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The Placebo Gene?

A study recently published in PLOS one (Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome) purports to have found a gene variant that correlates strongly with a placebo response in irritable bowel syndrome (IBS). The study is small and preliminary, but the results are interesting and do raise important questions about placebo responses.

Researchers are increasingly trying to tease apart the various components of “the placebo effect.” In reality we should use the term “placebo effects” as it is demonstrably multifactorial. “The placebo effect” really refers to whatever is measured in the placebo arm of a clinical trial – everything other than a physiological response to an active intervention. Within that measured response there are many potential factors that would cause an outcome from a fake treatment to be different from no treatment at all. These include statistical effects like regression to the mean and the natural course of symptoms and illness, reporting bias on the part of the subject, and a non-specific response to the therapeutic interaction with the practitioner.

It is also critical to realize that placebo responses vary greatly depending on the disease or symptom that is being treated and the outcome that is being measured. Placebo response is greatest for subjective symptoms of conditions that are known to be modified by things like mood and attention, while it is virtually non-existent for objective outcomes in pathological conditions. So there is a substantial placebo response for pain and nausea, but nothing significant for cancer survival.

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Posted in: Clinical Trials

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A PANDAS Story

One of the skills I try to teach medical students on their journey to becoming experience clinicians is to consider and address the patient’s “narrative.” Patients have a certain understanding of their illness, its cause, and its role in their life. They make sense of their situation as best as they can, resulting in a story they tell themselves. This is how humans generally deal with the complexities of life.

There is a potential problem when the clinical narrative of the health care provider conflicts significantly with the illness narrative of the patient. Patients, for example, often feel that a highly specific diagnosis is necessary for optimal treatment of their condition. Until they are given such a diagnosis they feel they need to keep looking – for better diagnostic tests or different specialists (what I call the “Dr. House” narrative). The appropriate diagnostic and therapeutic algorithm for that patient, however, may not require a specific diagnosis, but rather eliminating certain diagnoses and then treating the probable category or clinical syndrome that remains. The clinical narrative, in other words, may be one of considering risks vs benefits with incomplete and imperfect knowledge.

Increasingly, it seems, the conflict of narratives is taking on a larger scale – not just between one doctor and one patient, but between the medical community and patient communities. Perhaps this is one manifestation of the new social media generation. Take, for example, a recent controversy over a patient diagnosed with PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections).

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Posted in: Neuroscience/Mental Health

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More HIV Nonsense in Africa

It is estimated that 5% of people living in Sub-Saharan Africa are infected with HIV – that’s 22.5 million people. Infection rates vary wildly from country to country, with Swaziland having the highest rate at 25.9%. Gambia is below average, at 2% or 18 thousand people, but still has a serious HIV problem, and now finds themselves at the center of the HIV controversy in Africa.

This epidemic has been magnified by unfortunate realities on the ground. Africa has an insufficient public health and medical infrastructure to deal with the massive challenge such an epidemic presents. This has led the World Health Organization to contemplate partnering with local traditional healers, to make them into an extension of the effort to bring modern medical treatment to the HIV-infected in Africa. This desperate strategy is fraught with problems, not the least of which is that most traditional healers have had no prior contact with science-based medicine.

Former South African president Thabo Mbeki seriously set back his country’s HIV efforts by embracing crank HIV denial. Coupled with his denialism was efforts by Health Minister Manto Tshabalala-Msimang to use traditional medicines to treat HIV/AIDS. This combination resulted in restrictions on the distribution of anti-retoviral drugs in South Africa that is estimated to have cost hundreds of thousands of lives.

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Posted in: Herbs & Supplements, Public Health

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Patients Still Respect Evidence

A recent survey about patient attitudes and desires with regard to health care demonstrate that respect for scientific evidence is still the dominant factor in preferring treatments. (Full study) This is good news, although the numbers could be better.

Researchers asked subjects what factors were important in determining which treatments they would prefer, the scientific evidence, the experience of the clinician, or their own personal preferences. Not surprisingly, most subjects wanted it all, agreeing that all three are important. Scientific evidence, however, scored the highest with 71% rating it as very important (and over 90% as important or very important). Clinical expertise had 61% strongly supported and personal preference, 57%.

Further, patients wanted their doctors to talk to them about the evidence. The phrase they felt had the most impact on their decision to accept a treatment was, “What is proven to work best.”

All of this matches my personal experience as a clinician. At least for the self-selective population of patients who seek out a university physician, patients tend to find recommendations based upon published evidence compelling, and greatly appreciate when I take the time to tell them about the evidence, even if it goes against their initial interests.

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Posted in: Science and Medicine

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XMRV Chronic Fatigue Syndrome Update

Sometimes science works the way it’s supposed to. Scientists make hypotheses, test them by gathering preliminary evidence, and then argue about the inevitable conflicting results. Eventually better and better evidence is gathered until a consensus is achieved. Actually, I think that is how science usually works, it’s just that most questions in science are narrow and technical and don’t command media or public attention. Those that do tend to be the more enduring controversies or where a particular special interest (ideological, social, corporate, etc,) is involved.

In medicine scientific controversies may take on a life of their own, or become manufactured controversies (manufactroversies) that endure long past any genuine scientific debate. Such false controversies are often driven by patient groups who feel they are not being treated fairly or honestly, or by practitioners who do not want to give up on their favorite (lucrative) modality. This leads to a disconnect between the scientific controversy and the public controversy – a frequent theme on SBM.

I am happy to report that one such controversy has taken a turn for the good – a recent study has provided fairly definitive evidence that chronic fatigue syndrome (CFS) is not associated with either the XMRV or the pMLV viruses. The study was a consensus trial with both sides in the controversy collaborating to address all the criticisms of the earlier conflicting studies.

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Posted in: Science and Medicine

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The Sweetener Wars – HFCS Strikes Back

The health conscious and trendy public are a bit obsessed with the food they consume. This can be a good thing, to the extent that it results in a more healthful diet, but unfortunately those interested in improving their diet must wade through a great deal of misinformation before getting to accurate and helpful information.

For example, I recently gave a lecture (ironically on health information) at Google (you can view the entire talk here). Google is a progressive company that tries to help their employees stay healthy. They provide many snack stations and helpfully divide snacks into red, yellow, and green shelves. Employees can freely choose whatever snacks they want, but they are gently encouraged to choose from the more healthful green shelf and avoid the unhealthy red shelf. I noticed that beverages sweetened with sugar cane were placed on the green shelf, while those sweetened with artificial sweeteners like aspartame or Splenda were slumming on the red shelf. It was ironic to see such a high-tech company falling for the naturalistic fallacy.

Sugar cane sweetened sodas are becoming fashionable, mainly to avoid high fructose corn syrup (HFCS), which many claim is associated with obesity and increased cardiovascular risk. Jim Laidler did an excellent job reviewing this controversy two years ago on SBM. To me this represents a general tendency to try to understand a complex question by oversimplifying, specifically by avoiding perceived “villains.” It may seem overwhelming to grapple with all the complex information involved in basic dietary health choices, like which beverages are best. Following simple rules, such as avoiding single ingredients that are perceived to be “bad,” therefore has an appeal. I also think this is part of the appeal of the naturalistic fallacy, a simple litmus test to what is good vs bad.

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Posted in: Epidemiology, Nutrition

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An Acupuncture Meta-Analysis

A recent meta-analysis of acupuncture studies for chronic pain by Vickers et al is getting a great deal of press. The authors’ conclusions are:

Acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo. However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.

News reports generally reflect this conclusion – acupuncture works, but mostly (although not entirely) through placebo effect, but that’s OK.

I took a close look at the study and find that the authors display considerable pro-acupuncture bias in their analysis and discussion. They clearly want acupuncture to work. That aside, the data are simply not compelling, and the authors, in my opinion, grossly overcall the results, which are compatible with the conclusion that there are no specific effects to acupuncture beyond placebo.

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Posted in: Acupuncture

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No Health Benefits from Organic Food

A recent review of 240 studies has concluded that:

 The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria.

Organic produce has become increasingly popular in recent years. There are several reasons that consumers might prefer organic produce, including the belief that organic farming is better for the environment and more sustainable. I am going to focus in this article about the health effects of organic produce. Environmental claims for organic farming are complex and controversial – I will just say that such claims largely fall prey to the naturalistic and false dichotomy fallacies. In my opinion, farming practices should be evaluated on their own merits individually, based on evidence rather than philosophy. Sustainable and environmentally friendly farming are certainly laudable goals and I support farming practices promote them, however they are labeled.

The alleged superiority of organically grown produce is a separate question. In a 2003 survey 68.9% of people who purchase organic food said they did so because they believed it to be healthier (more than any other reason given).  However, fifty years of research has so far not produced convincing evidence that there is any health benefit to consuming organic food.  Likewise, systematic reviews of nutritional quality of organic produce also reveals no difference from conventional produce.

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Posted in: Nutrition

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The Power of Replication – Bems Psi Research

I love reading quotes by the likes of Karl Popper in the scientific literature. A recent replication of Bem’s infamous psi research, Feeling the Future, gives us this quote:

Popper (1959/2002) defined a scientifically true effect as that “which can be regularly reproduced by anyone who carries out the appropriate experiment in the way prescribed.”

The paper is the latest replication of Daryl Bem’s 2011 series of 9 experiments in which he claimed consistent evidence for a precognitive effect, or the ability of future events to influence the present. The studies were published in The Journal of Personality and Social Psychology, a prestigious psychology journal. All of the studies followed a similar format, reversing the usually direction of standard psychology experiments to determine if future events can affect past performance.

In the 9th study, for example, subjects were given a list of words in sequence on a computer screen. They were then asked to recall as many of the words as possible. Following that they were given two practice sessions with half of the word chosen by the computer at random. The results were then analyzed to see if practicing the words improved the subject’s recall for those words in the past. Bem found that they did, with the largest effect size of any of the 9 studies.

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Posted in: Neuroscience/Mental Health, Science and Medicine

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Homeopathy’s Recent Woes

Be careful what you wish for. In the last few decades purveyors of dubious medical treatments and products have been trying to go mainstream, and they have had some unfortunate success. They asked for serious scientific investigation into their claims – and they got it. They asked to be treated like real medicine (but not really, they only want the trappings of legitimacy, not the substance), and when they actually are treated with the standards similar to science-based medicine, they cry foul.

The response of the fake-medicine lobby is not to alter their claims to fit the evidence, or to carry out better studies, or to clean up their act when problems are brought to their attention – but to attack their critics.

Homeopathy is perhaps the best example of this behavior. Homeopathy’s biggest marketing advantage is that most people don’t know what it really is. They think it’s “natural” medicine or herbs. That is why, during homeopathy awareness week, I was happy enough to oblige. I want people to know exactly what homeopathy is – sugar pills. They are placebos on which the equivalent of a magical ritual has been cast. Active ingredients, which themselves are as fanciful as fairy dust, are diluted into non-existence.

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Posted in: Homeopathy

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