ counts, viral load, or hormonal outcomes compared with controls.

Conclusion

Overall, stress-management interventions for HIV+ adults significantly improve mental health and quality of life but do not alter immunological or hormonal processes. The absence of immunological or hormonal benefits may reflect the studies' limited assessment period (measured typically within 1-week post-intervention), participants' advanced stage of HIV (HIV+ status known for an average of 5 years), and/or sample characteristics (predominately male and Caucasian participants). Future research might test these hypotheses and refine our understanding of stress processes and their amelioration.

…
To our surprise, we did not find evidence that stress reduction interventions improved immune functioning or hormonal mechanisms that could influence immunity. These findings contrast with the PNI perspective that guided our work and most of the interventions included in our review (Antoni, 2003; Robinson et al., 2000). Thus, even though chronic stressors are known to suppress both cellular and humoral markers (see Segerstrom & Miller, 2004); the short-term use of stress management strategies does not seem to reverse these processes in patients with HIV. Before concluding that stress management interventions are ineffective in improving the immunological health of people living with HIV/AIDS, however, it is appropriate to consider potential alternative explanations for these null effects. For example, it is possible that even the most potent stress management intervention will be unable to overcome the devastating effects of HIV on the immune system. …

And yeah, before "concluding that stress management interventions are ineffective" one should however try to rationalize a lot (and then some) that it was "just this time" that your psych*–woo did not work, because HIV was so devastating.

And why is not enough for these psych*-quacks to "improve mental health and quality of life"? Why do they have to cling on to their idealistic (and anti-evolutionary) mind-body BS that "IT'S THE MIND THAT CAUSES ILLNESS!"?

(via)

Psychosomatic Model fails in Cancer – again and again

Good gracious:

…
The Cancer to Health (C2H) intervention package is based on the assumption that psychological variables have clinically significant effects on physical health via the immune system. Despite the lack of support for this idea with respect to cancer, the idea remains highly attractive and resistant to rejection because it lends prestige to psychosomatic and behavioral medicine. …

Subtitling his commentary “To Light a Candle,” Kaufmann conceded that my colleagues and I had raised valid criticisms about the design and interpretation of the C2H intervention trial. However, he took issue with our recommendation that clinical trials of this kind be suspended until putative mechanisms could be established by which psychological variables could influence survival. Quoting our statement that an adequately powered trial would require “huge investments of time, money, and professional and patient resources,” he nonetheless called for dropping a “preoccupation with mechanisms and secondary aims,” and instead putting the resources to increasing the sample size and quality of an intervention trial.
…

Learn from psych*somatic medicine, never let a lack of putative mechanisms stop you! Psych*somatic medicine and homeopathic medicine seem to be made from the same cloth, both say "Trusst me, it works, just because!"

This PNI bunch really tries hard to take the woo-cake.

… If we compare this overall pattern of results to what was stated in the abstract, we see a gross confirmatory bias in the suppression of negative results and highlighting of positive ones. …

… Reviewers must have been swayed by the consistent confirmatory bias in presentation of the results of C2H. …

… PNI cancer researchers remain a self-congratulatory group with a strong confirmatory bias in their mutual citations of the field’s claimed successes. Judging by citation patterns in the incestuous journal Brain, Behavior, and Immunity, one can readily get the impression that there are never any negative studies in the PNI cancer literature.

The articles reporting results for the C2H trial continue to be highly cited, with little apparent effect of our criticism. With a lack of other positive trials that can be cited, particular importance in the PNI literature has been attached to the claims that C2H extend survival of cancer patients. There is apparently little concern about conveying unrealistic expectations to patients concerning effects of psychosocial intervention on their immune system, and these claims fit with patents’ impressions and motivations for going to peer support groups and group therapy.

Cancer patients sometimes faced difficult choices about medical interventions to manage their disease. It is unfortunate if they are provided with misinformation that all they need to do is get stress management interventions to slow progression and extend their survival. Belief that these interventions are effective can discourage them from committing themselves to more effective, but painful, fatiguing, and disfiguring medical interventions.

I guess I have to add "psychoneuroimmunological (PNI) interventions" to my dictionary of woo.

The White House Cookbook And Longevity In The 1800s

Tom Naughton on The White House Cookbook And Longevity In The 1800s and how to answering the “All those people died before they turned 40!” crowd.

Study "No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome"

A negative HHV-6 study from Bethesda.

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome

Peter D Burbelo, Ahmad Bayat, Jason Wagner, Thomas B Nutman, James N Baraniuk, Michael J Iadarola

National Institutes of Health, Bethesda, MD
Georgetown University, Washington, D.C.

Abstract:
Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases.

Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101).

Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors.

Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region.

In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity.

To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies.

While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B.

However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients.

These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.

Not really a particularly large CFS patient cohort in this study. Especially considering that I don't know how the CFS patients were selected, nor by whom – none of the names ring a bell for me.

While I don't think that any one of the herpes viruses is the root cause of ME/CFS, this study from Bethesda does not instill confidence for me – oh well.

Here we have researcher from Bethesda who know something about HHV-6, but I don't know if they know much about CFS patient populations. And then here we researchers from Latvia who don't seem to know much about HHV-6, but may (or may not) know more about CFS. And those who know both HHV-6 and CFS produce underwhelming results. It's a sad world.

Is Acne caused by the Hormones in Milk and Dairy?

So, do the hormones in milk cause acne? I isolated pasteurized cow milk (and dairy) as the cause my acne.

• If I eat cheese made from raw milk, I get no acne
• If I eat cheese made from pasteurized milk, I get acne

I think the hormone levels in both raw and pasteurized products should be comparable. Of course it is possible that some producers of raw milk use different production methods, and the raw milk might contain less hormones – but then again I tried three different brands of raw milk cheese, and ate each time a large amount of raw milk cheese in one go, without getting acne. So, I don't think it's the hormones.

Another thing that makes me think it is not the hormones in milk, is that if I eat some dairy, I get about three distinct points of acne (pimples/papules/nodules) for about 100 to 150 grams of dairy from pasteurized milk. If it were hormones, I would expect slightly increased inflammation everywhere. But instead I see "the winner takes it all" with a mainly "all or nothing" inflammation.

Now this is pure speculation, but I suspect that "something" from milk (bovine IgA immunoglobulins?), that was changed during pasteurization, traverses intact from the gut to the blood. Then human immunoglobulins attach to this "something" and start forming immune complexes. Some of these immune complexes either dock to the relevant skin tissue, or they form there in the first place – and these would be the distinct points were then inflammation arises, because now leukocytes rush in and start a giant gang-bang at the expense of my no longer acne-free skin.

Still much to learn…

Thoughts on psychological/psychiatric problems

Some speculation on psych* problems after my recent post on depression:

1. Psych* (psychological/psychiatric) problems exist (I'd be stupid to deny that)
2. Many (if not most or even all) psych* problems haven an organic root cause (environmental / dietary / pathogenic / etc.)
3. Even those psycho* problems with an established psych* cause (PTSD comes to mind) have an substantial environmental/organic component
4. Therefore few (if any at all) psych* problems have a psychiatric root cause, and few are therefore actually psych* problems
5. Furthermore, the response of such an psych* problem with an organic cause to psych* treatment will be weak – at best

And as a addendum: Good psych* therapy, with a good understanding of the pathological problems, and a good understanding of its own limitations, can (at best) improve the quality of life – but should be careful not to mistake improved quality of life with an cure.

Cognitive Behavioural Therapy (CBT) fails for Depression

Cognitive Behavioural Therapy (CBT) fails for depression.

Who would have thought?

(Saturated) Fat improves Cognition

Seth Roberts: Short-Term Effects of Fat, Protein and Carbohydrate on Cognition: Fat Best

Omega 6 fatty acids – The cause of obesity?

Evolutionary Psychiatry has the details:

…

Mice with 8% linoleic acid diets (comparable to modern human diets) had elevated levels of linoleic acid and arachdonic acid in the cell membranes (not surprising) compared to the historic 1% mice (ahem, human) diets. Levels of the endocannabinoids were tripled in the 8% LA diets. Dietary LA increased body weight, food intake, and fat tissue in the mice.

Here's the key, however: Adding 1% EPA and DHA omega 3s to the mouse diets seemed to undo much of the problems caused by the gallons of omega 6. Omega 6 in the cell membranes dropped, as did the levels of endocannabinoids, as did the fatty tissue, weight, and overeating in the mice. These mice didn't look quite as nice metabolically or had as beautiful cell membranes as the 1% LA mice, but it was loads better than the 8% LA omega 3 deficient mice.

Dietary LA also increased leptin and decreased adiponectin.

In the human population, dietary consumption of soybean oil, poultry, shortening, and sugars (but not grains, beef, fish, eggs, dairy, or vegetables) were positively correlated with obesity in several epidemiology cohorts from 1909 to 1999.

…

Fodder for thought about the immune system

Interesting things about the immune system:

…

Popular culture also its myths. Take the immune system. Please. It is not a bicep that can be made stronger with a little exercise. It is a complex network of cells and proteins. There are antibodies (IgG (with five subtypes, IgM, IgA, IgE), the complement pathway, polymorphonuclear cells, monocytes, lymphocytes in a profusion that rivals beetles. God, I think, has an inordinate fondness for lymphocytes. There is the Toll system, the cytokines and lymphokines, the non-specific defenses like cilia and mannose binding lectin and on and on and on.

I have a journeyman’s understanding of the immune system, what is needed to understand why a given patient has an infection, although there is little I can do to reverse the immunologic defects: abnormal antibodies from Waldenström’s or low mannose binding lectin levels from liver disease are not amenable to clinical intervention. The most interesting discoveries concerning the immune system over the last few year has been the elucidation of the many polymorphisms in the immune system that can increase or decrease the risk of a variety of infections.

The fault, dear Brutus, is not in our stars,
But in ourselves, that we are underlings.

Often what determines health or infection, life or death, is a single amino acid substitution, say, in a Toll like receptor or the structure of our snot.

Of course these variations in the immune system are not absolute risks, they are relative risks. Health and illness are complex and a career medicine and infection control has continually emphasized that it is rarely one thing that leads to health or illness. It is the confluence of multiple factors, death by a thousand cuts.

…

Maarten Maartens on Psycho*

Maarten Maartens is having a go at "Psychos":

How to write and think like a real psychiatrist (psychologist, psychotherapist)

…
In order to be well understood, I have to start with

-- ** A Warning ** --

There are, in these difficult times, still a few psychiatrists, psychologists and psychotherapists who "mean well" with their patients, and who occasionally even may "help" them, rather than themselves, as is and should the rational moral goal of any medical health carer: The health carer is there to care - for himself or herself, and for his or her family and friends.

This Easy-In-One-Lesson program is not for or about these few "do-gooders", but is exclusively for real professionals, by which I mean that group of great and deserving human beings who form the ordinary run and core of the well-to-do soundly careerist and happily conformist majority, also among psychiatrists, psychologists and psychotherapists, who - being of such diverse educational attainments - might perhaps be further referred to collectively as "psychos", so as not to prejudice the value of their diverse degrees.

The fact is that these few "do-gooders" I mentioned usually have as little real knowledge of how the human brain works, or of how people think, feel, err, understand meanings, have selves, have consciousness, or desires, as do the far larger group of professional psychos - but then some of these "do-gooders" may have a native or cultivated knack, talent, or art that helps them help others, rather than themselves.

This is not the sort of moral behaviour or sense of values that the well-to-do soundly careerist and happily conformist psychiatrist, psychologist or psychotherapist, likes to behold:

These "do-gooders" - who really try to help others, rather than pretend to do so in order to help themselves - generally are the curse and mockery of the professional majority, whose professional moral and human goal - like most anyone in any profession! - is to get rich or at least well to do, namely by practising the "evidence-based medical science" that seeks to cure psycho-therapeutical professionals from the horrible blights of personal debts, poverty, hard work, or honesty, in which the sciences of psychiatry, psychology and psychotherapy have happpily prospered now for over a 100 years with many great successes:

Generation upon generation of psychobabblers has found financial well-being, and social support and acclaim, and also found political financial support from tax money for furthering "research" in what they all agree should not and never be called "the art of psychotherapeutical conmanship", even though that is what it really is.
…

Very much enjoyable.

Seth Roberts articles on Dairy, Grains and Acne

Seth Roberts is collecting some articles about dairy, grains and acne.

"One Diagnosis - Several Fatigue Diseases"

Via the CO-CURE.org maillist (emphasis mine, and I corrected a few sentences that seem to be roughly translated):

A diagnosis - several diseases Fatigue.

Prejudice among many in the medical profession scares away most people who are interested in researching the ME's biological basis.

Lars Th. Narvestad- earlier Ass. Director of Hydro, now bedridden patient Published: 10.okt. 2012

Fatigue comes in many shapes and forms, and is one of the most common symptoms associated with the disease. It is associated with a variety of physical and mental disorders. Because it is so common and associated with so many different diseases, fatigue isolated symptom, not suitable as a basis for a medical diagnosis.

In spite of this it is prevailing practice in health-Norway that patients with some form of fatigue lasting more than four months (plus one additional symptom of a list of ten) are diagnosed with Chronic Fatigue Syndrome (Chronic Fatigue Syndrome - CFS), so while other known disease can not be detected with blood tests or other objective tests (NICE criteria).

One need not be a doctor to understand that such a diagnosis, which more or less exclusively based on the symptom of fatigue, will accommodate several different diseases and conditions.

One of the populations that have ended up in this bag diagnosis, patients with a distinct neuro-immune disease that historically only had the name Myalgic Encephamyelitis (ME). Under unfavorable circumstances, the term CFS introduced in the mid 1980's and is now used CFS and ME interchangeably when patients with this diagnosis should be described (CFS / ME), although prevalence studies show that there may be as few as one in five patients actually ME using broad diagnostic criteria for CFS.

Different patients - different forecasts

Mixing of disease descriptions with different patient groups has created great confusion and skepticism to these patients in the medical community and the public. Who what's wrong, and is it really any of those patients who have a severe physical illness? The impression is reinforced by the health authorities' experts argue that most with this diagnosis are cured, and some patients are presented in the media and declares himself fully with various forms of alternative therapy.

This picture is in stark contrast to the clinical experience of physicians who follow ME patients over time doing it. One of them, Professor of Medicine Anthony Komaroff of Harvard Medical School, who has followed over 400 patients over 25 years, says that very few of his patients recover. Almost all [live with the] disease [for] the rest of [their lives], often with a gradual deterioration. Many are very crippled, the sickest in an almost vegetative state.

Questionable Research

This experience, and all the studies that point to biological causes of disease, have been overlooked by health authorities with regard to the research conducted by a group of British psychiatrists and their allies. These researchers argue that their study provides evidence that cognitive behavior therapy (CBT) and graded exercise (GET) is a safe and curative treatment for patients with this diagnosis, despite the fact that research shows that the vast majority of ME patients whatsoever not noticed any effect of this kind of treatment. Then the seriously ill patients, who are worse by minimal effort, not included.

Weak results and strong criticism of criteria that include different patient groups, has not stopped these researchers from getting a steady stream of studies with the same topic for the past 20 years. The need to repeat itself, coupled with the constant attack from all studies that indicate biological causes of ME, memories suspicious about the research and propaganda tobacco industry sponsored to inactivate, dilute and disguise the damage to health caused by smoking.

Unexplained illness

Unfortunately, one of these methods succeeds in spreading a perception in the medical community that ME is a psychosomatic disorder, and research on MES biological basis and reason has as a consequence been virtually eradicated from public budgets for decades.

It is therefore no coincidence that […] ME is still an unexplained illness. If the biopsychosocial school [has their way, then ME] remains mysterious. Then they periodically go on the podium and continue their guesses, and theorizing about ME. For patients and relatives whose lives are ruined by this disease, it is a sickening thought. However, there is evidence to suggest that it might be the idea.

Over Diagnosis

Health Directorate works fortunately now to have realized that they have long relied on incorrect information and that it is necessary with the introduction of new and more stringent diagnostic criteria for ME. This is an important step in stopping the overdiagnostiseringen which unfortunately taking place, and with it form the basis for the right patient gets the right treatment.

When Haukeland GPs Fluge and Mella published their study on the effects of the cancer drug Rituximab in ME last fall, it was given its great hope for ME sufferers. In a small, but very well done study experienced two thirds of patients clear improvement after treatment. The results attracted attention around the world and received great attention because discovery could potentially change the lives of hundreds of thousands of ME patients while providing an understanding of disease biological mechanisms.

Conspiracy Theories

In response to these brilliant news managed Journal of the Norwegian Medical Association for two leaders in quick succession to put forward conspiracy theories and more strange comparisons that seemed to have intended to ask the authorities, patients and Rituximab study in a bad light. It was given the impression that CFS patients as a group scares scientists and clinicians away from the disease. The reality is unfortunately that there are prejudices of many in the medical profession that scares away most people who are interested in researching the MES biological basis. There is nothing patients want more than biomedical research. There, however, they do not want is doctors who are researching various forms of fatigue and presents it as ME research.

The media's lack of critical attention on the dilution of diagnostic criteria contributes to blurring and polarize public debate on ME. This leads to a deep despair and frustration for thousands of Norwegians living with a life-long disease.

Political responsibility

Last year's report from SINTEF and the two leaders of the Medical Association Journal has exposed attitudes and beliefs that dominate in the medical community about ME. When you also know that ME / CFS costs the Norwegian society in excess of $ 1 billion annually in lost income, benefits, and nursing and care costs, a Norwegian politicians no longer leave important decisions about health care in this patient group to traditional agencies. One must ensure that the necessary resources and influence given to the academic communities who want and are able to differentiate ME patients from patients with other disorders.

Cancer doctors at Haukeland need 11 million to complete a large multicenter trial of Rituximab, and it is successfully write medical history. Should Council, contrary to expectations, reject the application for funding this world leading research, the patient wilderness continue.

Well, I disagree that there is one "distinct neuro-immune disease that historically only had the name Myalgic Encephamyelitis (ME)" – I think there are a few distinct diseases that will be found under the label ME. But otherwise it is

What’s Wrong With Wheat?

The Problems with Modern Wheat from Mark's Daily Apple (Mark Sisson):

… Wheat avoidance tends to be the rule in our circle. Still, though, haven’t you had that moment where someone asks “What’s wrong with wheat?” and you mutter something about gluten and the advent of agriculture that doesn’t really sound convincing, even to you? Consider today’s post a crash course in exactly why modern wheat in particular is a problem. To borrow a horrible concept that has helped politicians and their cronies obfuscate the truth for decades, these are “talking points” to which you can always refer when asked. The only difference is that these talking points are based on actual research.
…

It’s less nutritious.
…
Between 1843 and the mid 1960s, the mineral content, including zinc, magnesium, iron, and copper, of harvested wheat grain in the experiment stayed constant. But after that point, zinc, magnesium, iron, and copper concentrations began to decrease – a shift that “coincided with the introduction of semi-dwarf, high-yielding cultivars” into the Broadbalk experiment.
…

It’s more damaging to celiacs and gluten-sensitives.
…
So what’s the deal with modern wheat? Well, celiac disease is on the rise, and some researchers have suggested that this is caused by the prevalence of certain gluten proteins that predominate in the new varieties of wheat.
…

It’s prepared differently.

Consider how bread is made today:

With refined, old (often rancid) white flour instead of freshly ground wheat.

Using quick rise commercial yeast instead of slowly fermenting with proven sourdough cultures.

…

Look AHEAD trial stopped

Look AHEAD trial stopped
Eat less, move more, have your heart attack on time!

With apologies for lack of any attention to the blog recently (which may be set to continue for some time) but this snippet just had to get passed on. This link from Karl:

http://www.theheart.org/article/1458351.do

More info here

http://www.nih.gov/news/health/oct2012/niddk-19.htm

And the glowing anticipation of success here from the planning stage:

https://www.lookaheadtrial.org/public/home.cfm

Pubmed gives a series of genuine success stories from the early days on all sorts of parameters. But the cardiovascular end points show how utterly useless these interventions are long term.

However the massive omission, from the quick look I've managed, is of any intention to report the all cause mortality. It seems very likely to me that more people died in the intervention group than in the usual care group, but p was > 0.05.

Call me a cynic, but I think they stopped the trial because they could see where that p number was heading. Has anyone seen a body count from anywhere in the trial?

Also, what might the outcome have been if the intervention group had been repeatedly bullied, harassed and indoctrinated to maintain a normoglycaemic, low grade ketogenic diet for 13.5 years? Say to an HbA1c of around 5%?

Ha ha ha bloody ha.

Peter

[Update]: And Seth Roberts on the topic.

Gene Sequencing growing faster than Moore's Law

Gene Sequencing growing faster than Moore's Law:

Wow.

José Montoya's new paper

Via CO-CURE:

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein–Barr virus IgG antibody titers

Tessa Watt, Stephanie Oberfoell, Raymond Balise, Mitchell R. Lunn, Aroop K. Kar, Lindsey Merrihew, Munveer S. Bhangoo, José G. Montoya

Article first published online: 10 OCT 2012

J. Med. Virol., 84: 1967–1974. doi: 10.1002/jmv.23411

Abstract

Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) IgG antibody titers.

This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients.

An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks).

Antibody titers were considered high if HHV-6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160.

Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness.

Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning.

Thirty-two patients (52%) were categorized as responders.

Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively.

Baseline antibody titers showed no significant association with response.

After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001).

Longer treatment was associated with improved response (P = 0.0002).

No significant difference was found between responders and non-responders among other variables analyzed.

Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies.

Longer valganciclovir treatment correlated with an improved response.

An uncontrolled, unblinded retrospective chart review? With self-rated improvement? I am seriously underwhelmed.

If you have high titers, I won't blame you if you might want to give it a shot. If someone else pays for it, or if you have the money, that is.

And don't expect any miracles and don't bankrupt yourself on Valganciclovir.

Herpes viruses seem to be a contributing factor for some people with ME/CFS, but I would be seriously surprised if it turns out to cause ME/CFS in a larger sub-group of ME/CFS.

Hobbesianism in the pharmaceutical Industry

Ben Goldacre:

Question: Do you think there are any pharmaceutical companies that stand out in terms of transparency of trial results? And at the other end of the scale, are there any companies that consistently fail to publish negative trials?

Ben Goldacre: No. I have no reason to believe that any one is any better than the other. If you have bad regulations, incoherently enforced, then everybody does what they have to do, to succeed in the marketplace.

Of what reminds me that, that "everybody does what they have to do, to succeed in the marketplace"?

"That which is now to be expropriated is no longer the labourer working for himself, but the capitalist exploiting many labourers. This expropriation is accomplished by the action of the immanent laws of capitalistic production itself, by the centralisation of capital. One capitalist always kills many."
-- Karl Marx on the primitive accumulation of capital

"Je ein Kapitalist schlägt viele tot."
-- Karl Marx über die ursprüngliche Akkumulation

Yes, the "expropriation of many capitalists by few capitalists", everybody has to do what he has to do to succeed – aka Hobbesianism.

Money and Fraud

Too little money for research, and you get fraud as a result. Though too much money seems to be a problem as well:

Texas's $3 billion [per 10 years] cancer research agency is in trouble again: Its peer review system appears to have come apart. The entire eight-member scientific review council of the Cancer Prevention Research Institute of Texas (CPRIT) is stepping down, with most citing concerns about the integrity of the agency's peer review process. Many members of CPRIT's 100-strong roster of peer reviewers have begun to follow.

Looks like the NCI isn't the only one that got a little bit sloppy with billions from the "war on cancer".

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.
…

“Actually, it’s worse than you know…”

The life of frauds and whistleblowers in the medical sciences:

…
I travelled to Telford last month to hear Wilmshurst give a lecture to the Royal Statistical Society on libel and other barriers to exposing research misconduct. It took me back to 1996 when we invited him to come to the BMJ and give a talk—behind closed doors—to our staff and advisers and colleagues from the Lancet. He reeled off case after case of misconduct, many of them involving prominent people. The audience listed intently, but I was unsure of the reaction. Might somebody leap up and say “How dare you accuse x of misconduct. He is one of the great men of British medicine”? In fact in my memory the reaction was the opposite. People said things like “Actually, it’s worse than you know…”
…
Now 16 years later Wilmshurst has a longer and updated list, and somebody in the audience asked if he thought things are getting better or worse. He thinks probably worse: he’s had seven whistleblowers contact him in the last two months.
…

Lot's and lot's and lot's of anecdotes and case studies, but when will there be more research as to causes and mechanisms, and when will there be real consequences to prevent this in the future?

Perhaps strangely it was his first story that best captured the corruption that Wilmshurst has been fighting all his professional life. It was the early 80s at St Thomas’ Hospital in London, and Wilmshurst was doing research into amrinone, a new drug for heart failure manufactured by Sterling Winthrop, a company since taken over. The drug was supposed to increase myocardial contractility, but Wilmshurst found that it didn’t. Worse, it had serious side effects. Wilmshurst and his boss prepared to publish, but Sterling Winthrop, the manufacturers of the drug, threatened legal action. The company also asked if Wilmshurst and his boss would be willing to meet with their experts. They agreed. The message was that St Thomas’ was getting very different results from everybody else and that their lab would be discredited if they were to publish.

And by the way, the next person who ignores the countless lifes of patients that have been endangered by medical fraud and says "Well, but science is self correcting" will be diagnosed with a mental disorder, pumped full of fraudulently tested pharmaceuticals and put into a lunatic asylum for the rest of his life.

One of the things that seems to make Wilmshurst so cheerful is the black humour of his stories. Many of them involve doctors who are guilty of misdemeanours but who sit in judgement on others. He told the story of Peter Richards who decided to bury the fact that Clive Handler, a doctor, at Northwick Park Hospital, was found guilty of using NHS research funds to subsidise his private practice at a time when Richards was medical director of the hospital and chair of the professional conduct committee of the GMC. Previously he had been dean of St Mary’s Medical School, prorector for medical education at Imperial College, and chair of the Council of Deans of UK Medical School and Faculties. When Handler eventually appeared before the GMC, the GMC’s lawyers ask that Richards stand down from chairing the committee. As Wilmshurst said, it’s as if a judge at the Old Bailey were to say “I’ll have to excuse myself from hearing this case as I helped the accused bury the body.” After having to stand down from this committee Richards continued to chair other conduct committees. Wilmshurst told several stories of doctors who had been found guilty of research misconduct but gone on to be deans and others in charge of researchers.

Like we have independent investigation, prosecution and courts for criminal cases, we need a similar criminal law with similar independent institutions for medical fraud.

Is Myalgic Encephalomyelitis (ME) an Neurological Disease?

First of all, let me say that Myalgic Encephalomyelitis (ME) is classified as a Neurological Disease (ICD 10 G93.3, or F286).

And I don't want to change that.

At least not now. Not until we know whether ME is one disease, or several distinct diseases, and until we know what the pathological processes at the root of ME are.

So regardless how ME is classified, what is the reality of ME? About that I want to speculate a bit.

Personally, I think it will turn out that the ME patient population, very much like CFS, will be composed of several diseases. Maybe there are, compared to CFS, less people who are (mis-)diagnosed with ME but have actually something else – but I doubt that ME is only one disease.

From the Norwegian Rituxan study by Fluge and Melle we know that a sizable portion of ME/CFS patients may have an autoimmune condition – which may or may not exclude neurologic problems to be the root cause. We can't tell from the Norwegian study one way or the other.

From the studies by Christopher Snell we know that VO2 max and exercise tolerance are reduced in a CFS patient population, which would point to cardiovascular causes, lung causes, or muscle-metabolic causes – a neurological root cause seems IMHO unlikely in the sub-group characterized by Dr. Snell, but still possible. The results from Dr. Snell are not particular specific and can be caused by different pathological processes, so there could be several diseases out there having the same VO2 max presentation (as seems already to be the case with other known non-CFS diseases).

From the studies by Kathleen and Alan Light we know that there are at least two sub-groups in the ME/CFS (and FM) patient population:

• People with a specific presentation of POTS like gene-expression
• People with a nonspecific presentation of fatigue and pain gene-expression

The specific POTS presentation may be indicative of a cardiovascular orgin, possibly with the involvement of endocrine system (beta-receptors seem to be implicated in a sub-group in the Lights studies). So the POTS sub-group IMHO may be one distinct disease, and I think it is unlikely to be several diseases.

The later sub-group (fatigue/pain) may IMHO most likely originate from metabolic problems in the muscle. It could be possibly caused by several pathways, which would possibly mean several distinct diseases.

These problems could in turn affect the brain in a negative way, showing up as neurological symptoms ("brain fatigue" or "brain fog", etc.)

So in conclusion, at the moment a sizable portion of patients seem to have a non-neurological root cause, especially hinted by the work of Kathleen and Alan Light.

Still, a minority of ME/CFS patients may be suffering from one (or more) – as of now – unknown and/or poorly understood neurological diseases – though it seems unlikely to me that a majority of ME/CFS patients have a neurological problem as root cause.

Of course, this does not preclude an neurological involvement in ME/CFS patients with non-neurological root causes.

This picture may change when more research brings us more data, until then we have to consider non-neurolgical etiologies for a majority of ME/CFS patients – I would not cling on to the neurological label forever.

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.

Some CFS patients have "fatigue kinds … constructed by the … mind"?

While it has always been essential, it has now also become urgent to segregate the subset that we are calling ME more clearly, using the ME International Consensus Criteria, so that researchers can confirm/disconfirm their results using patients who have chronic fatigue of this clearly bio-pathological origin. Otherwise the all-inclusive umbrella of “CFS”, in ambiguating natural and psychosocial kinds of fatigue, will continue to dilute the results of any investigations and maintain the pervasive confusion resulting when biopathological kinds are mixed indiscriminately.

Conclusion
The results of Jason et al’s studies have confirmed that the Canadian Definition of ME/CFS had clearly separated cases who have ME (fatigue of bio-pathological or natural origin, arising out of a pathological causal structure present in the world apart from the mind that is observing it) from those who have CFS (which includes the minority of the specific natural kinds we are calling ME plus a majority of fatigue kinds that are secondary to other diseases, plus parts of the normal homeostatic activity-rest cycle designed by evolution, plus fatigue kinds constructed by the re-presentational observing/thinking and thus dualistic model-making mind).

Guess who has written that, as one possibility for the cause of fatigue in CFS patients?

Reeves? Straus? Wessely? Wrong, it was Dr. Carruthers, co-author of the International Consensus Criteria (ICC) for ME.

Dualistic body-mind BS at its idealistic best low.

So the people pushing ME have no problem leaving people with "only" CFS behind for the psychobabbler, no matter whether rightly or wrongly diagnosed so.

To hell with the ME advocates I say.

And the following sounds like classic post-modernist Sokal:

The prevalent use of symptom-based definitions has been adding to the confusion by analyzing complex syndromes using a Cartesian [?] method of analysis that isolates symptoms by putting them onto standardized lists of separated [?] subjective entities [?], thereby bypassing [?] the dynamical [?] subjective/objective interactive [?] processual [?] causal [?] on-line [?] context [?] that points to an underlying interactive [?] causal [?] organization [?], even if we are as yet unaware [?] of its details.

Contrariwise the new ICC encourages that symptom structure [?] be observed on-line [?] as interacting [?]  embodied [?] and embedded [?] causally [?] interactive [?]  dynamical [?] process(es) [?] that have multiple subjective/objective manifestations [?]. These are first observed (or ignored [?]) in a clinical dialogue as (subjective) symptoms and (objective) confirmatory [?] signs which are disambiguated [?] on-line, in their natural [?] context [?], as temporally [?] dense [?] and as having felt/observed [?] causal [?] efficacy [?]. These individuated observations are in turn [wishful thinking at the moment] confirmed by objective biochemical measures, pathophysiological functional testing and imaging. The “same” phenomena can also be studied off-line [?] using epidemiological studies which observe the generalisable constancies found in groups of variously homogenous groups of cases using standardizing techniques of questioning and observation to obtain generalisable results and case definitions. In the standardized and properly randomi­zed environments of scientific experiments, the effects of interventions can be properly controlled, and thus general rules of causality [?] inferred and quantified.

WTF? The ICC are a Cartesian list of individual symptoms! I don't know where to start with all this. I say Carruthers may be partially unclothed.

CFS, the cash cow that keeps on giving!

Not enough that we have Simon Wessely making a living out of treating CFS patients the right way (wink, wink), not enough that we have the CDC having their hand on CFS research money, not enough that we have the NCI having their hand on CFS research money, not enough that we have a lot of good friends like Harvey Alter, Judy Mikovits, Michael Maes and Kenny De Meirleir, no, we have a good old friend with Hemispherx having their hands on CFS research money!

http://www.thestreet.com/story/11730475/1/hemispherx-atm-withdrawals-raise-a-red-flag.html
…
Hemispherx used a Friday night SEC filing to disclose the sale of 10.9 million shares of stock at an average price of 92 cents per share. After expenses and commissions, Hemispherx net $9.5 million from the sale.

You said this stock sale was stealthy. Why?
…
An FDA advisory panel is scheduled to review the chronic fatigue syndrome drug Ampligen on Dec. 20. Presumably, a positive panel vote will push Hemispherx shares much higher than where they trade today. Yet, Hemispherx is rushing to raise money now. That's not a good sign.

Maybe Hemispherx wants to raise a small amount of money now and then plans to raise more money later, hopefully at a higher share price if the Ampligen panel votes to recommend approval.
…
Ha! That's funny. The FDA rejected Ampligen as a chronic fatigue syndrome therapy in late 2009. Yet for the past three years, Hemispherx has done nothing to advance Ampligen, including refusing to run a new clinical trial that FDA asked for. Hemispherx has plenty of cash to develop Ampligen. The problem is that management is hoarding cash to pay its outrageously high salaries, not to spend on Ampligen.

How much does Hemispherx CEO Bill Carter earn?

Carter was paid $1 million in salary in 2011. With bonuses, stock options and other perks, his total compensation for the year was $1.5 million. Carter's salary alone has doubled since 2009 -- the year that Ampligen was rejected.
…

I can hardly believe that!

It must be a lie!

Surely the invisible hand of the free markets will intervene! Let us all pray to the invisible hand of the free markets! Capitalism, in whom I trust, praised be your name, blessed be your trickle-down-economy!

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!

On Christopher Snells 2012 ME/CFS Exercise Challenge Lecture

On Christopher Snells 2012 ME/CFS Exercise Challenge Lecture, this came in via Tom Kindlon and Jan van Roijen (via the CO-CURE maillist):

I have omitted a lot of the discussion on the advantages/disadvantages of various scientific methods etc. and stuck mainly to the items that I would assume a non-scientific interested person would wish to know.

If you’re of a scientific bent, you would probably get more benefit from watching the actual lecture. All credit to Professor Christopher R Snell of the Pacific Fatigue Laboratory, California (USA).

If you’re a sufferer, I recommend watching from 54:00 through to 59:20 – they go through a brief summary of energy conserving techniques, which could be very useful! Following this there is a case study of how they applied some of these techniques to a 17 year old sufferer to allow her to manage the condition better.


Clinical exercise testing in CFS/ME research and treatment: A summary

On an exercise test where a person has to exercise until they are exhausted, a healthy person will recover usually within a day, definitely within 48 hours (on the outside).

When they did this with CFS patients, they had only one person recover within 48 hours – the average recovery was 4 days.

CFS patients also had symptom flares as a result of this test.`

`````` There are problems with the PACE trial:

* they very selectively reported results

* they only took high-functioning CFS patients

* they used the 6-minute walking test (see below)

* patients at the end of the trial, were still walking at a severely disabled speed, even when they had improved the distance they could walk. If a patient who needed a heart transplant could only walk this speed due to a lung problem, they would not be allowed onto the transplant list because they would not be deemed well enough to actually survive.

* there is no mention of any improved functioning in any other area for any of the trial participants


There are problems with the 6-minute walking test (as used in the PACE trial as a measure of functioning) and other similar tests

* they assume that the patient does not exercise to exhaustion, or anywhere near exhaustion. All the understanding of the results are based on the assumption that it was just a casual exercise experience that they could easily repeat.

* it does not work for specific groups of unhealthy people, it is designed only for a healthy population, so results from an unhealthy group can’t be interpreted validly. This is because they rely on the heart rate as a measure of energy production, but the way the heart rate and energy production are linked in a healthy person is not necessarily the same in a sick person. Many studies in fact show that the link between them in certain diseases is very different – meaning you cannot rely on these tests in sick individuals, without first carrying out studies to determine what the connection is.

* the american heart association says not to use tests with heart-rate measures, as many people use heart-rate controlling medication (eg: for POTS, migraines)

The best way to assess physical function is to use

“cardio-pulmonary exercise testing”, which is to measure:

* oxygen consumption (as oxygen is used directly to produce energy, this will always be a correct measure). This is effected by lungs, heart and muscles.

* the “anaerobic threshold” – which is the point at which the carbon dioxide you breathe out is greater than the oxygen you take in. In a healthy person this is 50-60% of max. oxygen consumption; in an athlete it may be as high as 90%. In CFS patients it is very very low, and going above it makes you worse – and is very easy to do

* you can prove beyond doubt that someone is not faking these results because you are measuring the amounts of oxygen and carbon dioxide in the air they breathe in and out.

* you can establish beyond doubt that the persons capabilities in the test have nothing to do with motivation/effort because the “effort” of the person is shown in the oxygen intake/carbon dioxide given out

* these are a good measure of function, they are very reliable and accurate

* there are alreasy established measures of this for many other healthy people and disease states, meaning you can compare ME patients to others easily


Exercise will not cure ME/CFS. But – people who do not exercise will suffer the effects of a sedentary lifestyle, so if you can do some exercise without making symptoms worse, it is probably beneficial to do so

Post exertional malaise occurs across all the spectrum of ME/CFS patients – regardless of how severe they are

It does not show up in an single exercise test – you need to test again (they do it 24 hours later). This allows them to measure the post-exertional effect. (Many ME/CFS patients could be assessed as normal on a single test, due to eg: having rested beforehand, it is the second test which shows they are ill)

It is hard to separate the effects of deconditioning from the effects of CFS with a single test

* but with multiple tests you can see what CFS has done.

At 37 minutes there is a table of results for ME patients


The second test shows:

* ME/CFS patients do worse on the second test; they are significantly worse (in terms both of workload they accomplish, and the oxygen/anaerobic measures)

* non-ME/CFS patient will improve on the second test (graph at 42mins).

* ME/CFS patients have a drop in the oxygen consumption, but a much much worse drop in the amount of work actually achieved. This shows that the exercise on the second test is less effcient

* the drop in peak-oxygen consumption is actually less for severe patients than for milder patients; but severe patients start out with a much lower oxygen consumption than a milder patient.

* the drop in workload done is more in severe patients than milder patients

* The theory is that there is a basic level of oxygen consumption that you need to survive, and the more severe you are the closer you are to this base level. So severe patients cannot drop any lower or they would die, so they reduce workload instead.

This is a reproducable, reliable test which shows the extent of the post-exertional malaise; other research groups have replicated these results

Their tests show objectively for CFS patients:

* an atypical recovery

* an abnormal stress-test

* post exertional malaise

There are many theories as to why post-exertional malaise occurs

Their research shows ME/CFS patients

* have a reduced physical working capability

* the aerobic energy generation (the production of energy in the presence of oxygen) is impaired

* activity exacerbates symptoms ( every ME/CFS patient has post exertional malaise)


Their research can be used as an objective proof of disability (for example, for disability assessments and clinical trials)

It is quantifiable – ie: it can measure accurately to a degree how ill the patient is

It reveals abnormality across many systems


Cognitive behavioural therapy is not a cure for ME/CFS – but it can be useful to help patients manage/adjust to their illness

ME patients can go a very long way into the anaerobic threshold (longer than most people manage) because they have adjusted to being ill; but this results in huge PEM. So short-term, patients can often manage a lot more than they can manage long-term.


Avoiding activities above the anaerobic threshold will help patients avoid PEM

* heart rate monitors can help; they are set to go off just before you hit the anaerobic threshold, to get you to rest instead of using too much energy

* activity logs can help; you can identify activities which make you worse (what activities make you ill? How do you feel the next day? Do you get PEM? Can you carry out other normal activities and these activities?)

* “rates of perceived exertion” can help; this is a fancy way of saying, if it feels like a lot of effort, it is a lot of effort – stop!


Resting will help recovery from going into the anaerobic threshold

If you go above the anaerobic threshold, you will have to pay back far more energy


Physiotherapy can help – but physios often need to be re-trained to understand ME/CFS

* reconditioning will not work with ME/CFS patients


They have a therapy called “energy conservation therapy” – I think this is basically working out how to manage your life now with less energy. It involves

* pacing

* body positioning (ie: sit instead of stand to use less energy)

* protecting joints

* using assistive devices

* planning activities (to make sure you don’t over-exert)

* using any energy saving thing you can do etc.


They also have a “theraputic exercise program” (nothing like GET!) – this can be aided by trained physios

* learning to breathe properly

* training the anaerobic system, not the aerobic system

* exercise must be recovered from within 24 hours – if you take longer than that to recover, it is harming you, not helping

* stretching

* only doing a little bit at a time

* only ever increase amounts if you aren’t experiencing symptom increase – decrease amounts if you experience symptoms


He closed with the comment:

“It doesn’t really matter what you call it, there are hundreds and thousands of people who are really really sick; if the medical profession is not helping them, their government representatives are not helping them; they need help urgently.”

Mark Sisson on Self-Experiments

Mark Sisson on Self-Experiments:

…

• Start with a sensible premise drawn from reliable sources.
  
  Like your own experience, another’s, or results from clinical studies.
  
  An example: you forget to eat breakfast and feel stronger during the afternoon lifting session. Was it the lack of breakfast? Maybe; test it.
• Eliminate outlandish premises.
  
  I wouldn’t advise testing whether the trans-fats in Crisco are actually harmful by eating a tablespoon every morning,
  
  and breatharianism [life without food] almost assuredly won’t work; the literature is quite consistent.
• Be prepared to discard a hypothesis.
  
  Things won’t always work.
  
  And things that seemed to work for a while might suddenly stop working.
  
  Or, things that seem to work won’t actually work, or they’ll be working for entirely different reasons than you supposed.
  
  In other words, you’re probably never going to know with absolute certainty that something is working for the reason you thought it was.
  
  Just be ready to ditch failed hypotheses and change them on the fly.
• Don’t extrapolate to others.
  
  Just as your experiences didn’t jibe with results from randomized controlled trials, the solutions you discovered from your own experiments may not always work for other people.
  
  They’ll have to test it on themselves.

…

Huh.

Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus.
Sildorf SM, Fredheim S, Svensson J, Buschard K.

Paediatric Unit, Copenhagen University Hospital, Herlev, Denmark.

A 5-year and 10-month old boy was diagnosed with classical type 1 diabetes mellitus (T1DM) without celiac disease.

He started on a gluten-free diet after 2-3 week without need of insulin treatment.

At the initiation of gluten-free diet, HbA1c was 7.8% and was stabilised at 5.8%-6.0% without insulin therapy.

Fasting blood glucose was maintained at 4.0-5.0 mmol/l.

At 16 months after diagnosis the fasting blood glucose was 4.1 mmol/l and after 20 months he is still without daily insulin therapy.

There was no alteration in glutamic acid decarboxylase positivity.

The gluten-free diet was safe and without side effects.

The authors propose that the gluten-free diet has prolonged remission in this patient with T1DM and that further trials are indicated.

Yes indeed, further trials are indicated.

(via)

"Even short-term Paleo type diet improves BP, … increases insulin sensitivity and improves lipid profiles"

Ok, I am late to this party…

Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.
(PDF)
Eur J Clin Nutr. 2009 Aug;63(8):947-55. Epub 2009 Feb 11.
Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC Jr, Sebastian A.
Source

Department of Medicine, University of California San Francisco School of Medicine,

Abstract

BACKGROUND:
The contemporary American diet figures centrally in the pathogenesis of numerous chronic diseases-'diseases of civilization'.

We investigated in humans whether a diet similar to that consumed by our preagricultural hunter-gatherer ancestors (that is, a paleolithic type diet) confers health benefits.

METHODS:
We performed an outpatient, metabolically controlled study, in nine nonobese sedentary healthy volunteers, ensuring no weight loss by daily weight.

We compared the findings when the participants consumed their usual diet with those when they consumed a paleolithic type diet.

The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleolithic type diet comprising lean meat, fruits, vegetables and nuts, and excluding nonpaleolithic type foods, such as cereal grains, dairy or legumes, for 10 days.

Outcomes included arterial blood pressure (BP); 24-h urine sodium and potassium excretion; plasma glucose and insulin areas under the curve (AUC) during a 2 h oral glucose tolerance test (OGTT); insulin sensitivity; plasma lipid concentrations; and brachial artery reactivity in response to ischemia.

RESULTS:
Compared with the baseline (usual) diet, we observed (a) significant reductions in BP associated with improved arterial distensibility (-3.1+/-2.9, P=0.01 and +0.19+/-0.23, P=0.05);(b) significant reduction in plasma insulin vs time AUC, during the OGTT (P=0.006); and (c) large significant reductions in total cholesterol, low-density lipoproteins (LDL) and triglycerides (-0.8+/-0.6 (P=0.007), -0.7+/-0.5 (P=0.003) and -0.3+/-0.3 (P=0.01) mmol/l respectively).

In all these measured variables, either eight or all nine participants had identical directional responses when switched to paleolithic type diet, that is, near consistently improved status of circulatory, carbohydrate and lipid metabolism/physiology.

CONCLUSIONS:
Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

Some quibbles:
Why the heck did they do "three ramp-up diets of increasing potassium and fiber for 7 days"?

And more in the comments:

The only thing I noticed was the lean meat prescription – it would have been interesting to see the results with nice fatty meat.

And it seems it was not really a Paleo type diet…

Treat Fatigue with Iron Supplements?

Fatigue can be caused by an array of conditions.

Iron deficiency is a common cause, though whether iron supplements offer benefit in the absence of anemia remains to be established.

Children and women, particularly pregnant women, need adequate iron in their diet.

While low-dose supplements are considered safe and may be helpful in meeting daily requirements, specific supplementation isn’t necessary or advisable in the absence of a clear deficiency.

And just because it’s a supplement doesn’t mean it can’t be harmful.

Iron supplements can be toxic in children, and should be stored like any other potential poison.

What is true for iron as supplement, should be taken as guideline for other (mineral or vitamin) supplements as well: Low doses may be OK, but high doses of (some) supplements can harm you – and any supplement might mainly give you expensive urine.

--

And personally, my advise to increase iron is:

• Ditch cereal grains
  (see Loren Cordain' Cereal Grains: Humanity's Double-Edged Sword for details how grains hinder mineral absorption)
• And eat more beef

Psychology and Denialism

Some time ago I notice that the tendency of psychologists to take "medically not explainable" symptoms (or rather symptoms that are with the current medical knowledge not explainable) and explaining these symptoms as psychological (psychosomatic, somatoform, etc.), that this practice by psychologists places the psychological discipline firmly outside the medical discipline.

Furthermore I would venture that the psychological discipline is dominated by confirmation bias, and until the psychological discipline gets an proper foundation in reality – which can only be a evolutionary foundation –  I will consider it a pseudo-science.

So the rhetoric question that arises is: If psychologists try to redefine the reality of the CFS patient population contrary to reality, does that not count as denial of reality? And shouldn't there be an outcry in the medical profession as to such an quackish behavior of psychologists?

(And taking the CFS patient population with measurable peripheral pain and fatigue, with measurable reduced exercise tolerance, and explaining these symptoms as originating in the brain, as in the "biopsychological" approach, should that not count as denialism as well?)

Christopher Snell 2012 Lecture – "Clinical exercise testing in CFS/ME research and treatment"

Christopher Snell 2012 Lecture – "Clinical exercise testing in CFS/ME research and treatment"


After mentioning the lecture in the last post, I'm giving this very excellent lecture of his an post of its own.

I think the lecture is very helpful and ties in nicely with the work done by Kathleen and Alan Light (see Alan Light's 2007 and 2011 lecture).

If I had some more energy, I would write down some take home message – but alas, this has to suffice for now.

Update:
This came in via Tom Kindlon and Jan van Roijen.

The Hammer Syndrome – Snell on Exercise Beliefs

Prof Snell on exercise beliefs (at 0:45):

I originally came out of exercise and sports science.

So to come up on a population were exercise did not seem to cure everything that was wrong with them, was antithetical to my beliefs at that time.

That seems to be another case of "hammer syndrome": When your favorite tool is an hammer, everything looks like a nail.

I guess there are a lot examples out there, were people wrongly think they have found one hammer to solve all problems. Some examples (some taken straight out of my QDC) where a (more or sometimes less) legitimate diagnoses in one sub-field is used as an "solve it all hammer":

• It's lack of exercise ("Common sense! Duh!")
• It's the psyche (Psychologists and Psychiatrists, but everybody else as well)
• It's the bones (Chiropractors, Osteopaths)
• It's meat (Vegans, "nutritionists", and other puritanic upholders of moral standards)
• It's Candida, Lyme or other pathogens  (Pathogen quacks)
• It's heavy metals, pesticides or other unnamed "toxins" (Environmental quacks)
• It's neuro-transmitters, inflammation, free radicals or the mitochondria (Pseudo-biomed quacks)
• It's the thyroid, adrenals or other endocrine problems (Pseudo-endocrinologists)
• It's some idealistic/metaphysical woo like "energy", qi, "balance" (Alternative medicine legerdemain)

So my advise would be: If someone wants to use an hammer on you, stay away from that person (unless you are actually a nail).

And just to be clear: I think Prof. Snell is a trustworthy as he relinquished his "hammer" – his lecture is very much recommendable.

Psychologists and Black Crayons

Psychologists and Black Crayons – priceless.

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.

…

The Big Pharma Conspiracy

Ben Goldacre at his best:

When the paper describing this situation was published in Jama, Lif, the Danish pharmaceutical industry association, responded by announcing, in the Journal of the Danish Medical Association, that it was "both shaken and enraged about the criticism, that could not be recognised". It demanded an investigation of the scientists, though it failed to say by whom or of what. Lif then wrote to the Danish Committee on Scientific Dishonesty, accusing the Cochrane researchers of scientific misconduct. We can't see the letter, but the researchers say the allegations were extremely serious – they were accused of deliberately distorting the data – but vague, and without documents or evidence to back them up.

Nonetheless, the investigation went on for a year. Peter Gøtzsche, director of the Cochrane Centre, told the British Medical Journal that only Lif's third letter, 10 months into this process, made specific allegations that could be investigated by the committee. Two months after that, the charges were dismissed. The Cochrane researchers had done nothing wrong. But before they were cleared, Lif copied the letters alleging scientific dishonesty to the hospital where four of them worked, and to the management organisation running that hospital, and sent similar letters to the Danish medical association, the ministry of health, the ministry of science and so on. Gøtzsche and his colleagues felt "intimidated and harassed" by Lif's behaviour. Lif continued to insist that the researchers were guilty of misconduct even after the investigation was completed.

No dairy? "But you NEEEEED the calcium!"

An interesting encounter today at the medical specialist, when I mentioned that I avoid dairy as dairy gives me acne and I was getting worse until I stopped eating dairy and grains:

If you don't eat dairy, then you must take calcium supplements. Otherwise you don't get enough calcium from nutrition.

Yeah, right.

Somehow the information that I tried to convey to her, that "Milk makes me ill", somehow that did not register for her. I know, it's only an anecdote to her, but still.

"If I eat this it makes me ill, if I stop eating it I get better" should be an easy to understand concept.

But I guess I am some sort of freak of nature and the only person in the world that has adverse health effects by dairy? And after all, don't all adult animals need calcium, well, because.

Yeah, right.

Maybe in 10 or 20 years we know much more about the adverse health effects of (pasteurized) dairy, and then she'll look back on what she told me about milk – or maybe not.

I wasn't in the mood to argue, so I just said "I am trying raw-milk dairy and it does not give me acne so far."

I guess she hears all kind of BS, so she'll file it under "Another Nutter", oh well. Whatever happened to being your own experiment, of being your own n-1?

Failed Replications and Fraudulent Researchers – Psychological Research is a "Mess"

Last Wednesday, Nobel laureate Daniel Kahneman sent an email to a group of a dozen or so psychologists telling them that the credibility of their field was in danger. The recipients all worked on social priming – the study of how subtle unconscious cues can influence our behaviour. It’s an area that has attracted controversy of late, due to failed replications of classic results[!], the outing of fraudulent researchers, and a more general concern among psychologists about the validity of their field’s results.

Kahneman meant the email as helpful advice, but his wording couldn’t have been stronger: “Your field is now the poster child for doubts about the integrity of psychological research… I believe that you should collectively do something about this mess.” His solution: a “daisy chain” of replications, where laboratories collaborate to check the results of their neighbours, in an open, transparent, and pre-established way. …

And:

“It doesn’t follow that people who are doing priming are committing fraud; it’s more likely that people who are committing fraud are drawn to that field. It’s important not to invert the logic of that.”

A Modest Proposal for CFS Patients

I throw this out, in the spirit of "A Modest Proposal" – which seems to be in line with what the British press likes to publish about CFS patients.

While I am not saying that this is the case, we still have to at least think about whether it might be the case all __________________* are ___________________**, and therefore the only way to deal with these people might be to force them to do some work, so they know how to behave.

*Choose one of the following options:

• Blacks
• Jews
• Muslims
• Immigrants
• Gays
• Communists
• Climate Change Deniers
• CFS Patients

** And choose one of these options:

• Retarded
• Sub-human
• Malicious
• Dumb
• Mentally ill
• Degenerate worthless scum
• Evil monsters
• Freeloading parasites

New study confirms researcher's biases

New Robust Ways To Confirm Biases
Journal of Applied Redefinition of Reality

Simon Mustelids 1
Mikhailovich Mannovjev 2
Stephanos Lewandopolis 3

1 King's College London, Institute of Confirmation Bias, Department of Confirmation Bias Medicine
2 Pennsylvania State University, Departments of Confirmation Bias and Failed Anger Management
3 University of Western Australia, School of Confirmation Bias, Conspiracy Theories Laboratories

Abstract:
In this study we set out to confirm our biases. For this, we selected some test subjects (n = some low double digit number) that could confirm our biases, and selected some control subjects (n = some low double digit number) intended to strengthen our confirmation biases. To ensure proper confirmation of our bias we designed a questionnaire allowing us to confirm our biases. Both questions and answers were designed from our point of bias, in accordance to the standard in our field, so that we hear what we want to hear. We furthermore fooled ourself into confirming our biases by using our poor understanding of statistics and choose a multivariant statistical analysis method ("meat grinder") that yielded the expected results we desired in the form of spurious correlations.

Discussion of results:
Our study confirmed our biases (p < some low number), something we already knew before we began our study. From the standpoint of our biases, other explanations for the results seem unlikely. This result is strengthened by other groups having the same biases confirmed. With the question of our biases settled, there are some minor questions (e.g. the so called "reality paradox") that remain in our field. We are confident that these latest results in confirming our biases offer a way forward to solving these remaining questions in accordance to our biases.

Disclosure of Responsible Behavior:
The financial interests of the involved researchers were not endangered by either the conduct of research, or the publication of the results. The involved research subjects were properly blinded to the conflicting interests of the researchers, and were prevented from realizing what would be in their own interests.