Known unknowns and unknown unknowns in herbal veterinary medicine.

I am afraid I can't resist stealing my title from Donald Rumsfeld, because I think it describes the problems of using herbal remedies in different species quite well. What are the risks of using herbal products in animals?

There are the known problems common to herbal treatments such as unknown and.or variable concentrations of active compounds in herbs from different sources and even from the same source but harvested at different times and under different conditions. Sometimes demand for herbs or other natural products can lead to damage or even extinction to rare species used in various healing traditions. There are many examples of contamination of herbal products, and some traditional remedies that may be represented as natural or herbal may be neither. When demand for a certain herbal product rises quickly (Such as the use of Chinese Astragalous for influenza viral infections) there may be a strong motivation to use different portions of the plant than usual or to substitute other related plants or to adulterate the product with something else to make up the volume.
These types of problems are common to many if not all herbal remedies sold and are what I consider known unknowns when dealing with these types of products in veterinary medicine.



When herbal products that may have been used traditionally for humans (it is fairly common for veterinarians to use Chinese herbal medicines on their patients) unknown unknowns come into play.
Often different species absorb and metabolize the same plant or drug very differently, and sometimes unexpected toxicities can arise in different species. Even in herbivores, different species can react differently to toxic plants, and one species may be able to consume a given plant safely, while another species may not.
Once you give a carnivorous animal (especially cats) herbs other problems arise. Cats have much lower levels of some liver enzymes such as glucuronosyltransferase(1) which converts toxic metabloites of drugs such as acetaminophen to less toxic compounds. One reason cats may have lower levels of such enzymes is that cats are obligate carnivores, and eat less plant material than other carnivores such as canines and bears, and probaly have less need to metabolize plant toxins.

Cat's red blood cells are also more sensitive than those of other species to oxidative damage, and small amounts of onion or garlic can cause Heinz body anemia in cats. when I was in veterinary school in the late 1980's, it was common to syringe or tube feed sick cats baby meats. Some baby meats have onion powder added for flavor, and there were cases of cats developing heinz body anemia after a few days of feeding baby meats containing onion powder. Now special diets are available for critically ill pets and this problem is not so common. Cats are also more sensitive than dogs to plant-based insecticides such as Pyrethrins and "natural" insecticides such as essential oils. Both dogs and cats have been poisoned by the use of pennyroyal oil, a popular substitute for flea and tick control products (2).

While some of these examples are well known and documented, I call this type of problem "unkown unkowns" because these issues are often unanticipated and are discovered when someone gives their pet a product and then discovers that the animal is not responding well. Other examples of this type of discovery include grape/raisin toxicity in dogs, and Lilly toxicosis  in cats (3).

Because of the variable nature of herbal remedies and the potential for unknown and unforeseen toxicity, I think veterinarians and pet owners should be very cautious when using these types of products in animals. Unfortunately, the primary reference for veterinary herbal medicine, while giving lip service to these issues, also seems to put great value in untestable concepts such as Chinese and Ayurvedic forms of vitalism,   and repeats standard CAM claims that natural products are always safer and  less toxic than standardized pharmaceuticals. While they do state that essential oils should be avoided, they often state that many of these products "appear to be safe", without much consideration for the variables and unknowns I have discussed here. The book does not inspire confidence in me at least.

References;

1. Sellon, R.K. Acetaminophen, pp. 550-558 in Small Animal Toxicology, 2nd ed. 2006, Peterson and Talcott, eds, Elsevier/Saunders, St. Louis.
2. Poppenga, R.H. Hazards Associated with the Use of Herbal and Other Natural Products, pp. 312-344 in  Small Animal Toxicology, 2nd ed. 2006, Peterson and Talcott, eds, Elsevier/Saunders, St. Louis.  
3. Mason, J.A., Khan, S.A. and  Gwaltney-Brant, S.M. Recently Recognized Animal Toxicants pp. 138-143 in Current Veterinary Therapy XIV, 2009, Bonagura and Twedt, eds.Elsevier/Saunders, St. Louis.
   

Ray Comfort edition of "Origin"

A local church group was handing out free copies of  The Origin of Species with a special introduction by "banana man" Ray Comfort.  This introduction contains many fallacious arguments that have been refuted many times, such as the idea that Darwin is directly responsible for Adolf Hitler and the holocaust, and ideas that there are no transitional forms or "missing links" in the fossil record.

It is interesting to note that the announced date of distribution was the 19th, but apparently fears of handouts of information countering the introduction from the NCSE led them to bear false witness yet again and change the date. Unfortunately typical behavior from the young earth creationist crowd.

Music with a Skeptical theme.

I am a fan of traditional and folk music, and just found a new album that I have been waiting for for several months. The Darwin Song Project was sponsored by the Shrewsbury folk festival for the Bicentennial of Darwin's birth. One of the singer-songwriters who participated was one of my favorites, Karine Polwart, from the Scottish Borders. Her song "We're All Leaving" is on the album. Karine's EP "Daisy" also has songs with scientific and skeptical themes. I was not familiar with some of the other artists from both the UK and the US, but I am impressed with the results of the one week retreat where the songs were written. If you enjoy traditional/folk music, this is an enjoyable album.

Last week an interesting discussion occurred on VIN and spilled over onto The SkeptVet Blog. Coincidentally, NPR's Science Friday for October 9th was about veterinary medicine, and included some discussion of Stem Cell research. Dr. Lisa Fortier is an equine surgeon who is active in research in the areas of cartilage and tissue repair. She mentioned that there is still a lot of basic research that needs to be done to answer questions about what types or stem cells will be most effective for certain treatments, and to evaluate the safety and effectiveness of stem cell treatments. She also made a good comment in response to a question about Lyme Disease regarding the difficulty of diagnosis, and the fact that the antibiotics used to treat Lyme disease can have anti-inflammatory effects that can cause improvement in lame horses that may not have had lyme disease in the first place. I thought this comment demonstrated the problem of confusing correlation and causation quite well.

There was also a small animal veterinarian on the panel, Dr. Sarah Meixell from Veterinary Care of Ithaca. During the question and answer period, at about the 33minute point in the show, Dr. Meixell stated that acupuncture and Chiropractic were very effective treatments for animals, with no mention of any evidence to support the claim. Even worse, a minute or two later, someone asked about "organic" treatments and she said that there are Homeopathic vets who treat animals. When the show host Ira Flatow gently challenged this statement by saying that homeopathy might just keep the owner happy, she said "No it actually helps the pet".

I thought the show demonstrated the contrast between science and evidence-based veterinary medicine and alternative medicine in an interesting way. While the other veterinarians on the show seemed to be careful to emphasize science and evidence, Dr. Meixell boldly asserted that several CAM modalities, including homeopathy, were effective. She does not seem to practice CAM herself, at least from what I can see on the Veterinary Care of Ithaca website, but she appears to accept it's use uncritically, and gave many listeners the impression that it works.

This is exactly the type of situation that many veterinarians tend to find themselves in when trying to discuss CAM critically. If we challenge statements supporting modalities that are not supported by the evidence, we are accused of being rude, no matter how politely and discreetly the challenge. It was interesting to see the researcher involved in studying stem cells qualify her answers and explain what still needed to be discovered, while another vet seemed to accept several varieties of CAM uncritically.

More rabies information.

Related to my last post is this paper on a current rabies epidemic in China, the result of low levels of rabies vaccination in dogs, and transport of infected dogs as food animals from one aea to another. Over the last 15 years the number of human rabies cases in China has risen from about 150 in 1996 to over 6000 in 2005. This is a dramatic demonstration of how effective vaccination, animal control and other public health efforts can be, and how severe the consequences are when such measures are neglected.

Rabies vaccine fears and relative risk.

People are often not very good at assessing relative risks. This can be expressed as a fear of flying, even though the relative risk of dying in a car accident on the way to the airport is probably much higher than the risk of a commercial airline crash. Two papers published in the September 15th issue of JAVMA (Rabies surveillance in the United States during 2008, Blanton, et. al. and Rabies in vaccinated dogs and cats in the United States, 1997-2001, Murray, et. al.) and a post and discussion on Dolittler concerning these papers illustrates how the relative risk of side effects of a vaccine versus the risk of the disease and related consequences. The comments related to the post are particularly revealing, and I believe show how veterinarians and their clients sometimes approach an issue from different angles and can end up talking past each other, especially when a client may be mistaking the relative risks involved.

So what are the risks of vaccination versus the risk of disease as illustrated by these two papers and the discussion on Dolittler?

Risks related to vaccination mostly involve adverse effects of vaccination. Adverse effects include allergic reactions, delayed reactions such as granulomas at the injection site and then the well-known and well-publicized vaccine associated sarcomas which occur mostly in cats, but can happen very rarely in dogs.
Most of these adverse effects are treatable and/or preventable (allergic reactions) and may happen a few times in 1,000 vaccinations. More serious life threatening reactions to vaccines are very rare, and many vets may see very few in their career. Vaccine associated sarcomas in cats may happen in one in 1000 cat to 1 in 10,000 cats over their lifetimes, depending on which study you would like to read. These sarcomas can be very difficult to remove depending on the location they form in, and can be caused by inflammation not related to vaccination. There are newer vaccines for cats that do not have the adjuvants suspected of causing sarcomas to form.
Some other serious diseases and problems such as generalized allergies, autoimmune diseases and "vaccinosis" (a general term for ill health blamed on vaccines that does not have any real meaning or definition) have never been clearly linked to vaccines and are probably not directly or specifically caused by vaccines.

What is the risk of any given pet being exposed to Rabies? This risk may be higher than most people think. The first Rabies surveillance paper shows that Rabies exists in wildlife in every state except Hawaii, and that various bat strains are the most widespread type. There are also regional variations-Raccoon rabies along the east coast, several skunk variants in the midwest, southwest and California, and fox variants in the southwest. A new strain of bat rabies has recently made the jump to skunks and foxes in Arizona. Canine rabies strains have been eradicated in the U.S. due to vaccination and animal control efforts, so all cases of rabies in domestic animals come from wildlife. Any animal that goes outside at all is at risk of being exposed to rabies. Since bat rabies is so widespread, it is possible for a pet to be exposed anywhere bats occur. Rabid bats have an annoying habit of turning up in strange places, including inside homes, so keeping cats indoors is no guarantee that they will never be exposed.

Another risk of having a pet that is not vaccinated against rabies or that is not current on rabies boosters is what could happen if the pet happens to bite someone or is exposed to a rabid animal.
Animal bites treated by doctors legally have to be reported to local health departments, so that appropriate follow up and rabies preventative treatment can be done in a timely manner. In the second JAVMA paper, reports from 20 states on dogs and cats tested for rabies between 1997 and 2001 are listed. There is no way to test a live animal for rabies infection, so all of these animals were euthanised because of a bite or died of neurologic disease that raised a suspicion of rabies. During that period these stated tested 78,669 dogs and 92,318 cats for rabies. 248 dogs (0.32%) and 685 cats (0.74%) tested positive. many of these animals may have been strays, but some of them were pets that were not vaccinated. 13 dogs and 22 cats had a history of rabies vaccination, but only 2 dogs and 3 cats were classified as currently vaccinated. As with any vaccine, failures can happen, but are very rare. This also indicates that one vaccine or an extended schedule of rabies booster does increase the risk for rabies infection.
If an unvaccinated pet bites someone, the local health department can have the pet euthanised and tested for rabies if they think they need to. This is a risk to the pet that is unrelated to the actual risk of rabies infection, as shown by this study-over 99% of dogs and cats tested for rabies were negative. Other states undoubtedly tested many animals as well, but did not agree to participate in this paper, so these numbers are probably even more dramatic across the entire country.

Some of the comments on Dollittler were common arguments many veterinarians hear. "My cats never go outside, they are always in the yard, etc." These papers show that rabies is common and widespread in wildlife, and that hundreds of unvaccinated and even a few vaccinated pets do get rabies, and tens of thousands of unvaccinated pets were killed for rabies testing over a five year period. This is the perspective veterinarians are coming from when they recommend rabies vaccines. The risk to pets and humans from rabies is real and the consequences of infection are severe. Some people who do not want to vaccinate their pets consider information like this fear-mongering, but failing to inform pet owners of these risks, along with a discussion of the rare but serious side effects of vaccines would constitute negligence on the veterinarians part.
Failing to keep a pet current on it's rabies vaccination can result in the death of the pet even if it does not get rabies. This is a result of the need to ensure that humans receive appropriate treatment in a timely manner when exposed to a potentially rabid animal and is a risk that most pet owners are not aware of. Just because a client thinks their pet will never bite anyone or will never get outside, does not mean that it will never happen. It does not mean that your vet thinks you are lying, but we understand the relative risks of vaccinating versus not vaccinating in a way that the pet owner may not.

Mushroom extracts for cancer?

A recent question from a client about mushroom extracts for "immune modulation" in cancer patients led me to look into the evidence for these supplements. While the idea that mushrooms could contain medically effective compounds is reasonable, (there are many active chemical compounds, including some very toxic compounds) the evidence for their use is still weak. There have been traditional uses of mushrooms in cancer treatment for centuries or longer, and preliminary testing of mushrooms and compounds in mushrooms since at least the late 1970's. As is the case with many things which fall under the DSHEA as nutritional supplements, mushroom extracts are not required to be tested for efficacy or safety before being sold.

This website is the one my client was asking about. They claim that their two supplements, K9 Immunity and K9 Transfer Factor will help to modulate the immune system which will help to prevent cancer and also help the immune system to recognize the cancer and eliminate it if it is already present. They really have no data to support these claims, and so resort to vague, nonspecific claims of "immune modulation", "detoxification" and "support". One of the videos they have produced looks like a news feature, but is really the president of the company promoting the products. He is careful in that video to avoid specific claims, and says repeatedly that pet owners should pursue appropriate treatment, but their supplements can "improve quality of life". All of the testimonials indicate that the dogs that have done well received appropriate treatment for their cancer including surgery, radiation and/or chemotherapy.
There is never any evidence presented that using the supplements changed the outcome or course of therapy for any of these pets. A paper presented on the website as evidence of effectiveness is basically a series of uncontrolled, unblinded case reports with no controls for
comparison of outcomes, and does not really address the main claims of "immune modulation"
made by the site. Some of the dogs in the report died of their disease, some needed adjustments to their treatment due to side effects, (including immune suppression) and others had progression of their disease. Their definition of cancer as a failure of the immune system to recognize aberrant cells is very simplistic, and does not account for the complexities of cancer biology.

The website seems to be named to attract people searching for information about canine cancer, and has a discussion forum and pages giving basic information about four of the most common types of cancer in dogs, but every page and nearly every paragraph leads to a link or button to order their products. As with many unproven and untested products, the people who seem to be providing such sympathetic and valuable information are really just pushing their specific products. The cost of their two supplements would be between $240 and $300 per month for a giant breed dog (120lbs). That seems like a lot to spend for an unproven and probably ineffective treatment. If they are going to support research, they could at least do a randomized, controlled trail rather than a poorly done case series.

Supplements; the sales call.

Yesterday the sales rep from our major supplier of veterinary supplies and drugs stopped by with a rep from a supplement company in tow. Since it was a hot day, and no one in Flagstaff has air conditioning, we decided to sit at the table out back under an awning (this will be important later). The supplement rep (SR for the rest of this post) was very nice, and is a sales rep, not a veterinarian or scientist-she was just doing her job. I did find the methods and claims she used interesting however. Because of DSHEA, supplement makers are not required to test their products for safety or efficacy and also cannot make specific claims to diagnose or treat disease.


The first type of supplement the SR talked about was a joint support supplement containing mostly Glucosamine and MSM. The company has scientific evidence to support their claims for this product. After the sales reps left, I had time to examine these claims more closely. Two of the studies they cite are in vitro studies, shich are fine, but say noting about actual clinical effectiveness, and the third looks better as it involves a randomized, blinded study that used force plate analysis and evaluation of inflamatory factors in the synovial fluid. The problem with this study is that only a summary written by the company is available, the actual paper has not been published, so there is no way to evaluate the methods and data they used.

Next came liver support supplements. My baloney detectors were activated when the SR said that it was "completely natural, and safe, with absolutely no side effects." Apparently it can also help to "detoxify" the liver. the references for the flier on this product have a lot of studies of the pathophysiology of various liver diseases, mostly in humans, and very little or nothing on the acutal clinical effectiveness of most of the ingredients.

Most of the information provided on this company's products was written by Susan Wynn, DVM, who the sales rep said was from the University of Georgia's College of Veterinary Medicine. Actually, Dr. Wynn is the past president of The American Holistic Veterinary Medical Association, and is an adjunct (generally nonsalaried and paid per class or lecture given) professor at Georgia. She is probably paid much better by this supplement company than she is for whatever talks or classes she gives at the veterinary school. She does not have any scientific publications that I could find (there is one case report of treatment of gastrointestinal problems with herbs) and she is the author of a book on veterinary herbal medicine. No controlled trials, but lots of dicussion of the "energetics" of different herbs-yet another type of energy medicine that I was not previously aware of.

Finally, at the end of the visit, the SR said something that I was hard pressed not to laugh at.
She looked around at the backyard, which I have spent the last 10 years making as pleasant as possible (rebuilding the patio, installing a pond and vegetable garden, planting trees, etc) and said; "you have really good feng-shuei here". Feng-shuei was one thing I never considered while improving the backyard. That comment mae me think that maybe the SR was not just doing her job as trained by the company, and maybe was more of a true believer than I thought.

Apparently this sales pitch works on many veterianrians, natualistic fallacies, vague references to toxins and all. It did not inspire me to start selling any of these supplements however.

Cognitive Dissonance

Recent discussions on the alternative veterinary medicine e-mail list and on Pet Connection have made me think more about Cognitive Dissonance and the other ways humans can deceive themselves. Prometheus at Photon in the Darkness coincidentally has an excellent post up about cognitive dissonance today.

Unfortunately, Narda Robinson seems to be an excellent example of cognitive dissonance as well. For those of you who are not familiar with Dr. Robinson, she is the Director of Colorado State University's Center for Integrative Pain Medicine. While she seems to be very skeptical and science based in her analysis of many alternative modalities such as homeopathy, herbal medicine, and others, she often credulously endorses Reiki and possibly therapeutic touch, and teaches a $4,400 dollar course in acupuncture at CSU. She has studied the "neuroanatomical" approach to acupucture for many years. There is no doubt that sticking needles into living bodies causes a reaction in the nervous system. This reaction seems to include an effect on nerve transmission and can cause the release of endorphins in the central nervous system. The question is, does this have any significant clinical effect? Increasingly, the answer seems to be no.
Detailed and well-referenced discussions of the scientific evidence for the efficacy of acupunture are available here, and here. The acupucture archive at Science-Based Medicine is well worth a look as well. In short, the development of sham acupucnture procedures such as placing needles in random points, the use of fake needles that do not puncture the skin but appear to and tricking patients into thinking they are being needled by using things like toothpicks to create an illusion of being needled all seem to be as effective as "real" acupucture. This would indicate that the act of inserting needles has a potent psycological effect that can induce a placebo efect in humans, and possibly animals as well. (My previous post discussing the placebo effect in animals and their owners shows how thismight happen.) People often like to do something, indeed anything to help alleviate their animal's suffering. Unforunately, using an inefective or minimally effective treatment may convince the owner and veterinarian that they are helping, but the animal may still be suffering.
This is my foremost concern with the promotion of veterinary acupuncture. It is quite common for the proponents of veterinary acupuncture to claim that acupucture can reduce the need for anesthetic drugs, or help with postoperative pain and chronic pain. This may result in the use of inadequate doses of other, effective analgesic drugs and techniques. Veterinary pain relief has come a long way in the past few decades, and acupuncture to me seems to be a step backward rather than an improvement.
The reason I think that Dr. Robinson is an excellent example of cognitive dissonance is because she tries to force unscientific isdeas into her inconsistent idea of what the evidence shows. A true scientist and skeptic will put all their ideas, no matter how treasured, to the test of the evidence. While acupuncture is more plausible than homeopathy, the results of the best trials do not show much effect. Dr. Robinson and CSU are making a lot of money from their courses in acupucture and from treating pets with acupucture and other therapies with weak evidence. It is their responsibility to produce good evidence or effectiveness or to stop deluding themselves and others.
M

Orac's Friday dose of woo.

Orac has his Friday dose of woo up and it is about veterinary medicine this week. A good example of woo, which unfortunately is all too often practiced by licensed veterinarians due to the nature of veterinary practice acts in the US and UK at least.

"Not testable by science"

It is very common for practitioners of many "alternative" healing modalities to claim that the energy, vibrations, or "auras" they manipulate cannot be detected by modern science. Statements like this show a depressingly weak understanding of what we already know and what we are capable of measuring. The electromagnetic spectrum has been well known for over a century, and there are not any gaps in our understanding of it (there is no room for new unknown wavelengths or particles in the range of energy that exists in living bodies). We know in great detail how nerves, muscles and other tissues create and utilize energy, both chemical and electric and are continuously learning more details, none of which suggest any new, unknown mysterious force.
Our ability to measure incredibly small amounts of electromagnetic energy has also improved past the point that the discovery of some new unknown energy or vibration having a physiologic effect is vanishingly small. We can detect light and other wavelengths that have traveled for billions of years across the universe. We can also detect the light emitted by chemical reactions in human bodies. To get these types of images requires cameras that can detect light one photon at a time. Very weak signals in all other wavelengths (radio through gamma) can also be detected.
This understanding of the electromagnetic spectrum combined with extremely sensitive detectors makes the likelihood of discovering some new type of energy affecting bodies vanishingly small. Claims by CAM practitioners that science cannot measure what they do reflect either a profound ignorance on their part or a criminal disdain for the intellect of their customers.
An interesting exercise when confronting quacks is to ask how whatever they do works. If you get vague answers, keep asking questions. Often you will find that their ultimate answer is that it cannot be measured by science. This is a strong indication that their claims are unsupported by the evidence, and are not worth risking your money or your health (or your animals health).

The problem of Prior Probability, or why controlled trials of improbable propositions are a waste of time and money.

A common criticism aimed by supporters of alternative medicine modalities at those who are skeptical is that we are closed-minded and intolerant. "It can't hurt to study homeopathy, acupuncture, etc. We might find out that it actually works!" There are many studies that show that many types of CAM are at least mildly effective, but I would like to suggest that there are good reasons why a mild effect might show up in research, and why skeptics do not accept these types of results.

Some of the reasons a treatment may seem to work include the placebo effect as discussed previously, selection and observation bias, and unfortunately outright deception (this can be unintentional). This can result in studies being published that appear to show an effect. Often negative studies are not published at all (publication bias) as researchers and institutions often do not like to publish negative studies. Since the evidence-based medicine movement considers controlled trials the gold standard, reviews of CAM research can show potential mild effects or a need for further research that do not really exist. The prior probability of the modality may not be considered at all.

What is prior probability? It is simply defined as the scientific basis for something. CAM modalities such as Homeopathy, Reiki, Therapeutic Touch and other forms of "energy medicine" have extremely low prior probabilities because they either defy all known principles of physics, chemistry and biology (homeopathy) or are based on "energies" which no one can measure or demonstrate the existence of. Other types of CAM such as herbal medicine may have higher prior probabilities because they actually contain measurable amounts of chemicals that may or may not have an effect. This concept of prior probability is why skeptics say that extraordinary claims require extraoridnary evidence. An idea of how this applies can be gained from an understanding of Bayes theorem, which uses prior probability to evaluate the likelihood that a hypothesis may be true. Bayes theorem can be used in place of p-values (which can be misleading because they may not have a sound theoretical foundation). Kimball Atwood gave an excellent overview of these ideas at the Science-Based Medicine conferece jsut before TAM7 last week. His bibliography is here. This bibliography contains much more detailed discussions of these concepts than I have presented here.

A good understanding of basic statistics and of Bayes Theorem demonstrates why extraordinary evidence is required to prov extraordinary claims. When the plausibility and/or probability of a claim is exceedingly low, weak evidence is not sufficient to prove that it is true or even suficcient to justify spending further resources researching it.

The Placebo Effect in Animals, and Their Owners.

A common reason people give as "proof" that various questionable therapies work is that "animals do not get placebo effects, because they don't know they are supposed to feel better".
This seems to make sense-animals do not "know" that a given treatment is supposed to do something, and I have been known to say this myself in years past. However, there are several reasons why this view may not be accurate.
One reason is conditioned responses, otherwise known as a Pavlovian response. Animals learn to respond in certain ways to actions or treatments. This response becomes automatic or subconscious. Humans are susceptible to conditioned responses just as animals are, and a conditioned response may affect our expectations or the way we perceive a given situation.
It does take time for a conditioned response to develop, but it may happen fairly quickly, sometimes over the course of a few treatments. When combined with effective treatments, regression to the mean and/or the normal healing process, the effect can seem dramatic. We (both owners and veterinarians) have a tendency to think that what we are doing is helpful because we want it to be helpful. This is a normal part of human nature, and is why randomized, blinded and controlled trials have been devised to help eliminate sources of error and bias, and why such trials are considered stronger, more reliable evidence than case reports, anecdotes, and unblinded, uncontrolled trials.
Another thing that has been demonstrated to affect both animals and humans is expectation.
It is not unusual for dogs to be more active and lively even after a simple, quick treatment like a vaccination. The dog has learned that a trip to the vet involves a brief, mildly unpleasant episode, then often a treat or car ride that the dog enjoys. The same expectation on the human owner's or veterinarian's part of improvement can also affect the way we perceive how a treatment is working.
What is the evidence that this expectation on the part of a caregiver can create a "placebo effect" in the caregiver as well as the patient? There have not really been any studies done in the veterinary field, but a some studies of preconceptions held by parents demonstrate how such an expectation may affect how caregivers can be affected by treatments. This report discusses how the common perception that sugar or other foods cause hyperactivity in young children is unfounded, and a recent review shows how parents, teachers and medical personnel can be effected by knowledge and expectation of treatment. I have seen several clients give their pets rescue remedy, a bach flower remedy which is a type of homeopathic remedy to their pets to help with anxiety just before a visit. I have always thought that the remedy seemed to calm the owner down more than the pet, and these reports help to explain why that may be.
A reasonable understanding of these effects on caregivers should instill some humility in any caregiver, and a critical analysis of how effective any treatment is. Unfortunately, such humility and critical analysis seems to be nearly entirely absent in many practitioners of alternative treatments and often in conventional practitioners as well. The difference between the effective treatments that have been developed over the last century or so and ineffective alternatives is testing and analysis by the scientific method. If someone claims that a treatment is not testable by science, or that science cannot detect the effect, that should be a red flag that the claim that the treatment works is bogus.

Spread of bat-variant rabies virus in other species.

I started to hear rumors about rabies virus spreading through the air from clients today. Then I got an e-mail referencing this article from National Geographic today. Apparently the article is the source of the rumors. There are a couple of problems with the article that make it difficult for people unfamiliar with the science involved to interpret.
First, calling this a new rabies virus in the title makes people think that the current outbreak of Rabies in foxes and a few skunks in the Flagstaff area might be something new and different.
The Rabies outbreak in foxes is a bat variant rabies virus that has crossed into other species several times in the last decade in the Flagstaff area. The thing that is different about these outbreaks is that the virus seems to be better at spreading in a new species of animals than bat variants usually are.
Rabies virus has many different genetic variants that are adapted to different species. All of these variants are capable of infecting other species, and basically all mammals are susceptible to infection with rabies. Often, when an animal or human is infected with a variant of rabies from another species, the new host is considered a "dead end" because the disease is fairly rapidly fatal after the virus reaches the central nervous system and the new host may not spread the virus very efficiently. When a host is infected with a variant of rabies that is adapted to that host, it is more likely to spread to another animal. The primary mechanism of spread is by bites or scratches that are exposed to saliva from the infected animal. On rare occasions the virus can spread by oral or nasal inoculation as well. This still requires close contact with the saliva or tissues, especially nervous tissue or salivary glands of an infected animal. There are several different places around the country with different variants of rabies in their respective species.
The CDC publishes annual reports on rabies epidemiology which list the number of animals tested positive for rabies and the human cases along with the variants that caused the disease in humans. This shows that Rabies is a common disease in wild mammals, and it is not unusual for it to be spread from one species to another. It is less usual for the virus to mutate and then spread widely in the new species. Apparently the outbreaks of bat variant rabies in foxes, skunks and bobcats in Northern Arizona over the past decade is the first time that humans have observed the mutation of the virus and its spread in a new species. This has obviously happened many times in the past, hence all the different rabies variants in many different species. It is even possible that bats are the initial reservoir for all rabies viruses and occasional mutations in the virus result in new variants that are better adapted to other species of mammals.
This paper documents the original outbreak of the bat variant rabies in skunks in Flagstaff in 2001. The current outbreak in foxes is also a bat variant, and is probably the same or a similar variant as the previous outbreaks were.
The main problems I have with the National Geographic article are the author's assertion that skunks described in the paper by Leslie, et. al. were spreading the virus "passively" whatever that means. Some people in the Flagstaff area have already interpreted this to mean that rabies is being spread as an airborne virus. It is spreading in a new species, but there is no reason to suspect that the virus is not spreading through bites or very close contact just like Rabies has always spread. The other problem I have is the quote from Barbara Worgess, the head of the Coconino County Health Department that "It shouldn't be able to spread from skunk to skunk."
There is no reason that the virus cannot spread from animal to animal, it is just unusual and does create a concern for the Health Department. Unfortunately Ms Worgess seems to say things like this to the media which make it look like she really does not know what is going on.
Fortunately, this new variant of the Rabies virus can be prevented by the same Rabies vaccinations that have been available for years. The fact that bats are often carriers of Rabies is an excellent reason to keep your pets vaccinations (including cats!) up to date, and the spread of the virus in a new species is a good reason to be cautious in the woods and around any wild animal that is acting sick or agressive. People that have been exposed to Rabid foxes in the Flagstaff area have been effectively treated with standard protocols just like other exposures to other rabies variants. Any time someone has been bitten by a wild animal or exposed to a bat (bat bites can be very hard to identify due to their small size) they should seek medical attention immediately. Rabies antisera and vaccinations do not work once symptoms appear.
The Natonal Geographic article is another example of the media publishing an overly sensational, inaccurate story. No one should panic, but should take sensible precautions.

Homemade and raw pet food diets-NOT safer.

Homemade and raw pet diets have gained in popularity over the last year or two, especially after the boost they gained with the melamine contamination problems in many commercial pet foods.
Raw diets for dogs and cats often use meat and organs from commercial sources and can contain harmful bacteria such as Salmonella, Campylobacter, E. Coli and Klebsiella among others. Some raw diets contain whole bones or large pieces of bone that can break teeth or cause intestinal obstruction.
A paper published last week in JAVMA last week illustrates another potential problem with this type of diet. There are several suppliers of diet mixes that are designed to be mixed with raw or cooked ingredients by the owner and then fed to the pet. Most claim to be complete diets appropiate for feeding to puppies and adult dogs, or kittens and cats.
In this case at least, the diet was profoundly insufficient in minerals and vitamins and nearly killed the puppy. The dog recovered after several months on commercial dog food. Diets should be tested and approved by the Association of American Feed Control Officials (AAFCO). Food with this approval should have the appropriate levels of nutrients for the life stage of the pet you are feeding.
The abstract of the paper is quoted below as it requires a subscription to view;

Diffuse osteopenia and myelopathy in a puppy
fed a diet composed of an organic premix
and raw ground beef
Mark B. Taylor, ma, dvm; David A. Geiger, dvm;
Korinn E. Saker, dvm, phd, dacvn; Martha M. Larson, dvm, ms, dacvr
Case Description—An 8-month-old Shetland Sheepdog was evaluated because of the
sudden onset of signs of neck pain, collapse, and inability to rise. A cursory diet history
indicated that the dog had been fed a raw meat–based diet.
Clinical Findings—Initial evaluation of the dog revealed small physical stature, thin body
condition, and signs of cranial cervical myelopathy. Radiographically, diffuse osteopenia of
all skeletal regions was identified; polyostotic deformities associated with fracture remodeling
were observed in weight-bearing bones, along with an apparent floating dental arcade.
Hypocalcemia and hypophosphatemia were detected via serum biochemical analyses. The
dog’s diet was imbalanced in macronutrients and macrominerals.
Treatment and Outcome—The dog received supportive care and treatment of medical
complications; neurologic abnormalities improved rapidly without intervention. Dietary
changes were implemented during hospitalization, and a long-term feeding regimen was
established. Following discharge from the hospital, exercise restriction was continued at
home. Serial follow-up evaluations, including quantitative bone density measurements, revealed
that dietary changes were effective. After 7 months, the dog was clinically normal.
Clinical Relevance—In the dog of this report, vitamin D–dependent rickets type I and suspected
nutritional secondary hyperparathyroidism developed following intake of a nutritionally incomplete
and unbalanced diet. The raw meat–based, home-prepared diet fed to the dog was not feedtrial
tested for any life stage by the Association of American Feed Control Officials, and its gross
nutrient imbalance induced severe metabolic, orthopedic, and neurologic abnormalities. Inadvertent
malnutrition can be avoided through proper diet assessment and by matching nutrient profiles with
patients’ nutritional needs. (J Am Vet Med Assoc 2009;234:1041–1048)

Another reason not to use the Argument from Antiquity

The Argument from Antiquity is a logical fallacy that is used very commonly in support of various types of alternative medicine. The fact that a particular treatment has been used for hundreds or thousands of years says nothing about the efficacy or safety of that treatment. Treatments used before scientific understanding of biology and medicine were invented by trial and error at best and were often based on profound ignorance or misunderstanding of the processes involved. At the time they were invented, all medicine veterinary or human, was in the same category. Some of the treatments used for many years were dangerous and harmful (bleeding, treatment with toxic heavy metals, etc.). Some treatments are "safe" and cause no toxicity or side effects because they have no effect at all. Some of these treatments may have survived for exactly this reason-they were safer than some treatments simply because they had no effect other than a placebo effect.
A recent paper provides another reason to be skeptical of traditional treatments. In this paper, the authors have developed a mathematical model to show how medical treatments can spread in populations. They included variables for the efficacy of the treatment, conversion and abandonment rates for the treatment, death rate due to the disease, and other variables. When they ran the calculations, they found that ineffective treatments were often more culturally fit than effective treatments. The main reason for this is that an ineffective treatment is often demonstrated more frequently than an effective treatment. This results in a larger number of people adopting the treatment, even if many of them later abandon it. In many cases the recruitment rate was much greater for ineffective treatments and the ineffective treatments had a greater cultural fitness than effective treatments.
This model is very interesting in that it shows how ineffective treatments can develop and persist in a population often better than effective treatments do. This is not earthshaking news to skeptics, and the model does not take into account other factors such as tradition or religious ideas that can also help ineffective treatments to survive. Herbal medicines are one of the most plausible traditional medical treatments, and some traditional herbs have been developed into modern medicines (aspirin is a good example). This model shows why even plausible treatments such as traditional herbs need to be evaluated scientifically before being accepted as an effective treatment. People are likely to favor ineffective treatments. The authors were able to apply their model to both human and veterinary treatments, and even self treatment by non-human primates.

I saw this press release today about genistein, a compound found in soy that has been promoted as a supplement that can prevent and treat cancer. A couple of red flags came up for me in the press release such as this;

The researchers found that a commercially available form of genistein called GCP was effective in killing canine lymphoid cells in a laboratory setting, and that GCP is "bioavailable" in canines - meaning it is absorbed into the bloodstream where it can affect cancer cells in the body. The researchers hope that their findings will lead to the use of GCP for their canine patients in conjunction with traditional cancer treatments like chemotherapy.

This by itself sounds OK, but it does not mean that the concentrations of the compound which killed the cancer cells in vitro are safe or even achievable in dogs or humans. Then comes a claim that humans use genistein as a complementary cancer therapy;

"Humans have been using soy in conjunction with traditional chemotherapy for some time as a chemo potentiator," Suter says. "This means that the GCP makes the chemotherapy work more efficiently and faster, which translates to less stress on the patient and less money spent on chemotherapy."

That is a huge leap from killing cells in a petri dish, and is not substantiated by much evidence. Indeed Genistein is know to have estrogenic effects and may actually make certain types of cancer, especially breast cancer grow more quickly.

Finally the biggest red flag in the entire press release was the last paragraph;

"Since GCP is a dietary supplement, it is harmless to patients," he adds. "Plus it's inexpensive and easy to administer in a pill form. There's really no downside here."

A product such as this is not harmless to patients, and saying so could be dangerous to patients, human or animal, who have estrogen responsive tumors. There most definitely is a downside. They have also not established any toxic effects in living animals or humans of the concentrations required to kill canine lymphoma cells.

The paper this press release is referring to was published in the February 15, 2009 issue of Clinical Cancer Research. This paper is a report of a preliminary study of Genistein that was evaluating it's effect on one specific cell type, and they were unable to achieve high enough concentrations in dogs in a 72-hour dose escalation study. The study showed a potential effect for the compound for certain cancers, but there is still a long way to go before the correct dosage is identified and genestein is proven to be a safe and effective treatment. The author's conclusions were much more modest and reasonable than the press release indicated;

The results of these studies support the notion that canine high-grade B-cell lymphoma may represent a relevant large animal model of human non-Hodgkin's lymphoma to investigate the utility of GCP in chemopreventive and/or treatment strategies that may serve as a prelude to human clinical lymphoma trials.

The press release is misleading and could be dangerous if people read it and decide that this over-the-counter product is completely safe and useful for treating or preventing any type of cancer. This is an excellent example of why dietary supplements should be regulated similarly to drugs, and not declared "harmless".

Hot Chicks

New Americauna chicks to keep our backyard flock going. These will lay green-shelled eggs starting in 6 months or so. They will also keep our grasshoppers and dandelions under control this summer.

What is CAM?

Complementary, Alternative, or Integrative medicine (human or veterinary) is not one particular modality or treatment. There are many treatment methods which fall under these classifications.
Ideally, there is only medicine which has been shown to be effective scientifically, and that which has not. Veterinarians tend to use more treatments that have not been proven effective by well controlled clinical trials than are used in human medicine for a variety of reasons. These reasons include research limitations-there is much less money for veterinary medical research than for human medical research-the wide variety of different species veterinarians treat, and the financial limitations of animal owners. Since veterinary critics of alternative medicine are often criticized for using treatments that are not completely proven while attacking other unproven therapies, I will define complementary, alternative or integrative medicine as treatments that may require drastic changes in what is known about science to even work (improbable or impossible mechanism of action), treatments that may possibly have an effect but have not ever been tested or shown to be effective, and treatments that may have been proven, but are often co-opted by unscrupulous practitioners to either give themselves more credibility or take the treatment and exaggerate or twist it into something which is different than it was.
Of course, there is a wide spectrum of alternative therapies which range from completely ridiculous and improbable treatments such as homeopathy or therapeutic touch, treatments like acupuncture or chiropractic which might possibly have a physiologic effect but have still not been proven, to things like physical therapy, nutrition, exercise and vitamin supplementation that are part of any 'definition of medicine but are often claimed or abused by "alternative" practitioners. Some red flags for unproven therapies can include claims that the effect cannot be measured by scientific methods, large amounts of testimonials and/or anecdotal evidence, appeals to antiquity ("acupuncture has been used for 3000 years") claims that the treatment can only be explained by quantum mechanics, or claims that their treatment is being suppressed by some sort of conspiracy by big pharma and organized medicine.
Some of the people who practice these types of unproven treatments honestly believe that they work, and some are just out to make as much money as possible from gullible patients. In either case, it is unethical for a veterinarian and unfair to our patients to subject them to treatments that probably or definitely do not work. It is equally unethical to charge for such services and to encourage delusions that the pet is benefiting from them. Sometimes such delusions can lead to great harm and unnecessary suffering. Since veterinary patients are not able to choose for themselves, veterinarians have an added responsibility to advocate for their patients and to discourage treatments that are unproven, ineffective and potentially harmful.

Introductory post

When I graduated from veterinary school nearly 20 years ago, there was no "training" in alternative medicine for veterinary students. Very few licensed veterinarians practiced things such as acupuncture, herbal medicine, therapeutic touch or chiropractic. In the time since I graduated, many veterinarians have "integrated" some of these modalities into their practices, with at least the silent acquiescence of their state veterinary boards. This blog is intended to examine alternative practices in veterinary medicine and the evidence (or lack of evidence) for them.
There may be occasional rants and there will be posts on other topics such as vaccinations in veterinary medicine and the sometimes bizarre claims made about them, interesting occurrences in biology, cryptozoology and the conflict between faith and science and evidence.

I hope you enjoy the ride.