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Flavors of Nonsense

Neurologica Blog - 10 hours 57 min ago

I, like most people, like to categorize things. It helps me keep my mental space organized and tidy. A good system of categorization is also like a framework on which I can hang specific facts and details. Categories are most useful when they reflect underlying reality, rather then superficial or arbitrary features. Categories are therefore often at the nexus of facts and theory in science – they can organize the facts in a way that reflects the underlying theory. 

You have to be cautious, however. Reality often does not cleave in clean straight lines. There are likely to be exceptions to any rules one devices for defining specific categories. Groups tend to be fuzzy around the edges. While categories can be a useful tool for organizing ideas, they can also become a mental prison or straightjacket.

Is Pluto a planet? It depends on how you define planet, and why you would define planet in any particular way. Is there a difference between planets, dwarf planets, and planetoids? Or do these objects exist along a spectrum and scientists are simply drawing arbitrary lines for convenience? Is schizophrenia one disease or a group of diseases, how to we categorize the subtypes, and do they reflect real underlying differences in cause? Are such labels helping or hindering research?

I spend a lot of my time thinking about pseudoscience and nonsense, so it should come as no surprise that I think about how to describe the many topics I deal with as types or categories. It’s tricky, because it seems to me we are dealing with many overlapping and fuzzy areas. There are no clean categories. I do think, however, that certain cognitive patterns tend to cluster. So here are a few categories of nonsense and what I think are their dominant cognitive patterns.

Religious / Paranormal Beliefs

Religious and paranormal beliefs often revolve around the notion that there is a spiritual or mysterious dimension to reality and often involves the notion of transcendence. This is an assumed worldview – philosophical supernaturalism, if you will. From this perspective the dividing lines between mainstream religions, new age spiritualism, Eastern mysticism, cults, and pop supermaturalism are superficial. These subtypes are largely culturally and historically determined. Intellectually, however, the cognitive processes are the same.

The supernatural world view advocates the use of intuition, revelation, and “other ways of knowing” over science and reason. This often takes the form of a centuries old turf war between science and religion, although sometimes there is an effort to accommodate the two. Individually people simply compartmentalize their beliefs, and culturally may keep them in separate “magisteria.”

Paranormal beliefs are generally supported and reinforced by basic cognitive biases, such as confirmation bias, flaws in perception and memory, and pattern-seeking behavior. Often the surrender of will to a charismatic guru or religious leader is involved.

Pseudoscience

Pseudoscience is not anti-science, and does not require a rejection of naturalism, but rather it uses the tools and language of science but in a fatally-flawed manner. Pseudoscience often begins with a desired conclusion, and then tries to justify that conclusion with scientific evidence. The major flaw here is in process.

The pseudoscientist tends to use vague or shifting definitions, and jargon is designed to obfuscate rather than illuminate. Evidence is used if a highly selective manner, in what is called “cherry-picking.” Often weak forms of evidence, such as anecdotes, are used to trump much more rigorous forms of evidence, such as controlled experiments. Pseudoscience often occurs at the fringe, by lone or small groups of advocates, who fail to meaningfully engage with the scientific community at large.

I discuss the demarcation between science and pseudoscience at greater length here.

Conspiracy Theories

Conspiracy theories and theorists definitely warrant a category of their own. When skeptics talk of conspiracy theories, we are referring to the grand conspiracies, those that would by necessity involve many individuals across institutions, nations, and sometimes generations. Grand conspiracies often follow the format of dividing the world into three groups:

The conspirators are an evil and powerful group with the darkest of intentions – to enslave the world, for example. They have tremendous power and resources, but also reveal themselves in idiotic ways. The conspiracy theorists are part of an army of light, fighting to expose the conspirators. Everyone else are the dupe, or sheeple. 

Conspiracy theorists like to think that they have special insight, giving them privileged knowledge that everyone else is simply too dumb or naive to see. The powerful cognitive trap of the conspiracy theory is that it is a self-contained belief immune to refutation. Any evidence against the conspiracy was planted by the conspirators. The reason there is no evidence to support the conspiracy is because it is being suppressed by the conspirators.

Denialism

The denial of established scientific conclusions is the flip side of pseudoscience – rather than establishing a dubious belief, it seeks to knock down a legitimate theory. The basic strategy is often referred to as FUD – fear, uncertainty, denial. Another common term is manufactroversy, a fake or manufactured popular controversy where there is no real scientific controversy.

Denialism of often politically or otherwise ideologically motivated.  The primary cognitive process involved seems to be motivated reasoning. The specific tactics include magnifying any doubt or uncertainty about the relevant facts and science. Part of this is to deny that there is a consensus of scientific opinion, or even that a consensus can exist in science (or is relevant). Disputes among scientists about details are used to argue that more fundamental conclusions are in doubt.

Common topics in this category include the antivaccine movement, opposition to GMO, excessive doubt regarding global warming, and evolution denial (creationism). There are countless less widespread examples, however, including HIV denial, holocaust denial, germ theory denial, and many others.

This category can alternately be described as ideology trumping science through motivated reasoning. This does not necessarily have to involve denying clearly established science, but can be broadened to include any situation in which a scientific position is taken for ideological reasons. There are many scientific questions that have strong political implications. For example, is sexual orientation more biological or personal choice, is recycling effective, is circumcision a beneficial medical procedure, are gun laws effective in reducing violent crime, and does abortion cause harm to the pregnant woman. These are all questions that can at least be addressed scientifically, and yet people tend to form opinions on the facts that are in line with their political views.

Conclusion

As I warned at the beginning of this article, these categories all hugely overlap. Conspiracy theories are used to justify pseudoscience which in turn is used to justify the denial of science that conflicts with a religious view. Still, I maintain that the categories above are distinct intellectual phenomena, just ones that interact with each other and can coexist within the same belief, playing off of each other.

As people become familiar with critical thinking and skeptical philosophy, I think they begin to recognize these various forms of nonsense and the main cognitive flaws on which they are based. It is also typical to recognize them first in the beliefs of others. It generally takes much more time and intellectual effort to apply the lessons learned to one’s own beliefs.

That is why I think it is important to really learn and understand the nature of the logical flaws that lead to these patterns of beliefs, so that they can be recognized no matter what specific topic they are hiding in. It’s also necessary to have a strong commitment to the processes of critical thinking, scientific empiricism, and philosophical validity. This commitment has to trump whatever emotional needs and cognitive biases are driving your current beliefs.

It’s not easy. It’s an endless journey without a destination. But the alternative is to remain stagnant in a set of beliefs that fate has handed you.

Categories: Medicine

Bad News and Good News from Down Under: Science-Based Medicine in Australia

Science Based Medicine - 17 hours 21 min ago

The bad news: in a disturbing attempt to woo customers, some Australian pharmacists are offering in-store consultations with naturopaths. The good news: Australian skeptics and supporters of science have had a lot of recent successes in combatting quackery.

Non-Doc in a Box

In an article in the Australian magazine The Skeptic, Loretta Marron reports on naturopaths in pharmacies. You can read it here.  Pharmacy customers who want natural treatment alternatives are referred by pharmacy staff to an in-house naturopathy clinic. The cost, $90 for a one-hour consultation, is often covered by insurance. You can even get a Loyalty Card to make your fifth consultation free. They claim to “correct underlying causative factors,” advise about stress, diet, how to promote your vitality and immune system, etc.  And they help you make informed decisions about your health (informed by their brand of misinformation).

They offer disproven diagnostic methods like iridology, live blood analysis, and bio-energetic screening with bogus machines that they claim can detect everything from vitamin deficiencies and parasites to “spinal energy” and “vaccination disturbance.” Marron doesn’t describe the treatments they recommend, but we can assume they are offering the usual naturopathic remedies, including homeopathy, in lieu of the pharmaceuticals that are the reason for the pharmacy’s existence.

As Marron points out, pharmacists have a duty to be personally and properly persuaded of the safety and effectiveness of what they offer. If they believe in naturopathy, they are misguided; if they don’t believe in it, they are unethically misleading their customers for profit. She urges honest science-based pharmacists to speak out.

The Other FSM (Not the Flying Spaghetti Monster)

Loretta Marron is Secretary, Chief Executive Officer and web administrator for Friends of Science in Medicine, an organization founded in Australia in 2011 to emphasize “the importance of having health care based on evidence, scientifically sound research and established scientific knowledge.” It now has over a thousand members from all over the world, including a Nobel Prize winner, many distinguished academics in medical and non-medical fields, and most of the writers on the SBM blog. Their activities are described on their website.

Marron’s personal efforts to combat quackery in Australia have included writing articles, giving radio interviews, and even going undercover to expose cancer quacks.  She has twice won the “Skeptic of the Year” award.

Engaging Government Agencies and Spreading the Word

FSM has issued formal recommendations on pathology tests  and other subjects and its members have engaged the mainstream media with countless articles. See here and here.

Australian skeptics have actively engaged with various government authorities like the Therapeutic Goods Administration (TGA) and the Australian Health Practitioner Regulation Agency (AHPRA), submitting written protests on issues like VEGA and other bogus electrodiagnostic devices,  Essence of Kangaroo testicle , and Esoteric Breast Massage for breast cancer, to mention just a few.

After exposure of pseudoscience in universities, a number of courses were cleaned up, for instance, craniosacral therapy at Victoria University was dropped from the curriculum, and Maquarie University stopped offering a degree in chiropractic.  A prominent Australian academic quit his job when his university made a deal with a vitamin manufacturer as a step towards establishing a complementary medicine center.

Inappropriate information was removed from the websites of high profile organizations, including a WHO webpage on acupuncture; a Woolworths page on craniosacral therapy; the Victoria state government’s Better Health Channel information on acupuncture, homeopathy, Bowen Therapy, and kinesiology; and the Asthma Foundation of Western Australia’s statement on alternative medicine for asthma. APRA withdrew approval of antivaccination courses and courses on practice-building that targeted babies and children.

They have spread the word on Australian national television and YouTube. Australian television did an exposé on chiropractic.  Australian Skeptics president Richard Saunders tested Power Balance wristbands on television, revealing that the sales demonstrations and testimonials were illusions due to the ideomotor effect and suggestion. There was a public outcry, and the government forced the company to remove false advertising claims. Soon after, it stopped doing business in Australia.

The Australian Skeptics have been very energetic in fighting quackery with numerous articles in their journal The Skeptic and campaigns like the Open Letter to the Pharmacists of Australia.

The Chiropractic Association of Australia and the Chiropractic Board were targeted, exposing rampant fundamentalist/antivax views and revealing that the Board had approved over 100 courses that were either based on pseudoscience or which made false, misleading, or exaggerated claims of treatment efficacy. A chiropractic surge into some primary schools into Victoria for free health checks was thwarted.

The misleadingly named Australian Vaccination Network was forced to change its name to the more accurate Australian Vaccination-Skeptics Network, and it lost its charity status for fundraising over misinformation claims.

Conclusion

If naturopaths belong anywhere, they certainly don’t belong in pharmacies. I hope Loretta Marron’s information on naturopaths in pharmacies will be widely disseminated and I hope Australian pharmacists will be shamed into acting more responsibly. Countering quackery and misinformation with science-based medicine is a constant struggle, a Sisyphean task with successes but with no prospect of complete “victory.” Australia is doing a commendable job and setting an example for other countries to follow.

 

Categories: Medicine, Skepticism

Vandana Shiva and GMOs

Neurologica Blog - Mon, 09/22/2014 - 13:53

A recent New Yorker article by Michael Specter does an excellent job of putting the activism of anti-GMO campaigner, Vandana Shiva, into perspective. Shiva has since written a very critical response to Specter, and The New Yorker has responded to Shiva. The exchange is very enlightening.

Shiva is a dedicated anti-GMO activist, perhaps the most widely known and successful in the world. Specter paints a picture of Shiva as more than an ideologue – a “demagogue” who has created a dramatic narrative that is meant to frighten the public about GMOs, but has little to do with reality. For Shiva, her anti-GMO stance is part of a broader economic and social ideology. In her vision of the world, local farmers would feed the world with organic farming, without fertilizer or corporate involvement. The actual science about GMOs seems to be irrelevant to her narrative.

Specter illustrates several example. There are definitely religious undertones to her activism. For example, Specter quotes her from a speech earlier this year:

“G.M.O. stands for ‘God, Move Over,’ we are the creators now,”

Shiva’s tweets have often been notorious, such as this one comparing selling GMO seed to rape:

#MarkLynas saying farmers shd be free to grow #GMOs which can contaminate #organic farms is like saying #rapists shd have freedom to rape.”

When criticized for this tweet, Shiva responded:

“We need to move from a patriarchal, anthropocentric worldview to one based on #EarthDemocracy,”

It’s clear she has what most people would consider an extreme political view, mixed with religious sentiments. I actually have no problem with that – people can believe whatever they want. They can advocate for the values and morals that suit them.

I think it’s a strength of an open society that many points of view can be championed. We are all better off if no one has absolute power and if various interests are being championed, keeping an important check on each other. Hopefully a good compromise will emerge.

What I do have a problem with is the other feature of Shiva that Specter discusses – getting the facts wrong. She uses dubious science and questionable claims in order to support her ideological position. As I have pointed out many time, this is a double failure. It puts misinformation out into the public, and it squanders the credibility of her own position (which, even if I disagree with it, has its place in the discussion).

Specter recounts a number of pseudoscientific positions that Shiva has used to defend the purity of her message. I get that this probably makes her more effective as an advocate – reality is a mess, and it complicates communication. Here are some examples of Shiva’s reality-challenged rhetoric:

“Fertilizer should never have been allowed in agriculture,” she said in a 2011 speech. “I think it’s time to ban it. It’s a weapon of mass destruction. Its use is like war, because it came from war.”

With regard to the apparent increase in autism, she wrote:

“That question’s been answered. If you look at the graph of the growth of G.M.O.s, the growth of application of glyphosate and autism, it’s literally a one-to-one correspondence. And you could make that graph for kidney failure, you could make that graph for diabetes, you could make that graph even for Alzheimer’s.”

She also continues to perpetuate the myth that Monsanto is responsible for Indian farmer suicides, even though the evidence is soundly against her. (I discuss this issue further here.)

Even though he selectively quotes from scientific studies as it suits her narrative, she can also be utterly dismissive of any evidence she finds inconvenient:

In a recent speech, Shiva explained why she rejects studies suggesting that genetically engineered products like Pental’s mustard oil are safe. Monsanto, she said, had simply paid for false stories, and “now they control the entire scientific literature of the world.” Nature, Science, and Scientific American, three widely admired publications, “have just become extensions of their propaganda. There is no independent science left in the world.”

This, of course, is the “shill gambit” with which science communicators are all-too familiar. Mark Lynas is a journalist who started out ant-GMO, but eventually decided to really take a look at the scientific evidence and was convinced to change his mind. He now calls out the anti-GMO community on their conspiracy claims.

In that regard they are no different than the anti-vaccine community or the global warming denial community. All will invoke a grand conspiracy that the entire scientific community is systematically wrong because they are controlled by outside interests (for vaccines and GMO it’s corporate interests, and for AGW its government and leftist interests).

Two cases dramatically illustrate the negative effects of Shiva’s extreme ideology trumping even a basic respect for science and reason. The first is the Orissa disaster:

In 1999, ten thousand people were killed and millions were left homeless when a cyclone hit India’s eastern coastal state of Orissa. When the U.S. government dispatched grain and soy to help feed the desperate victims, Shiva held a news conference in New Delhi and said that the donation was proof that “the United States has been using the Orissa victims as guinea pigs” for genetically engineered products.

Essentially, there was an unusual emergency leaving millions of people homeless and potentially starving. Oxfam and the US sent emergency food supplies to relieve the refugees, and Shiva decided that what was most important was that the corn and soy they sent contained GMO. Rather than simply make an exception in extraordinary circumstance, she saw this as an attempt by the US to illegally import GMO into India, and moved to block it. She is a purist of the highest order – not in a good way.

Shiva characterized the move as an attempt to “force feed” GMO to Indians. I wonder if starving refugees offered food would have felt “force fed.” Maybe they could just eat cake?

The second issue that brings the ideology of Shiva and others into view is Golden Rice. I discuss this issue here, but to summarize: Golden Rice is a GMO rice with genes added to produce beta carotene in the rice itself (normally rice only produces it in the leaves). The GMO is in the hands of a non-profit who is making it available openly. There are no environmental issues, no issues of cross contamination, no issues of pesticides. There are no human health risks as beta carotene is a vitamin A precursor and known to be safe.

In other words – all the usual objections of anti-GMO activists are simply not relevant here. There is no legitimate reason to be against the development and deployment of Golden Rice. There are also plenty of reasons to be for it. Vitamin A deficiency is a major cause of blindness and death in the developing world. Efforts to provide vitamin A rich foods are underway, but inadequate.

Rice is a staple food in much of the world, but it is nutritionally very poor. Adding beta carotene would make this staple food into an important source of vitamin A. This would likely not entirely solve the problem but can be hugely effective. Shiva opposes Golden Rice on purely ideological grounds. Specter reports:

Two economists, one from Berkeley and the other from Munich, recently examined the impact of that ban. In their study “The Economic Power of the Golden Rice Opposition,” they calculated that the absence of Golden Rice in the past decade has caused the loss of at least 1,424,680 life years in India alone.

She is condemning millions to blindness and death by opposing an effective intervention based only on ideological purity.

At a certain point, good intentions no longer matter. When you are an influential activist on the world stage, you have a responsibility for the positions you take. You have a responsibility to get it right.

Those who oppose Golden Rice have only the weakest of arguments, as they are deprived of any actual objections. They argue that it may not work, or that other interventions may work. That’s really all they have. Meanwhile, other methods are already being used and are not adequate, and the current evidence shows that Golden Rice will be an additional useful tool.

Conclusion

As with many of the politically controversial issues that skeptics and science communicators typically deal with, there are a variety of ideological positions and differing values that people will have. A vigorous discussion on such issues can be highly valuable.

Unfortunately, most people seem to think that being entitled to their own opinion means they are also entitled to their own facts. Motivated reasoning kicks in. We crave the simplicity that occurs when the facts all align with our ideology. However, life is rarely ever so simple.

With regard to agriculture there are actually many difficult issues to contend with, and we are far from implementing optimal solutions. It is a challenge to feed earth’s billions without harming the environment, and in a way that achieves an optimal and fair distribution of food, and meets the demands of everyone involved, from the farmer to the consumer.

We have problems with the overuse of monoculture, the inevitable development of pests and diseases, of resistance to whatever methods we use to fight pests and diseases, of fertilizer runoff, effects on local insect species, maintaining food safety and nutrition, and sustaining the soil and water supply – all while feeding a growing population on finite arable land.

Our best hope is for everything to be on the table, and to use a variety of methods, including availing ourselves of the best our technology has to offer. All of this needs to be strictly evidence-based.

Here, ideology is our collective enemy. Shiva would have her followers believe that we can feed the world with small farms using organic farming without fertilizer. Only the most extreme ideologues think this is anything but utter nonsense, or that following such a plan would result in anything other than the starvation of millions.

Categories: Medicine

Do doctors pay attention to negative randomized clinical trials?

Science Based Medicine - Mon, 09/22/2014 - 03:32

We at the Science-Based Medicine blog believe that all medicine, regardless of where it comes from, should be held to a single science-based standard with regards to efficacy, effectiveness, and safety. We tend to focus primarily on “complementary and alternative medicine” (CAM), now more commonly known as “integrative medicine,” because (1) we believe it to be undermining the scientific basis of medicine and allowing outright quackery (or, as I like to refer to it, quackademic medicine) to infiltrate medical academia, which is fast becoming medical quackademia and (2) because when it comes to the other threats to the scientific basis of medicine as it is practiced today, such as pharma influence and various medical dogmatism, there are a whole host of active critics better equipped and more energetic than we are who can do the job (usually) better. That is why, whenever I hear advocates of CAM/”integrative medicine” attack us for not spending enough time on various corruptions of clinical trial processes or the perfidy of big pharma, I tend to gently tell them in my characteristically diplomatic manner that that’s what I like to call the “Why don’t you blog about what I think is important and interesting instead of what you think is important and interesting?” criticism, then I refer them to our posts on John Ioannidis, overdiagnosis and overtreatment, the shortcomings of mammography, or any number of other posts we at SBM have done through the years pointing out where current medical practice falls short. Indeed, it never fails to amuse me to point out how angry an eminent radiologist became at me for my posts criticizing him for his misleading attacks on certain studies that question the value of screening mammography.

In particular, though, I like to point out a post I did on vertebroplasty as a treatment for vertebral compression fractures (VCFs) due to osteoporosis. Basically, I discussed then recent evidence showing how vertebroplasty for such fractures is, basically, placebo medicine, no better than acupuncture. Indeed, I likened the state of evidence regarding vertebroplasty to that of acupuncture, in which small, pilot studies appear to be positive, but then the followup rigorous randomized clinical trials fail to find a benefit greater than that of placebo. It turns out that a rather telling study regarding vertebroplasty was published earlier this year that I somehow missed that addresses a problem we have in “conventional” medicine.

I became aware of this new study when I was perusing the latest issue of the Journal of the American College of Surgeons (JACS), hot off the presses. (OK, in reality it wasn’t the latest issue. It was the September issue; I’m more than a month behind in my perusing of the medical literature.) This study, however, had been published online back in April. It must not have gotten much news coverage then, but it’s an important study, because it is one of the few studies out there that look explicitly at the effect of randomized clinical trials with negative results. The study is by Fabrice Smieliauskas, PhD, Sandi Lam, MD, MBA, and David H. Howard, PhD, and is entitled Impact of Negative Clinical Trial Results for Vertebroplasty on Vertebral Augmentation Procedure Rates. Smieliauskas et al set the stage by describing what vertebroplasty is. Basically, it’s a procedure that’s done by either spine surgeons or radiologists in which bone cement (polymethelmethacrylate, or PMMA) is injected into the fracture site under radiologic guidance. The intent is to stabilize the fracture and relieve the pain. Kyphoplasty is a variant of vertebroplasty in which a device, such as a balloon, is inflated or expanded in the vertebral body. In theory, this restores vertebral body height and creates a cavity for the PMMA to enter. These procedures are considered similar enough that they are often referred to as “vertebral augmentation procedures” (VAPS).

Now here’s the real issue:

In August 2009, the New England Journal of Medicine published 2 randomized controlled trials testing vertebroplasty vs sham surgery for patients with osteoporotic VCFs. Both found that patients randomized to vertebroplasty did not experience decreases in pain or disability relative to patients in the placebo arm. In these studies, both groups showed improvement over time, suggesting a natural history for reduced pain and/or placebo response. The trials were covered in the lay press in newspapers, internet articles, and television news reports. In September 2010, the American Academy of Orthopaedic Surgeons (AAOS) issued a guideline that advised against the use of vertebroplasty for patients with osteoporotic VCFs. The guideline listed kyphoplasty as a treatment option but noted that evidence to support its use is “limited.” Many payers have restricted coverage of VAPs to patients whose symptoms have failed to resolve after a course of optimal medical therapy, but these types of coverage restrictions can be difficult to enforce in practice.

These are the studies that I blogged about five years ago, as well as four years prior to that for my not-so-super-secret other blog, where I used the whole question of VAPS as an example of a scientific delusion in reference to earlier studies of VAPS and the anecdotal evidence used to justify it, which I characterized as testimonials not unlike alternative medicine testimonials. Of course, given that randomized clinical trials (RCTs) are the “gold standard,” what’s of most interest is whether practice changes after major negative RCTs, like the the two negative RCTs (linked to here and here). I discussed them in detail at the time. Suffice to say, taken together, they were pretty definitive evidence that VAPS for osteoporotic vertebral compression fractures do not work. Besides having been published in a journal as high visibility as the NEJM, these two RCTs got a lot of publicity in the lay press, including a major article in the New York Times. The question that remained to be answered is whether physicians changed their practice in response to two resoundingly negative clinical trials that capped off a series of smaller studies questioning the value of VAPS.

The answer is: Yes and no, at least in Florida. Also, as they say in Facebook status updates, it’c complicated, as you will see.

So what did Smieliauskas et al do? They examined quarterly trends in VAPS use using the Florida hospital inpatient discharge and ambulatory surgery databases from 2005 to 2012, which capture a 100% sample of surgical spine procedures performed in the state in hospitals, hospital surgery centers, and freestanding surgery centers. They chose Florida because it is large and sociodemographically diverse. Discharge data was supplemented with data on physician specialty from the Florida Practitioner Profile, and population counts were obtained from the 2000 and 2010 Censuses and US population counts from the 2012 Census Population Estimates. This allowed the investigators to adjust for population growth during that period. So, yes, one weakness of this study is that it only covers Florida, and, as already mentioned, there is a huge regional variation in the use of VAPS throughout the US. The investigators also cautioned that it’s possible that some of the decline in some procedures was due to the recession due to the financial meltdown that occurred in 2008, but if that’s true, then these results would look even worse.

First up, we see that the average age of patients was 76 years, with Medicare being the primary payer in 85% of cases. Procedures were done by interventional radiologists (27.9%); orthopedic surgeons (32.2%); neurosurgeons (22.3%); other specialties (7.1%) and “unidentified” (10.6%). Interventional radiologists performed 57% of vertebroplasties and 18% of kyphoplasties, while orthopedic surgeons performed 13% of vertebroplasties and 38% of kyphoplasties. A little more than half of the vertebroplasties were performed on an outpatient basis, while most kyphoplasties were preformed in an inpatient setting.

Here’s the money figure. The TRIALS line indicates quarter before publication of vertebroplasty trials in the NEJM. The AAOS line indicates quarter before release of the American Academy of Orthopaedic Surgeons statement on vertebral augmentation procedures:

Looking at the graph, it looks as though VAPS rates did decline after the studies. Indeed, as the authors reported:

The interrupted time series estimates of the effect of the trials generally confirm the observations in the figures (Table 2). Overall, the vertebroplasty rate declined by 51.5% (column 1) and the kyphoplasty rate declined by 40.0% (column 2). Both results were statistically significant (p < 0.010). Similar declines (53.8% and 38.9%; columns 3 and 4, respectively) were observed for these procedures when restricting the sample to patients with osteoporotic fractures only. The change in the vertebroplasty rate was driven by a time trend effect, while the change in kyphoplasties was driven by a level effect and a time trend effect.

The interesting observation really comes when the investigators break down declines in VAPS by specialty:

The striking differences by physician specialty were confirmed in the regression results. Interventional radiologists responded to the trials (column 7) with an increase in time trend of the vertebroplasty rate (+0.019, p = 0.046) and a percentage change after the trials that was not significantly different from 0. This was very different (p < 0.010) from physicians in other specialties, whose vertebroplasty rate declined by 73.1% after the trials (column 8). Interestingly, radiologists exhibited a greater decline in the kyphoplasty rate (−46.9%) than did other specialists (−21.7%, p < 0.010) (columns 9 and 10).

Remember, according to this database, interventional radiologists do far more vertebroplasties than they did kyphoplasties, while surgeons do more kyphoplasties than vertebroplasties. Also, kyphoplasty is viewed as a more “invasive” procedure than vertebroplasty, mainly because of the inflation of the balloon in the vertebral body. So it might be that radiologists were more willing to shy away from kyphoplasty, leaving that to surgeons, than they were vertebroplasty. Moreover, surgeons, viewing the “more invasive” kyphoplasty procedure as more “surgical” in nature, might be less willing to give it up, given that the two studies didn’t directly address kyphoplasty. However, it is disturbing that the rates of vertebroplasty done by interventional radiologists haven’t declines in Florida at all since these 2009 studies, while among other specialties have decreased their use of vertebroplasty markedly.

So, yes, as I’ve described before, physicians really do abandon the use of procedures that are shown to be ineffective in large randomized clinical trials, but the process is messy and often arguably takes longer than it should. One other aspect of this process is that specialty society recommendations matter. Note that it took only a year for the AAOS to issue its guideline that strongly advised against the use of vertebroplasty for patients with osteoporotic VCFs. And so vertebroplasty use among specialties other than interventional radiology (the vast majority of whom were orthopedic surgeons or neurosurgeons) declined by nearly three-quarters. However, the guideline noted that evidence to support the use of kyphoplasty is “limited” but still retained it as an option for the treatment of osteoporotic VCFs. As a result, the decline in use of kyphoplasty was much more modest among surgeons. The authors note that:

Perhaps not coincidentally, the specialty societies’ practice guidelines after the trials interpreted the clinical trial evidence differently. The AAOS guidelines strongly recommended against vertebroplasty for osteoporotic VCFs, implying that physicians should follow the recommendation “unless a clear and compelling rationale for an alternate approach is present.” In contrast, kyphoplasty was described as a treatment option with a limited strength of recommendation. Other professional specialty organizations such as the North American Spine Society, the Society of Interventional Radiologists, and other groups did not issue recommendations against vertebroplasty or vertebral augmentation.

There are also practice patterns to consider, as the authors note. Interventional radiologists invented vertebroplasty, while orthopedic surgeons invented kyphoplasty, with each specialty retaining their dominance in the practice of the procedures they each invented. Indeed, for a time, for a time kyphoplasty training was restricted to surgeons. History, turf, and politics all too frequently intrude to prevent the rapid widespread adoption of guidelines, particularly for procedures that just seem so damned plausible. However, as I said in my article in Trends in Molecular Medicine last month and mentioned in my recent article in Nature Reviews Cancer on integrative oncology, although a prior plausibility that is clearly close to zero (as for homeopathy, for example) is a good predictor that a treatment will not be shown to work in RCTs, plausibility by itself is not anything close to a guaranteed that a procedure will be shown to work in RCTs.

Also, physicians practicing science-based medicine are human beings as well. They’re just as prone to biases and not wanting to admit that something they believed in before isn’t helping patients. This leads to a phenomenon described by the authors, but not explicitly addressed:

Although publication of the trials and the AAOS guideline influenced the use of vertebroplasty and kyphoplasty, our results indicate that both procedures are still widely used to treat patients with osteoporotic spinal fractures. Both trials were subject to criticism over their design and execution, and the appropriateness of vertebral augmentation continues to be widely debated. Multiple studies, analyses, and systematic reviews have been published since 2009 without consensus. In light of the controversy of the trials’ design and conflicting evidence from other studies, many physicians may feel free to ignore the “inconveniently negative” results from the trials and continue to offer VAPs to patients with osteoporotic spinal fractures.

You’ll note a similarity here. Remember what happened in response to the report of the Canadian National Breast Screening Study (CNBSS), which failed to find a benefit in terms of breast cancer survival due to mammographic screening. I put it all into context as best I could, but when I did that I caught some of the nastiness that was directed at the CNBSS itself and its investigators. And, of course, the VAPS studies encountered considerable criticism, nearly all of it not well grounded in science and nearly all of it coming from radiologists and their societies

Like CAM practitioners, some have even argued that the placebo response is a legitimate endpoint for these procedures. If you don’t believe me, check out this article in Radiology by authors of one of the VAPS trials in the NEJM entitled Vertebroplasty and the placebo response, where such arguments are actually described. The authors conclude:

In conclusion, our interpretation of the evidence for vertebroplasty has distinctive implications for clinical practice and health policy. If the benefits of vertebroplasty derive from the placebo response, it is difficult to justify the continuing use of this procedure in clinical practice. The reason for this is not that benefit from the placebo response is lacking in therapeutic value; rather, it is doubtful that the placebo response benefits from vertebroplasty are sufficiently large to justify the risks. Moreover, although it is unknown what the outcomes would be for patients who are candidates for vertebroplasty and informed about the evidence that this procedure is no different from a sham intervention without injection of cement, they are likely to be lower than the benefits observed in clinical practice or in the Vertos II trial. Hence, on the basis of the placebo response hypothesis, the risk-benefit ratio of vertebroplasty does not appear favorable. Finally, whether continued evaluation of vertebroplasty within clinical trials might be justified is debatable—indeed, we are not in consensus on this issue.

What is being described here is the justification of a procedure that has no specific benefits but has a placebo response, which the authors refute. How many times have we here at SBM refuted the exact same sorts of arguments. It just goes to show that even ostensibly evidence-based physicians can fall prey to such arguments. Indeed, even the authors of one of the VAPS studies have implicitly accepted such arguments. The reason they reject them is not because they are not clinically significant but rather because they deem the risks of vertebroplasty not to be worth the placebo benefit.

I’ve been following the vertebroplasty story intermittently since 2005. It struck me an example of just how easily we in “conventional” medicine can fall prey to the same sort of fallacious thinking that drives the advocacy of modalities such as homeopathy or acupuncture. It’s an example that helped me in my journey towards skepticism and science-based medicine. We all like to assume that negative well-designed RCTs will result in physicians abandoning a procedure, and in general they do. However, the lesson of VAPS tells us that the process is…complicated. It’s not straightforward, and it’s messy. (There are still radiologists out there advertising vertebroplasty as if it were a miracle cure.) Still, five years on, the process for VAPS procedures appears to be well under way. just try comparing that to the continued use of acupuncture, where no amount of negative evidence causes its abandonment, even after a period of time much, much longer than five years.

Categories: Medicine, Skepticism

Announcement: “Integrative oncology” – Really the best of both worlds?

Science Based Medicine - Fri, 09/19/2014 - 09:00

One of our goals here at SBM is to do more than just blog about the issues of science and pseudoscience in medicine that are our raison d’être. We also want to publish our science-based critiques in the peer-reviewed medical literature. Our first crack at this was an article by Steve Novella and myself published last month in Trends In Molecular Medicine entitled Clinical trials of integrative medicine: testing whether magic works? Even better, thanks to a press release and how the editors made the article free to all, it garnered more social media attention than any article previously published in TMM, and the editor has informed me that it “shot straight to the top of TMM’s ‘Most read’ article list and I anticipate it staying there for quite some time.” For this, Steve and I thank you, our readers, and those of you who spread the news. We’re hoping that this success garners more offers to write review and commentary articles for the peer-reviewed literature about topics near and dear to us.

Now, I’m happy to announce another commentary in the peer-reviewed literature. It’s an article I wrote for Nature Reviews Cancer that just appeared online yesterday entitled Integrative oncology: Really the best of both worlds?. I must say, I’m quite proud of this one, and it is a big deal, hopefully to more people than just me. If you look up the impact factor for NRC, you’ll see it’s around 35, which is between The Lancet and JAMA.

Accessing this article is a little more difficult than accessing the previous one was, but not that much. Normally, NRC articles are behind a paywall. In this case, my article is not behind a paywall, which is unusual, nor does it require a subscription to NRC or any Nature journal to be accessed. It does, however, require registration of a Nature.com login, which can be obtained for free, at, yes, Nature.com. Yes, I know it’s a bit of a pain and that many of you won’t want to register yet another login, but I assure you it will be worth it. Not only do you get access to my article, but there’s a lot of other cool science stuff at Nature even for free. That’s why I hope that a lot of you will do it and download the article. Read it, learn from it, and, hopefully, enjoy it. Let’s see if we can do it again and make this the most accessed article in NRC history.

Finally, consider this the comments section for the article. Therein lies another advantage of having access to a well-trafficked blog.

Categories: Medicine, Skepticism

How To Be a Science Denier

Neurologica Blog - Fri, 09/19/2014 - 08:23

This Week Louisiana Governor Bobby Jindal gave an excellent lesson on how to be a science denier. Unfortunately, this was not a faux demonstration, he was sincere.

If you recall, in 2012, Jindal advised Republicans to stop being “the stupid party.” This was a provocative statement. I wondered at the time if this signaled a shift in the party away from having anti-science on their platform. Had party insiders finally realized they can’t hang their political future on denying undeniable science, that they need to embrace reality and stop fighting against it?

Alas, it seems that a more cynical interpretation is closer to the truth – that Jindal was simply worried about damage to the Republican brand caused by Republicans saying “offensive, bizarre” comments, but not by the substance of their positions on scientific issues.

At a recent breakfast hosted by the Christian Science Monitor, Jindal was introduced as a Brown graduate at the age of 20 with a biology major, then a Rhodes Scholar at Oxford, and having a 2 year stint as the president of the University of Louisiana, along with many other accomplishments. So he is a scholar and, to some extent, an academic, with advanced study in biology specifically.

During the breakfast, which included journalists, Jindal was asked about global warming. In response to this issue, Jindal performed a very deft dance. He said, “Let the scientists decide,” referring to whether or not global warming is happening. This, of course, is a clever denialist tactic. The hidden premise here is that the scientists have not already spoken with a unified and loud voice. They have decided – it is clear that human activity is increasing greenhouse gases in the atmosphere and warming the climate.

Jindal does go on to endorse taking steps to reduce emissions and increase efficiency, and notes that you don’t have to be a believer or denier to accept such policies. He says “let’s listen to scientists” but missed a huge opportunity to show that he actually has listened to scientists. I’m trying not to get too political here – but Jindal could have used this question as an opportunity to actually lead his party by example to a more overtly scientific position, rather than dancing around the issue.

Not content with his overtly political responses, Jindal was asked directly if he personally believes the climate is changing by human activity. His response was pure denial. He said (to paraphrase), of course the climate is changing, the climate is always changing, the question is by how much and what are the consequences. He also says, sure human activity is contributing to some degree, the question is how much. Let the scientists decide.

This is the ultimate denialist position. Climate change deniers have backpeddled from, the globe is not warming, to it’s warming but not caused by humans, to it is caused by humans but not by much, to it is mostly caused by humans but who knows what the consequences are and if we can do anything about it. Jindal is somewhere between the last two positions, a very precisely calibrated political position.

Again, he goes on to say, let’s focus on which policies will work. Great – that is where the debate should be, but he missed an opportunity to help his party stop being the “stupid party.”

The next question was also a direct question about what Jindal personally believes, this time whether evolution is responsible for complex life on earth. Amazingly, Jindal responds that he was not “an evolutionary biologist.” Let’s unpack that for a moment. He is implying that unless one has post-graduate training specifically in evolutionary biology one cannot be expected to have an opinion on whether or not evolution is accepted science.

Jindal has a university degree in biology. If that is not sufficient to convince him that evolution is the organizing theory of biology, over the next 2 plus decades of his life he could have cracked a book or two on evolution.

When pressed on the point of his personal belief, he retreated to, “I think local schools should decide for themselves what to teach.”

This is a clear dodge. He is applying a very common political tactic to these issues – when asked a specific question, answer the question you want to answer, rather than the one you were actually asked.

With both climate change and evolution, Jindal was asked about his personal beliefs. He deflected the question by saying, well, listen to the scientists, and here is the policy I favor. With regard to teaching evolution, saying he favors local school control is a clear pro-creationist and anti-science position (given the context of the question). Sure, there is a legitimate debate to be had over the optimal balance of local, state, and federal control of public school curricula. We can talk about standards vs flexibility, and giving teachers some breathing room.

But the issue of evolution is quite clear – teaching evolution denial or singling out evolution for unfair treatment is an unconstitutional violation of the separation of church and state. The Supreme Court has spoken quite clearly on this issue, which means the local school districts don’t get to decide. Local governments cannot decide to violate the US Constitution. I suspect that Jindal probably understands this.

Conclusion

Jindal, as a Republican celebrity and likely presidential candidate, has powerful influence over the tone and policies of the Republican party. He is a scholar and gives every indication of being and intelligent and accomplished individual. I understand the political calculus, but I can’t help being disappointed that Jindal decided to take the precisely calibrated path of least resistance, effectively denying evolution and climate change but with plausible deniability of his denial.

Rather, he could have used the opportunity to follow up on his prior comment that the Republican party should stop being the “stupid party.” They should also stop being the party that denies evolution and climate change. He could have said – there is a clear scientific consensus that evolution is the accepted theory of life origins, and man-made activity is warming the climate. As a party, Republicans should stop denying these realities. Let’s focus on policies that will improve education, and that will improve our energy infrastructure and help the environment without wrecking our economy.

As I have discussed before – it is always best to advocate for one’s personal or political values within a framework that acknowledges the scientific consensus. It is an ultimately failed strategy to tie one’s values to specific scientific conclusions that may turn out to be wrong, or that have already been demonstrated to be wrong.

Categories: Medicine

Rationalizing the Ridiculous

Science Based Medicine - Fri, 09/19/2014 - 03:03

I remain flummoxed. How do physicians and health care systems, trained in all the sciences that lie at the heart of medicine, justify the use of pseudo-medical interventions with no basis in reality? Rationalization. Making excuses:

a defense mechanism in which controversial behaviors or feelings are justified and explained in a seemingly rational or logical manner to avoid the true explanation, and are made consciously tolerable – or even admirable and superior – by plausible means.

Rationalization of the ridiculous comes in many forms. It has been said that it is a mark of a first rate intelligence to able to hold two contradictory ideas in the mind at the same time and still retain the ability to function. Clever as it is, I suspect the opposite is true.

Acupuncture: Ignoring your own analysis

So often rationalization is as simple as denying your own data where the content of a pseudo-medicine paper is at odds with its conclusions. The most egregious example is the Cassidy study on stroke and chiropractic. But other examples are easy to find. Take Acupuncture and related techniques in ambulatory anesthesia, a review of the use on acupunctures (regular, electric and acupressure) for post operative pain and nausea.

They start off with an abstract that says

Research suggests that acustimulation may alleviate postoperative morbidities, although the body of evidence of the effect is equivocal.

‘Suggests’, ‘may’, ‘equivocal’. Hardly a ringing endorsement. The introduction is equally lukewarm:

trials of hands-on-therapies face inherent difficulties in the design of placebo controls, and the body of evidence is equivocal. The use of sham acustimulation as a placebo control is inclined to have high placebo effects

They compared a hodgepodge of acupunctures, with variable outcomes, some positive and some negative. There were very few double blind studies and most with a positive effect for a subjective endpoint (pain or nausea) often had no change in objective endpoints (use of pain or nausea medications).

If this were a real intervention based on real physiology, I would conclude the intervention did nothing. As an intervention with no prior plausibility, the results are even less impressive.

In this case? Well, they say,

With reservations, as some of the trials reviewed are small and must be perceived with caution, the results suggest that acustimulation may be beneficial in alleviating postanesthetic morbidities. The techniques are easy to perform, and adverse events and costs are minimal. In particular, acupressure is noninvasive, well tolerated, and may have a good patient acceptability. Acupressure can be applied by medical staff, patients or parents and maintained after discharge. A feasibility study shows neither delay in the surgical procedure, nor additional anesthesia time attributed to the introduction of acupuncture and acupressure. It may be profitable to consider implementing acustimulation to ambulatory patients.

I presume they mean profitable in the sense of beneficial or useful.

It is really remarkable how a therapy that in this analysis is questionable at best (an in other analysis worthless) is still suggested because it is cheap and easy to apply, not because it is effective and based on sound medical evidence.  It is difficult to imagine such a low standard for approval of an antibiotic.  But with antibiotics you would expect a real effect against a real infection.

Acupuncture Clinics

The National Research Center in Complementary and Alternative Medicine, Institute of Community Medicine in Norway might suggest using acupuncture for post operative pain and nausea. In the US major medical institutions do not suggest, they act. For example:

Loyola announces opening of new acupuncture clinic for patients with pelvic health disorders.

The usual nonsense is put forth to justify charging patients for fantasy-based therapies:

These conditions place a significant burden on our health-care system and the economy due to the prevalence and the fact that many patients don’t respond to traditional treatments, said Larissa Bresler, MD, a medical acupuncture doctor, Loyola University Health System, and an assistant professor of Urology, Loyola University Chicago Stritch School of Medicine. The goal of the clinic will be to offer patients another tool to help alleviate their symptoms without the side effects of medication.

That is the ‘since air travel and airplanes have problems we should rely on flying carpets’ argument.

Acupuncture has been used as a healing tool for more than 2,000 years.

The ever popular appeal to antiquity logical fallacy, and not even a true appeal since the use of needles is a recent development and as practiced at the turn of the century TCPM was gruesome:

Chinese doctors own that they know nothing at all of surgery. They cannot tie an artery, amputate a finger or perform the simplest operation. The only mode of treatment in vogue which might be called surgical is acupuncture, practised for all kinds of ailments. The needles are of nine forms, and are frequently used red-hot, and occasionally left in the body for days. Having no practical knowledge of anatomy, the practitioners often pass needles into large blood vessels and important organs, and immediate death has sometimes resulted. A little child was carried to the dispensary presenting a pitiable spectacle. The doctor had told the parents that there was an excess of fire in its body, to let out which he must use cold needles, so he had pierced the abdomen deeply in several places. The poor little sufferer died shortly afterwards. For cholera the needling is in the arms. For some children’s diseases, especially convulsions, the needles are inserted under the nails. For eye diseases they are often driven into the back between the shoulders to a depth of several inches. Patients have come to us with large surfaces on their backs sloughing by reason of excessive treatment of this kind with instruments none too clean.

They mention the mechanism by which acupuncture is alleged to work:

Acupuncture is based on the traditional Chinese teaching that energy flows through the body along channels called meridians. Illness occurs when energy is blocked or disrupted. The insertion of needles into designated points improves the flow of energy and releases feel-good hormones, beneficial chemicals and immune system cells to reduce inflammation, aid healing and promote pain relief.

Without mentioning that meridians and the energy it contains are nonsense, divorced from physiology and anatomy and has never been demonstrated to exist.

They will use acupuncture for

…pelvic pain, nausea from pelvic surgery, interstitial cystitis, painful bladder syndrome, postoperative pain, prostatitis and overactive bladder.

The reviews for use of acupuncture for the above conditions are typical: maybe it works but the studies are poorly done:

Evidence for the efficacy of needle acupuncture for treating the disorders evaluated remains inconclusive. The intervention showed promising results for reducing pelvic and back pain during pregnancy and climacteric vasomotor symptoms, although well-designed studies are needed to make the results more precise and reliable.

and

The evidence that acupuncture is effective for chronic prostatitis/chronic pelvic pain syndrome is encouraging but, because of several caveats, not conclusive. Therefore, more rigorous studies seem warranted.

Which is the same as it ever was. Acupuncture only has effects in studies with poor methodology. The better the study, the worse the effect until well designed studies that remove all potential bias fail to show acupuncture has any effect.

Which, given the prior plausibly that acupuncture would be effective for anything is zero, is what would be expected. But always more studies need to be done.

It hardly seems a solid foundation for a clinic for treating and charging the ill. I always wonder why the Board of Trustees of these institutions allow the use of magic in their hospitals.

But I hope that, since the acupuncturist involved also a urologist, there will finally be an answer to the question that has puzzled me for years: why they are no meridians and acupoints in the male genitals? Why no life energy flowing in the life generating organs? You can probably guess my answer.

Integrating Naturopathy

Forget acupuncture, what about using naturopaths?  Integrating naturopathy: can we move forward? The short answer is no.  I have discussed both naturopathic education and ND fitness as primary care providers in the past.

The jist of the article is the author wants to dump all his difficult to treat patients on naturopaths.

With so many of our patients presenting with chronic pain, functional disorders, and other difficult-to-manage chronic conditions, allopathic primary care physicians clearly need more compelling options for managing chronic disease…Naturopaths would seem ideally positioned to fill this partnership role.

Clever in a Machiavellian kind of way. Play up the holistic BS and send them off to the mostly harmless, although mostly fantasy-based, therapies that make up Naturopathic practice. If you have a troublesome patient what could be better than to identify another practitioner who can take care of them better than you? As a resident transferring a patient to another service (from medicine to surgery was most common) was not only for the patients benefit, you had a transient dip in the work load and no longer had a patient whose issues (bad gallbladder) you were not comfortable  managing.

The only problem is that referring to Naturopathy as a credible source for medical diagnosis and treatment doesn’t make it so. To say

Naturopathic medicine is a distinct method of primary health care—an art, science, philosophy and practice of diagnosis, treatment, and prevention of illness. In stark contrast to a narrowly interpreted biomedical model, where pharmaceuticals are administered to battle disease, Naturopathic physicians seek to restore and maintain optimum health in their patients by emphasizing nature’s inherent self-healing process …. This is accomplished through education and the rational use of natural therapeutics. The naturopathic physician thus uses holistic approaches to enhance and restore the body’s own innate healing systems. Naturopaths undergo a 4-year graduate-level course of study but are generally not residency trained.

Ignores the fact that they are trained in unproven, often irrational, fantasy: nutritional supplements, homeopathy, acupuncture, hydrotherapy and electrical stimulation. There is no nonsensical therapy that is not in the naturopathic armamentarium. That is part of the problem with naturopathy: any and all medical magic is in their purview. And they are usually anti-vaccine.

The author recognizes there are conflicting paradigms between the medicine and ND’s. You think? He gives several examples of the different approaches between MD and ND for some common diseases, but suggests that somehow these differences can be overcome. It would is like recommending raising an alligator as a household pet. In the end, it will end badly. Say, honey, have you seen the dog and the baby?

Despite his suggestions that education and medical standards could somehow integrate ND’s into a reality based practice of medicine, to do so would require the  ND to abandon the fantasies in which they have invested time and money. I doubt that will happen.

Establishing and improving lines of open, respectful, constructive communication will be a first step toward developing the type of collaboration between allopathic and naturopathic physicians that our patients deserve.

Our patients do not deserve naturopathic practice, although the lateral pass of the difficult patient might make clinic easier. To quote me, if you mix cow pie with apple pie, it does not make the cow pie taste better; it makes the apple pie worse.  Our patients need a better apple pie, not cow pie.

Categories: Medicine, Skepticism

Artificial Sweeteners and Diabetes

Neurologica Blog - Thu, 09/18/2014 - 08:12

A new study published in Nature is getting a lot of press, and it seems making a lot of people worried. The Nature News article discussing the study has the headline: Sugar substitutes linked to obesity. I think this headline is misleading. Here’s a breakdown of what the study does and does not tell us.

The study’s title is more descriptive, as one might expect: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. The authors (A team led by Eran Elinav of the Weizmann Institute of Science in Rehovot, Israel) studied three noncaloric artificial sweeteners (NAS), saccharin, sucralose, and aspartame. They fed mice that either had a microbiota (bacteria colonizing their gastrointestinal system) or those that were germ free either NAS or control food without NAS. After 11 weeks the mice fed NAS showed signs of glucose intolerance – their blood sugar rose more when challenged with a dose of sugar.

They also found that mice treated with antibiotics did not have this response. Further, they performed fecal transplants from NAS treated mice to germ-free mice and found that the glucose intolerance transferred with the bacteria.  They also cultured bacteria with NAS and transplanted that into mice, who then became glucose intolerant.

All of this strongly suggests that consuming NAS alters the but bacteria, which in turn has an effect of metabolism of the host, leading to glucose intolerance. Glucose intolerance is a risk factor for type II diabetes, which essentially is severe glucose intolerance. The study did not have anything directly to do with obesity.

To see if their results would apply to humans, the researchers fed 7 human subjects NAS and found that 4 of them developed glucose intolerance, just like the mice.

This is all a nice bit of research. It certainly raises some interesting possibilities that deserve follow up study. I don’t, however, think these results are sufficient to recommend ditching NAS, and definitely this research does not suggest that drinking sugary drinks is more healthful than drinks sweetened with NAS.

The scientific community is already starting to pick over the results of this study, and dampen public reaction by putting it into perspective. First, the majority of this work was done in mice, who have a different glucose metabolism, diet, and tolerance than humans. The small study with 7 human subjects is very preliminary, and far from sufficient to conclude that the mice data will be applicable to people.

The Science Magazine article points out that the study was published in a basic science journal, and that a clinical science journal would probably have been much more critical of their clinical speculations.

Another potentially serious criticism is that the researchers combined saccharin, sucralose, and aspartame data. It seems highly unlikely that three very different molecules would all have the same effect on gut microbiota. It’s possible that what the researchers are seeing is isolated to saccharin alone, which the research focused on. Earlier trials used aspartame, which had a smaller effect so the researchers switched to saccharin. The Science Magazine article reports:

“The authors are confounding their conclusions by addressing all these noncaloric artificial sweeteners together,” says Brian Ratcliffe, a nutrition researcher at Robert Gordon University in Aberdeen, U.K. That’s why the title of the paper, “Artificial sweeteners induce glucose intolerance by altering the gut microbiota,” is misleading, he says. “I cannot believe the journal allowed that title.” Still, he says, the data “certainly does suggest that there is something more that needs to be explored about saccharin.”

If this effect is unique to saccharin, that would also explain the disconnect with other data focusing on the consumption of diet soft drinks, which use aspartame and sucralose. A large European epidemiological trial published last year and involving cohorts with >10,000 subjects found an association between drinking sugary drinks and Type II diabetes. It also found an association with drinking NAS containing drinks, but this association vanished when controlled for energy intake and BMI. In other words, people drink diet soda because they are overweight, not the other way around.

A 2011 study of >40,000 men found:

Sugar-sweetened beverage consumption is associated with a significantly elevated risk of type 2 diabetes, whereas the association between artificially sweetened beverages and type 2 diabetes was largely explained by health status, pre-enrollment weight change, dieting, and body mass index.

The two large epidemiological studies are likely to be more reliable than the 7 subject arm of the recent Nature study.

Conclusion

The current study is rigorous and interesting, as far as it goes. It suggests that saccharin has the potential to alter the gut microbiota of mice and has some relationship to glucose metabolism. It would be interesting to work out the various mechanisms involved with future research.

The bottom line that is frequently being communicated to the public about this study, however, is not supported by this data, is misleading, and is likely to lead to poor health decisions.

It is unclear if these results apply to sucralose or aspartame (and therefore diet soft drinks), and it is further unclear if they apply to humans.

Meanwhile, other studies, some of which are massive epidemiological studies, show a clear connection between consuming sugar-sweetened drinks and type II diabetes, and no connection to drinking NAS sweetened drinks. This study should not motivate anyone to abandon their diet drinks for sugar-sweetened drinks, but the way the study is being reported may do just that.

Categories: Medicine

Missouri tackles primary care shortage with “assistant physicians”

Science Based Medicine - Thu, 09/18/2014 - 01:00

Medical school clinical training

A new law in Missouri will allow medical school graduates who have not completed a residency to practice in underserved areas.  They will be able to call themselves “doctor” but will be licensed as “assistant physicians” with significant limitations on their practice.  (The first link is to Senate Bill 716, the bill that was passed and signed by the governor.  It covers several subjects, so you will need to skip to page 8 to find the portion we’re discussing.)

The Missouri State Medical Association supports the new law and helped draft the original bill.  It is designed to address the state’s critical need for primary care physicians — 40% of Missouri’s population lives in underserved areas but only 25% of the state’s physicians practice there, according to a 2009 survey.  Underserved areas have high poverty rates, high infant mortality, large senior populations and fewer primary care physicians per capita.

To address this primary care shortage, other states have expanded nurse practitioner scope of practice and allowed pharmacists to give immunizations, but Missouri is the first state to create a new type of practitioner licensing. Chiropractors and naturopaths argue that they, too, are primary care physicians and can help ease the shortage. Fortunately, no one seems to be taking them seriously. (We’ll return to DCs and NDs as PCPs shortly.)

All other states require at least a one-year residency to be eligible for licensing as a physician.  Most physicians complete an additional 3-7 years of residency training before going into practice; usually 3 years for primary care family practice doctors, internists and pediatricians. Med school graduates who become assistant physicians are, according to medical ethics expert Dr. Arthur Caplan, “not likely to be the cream of the U.S. crop.” Prime candidates for assistant physicians are those who didn’t get into a residency, got low scores on the U.S. Medical Licensing Examination, foreign med school grads, and some who would simply prefer that role.  But Dr. Caplan also thinks we should give the program a chance and expresses optimism that it could work out.

According to Governing magazine:

The total number of residency applicants has exceeded the total number of positions available since the 1980s. In 2014, 29,671 available positions were filled by 28,490 students, but the number of active applicants topped 34,000. About 7,000 of those were non-U.S. citizens who graduated from international schools, and about half of them found residencies. 

The American Medical Association, the Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education (ACGME) all oppose this type of fast-track licensing.  The Missouri Hospital Association and the state’s medical board, which will write the regulations, did not take a position on the bill during the legislative session.  The American Association of Physician Assistants also opposes the law, saying it will be confusing to patients.

ACGME board member Rosemary Gibson told Governing:

“On the surface, it looks like a quick fix, but I think it really behooves [policymakers] to do their homework, to understand what it means to have a graduate of a medical school be called doctor, to have prescriptive authority for powerful drugs like narcotics, to accurately dose and treat people,” she said. “Primary care is not simple. If you have a lot of older people living in rural areas, they have a lot of co-morbidities [such as diabetes combined with heart disease].” 

Dr. Thomas Nasca, ACGME’s CEO, agrees:

“These are physicians with only rudimentary experience,” he told Medscape Medical News. “In Missouri, without direct supervision, they’d be able to manage patients with complex diabetes, congestive heart failure, arrhythmias, and malignancies. This doesn’t make sense.

“Physicians in the United States are not trained to enter practice upon graduation from medical school,” Dr. Nasca said. “They don’t have the skill sets required for independent practice. It’s a flawed assumption to suggest that novices are prepared to provide clinical care on their own in a rural area where any medical condition could present itself. This isn’t an emotional response. It’s a data driven response to a very bad idea.”

Despite recognizing the need to serve challenged areas, he doesn’t see this as the appropriate remedy. “I don’t underestimate the challenges we face in delivering care to rural populations and the urban poor. But to provide inadequate care is no solution. There is a dramatic difference between a medical school graduate and a doctor trained in a residency program. Why go back to the 1940s when doctors just out of medical school provided care without supervision? The idea that primary care is somehow simple is ludicrous,” Dr. Nasca said. 

The Missouri State Medical Society’s general counsel and government relations director Jeffrey Howell strongly disagrees with critics of the law.  He told Medscape:

“The opposition puzzles me . . . The physician shortage in Missouri is so bad that communities with 2,000 to 5,000 people barely have access to a doctor one day a week. And they share that doctor with 2 or 3 communities. The new rules are no different than those for older doctors who didn’t have to go through a residency program. They just graduated from medical school and began treating patients.”

Assistant physician practice

To be eligible for assistant physician licensing, a med school graduate (including graduates of osteopathic medical schools) must successfully complete the first two parts of the U.S. Medical Licensing Exam no more than 3 years after graduation.  He must clearly identify himself as an assistant physician, including an ID badge, and may use the title “doctor.”  The state medical board will work out continuing education requirements with med schools and primary care residency programs.  Rules regarding prescription drugs must be approved by the state pharmacy board and, if controlled substances, also the state health department.

All must have an “assistant physician collaborative practice arrangement” with a fully licensed physician, who can oversee no more than 3 assistant physicians.  These arrangements must be written agreements, jointly agreed-upon protocols or standing orders.  The arrangements can, but do not have to, include the authority to prescribe certain drugs and the physician can limit the locations where this may occur.  Patients at these locations must be notified they have the right to see the licensed physician.  If these drugs are controlled substances there are additional requirements.

The assistant physician must practice in the same physical location as the physician for 30 days, longer if he will prescribe controlled substances. After that, they must be within “geographic proximity” of one another.  The assistant physician must submit at least 10% of his charts to the collaborating physician every 14 days for review.  If controlled substance prescribing is allowed, that jumps to 20%.

The collaborating physician “is responsible at all times for the oversight of the activities and accepts responsibility for primary services rendered by the assistant physician.”  However, as long as the licensed physician follows the procedures set forth in the law, he won’t be held vicariously liable.

Compare and contrast

It is interesting to compare the cautious (but nevertheless controversial) medical approach to granting a limited, supervised primary care scope of practice license to an MD with that of chiropractors and naturopaths.  Missouri, by the way, saw naturopathic licensing bills introduced every year but one from 2000-2010.  None passed, and naturopaths are not licensed in Missouri.  In fact, there is case law holding that a naturopath who diagnosed and treated patients without a license to practice medicine can be enjoined as a public nuisance.

There is a movement among chiropractors to claim they are primary care physicians.  (We’ve discussed this before several times on SBM – see here for references to all posts.)  Some chiropractors seem to have the term mixed up with “portal of entry,” which means the patient can see a practitioner without a referral.  The notion that chiropractors can move beyond musculoskeletal care is not universally shared.  It’s not even agreeable to some to move beyond straight subluxation-based practice.  This simply reflects the internecine wars that have been going on in chiropractic for years.

The most eager proponents of full-scope primary care practice appear to reside in New Mexico, where the “advanced practice chiropractor,” with a few additional hours of education and a limited formulary, can practice. This has led to some interesting attempts to, shall we say, “specialize” among NM DCs. Fortunately, the legalization of an “advanced practice” DC scope of practice does not appear to have seeped beyond the state borders and we hope it won’t, although that was not for lack of trying elsewhere.

Naturopaths with “naturopathic doctor” degrees seem dead serious about their claim to PCP status, although their latest licensing successes have fallen far short. (Also here.) They even have the audacity to claim that their education and training “substantially equivalent to” the MD primary care physician. Never mind that a portion of these hours are spent learning pseudoscience, like homeopathy. This led to a misleading chart, handed out to legislators, trying to bend and stretch the two curricula until the chart showed, under torture, supposed similarities. (Chiropractors have attempted similar nonsense. Also here.) The American Academy of Family Physicians apparently took umbrage at these shenanigans, rightly so, and put together its own chart.  Using the same basic idea – that number of hours, and not content, is the relevant measure of comparison — the AAFP gave the naturopaths a dose of their own medicine.

AAFP — ND comparison. Click to embiggen.

And so it is we find that the MD assistant physician will have had twice as many hours, including over twice as many clinical hours, as a naturopathic “physician” who goes into practice straight from naturopathic school.  Even if the naturopath did a one-year optional residency (most don’t), which can be as few as 535 hours, the naturopath barely squeaks by the MD assistant physician in total hours, and will still have fewer hours than the MD clocked during the clinical portion of his education (the combined clinical and lecture hours of the last two years of med school).

Even without a residency, med students must practice in a variety of clinical settings and put in far more hours of clinical training.  Naturopathic students are mostly limited to school-based ambulatory clinics where they see a narrow range of diseases and prescribe fantasy treatments,  yet want full PCP scope of practice.

Of course, if you look at a board-certified family practice physician versus a naturopathic “physician,” even one with a residency, the NDs’ comparison becomes a joke.  So much for the “equivalent education and training” argument.  And if naturopaths would like to go toe-to-toe with the AAFP on actual content, we’d all love ring-side seats.

The contrast between the approaches of MDs/DOs and NDs to the limitations of practicing before education and training meets medical licensing standards is telling.

  • MDs/DOs obviously realize that med school grads are not ready for prime time without a residency and worked with the state legislature to ensure strict limitations.  NDs deny that a residency is necessary and sponsor legislation permitting full PCP practice right out of school.
  • MDs/DOs realized that supervision is absolutely necessary.  NDs deny that supervision is required to safely practice. (Interestingly, Maryland’s recently passed licensing act requires NDs to have a collaboration agreement with an MD or DO.  Needless to say, this wasn’t the NDs’ idea.)
  • MDs/DOs carefully limit the prescribing authority of assistant physicians.  NDs say they are ready for full prescription authority.
  • MDs/DOs enforce limitations on assistant physicians with chart review and other restrictions.  Even brand new ND going into practice don’t have to report to anyone.

Whatever you might think of Missouri’s new law, you’d have to agree that any patient is far better off getting primary care from an assistant physician than a naturopath or a chiropractor. Dr. Nasca made the very point I’ve argued before in opposition to ND licensing:

“Patients don’t come to primary care physicians sorted into simple problems and complicated problems. . . The idea that primary care is simple and this idea that primary care can be done by people who are not well trained is a flawed concept. It is wrong. The primary care physician, in my opinion, has the most difficult job in the healthcare delivery system. That’s because they must not make errors of omission. They must not make errors of failure to recognize. It is a very challenging task.”

Dr. Nasca is absolutely right when he says that  ”the idea that primary care is somehow simple is ludicrous.”  To which we might add: the idea that DCs or NDs can serve as primary care physicians is even more ludicrous.

 

Categories: Medicine, Skepticism

Privileged Antivaxxers

Science Based Medicine - Wed, 09/17/2014 - 08:21

The Hollywood Reporter recently published what is mostly an exposé on privileged Hollywood parents who have elected to delay, limit, or avoid altogether immunizing their children. The most common headline coming out of this article is that some LA communities have vaccination rates at third-world levels, such as South Sudan. The issues raises many questions pertinent to the promotion of science-based medicine – what leads an otherwise well-educated individual with financial security to make decisions that actually put their own children (and others) at risk?

Some background

We have often observed at SBM that the anti-vaccine movement is likely to experience a serious backlash once epidemics of vaccine-preventable diseases start to emerge. I think we are seeing the beginning of this prediction coming true. Vaccines are partly the victim of their own success. The diseases they prevent, such as polio, measles, whooping cough, and others, are now uncommon. Modern parents have the privilege of not fearing these diseases because the vaccination program has reduced them to sporadic cases. Therefore, when pseudoscientists or ideologues stoke fears against vaccines, the fear of the diseases they prevent is not there as a balancing force.

That may be changing, however. The CDC reports:

During 2012, 48,277 cases of pertussis were reported to CDC, including 20 pertussis-related deaths. This was the most reported cases since 1955. The majority of deaths occurred among infants younger than 3 months of age.

From January 1-August 16, 2014, 17,325 cases of pertussis have been reported to CDC by 50 states and Washington, D.C.; this represents a 30% increase compared with the same time period in 2013.

Vaccine refusal is clearly an important factor in the recent pertussis outbreaks. That doesn’t stop antivaxxers from distorting the science. They claim, for example, that most pertussis cases occur in those who are vaccinated. This is a common misdirection. It is true that most cases occur within those who are vaccinated, but that is not the relevant statistic. It’s misleading because most people are vaccinated. The relevant statistic is the risk of being infected with pertussis in vaccinated vs unvaccinated individuals, and the risk is clearly much higher for vaccine refusers. Further, pertussis outbreaks tend to cluster in communities with higher rates of vaccine refusal.

They also point to recent concerns that pertussis strains may be evolving resistance to the current acellular pertussis vaccine. While this is a legitimate concern, it is an emerging issue, and not the cause of the recent epidemics. Ironically, the acellular vaccine, which has narrower coverage, replaced the whole cell pertussis vaccine largely over unfounded fears of side effects.

Vaccine refusers

The Hollywood article includes this illuminating passage:

For instance, actress Ione Skye, herself a former Gordon patient (“I never had antibiotics growing up; he really went the natural route”) who now brings in her own two daughters to see the physician, believes that the alternative path she and her husband, musician Ben Lee, have chosen makes “instinctive” sense. “With my kids, I spaced them out and waited and missed some,” she says. “As a mother, it just felt better to me —and my kids never had any reaction.”

This sentiment captures what is perhaps the core problem with antiscience in general. People like to trust their instincts or “gut feelings.” We largely behave based upon what feels right. The problem is, there are numerous flaws and biases in the subconscious processes that result in our gut feelings. (A full discussion of which is beyond the scope of this article, but is explored at length in numerous blog posts here and at my other blog, NeuroLogica.)

Antivaccine propaganda talking points tend to resonate with our intuition, but not with scientific data. Such data can be abstract, counter-intuitive, and highly complex. People generally have a poor intuitive grasp of statistics (so-called innumeracy). A relevant example of the role of innumeracy was given just above – how easy it is to mislead with statistics, such as considering the number of people who become infected (vaccinated vs unvaccinated) vs the risk of getting infected.

Antivaccine rhetoric, for example, includes that notion that the current vaccine schedule is “too many too soon,” and that the tiny bodies of infants are being overwhelmed with too many antigens. However, the antigens in the vaccine schedule has actually decreased over the years (as the vaccines have become more targeted), and the number of antigens children face on a daily basis from the environment vastly outnumber the few additional antigens in vaccines.

The Hollywood Reporter article focuses its attention on West Hollywood communities that are wealthy and favored by celebrities, which have demonstrated the highest levels of vaccine refusals. In some schools vaccination rates are less than 20%. While overall vaccination rates remain high (>90%), these pockets of lower vaccination rates represent a local loss of herd immunity, and are therefore breeding grounds for communicable diseases. In fact, that is what the data shows.

In addition to overreliance on instinct and general scientific illiteracy and innumeracy, what other psychological factors among the privileged might be contributing to such high rates of vaccine refusal? This is a question that could use further exploration. What we can point to are the cultural environments that tend to be most conducive to distrusting science. The alternative medicine community in general has fostered an environment of distrust for authority, distrust of government and the medical establishment, and distrust of the institutions of science.

One might also argue that the powerful and privileged in particular would feel that “going along with the herd” cannot provide the best option for their children. Surely their privilege must afford them something better.

Filling that demand for an approach that rises above the herd are the “doctors to the stars.” Dr. Robert Sears and Dr. Jay Gordon have most famously filled that demand, with alternate vaccine schedules. They even admit that their schedules are not based on hard science, but their own intuition – what “feels right.” This sells well to the privileged.

Conclusion

The evidence is overwhelmingly clear, not only with vaccines but with medicine in general. Following scientific guidelines that are based on robust evidence leads to the best outcomes.

Further, one of the strengths of science is that it is both egalitarian and a meritocracy (at least when functioning optimally). Data is king, and privilege and intuition should have nothing to do with it. There is a democracy to science, which is universal.

In medicine this means that treatments based on rigorous science are the best option for everyone, and the standard of care applies equally to everyone. (Of course, a significant challenge is for the delivery of medicine to also be fairly distributed, but that is a separate issue.)

No amount of money or privilege can buy you better science. It is perhaps for this reason that some people choose “alternative” science. They think they are getting something better than the herd. Ultimately, however, this is just a cleverly marketed deception. In the case of alternative vaccine schedules, all they are buying is higher risk for their children for infectious and potentially serious diseases. Further, they are exporting this risk to others, perhaps with less privilege.

Perhaps we are seeing the beginning of a backlash from the real “99%.”

Categories: Medicine, Skepticism

The Genetics of the Schizophrenias

Neurologica Blog - Tue, 09/16/2014 - 08:22

A new study sheds further light on the genetic basis of the group of psychiatric disorders known collectively as schizophrenia. Further, the study (actually a collection of four studies) takes a new approach that might prove generally useful in associating genetic variation with disease risk, even beyond psychiatry.

Schizophrenia

In popular culture the term “schizophrenic” is often used to mean split personality or multiple personality, but this has never been the actual definition of the term. I’m not sure what the origin of this misconception is. The word “schizophrenia” does mean “split mind” but refers to mental illness characterized by disordered or delusional thinking. The “split” is between reality and mental function.

For at least several decades it has been clear that schizophrenia is not one discrete disorder, but rather it is a set of similar disorders. Symptoms include hallucinations, delusions (persistent false beliefs that do not have a cultural cause), impaired reality testing, bizarre thoughts and behaviors, often but not always paranoid in nature, a disconnection between thoughts and emotions, and lack of motivation or activity.

Part of the challenge of studying schizophrenia is that it is a clinically defined set of disorders, meaning that the category is based upon the signs and symptoms displayed, not any knowledge about underlying cause or biology. The brain, as you might suspect, is an incredibly complex organ with many interacting parts, and so there is likely to be a complex relationship between the underlying mechanisms of schizophrenia and the clinical manifestations.

This caused decades of debate about how to classify the different schizophrenias, and how many underlying disorders do they actually represent. Some researchers came to suspect that the clinical classifications might be fundamentally flawed, holding back basic research into genetics or other underlying mechanisms.

There has been a great deal of research into the genetics of schizophrenia. Researchers tried to find specific genetic mutations that would predict the development of schizophrenia. A recent review of twin studies found:

They yielded probandwise concordance rates of 41-65% in monozygotic (MZ) pairs and 0-28% in dizygotic (DZ) pairs, and heritability estimates of approximately 80-85%.

This means identical twins have about a 50% concordance (both either have or do not have schizophrenia), while non-identical twins have much lower concordance. This means that genetics are very important to the risk of schizophrenia, but not everything. There must be environmental factors as well. Overall, genes contribute 80-85% to the risk of developing schizophrenia.

Attempts to identify specific genetic variants that predict schizophrenia have been mixed. Specific gene variants seem to correlate with schizophrenia in some studies, but not others, or only in a subset of schizophrenic patients.

Such results are partly what lead to the hypothesis that schizophrenia is a set of related but distinct disorders. Certain genetic variants are found in some schizophrenics but not others because they actually are different disorders. The challenge then became identifying clinical subtypes of schizophrenia that were likely to reflect underlying genetic contributions. If our clinical categories did not cleave in the same places as the underlying genetics, attempts to correlate the two would be forever frustrated.

A New Approach

This brings us to the newly published paper. Arnedo et al, researchers at the Washington University of St. Louis, did a series of studies in which they looked at single nucleotide polymorphisms (SNP) in 4,200 people with schizophrenia and 3,800 healthy controls. SNPs are essentially point mutations in a single gene – one altered nucleotide. Instead of looking at the relationship between individual SNPs and schizophrenia, they looked at clusters of SNPs. The idea is that a cluster of SNPs would reflect a set of interacting genes that control the development and organization of the brain.

They also looked at the specific symptoms of schizophrenia in their patient population and identified 8 clusters of symptoms. When they looked at the SNPs in these patients they found 42 clusters of SNPs that were associated with a 70% or greater risk of having schizophrenia. Some of the clusters had higher risks, including some with 100% correlation with schizophrenia. They report:

These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%).

Equifinality means that multiple pathways can lead to the same outcome, or in this case, multiple gene clusters could correlate with the same clinical syndrome. Multifinality means that one cause can have multiple effects, or here that one gene cluster could correlate with multiple clinical syndromes. This is not surprising. We see this in may multigene disorders, even outside of psychiatry. Specific clinical manifestations often have a probabilistic relationship to markers of underlying cause.

Finally, the clusters of SNPs were more predictive than looking at cumulative predictive value of the individual SNPs. This highly suggests that it is the interaction among the various genes that is important, and not just the adding up of individual gene effects.

One of the authors, Robert Cloninger, is quoted as saying:

“What we’ve done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the ‘orchestra’ is either harmonious and leads to health, or disorganized in ways that lead to distinct classes of schizophrenia.”

Conclusion

This is an exciting study for two reasons. The first is that it sheds significant light on the genetics of schizophrenia. This may lead to a new consensus about the clinical subtypes of schizophrenia. It will be interesting to see if the 8 clusters of symptoms identified in this study become officially recognized as the clinical subtypes of schizophrenia.

Second, and I think more importantly, this study shows the power of this approach to correlating genetics and clinical syndromes – looking specifically at the interaction of clusters of genes, rather than the contribution of individual genes. Applying this technique to many psychiatric and even non-psychiatric conditions may prove highly fruitful.

What this reflects is that, not only is the brain extremely complex, but genetics is extremely complex as well. The genetics of brain development is therefore complex squared. We need to take an equally complex approach to asking questions about the relationship between specific gene variants and resulting neurological outcomes. This approach perhaps gets us to the next level, looking at gene clusters, although I would not be surprised if deeper levels of complexity await our discovery.

I would like to see the common public conception of genetics get away from the simplistic notion of “the gene for X,” or the false dichotomy between genes and environment. Genes are not blueprints. They do not work from the top down. Genes are complex dynamic instructions that interact with other genes and a variety of environmental factors. The field of epigenetics is essentially the study of those factors that affect genetic expression. But really genetics and epigenetics are part of the same big picture of how genes work.

The other take-home message is that many diseases and disorders are really categories of similar diseases and disorders. This is particularly true in psychiatry, although not unique to psychiatry. For all the above reasons we may never identify a pure schizophrenia subtype. Such categories will always be fuzzy around the edges and blur one into the other. That is simply the nature of a complex dynamic system.

Categories: Medicine

The Human Mold: Another Example of Self-Deception

Science Based Medicine - Tue, 09/16/2014 - 03:00

This cover picture is scientifically inaccurate. See explanation below.

José Jarimba believes that our bodies are physically molded into an asymmetric form by our mothers’ sleeping positions during pregnancy, that this has lifelong adverse impacts on health, and that shoe inserts can eliminate pain and other health problems by realigning the body. This is a silly untested hypothesis by a single individual. As such, it would be too minor to merit mention on SBM; but it is worth analyzing as a teaching opportunity. Jarimba attempts to bypass the scientific process; he provides a prime example of self-deception, confirmation bias, scientific ignorance, and the “Unpersuadables” I recently wrote about.

Much of alternative medicine originated with a “lone genius” who had an epiphany, thought he had discovered something no one had ever noticed before, extrapolated from a single observation to construct an elaborate theory that promised to explain all or most human ills, and began treating patients without any attempt to test his hypotheses using the scientific method. Some of them were uneducated laymen, others were scientifically trained medical doctors who should have known better. I wrote about one of them here, Dr. Batmanghelid, inventor of the Water Cure, who attributed a great variety of illnesses to dehydration after he thought he had cured a prisoner’s peptic ulcer disease by giving him a glass of water. Similar paths were followed by many others. Hahnemann invented homeopathy after he thought a malaria remedy gave him symptoms of malaria. Palmer invented chiropractic after he thought he had restored a man’s hearing by repositioning an out-of-place bone in his back. Nogier invented ear acupuncture after he imagined that the external ear looked sort of like a fetus. Shapiro invented EMDR after she noticed during a walk in a park that moving her eyes seemed to reduce the stress of disturbing memories. Bach invented Bach flower remedies after a walk in the country revealed his intuitive psychic connection to various plants. Jose Jarimba follows in their footsteps.

Jarimba has no medical or scientific training. His epiphany was a combination of two observations: he noticed that a man’s sideburns were asymmetrical and his hair coarser on one side, and he watched a film clip about a fetus. He thought: adults are not symmetrical, and when a mother lies on one side, that puts asymmetrical pressure on the fetus’ body. Eureka! He concluded that the mother’s sleeping position must cause physical deformation, organ deformation and malfunction, and various ailments.

He asked, what do pregnant animals do in the wild? He says that mammals alternate sleeping on one side and the other (Do they? How does he know? Are other mammals more symmetrical than humans?) and birds sleep on their feet because if they lay down their eggs would come out lopsided. (I think it’s because if they tried to lie down on their side they would fall off the branch where they are roosting.) He says pregnant women should sleep equal numbers of hours on the left and right side if they want a healthy baby.

He thinks the process of deformation begins at conception. He blames modern technology. Before we had machines, women worked and exercised. He thinks their fetuses were in an upright position and faced towards the mother. (Really? I don’t think so!) After the development of machines, pregnant women were advised to rest and got help with their domestic duties. Those who worked and were active throughout pregnancy had more symmetrically perfect babies. (Really? How does he know?)

He claims that physical misalignment occurs in proportion to the hours the mother sleeps on one side. 6 hours a night corresponds to 5-10% chance of misalignment, 16 hours to 60-70%. (Who sleeps 16 hours?) I asked him how he figured out those percentages. He explained that a day has 24 hours, and if a mother rests 8 hours a day, that’s 33 1/3%; then divide one inch by 3, and 8 hours equals one third of an inch. I asked where the figure of one inch came from, and he said that’s the measurement of deformity that can be corrected without surgery, and he cited a webpage about congenital hip dysplasia. (None of this makes a bit of sense to me; maybe it will to you.)

If the mother sleeps on her right side, he says it affects the baby’s left side. He seems to be assuming the baby’s left side will be down. The most common presentation at delivery is left occiput anterior, which would put the baby’s left side down when the mother slept on her left side. And the baby’s position is constantly changing. It only becomes fixed when the presenting part engages in the pelvis shortly before delivery; most breech babies turn head-first spontaneously by the 37th week. He thinks the internal organs are affected. He thinks the valves inside the heart can be malformed by fetal position; he thinks they become tilted towards the affected side and that this decreases oxygenation and cause heart attacks. He says resting on one side can cause upper body misalignment and on the other side, lower body misalignment (I asked him to explain how that would work, and he failed to answer.) He says sitting on a chair causes foot misalignment (how would that work if the baby was in the common head-down position?). He says vision is affected by position because the orbital muscles on one side become stretched toward the back of the head. He thinks too much sitting leads to breech deliveries. None of this is plausible; it’s impossible to visualize how gravity and pressure could accomplish those things.

I had never heard of Jarimba before he contacted me and sent me a copy of his book The Human Mold. We had a long e-mail exchange. I asked him what left-sided asymmetry meant and how he could determine which side was the abnormal one. His answer was nonresponsive: “When I say asymmetric from the left side, I mean that the left side is the abnormal side.”

I asked how he knew how many hours a woman slept on one side. He acknowledged that self-reports were unreliable, but claimed he could assess sleeping time accurately by measuring the degree of physical misalignment. He can tell the degree of misalignment from the number of hours, and he can tell the number of hours from the degree of misalignment. I pointed out that this is circular reasoning. He did not comment.

He says most women sleep on their right side “as recommended by the CDC.” He got that backwards: the left side is preferable, although not enough to matter. We know that in late pregnancy, the uterus may press on the vena cava, and lying on the back or on the right side may reduce blood flow; but in a normal pregnancy this is not significant. Women are encouraged to sleep in whatever position they find most comfortable.

He described an experiment he did with 17 women, asking them to alternate sleeping sides and finding that the babies were born more symmetrical. There was no blinding and no control group. When I asked him about that, he said, “I do understand very well that experiments with no control group might reach false conclusions, but in this case, I am proud to announce that my research produced no false conclusions.”

I asked how asymmetry could affect organ function, and he said when the structure is misaligned the weight of the imbalanced fluid pressing on the veins causes the veins to bend resulting in slow blood flow to the organs, heart, head (brain), and to all the body causing major health complications. He says a “tilted” kidney can’t function properly. I don’t believe any of those assertions.

I asked if he had talked to any obstetricians about his theories, and he said no, because he had studied their literature and found “a lack of deep knowledge into the development of our being.” His own lack of even basic knowledge is obvious in the cover illustration he chose to grace his book. It depicts a fetus in a woman’s abdomen. The fetus’ head is positioned just under the breasts at a height not reached even at full term. The fetus appears to be at about the 12 week stage of development and at that stage the uterus should be about the size of a grapefruit and still down inside the pelvis, and the fetus should be much, much smaller in relation to the woman. And the fetus’ position as shown is that of a footling breech, one of the rarest presentations for delivery.

He has treated over 2,000 clients. He doesn’t advertise, but he has an office where he sees them by appointment only. He charges $120, sees them only once, and gives them a shoe insert that he makes himself. He does no systematic follow-up.

He says you can analyze yourself by looking in a mirror, and you can analyze your friends. You will notice that one ear sticks out more than the other, one shoulder is higher than the other, one eye is smaller than the other (he says this is more noticeable at the end of the day), one leg is shorter than the other, one heel is more curved, etc. Once you know which is your bad side, you can sleep on the other side to counteract the asymmetry. He says the blood flows slower on your bad side.

He himself had 52 years of low back pain, foot pain, and overall body discomfort. All of these vanished after he put an insert in his shoe. He has plenty of patient testimonials. Back pain relieved. Back surgery avoided. More energy. Better sleep, more mentally focused, no headaches, no longer get sick. Alternating sleep sides during pregnancy produced a happy baby who doesn’t spit up and sleeps through the night. He apparently doesn’t understand that the plural of “anecdote” is not “evidence.”

He echoes the claims of chiropractors about spinal alignment, nerve interference, and disease. He cites the discredited Winsor Autopsies study from 1921 that supposedly correlated spinal misalignments with diseases of internal organs and concluded that 80% of chronic disease problems are linked to the spine. Jarimba comments that Winsor’s findings “indicate that most human physical deformities found in his autopsies were possibly caused by the mothers of the subjects sleeping/resting mainly on one side during pregnancy.” Winsor’s findings indicate no such thing!

He indulges in a bit of doctor-bashing, encouraging people to avoid dependence on the current health system. He says that reading media reports and visiting a doctor can cause stress and “lower” the immune system. He says overuse of medical care is wrecking your health. He says the mere act of purchasing health insurance may subconsciously prepare the mind and body to allow your health to break down. He says maintaining a positive attitude will help keep you healthy.

I suggested he might be risking prosecution for practicing medicine without a license. He said, “I do not practice medicine. I do not touch people physically.” Yet he is telling prospective clients he can relieve their pain and emotional symptoms, and on this Facebook page his occupation is listed as Family Doctor.

I asked him a lot more questions, but instead of answering, he replied, “I am sorry, since you haven’t witnessed my work in action (live), I see no need to keep on going.”

I eventually got him to answer 3 more questions:

  1. “Has what I wrote made you question your theory in any way?” “No.”
  2. “Do you think there is any possibility that you might be wrong?” “No, because it works, and if it works it is OK.”
  3. “If good scientific studies found that time sleeping on one side was not related to asymmetry, and that your shoe inserts worked no better than placebo, would that change your mind?” “There is not a single possibility of that happening.”
Conclusion

In his book, Jarimba says, “I hope that my observations will one day have a positive impact in the health system and the entire human population.” I think there is little chance of that.

This is yet another sad example of a person who has deceived himself. He has adopted a belief without ever putting it to a proper test, and has been fooled by his own experiences and by confirmation bias. He has a poor understanding of science, of critical thinking, and of the cognitive errors we humans are all subject to. He fails to understand what Druin Burch calls “Medicine’s beautiful idea,” the idea that we can easily be misled into false beliefs and must test even the most apparently obvious hypotheses using reliable scientific methods. Jarimba demonstrates the hubris of a layman who thinks he knows more than the experts, the Dunning-Kruger effect. He demonstrates the closed mind of an “unpersuadable” to perfection. Fortunately, he is only a single crank who has not yet spawned a movement, and what he does is not likely to harm his clients. He may even do some good here on SBM by serving as a bad example.

Categories: Medicine, Skepticism

Only two months until Skepticon

Science Based Medicine - Mon, 09/15/2014 - 13:00

I don’t recall if I’ve mentioned this before, but I will be speaking at Skepticon in November. (Holy crap, that’s just over two months away. I’d better get my talk ready. It’ll be about the central dogma of alternative medicine. Or some such medically-related topic.) In any case, now’s crunch time, the time of year when Skepticon’s fundraising needs to go into high gear, given that the bills are coming due for the conference.

So give. Give until it hurts. Or buy swag. Or both. And if you’re planning on going, register now instead of later. You’ll be glad you did.

Categories: Medicine, Skepticism

Stem Cell Transplant First

Neurologica Blog - Mon, 09/15/2014 - 08:21

NeurologicaBlog is very meta. I like to not only communicate science, but explore how best to communicate science, including thinking about how to communicate the need to think about thinking. (Cue the endless meta-regression.)

For example, there is often much to criticize about how science news is reported in the general media. Part of the problem is that science mostly advances by accumulating baby steps.  Baby steps, however, don’t always make for compelling headlines, and so every advance becomes a “breakthrough,” every mystery has scientists “baffled,” and every study may some day lead to the cure for cancer, rid us of the common cold, or produce a piece of technology similar to that found in popular science fiction.

Part of the challenge of being a skeptical science communicator is to convey simultaneously the deserved awe of cool science, including the potential implications of genuine advances, while also discussing the need for caution in interpreting results, and essentially throwing a wet blanket on premature hype. It can be a delicate balancing act.

I had all this in mind when I approached the main topic of today’s post – a rather exciting and anticipated advance in stem-cell technology. Japanese researchers have created a sheet of retinal epithelial cells from a patient’s own skin cells. First they had to induce pulripotency on the skin cells, which essentially turns them into stem cells (iPS cells). Then they had to coax these created stem cells into becoming the desired cell type which in this case is retinal epithelial cells.

The researchers have just surgically implanted this sheet of cells into the eye of the patient from whom the skin cells were taken – she is getting a transplant of her own tissue. She suffers from macular degeneration, a common cause of loss of vision resulting from loss of the retinal epithelial cells. The surgery is not expected to restore the patient’s lost vision, but it is hoped that the transplanted tissue may decrease further degeneration of the retina.

Why is this such an exciting advance? It is just a baby step, to be sure, but it is a noteworthy milestone and a good time to review where we are with stem cell technology.

Stem cells are any cell population that can differentiate into various mature cell types. There are many types of stem cells that are partially differentiated and serve as a source of new cells. For example, bone marrow contains blood stem cells that can differentiate into the various types of blood cells. A stem cell that can turn into many different types of cells is called pluripotent.

Embryonic stem cells are totipotent, meaning they can potentially turn into any cell type in the body. This is why they are so useful for research and have such promise therapeutically. They remain controversial, however, because they are harvested from embryos.

In the last decade, however, researchers have discovered how to induce at least pluripotency. By making just a few genetic changes, they can take adult derived skin cells and revert them to pluripotent stem cells. These are not as useful as embryonic stem cells, but they are still quite useful and have the advantage of not being controversial.

Stem cells derived from adult cells also have a huge potential therapeutic advantage – if you can induce stem cells from a recipient’s own cells, then you can ultimately give them a transplant of their own cells. This could eliminate the problem of rejection (which results from the immune system of the recipient recognizing the transplanted cells as foreign).

This, then, is the “holy grail” of stem cell therapeutics. Imagine a day when doctors can take a sampling of your skin cells or a cheek swab to gather a few epithelial cells, then culture those cells and revert them to a pluripotent state. They could then essentially have a vat of your own stem cells, from which they can make cells of any type they wish.

Such stem cells would have multiple possible uses. One use would be similar to the recent report – forming a tissue or even a full organ for transplant into the patient. A patient could theoretically receive an implant of their own kidney, eliminating the need for a donor, ensuring organ availability, and further eliminating the need for anti-rejection drugs. This would certainly be a game-changer for organ transplantation. The same could be done for blood transfusions, bone marrow transplant, skin grafts, or any organ that could be grown from the stem cells.

A second application is to inject the engineered stem cells into the body where they will repair or replace tissue in the body. Rather than growing a heart and then transplanting into a patient, therefore, you could inject cardiac stem cells into the existing heart, and those cells will form cardiac cells that will repair a damaged or weakened heart. There are already preliminary clinical trials of such treatments. Similarly, neural stem cells could be injected into a brain following a stroke, and those cells could repair the damaged brain tissue.

A third potential application is using stem cells not to directly replace damaged or lost tissue, but to support it in order to cure or mitigate the effects of disease. An engineered stem cell could be designed to deliver a steady dose of a drug, hormone, neurotransmitter, or other desired chemical. These nurse stem cells could keep a cell population from dying, preventing the progression of disease. Or they might just serve as an excellent drug delivery system.

It’s difficult to overstate the potential of stem cells (pun intended) – fully realized, stem cell technology could be an incredibly powerful therapeutic tool. This is exactly why there is so much hype surrounding stem cells.

But we also have to clearly state the reasons for caution. While the technology is advancing, this is very complex technology with many hurdles to overcome. The applications I listed above are still very experimental. One major potential problem is that transplanted stem cells might have the potential to form tumors and cancer. The reason our bodies are not naturally full of stem cells allowing us to regenerate any damage, disease, or degeneration is because of the neoplastic potential of stem cells. We evolved to get rid of them as soon as they were not absolutely necessary, to minimize the risk of cancer.

Further, it remains to be seen if adult-derived induced pluripotent stem cells will actually eliminate the possibility of rejection. Perhaps the process by which cells are made pluripotent and then made to differentiate into the desired cell type will also change them enough to still trigger rejection to some degree. Hopefully not, but until we do the research we won’t know for sure.

All this, of course, is on top of the basic technology of knowing how to get stem cells to become the exact kind of cell that we want. Creating organs is even more challenging – we need more than a sheet or clump of the desired cell type, we need to construct a three-dimensional complex structure. Researchers have been trying to do this using scaffolding, which is basically a donated organ denuded of its own cells. Results so far have been encouraging, but a long way away from transplantable organs.

Premature hype can be a problem. It created unrealistic expectations in the public, who then might become discouraged when the promised applications are not being realized. Perhaps worse, however, it can make some people vulnerable to exploitation. There are essentially phony stem cell clinics popping up around the world (in countries with poor regulation) promising stem cell treatments long before the technology actually exists.

Conclusion

Stem cells are a very exciting technology that has the potential to transform modern medicine. The current study represents a noteworthy milestone – the first implantation of tissue from induced pluripotent stem cells taken from the tissue recipient. It’s encouraging to see the technology continuing to advance.

We have to keep this one case and the potential for stem cells in perspective, however. Science advances by baby steps, and there are many incremental advances between where we are now and the dramatic stem cell therapeutics we hope to have one day. The applications we are waiting for will likely take longer than the general public realizes (or hopes).

Like many technologies, stem cells are likely to be disappointing in the short term, but then exceed our expectations in the long term.

Categories: Medicine

Medicine past, present, and future: Star Trek versus Dr. Kildare and The Knick

Science Based Medicine - Mon, 09/15/2014 - 03:24

I’ve been a big Star Trek fan ever since I first discovered reruns of the original Star Trek episodes in the 1970s, having been too young (but not by much!) to have caught the show during its original 1966-1969 run. True, my interest waxed and waned through the years—for instance, I loved Star Trek: The Next Generation, while Star Trek: Enterprise and Star Trek: Voyager pretty much left me cold—but even now I still find myself liking the rebooted movie series. In the original series, my favorite characters tended to alternate between Spock, the Vulcan first officer and science officer on the Enterprise, and Dr. Leonard “Bones” McCoy, the ship’s chief medical officer. I sometimes wonder if my love of these two characters had anything to do with my becoming a doctor and researcher myself. It probably did.

One aspect of all the Trek shows that always interested me was its portrayal of medicine in the 23rd and 24th centuries. After all, what doctor wouldn’t like to have a device like the tricorder that he could wave over the patient and come up with an instant diagnosis and course of treatment? Who knew, of course, that nearly 50 years after the first Trek episode first aired, we would have technology that makes the communicators on the original series (TOS, for those Trek non-fans) look primitive and large by comparison and that we’d be well on the way to developing devices that can do some of what tricorders did on the show. Throughout all the shows and movies, the medical technology of a few hundred years in the future is portrayed as vastly superior to what we have now, with 20th century medicine at times denigrated by “Bones” McCoy and other Star Fleet medical personnel as barbaric quackery.

A confluence of events and media led me to want to explore a couple of questions. First, which procedures that we consider state-of-the-art science-based medicine will be considered “barbaric” 50 or 100 years from now? Second, is the contempt expressed for the medicine of the past (e.g., by “Bones” McCoy) justified? These are questions that I’ll explore a bit with the help of the Star Trek universe, a recent new cable television drama series, and a couple of articles that appeared on medical sites as a result of the premier of that series.

Star Trek: 23rd century medicine vs. 20th century medicine

Perhaps the most amusing example of McCoy’s contempt for the “primitive” medicine of the 20th century occurs in the 1986 movie Star Trek IV: The Voyage Home. (I found it particularly amusing because I was a third year medical student when the movie came out.) For the purposes of this post, you don’t need to know the plot, other than that it involves the crew of the Enterprise time traveling to San Francisco in the year 1986 to obtain something from the past that would save the Earth of the year 2286. During their mission one of the crew, Chekov, is seriously injured fleeing from the military, captured, and as a result taken to Mercy Hospital for emergency surgery. When Dr. McCoy learns of this, he begs Captain Kirk not to leave Chekov in the hands of 20th century medicine. So Kirk and McCoy disguise themselves as doctors and infiltrate the 20th century hospital where Chekov is about to undergo emergency surgery in order to rescue him. It is during this part of the movie that this hilarious exchange occurs:

For those of you who can’t play the YouTube video, here’s a transcript that shows you what I mean. First, “Bones” encounters an old woman on a gurney in the hallway and asks her a question:

McCoy: What’s the matter with you?

Patient: Kidney… dialysis.

McCoy: Dialysis?! What is this? The Dark Ages? Here! You swallow that and if you have any more problems, just call me!

Later, as the crew is escaping, McCoy encounters the woman again, who’s telling everybody that McCoy had given her some pills and she grew a new kidney.

In another scene, Kirk and crew are in an elevator with some interns, and McCoy overhears the following conversation, not being able to stop himself from butting in:

1st Intern: So, Weintraub says radical chemotherapy or she’s gonna croak. Just like that…

2nd Intern: And Gottlieb?

1st Intern: Well, what’d you expect? All he talked about was image therapy. I thought they were going to punch each other.

McCoy [Muttering and shaking his head]: Unbelievable…

1st Intern [Turning to McCoy, having heard his muttering]: You…have a different view, Doctor?

McCoy: Sounds more like the goddamned Spanish Inquisition!

Kirk [Turning to the interns and shrugging shoulders]: Bad day…

Later, Kirk and McCoy kick a neurosurgeon about to operate on Chekov to drain what sounds like an epidural hematoma out of his operating room at phaser-point, and McCoy proceeds to save Chekov’s life with his 23rd century technology.

You get the idea: In the fictional Star Trek universe, to a physician of the 23rd century what physicians of the 20th century do appears as barbaric as the practices of 18th century physicians appear to us physicians of the 21st century. What really got me thinking about this question again was the premier of a new historical medical drama on Cinemax entitled The Knick, which tells the story of Dr. John Thackery, fictional chief surgeon at the Knickerbocker Hospital in 1900. As a surgeon, I can’t help but apply the same sort of eye to surgery as practiced 114 years ago as Dr. McCoy did to medicine practiced in 1986. Unlike McCoy, however, I can’t lather up the same level of contempt for the fictional surgeons of the Knick that McCoy can for the hapless doctors of Mercy Hospital.

The Knick: What a difference 114 years makes!

Although I subscribe to HBO, I don’t subscribe to Cinemax. Consequently, I was only able to view the first episode of The Knick using On Demand, and have since only seen the first three episodes because HBO happened to show them all in a block about a week after the third episode aired. I haven’t seen episodes four or five yet, although I’m seriously tempted to subscribe to Cinemax for the remainder of the season just to see the show and then to drop it after the show’s run ends. However, the episodes I’ve seen are enough to pique the interest of any surgeon interested in the history of surgery. Producer Steven Soderbergh likes to brag about the measures his team has taken to assure historical accuracy with respect to the medicine practiced and the surgical procedures portrayed, particularly how extensively his show has used the Burns Archive, a trove of more than a million historic photographs (a few of which are digitized and displayed here, unfortunately without much in the way of text or captions to tell the viewer what they are), to recreate the look of medicine in the early 20th century.

Of course, it being a fictional show, there are things that The Knick takes some creative license with, such that I wondered about them immediately. For instance, body snatching to supply hospitals with medical cadavers and fights between ambulance drivers over who gets to pick up patients were apparently not as prevalent as The Knick portrays, given that New York was one of the first states to pass “anatomical acts” in the mid-19th century to discourage trade in bodies and body snatching. By 1900, such activities would be a risky, at best, crime not likely to be particularly profitable. On the other hand, given the level of endemic corruption in New York in 1900, characters like corrupt Health Inspector Jacob Speight who takes kickbacks to refer patients he finds with reportable infectious diseases for which the city mandates treatment to the Knick and the equally corrupt hospital administrator who works with him are not implausible.

One thing I noticed in the very first operating room scene (and in all the operating room scenes in the episodes I’ve seen thus far), surgeons are depicted operating bare-handed. Instead of scrubbing up and using rubber gloves, as surgeons have done for many decades now, they dipped their hands into antiseptic solution right before the start of surgery. It turns out that the great surgical pioneer upon whom Dr. Thackery is loosely modeled, Dr. William Stewart Halsted had pioneered the use of rubber gloves in 1889 or 1890 because his scrub nurse (with whom he later fell in love and who ultimately became his wife) had begun to develop severe contact dermatitis as a result of the nasty chemicals (mercuric chloride and phenol) used to disinfect the hands of the operating staff at the time. Rather than have her reassigned, Halsted requested the Goodyear Rubber Company, as an experiment, to make “two pair of thin rubber gloves with gauntlets.” At first, only assistants used them, but within a couple of years, the surgeons at Johns Hopkins, where Halsted practiced, were using them. So it seems a bit of creative license that the surgeons at the Knick would still be operating bare handed. On the other hand, it’s not too beyond the pale that some surgeons might still be operating bare handed in 1900, given that it wasn’t until 1899 when Halsted’s protégé Dr. Joseph Bloodgood (what an awesome name for a surgeon!) published a report of 450 hernia operations using gloves, observing that the infection rate fell by nearly 100%. Bloodgood’s report led Halsted to take himself to task, asking “Why was I so blind not to have perceived the necessity for wearing them [rubber gloves] all the time?”

Think of it: A man with one of the most brilliant minds in the entire history of surgery responsible for so many surgical innovations, from emergency blood transfusions, to cancer surgery, to something as mundane as a bedside chart to track a patient’s vital signs and the use of surgical gloves operating room, a man who first laid down surgical principles still taught to all surgeons today, such as a completely sterile surgical field, hemostasis, gentle handling of tissue, careful anatomic dissection, and exact approximation of tissues, and Halsted couldn’t immediately figure out that wearing sterile rubber gloves instead of dipping one’s hand in caustic chemicals to disinfect them was a superior means of preventing surgical infection!

Other examples, although perhaps anachronistic, are found in the fictional world of The Knick. For example, the very first OR scene in the very first episode portrays the attempt by Dr. J.M. Christiansen and Dr. Thackery to perform a Caesarian section on a woman with placenta previa, after having failed at this procedure eleven times before. They fail again, with the mother and baby both dying. As a surgeon, I found this scene particularly disturbing and effective. As I watched the impressively realistic pools of blood form, overwhelming the ability of the pedal-driven suction to clear them, the surgeons frantically working, and the nurse reporting a faster and faster pulse (and ultimately no pulse), all as dozens of doctors and trainees observe the procedure, I couldn’t help but wonder how surgeons could actually save anyone in such an environment.

The same question came up later in the same episode, when a man with a bowel perforation had his injury repaired primarily. The surgeon who did the repair was taken to task by Thackery on rounds for not resecting. Later, the patient develops intra-abdominal sepsis, requiring Thackery to operate on him using an instrument he had constructed himself to resect the nonviable bowel and sew it back together. While I admit that this part made me wonder (bowel anastomoses were pretty standard procedures by 1900; so I’m not sure why this would have been so revolutionary), I still had to marvel how any surgeon could expect any patient with a bowel resection to survive intra-abdominal sepsis after a bowel perforation with no antibiotics as adjunctive care for the drainage and resection.

More examples included a man with an aortic aneurysm, for whom the treatment would be a galvanic procedure (using electricity to induce thrombosis of the aneurysm), an attempt to reconstruct a woman’s nose lost to syphilis using a tissue flap from the arm that necessitated the arm to be attached to the nose for several weeks to provide a blood supply (a technique still in use today for some reconstructive procedures), and the portrayal of Dr. Thackery anesthetizing a patient using a cocaine epidural. A lot of these weren’t exactly 1900 medicine, although they were generally from within a few decades. Dramatic license again. The point, however, is that medicine always operates within the context of the existing scientific and clinical knowledge of the time. Of course, The Knick is a vision of what medicine was like in 1900 imagined by a man of 2014. However, it’s also informative to look at medicine as portrayed in the media contemporaneously, as we will see. To do that, I leap from the world of The Knick to 50 years in its future.

Dr. Kildare, or I’d rather have a bottle in front of me than a frontal lobotomy

Over the last few years I’ve become a bit of a fan of old time radio, having discovered Radio Classics on Sirius XM Radio. In particular, I discovered The Story of Dr. Kildare. This particular radio show stared Lew Ayres as Dr. Kildare and Lionel Barrymore as the irascible Dr. Leonard Gillespie (the latter of whom was actually hilarious, by the way). It’s an episode of this show that demonstrates perhaps the clearest example of a standard of care that turned out to be disastrously wrong.

I sometimes listen to Dr. Kildare not so much for the stories themselves, but because of what a time capsule the show represents when it comes to how medicine is practiced. Most of the radio episodes I listen to tend to be from the early 1950s. One episode remains stuck in my mind, an episode that originally aired February 1, 1950 entitled “Angela and Steven Kester“. The episode begins with Dr. Kildare showing up in his office on a typical morning to cover a long shift on duty. He’s greeted with a phone call from an old friend named Angela Kester. Kester used to be a famous concert pianist, but in this phone call she frantically begs Dr. Kildare to come right away to her apartment because she’s convinced that her husband is planning to kill her. Dr. Kildare protests that he’s on duty and can’t easily leave the hospital, but she’s so upset that he tells her he’ll be right over. On his way out the door Dr. Kildare runs into Mrs. Kester’s husband Steven, who has come to visit him. Kester tells him that he’s very worried about his wife, who, according to him, appears to be exhibiting obsessive behaviors, playing the same piece over and over again, sometimes practicing 16 hours a day. Apparently, five years prior at a concert at Carnegie Hall, she suffered a breakdown and couldn’t perform in front of an audience after that. Kildare informs Kester that his wife had just told him that she thought Kester was trying to kill her. Kester, not surprisingly, is horrified, and the two of them rush over to the Kesters’ apartment, where they encounter Mrs. Kester feverishly playing and yelling that her hands are being controlled by the music.

Later, we learn that Mrs. Kester’s father had been a “second rate” pianist who had wanted his daughter to succeed where he failed. Recognizing Angela’s talent at a young age, he spent lots of money on lessons for her and pushed her harder than any father should push his child, taking pains to make sure that Angela was constantly reminded of just how much he had sacrificed for her. We also learn that she had undergone insulin shock therapy, a treatment in which large doses of insulin were administered to induce a hypoglycemic coma, a treatment that fell out of favor a few years after this particular episode aired because not only did it not work but it was very dangerous given that hypoglycemia can easily kill. We then learn that Angela Kester had undergone many cycles of electroconvulsive therapy, with little or no improvement. Much discussion occurs about how Angela couldn’t tolerate another course of ECT or insulin shock therapy.

Around this point, Angela tries to commit suicide by shooting herself in the chest, but fortunately for her all she did was to give herself a pneumothorax. Dr. Kildare operates and easily saves her life. Angela’s suicide attempt, however, leads Dr. Gillespie and Dr. Kildare each independently to delve into the medical literature looking for answers (one of the better aspects of this particular episode, as disturbing as the solution they both ultimately found was). The solution they come up with? They both decide that a prefrontal lobotomy is Angela’s only chance to be “cured” of her condition.

So, even though Dr. Kildare was a fictional surgeon, in this episode we see him diagnosing Angela with paranoid schizophrenia (which in all fairness was probably an accurate diagnosis), obsessive-compulsive disorder, and neuroses. In any case, not surprisingly, given the framing of the choice in such terms, the decision is made to go ahead with the operation, even though Dr. Kildare is not a neurosurgeon and appears not even to have performed this particular operation before. None of this stops Steven Kester from agreeing to the operation on behalf of his wife, and the operation proceeds. Dr. Kildare whips out the leucotome (a special instrument designed to use in performing prefrontal lobotomies) and does the operation, drilling a hole in Mrs. Kester’s skull and using the leucotome to cut the connections between the prefrontal cortex and the underlying structures. Naturally, Dr. Kildare’s surgical skill is copiously praised when he finishes the operation. After a few days of suspense, during which everyone wondered whether the lobotomy had been successful, Mr. Kester demands to see his wife, who is initially afraid of him, but then, after she recognizes him, declares that her “hands are free,” meaning that she didn’t feel the compulsion to play anymore. She is declared “cured.”

From the perspective of 2014, this episode is disturbing in any number of ways. First, there is the demonization of mental illness that shows through even a seemingly sympathetic script. Words like “lunatic” and “lunacy” were thrown about not by lay people but by Drs. Gillespie and Kildare themselves to describe Mrs. Kester’s mental illness. In some ways, the desperation is understandable. 64 years ago, there was little that could be done in such cases, and it is not entirely surprising that a sense of desperation led to the conclusion that desperate conditions call for desperate measures, such as insulin shock therapy (a dangerous therapy that didn’t work), ECT (which could work and is still occasionally used in the case of severe depression refractory to medication but was hugely overused then), and, of course, prefrontal lobotomy.

Interestingly, this particular episode of Dr. Kildare aired right at the height of the lobotomy craze (and, quite honestly, that’s what it is best described as, as is evident from Mo Costandi‘s description of the rise and fall of the lobotomy). It’s therefore no coincidence that this episode aired in 1950. No doubt the writers were doing what writers of medical series frequently do now: Feature a new medical or surgical treatment as the focus of drama.

Discovering this episode a few months ago simultaneously fascinated and appalled me. Like most TV and radio shows, Dr. Kildare is a time capsule both of the popular perception of how medicine was practiced during its time and of how medicine actually was practiced at the time. We had the young gun surgeon, highly skilled and compassionate, willing to take risks and push the boundaries paired with the old curmudgeon of a doctor who serves as his mentor and, despite his crankiness, is often revealed to have a heart of mushy gold. The show featured portrayals of medicine as practiced then, and, much like medical TV shows today, had medical advisors to guide the writers. In 1950, the prefrontal lobotomy, although admittedly controversial even then, was an accepted standard of care that we now view with horror. But how many others are there?

Is today’s standard of care tomorrow’s horror?

All of this brings us back to the central question of this post, which was mirrored when The Knick first premiered over six weeks ago, by Dr. Sanjay Gupta at MedPage Today, who asked the question Is Today’s Standard Care Tomorrow’s Horror? To supply fodder for the article, six physicians were polled by e-mail with this question. The answers were rather interesting, although some of them were more about politics than actual science-based medicine. For instance, Cherie Binns, RN, answered the question this way:

Talk of limiting care for geriatric patients or the multiply handicapped child (especially at birth) and limiting access to resources for those with chronic health conditions that utilize a majority of services and healthcare dollars available are certainly, if they become standards of care, something that will be mocked, misunderstood, maligned in another generation.

She also laments how the Affordable Care Act allegedly prevents patients from seeing skilled health care providers. Whether that’s true or not, it’s not really an answer to the question, at least not as far as I’m concerned. Even though few people would be unsympathetic to this point of view, her response is really is more a matter of value judgments and resource allocation than it is a matter of the scientific standard of care.

Disappointingly, a lot of the responses were like that. Only one respondent, Dr. Murali Doraiswamy, was bluntly honest:

Ninety-nine percent of treatments today will be viewed as harmful or unethical in the future; for example, most psychiatric treatments given to children or most back surgeries.

Personally, I think Dr. Doraiswamy vastly overestimates what percentage of treatments will be considered harmful or unethical in the future, given the high percentage of treatments currently used that are evidence-based. For instance, there are many surgical conditions that can’t be fixed unless the anatomy is fixed. The operations aren’t going to go away; they’ll simply evolve to become less invasive, as they are doing now with the introduction of laparoscopic and robotic surgery and as the treatment of breast cancer has evolved from radical mastectomy to much less invasive procedures. Conditions like hypertension are still likely to require medication, as lifestyle changes, although they alleviate a lot of hypertension, won’t be enough for many people.

A more common example that came up was the use of “shotgun-style” or “one-size-fits-all” treatments, or, as one doctor put it, a “carpet bomb” approach to medicine. Of course, one doctor, Dr. John P. Higgins, has the opposite problem to go along with demonizing the past, namely a Pollyanna view of the future, in which he proclaims that “targeted and individualized therapy for a patient’s unique physiology will be used, with precision efficacy and near zero side effects.” There is little doubt that we will be able to target our treatments more and more effectively, but “near zero side effects”? Whatever Dr. Higgins is smoking, I’d want some if I could stand to inhale.

Let’s take an example that our good Dr. McCoy aimed his contempt at. It’s a treatment that’s commonly demonized not just by those who are—shall we say?—not completely down with the whole science-based medicine thing but even some physicians, chemotherapy. If you do a quick Google search, it doesn’t take long to find posts decrying chemotherapy for cancer as setting the standard for barbarism in the field and even as “criminal.” Of course, there’s no doubt that chemotherapy is toxic and can be brutal (although it’s getting less so, thanks to better supportive care and more targeted therapies). However, as I’ve pointed out before, death from cancer can be far more toxic and brutal. When an ugly death is the consequence, chemotherapy’s risk-benefit ratio becomes more acceptable. Moreover, contrary to the claims of those who like to label chemotherapy as ineffective, chemotherapy, used appropriately, works. It’s also important to remember that most people who call modern treatments “barbaric” have an agenda that is not necessarily science-based.

Of course, there’s no doubt that chemotherapy has way more toxicity than we’d like, but to proclaim this issue a “crisis” is exaggerating. It’s more like a longstanding problem that will require research to overcome. Crisis or not, efforts are in full swing to find more targeted and less toxic therapies. It’s also true that individualized therapy, now more commonly referred to as “precision medicine”, will come to the fore. However, the process will not be as easy or fast as the hype promises. For every success, we will see failures. Moreover, we still don’t know what, exactly, “individualized” treatment will mean, even as quacks try to define it for themselves. Advancement in science-based medicine always occurs by fits and starts.

A rebuke to Dr. McCoy

As much as I love Dr. McCoy as a character, in that famous Star Trek IV hospital scene, he is dead wrong in his sneering contempt for medicine 300 years before his fictional time, just as I would be wrong to express the same sort of contempt for physicians from 1714 for believing diseases were a result of imbalances in the four humors, surgeons in 1900 who practiced without the benefit of antibiotics, or physicians in 1950 who were believing the case reports about frontal lobotomy. Physicians all practice according to the standard of the time, and that standard is based on the science as understood at the time. It is ridiculous to criticize physicians for not knowing something that hasn’t been discovered yet. In 2014 I hold in the palm of my hand a computer (my iPhone 5s) that is hundreds of times faster, drives nearly 2.5x more pixels, and holds thousands of times more data than my clunky Mac LCII. Should I heap scorn on the computer engineers of a mere 22 ago because computers then were so much less powerful than what we have now? Those engineers did the best they could with the technology they had.

I would also point out that science advances incrementally, building on what is known before, although there have been moments of rapid advance. It turns out that 1900 was a time of such advances in the field of surgery and medicine. Indeed, Dr. Thackery gives a remarkable eulogy in the very first episode for his friend who committed suicide, the very same Dr. J.M. Christiansen, who calmly walked into his office after his attempt at a C-section failed and the patient died, placed a sheet over the couch in his office, picked up a gun, laid himself on the couch, and shot himself in the head. This eulogy is particularly remarkable for its view of medical progress:

In particular, Thackery notes:

We now live in a time of endless possibility. More has been learned about the treatment of the human body in the last five years than was learned in the previous 500.

Many have said the similar things during the last few years, given the revolution in genomic medicine in which we currently find ourselves, and it’s true. We do live in a time of endless possibility, with amazing technology and science almost unimaginable by even the generation that preceded us. So, yes, I’d be shocked if some, or even a lot, of what we do right now as the standard of care is overturned even in the remainder of my career. I’ve already seen it just since I first entered medical school in the 1980s. It will continue, and that’s a good thing.

We are all products of the time in which we live, and we all have a tendency to view history through the lens of what is known now. To have a true understanding of the history of science, however, it’s important to try to put yourself in the shoes of physicians and scientists of long ago and take into account what they knew then and what tools they possessed. For example, the Halsted radical mastectomy is often decried as a “brutal” and “barbaric” operation. And so it seems to a surgeon of 2014. But remember: In the 1880s, when Halsted first conceived the operation, there was no chemotherapy, no radiation therapy, no adjuvant therapy of any kind. Breast cancers tended to present at an advanced stage. If a woman with breast cancer was to be saved, surgery alone was what would have to do it, without the highly effective help we surgeons now receive from our colleagues in medical and radiation oncology. In context, based on the understanding of cancer of the times, the operation made sense, and Halsted’s results were better than those of other surgeons. Similarly, today chemotherapy seems “brutal,” but it works. It’s the best that we have.

Going back to the fictional past of the Knick (and the real past), physicians in 1900 were just as clever, just as dedicated, and just as desirous of curing their patients as physicians are now. What they lacked then is the knowledge and technology that we have now that allow us to do what we do now. Medicine stagnated for hundreds of years, until the latter half of the 19th century, when it began to embrace science, and its failures tend to occur when it forgets science. Yet medicine advances nonetheless, thanks to science. It might do so in fits and starts. It might go down blind alleys. It might fall for fads based on less than rigorous science. But eventually, it advances, and we obtain the knowledge and develop the technology necessary to improve. Even in the fictional universe of Star Trek, I’d bet that the physicians of 1986 were no less clever and dedicated than Dr. McCoy. The difference is that Dr. McCoy had tricorders and other products of the science and technology of 2286. Science is what got us from the world of the Knick to where we are now, and science is what will get us to the world of Dr. McCoy.

Categories: Medicine, Skepticism

Fluoride: Still Not Poisoning Your Precious Bodily Fluids!

Science Based Medicine - Sun, 09/14/2014 - 03:00

We dentists are an evil group of sociopaths. When we’re not trying to kill you or give you chronic diseases such as multiple sclerosis with our toxic mercury saturated fillings, we are advocating for the placement of rat poison/industrial waste (i.e. fluoride) in your water supply by our governmental overlords. What is up with us?

The problem is, we’re failing miserably. Even after more than 150 years of placing silver amalgam restorations in our patients, thereby saving untold numbers of teeth, reducing pain and suffering, and improving chewing ability for millions upon millions of people, there is still no evidence worth a damn that shows any correlation or causative effects for any known disease or condition. And with fluoride, after adjusting fluoride levels in municipal water supplies throughout the U.S. and in many places world wide for over sixty years, after adding fluoride to toothpastes and mouthwashes, and giving fluoride treatments to patients in our offices, the only nefarious result we have obtained is the significant reduction of dental decay with its concomitant savings of billions of health care dollars and untold pain and suffering for our patients. Man, we can’t do anything right.

Now, with the help of the American Academy of Pediatrics (AAP), there’s a new strategy.

Our new strategy is to recommend the use of fluoride toothpaste as soon as the first tooth erupts, which is typically around six months of age. On August 25th, the AAP issued new guidelines to that effect. To summarize their position, which echoes the positions of the American Dental Association (ADA) and the American Academy of Pediatric Dentistry (AAPD), the AAP stated:

  • Fluoridated toothpaste is recommended for all children starting at tooth eruption, regardless of caries risk.
  • A smear (the size of a grain of rice) of toothpaste should be used up to age 3. After age 3, a pea-sized amount may be used. Parents should dispense toothpaste for young children and supervise and assist with brushing.
  • Fluoride varnish is recommended in the primary care setting every 3–6 months starting at tooth emergence.
  • Over-the counter fluoride rinse is not recommended for children younger than 6 years due to risk of swallowing higher-than-recommended levels of fluoride.

Dentists, myself included, are pleased that the AAP issued these guidelines, both because of the content but also because getting this information out to pediatricians and other physicians, nurses, and allied health professionals is instrumental in the education of new parents and the dental health of the child. The opportunity for interaction between parent and doctor during the first six months of the child’s life is going to be much greater at the physician’s office during well (and sick) baby visits than at the dentist’s. Moreover, we dentists are rejoicing at the increased role that Primary Care Providers (PCP) are playing in the dental health education of children, an area long neglected in the past. They, not we dentists, are almost always the earliest contact point between child and dental health, both in the clinic and in public health programs. In fact, last January, two extremely intelligent and handsome Science Based Medicine authors wrote a blog post about this very subject. However, if you look back at that article, it described the old guidelines for fluoride use, which stated that a fluoride containing toothpaste should be used as soon as the first tooth erupts in high-decay-risk children, and at two years old otherwise. Now, as stated above, it is recommended that fluoride-containing toothpaste be used at tooth emergence on all children. When followed properly, the benefit to the child can be significant while lowering risks (namely dental fluorosis) to nearly zero. And to reiterate the recommendations, if you’re brushing your precious lil’ nipper’s first tooth, do not use a full fledged nurdle, but instead place a tiny smear no larger than a grain of rice on the toothbrush to minimize swallowing any excess toothpaste.

When the AAP made its recommendations a couple of weeks ago, I prepared myself for the outrage and pushback from the likes of Mercola and other associated Woomeisters. But to my surprise, there was almost no backlash, no indignation, no accusations of sapping and impurifying our precious bodily fluids by dentists and school and public health outreach programs. Oh sure, there were a few cries in the wilderness, such as the one from a Susan Posel at OccupyCorporatism.com, who goes on a random and somewhat irrational screed about fluoride being a neurotoxin, and sometimes “…fluoride, among other neurotoxins are causational to the onset of neurodevelopmental disabilities (NDDs).

The researchers identify a few NDDs [sic] as:

  • Autism
  • Attention-deficit hyperactivity disorder (ADHD)
  • Dyslexia”

Fortunately and to my delight, Aimee Ogden at Mommyish.com wrote a witty piece in support of the AAP’s position, complete with a game of Anti-Fluoride Bingo to play with the comments to her post. I will unashamedly and with gratitude steal her bingo card for use here so you readers can play along at home.

So there you have it. Although there are no epidemiological studies that demonstrate a causative link between professionally applied fluoride or fluoride-containing products and any of the above disorders (or any other disorders for that matter), this is the tack the anti-fluoridationists take. Perhaps they cite a study from industrial pollution, or from areas of the world that have many times the recommended concentration of fluoride naturally occurring in their water supply. But in the case of optimal fluoridation of municipal water supplies, the literature is clear: tooth decay is significantly reduced (30-60%, depending on demographic factors), period, with almost no adverse side effects other than cosmetic blemishes on teeth. That’s it. No lowered IQs, no neurotoxicity, no calcification of the pineal gland which, as we all know, is the seat of the soul. Consequently, before you feel the need to run out and detoxify yourself, either by eating turmeric, a spice alleged in the Pharmacognosy Magazine to mitigate the effects of fluoride toxicity, or any of the other detox remedies on the market.

So rest easy gentle readers. No matter how hard we try, we dentists aren’t very good at poisoning you people. In fact all those things we recommend to you actually are beneficial to your dental and overall health and have a long track record of success as well as reams of solid scientific evidence to back up their safety and efficacy. And kudos to the AAP for updating their fluoride recommendations to better protect our young children from dental decay, the number one malady affecting children.

 

 

Categories: Medicine, Skepticism

Features of Denialism

Neurologica Blog - Fri, 09/12/2014 - 08:35

Denialism is a thing. What I mean is that denialism is a definable intellectual strategy, with consistent features that tend to cluster together. I first wrote about denialism 12 years ago, before global warming denial made the term more widespread. I pointed out that certain beliefs tend to follow the same fallacious arguments – HIV denial, creationism (evolution denial), holocaust denial, and mental illness denial. I would add now global warming denial and germ theory/vaccine science denial.

I characterized denialism as a subset of pseudoscience, one that tries to cloak itself in the language of skepticism while eschewing the actual process of scientific skepticism. But further, denialism exists on a spectrum with skepticism, without a clear demarcation in between (similar to science and pseudoscience). People also tend to use themselves for calibration – anyone more skeptical than you is a denier, and anyone less skeptical than you is a true believer.

Geneticist Sean B. Carroll (not to be confused with the physicist Sean M. Carroll) in his 2007 book, The Making of the Fittest: DNA and the Ultimate Forensic Record of Evolution, lists what he identified as the six core features of denialism. I think they make an excellent list, and would like to expand on them:

1) Cast doubt on the science.
2) Question the scientists’ motives and integrity.
3) Magnify any disagreements among the scientists; cite gadflies as authorities.
4) Exaggerate the potential for harm from the science.
5) Appeal to the importance of personal freedom.
6) Object that acceptance of the science would repudiate some key philosophy.

As you will see, all of these strategies are insidious because they are extreme versions of reasonable positions. Their underlying principles are sound, it is their specific application that is the problem.

Doubt, for example, is key to skepticism and science. The absence of doubt is gullibility. This feature, most of all, is what makes denialism pseudo-skepticism. The problem with the denialist approach is that doubt is not used as a tool of honest questioning, but rather of undermining a belief one does not like. As with pseudoscience in general, they start with the conclusion then work backwards.

This strategy can also be called, “just asking questions” or “JAQing off.” You can often tell the difference because, when a true scientists ask a question they want an answer, and will give due consideration to any possibilities. Deniers, however, will ask the same undermining questions over and over, long after they have been definitively answered. The questions, used to cast doubt, are all they are interested in, not the process of discovery they are meant to inspire.

Questioning motives is extremely common among the opponents of science, in my experience. Just read the comments to any article on GMO and count how long it takes for anyone defending the science of GMO to be labeled a Monsanto Shill. Any critic of pseudoscience in medicine is automatically a Pharma shill. Climate scientists are just trying to use hysteria to get grants, and evolutionary biologists are secretly promoting atheism (even, apparently, when they are not atheists).

At the reasonable end of the spectrum is the sensible requirement for the full disclosure of potential conflicts of interest, so readers can judge for themselves the integrity of the source. This can easily slide into a witch hunt, however, with even the thinnest and post tenuous connection used to argue that a scientist is actually a paid shill and should be completely discounted.

Magnifying disagreements among scientists is easy to do, because such disagreements are always present. This can take two basic forms: The first is to magnify the implication of the disagreement – in other words, present a disagreement over small details as if they call into question much more fundamental aspects of the science. This feature was on my list as well, “Confusing internal debate over details with negation of the whole.” Creationists, for example, will use debate over the exact sequence of evolutionary branchings to argue that no evolution occurred at all.

The second aspect of this strategy, as Carroll implies with his reference to gadflies, is to present a small minority dissent as if it is a mainstream controversy. You can almost always find some scientists somewhere to disagree with even the most solid scientific consensus. I have argued that this is a good thing. Complacency can lead to stagnation in science, and it’s always good to have someone shaking the tree. But we have to put such dissent into context. Sometimes it’s a genuine controversy, and the science can go either way. Other times the science is solid and the dissent is insignificant.

Exaggerating the potential for harm also suffers from the demarcation problem. A reasonable application of the precautionary principle means that we anticipate potential harm and err on the side of avoiding it. Denialists, however, can take rare or insignificant risks and magnify them, even arguing that the slightest potential for harm is unacceptable. Vaccine deniers, for example, demand zero risk from vaccines. HIV deniers exaggerate the side effects of anti-HIV drugs, while minimizing their efficacy.

Personal freedom is highly valued in US culture (and elsewhere), so the appeal to personal freedom is especially effective. This is why appealing to freedom is so common. Laws meant to shield charlatans from the standard of care in medicine are sold as “healthcare freedom” laws. Creationists attempts to undermine the teaching of evolution are framed as “academic freedom.” Anti-vaccinationists, of course, are constantly advocating for the parents right to choose.

Finally, I agree that noting that accepting a particular science would be inconvenient for a particular political or religious ideology is also extremely common. Creationists argue that accepting evolution will undermine belief in God, and even result in moral decay. Global warming deniers argue that accepting the “alarmist” claims about climate change will result in a government take over of private industry. I characterized this strategy as an argument from final consequences logical fallacy – evolution is wrong because if it were true society would suffer moral decay.

This feature also often provides a clue as to the true motivation of the denial. The science is secondary – it is the moral hazard they are truly concerned about.

I have also pointed out that this is an inherently flawed strategy. If you truly wish to advocate for a particular moral or ethical position, the worst thing you can to is tie that position to a false scientific position. Doing so allows opponents to attack your moral position by attacking the pseudoscience to which you have anchored it. You are far better off acknowledging legitimate science, and advocating for your moral position on moral grounds.

If you ideologically favor free markets, then don’t deny global warming, rather offer free-market solutions.

In my 2012 discussion of denialism I also pointed out several other common features, although they are related to the list above. For example, in order to manufacture doubt about a particular science or scientific conclusion, deniers use several specific strategies. They often use semantic arguments in place of substantive arguments, sometimes playing on the difference between colloquial and technical definitions of terms. Mental illness deniers, for example, try to define mental illness out of existence by defining “illness” in a narrow way that is meant to exclude anything cognitive or behavioral.

Evolution deniers do the same thing, defining science in a deliberate narrow way in order to exclude all historical sciences, including evolution.

Deniers also use some generic strategies of pseudoscience, such as making selective use of evidence or cherry picking. Global warming deniers, for example, point to the pause in warming of global surface temperatures, while ignoring ocean temperatures. Or they point to the recent increase in arctic ice, while ignoring the longer term decreasing trend, or the increase in antarctic sea ice, ignoring the decrease in antarctic land ice, or the global decrease in all ice.

Deniers further like to move the goalpost. No matter how much evidence you can produce to support the science they dislike, it isn’t enough. Fill in one gap, and they will point to the smaller gaps. At times they move the goalposts forever out of reach – “show me one study that proves, by itself, that HIV and only HIV causes AIDS .” That sort of conclusion requires dozens of studies. This is similar to the challenge to “show me one fossil that proves evolution.”

Vaccine deniers ask for evidence of vaccine safety, but no amount of evidence is enough. Thimerosal is mostly removed from vaccines, and they just move onto the the next “toxin.” They demand the one kind of study that will never happen, a randomized vaccinated vs unvaccinated study (because you ethically cannot randomize children to not receive standard medical care). This is identical to the strategy of denial used by the tobacco industry, demanding a randomized controlled study of smoking vs non-smoking.

Related to this is the abuse of the caution not to assume causation from correlation. It is true that correlation is not necessarily causation, but it might be. Multiple independent correlations can be used to arrive at a high probability of a specific causation, such as smoking causing lung cancer.

Finally, deniers of fond of claiming that there is emerging skepticism towards the science they are denying. Creationists argue that evolution is a “theory in crisis” that is on the verge of being rejected by the mainstream. Global warming is a hoax that is being exposed. The public is starting to wise up about vaccines and will soon reject them. Just you wait – we will be vindicated in the near future.

Conclusion

Denialism is essentially a form of pseudoscience. It begins with the conclusion and then works backward to fill in arguments that support the desired conclusion, which in the case of denialism is opposition to a scientific conclusion (rather than support for an unscientific one).

Denialism is common because this appears to be the default mode of human psychology. People tend to cling to their beliefs (even when those beliefs are arbitrary, or have been assigned to them), and then will jealously defend those beliefs. The more intelligent and even informed someone is, the better they are able to marshal arguments in support of their belief and rationalize away inconvenient data. This behavior seems to be directly proportional to the emotional investment in the belief.

The only solution I can see is to make a conscious effort to become emotionally uninvested in any particular belief. This is easier said than done, but it is a worthy goal. Instead we should be invested in using a valid process, and then accepted whatever conclusion that process leads to. This is a high energy path to follow as it seems to go upstream against our inherent human nature. It is a path worth taking, however.

 

Categories: Medicine

Legislating Ignorance

Science Based Medicine - Fri, 09/12/2014 - 03:00

Science is under attack, and not just from anti-vaccine celebrities and parents with degrees from Google University. Scientific illiteracy is being woven into the very fabric of our society through legislative assault. If you dismiss this as alarmist hyperbole, you haven’t been paying close enough attention.

Every day thousands of pediatric health care providers throughout the country provide safety advice to patients and their parents during routine health maintenance visits. As part of this important routine we ask a series of standard questions to assess the safety of our patients’ environment. Some of these questions are easy and straightforward, and some are more personal and potentially awkward for patients and their parents, including questions pertaining to sexual practices and preferences and psychosocial history. An important series of questions focuses on potential hazards in the home, such as how toxins and medicines are stored, how pools are secured against curious toddlers, and whether there are guns in the home and how they are stored and secured. Parents are usually appreciative of the advice we provide, and thankful for our concern and attention to these issues. Occasionally patients or parents are taken aback by some of these questions, and very rarely they prefer not to answer them (in my 20 years in practice, I can recall only one time this has occurred). We ask these questions because accidental injuries and deaths are common occurrences in the pediatric population, and there is good evidence that patients tend to follow the advice we provide our patients.

Subverting science and endangering health

In 2010, as part of a routine health maintenance visit, a pediatrician in Ocala, Florida asked the mother of one of his patients whether there were guns in the home. The mother was angered by this question and refused to answer. By the end of the visit, she had been asked to find another pediatrician. This argument eventually led to the creation of the Florida Privacy of Firearm Owners Act, which, with support from the NRA, was signed into law in June of 2011. This law made it illegal for healthcare providers to ask about the presence of guns in the home. In 2012 the law was blocked by an injunction as a result of a lawsuit filed by the Florida chapters of the American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), the American College of Physicians (ACP), and individual plaintiff physicians. In July the law was upheld on appeal, though the injunction remains in effect until the 11th U.S. Circuit Court of Appeals makes a final ruling. The judge who upheld the law weighed in stating:

the practice of good medicine does not require interrogation about irrelevant, private matters.

Despite this law, if I were practicing in Florida, I would not change the way I inquire about guns in the home. The law specifically states that a health care practitioner:

may not intentionally enter any disclosed information concerning firearm ownership into the patient’s medical record if the practitioner knows that such information is not relevant to the patient’s medical care or safety, or the safety of others.

It goes on to state that:

a health care practitioner or health care facility that in good faith believes that this information is relevant to the patient’s medical care or safety, or the safety of others, may make such a verbal or written inquiry.

While this leaves it wide open as to what constitutes information relevant to a patient’s safety, most pediatricians, and all rational people, would have no problem assuming knowledge about the presence and safe storage of firearms in the home to be always relevant. The NRA and certain members of Congress would disagree, and that is where the chilling effect of this law comes into play. The intent of the law is clearly to prevent health care providers from pursuing this line of questioning, and places the second amendment squarely above the first.

My patients’ medical records can and do contain information about a wide range of environmental, health, and social information. Information that I have obtained because I, as a trained clinician, think it may be important to the health and safety of my patients. This includes information about a wide range of issues from what kinds of pets are in the home and whether carbon monoxide detectors are installed, to family medical histories, patient’s sexual activities, and often-complex social and family dynamics. But for some segments of society, those who cling to the second amendment with end-times religious zealotry, questions about guns in the home cross the line. This line of inquiry is just too personal and threatening for them to bear. And now, thanks to this Orwellian legislation, health care providers in Florida can’t do their job of advising and protecting their patients without fear of prosecution. Somehow, by asking a routine question about home safety, pediatricians are violating the second amendment rights of their patients. As if simply by asking about the presence of guns in the home denies a parent the right to own a gun. This has to be one of the most preposterous pieces of legislation passed in modern times, and it speaks to just how dangerously gun-centric our country has become.

Anti-science legislation prohibits research into gun safety

So just how is this an example of anti-science legislation? The tragic irony is that another piece of anti-science legislation, specifically developed to block research on gun safety, prevents us from gathering and analyzing the data to adequately answer this question. In the 1990s, NRA-backed lawmakers inserted into The Consolidated Appropriations Act, (P.L. 112-74, Section 503, Division F, Title V) language prohibiting the CDC from using funds to promote:

any activity to advocate or promote … any proposed, pending, or future requirement or restriction on any legal consumer product, including its sale or marketing, including but not limited to the advocacy or promotion of gun control.

Additional Requirement 13 adds the following language,

None of the funds made available for injury prevention and control at the Centers for Disease Control and Prevention may be used to advocate or promote gun control.

In 2011, Congress extended this restriction to include not just the CDC, but also the National Institutes of Health and the Department of Health and Human Services.

While at first glance this language may not seem to explicitly prohibit these agencies from funding studies on gun related injuries, deaths, and gun safety, the fact that such research could be used to lobby Congress has blocked them from doing so. No such restrictions apply to the study of obesity, heart disease, or overall accident and injury prevention even though these areas of research could also be used to lobby for changes to policy. Yet because of the political reach of the gun lobby, an entire line of scientific inquiry has been effectively halted, with far-reaching and profound consequences for public health and safety. It is the main reason we do not have answers to some very important and basic gun safety questions such as:

  • What is the overall number of accidental gun deaths?
  • How many children are behind the trigger in gun-related injuries and fatalities?
  • How many children are the victims of accidental shootings?

Despite these limitations, the data we do have regarding children and guns clearly indicates that the presence of guns in the home increases the risk of accidental injury and death, homicides, and suicides. The American Academy of Pediatrics and American Medical Association recommend that firearms in the home be kept locked and unloaded, and stored separately from ammunition. A study demonstrating that a large percentage of unintentional firearm deaths occur in states where guns tend to be stored loaded supports these recommendations. The greatest risk occurs in states where loaded guns are also more likely to be kept unlocked. This association held true after controlling for rates of firearm prevalence, poverty and urbanization. In another study looking at the impact of safe gun storage, four safety practices (keeping a gun locked, unloaded, storing ammunition locked, and storing guns and ammunition in separate locations) were found to independently protect children from unintentional and self-inflicted injury and death.

Despite this, 2.6 million children in the US are exposed in their homes to firearms stored either unlocked and loaded, or unlocked, unloaded, and stored with ammunition. According to the CDC, there were 269,871 gun-related fatalities in the 8 years between 1999 and 2007. This included nearly 20,000 child fatalities. Because of the limitations on data collection and analysis, we do not know how many of these were a result of children getting their hands on dangerously stored and accessible guns.

Now, back to the Florida physician’s gag law. We know we can’t answer precisely how anti-science this legislation is because of the anti-science restrictions placed on gathering the data to begin with. We certainly have good evidence about the positive impact of physicians asking general questions about safety and providing guidance on accident and injury prevention. Several studies (Bass, et. al., Miller, et. al.) have demonstrated that providing office-based, standardized injury prevention advice can significantly decrease the incidence of childhood injuries. Other studies have shown that parents prefer and are most likely to follow safety information provided by their pediatrician (Stylianos, et. al., Laraque, et. al.).

But even with the current restrictions imposed on the study of gun safety, we do have some compelling evidence for the positive impact of provider-instituted gun safety counseling as well. A variety of simple, office-based intervention strategies have been shown to have a positive impact on the safe storage of guns in the home (Albright, et. al., McGee, et. al.), and the use of trigger locks (Grossman, et. al.). It has also been shown that parents are likely to follow their pediatrician’s advice about safe gun storage (Webster DW, et. al.).

So from what we do know about the positive impact of gun safety counseling, it appears safe to conclude that the Florida “physician’s gag law” is solidly anti-science. And because anti-science seems to be spreading like a vaccine-preventable plague, similar legislation has now been introduced in 12 other states. Most have been overturned, but laws are still pending in Oklahoma, Wisconsin, Ohio, and Minnesota. And now, thanks to the NRA’s influence on Harry Reid, even the Affordable Care Act contains stealth language further restricting health care providers, insurance companies, and the Department of Health and Human Services from collecting information about gun use or the presence of guns in the home (See page 19 here).

The intrusion and detrimental effects of politics on the advancement of science and public health is not new, though it has become more and more flagrant and potentially dangerous. Lawmakers with political agendas, constituents to please, and a poor grasp of science have been able to enact legislation and influence policies with the potential to produce extremely dangerous and long-lasting consequences. From climate change deniers such as Senator James Inhofe of Oklahoma, and anti-vaccine fear-mongers like former Congressman Dan Burton and now Darrell Issa, to presidential candidates mocking important scientific research, anti-science politicians have been weighing in and eroding science policy in this country with alarming frequency. The frequency with which antievolution legislation is introduced in this country should make us all shudder with fear. Perhaps the most flagrant and troubling anti-science legislative effort at the moment is that of Representative Lamar Smith of Texas (ironically, chair of the House of Representatives Science Committee), who is pushing a bill that would replace the peer-review system at the National Science Foundation (NSF) with a system based on a set of Congressional funding criteria. This “High Quality Research Act” is intended to eliminate what a select group of politicians deem to be areas of inquiry undeserving of federal support. Such politically and ideologically motivated restrictions on scientific inquiry are truly horrifying, and could have devastating consequences.

The unhindered progress of science is central to the advancement of public health and societal good, yet political forces and personal belief continue to impede and influence the path to progress. Perhaps what we need is a Committee on Scientific Integrity to vet legislation that could impact public health and safety. Whatever steps we take, clearing a path for science and giving it the place it deserves in our society is long overdue.

Categories: Medicine, Skepticism

19 Years of Feeding Animals GMO Shows No Harm

Neurologica Blog - Thu, 09/11/2014 - 08:38

Often GMO critics will argue that the biotech industry is conducting a massive experiment with our food supply by introducing genetically modified organisms. The implication is that GMOs are not adequately studied, which is at best debatable, but in a way they are correct. We can look at what has happened in the 19 years of GMO use starting in 1996 to see if there have been any adverse effects.  A newly published study, Prevalence and impacts of genetically engineered feedstuffs on livestock populations, does just that. (Full study, may be behind a paywall.)

The study authors, Van Eenennaam and Young, first review the existing literature on animal feeding studies. They then review available data on livestock outcomes to see what effect feeding them mostly GMO since 1996 has had, if any.

GMO Feeding Studies

The first regulatory hurdle for safety testing of GMOs is to establish “substantial equivalence.” Researchers must show that the genetically engineered crop is essentially the same as the parent variety in all ways except for the desired introduced genetic change. The authors report:

Over the past 20 yr, the U.S. FDA found all of the 148 GE transformation events that they evaluated to be substantially equivalent to their conventional counterparts, as have Japanese regulators for 189 submissions.

The authors point out that the same testing is not required for conventional breeding or even mutation farming. It also cannot be assumed that such techniques are without risk.

There have been instances where plants bred using classical techniques have been unsuitable for human consumption. For example, the poison α-solanine, a glycoalkaloid, was unintentionally increased to unacceptable levels in certain varieties of potato through plant breeding resulting in certain cultivars being withdrawn from the U.S. and Swedish markets due to frequently exceeding the upper safe limit for total glycoalkaloid content.

They further point out that proteins, DNA, and RNA from the food we eat are digested. Whole proteins or genes from GMO have never been detected in the tissue of animals fed GMO feed. There is also no reason to suspect that transgenic genes or proteins present any more of a health risk than the countless other proteins and genes we consume. It is therefore implausible that eating an animal fed GMO poses any health risk to humans. But what about the animals themselves?

Animal feeding studies are a mainstay of testing the safety of GMO plant varieties. The authors summarize this research:

Several recent comprehensive reviews from various authors summarize the results of food-producing animal feeding studies with the current generation of GE crops (Deb et al., 2013; Flachowsky, 2013; Flachowsky et al., 2012; Tufarelli and Laudadio, 2013; Van Eenennaam, 2013). Studies have been conducted with a variety of food-producing animals including sheep, goats, pigs, chickens, quail, cattle, water buffalo, rabbits and fish fed different GE crop varieties. The results have consistently revealed that the performance and health of GE-fed animals were comparable with those fed near isogenic non-GE lines and commercial varieties.

Some of these studies were long term, conducted up to two years, and with multiple generations of animals, 2-5 generations. A recent review of these studies by Snell et. al found:

Results from all the 24 studies do not suggest any health hazards and, in general, there were no statistically significant differences within parameters observed.

Some differences were found, but they were not biologically significant and likely represent background variation. Snell et al point out that 90 day feeding trials show the same results as long term and multigenerational trials, therefore the results of the standard 90 trials are highly reliable. In other words, doing longer term trials has so far not revealed any health risks that were missed during the shorter trials.

There are only a few outliers in the feeding trials showing possible harm, such as the now infamous Seralini study. All of these studies are of dubious methodology and are not published in peer-reviewed journals (Seralini was withdrawn and then republished without peer-review).

The bottom line is that there are many short term, long term, and multigenerational feeding trials with GMO varieties and many species of test animal, many by independent scientists, all showing that current GMOs are safe and nutritionally equivalent to their non-GMO counterparts.

One Big 19-year Experiment

Van Eenennaam and Young then approach the question of GMO feeding from a different angle. Since 1996 90-95% of animal feed in the US has been GMO. Prior to 1996 0% was GMO. This offers the opportunity for a large observational study to see if the rapid and thorough introduction of GMO feed in the US resulted in any adverse health effects for the animals.

This data is observational, meaning the authors are looking at data collected out there in the world and not part of any controlled prospective experiment. Observational data is always subject to unanticipated confounding factors. However, robust observational data is still highly useful, and has the potential to detect any clear signals.

In this case the data is particularly useful for a couple of reasons. First, the number of animals for which there is data is massive – in the billions per year. Second, the industry actually carefully tracks certain outcomes, as it is necessary or critical to their business.

For example, cattle are examined both premortem and postmortem for any abnormalities, such as tumors or signs of infection or other illness. Any sign of illness and that cow is not approved for meat. The percentage of cattle that are found to have such abnormalities is called the condemnation rate, and annual condemnation rates are kept in public databases.

The authors pooled data from various such databases for various animal industries before and after the introduction of GMO into animal feed:

Livestock production statistics for the US before and after the introduction of GE feed crops in 1986 are summarized in Table 4. In all industries, there were no obvious perturbations in production parameters over time. The available health parameters, somatic cell count (SCC; an indicator of mastitis and inflammation in the udder) in the dairy data set (Figure 1), postmortem condemnation rates in cattle (Figure 1), and postmortem condemnation rates and mortality in the poultry industry (Figure 2), all decreased (i.e., improved) over time.

So, multiple health parameters for multiple animals, including billions of animals over about 15 years showed no adverse effects from the rapid introduction of GMO animal feed. If there were any significant adverse effects from GMO it seems reasonable that it would easily show up in this data.

The reason for the background improvement in health parameters is likely due to improved genetics and handling. This slow improvement over time continued without change through the introduction of GMO.

Conclusion

We now have a large set of data, both experimental and observational, showing that genetically modified feed is safe and nutritionally equivalent to non-GMO feed. There does not appear to be any health risk to the animals, and it is even less likely that there could be any health effect on humans who eat those animals.

In order to maintain the position that GMOs are not adequately tested, or that they are harmful or risky, you have to either highly selectively cherry pick a few outliers of low scientific quality, or you have to simply deny the science.

Here is a comprehensive list of animal feeding studies. Many of these studies are independent. The list included systematic reviews, all of which conclude that GMO feed is safe.

There is as strong a scientific consensus that GMOs do not present any novel health risk, that those in current use are safe, and that they pose no health risk to animals or humans, as there is a consensus for the safety and efficacy of vaccines or that humans are contributing significantly to global warming.

Categories: Medicine

Side effects may include liver failure

Science Based Medicine - Thu, 09/11/2014 - 07:00

“Safe and natural.” It’s a marketing phrase attached to dietary supplements that’s often accepted as self-evident. The marketing works. Supplements have a strong health halo. But evidence suggests that this reputation may be undeserved. Not only are there continued questions about whether most supplements have any health benefits whatsoever, there is also evidence that they can be harmful. We can’t even be confident that what’s on the label is actually in the bottle. Just two days ago I was notified of another long list of supplements and remedies that the FDA had identified that were contaminated with prescription drugs. These warnings about products sold as supplements appear regularly. Some time ago I asked, “What’s in your supplement?“, and noted that contamination and poor product quality standards continue to raise questions about whether supplements can be used safely at all, because the harms, when they occur, can be catastrophic. No matter how you feel about their efficacy, we can probably all agree no consumer should lose an organ from taking a health supplement. But it can happen. Like any other drug products, supplements have chemical ingredients that, once absorbed, are processed (metabolized) by the body. Our liver’s an amazing organ. Millions of years of evolution have given us the capacity to metabolize and detoxify pretty much everything we can eat. But sometimes we’ll encounter something that our liver can’t respond to. And sometimes those products cause organ damage, in the form of liver failure. It may be the labelled ingredient, or it could be something else – a contaminant that causes the harm. Unless there’s a lot of cases, it may be difficult to spot, or link harms to a specific product.

Supplements are popular – and growing in their popularity. We’re in the midst of a 40-year trend of increasing supplement use that shows no likelihood of slowing down. This is big business, a $30-billion-per-year (USD, 2011) industry with little regulatory oversight. Importantly, dietary supplements are not held and inspected to the same manufacturing and quality standards as pharmaceutical drugs – hence the persistent and worrying questions about their quality. The driver of this loose regulation is the legislation called DSHEA, which removed the onus of demonstrating safety and efficacy from the manufacturer, and put the requirement to demonstrate harm on the FDA. Yet calling a product a supplement doesn’t make it harmless. Those ingredients can harm, just like drug products. Do they deserve the same regulation? I’d argue yes – we should not have two different efficacy and safety standards, just because something is “natural” or deemed a “supplement”. The supplement industry would disagree. They may cite a lack of evidence of harms. And from one perspective, that is true. Despite their widespread use, surveillance of supplements (the limited amount that occurs) reveals generally few adverse events. It could be that many products simply don’t do anything at all – either positive or negative.

Now a new analysis from the US-based Drug-Induced Liver Injury Network gives some cautionary statistics on the harms related to dietary supplements. The study looked at data from eight referral centres, and captured data on any case of liver injury attributed to herbal and dietary supplements. Importantly, this analysis excluded cases of liver injury from acetaminophen (Tylenol). Acetaminophen poisonings, whether intentional or not, cause harms that dwarf anything else – even dietary supplements. In the USA, poisonings from this drug alone result in 56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year. [PDF] Acetaminophen is responsible for more overdoses, and overdose deaths [PDF], than any other pharmaceutical product. In this latest report, patients were followed if they had documented liver toxicity that was suspected as being either medication- or supplement-related. A standardized protocol was used to determine the relationship and assess causality. Cases were only included if the likelihood of a causal relationship was at least probable. Other causes of liver damage were ruled out. Rates of hospitalization, and outcomes like liver transplant or death were also followed. The analysis divided the cases into two groups: those with injuries attributed to bodybuilding supplements, and those from other supplements. Given the statistics, one of the best ways to avoid liver damage from supplements seems to be to avoid anything related to bodybuilding, as they are the most common cause of supplement-induced liver damage. These injuries occur predominantly in younger men and they tend (according to the authors) to cause a similar injury: prolonged jaundice and eventual recovery. Liver injury caused by other supplements is more varied, and has different outcomes, including a greater risk of liver transplant or death.

Between 2004 and 2013 the researchers found 839 cases of liver injury eligible for consideration: 709 were from drugs, and 130 from supplements. In the pool of 130 injuries linked to supplements, 45 (35%) were from bodybuilding supplements and 85 (65%) were from other supplements. The analysis found no patient that took bodybuilding supplements died or required a liver transplant. In the non-bodybuilding group, 13 patients died or required a transplant. Interestingly, the severity of the reaction to supplements was greater than the liver toxicity from conventional meds, though conventional med reactions were associated with a greater risk of death (7% vs. 4%, respectively.) Here’s the list of the products that caused death or led to a liver transplant, and the full list of all implicated supplements may be downloaded here:

What’s surprising? There’s a lot of products on the full list that should not be associated with liver problems at all, like multivitamins. It’s highly unlikely that a product like a multivitamin would cause liver damage. What’s also possible (and probably more likely) is product contamination. The authors note that the pattern of liver damage associated with bodybuilding products is consistent with what might be expected if the products were contaminated with anabolic steroids. But we don’t know for sure – to truly identify the cause, it would be necessary to assay and test every single product associated with liver damage, in order to determine the actual ingredients and the most likely cause. In this survey, 217 products were associated with the 130 cases of liver injury. Amazingly and frighteningly, only about 80% had identifiable ingredients according to the label. And given the product quality concerns that continue to plague the supplement industry, determining which products and ingredients are the real risk factors is all-but impossible, as we can’t trust the labels to be accurate.

Tip of the harms iceberg?

Liver damage and liver failure is both catastrophic and fairly easily identified. Other harms may not be immediately attributed to supplements, which may mean that harms from supplements may be under-reported. I’ve mentioned several factors before, which include:

  • The belief that supplements are harmless, accentuated by beliefs that “natural” substances don’t harm, so the link is never suspected.
  • The lack of routine health professional monitoring.
  • The reluctance to disclose harms and side effects to a health professional, in part because they may not want to disclose they’re taking a supplement at all.
  • Not knowing that adverse events should be reported, or how to report them.
  • Use may be driven through consultation with “alternative” medicine providers, and those experiencing harm may be reluctant to report experiences to “conventional” health providers like physicians or pharmacists.
  • Concern about the risk of additional regulation, leading to a reluctance to report harms.
  • Supplements may be used short intervals for self-limiting conditions, and long-term harms may not appear (or be detectable).
Reducing the risk

If you don’t look for it, you won’t find it. And if you set the system up to minimize the likelihood of finding harm, it should be no surprise that supplements are not associated with a lot of safety concerns or reports. Given the way this data was assembled, it’s not possible to estimate a relative risk of harm, or even assess the any change in incidence of liver damage associated with supplements. But it should put to rest any claims that supplements are without harm. Even more troubling, it doesn’t look like there’s any way to avoid the risk of supplement harms, unless you decide to avoid them completely. There’s no question that drugs can cause liver problems, and they do so with more frequency than supplements. But these harms are not related to widespread product contamination – a risk that is very real, and difficult to avoid, with any dietary supplements sold today. Until regulations are tightened, I don’t expect manufacturers to do much to improve the quality of their products. Which is unfortunate, because until we can consistently trust what’s on the label, it’s going to continue to be hard to accept dietary supplements as either safe or effective.

Reference

Navarro V.J., Herbert L. Bonkovsky, Timothy Davern, Robert J. Fontana, Lafaine Grant, K. Rajender Reddy, Leonard B. Seeff, Jose Serrano, Averell H. Sherker & Andrew Stolz & (2014). Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network, Hepatology, n/a-n/a. DOI: http://dx.doi.org/10.1002/hep.27317

Categories: Medicine, Skepticism
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