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Mouse Model of Sepsis Challenged

A recent study published in the Proceedings of the National Academy of Sciences calls into question the standard mouse model of sepsis, trauma, and infection. The research is an excellent example of how proper science investigates its own methods.

Mouse and other animal models are essential to biomedical research. The goal is to find a specific animal model of a human disease and then conduct preliminary research on the animal model in order to determine which research is promising enough to study in humans. There are also non-animal assays and “test tube” type research that is used to screen potential treatments, but scientists still prefer a good animal model.

It is also understood that animal models are imperfect – mice are not humans, after all. Animal research is therefore not a substitute for human research. I and other SBM authors have regularly criticized proponents of dubious treatments who make clinical claims based upon preliminary animal research. Until something is studied in humans, we cannot make any reliable claims about its safety and efficacy in people.

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Posted in: Clinical Trials, Science and Medicine

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Dynamic Neural Retraining

Snake oil often resides on the apparent cutting edge of medical advance. This is a marketing strategy – exploiting the media hype that often precedes actual scientific advances (even ones that don’t eventually pan out). The slogan of this approach could be, “Turning tomorrow’s possible cures into today’s pseudoscientific snake oil.”

The strategy works because, to the average person, the claims will sound plausible and scientific and will contain familiar scientific buzz words. There is therefore a proliferation of stem cell clinics, anti-oxidant supplements, and personalized genetic medicine.

We can add to the list of cutting edge pseudoscience, neural plasticity and brain training. Neuroscientists are discovering that even the adult brain has greater capacity for plasticity than was previously thought. Plasticity is the capacity of the brain to rewire itself, to acquire new abilities or compensate for damage. Mostly this is simply a technical description of a very common phenomenon – learning. Shoot a basketball 1000 times and (surprising to no one) you (meaning your brain) will get better at shooting baskets. Some of this is physical, such as developing the necessary strength in the involved muscles, but mostly this is the brain learning how to shoot baskets through plasticity.

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Posted in: Neuroscience/Mental Health

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Are You Ready For the Oz Manifesto

“Medicine is a very religious experience. I have my religion and you have yours. It becomes difficult for us to agree on what we think works, since so much of it is in the eye of the beholder. Data is rarely clean. You find the arguments that support your data, and it’s my fact versus your fact.”

- Mehmet Oz

The above quote is from a recent article for the New Yorker by Michael Specter about Dr. Oz, the most currently popular TV doctor. Specter described this sentiment as “chilling.” To me it sounds like a manifesto – a postmodernist attack on the scientific basic of modern medicine.

In my experience, this sentiment is often at the core of belief in so-called complementary and alternative medicine (CAM). In order to seem respectable and infiltrate the institutions of medical academia, proponents of CAM will say that their treatments are evidence-based and that they are scientific. They have a serious problem, however – their treatments are not evidence-based and are often grossly unscientific. Whenever someone bothers to look at their evidence and examine their science, therefore, they start to backtrack, eventually arriving at their true position, a postmodernist dismissal of science resembling Oz’s statement above. I have heard a hundred versions of the Oz manifesto from CAM supporters.

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Posted in: Homeopathy, Science and the Media

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Pandemrix and Narcolepsy

In 2010, following the H1N1 pandemic and the vaccination campaign to reduce its impact, researchers noted a significant increase in a rare neurological disorder, narcolepsy, in Sweden and Finland. Since then researchers have been studying a possible association between a specific H1N1 flu vaccine, Pandemrix by Glaxo-Smith-Kline (GSK) and a sudden onset of the sleep disorder narcolepsy. In those two countries the association seems strong, but the full story is still complicated with many unknowns.

Narcolepsy is a neurological disorder marked by excessive sleepiness, cataplexy (sudden loss of muscle tone, usually triggered by emotions) and disordered sleep. Almost all cases are associated with low levels of hypocretin in the hypothalamus – this is a hormone involved in sleep regulation.  Further there is a strong HLA (human leukocyte antigen) association – specifically DQB1*0602. HLA is a group of proteins involved in regulating immune activity. An HLA association strongly suggests that narcolepsy may be an auto-immune disease.

The current synthesis of this information is that narcolepsy occurs in genetically susceptible individuals after some environmental trigger, such as in infection, that causes the immune system to attack and destroy hypocretin cells in the brain.

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Posted in: Vaccines

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The Placebo Narrative

Science journalist Sharon Begley wrote a recent piece in The Saturday Evening Post about Placebo Power. The piece, while generally better than the typical popular writing on placebos, still falls into the standard placebo narrative that is ubiquitous in the mainstream media. The article is virtually identical to a dozen other articles I have read on placebo effects in the popular press, and most significantly fails to even question that narrative.

Begley is generally one of the better science journalists, although I have had my disagreements with her – specifically over her attitude toward the relationship between skeptics and the media. She seems to have a distorted and negative view of skeptics and does not think that the media can or should help us in our “debunking crusade.” (The term itself speaks of a fundamental misunderstanding of the modern skeptical movement.)

I have also parted ways with Begley over her view of the relationship between science and medicine. She seems to have a fairly negative view of doctors, fueled in part by her imperfect grasp of medical science. This is the risk with even the best lay science journalists – science is often complex and it is difficult to master the nuances if you are not an expert and steeped in the evidence and the community. Further there is a tendency for people in general (including journalists) to go along with an appealing and available narrative. (For journalists those narratives that are appealing are the ones that make good headlines.) These shortcomings are present throughout her recent article on placebos.

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Posted in: Science and Medicine, Science and the Media

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Alternative Arthritis Treatments

A recent report commissioned by Arthritis Research UK reviewed 25 so-called “alternative” therapies for arthritis. They found, not surprisingly that there is little evidence to support most the studied treatments.

“There’s either no evidence that they’re effective or there’s some evidence that they are not effective.

Says lead author, Dr Gareth Jones.  It is important to note that we are not just talking about that these treatments are poorly studies, but also that to the extent they are studied the evidence is mixed or shows lack of efficacy.

I want to discuss, however, the exceptions – the treatment the report found were effective. They include acupuncture, tai chi, yoga, and massage.  Tai chi and yoga are basically forms of exercise and stretching, so it is not surprising that they are helpful in treating musculoskeletal disorders. It is deceptive, in my opinion, to even consider them “alternative” and lump them into the same artificial category as copper bracelets and magnet therapy. Exercise is not alternative – it is a very basic form of science-based activity for health, conditioning, and for musculoskeletal symptoms. The same is essentially true for massage, which is known to relax muscles (at least temporarily). Relaxation therapy should also not be considered “alternative” and existed long before this category was invented.

The only item on the list of treatment modalities that the report concluded showed some efficacy that is reasonably defined as “alternative” was acupuncture. This claim caught my attention because other reviews of the literature indicate that acupuncture is not effective for arthritis (or anything else). The report itself is not published in a peer-reviewed journal (at least not yet), but the lead author, Gareth Jones, has published prior systematic reviews.

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Posted in: Acupuncture

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Nutrigenomics – Not Ready for Prime Time

Quackery in medicine takes many forms – use of bad science (pseudoscience), fraud, and reliance on mysticism are a few examples. Perhaps the most insidious form of dubious practice, however, is to use genuine and promising medical science to promote treatments that are simply not at the point of clinical application. New treatments, and especially new approaches to treatment, in medicine often take years or decades of research before we get to the point that we have sufficient clinical evidence of safety and effectiveness to apply the treatment in clinical practice.

One example of the premature promotion of an otherwise legitimate scientific medical treatment are the many dubious stem cell clinics promising cures for serious diseases. Stem cell science is real, but we are still in the long period of build up when we are mostly doing basic and animal research. Human clinical trials are just beginning.

Another treatment approach that is being prematurely promoted by some is nutrigenomics. The claim is that by analyzing one’s genes a personalized regimen of specific nutrients can be developed to help their genes function at optimal efficiency. One website that promises, “Genetics Based Integrative Medicine” contains this statement:

Nutrigenomics seeks to unravel these medical mysteries by providing personalized genetics-based treatment. Even so, it will take decades to confirm what we already understand; that replacing specific nutrients and/or chemicals in existing pathways allows more efficient gene expression, particularly with genetic vulnerabilities and mutations.

The money-quote is the phrase, “it will take decades to confirm what we already understand.” This is the essence of pseudoscience – using science to confirm what one already “knows.” This has it backwards, of course. Science is not used to “confirm” but to determine if a hypothesis is true or not.

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Posted in: Nutrition

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Why Do People turn to Alternative Medicine

Any sociological question is likely going to have a complex answer with many variables that are not easy to tease apart. We should therefore resist the temptation to make simplistic statements about X being the cause of Y. We can still, however, identify correlations that will at least inform our thinking. Sometimes correlations can be triangulated to fairly reliable conclusions.

When the data is complex and difficult to interpret, however, evidence tends to be overwhelmed by narrative. The recent Sandy Hook tragedy is an excellent example. No one knows exactly why the shooter did what he did, so it is easy to insert your own preferred narrative as the explanation.

Another example is the phenomenon of so-called complementary and alternative medicine (CAM). Why has it been increasing in popularity (and is it, really?). Is it slick marketing, relaxed regulations, scientific illiteracy, a gullible media,  or the failures of mainstream medicine? You can probably guess I think it’s all of these things to some degree. The most common narrative I hear by far, however, is the latter – if people are turning to CAM it must be because mainstream medicine has failed them. This version of reality is often promoted by CAM marketing.

The evidence that we have, however, simply does not support this narrative. Studies show that satisfaction with mainstream medicine is not an important factor in deciding to use CAM, that CAM users are generally satisfied with their mainstream care, and they use CAM because it aligns with their philosophy, and they simply want to expand their options.

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Posted in: Science and Medicine

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Brain-Machine Interface

We spend a great deal of time in the pages of Science-Based Medicine taking down every form of pseudoscience in medicine. Of course, what we see as pseudoscience, proponents often see as emerging or cutting edge science. They are taking advantage of the fact that there is a great deal of legitimate emerging science, and they hope they can sneak past the gates by cloaking themselves in the trappings of real science (jargon, studies, their own journals, etc.). Emerging science, however, no matter how plausible and earnest, still has yet to prove itself (by definition), and has to go through the rigorous process of scientific evaluation to slowly gain acceptance. That process – sorting out what works from what doesn’t, the real from the fake – is where all the action is in SBM.

It is refreshing sometimes to talk about an emerging field that, while still experimental, is legitimate and has the potential to usher in a genuinely revolutionary treatment.

I have been following the research into brain-machine interfaces for some years, and reporting on many of the significant “baby steps” in the advance of this new technology. A recent study published in The Lancet represents another incremental and encouraging advance. Researchers at the University of Pittsburgh implanted two strips of 96 electrodes into the motor cortex of a 52 year-old woman with tetraplegia. The electrodes are capable of detecting the firing of neurons in the motor cortex and transmitting those signals to an external processor that in turn controls a fairly sophisticated robotic arm. The arm is described as having seven degrees of freedom – three dimensions of translation, three dimensions of orientation, and one dimension of grasping.

After two days the subject was able to move the robotic arm with her thoughts alone. Over the course of the 13 week study she progressively gained control of the arm and eventually was able to feed herself with the arm. While this is still very far from a “cure” for paralysis or a restoration of full function, for someone who is tetraplegic (all four limbs are paralyzed) having any independent function is a huge improvement in quality of life.

So where are we with this technology?

Posted in: Neuroscience/Mental Health

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