Board Certified Woo — Or Should I Say Meow?

Posted on October 12, 2009 by skeptvet

CAM proponents generally struggle against government regulation of their industry, though they will also often cite state licensure, when it is required, as evidence that their approaches are legitimate. However, in the absence of such a government imprimatur of legitimacy, CAM providers organize themselves into private “accrediting” organizations to lend gravitas to their business cards. As this article indicates, however, the standards are sometimes less than rigid. Apparently, even being a human being is not always required.

“Chris Jackson, presenter of Inside Out in the North East and Cumbria, registered pet [cat] George with three industry bodies. George was registered with the British Board of Neuro Linguistic Programming (BBNLP), the United Fellowship of Hypnotherapists (UFH) and the Professional Hypnotherapy Practitioner Association (PHPA).”

And lest we be tempted to assume the British system is somehow more lax than here in the U.S., Dr. Steve Eichel, a psychotherapist, managed not only to get his cat, Zoe, certified by the “National Guild of Hypnotists, the American Board of Hypnotherapy…the International Medical & Dental Hypnotherapy Association…[and] the American Association of Professional Hypnotherapists,” he even secured Diplomate status as a board certified member or the American Psychotherapy Association.

Just something to think about the next time someone rattles off an impressive string of professional credentials in support of some questionable therapeutic approach.

Posted in Humor | Leave a comment

Doctor Indicted for Selling Bogus “Cure” to Cancer Patients

Posted on October 11, 2009 by skeptvet

I’ve discussed previously why it is both understandable that desperately ill people turn to unproven or bogus therapies and why it is immoral to take advantage of this desperation and sell them such therapies. It is comforting, then, to find that even in today’s CAM-friendly climate that selling lies and false hope to sick people is still illegal, at least sometimes. This case involves a doctor  who allegedly made $1.1 million dollars over three years selling a mysterious concoction of unknown provenance  and claiming it would treat cancer, hepatitis, Alzheimer’s, Parkinson’s, and other diseases. According to the Associated Press article, the doctor also instructed at least some of her patients to discontinue conventional therapy.

It is interesting, and a little disappointing, that the prosecution is focused on wire and mail fraud charges, since the law still is unable to deal directly with medical lying. Apparently, a California Medical Board investigation is underway, but I suspect the outcome will hinge more on the results of the criminal prosecution than the scientific facts about the treatment the doctor charged provided. After all, California licenses and promotes the legitimacy of acupuncture, chiropractic, and other questionable therapies.

Still, such cases serve to illustrate the reality behind the PR rhetoric of some CAM promoters. CAM providers, on balance, are likely honest believers in the therapies they sell. But their claims to the contrary notwithstanding, their ranks contain the recklessly negligent and the outright dishonest, so the stones they cast at scientific medicine’s faults are ill-advised coming from within their own glass house. And rather than providing comfort or real help to the truly ill, unproven therapies offer only the illusion of help while often taking away the potential benefits of real medical treatment.

Posted in Herbs and Supplements, Law, Regulation, and Politics | 4 Comments

Cognitive Dissonance and Evidence-Based Medicine

Posted on October 8, 2009 by skeptvet

Cognitive dissonance is the emotional reaction to becoming aware that one holds two contradictory ideas or feelings simultaneously. It is a term from a rich area of cognitive psychology looking at how people derive and maintain beliefs. One of the best and most accessible works on the topic for the general public is Mistakes Were Made (But Not by Me) written by Carol Tavris and Elliot Aronson. The phenomenon of cognitive dissonance has relevance for the practice of  evidence-based medicine (EBM), as for most complex human endeavors, because it affects how we maintain old ideas and react to new ones.

One of the core principles of EBM is that due to a host of well-established factors both doctors and patients (or pet owners in veterinary medicine) often evaluate the effects of medical interventions inaccurately. Personal experience and observation, even by someone with extensive training and practice, is less reliable than controlled scientific study. The evidence for this is overwhelming, and a central reason for adopting the EBM approach is the acknowledgement that our common strategies for evaluating medical treatments are inferior. Unfortunately, but not surprisingly, telling people (especially doctors) this generates resistance, and sometimes hostility.

We generally view ourselves more positively than we view others. This extends not only to how we evaluate our own intelligence, attractiveness, and so on, but also how we evaluate our own objectivity, fairness, and rationality. When we are presented with evidence or argument that challenges not only the facts we accept to be true, but our own intellectual and personal qualities, cognitive dissonance comes into play. We tend to rationalize or outright reject our own mistakes, misperceptions, and errors partly because accepting them involves not only changing our beliefs about something else which is hard enough, but re-evaluating our beliefs about ourselves. (An excellent review of this topic is Emily Pronin’s paper How we see ourselves and how we see others. Science 320;1177-1180; 2008.)

Veterinarians (and MDs) are generally smart, conscientious people who genuinely want to provide the best possible care for their patients. And most of them likely see themselves this way. Most accept the general principles of EBM because they makes sense and are consistent with how they already see their work. Most doctors think they already practice EBM, despite data that show that not as much of conventional medical practice is founded on high-quality evidence as is generally believed (though certainly far more than CAM practices). Suggesting that they may be routinely mistaken about their diagnoses or therapies challenges this self-assessment, and this adds to the resistance to the conclusion. Research in human medicine shows much greater inconsistency and error rates among doctors then they themselves believe. There is no reason to suspect we veterinarians do any better in this respect.

One of the challenges, then, in promoting science-based medicine is to present the advantages of it in ways that minimize the dissonance and resistance that inevitably arise when the inadequacies of current practices are pointed out. When I criticize CAM or other approaches or attitudes within the profession, I am routinely accused of arrogance or of belittling the clinical experience of others. Of course, I feel I am simply advocating for a better and healthier approach to veterinary medicine, and my honest intent is to contribute to the growth and betterment of the profession. I have spent a great deal of time and effort evaluating the epistemological theory and the specific evidence for the subjects I discuss, and I think I have generally sound conclusions drawn from theory and evidence. But since I undoubtedly  have all the same cognitive weaknesses as everyone else, it is likely that sometimes I unskillfully or carelessly make my case in ways that are unnecessarily antagonistic. And it is likely that sometimes my conclusions are simply wrong.

There is a complex balancing act between acknowledging one’s own limitations and weaknesses while at the same time vigorously acting on one’s values and beliefs. The result is never perfect, but it is undoubtedly superior to unquestioning trust in one’s own intuition and experience. It requires personal and intellectual humility and also the converse, the willingness to confidently and assertively put forward one’s conclusions. And it is inevitable that EBM will generate resistance and controversy because it requires challenging and changing accepted practices, so one must be willing to be as honestly self-critical as possible yet still respond vigorously to such resistance.

In an odd way, the degree of cognitive dissonance one encounters is perhaps greatest when one is challenging approaches in the gray zone between established science-based medicine and outright CAM. Subjects I’ve addressed previously, such as probiotics, are ideas based on sound scientific principles and supportive preliminary laboratory data, unlikely clearly unscientific practices like homeopathy. And yet, when they are put into practice, usually as commercial products, before there is sufficient evidence to support such use, these ideas fall into conflict with the principles and practice of EBM. Yet because of their underlying plausibility and relationship to established medical practices they are often quickly accepted by veterinarians and doctors who have a generally scientific medical philosophy. These clinicians, then, are especially resistant to the suggestion that they are not adhering to their stated scientific values when they justify using such approaches because in their personal experience they seemed to have helped individual patients. Unlike the dedicated alternative medicine provider, who can always reject evidence by casting doubt on the relevance of science to what they are doing, doctors who support EBM in principle may experience cognitive dissonance when such gray-area practices are questioned.

The following are some excellent resources for investigating more deeply cognitive dissonance and the inevitable limitations and weakness in human reasoning that require us to rely on science to more closely approach a reliable understanding of reality, in medicine and life generally.

Don’t Believe Everything You Think: The 6 Basic Mistakes We Make in Thinking by Thomas Kida

Snake Oil Science by R. Barker Bausell

Predictably Irrational by Dan Ariely

On Being Certain: Believing You Are Right Even When You’re Not by Robert Burton

The Drunkard’s Walk: How Randomness Rules Our Lives by Leonard Mlodinow

Posted in General | 7 Comments

Veterinary Stem Cell “Research” — Is This the Best We Can Do?

Posted on October 4, 2009 by skeptvet

As I discussed in a previous post, the call for a reliance on sound evidence in veterinary medicine resonates less strongly that we might hope because of the paucity of such evidence. Financial resources are the main limiting factor in obtaining good-quality basic and clinical research evidence, but apparently the attitude or culture of the profession may be a factor as well. According to a recent news story from the Veterinary Information Network (VIN), a widely used information and social resource for veterinarians, Dr. Richard Vulliet, a researcher and professor at the UC Davise School of Veterinary medicine has accepted a $100,000 grant from the AKC to study the use of bone marrow stem cells in degenerative myelopathy, a mysterious and all too common disease in which older dogs gradually lose the function in their hind legs.

Dr. Vulliet is clearly a trained, experienced researcher who should understand the importance of properly designed and conducted trials. Unfortunately, if the comments and attitude attributed to him in this article are correct, his frustration with the pace and limitations of proper research have led him to use the resources he has to “try out” some ideas without the structure or controls that make the results meaningful or useful to the rest of the profession.

According to the article, “Vulliet has treated four dogs with degenerative myelopathy with their own stem cells…Vulliet derives the mesenchymal stromal cells from bone marrow. He injects the cells systemically into the circulation because it appears that they home to an area of injury.”

The idea for the project apparently came from some laboratory rat research. “Vulliet says he got interested in treating these conditions because he was working with mesenchymal stem cells and their interaction with connective tissue, and it was boring. Then he came across two papers. In one of the papers, Japanese researchers described treating induced cardiomyopathy in experimental rats (Circulation 2005;112:1128-35)…Vulliet has not treated any dogs with dilated cardiomyopathy. But he has been in contact with Doberman groups to recruit possible subjects…In the other paper, researchers at Tulane University in New Orleans induced spine injuries in experimental rats and treated them with mesenchymal stem cells.”

Clearly, Dr. Vuillet recognizes some of the limitations of a research project based on limited information about plausibility and mechanism, “When I talk to possible clients, I generally get the impression they think I know what I am doing. But no, this is research.” Unfortunately, the limitations don’t seem to bother him as much as those of properly conducted scientific research, which he has chosen not to pursue because “the protocols he would be forced to adhere to at the university, working with pet dogs, would be too cumbersome.”

The article goes on to describe the haphazard followup of subjects, including one dog whose owner, apparently a neighbor of Dr. Vuillet, almost forgot to mention that she believed the dog had improved after treatment. The issue of potential hazards also arises, when the article  mentions that 1 of the 4 dogs treated so far eventually developed a “malignant tumor on its spleen.” Clearly, splenic tumors are quite common in elderly dogs of the breeds Dr. Vuillet is studying, but any association, causal or chance, between the treatment and such disease is unlikely to be detected by casual, unsystematic followup.

What Dr. Vuillet seems to be doing is selecting a few owner with dogs who appear to have degenerative myelopathy (though how that is confirmed is unclear from the article) and who appear to have sufficiently low expectations for benefit from the procedure, and then giving them some stems cells and asking the owner someday how things are going. The value of data collected this way is so low that it is hard to justify spending $100,000 of the scarce funds available for veterinary research on it. Even more disturbing, from someone who clearly ought to know better, are statements suggesting this independant,  idiosyncratic, approach to research is somehow superior to proper clinical studies; “ I think we will learn more from these dogs than from the thousands of Ph.D.s who are experimenting in the labs.”

If this is the attitude towards science that professors at our veterinary schools are teaching to their students, I fear that better studies and better data will not be more available in the future. And while I am only speculating, I will be very interested to see if Dr. Vuillet eventually introduces some version of stem cell therapy to the veterinary market as an entrepreneurial inventor in the coming years. Such a therapy would be more than welcome, and I would be eager to provide it to my clients, if the proper evidence for its safety and efficacy were available. I am doubtful, however, that such evidence will come from projects such as this one.

Posted in Science-Based Veterinary Medicine | 27 Comments

PEMF Device for Pets

Posted on October 1, 2009 by skeptvet

Bioelectronics corporation has announced its intent to market a new device for treatment of osteoarthritis in pets. The device, the HealFast®Therapy PetPatch™, is a pulsed electromagnetic field (PEMF) device that attaches over a swollen or painful joint ad is intended to “to reduce swelling, relieve pain and enhance the healing of surgical incisions, accidental wounds, sprains, strains and chronic wounds.”

PEMF devices are widely available for human use, and as usual for CAM nostrums they are based on some suggestive in vitro and laboratory studies and weak clinical trial evidence. Electromagnetic fields do have measurable effects on cells in vitro, and there are some recognized medical uses for them. Some evidence suggests an improvement in outcome for non-union fractures, and there may be some benefit in terms of reduced pain and swelling following surgery. However, overall the evidence for clinical benefit is equivocal, as indicated by a number of review studies:

“All trials examined knee OA and one also performed a separate evaluation for cervical OA patients. The results of this analysis show improvements in all measurements for knee OA, but their clinical significance from a patient’s perspective was questionable. Only two outcomes favoured treatment for cervical OA trial and none were considered clinically important. There were no reported side effects. The reviewers conclude that there is an urgent need for further large-scale studies of pulsed electric stimulation with a focus on knee OA to establish the clinical relevance of treatment.” Cochrane Review

“We cannot make any definitive statements on the effects of electrotherapy for people with acute or chronic mechanical neck disorders (MND). Based on this review of 11 trials and 525 people with MND, the current evidence on Galvanic current (direct or pulsed), iontophoresis, TENS, EMS, PEMF and permanent magnets is either lacking, limited, or conflicting.” Cochrane Review

“McCarthy and colleagues (2006) noted that the rehabilitation of knee osteoarthritis often includes electrotherapeutic modalities as well as advice and exercise.  One commonly used modality is PEMF.  Its equivocal benefit over placebo treatment has been previously suggested.  However, recently a number of randomized controlled studies have been published that have allowed a systematic review to be conducted.  The authors concluded that this systematic review provides further evidence that PEMF has little value in the management of knee osteoarthritis.  There appears to be clear evidence for the recommendation that PEMF does not significantly reduce the pain of knee osteoarthritis.”AETNA insurance company literature summary

“In a randomized, placebo-controlled study, Ay and Evcik (2008) examined the effects of PEMF on pain relief and functional capacity of patients with knee osteoarthritis.  A total of 55 patients were included.  At the end of treatment, there was statistically significant improvement in pain scores in both groups (p < 0.05).  On the other hand, no significant difference was observed within the groups (p > 0.05).  These investigators observed statistically significant improvement in some of the subgroups of Lequesne index (e.g., morning stiffness and activities of daily living) compared to the placebo group.  However, these researchers could not observe statistically significant differences in total of the scale between two groups (p > 0.05).  Applying between-group analysis, the authors were unable to demonstrate a beneficial symptomatic effect of PEMF in the treatment of knee osteoarthritis in all patients.  They stated that further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in knee osteoarthritis and other conditions.” AETNA insurance company literature summary

“Furthermore, in a systematic review on wound care management, Cullum, et al. (2001) concluded that there is generally insufficient reliable evidence to draw conclusions about the contribution of laser therapy, therapeutic ultrasound, electro-therapy and electromagnetic therapy to chronic wound healing.  Flemming and Cullum (2001) also concluded that there is currently no reliable evidence of benefit of electromagnetic therapy in the healing of venous leg ulcers.” AETNA insurance company literature summary

 

This would seem to suggest that a responsible company would make an investment in investigating a promising therapeutic concept in the hopes of eventually finding a beneficial, and presumably profitable, product. Unfortunately, as I’ve discussed before this instead is seen as a perfect opportunity to make a quick buck selling something based on its promised rather than its demonstrated value. What is especially disturbing about the Bioelectronics’ press release is the unabashed trumpeting of the potential profit to be made and the clearly stated intent to market the device directly to consumers, bypassing the veterinarians who presumably might have troubling questions about the evidence behind the company’s claims: “A comprehensive direct to consumer marketing program will support the launch of the new product. The centerpiece of the campaign is a new TV commercial which will begin rolling out next week.”

 

So for those of you who are veterinarians, be prepared for the clients who will soon be coming to you having seen the new commercial. Hopefully, they’ll be seeking you advice, but unfortunately it’s always dissatisfying for client and vet alike to have to answer the glowing testimonials and marketing hype for one of these products by a sober and bland summary of equivocal research evidence. Still, that’s our job!

Posted in Miscellaneous CAVM | 17 Comments

CAM and Religiosity

Posted on September 29, 2009 by skeptvet

I have often referred to CAM as “faith-based medicine” due to its reliance on belief over evidence for validation, and I have commented on my perception that such a belief-based approach resembles religion, for which I have been soundly chastised by some as raising a divisive issue. Nothing stirs passions and animosities like a discussion of religion in America. Nevertheless, while I respect people’s right to believe as they choose, and I see a lot of good come from many religious traditions, there does seem to me to be a strong relationship between various forms of non-evidence based belief. A recent article in the Journal of Alternative and Complementary Medicine would seem to support the link between religion, or at least religiosity, and CAM. Unfortunately, without paying for a subscription, I can only access the abstract and first page, but here are some tidbits:

“Naturopaths and acupuncturists were three times as likely as internists and rheumatologists to report no religious affiliation (35% versus 12%, p<0.001), but were more likely to describe themselves as very spiritual (51% versus 20%, p<0.001) and to agree they try to carry religious beliefs into life’s dealings (51% versus 44%, p<0.01). Among physicians, increased spirituality and religiosity coincided with more personal use of CAM and willingness to integrate CAM into a treatment program.”

“Religion, spirituality, and complementary and alternative medicine (CAM) are related to one another in complex ways. Religious practitioners and CAM supporters are critical of conventional biomedicine’s reductionism and impersonality…Additionally, reflecting religious traditions, CAM supporters see patients as “whole persons—spiritual beings.” Thus, we might expect those who are more religious to be attracted to CAM practices.”

The article does discuss the concern of some fundamentalist members of mainstream religions with the “universal notion of spirituality over particular and concrete practices of religion,” but it does suggest that overall a supernaturalist outlook is correlated with an openness to vitalist, non-scientific approaches to medicine.

We generally believe ourselves in this country to be past the days when one’s religious faith determined one’s beliefs about the ordinary physical world. Most people of faith accept the reality of the geocentric model of the universe, evolution by natural selection, probabilistic quantum mechanics, and many other scientific discoveries that explain phenomena previously given supernatural explanations. CAM, however, is an area in which all too often faith trumps reason, and belief is considered sufficient to validate a practice that cannot be supported by objective scientific evidence.

If we acknowledge the clear connection between a bent towards vague, supernaturalist beliefs and CAM, I think we can strip away the misleading patina of science that disguises much CAM and lends it an undeserved appearance of legitimacy. Certainly, there are CAM proponents  who are committed to a scientific, evidence-based approach, and we should encourage and support these. But when others clearly base their practices on spiritual belief rather than real science, we should make that clear for all to see as well.

 

Addendum

 

A reader was kind enough to forward a complete copy of the article, and there were a few more interesting comments I wanted to pass along. Overall, the article makes a strong case, though with limited data, that CAM use is about worldview more than about safety and efficacy. The authors state “[Astin, JA, 1998] hypothesized that ‘growing interest in alternative medicine may represent a type of cultural (Kuhnian) paradigm shift regarding health beliefs and practice…part of a broader value orientation and set of cultural beliefs, one that embraces a holistic, spiritual orientation to life.” Our finds support this hypothesis.”

They also argue their paper is “another in a growing body of research that underscores the important roles religion and spirituality play in shaping physicians’ clinical judgment.” Personally, I find this idea frightening. I would prefer my doctor to use science and facts as the  basis of clinical judgment, not religious beliefs. Sure, religion may play a role in how a physician approaches personal interactions and ethical questions. But their medical judgment should not be a reflection of their religious beliefs, since science and history illustrate quite clearly that religious approaches to medicine are inferior to scientific approaches. All the holy water and burning sage in the world won’t cure a staph infection.

Finally, the authors give a strategic suggestion which I suspect their peers will be likely to accept readily: “In light of these findings, proponents of CAM may ant to focus their efforts on healthcare providers who are more self-consciously spiritual, and/or focus on spiritual themes, encouraging such providers to consider integration of CAM into their practices.” Having failed to make their case on the basis of evidence, they hope to persuade people to adopt their approaches out of respect for faith and religion. I would like to believe such a strategy would be as unsuccessful as it is misguided, since it clearly will not be in the best interests of patients. I fear, though, such will not be the case.

Posted in General | 9 Comments

From CFI – Paying for Non-Evidence Based Health Care

Posted on September 28, 2009 by skeptvet

The Office of Public Policy of the Center for Inquiry, a think tank an lobby devoted to science and reason in public policy, has issued a report warning of attempts by notorious CAM booster Tom Harkin and others to insert language into health care reform legislation that would prevent “discrimination” against CAM providers. This means that insurance companies, and any public health funding, would be required to pay for services regardless of whether they work! The report discusses Therapeutic Touch as an example, and there’s always the Big Three of CAM (Homeopathy, Acupuncture, and Chiropractic, which are often already paid for by insurance)but it’s not hard to imagine even more ridiculous methods getting protection from “discrimination.” How about faith healing, psychic surgery, aromatherapy, and so on? Isn’t the $2.5 billion in taxpayer dollars we’ve already wasted on the National Center for Complementary and Alternative Medicine enough?!

The report’s conclusion sums up clearly and cogently why we should all contact our representatives and oppose the efforts to use health care reform as a back door to require funding of unproven and outright quack therapies:

“The Center for Inquiry strongly urges that the government should spend no taxpayer dollars in support of any alleged medical treatments or healing protocols, such as Therapeutic Touch, that have no grounding in experiment or in our understanding of basic scientific fact. The United States faces an urgent challenge in attempting to make quality health care available to those who need it, while simultaneously reining in the ballooning cost of medical care. Every dollar of health care funding is needed to provide tested, proven medical treatment to those who require it. It is inexcusable to squander scarce resources by funding unsubstantiated, non-evidence-based medical techniques that have no basis in theory or experiment.”

Here is are sample letters I sent to my senators and representative on this topic. Anyone who wishes to is free to use them as templates for contacting your own legislators on the subject.

Senator X,

I am writing to urge you to oppose a recent amendment to the Health Care Reform Bill offered by Senator Tom Harkin (Sec 2713 Non Discrimination in Health Care, http://help.senate.gov/BAI09I50_xml.pdf). This amendment would force insurers and any government health plan to cover unproven or outright useless alternative medical therapies not based on any reasonable scientific evidence.  As one of your constituents, I strongly support the following statement from a recent position paper on this topic from the Center for Inquiry about this topic:

“the government should spend no taxpayer dollars in support of any alleged medical treatments or healing protocols…that have no grounding in experiment or in our understanding of basic scientific fact. The United States faces an urgent challenge in attempting to make quality health care available to those who need it, while simultaneously reining in the ballooning cost of medical care. Every dollar of health care funding is needed to provide tested, proven medical treatment to those who require it. It is inexcusable to squander scarce resources by funding unsubstantiated, non-evidence-based medical techniques that have no basis in theory or experiment…

any health care reform bill Congress passes should prohibit the use of taxpayer dollars to cover non-evidence-based medicine. CFI further recommends that Congress greatly reduce or eliminate funding for the NIH National Center for Complementary and Alternative Medicine (NCCAM), as a decade of study has shown that most alternative cures work no better than placebos. The United States can ill afford to continue wasting precious resources on unproven – and often disproven – medical techniques.”

The version I sent to my Representative replaced the first paragraph of the above with the one below and was otherwise the same.

I am writing to urge you to oppose recent efforts to include mandatory coverage of unproven alternative medical therapies in the health care reform legislation congress is currently considering. Under the guise of so-called “health care freedom” or “health care choice,” these efforts would force insurers and any government health plan to cover unproven or outright useless alternative therapies not based on any reasonable scientific evidence. As one of your constituents, I strongly support the following statement from a recent position paper on this topic from the Center for Inquiry about this topic:

Posted in Law, Regulation, and Politics | 6 Comments

From Respectful Insolence – New Study on CAM and Vaccines

Posted on September 22, 2009 by skeptvet

Orac at Respectful Insolence has posted a summary of a recent paper examining the relationship between usage of CAM (specifically defined as being treated by chiropractors, naturopaths, acupuncturists, and massage therapists) treatments and vaccine rates. The study looked at children enrolled in two non-Medicaid insurance programs in Washington state, a notoriously woo-friendly place that requires insurance to cover CAM providers. The key findings were stark:

1. ” children using CAM who saw a chiropractor were between 25% and over 40% less likely to have had the four major vaccines studied, against the MMR, chickenpox, diptheria/tetanus, or H. influenzae type B. It was even worse for children who had been under the care of naturopaths. These children were over 75% less likely to have been vaccinated.”

2.  Children who had been cared for by a naturopath had significantly higher incidence of vaccine preventable disease. So did children who had a family member who used CAM therapy.

As Orac points out, it is not possible from these data to determine if the association is due to parents who are suspicious of vaccines seeking our CAM providers rather than science-based medical doctors or if the CAM providers influenced the parents’ decision whether or not to vaccinate. Likely, both factors play a role. And while the study did not find a positive association for use of acupuncture, and did not examine homeopathy, herbal remedies, TCM, or many other CAM modalities, it does support the general contention CAM use is associated with less use of science-based medical care and potentially greater health risk. This should add further weight to the contention that even ostensibly harmless AM methods may contain “hidden harm” in the form of a general belief system or world view that is inconsistent with science and that leads to underutilization of the beneficial medical therapies science offers.

Posted in General, Vaccines | 4 Comments

Nutraceuticals and Cognitive Dysfunction

Posted on September 20, 2009 by skeptvet

There is widespread agreement among veterinary behaviorists, and veterinarians in general, that one consequence of the improved longevity of our patients has been an increase in clinical behavior problems associated with brain aging. Changes in sleep/wake cycles, activity level, housetraining behavior, recognition of familiar humans and other animals, and cognitive abilities are often seen in older pets, and these can severely affect the pets’ quality of life and the relationship between pet and owner. No standardized diagnostic test for these age-related changes exists, and each pet may experience different specific changes in behavior and ability. However, there is enough similarity in the types of changes seen in older pets that it is reasonable to discuss and address them as a syndrome until research allows us to identify more specific categories of age-related dysfunction and to elucidate the specific pathophysiology of each.

Likewise, there are a number of anatomical changes seen in dog and cat brains with age and associated with clinical symptoms or functional deficits. These include reduction in brain mass, cell and axonal degeneration and changes in the relative number of different cell types in the brain, and accumulation of beta amyloid.  In dogs, these changes show some striking similarities with those seen in people with Alzheimer’s and other age-associated cognitive disorders. There are, however, significant differences as well, such as the absence in dogs of the characteristic neurofibrillary tangles seen in humans afflicted with Alzheimer’s disease. Therefore, though the similarities may justify tentatively viewing age-associated cognitive and behavior changes in dogs and humans as sufficiently alike to suggest that research findings in one species may have relevance to the other, we must be careful not to simply assume they are the same disorder with the same pathogenesis or the same response to pharmacological manipulation.

There are no universally or highly effective therapies for age-related cognitive and behavioral dysfunction. Some drugs, such as selegilene, have shown limited ability to improve clinical symptoms, but it is a disorder for which veterinary medicine has little to offer in the way of amelioration. Much more research must be done to understand the causes of the clinical problem and how these may be addressed.

As always, when there is a poorly understood problem with no ready medical solution, potential therapies abound and the standards of evidence required to justify their marketing and use are generally low. A number of nutraceutical products, vitamins or other dietary supplements used with the intent of achieving a beneficial pharmacological effect, are marketed for age-associated behavioral problems. Most of these are supported by reasonable theoretical rationales, suggestive in vitro research, some promising laboratory animal studies, and limited clinical research with few subjects and generally poor methodological quality.

As with probiotics, these remedies fall in an intermediate category between CAM and scientific medicine. There is reason to believe they may eventually prove useful, but the available data is not currently adequate to demonstrate this, and it is certainly not adequate to justify producing and selling such products to the general public. But manufacturers of neutraceuticals consider the time between the proposal of a hypothesis that a supplement might be beneficial and the accumulation of sufficient data to decide the truth as a golden time for marketing. As a recent article from the Los Angeles Times news service put it regarding one of these compounds:

For the purveyors of vitamins, minerals and herbal remedies, that is a five- to seven-year opportunity not to be missed. Consumers’ dreams of forestalling the ravages of age have been engaged, and they will buy and swallow anything that gleams with the luster of science. While they wait for science to flesh out resveratrol’s promise, consumers’ demands for the stuff can be built, tapped and satisfied with products that offer plenty of promise but tread lightly around the preliminary state of the scientific evidence.

“There’s a watershed time for a good nutraceutical,” says Dr. Joseph Maroon, a University of Pittsburgh neurosurgeon, author of a book titled “The Longevity Factor” and co-founder of a company, Xenomis, which rolled out a line of resveratrol-based supplements last May.

Resveratrol, in short, stands at the juncture of hope, profit and scientific promise — a social phenomenon galloping ahead of research that is undeniably intriguing but very incomplete.

Most of the products marketed for cognitive and behavior problems in older pets are combinations of multiple substances, which makes any rigorous scientific evaluation of them difficult. It is also the case that many of the studies available have been sponsored or conducted by companies marketing the product being tested, and while this does not invalidate the results, it is well-documented that such studies are more likely to be positive than independently conducted research.

Hill’s Pet Nutrition has created a veterinary diet fortified with Vitamins C and E, L-carnitine, omega-3 fatty acids, and lots of fruit and vegetable ingredients. The company has published results of several studies which support the contention that the diet has some protective benefits in terms of cognitive decline and age-associated behavior problems. It is impossible to identify which ingredients, singly or in combination, might account for this effect, but the evidence is good that there is some clinically significant benefit. As always, replication by independent investigators would strengthen the case, and further research to identify which components of the diet are of relevance would be useful.

Other products, such as CEVA Animal Health’s Senilife and VetPlus’ Aktivait, contain multiple ingredients each proposed to prevent or treat age-related cognitive dysfunction via plausible mechanisms based on in vitro or laboratory animal studies. Again, which if any of these ingredients might actually be beneficial is impossible to determine from clinical studies using the combination product. And so far the clinical research evidence is weak, consisting mostly of small, inadequately controlled trials often sponsored by the manufacturer. I will try to discuss each ingredient independently and then review the available literature on some combination products.

Phosphatidylserine-

Phosphatidylserine (PS) is a phospholipid that occurs in cell membranes. It is hypothesized, based on laboratory studies, to facilitate normal function of nerve cell membranes and influence levels of various neurotransmitters. A 2003 FDA report reviewed the clinical literature in humans and concluded that the evidence did not support assertions that this compound has preventative or treatment benefit for cognitive dysfunction and dementia in people. The agency did approve a highly qualified claim for the product:

Dementia claim and disclaimer:

“Consumption of phosphatidylserine may reduce the risk of dementia in the elderly.

Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim.”

Cognitive dysfunction claim and disclaimer:

“Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.

Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is little scientific evidence supporting this claim.”

One important caveat to the data the FDA analyzed is that most research has been done on PS derived from bovine brain tissue. Due to the risks of acquiring bovine spongiform encephalopathy (BSE or “Mad Cow Disease”) from this source, the FDA prohibited its use, and the proposed commercial products contain PS derived from soybeans. The plant derivative differs structurally from bovine-derived PS, so there is some question about whether data regarding one is applicable to the other. I was not able to identify the source of the PS in the various veterinary products and research trials.

I was also not able to find any veterinary clinical trials for cognitive dysfunction examining PS alone. It is included in a couple of combination products, including Senilife and Aktivait. As discussed below, the clinical research evidence for these products is weak. No evidence regarding the safety of the substance was found, apart from the theoretical concerns about BSE discussed in the FDA report.

Ginkgo Biloba-

This is a very popular herbal product which is purported to have a wide range of beneficial effects on cognition, memory, depression, anxiety, tinnitus, and headache. It has vasodilatory effects and acts as a scavenger of oxygen free radicals in vitro and in laboratory animal studies. The clinical trial evidence in humans does not support a beneficial effect for cognitive impairment or dementia, as summarized in a Cochrane review below.

Many of the early trials used unsatisfactory methods, were small, and publication bias cannot be excluded. Overall, evidence that Ginkgo has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unreliable. Of the four most recent trials to report results, three found no difference between Ginkgo biloba and placebo, and one reported very large treatment effects in favour of Ginkgo biloba

The review also concluded that there were no significant safety concerns for it’s use. The NCCAM summary of this product indicates no benefit seen even in a large NCCAM sponsored study of Alzheimer’s patients, and lists a number of possible toxic effects.

Again, I have found no veterinary clinical trials looking at Ginkgo biloba alone as a preventative or treatment for age-associated cognitive and behavior problems. It is included in Senilife, which I discuss below has limited weak evidence to support a beneficial effect.

Resveratrol-

Resveratrol is a chemical extracted from grapes that has been touted as a general anti-aging panacea. There are numerous in vitro and lab animal studies that suggest the compound may act as an antioxidant and have a variety of effects promoting and inhibiting the expression of a number of genes. There is mixed evidence in lab animals that it may prolong life and inhibit, or in some cases promote, cancer. Human clinical trials for a number of possible uses are ongoing, but no data is available to suggest safety or efficacy for any particular use.

Likewise, there are apparently no veterinary clinical trials of resveratrol alone for cognitive and behavior dysfunction. As the newspaper article quoted above suggests, it is a promising but unproven compound which has been marketed well in advance of reliable evidence to its safety and efficacy. Resveratrol is an ingredient in Senilife, which has only weak supporting research evidence for clinical benefit in veterinary patients.

Pyridoxine (Vitamin B6)-

Pyridoxine is believed to have anti-oxidant properties and may be a co-factor in the synthesis of some neurotransmitters. According to a Cochrane review, clinical research in humans has not demonstrated any benefit in terms of mood or cognition in elderly people, and no high-quality studies are available investigating its use for dementia or cognitive impairment.

Two trials of vitamin B6 supplements for healthy elderly people qualified for this review, with no beneficial effects on mood or mental function detectable. Homocysteine levels were not assessed. No ill effects of vitamin B6 were observed. No trials studying effects of vitamin B6 treatment for people with dementia or cognitive impairment were identified.

The NCCAM has also published an evidence review which concludes, “Human studies were generally of poor quality. Weak evidence suggests possible benefits of B1 supplementation and injected B12 in AD. The effects of B6 and folate are unclear. Overall, dietary intake studies do not support an association between B vitamin intake and AD. Studies evaluating B vitamin status were mostly inadequate due to poor study design. Overall, studies do not support an association between B vitamin status and age-related neurocognitive disorders.”

While these reviews did not find evidence of health risks with pyridoxine supplementation, neurologic disorders have been reported with pyridoxine supplementation in humans and in dogs (Study 1, Study 2). No clinical trials were found investigating pyridoxine use for treatment or prevention of age-associated behavior disorders. It is a component of Senilife.

Vitamin E-

Vitamin E is purported to have benefits in a number of conditions due to its anti-oxidant properties. However, a Cochrane review of the research regarding the compound and Alzheimer’s Disease or cognitive impairment in humans found:

To date only one randomized controlled trial has assessed the efficacy of Vitamin E in the treatment of AD patients and only one assessed the role of Vitamin E in patients with mild cognitive impairment (MCI). In the Vitamin E study for moderately severe AD patients a lower number of those taking Vitamin E declined to incapacity over a two year period compared with the placebo group. However, AD patients taking Vitamin E experienced a greater number of falls. In the MCI study, Vitamin E 2000 IU daily produced no significant difference in the rate of progression to AD compared to the placebo group… There is no evidence of efficacy of Vitamin E in the prevention or treatment of people with AD or MCI. More research is needed to identify the role of Vitamin E, if any, in the management of cognitive impairment.

No clinical trials have been done on Vitamin E for cognitive dysfunction in veterinary patients. As I’ve previously discussed, Vitamin E supplementation has been shown to have potential risks, including increasing the risk of heart failure and possibly cancer.

S-Adenosylemethionine (SAMe)-

SAMe is a molecule already present in the body that has anti-oxidant properties and that is involved in the synthesis and regulation of some neurotransmitters. It also appears to play a role in the regulation of nerve cell membrane structure and function. There is some in vitro and laboratory animal evidence suggesting it might be of benefit in cognitive disorders in humans, though the clinical trial evidence is limited and mixed.

A small, short-term study sponsored by Virbac Laboratories investigated the use of SAMe to reduce symptoms of age-related cognitive dysfunction. Despite its limitations, the study was well-designed and showed convincing evidence for an improvement in daytime activity and possibly some improvement in sleep problems. It did not show any benefit for confusion or disorientation. No adverse effects were seen in the study subjects. Further study of this compound is certainly warranted.

Co-Enzyme Q10-

A component of the energy production pathways in mitochondria, CoQ10 has been suggested to be of value in Alzheimer’s disease in humans. The laboratory animal study evidence is mixed, with some trials showing reduction in beta amyloid in mice and others showing no effect or even a worsening of cognitive function in mice. A 2003 review found no reliable evidence of benefit in humans and suggested more study is needed. No trials appear to have been conducted in aged dogs or cats with cognitive dysfunction. The compound is an ingredient in the combination product Aktivait. 

 

Combination Products-

 The manufacturer of Senilife indicates in its marketing literature that some sort of research demonstrates the efficacy of the product. There are lots of charts and graphs and “percentage improvement” numbers, but no information about study subjects, protocol, blinding, placebo control, or anything else that would allow evaluation of this purported data. However, there have been some clinical studies published looking at the product. An open-label study of eight dogs done in Italy showed some beneficial changes in some clinical parameters. Of course, this is a very weak level of evidence appropriate only for suggesting that further study is warranted.

 Another study looked at Senilife in a group of nine laboratory beagles ranging from 7-13 years of age and evaluated performance on a short-term memory test. The study reported marked improvement in performance of the animals on the supplement. However, the study was small, examined a laboratory cognition task that might or might not have relevance to clinical disease, and was not randomized or blinded. It also utilized a crossover design, which is inappropriate for a progressive disorder such as age-associated cognitive dysfunction. Additionally, during the second phase in which the original treatment group became the control group, there was no difference in the performance of this group between treatment and control. The authors interpret this as a persistent effect of treatment, but they did not clearly eliminate other possible explanations, such as differences between the groups not related to the intervention.

Another combination product, called Aktivait is marketed for age-relative cognitive and behavior problems. It contains the essential fatty acids DHA and EPA, N-acetyl cysteine, Vitamin C, L-carnitine, Vitamin E, Coenzyme Q10, phosphatidylserine, and selenium. A clinical trial of 41 dogs has been published which found a benefit for some measures of dysfunction in naturally occurring disease. The trial was randomized, placebo-controlled, and double-blinded. It reported significant improvements in some measures (daily scores for activity and recognition of owner and global score for housetraining) but not others (daily scores for sleep disturbances, social interaction, incidents, locations, and substrates for inappropriate toileting and global scores for disorientation, sleep patterns, and social interaction). This suggests that the authors conducted multiple comparisons and focused only on those that showed a positive effect while downplaying the majority that did not, but they way the data is presented it is not clear if this is the case. The study also reported that for one of the assessments which improved, housetraining, the treatment group had a significantly higher rate of problems that the placebo group at the beginning of the trial, so the groups were clearly not matched properly for this measure.

So far, the available evidence for Senilife and Aktivait is suggestive of benefit but generally very weak. This is always the case in the early stages of investigating a potential therapy, and does not reliably indicate what the results of larger, better-designed studies will determine to be the real truth. However, there are serious ethical questions associated with marketing and selling such remedies on the basis of such weak evidence given the large proportion of therapeutics that show early promise and later turn out to be useless or even dangerous. I certainly support further study of possible interventions for age-associated cognitive and behavioral problems, but I think such research would be better done on elucidating the underling pathophysiology and on single interventions targeted at understood elements of the syndrome, rather that clinical trials of shotgun-type combinations therapies supported by companies looking to sell these products.

References

Araujo, J., Lansberg, G., Milgram, N., Miolo, A. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine. Canadian Vet J, 49(4):379-385; 2008.

Dalton, K., Dalton, MJT., Characteristics of pyridoxine overdose neuropathy syndrome, Acta Neurol Scand 76:8-11, 1987.

Dodd, CE., Zicker, SC., Jewell, DE. Can a fortified food affect the behavioral manifestations of age-related cognitive decline in dogs? Vet Med 98:396-4080; 2003.

Heath, S. et al. Nutritional supplementation in cases of canine cognitive dysfunction: Results of a clinical trial, Proceedings 29th World Congress of the Small Animal Veterinary Association, 2004.

Osellaa, M/C, et al. Canine cognitive dysfunction syndrome: Prevalence, clinical signs and
treatment with a neuroprotective nutraceutical. Read online Sept. 20, 2009 at  http://www.crashinggoodtime.com/CDS.html
Reme, C.A., et al. Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial. Vet Ther 9(2):69-82; 2008.

Posted in Herbs and Supplements | 35 Comments

The Gonzalez Trial – The Cost of Studying The Unlikely

Posted on September 9, 2009 by skeptvet

 First, I just wanted to point out that I have added another example to the list of harm done by use of CAM. In this case, it’s a tragic story about a young women suffering needlessly yet unwilling to give up on useless therapy.

On a larger scale, but just as tragic and infuriating, the results are available for the NCCAM-funded study of the Gonzalez cancer therapy.* Dr. Kimball Atwood has written extensively about the therapy and the NCCAM trial (The Ethics of “CAM” Trials: Gonzo Part I, II, III, IV,V, VI, and VII). Despite a host of serious ethical concerns, which Dr. Atwood has detailed extensively, the government funded a study in which people were allowed to elect a CAM therapy with no scientific plausibility or standard chemotherapy for their pancreatic cancer. It should surprise no one that the outcome clearly shows the Gonzalez regime to be ineffective. People on conventional chemotherapy lived 3 times longer than those on CAM treatment (14 months vs 4.3 months), and contrary to the usual CAM propaganda about cancer therapy, those who elected the alternative regime had a significantly poorer quality of life for those 4 short months.

It is true that the conventional therapy for this disease does not offer great hope for people with this disease. And the patients who followed the Gonzalez treatment did so by their own choice (the trial was originally randomized, but most patients refused to accept random allocation to treatment groups). But as I’ve argued before, the understandable desperation of people in this situation does not justify giving them false hope for help from methods unlikely to be of any real benefit. And the irrational pursuit of such hope cost the people in the CAM arm of this study almost a year of life on average and a great deal of suffering. Of course, it is difficult to argue that people should not be permitted to choose irrational hope over bleak reality. but it seems obvious that doctors who encourage such a choice by promoting, or refusing to critique, such therapies are failing in their duty to their patients. And this study illustrates nicely how NCCAM is complicit in this by giving a patina of legitimacy to bogus treatments.

CAM proponents frequently argue that unless their methods have been thoroughly investigated by large, well-designed and well-conducted clinical trials, critics of them are not adhering to their own standards of evidence. Because some ideas which seemed implausible in the past turned out to actually be true, they argue that any attempt to focus our research efforts based on scientific plausibility is mistaken. Such an argument seems very effective in supporting the work of NCCAM and in getting a foothold for unlikely therapies in mainstream medicine, but it is riddled with weaknesses.

Firstly, it ignores the fact that most ideas which seem implausible at first really are wrong, and they fail when tested. The fact that there are exceptions, and that the availability bias makes them seem more representative than they really are, does not support investigating anything and everything regardless of its provenance or consistency with well-established scientific principles. The argument also would require our desperately limited resources for scientific research to be spent indiscriminately, especially on popular or catchy ideas rather than the more mundane concepts that have a solid foundation in basic science and pre-clinical research.

As this study shows, testing anything and everything also exposes test subjects to avoidable risk and suffering. Even in cases where there is little hope in mainstream, scientific therapy there is no reason to think the false hope CAM offers is the better choice. No CAM therapy which is implausible or mysterious in its principles, or outright contrary to what we understand about the universe, has demonstrated under rigorous clinical testing to be the miracle its proponents have claimed for it. Progress comes far more often from laborious and careful work building on what is known than from wild guesses by lone geniuses.

Lastly, the clinical testing of implausible CAM methods seems likely to be futile even when the results are as clear and stark as in this trial. One might hope that this study will dissuade people from pursuing the Gonzalez therapy, and even cause them to question the underlying marketing of CAM methods, which use anecdote and the limitations of scientific medicine to claim far more than they can really provide to sick people or animals. But the past does not suggest this will be true. Faith-based medicine ultimately does not rely on empirical validation, and its followers rarely accept any evidence that they are mistaken. The spinning of these trial results will likely begin shortly, and the proponents of the method will continue to offer it, and it’s false hope, to vulnerable cancer patients without a qualm.

 

*Pancreatic Proteolytic Enzyme Therapy Compared with Gemcitabbine-based Chemotherapy for the Treatment of Pancreatic Cancer

John A. Chabot, Wei-Yann Tsai, Robert L. Fine, Chunxia Chen, Carolyn K. Kumah, Karen A. Antman, and Victor R. Grann*

From the Herbert Irving Comprehensive Cancer Center, Department of Medicine and Surgery, College of Physicians and Surgeons; and Departments of Biostatistics, Epidemiology, and Health Policy and Management, Joseph L. Mailman School of Public Health, Columbia University, New York, NY; Boston University Medical Center, Boston, MA; and Department of Statistics, National Cheng-Kung University, Taiwan.

* To whom correspondence should be addressed. E-mail: vrg2@columbia.edu

Purpose: Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma; thus, many patients seek alternative treatments. The National Cancer Institute, in 1998, sponsored a randomized, phase III, controlled trial of proteolytic enzyme therapy versus chemotherapy. Because most eligible patients refused random assignment, the trial was changed in 2001 to a controlled, observational study.

Methods: All patients were seen by one of the investigators at Columbia University, and patients who received enzyme therapy were seen by the participating alternative practitioner. All met strict clinical criteria for eligibility. Of 55 patients who had inoperable pancreatic cancer, 23 elected gemcitabine-based chemotherapy, and 32 elected enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. Primary and secondary outcomes were overall survival and quality of life, respectively.

Results: At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P < .001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01).

Conclusion: Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment.

Posted in General, Miscellaneous CAVM | 2 Comments