Low-level Laser Treatment does not Improve Healing after TPLO Surgery in Dogs

I have been covering the subject of low-level, or “cold” laser treatment for many years. While there is some plausibility to the idea that laser light might have beneficial effects on tissue, very little convincing evidence of actual benefits in real patients. This is not surprising since the majority of good ideas that look promising on paper or in the lab fail to ever turn into safe and effective clinical treatments. Real life is more complicated than the research lab.

There have been very few clinical trials in dogs and cats, and most have had significant methodological limitations, so we can’t have much confidence in their findings. These findings, such as they are, have been mixed, with little consistent or compelling evidence of real-world benefits.

While this doesn’t mean lasers can’t be useful, it does mean that claims made for them by proponents, and the widespread use for many problems in dogs and cats, are based primarily on theory and anecdote, not on reliable research evidence. For something that is promoted as a dramatic breakthrough and is heavily marketed and widely used, it is surprising that it has been so difficult to actually demonstrate the supposedly amazing benefit in controlled research.

Another study has recently been published which follows up on the laboratory research suggesting laser might improve healing of bone and soft-tissue wounds. This is a well-conducted study with a reasonable number of patients, good control for bias and error (randomization, blinding, placebo controls, etc.), and reasonably reliable outcome measures. To steal my own thunder, it doesn’t look very good for laser therapy.

Renwick SM. Renwick AI. Brodbelt DC. et al. Influence of class IV laser therapy on the outcomes of tibial plateau leveling osteotomy in dogs. Veterinary Surgery. 2018: epub before print.

About a hundred dogs undergoing a TPLO (a common orthopedic surgery for cruciate ligament disease) were randomly assigned to receive laser treatments or placebo laser after the procedure. Though it’s not entirely clear if the people conducting the actual treatment were blinded to whether they were giving actual laser or placebo, everyone else (owners, surgeons, staff reading x-rays, etc.) appears to have been. The study used a couple of questionnaires to evaluate owners’ perceptions of comfort, function, and wound healing and had a surgical specialist evaluate the healing of the cut in the bone made as part of the procedure. Overall, none of these outcome measures showed any difference between real and fake laser treatment.

A subset of one questionnaire, looking at gait, did show a statistically significant difference between the treatments. This is not surprising since it is common for at least one outcome measures compared to show a statistical difference between treatments when many things are measured and compared. However, without a consistent pattern of such difference across outcomes, and with the difference in this particular measure being so small it is doubtful that it would be meaningful to the patients in terms of their comfort or function, the study provides pretty strong evidence against any value of laser therapy in these patients.

The authors, not surprisingly, emphasize the one small difference seen and suggest this might provide at least “mild clinical justification” for using lasers in patients undergoing TPLO. Personally, I think it is more reasonable to view the difference as a statistical fluke and to emphasize the failure to find any benefit in all the other measures evaluated, as well as the failure to show strong results in other clinical trials. Of course, there are many different techniques for using laser therapy, and proponents can always claim any single negative study is only negative because the technique used wasn’t quite right. This is the kind of “Yes, but….” Argument that supports the use of a lot of therapies even when clinical trial results consistently fail to find benefits. It is a reasonable argument up to a point, but eventually the failure to find positive effects does begin to suggest that there are none to find.

Absence of evidence can be evidence of absence once we’ve tried hard enough and long enough to find support for a scientific hypothesis. I don’t think we have reached that point yet with cold laser, and I do think more research is justified. However, it would be worthwhile for veterinarians and animal owners to be mindful that all the time and money being spent on laser treatment has so far not been proven worth it by good research, and in fact the balance of the evidence is not that encouraging.

 

Posted in Science-Based Veterinary Medicine | 22 Comments

Lysine for Feline Herpesvirus: A Therapeutic Zombie

Introduction
Science is a process for developing and refining our understanding of nature over time. The work of a community of scientists, often with vigorous competition and conflict between individuals, gradually improves the accuracy of our understanding. Perfect comprehension of something as complex as the health of living organisms seems unachievable, but little by little we get better at knowing how nature works and how we can influence natural phenomena. This progress often involves realizing that some aspects of our current understanding are actually wrong, and that our strategies for manipulating nature based on this flawed knowledge may turn out not to be effective.

In medicine, this process creates a kind of life cycle for medical interventions. The popular conception of this life cycle is the story of effective treatments. An insight or accident leads to a hypothesis, which is tested at various levels from in vitro to animal model to clinical use, and ultimately we validate the hypothesis and conquer the original problem.

Unfortunately, this is the exception rather than the rule. Far more often, the life cycle of medical therapies involves an insight or accident leading to a hypothesis which early, flawed evidence appears to support but which ultimately turns out to be wrong. This is a well-established phenomenon of the clinical trial literature, often called the Decline Effect or the Proteus Effect.1-2

Treatments based on such hypotheses are eventually abandoned in most cases, though some prove quite tenacious. Anecdote and personal experience frequently lend ineffective interventions a prolonged post-mortem existence, therapeutic zombies that stagger on long after the scientific evidence should have put them to rest. A great example of the life-cycle of an ineffective treatment is the use of L-lysine for the prevention and management of feline herpesvirus (FHV-1).

Herpesvirus & Lysine: The Scientific Evidence
Early in vitro work on human herpesvirus (HHV-1) suggesting lysine might inhibit replication and could potentially have clinical utility first appeared in the mid 1960s.3 This was followed by the first clinical studies of lysine for HHV-1 about ten years later.4 By the 1980s, the literature on lysine and HHV was glowing, and it seemed a safe and effective therapy had been found.5

Veterinary medicine caught the coattails of this process in the 1990s, with the first published in vitro study of lysine for FHV-1 appearing in 1995.6 Clinical studies followed in the early 2000s, and lysine quickly became a widely available supplement used for FHV-1 management.7

However, the scientific process rolled on, and despite the enthusiasm of clinicians and researchers, cracks in the lysine narrative soon appeared. Limitations and potential sources of bias in the early literature were addressed in subsequent studies, and the apparent benefits melted away. The most recent reviews in human medicine have concluded that there is no reliable evidence to support the use of lysine for herpesvirus management, and it is not included in current treatment guidelines.8-10 Lysine supplements are still available and marketed for this use, of course, because patients and some clinicians cling to their belief in the efficacy of this treatment despite the evidence, based predominantly on anecdotal experience. That patients do this is understandable, but it is always disappointing to see clinicians choose anecdote over science when they have the training to know better.

The story has played out in a similar way in veterinary medicine, with the usual time lag. The initial theoretical rationale for use of lysine, for example, has not held up to subsequent study. According to the theory, lysine should antagonize arginine and reduce the level of this amino acid. This, in turn, should inhibit FHV-1 replication and reduce clinical symptoms and viral shedding. However, research in cats has failed to validate any of the steps in this chain of reasoning. Oral lysine does not appear to antagonize or reduce intracellular levels of arginine, and it does not seem to inhibit FHV-1 replication under normal physiologic conditions.7

A similar fate has befallen the initial claims for clinical effects of lysine Early studies, with small numbers of patients and methodological limitations, produced some positive results which could not be reproduced in larger, better-controlled research.7

The most recent comprehensive reviews of the evidence for lysine in FHV-1 patients are not encouraging.7,11 The more optimistic of the two states that “there is considerable variability” it the research results and that while “data from these studies suggest that lysine is safe when orally administered to cats and, provided that it is administered as a bolus, may reduce viral shedding in latently infected cats…the stress of bolus administration in shelter situations may well negate its effects and data do not support dietary supplementation.”11

A comprehensive systematic review of the subject by Bol and Bannik (2015) is considerably more blunt, systematically rejecting every aspect of the rationale for lysine use:

There is no evidence for lysine-arginine antagonism in the cat.

Lysine supplementation does not have an inhibitory effect on FHV-1 replication in the cat.

The claim that lysine supplementation is effective for the prevention or treatment of herpetic lesions in humans cannot be supported by scientific evidence.

Lysine supplementation is not effective to prevent cats from becoming infected with

FHV-1, it does not decrease the chance of developing clinical signs related to active FHV-1 infection, and it does not have a positive effect on the clinical course of its disease manifestations.

Based on the complete lack of scientific evidence for the efficacy of lysine supplementation, we recommend an immediate stop of lysine supplementation for cats.

The accumulation of evidence against the use of lysine for FHV-1 cases has had an impact. Some shelter medicine specialists, for example, now recommend against this practice.12-13 However, there has also been resistance to abandoning this treatment despite the evidence. Unfortunately, such resistance has not been based so much on any substantive dispute about the science but instead on the seductive power of anecdotal evidence.

When the review by Bol and Bannik (2015) was reported in Veterinary Practice News, for example, objections from some respected veterinarians explicitly cited anecdotal experience as a reason for continuing the use of lysine:14

Anecdotal evidence should not be discarded…I have clients who tell me that every time they take the cat off lysine the problem returns…Maybe it’s just as well to leave those cats on lysine if the clients genuinely feel that it’s making a difference.

[Lysine] is used frequently by many of my clients at the recommendation of Dr. Google…Some cats have a very convincing response in spite of what the science says…Its use should be based on response, whether scientific or not.

Science is, by nature, a competitive community process. Disagreement between individuals is healthy and an integral part of this process, spurring replication of research that helps compensate for the inevitable blind spots and biases we all suffer from. However, the explicit preference for anecdote over controlled research evidence is counterproductive and lends itself to the retention of treatments that do not truly help our patients and which deserve to be abandoned.

There is some limited evidence suggesting lysine could actually exacerbate FHV-1 symptoms, which would certainly make abandoning it the right choice.7 Even if it is completely harmless, however, wasting resources on treatment that has been through the scientific vetting process over 50 years and has still failed to show convincing evidence of benefits is not justified.

As I argued last month, evidence-based medicine is a necessary pillar of effective and ethical clinical practice. This means we must be willing to acknowledge our limitations and set aside anecdotal evidence, even our own, when appropriate research evidence indicates we are mistaken.

References

  1. Lehrer J. The truth wears off: Is there something wrong with the scientific method. The New Yorker. 2010. pp. 52-7.
  2. Alahdab F. Farah W. Almasri J. et al. Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study. Mayo Clin Proc. 2017. Epub before print. Available at: http://www.mayoclinicproceedings.org/article/S0025-6196(17)30836-4/pdf Accessed February 21, 2018.
  3. Tankersley Jr RW. Amino acid requirements of herpes simplex virus in human cells. J Bacteriol. 1964;87:609–13.
  4. Griffith RS, Norins AL, Kagan C. A multicentered study of lysine therapy in Herpes simplex infection. Dermatologica. 1978;156(5):257–67.
  5. Griffith RS. Walsh DE. Myrmen KH. Et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica.1987;175(4):183-90.
  6. Collins BK. Nasisse MP. Moore CP. In vitro efficacy of L-lysine against feline herpesvirus type-1. Proc 26th Ann Meeting Amer Col Vet Opthalmologists. Newport, RI. 1995;141.
  7. Bol S. Bunnik EM. Lysine supplementation is not effective for the prevention or treatment of feline herpesvirus 1 infection in cats: a systematic review. BMC Vet Res. 2015:11:284.
  8. Chi CC. Wang SH. Delamere FM. et al. Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database of Systematic Reviews.2015;8. Art. No.: CD010095.
  9. Mailoo VJ. Rampes. S. Lysine for herpes simplex prophylaxis. Integrative Medicine. 2017;16(3):42-46.
  10. WHO Guidelines for the Treatment of Genital Herpes Simplex Virus. Geneva: World Health Organization; 2016. Available from: https://www.ncbi.nlm.nih.gov/books/NBK396232/
  11. Thomasy SM, Maggs DJ. A review of antiviral drugs and other compounds with activity against feline herpesvirus-1. Vet Opthalmology. 2016;19(Suppl 1):119-130.
  12. UC Davis Koret Shelter Medicine Program. Feline upper respiratory infection aka URI. 2015. Available at: https://www.sheltermedicine.com/library/resources/?utf8=%E2%9C%93&search%5Bslug%5D=feline-upper-respiratory-infection-aka-uri Accessed February 21, 2018.
  13. Slater M. Interpreting research (and making it work for you): Is lysine a good investment for shelters wanting to prevent URI in cats? Available at: https://www.aspcapro.org/blog/2017/05/03/interpreting-research-and-making-it-work-you-lysine-good-investment-shelters-wanting Access February 21, 2018.
  14. Niedziela K. Researchers question lysine use in FHV cases. Vet Pract News. 2016;28(1):36-7.

 

Posted in Herbs and Supplements | 9 Comments

Ethics and Evidence-based Medicine

The relationship between evidence-based medicine (EBM) and ethics may not be immediately apparent. EBM focuses on facts and data, safety and efficacy, and determining what we know and don’t know. Veterinary ethics is about what is right or wrong to do in the context of veterinary practice. The values that inform ethical principles are subjective and not always shared between individuals or different segments of the profession. The evidence used to evaluate the safety and efficacy of medical treatments, in contrast, should ideally be produced by methods broadly agreed to be the most objective and reliable possible. However, EBM turns out to be a key tool for achieving ethical clinical practice.

Despite inevitable controversy and disagreement, there are some ethical principles broadly accepted by most veterinarians. Some of these are articulated in statements such as the American Veterinary Medical Association’s Principles of Veterinary Medical Ethics.1 This document was adapted from the principles established for physicians by the American Medical Association, and similar statements have been adopted by veterinary associations around the world.2-6

Other widely accepted ethical standards are simply common elements of more basic cultural norms. For example, most of us would likely agree that we should try to help our patients and our clients, we should be honest with clients, and we should do our best to be technically competent and familiar with the current scientific knowledge that underlie clinical medicine.

These basic ethical precepts are formalized in the domain of medical ethics as several core principles, which usually include:

Beneficence–  Clinicians should attempt to help their patients, to benefit them.7

Non-maleficence– Clinicians should attempt to avoid harming their patients or to do more good than harm.7

Autonomy– Patients (or in veterinary medicine, their owners) have the right to accept or reject treatment. This is the foundation for the more specific concept of informed consent.7

Informed Consent– Clients have the right to make choices about the treatment of their animals based on accurate, relevant information they can understand.8

So what does EBM have to do with meeting these ethical obligations? Well, ethical judgements cannot be made without facts. The best path to abide by one’s ethical principles cannot be determined without an accurate understanding of the context. EBM informs ethical practice by giving us, and our clients, an accurate understanding of the risks and benefits of our actions as well as the degree of uncertainty about these.

In terms of beneficence and non-maleficence, for example, one cannot successfully help patients and minimize harm without an accurate understanding of the causes of disease and the effects of our treatments. If we attribute illness to the wrong cause, we are unlikely to stumble across an effective remedy. And if our treatments don’t actually work, or if they have risks that we are not aware of, then we are less able to do good and avoid harm to our patients.

Similarly, we deny clients their right to informed consent if we give them incorrect information about diagnosis, prognosis or the likely outcome of our treatments. This is equally true whether we are deliberately lying or are simply mistaken. The history of medicine is a long, frightening tale of incorrect beliefs about disease and of ineffective, even harmful treatments enthusiastically applied by well-meaning doctors. We are no smarter or better intentioned than our predecessors, but thanks to science, we are better informed.

Evidence-based medicine, then, is arguably a necessary component to ethical veterinary practice. It serves to provide clinicians with the most current and accurate understanding of the causes of disease and the risks and benefits of our therapies. EBM also helps us quantify the inevitable uncertainties we must accept and communicate to our clients.

There is rarely optimal evidence, so the most conscientious practitioner of EBM will often not be able to accurately predict the outcome of his or her treatments. However, even in this situation, EBM is useful because it supports truly informed consent. If the evidence supporting a particular therapy is weak, I may well still offer that therapy. However, I am able, even obligated, to understand the limitations of the evidence and share this with the client to help support informed decision making.8

There is often anxiety among veterinarians about disclosing uncertainty to clients. We fear they may not trust in our competence or may eschew beneficial treatment if we express any uncertainty or discuss the limitations of our knowledge. However, there is evidence that may allay this anxiety. Surveys have shown that clients expect to be told about the uncertainty associated with our recommendations and that they do not lose confidence in us as a result.9 Even more significant from an ethical perspective, clients in one study emphasized that their central expectation for the information they were given by their veterinarians was that it be the truth.10 EBM helps us meet the ethical obligation and client expectation that we communicate truthfully about our recommendations and our uncertainty.

So far, this idea that EBM can facilitate ethical veterinary practice by giving us the most accurate information and helping us measure our uncertainty may not seem especially controversial. Unfortunately, if we commit to EBM as the best source of information to support effective and ethical medicine, we eventually enter more tendentious territory.

For example, EBM includes the presumption that some sources of evidence are more reliable than others.11-12 This often leads to a conflict between what we believe, based on anecdote or personal experience, and what scientific evidence supports. Clinicians dislike being told that therapies which seem and effective in use are either scientifically unproven or have significant evidence against their safety or effectiveness. Yet our obligation to be informed and competent, and to provide accurate and truthful information to clients, can sometimes mean accepting the unreliability of anecdotal experiences, even our own.

An even more contentious topic is the ethical appropriateness of theoretical systems and treatment methods with core principles that conflict with established science. Much of what is often called alternative medicine consists of beliefs about the causes of illness and methods of treatment that are either scientifically unproven or even demonstrably incorrect based on research evidence.13-14 Alternative medicine raises many complex ethical issues,15 and it has been argued, in both human and veterinary medicine, that the use and sale of such approaches, however honest and well-intentioned, violate some broadly held ethical principles.14-19

Informed consent and autonomy are denied when clients are given information about their animals’ health that is inaccurate by the best available standards of evidence and scientific consensus. Beneficence and nonmaleficence cannot be maintained if ineffective treatments are offered.16

Often of course, there are legitimate disagreements about the meaning or strength of the evidence. However, there must be some generally accepted standard of proof required beyond simply the personal belief of the individual clinician to justify our treatments. If not, then there is no purpose to the systems of licensing and regulation intended to protect the public from unsafe and useless medical treatment. The caveat emptor free-for-all of medicine in the 18th and 19th centuries was ultimately rejected in the 20th as unsafe, and this was predicated on the belief that scientific evidence could provide a common basis for evaluating medical practice. This is a key pillar of the ethical structure of modern medicine, and EBM is an important tool for supporting ethical, science-based practice.

References

  1. AVMA Principles of Veterinary Medical Ethics. Available at: https://www.avma.org/KB/Policies/Pages/Principles-of-Veterinary-Medical-Ethics-of-the-AVMA.aspx Accessed January 31, 2018.
  2. AMA Principles of Medical Ethics. Available at: https://www.ama-assn.org/delivering-care/ama-principles-medical-ethics Accessed Access on January 31, 2018.
  3. CVMA. Principles of Veterinary Medical Ethics. Available at: https://www.canadianveterinarians.net/documents/principles-of-veterinary-medical-ethics-of-the-cvma Accessed January, 31, 2018.
  4. FVE. European Veterinary Code of Conduct. Available at: http://www.colvetalbacete.es/images/contenidos/cecv.pdf Accessed on January 31, 2018.
  5. AVA. Code of Professional Conduct. Available at: http://www.ava.com.au/conduct Accessed January 31, 2018.

6.Veterinary Council of India. Code of Ethics. Available at: http://www.tnsvc.org/forms/codeethics.pdf Accessed January 31, 2018.

7.Beauchamp TL. Childress JF. Principles of biomedical ethics. 5th Ed. (2001) New York, NY: Oxford University Press.

  1. Fettman MJ. Rollin BE. Modern elements of informed consent for general veterinary practitioners. J Amer Anim Hosp Assoc. 2002;221(10):1386-1393.
  2. Mellanby RJ. Crisp J. De Palma G. et al. Perceptions of veterinarians and clients to expressions of clinical uncertainty. J Small Anim Pract. 2007;48(1):26-31.

 

  1. Stoewen DL. Coe JB. MacMartin C. et al. Qualitative study of the information expectations of clients accessing oncology care at a tertiary referral center for dogs with life-limiting cancer. J Amer Vet Med Assoc. 2014;245(7):773-83.
  2. McKenzie B. A new perspective on evidence-based medicine. Vet Pract News. July, 2017. Available at: https://www.veterinarypracticenews.com/a-new-perspective-on-evidence-based-medicine/ Accessed January 31, 2018.
  3. Cockroft, P. Holmes, M. (2003). Handbook of Evidence-Based Veterinary Medicine. Oxford: Blackwell.
  4. McKenzie, BA. Is complementary and alternative medicine compatible with evidence-based medicine? J Amer Vet Med Assoc. 2012;241(4):421-6.
  5. Ramey, DW. Rollin, BE. (2004). Complementary and Alternative Veterinary Medicine Considered. Ames: Iowa State Press.
  6. Nuffield Council on Bioethics. Complementary medicine: ethics. 2014. Available at: http://nuffieldbioethics.org/wp-content/uploads/Complementary_medicine_FINAL_FL_paper-1.pdf Accessed January 31, 2018
  7. Smith K. Against homeopathy-A utilitarian perspective.Bioethics2012;26(8):398–409.

 

  1. Ernst E. Cohen MH. Stone J. Ethical problems arising in evidence based complementary and alternative medicine. J Med Ethics. 2004;30:156-9.

 

  1. Milstein M. The case against alternative medicine. Can Vet J. 2000;41:769-72.

 

  1. Macdonald C. Gavura S. Alternative medicine and the ethics of commerce. Bioethics, 30: 77–84.

 

Posted in General | 7 Comments

Veterinary Practice News Evidence-based Medicine Column

Last summer, I was asked to take over the Evidence-based Medicine Column (previous the Alternative Medicine Column) in the trade magazine Veterinary Practice News from Dr. Narda Robinson. This was an excellent opportunity to  illustrate the principles and techniques of evidence-based medicine in action, evaluating specific medical practices and discussing general issues related to EBM. Some of these columns will cover alternative therapies, but many focus on conventional medical therapies as well, since I have always advocated evaluating all therapies by the same, science-based standards. I will keep a running collection of links to these columns here as each becomes available to the public, as well as occasionally posting those with content that hasn’t appeared here before. Enjoy!

A new perspective on evidence-based medicine
July 27, 2017

Cannabis-based remedies lack reliable clinical evidence for veterinary use
August 9, 2017

Pros, cons of surgical sterilization, neutering options for females
September 14, 2017

Surgical sterilization, neutering options for male cats, dogs
November 21, 2017

Yunnan baiyao for patients with hemorrhage, neoplasia
December 11, 2017

Probiotics and today’s pets
January 10, 2018

Why do we run diagnostic tests?
February 7, 2018

Pheromones’ therapeutic use in animals
March 14, 2018

Evidence-based Medicine is Key in Achieving Ethical Clinical Practice
April 17, 2018

Lysine: A therapeutic zombie?
May 16, 2018

Is tramadol an effective analgesic for dogs and cats?
June 26, 2018

What is a placebo?
July 10, 2018

Uses, evidence, and safety for laser therapy.
August 16, 2018

Assessing claims of vaccine-induced ITP, IMHA
August 29, 2018

Is cancer increasing in dogs and cats?
October 2, 2018

Responses to the virtual mailbag
November, 2018

What is screening and is it beneficial?
December, 2018

Debating raw diets
January 2, 2019

Is there a gold-standard test for adverse food reactions?
February 14, 2019

Is banning “artificial” ingredients based on fear or science?
March 1, 2019

Asymptomatic Bacteriuria- To Treat or Not to Treat?
March 28, 2019

The Veterinary Antivaccine Movement
May 22, 2019

Vegan and Vegetarian Diets for Dogs and Cats
June 24, 2019

A Conclusion on Cannabis?
July 30, 2019

Canned or Dry Food: What’s Better for Cats?
August 22, 2019

Debating Raw Diets
September 9, 2019

Healing with Acupuncture
October 8, 2019

The efficacy of metronidazole
November 1, 2019

Veterinary Homeopathy: Why Are We Still Talking About This?
November 22, 2019

Do pulsed electromagnetic field devices offer any benefit?
January 2, 2020

Is Keto Kind to Pets?
January 28, 2020

Are ACE inhibitors effective in treating heart disease?
February 26, 2020

The efficacy of metronidazole.
March 2, 2020

Early or delayed neutering? What to tell clients
March 27, 2020

From the Trenches: How life has changed since COVID-19
April 23, 2020

Fecal Microbiome Testing
May 7, 2020

What Conditions Might Benefit from Platelet-Rich Plasma Treatment?
May 31, 2020

A closer look at popular pet food myths… and why they are just that
June 2, 2020

Is glucosamine effective for treating osteoarthritis?
July 27, 2020

Acupuncture—A sticking point among veterinary professionals
September 10, 2020

New tools to help make evidence-based clinical decisions
September 16, 2020

Conflicts of interest in narrative reviews can be especially problematic (Diet-associated heart disease in dogs)
September 29, 2020

COVID pandemic exposes science denial—even in veterinary medicine
October 29, 2020

Veterinary chiropractic: A Friend or Foe to Your Patients? (VPN+)
November 18, 2020

Neutering: The risks and benefits in the context of breed, sex, and age.
December 29, 2020

Should veterinarians adhere to scientific standards for acceptable practice?
February 11, 2021

Cannabis products continue to rise in popularity, but is there proof they work?
March 9, 2021

Where does gabapentin fit in pain control?
April 13, 2021

Pre-anesthetic fasting: What’s the right number?
May 11,2021

Vaccine questions and resistance
June 2, 2021

Current Lifespan Patterns in Dogs (.pdf)
June 3, 2021

The Process of Aging
August 6, 2021

Tummy troubles: Empirical treatment of acute vomiting
September 20, 2021

How do Fresh Food Diets Compare to their Commercial Cousins?
November 4, 2021

Why research can be so satisfying.
November 16, 2021

Risks and Treatments Surrounding Cancer
December 3, 2021

What does the evidence say about feline fitness and dog aerobics?
February 1, 2022

Genes, environment, and DNA sequence.
February 8, 2022

Revisiting the world of canine raw diets
March 1, 2022

When in doubt, cut it out! But by how much?
April 13, 2022

Learn the Truth about Carbs and Cats
May 26, 2022

Does Music have a Calming Effect on Pets?
June 28, 2022

Posted in Presentations, Lectures, Publications & Interviews | 10 Comments

SkeptVet Gets Hate Mail 2018

It will come as no surprise to readers that I receive a steady stream of hate mail in the form of email and comments on the blog. Occasionally, someone calls me up at work, sends me a snailmail letter, but the vast majority of the negative comments I get are anonymous through the internet. In contrast, the positive comments I get, which are often accompanied by the name of the reader or given to me directly in person. Something about the anonymity internet frees people to say the darkest things in their heart without the usual social restraints that prevent us from being shitty to one another. (Before anyone cries “hypocrite” let me point out once again that this blog is not anonymous. My identity and credentials are easily found here and online, and I take ownership of the blog openly in my public lectures. I choose not to make myself the center of attention here, since I think the ideas and evidence should be the focus, but I am not hiding behind any serious attempt at anonymity).

I don’t, of course, allow people to post abusive comments directly on the site. Civil and substantive disagreement is welcome, but I am under no obligation to give people a platform to rant or abuse me or my profession. However, I do periodically review the best of my hate mail for several reasons. On one level, it is instructive to see the patterns in how people respond to my critiques of unproven or quack therapies. These comments give an insight into how people think and why they are attached to these kinds of treatments, which is useful for anyone trying to oppose pseudoscience.

It is also worthwhile to point out that advocates of the practices I challenge are hardly peaceful, saintly individuals minding their own business when vicious skeptics like myself come along to attack them. As I’ve discussed in detail before. Alternative therapies are marketed primarily by attacking the safety and efficacy of science-based medicine and the motives of mainstream doctors. Skeptics such as myself are responding to the assault of pseudoscience on scientific medicine, we are hardly the instigators of conflict. And apart from the occasional slip into sarcasm, most of my critique is aimed at claims and arguments and based on reason and evidence. I am far more likely to be the subject of vicious personal attacks than the perpetrator.

Finally, I have to admit that much of the angry feedback I get is amusing in its own right. Just as Jimmy Kimmel turns his hate mail into comedy I enjoy a chuckle over some of the outrageous things people say to me from the safety of their keyboards.

Some of the trends in the negative comments I get are obvious. There is a constant drumbeat of paranoia and conspiracy theorizing, blaming “Big Pharma” and the greed and immorality of mainstream medicine for all sorts of horrors which supposedly justify quack alternatives. There is the deep distrust of government and regulators, scientists and intellectuals, and anyone who makes a living in medicine except alternative medicine practitioners, supplement companies, and others who profit from “alternative medicine.”

There is also an obvious but rage in many of these comments that is harder to understand. Apart from a few individuals I have written about directly, the majority of those who write furious, hateful comments have no particular reason to be taking what I say here so personally. My blog doesn’t come into people’s living rooms or business. They have to search the internet, find the blog, and choose to read it. If they disagree, they are free to ignore me with no harm done. But even those who shout “No one cares what you think!!!” clearly do care enough to spend time writing angry comments (though they clearly don’t take much time to proofread these comments). I still find that puzzling.

Lastly, I have to point out that not once have any of these folks I’m quoting ever presented a piece of scientific research evidence to support their objections or challenge my claims. Plenty of commenters say “I don’t care what you/science/anyone says, I’ve seen XX work for myself.” None, however, have backed up their anger with anything other than anecdote or argument from authority.

Here are my previous hate mail collections:
Hate Mail 2011

Hate Mail 2015

I have organized the selections below into broad, loosely defined categories, and I will occasionally insert comments like so: [SV: Xxxx] Enjoy!

 

Being Nice?
[SV: Some commenters don’t seem to appreciate the strange and humorous inconsistency in tone when they simultaneously chastise me and wish me well. Perhaps they recognize that they are being much harsher than would ever be acceptable in person and are trying to soften the message, or maybe just make themselves look like they are taking the ”high road?”]

You are such a rabid skeptic and that keeps you from some great things in life. By the way, the crap works- do more research on it- ask a client if they want to try it- One that has NOTHING to lose and see. Hope your life gets better and you quit being so negative. Wishing you the best.

You are clearly uneducated…Bless you though.

After reading a few articles on this page, I come to the conclusion that it is not necessary to read the other’s content, as anything and everything mention here the author is clearly AGAINST. Its a bit pitiful, I think to be SO sceptical, how can you enjoy life at all.

i can feel the intense negative emotion you are feeling toward Dr. Plechner and other doctors that don’t follow the herd. I am sorry you are festering in this emotion. Does it upset you to think of all the success stories?

are just a Big Pharma shill. That’s OK. Everyone has the right to protect their interests. I wish you luck in your endeavor to frighten people away from innexpensive therapies which might save their termial pets’ lives. If it makes you happy, I wish that for you sincerely.

your ignorance and pride is a disgusting excuse for lack of wisdom. You obviously must be carrying a lot of disease in your own body and soul. Bless your heart, poor thing. Hope you get well soon.

You sound like a pompous ass. ..I don’t think anyone stands a chance of turning on a light for you at all. Just had to express my irritation on wasting my time trying to find an unbiased opinion from your site. Good luck with your journey on the narrow path you travel.

Hahahahahahahahahaha. You think that you’re enlightened, hahaha, you’re not, you’re nescient at best and ignorant at worst. Enjoy your pontificating though.


IN MY HUMBLE OPINION, YOU ARE PURE EVIL, MAKING MONEY OFF YOUR BLOG’S, AND SCREWING OVER THOUSANDS OF DOGS AND CATS, AND OTHER CREATURES, WITHOUT A SINGLE PIECE OF EVIDENCE SUPPORTING YOUR CLAIMS IT DOESN’T WORK ANY BETTER THAN A PLACEBO,..

I hope that GOD FORGIVES YOU for YOUR NONSENSE, MISLEADING PEOPLE, CAUSING THEM TO END UP GIVING UP, WITHOUT TAKING A MINOR CHANCE ON GIVING THEIR LOVED ONE’S A DAMN CHANCE AT LIVING LONGER!!!

IMHO, YOU CAME STRAIGHT OUT OF HELL!

AGAIN, THIS IS STRICTLY MY OPINION,…

 

The Shill/Evil Industry Conspiracy Tactic
[SV: This is, by far, the most common objection raised. The idea that someone could honestly disagree with their beliefs after careful, open-minded evaluation of the arguments and evidence is apparently inconceivable for these people. They accuse me or arrogance freely yet imagine that any belief other than theirs is willful ignorance or deliberate dishonesty. Irony meter broken!]

FDA are the real killers of USA that only approve side effect medications to cause more problems in your body. I agree with Alex Corp. FDA stands For Death Administration and that to the point. FDA should be banned from the whole of USA. They just as corrupt as the Government!!!

You are correct about herbalist? Seriously? They why are so many being killed off? Around 100 within a year as of May of 2016. Read about it already. I guess it is because what they practice and treat never works?????

Homeopathy has worked for me many times in treating both my family and our pets. It is safe, effective, and inexpensive if you choose the right remedy. It is so diluted that there is almost nothing left of the original substance in the remedy. Those who don’t want to use it don’t have to, but those of us who recognize how miraculously effective it is have the right to continue to buy it easily, cheaply, and over the counter. It’s just the exorbitant pharma companies who want to rub out their much more effective competition.

The only reason I don’t follow up on this is I’m afraid the FDA will get a hold of these and find out how well they work and shut them down! As a typical bumbling corrupt (Paid off by the pharmasudical industry) government agency should!

If I want to live long and healthy I almost always do the exact opposite of what the government, media and scientific communities tell me to do.
Seriously. Yeah.
Big pharma underwrites the nation’s medical schools.

It’s a shame you and so many other conventional veterinarian’s are brainwashed by Big Pharma, The Big Pet Food companies, the FDA, the USDA, the CDC, and the media!!.. WAKE UP from your brainwashed, sheeple coma and gain some knowledge before writing an article you know nothing about!

But you must get paid well by druggies as I call the big pharm guys.
This is not funny, this is criminal brain washing of the gullible for the purpose of gazillions made on ignorance of the many. Good job.

This blog is paid for by drug companies either directly or indirectly. Any time you see the word “Skeptic” you know the website is written by paid liars and shills for the drug cartels.

I remarked to my wife when I ordered tha stuff that if it actually worked it would would either disappear from the market or sales forbidden. Why, you might ask?

There are two obvious reasons :- first, if it worked, if would deprive doctors, nut press, opticians and a whole host of other of MONEY. The entire medical profession is a giant hamster wheel. If CURES were actually found for things like cancer ‘flu, and a whole host of other diseases, it would throw millions of people out of their jobs. Just think about it. Learned professors spouting the bullshit that the Govt tells then to, doctors, nurses, drug companies, high street pharmacies. We can’t have that now can we?

You have to be a guy paid by pharmaceuticals to bash these people and their products. What are you afraid of? That millions will stop taking your drugs with mike long lists of side effects? Lots of money at stake right?  I say go f yourself! Clinical studies you want? Are you really satisfied with the non transparency of clinical studies used to validate the safety of the pharmaceuticals prescribed by docs like candy? I am not! You know why? Because there is no money in telling the truth! The money is in misinformation!

So I tell you what! Your bitch ass should go to your doc and refill your script for statins, psycho drugs and dick hardeners and let those who want to take bogus supplements do so!

Please help me understand why you would write such a horrible article. Do the vets and pharmaceutical companies just want to make more $ at the expense of our best friends?… I’m really disgusted by your article. Your thoughts?

Most vets are against Raw feeding because they have been brain washed by Big Business in their training to sell bags of dried ‘food’ to pets (to make money on) instead of proper food.

I think Skeptvet ought to change his handle to PhillipMorrisVet or perhaps ExxonMobilVet.

Mainstream vets are like mainstream vets under the FDA – they discourage you from the truth about products that work and encourage you to the harmful drugs that keep them in business.
Stick with your chemicals and I’ll stick with my natural plants that God created, not man. Don’t give a hoot about clinical trials or what the FDA says because none of you want a cure for cancer cuz there’s too much money to be made.

This person is obviously blinded by the pro big med drugs training/our system ( anti biotics are big biz people)… This article is a blatant lie and so, so, so many people have gotten fabulous results with this supplement, but what’s the problem – no kick backs from the med company for you?

Who is getting paid by the pharmaceutical companies to do fear mongoring ah??? that would be you. You are an uninformed moron who has NO experience what so EVER in what you talk about! what a joke! go do something useful that would really help the animals!!! there’s a thought! but no too busy getting paid off arnt you…


Vaccines CAUSE allergies. You are nothing but a pHARMa shill.

some vets are upset because this product works better than their surgery attempts and they are bitter enough to call the FDA to stop the production and sale of this lifesaving product dooming thousands of pets to an agonizing death! The FDA and Big Pharma are in bed with each other and totally corrupt!

Big Pharma, and their lackeys like skepvet like to use clinical trials as a bludgeon for their own distortions. If you are not pimping one of their patented drugs they will tell you [ypur evidence isn’t good enough].

What a nasty article full of menace and lies… It is only the studies of the articles and videos of vets like the one you are battering unjustly, that I realize how the crooked pharma and commercial petfood industry lies to us, owners, making our pets sick while earning more by ‘treating’ them even sicker medicine, creating thus a viscious circle, making us feel dependent on them.

 

Simplicity and Creative Writing
[SV: Some commentators go straight for the simple, direct approach without a lot of complex thinking or argument. Others engage in a bit of creative writing at my expense.]

You know SkypeVet , you have to be connected to the world of Big Pharma and anything natural is beyond your way of thinking ..

I’ve read your negitive articles for a very long time now. I hope ppl see you for what you really are… Your a complete joke !

All pets under your care will suffer because of your ignorance and arrogance. You should have studied accounting.

Who so ever is the author of the article is an ass of the highest order.

Get lost loser

Who ever wrote this information on this website is an idiot.

Skepvet here is just a dinosaur coughing up a death rattle.

I find you a worthless drug pusher…and you need to seek another profession,


You slam all who disagree with you, are you related to Donald Trump?

I have seen miracles at Dr. Plechner’s hands, so take your contempt and put it where the sun don’t shine.

Skeptvet is a moron.

I found your comments/post/whatever to be obnoxiously close to exactly what I’d expect to hear from another incompetent, undereducated, but still egomaniacal, “old school” veterinarian

Ur ignorant idiot

skepvet is a quack…Skepvet is a shill for Big Pharma,

Skeptvet. You are a complete moron… Shut down and shut up. The people have spoken.

Your a fear mongering putz!

Arsehole! arsehole arsehole

To be honest you sound like a frustrated raving idiot… Your qustions are a rant of arrogance and self importance. See ya. Wouldn’t want to be ya.

If your practice was worth a crap you wouldn’t have time to babble on here

What a load of old rubbish.

You are full of shit.

You are all ignorant idiots.,,The traditional medical system and vets are crooks and under trained and under exposed. Shame on you

One should remind you that anyone with an Average IQ can Discern that you are What you are Complaining about, and that Morally, if not Ethically, and possibly Legally; you engage in Freely Committing Slander.


you are a real fool and an idiot. As stated you are the biggest fool I have EVER seen in my 30 years of using ozone in my practice.


You have both demonstrated you are nothing but babbling blow hogs with nothing better to do than babble about something you know nothing about. Get a job and stay off the internet!


What a sad human you are and I’m glad I found your blog so I can safely steer clear of you in the future.

This blogger is merely weaving a carpet of self enhancement thinking perhaps it will take him to the White House or some delusion of grandeur !


Someone is paying you to discredit vitamins, glandulars and minerals as beneficial remedies. You probably are a stupid medic. Breast feeding at age 80 off the pharmaceutical TIT. Die quickly so u can be reborn and do something to help someone.go pop a pill. You are an idiot.


So my remedy for someone like you and your advice…is to shut it.

What a pedantic piece of dog poop…. You sir apparently have a hidden agenda or are trying to prove your self esteem to yourself.

Maybe u should do like I was raised…if you can’t say something nice then keep ur mouth shut.

You are such a pompus ass egomaniac… I was trying to give you benefit of doubt until you went to espousing the global warming bullshit. You have shown your true colors – brown like the bs you write.

OMG, do you have any idea what sort of fool you sound like writing this post? Get your head out of your ass

You are probably one of the most arrogant people I have encountered on a forum that is meant to help people. You are not a help to anyone with your condescending attitude. EGO- look it up. Your lack of compassion is a testiment.

I read your article in its entirety and have to ask: what rock did you just crawl from under?

i cured high blood pressure arthritis and arithmia with these supplements – this article is moronic

Are you living under a rock dude?

 

Really Mad
[SK: Obviously, all of the critics here are mad. But with some comments, the visceral rage radiates from the monitor like heat. Whether it’s the use of ALL CAPS, exclamation marks!!!!!! Or just the language, these folks are making it clear that they are REALLY MAD!!!!!!!]

To say that I find this piece appalling, unprofessional and slanderous is an understatement… I would ask out of respect and decency that before publishing such a slanderous, potentially damaging piece you would at LEAST have the courage and courtesy to call your colleagues before marring their reputation and being so utterly vitriolic. As you have made it your life’s mission to brutally eviscerate anyone who speaks out in favor of any holistic modality. Which is especially admonish able considering the high rate of suicide and anxiety in our profession. [SV: This is actually one of the few comments from an individual I have written about (1, 2 While I understand that no one appreciates being criticized, public comments are fair game. I did respond to Dr. Conway offering to have a more thoughtful and civil dialogue about our disagreement (**see below), but she never responded.]

 

Big devious lie of an article!!!…in my opinion it’s like a miracle medicine and it’s a must habe for all pets with kidney failure!!!!!!any !, any one telling u otherwise is Probably working for the misinformation industries!!!!!!
THANK U THESE PEOPLE R JUST JEALOUS THEY DIDNT COME UP WITH #NZYMES
.I START NEXT WEEK… GO TO HELL SKEPTVET

This article you have written skepvet is absolute rubbish, oozes with hatred, ignorance, pouting, sulking and immaturity. Once again an stupid, narrow minded and unedcuated article by THE conventional vet that has more time on his hands than he should…. What has troubled your childhood that badly that you just can’t stop your endless fight against mother nature and you need to voice your opinions, that truly nobody cares about… Dr Xie. He trains thousands of vets on planet earth yearly, yet have the atrocity to criticize a man in a field you have ZERO KNOWLEDGE about. Why are you opening your mouth? Wake up. The world doesn’t care about your opinion.


THIS IS MY OPINION OF SKEPTVET and HIS BLOG!!!!!!! HE IS MAKING MONEY FROM THESE MISLEADING STATEMENTS!!!!!

Here is what I believe,.. I believe that YOU are MAKING MONEY from a BLOG, from the advertisements, and that is why you continue to say something but say ABSOLUTELY NOTHING,…. STOP MISLEADING PEOPLE, WITH YOUR OWN SNAKE OIL CLAIMS, BECAUSE YOUR MAKING MONEY OFF A BLOG’s AD’S, and AT THE END OF THE DAY, YOU GO TO BED, PROBABLY ALLOWING THOUSANDS OF DOGS AND CATS GO TO THEIR DEATHS, WITHOUT HAVING ONE LAST CHANCE AT LIFE!


Once again old man skeptvet is bashing another product. You want to keep killing dogs with Rimadyl. Just shows what a worthless vet you really are… As I have said before, your opinion is irrelevant. You have made a fool of yourself time and time again. You think you are a know it all but you are a know nothing. Nobody cares what you have to say anyway.


Slept-vet you remind me of a man named Hitler that everything he said was taken as the truth and no-one else was correct.

What shocks me – and I consider particularly evil – is the fact that [my name] went after the blood bank. Ridicule all you want, [my name]. But you, [my name], as a vet, should know better. You put dog lives in danger by refusing veterinary emergency medicine. Your statements, [my name] DVM of Northern California, make you ultimately a pet killer. Dr. [my name], you are on the same level as Kristen Lindsey, the veterinarian who killed the cat with an arrow. You, Dr. [my name] probably agree that cats should have arrows through their heads and wave them gallantly over your head in triumph, [my name] aka SkeptVet. [SV: This person apparently felt very clever in discovering my name and imagined inserting it repeatedly in this comment would show me a thing or two.]

Just wanted to let you know you are a fraud….your science sources are all either anonymous, just like you to avoid all accountability for your fraudulent non-advice or obvious industry sites. You should be ashamed of yourself. You are a disgrace! Disgusting!

MD’s and vets are lying criminal drug pushers who do not cure anything. They pump unnatural crap into gullible people’s pets and still sleep at night in satin sheets.

SkeptVet, You sound like the precise commercial kibble peddling Vet that has ended up killing dozens of dogs with your conventional passive income steroid therapies and regular income generating vaccinations

Your aggressiveness and that of your tribe is distasteful and a signal that you’re swayed by commercial interests.

Any moron can create a free blog and become an expert. It takes a particular jackass to use it with the viciousness that you do. You’ll pay for your selling yourself to conventional medicine.
I AM LIVID THAT POINTED HEADED CORPORATE DOCTORS CAMPAIGN AGAINST NATURAL TREATMENTS THAT WORK SO THEY CAN PROMOTE INEFECTIVE FDA APPROVED CHEMICAL PHARMACEUTICALS…I hope you are happy Dr. DEATH. You scumbag SkepVet.

Go take your drugs and destroy your kidneys and liver. And kill all our animals that way as you promote drugs and surgery and toxic immunization a. You are a total moron

It is a great product it reversed my cat numbers until he wasn’t showing signs of kidney failure , even his urine started to have a smell to it again. But what you think the FDA should do their barbaric tests to see how much cats and dogs need to take before the die! The tests are terrible and should be out lawed.

 

Just Plain Weird
[SV: Some comments go beyond paranoid conspiracy theories and personal outrage to the realm of the bizarre]

This article is a perfect example of someone who obviously has zero ability to communicate with animals. Just because you cannot understand and talk to animals, doesn’t mean others can’t. Yes, animal communication is real and to someone who said what turkeys are saying in heaven after you ate them for your thanksgiving, know that they are cursing you and it’s accumulating in your bad karma.

Typical douchbag blog crusader…Enjoy eating your cheese.

Don’t let people take the reproductive parts off of their pet.
Zoosexuals need to not be rejected too even as your harmless selves don’t want to be rejected. Non-human animals have their way of communicating. Please your pet even as you want to be pleased. Both sexes.  It should not be a crime to be seen pleasing or being pleased by a non-human animal.

 

 

** Here is my response to Dr. Conway’s outrage.
I saw your comments posted to my blog, and I’m sorry you feel my characterization of your comments was unfair. However, I believe my review of your interviews was both fair and accurate, and I think terms like “brutal evisceration” and “slanderous” are unreasonable hyperbole. I notice that you completely ignore the section of my article that is complementary towards you and Dr. Raditic:

“To be fair, both Dr. Raditic and Dr. Conway acknowledge the importance of basic science and conventional veterinary medicine, and I don’t doubt they are sincere. Like most CAM vets I have met, they are most likely nice people and competent conventional clinicians. However, despite their genuine belief that they are working in the best interests of patients and veterinary medicine and in a way consistent with the principles of science, the reality is that their statements and actions are deeply inconsistent with the principles of scientific medicine.”

We clearly disagree about the concept of integrative medicine and the legitimacy of most of the therapies you wish to integrate into our profession, such as chiropractic, homeopathy, and TCVM. I don’t believe this disagreement requires personal antipathy, and as I’ve said I have no doubt you are a good clinician with a genuine desire to do what seems best to you for your patients. I do, however, believe you are mistaken as to what that is, that your belief in the alternative therapies you mention is contrary to the best evidence concerning their efficacy, and that ultimately the research and integrative training you recommend and that AHVMA and Mercola are funding will serve only as a marketing tool to persuade people of the value of alternative therapies, not rigorous research which will elucidate the real effects, or lack thereof, for these methods.

You are correct that public comments on these issues have consequences, and these include enduring criticism of your comments from those who disagree with your views and assertions. If you intend to advocate for alternative therapies, that advocacy will draw criticism. This is a natural and appropriate part of the competition of ideas within our profession. Believe me, I have been the subject are far more hostile public comments for my views than anything I have written about you.

If you want an opportunity to clarify your position and respond to what you believe is inaccurate in my article, I am happy to let you do so in the comments section of the article. However, any such response needs to address specifics and avoid the kind of emotional language in the comments you attempted to post. Despite your view of the article, I did not use such language directed at you, but instead focused on the implications and assumptions in your actual words. You can say whatever you like elsewhere, but while I am happy to entertain disagreement and debate on my blog, I am under no obligation to provide a platform for you to attack me just to vent your anger without a substantive response to what I have actually written.

Dialogue can be productive, but argument rarely is. I am open to dialogue, but I don’t get the impression from your messages that you want anything more than to yell at me for saying things about your words that you don’t appreciate, and I don’t see how anything useful will come from that.

 

Posted in Humor | 20 Comments

Presentation on Placebos in Animals

Here are the notes and slides for a recent presentation on placebo effects in veterinary medicine.

WHAT IS A PLACEBO?
Despite the fact that most people have heard of the placebo effect and feel they have some understanding of what it means, the concept is a complex and contentious one. There is no consensus definition of a placebo or of the placebo effect. However, it is generally accepted that placebos are inert, and they have no direct physiologic effect on a patient’s disease or symptoms. Placebo effects, then, are effects associated with the administration of an inert substance or treatment, and these effects are perceived as beneficial by the patient or observers. Negative effects associated with inert treatments do occur, and these are referred to as nocebo effects.1

There are a number of mechanisms by which an inert treatment can lead to reported or observed responses. Many placebo effects are psychological responses based on belief and expectation, which influence a patient’s perception of his or her symptoms or have physiologic effects through centrally mediated changes in autonomic function.1-2 Placebo effects may also be caused by classical conditioning, in which physiologic responses to active treatments are paired with inert stimuli that are eventually able to elicit the same responses as the active treatment.2

Some effects associated with inert treatments in clinical research studies are actually not placebo effects mediated by conditioning or expectations. Research subjects in a placebo control group may experiences changes in their symptoms or other outcomes for a variety of reasons, and the use of an inert treatment can reveal that these changes are not due to the active treatment. However, not all such changes are true placebo effects.

For example, the Hawthorne Effect is a phenomenon in which subjects improve simply as a consequence of being enrolled in a research study.3 Subjects get more care and attention, they tend to be more compliant with existing treatments because they are being monitored, and their condition may improve due to better overall care regardless of any active test treatment or expectation-based placebo effects.3

Regression to the mean and the natural course of disease are other phenomena that can be seen in subjects receiving placebos in a research study which is not actually a true placebo effect.4 With chronic conditions, symptoms tend to wax and wane spontaneously. And some conditions may resolve spontaneously Patients are more likely to seek care, or enroll in research studies, when their symptoms are waxing, and thus they tend to improve after receiving care or beginning a study due to the natural course of disease. This, again, can be revealed by placebo assignment, but it is not an effect of the administration of the inert treatment.

It is worth noting that all of the factors that cause placebo effects and apparent response to inert treatment can also be seen with active treatments. Pain relievers with direct physiologic activity can elicit a greater reported response than explained by the pharmacological effects of the treatment. Part of the purpose of inert treatments in research trials is not only to assess whether treatments have specific effects but what proportion of the apparent response may be explained by concurrent non-specific effects and placebo responses.

In general use, placebo effects refer to those changes in reported or measured symptoms associated with beliefs or expectations about treatment. However, in the context of medical research, any effect seen in the placebo control group is classified as a placebo effect even if it is due to other factors.1 This complicates the clear use of the term and an understanding of what effects can be attributed to inert treatments and the associated mechanisms. It also impacts the relevance of placebo effects to veterinary patients, in which the relative role of various causes for non-specific treatment effects likely differ from human patients.

PLACEBO EFFECTS IN ANIMALS
It is clear that animal subjects in research studies exhibit changes in symptoms commonly identified as placebo effects when seen in human research subjects. These include subjective symptoms reported by owners or observed by investigators and clinicians as well as objectively measured outcomes.2,5-8 There is no clear research evidence showing such effects in clinical veterinary patients not participating in research. However, the circumstances and variables responsible for placebo effects seen in veterinary research studies are usually also present in the clinical context, so it is likely such effects exist in clinical patients as well as research subjects.

Animals receiving inert treatments often show improvement in subjective outcomes, such as pain, which are assessed by caregivers, clinicians or researchers. While it is generally accepted that most animals are not cognitively capable of having beliefs and expectations about their medical care, and so cannot have the classic direct placebo response, caregivers and other humans involved in these studies are susceptible to such effects. The caregiver placebo effect, in which humans report improvement in subjective  symptoms for animals receiving inert treatment, has been clearly demonstrated.5,7

It is also likely that animals receiving inert treatments may show improvement due to causes other than direct placebo effects. Research has shown human contact has predictable effects on behavioral and physiologic responses in domesticated animals, and these effects can easily be interpreted as improvement in clinical symptoms.2,9 And just as classical condition contributes to placebo effects in humans, such conditioned responses are certainly present in other animals and likely generate changes in the condition of animal patients and research subjects receiving inert treatments.

Even relatively objective outcome measures have been shown to change in response to the administration of inert treatments. Seizure frequency, heart rate, and other objectively measurable outcomes show non-specific treatment effects in animals just as in humans.2,8 Conditioning, the Hawthorne Effect, general response to human contact, and other variables are likely responsible for these apparent placebo effects.

 CLINICAL IMPLICATIONS
The presence of placebo effects and other responses to inert treatments has several important implications for clinical care. One is that apparent responses to treatment, especially in subjectively experienced symptoms such as pain, nausea, and fatigue, may reflect placebo effects rather than true improvement in the underlying condition. Human asthma patients, for example, may report improvements in the symptoms experienced during an asthma attack when given a placebo inhaler.10 However, such responses are not typically seen in objective signs of disease, especially in patients not in clinical trials receiving more intense and comprehensive monitoring and care than clinical patients. For example, the asthma patients who reported feeling better with placebo inhalers had no measurable improvement in lung function, unlike those patients receiving bronchodilator therapy.10

This demonstrates that placebo effects generally improve the perception of symptoms but not the actual physical disease. Such effects can fool patients, caregivers, and clinicians into believing they have provided effective treatment while allowing the disease to remain of progress. Asthma patients consistently treated with an ineffective medication would likely perceive some relief, but they could also be experiencing ongoing lung damage and ultimately have poorer outcomes due to the lack of objectively effective treatment. It is critical, then, that clinical therapies be demonstrated to be truly effective through clinical trial research because uncontrolled clinical observation is an unreliable guide to efficacy.

There are also ethical implications to placebo effects.11-12 In human medicine, there may be some benefit to improving the perception of uncomfortable symptoms, with a placebo or with placebo effects attached to active treatments. However, such effects are typically negligible if patients are informed that they are receiving inert treatments. Obtaining the subjective benefits of placebo effects requires misleading patients into believing they are receiving an active therapy, which is arguably unethical.11

In veterinary patients, placebo effects are largely obtained by proxy through caregivers.5,7 This creates an additional ethical challenge since caregivers and clinicians may perceive benefits the patients are not actually experiencing. This makes the necessity of objective research validation for treatment efficacy even more critical in veterinary medicine.

CONCLUSIONS
Placebo effects, and other related factors that create true or perceived improvement in clinical symptoms, are manifest in veterinary patients and animal research subjects. Controlling for these effects in research studies is crucial to identifying the true benefits of the treatments we employ. The existence of such effects also makes clinical observation of response to therapy highly unreliable as a measure of the true efficacy of our treatments. We, and our clients, often see what we hope or expect to see in response to the therapies we employ, and it is possible to be fooled into believing ineffective treatments are working without appropriate controlled research evidence. This creates an ethical imperative to base our interventions on good-quality research evidence rather than uncontrolled observations. Fortunately, some kinds of non-specific effects seen with inert treatments can also add to the real benefits of active treatments, and we can take advantage of this to maximize the benefits of our therapies once we have established objective efficacy.

REFERENCES

  1. De Crae AJM. Kaptchuk TJ. Tjissen JGP. et al. Placebos and placebo effects in medicine: historical overview. J Royal Soc Med. 1999;92:511-15.
  2. MacMillan FD. The placebo effect in animals. J Amer Vet Med Assoc. 1999;215(7):992-9.
  3. McCarney R. Warner J. Iliffe S. et al. The Hawthorne Effect: a randomised, controlled trial. BMC Med Res Methodol. 2007;7(30).
  4. McDonald CJ. Mazzuca SA. Mcabe PG. How much of the placebo ‘effect’ is really statistical regression? Statistics Med. 1983;2:417-27.
  5. Conzemius MG. Evans RB. Caregiver placebo effect for dogs with lameness from osteoarthritis. J Am Vet Med Assoc. 2012;241(10):1314-9.
  6. Malek S. Sample SJ. Schwartz Z. et al. Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis. BMC Vet Res. 2012;4(8):185.
  7. Gruen ME. Dorman DC. Lascelles BDX. Caregiver placebo effect in analgesic clinical trials for cats with naturally occurring degenerative joint disease-associated pain. Vet Rec. 2017;180(19):473.
  8. Muñana KR. Zhang D. Patterson EE. Placebo effect in canine epilepsy trials. J Vet Intern Med. 2010;24(1):166-70.
  9. Zulkifli I. Review of human-animal interactions and their impact on animal productivity and welfare. J Anim Sci Biotech. 2013;4(1):25.
  10. Wechsler ME. Kelley JM. Boyd IOE. Et al. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med 2011;365:119-126.
  11. Asai A. Kadooka Y. Reexamination of the ethics of placebo use in clinical practice. Bioethics.2013;27(4):186-93.
  12. Gold A. Lichtenberg P. The moral case for the clinical placebo. J Med Ethics. 2014;40(4):219-24.

Placebos in Veterinary Medicine Slides

Posted in Presentations, Lectures, Publications & Interviews | 1 Comment

Presentation on Choosing Diagnostic Tests

Here are the notes and slides for a recent presentation on strategies for effectively choosing diagnostic tests.

GOALS OF DIAGNOSTIC TESTING
Ultimately, the goal of any test we run should be obtaining information that allows us to more effectively treat or prevent health problems in our patients. This seems obvious, but it is all too easy to lose sight of this core purpose. We may feel obligated to run tests to confirm a diagnosis even when the level of confidence is already high and the outcome of the test won’t change what the client chooses to do. We may employ diagnostic tests as a preemptive defense against litigation or because of a perceived pressure from the client to do something even when our action likely won’t change the outcome for the patient. In some situations, we may be completely confused by a case and throw a bunch of tests at it hoping for some insight to emerge.

All of these are understandable, and all too common, reasons for using diagnostic tests, but unfortunately such approaches reduce the reliability and utility of the tests themselves. Effective testing requires not only an understanding of the strengths and weaknesses of the tests we use but also a clear understanding of how to employ them and how to integrate the results into our clinical decision making. We need a rational strategy for when and how to test, how to interpret results, and somewhat counterintuitively, when not to test at all.

BEYOND SENSITIVITY AND SPECIFICITY
The most common measures used to describe diagnostic test are sensitivity and specificity . These are characteristics of the tests themselves, and they indicate how likely, compared with some gold standard, a test is to correctly identify a disease which is present or to correctly identify that a patient does not have the disease. Unfortunately, the meaning of these numbers is often misunderstood. If a test has, for example, a 98% sensitivity, this is the proportion of patients with the disease who will correctly test positive. It is NOT an indication that any patient who tests positive has a 98% chance of having the disease. Under certain conditions, the majority of patients testing positive on such a test may actually not have the disease even with such a high sensitivity.

More clinically useful measures of a test’s reliability are the positive predictive value and the negative predictive value (Fig. 1). These are, respectively, the probability a patient with a positive test actually has the disease and the probability a patient with a negative test result does not have the disease. These numbers depend not only on the test but also how common the disease is in the population being tested.

As an example, if a population of feral cats has an FIV prevalence of 2%, 2/100 cats tested will test positive with a perfectly sensitive test (sensitivity=100%). If the test also has a specificity of 98%, then about 2/100 cats will test positive even though they do not have FIV. The positive predictive value, then, is 50%, meaning half of the cats who test positive do NOT have FIV. Even with a great test, this is a pretty big error rate, especially if we are planning on euthanizing cats diagnosed with FIV!

This example illustrates how important it is we have some idea how likely a disease is to be present before running a test for that disease if we want our test results to be reliable. Which brings us to a new and somewhat fashionable way to look at diagnostic testing….

BAYESIAN ANALYSIS FOR THE MATHEMATICALLY CHALLENGED
The work of 18th-century mathematician Thomas Bayes is enjoying something of a renaissance as an alternative, in some respects, to the frequentist statistical methods most of us were taught in vet school. The details of the math involved are complex, but the logic of the approach is simple and intuitive. Diagnostic tests should not be viewed as determining whether or not a disease is present. They should be viewed, instead, as one piece of evidence shifting the existing probability of a diagnosis higher or lower.

If, as in the example above, I know that the prevalence of FIV is 2% in this population of cats, I can say the probability of any given cat having FIV is very low. A positive test does not mean a cat has FIV, only that the probability it might have the disease has increased a bit. The test doesn’t make or break the diagnosis, it simply shifts out understanding of the likelihood of the diagnosis.

In a practical sense, then, a Bayesian approach means estimating the probability of a diagnosis based on all of the usual factors we consider (signalment, personal history, prevalence rates, physical exam findings, other test results, etc.). If this probability is high enough or low enough to make or rule out a diagnosis, no additional test is needed. If, however, the probability leaves significant uncertainty, then we should select a test that will meaningfully raise or lower that probability to help us make the diagnosis.

SCREENING
Screening is a special case in which we are testing asymptomatic individuals with the idea of detecting preclinical disease so we can more effectively intervene to reduce symptoms and mortality. Because the prior probability of disease is usually very low by definition in screening, since patients have no symptoms, the positive predictive value of even very good tests is low. It has been recognized in human medicine that screening can often lead to overdiagnosis and overtreatment, which can waste medical resources and ultimately do more harm than good for patients.1There are, therefore, requirements for screening programs, and these include not only accurate tests but proven interventions that actually improve outcomes for patients diagnosed with the disease and rational plans for confirming and following up both positive and negative test results.

In veterinary medicine, we often employ diagnostic tests in asymptomatic patients “just in case” we might find subclinical disease. Whether or not such testing improves outcomes for patients or leads to significant overdiagnosis is almost never evaluated, so the benefits and risks of screening are often assumed but not truly known. This means that significant caution is warranted in conducting screening and interpreting the results of diagnostic tests in clinically well individuals.

 

CARDINAL RULES OF DIAGNOSTIC TESTING

Based on this understanding of the limitations of diagnostic testing, there are a few cardinal rules we can apply to reduce the potential mistakes and harms resulting from our tests:

Cardinal Rule #1

If the results of the test isn’t going to change what you do, don’t run the test.

Cardinal Rule #2

If the prior probability of a diagnosis is very high or very low, don’t run the test.

Cardinal Rule #3

Don’t screen (test asymptomatic individuals) without a plan of action based on solid evidence that the benefits of testing and diagnosis outweigh the risks.

REFERENCES

  1. McKenzie, BA. Overdiagnosis. J Amer Vet Med Assoc. 2016;249(8):884-889.

 

Choosing and Using Diagnostic Tests Slides

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Presentation on Surgical Neutering Techniques

Here are the notes and slides for a presentation I recently gave comparing various surgical sterilization and neutering techniques.

INTRODUCTION
Among the most common surgical procedures in small animal practice are those for sterilization (preventing reproduction) and neutering (removing the gonads). The goal of these procedures is both to prevent reproduction and to provide a net health benefit for the patient. This benefit may include avoiding the risks of reproduction, reducing the incidence of those disease that are more common in intact animals, and reducing behaviors associated with intact status that can lead to relinquishment.1-2

There are many variations on these procedures, and the specific techniques used by individual veterinarians seem to depend more on tradition, personal habit, and cultural preference than on explicit evaluation of the pros and cons from a scientific perspective.3 There is, however, research evidence concerning some of these procedures which we can use to make rational decisions about our choice of technique. We can also use this research to inform the recommendations we make to clients. Pet owners are increasingly aware that there are multiple alternatives to choose from, and they may come to us with strong opinions or misconceptions about the most appropriate procedure to their pets.

Most procedures are intended to prevent reproduction. Some also involve gonadectomy, which has a complex array of both beneficial and harmful effects that depend on breed, sex, age, timing of surgery, and many other factors. The long-term pros and cons of gonadectomy are controversial, and I have reviewed them in detail elsewhere.2 In brief, there appears to be a net health benefit for most female dogs and cats from neutering, though the details of the risks and benefits and the effect of the timing of neutering are quite variable. There is much less evidence for a net health benefit in neutering males, though there are other justifications for doing so. Today I will consider the relative advantages and disadvantages of different surgical sterilization methods for males and females.

STERILIZING FEMALES
The most common spay procedure in the United States is ventral midline ovariohysterectomy (OVH). This is an effective technique for sterilization and neutering of both dogs and cats with very low complications rates when performed by experienced surgeons.4-6 There are many minor variations with no research evidence comparing the relative merits of most.

One exception is the flank approach to ovariohysterectomy, preferred in some countries for cats and small dogs. There are theoretical advantages and disadvantages to this approach, and research evidence comparing flank and midline approaches is mixed. Some comparisons suggest the flank approach is faster with fewer complications,7 but other studies find no difference8, and some indicate more discomfort associated with the flank approach.9-10 Access to both ovaries is more difficult with the flank approach unless bilateral flank incisions are made, which significantly complicates the procedure, and hysterectomy can be difficult by this method.11 The flank and midline methods both achieve the goal of gonadectomy and sterilization.

Traditionally, ovariohysterectomy has been preferred in the United States while ovariectomy (OVE) is the more common choice in some other countries.12 Both techniques are equally effective at achieving gonadectomy and preventing mammary carcinoma and pyometra.12-14 Some studies have suggested that OVE is less painful than OVH15, however other studies have not identified any difference in post-operative pain or other complications.10,16

A relatively recent option is the laparoscopic spay. Both laparoscopic ovariectomy and ovariohysterectomy have been reported, using a variety of equipment and techniques. Comparisons are difficult given the many different approaches, equipment, and assessments used in published studies. In general, the disadvantages of laparoscopic OVE and OVH include the cost of equipment, the need for extensive training and practice to achieve proficiency, and the longer surgical time.17-20 Laparoscopic spay may have the advantage of decreasing post-operative pain, complications, and recovery time, though the literature is not consistent and there is a lack of high-quality studies.21

With a growing awareness of the potential negative effects of neutering, there has been some increased interest among breeders and pet owners in sterilization procedures that do not involve gonadectomy. For females, two such procedures are hysterectomy (sometimes called an “ovary-sparing spay”) and ligation of the fallopian tubes or uterine horns. Both procedures have been described in the literature,22-23 but neither have been widely adopted.

There are no controlled research studies comparing tubal ligation or hysterectomy to OVE or OVH. While ligation of the fallopian tubes or uterine horns can prevent reproduction, it is highly likely that any risks and benefits associated with the presence of ovaries2 are the same for females having a tubal ligation as for those not spayed at all. A complete hysterectomy, including removal of the cervix, likely eliminates the concern for pyometra while the other risks and benefits of intact status remain unchanged.

STERILIZING MALES
Despite the uncertainties, surgical neutering is the most common approach to sterilization of male cats and dogs. For dogs, frequently used techniques include closed castration (removal of the testes without opening the vaginal tunic) and open castration (which involves opening the vaginal tunic prior to ligating the vessels and ductus deferens). Both procedures can be performed through a scrotal or pre-scrotal incision, and there are a number of variations of each.

There is much debate about the relative merits of open and closed castration in dogs, but it is based mostly on theoretical reasoning and anecdotal evidence. Some argue that closed castrations are safer because there is no direct communication with the abdomen, reducing the risk of ascending infections or herniation of abdominal contents. Others claim that open castrations are less likely to lead to hemorrhage or scrotal hematomas. Typically, closed castration is recommended for small dogs and cats and open castration for larger dogs.

There is little research evidence to inform these debates. One prospective randomized trial did find more overall complications in dogs undergoing open castration.24 However, problems with recruitment of subjects for this study significantly limit the strength of this evidence. Overall, serious complications are few in dogs undergoing castration, and it is unclear if there is a consistent advantage to either technique.

The research evidence comparing scrotal and pre-scrotal approaches in dogs is also quite sparse. A randomized, prospective study comparing the two approaches found similar complication rates.25 The scrotal approach had the advantage of inducing less self-trauma and of being about 30% quicker to perform (though the absolute difference, from about 5 minutes to 3 minutes, is of doubtful clinical significance). Once again, both techniques are effective, and it is not clear that one is superior to the other.

Several techniques have been described for neutering male cats,26 but there is virtually no formal research comparing complication rates. A scrotal approach appears to be the most common, and methods for securing the ductus and vessels include suture ligation and various methods of tying the tissues on themselves. One comparative study of these ligation methods found no significant complications and no difference between methods.27

An uncommon surgical technique used for male dogs in some resource-poor countries is pinhole castration. The spermatic cord is ligated with suture percutaneously to induce necrosis of the testes.28 While this technique is less expensive than standard surgical castration and it does reduce functional testicular tissue volume, it is unclear how effective it is as a means of sterilization, and some reports suggest a higher rate of infection, pain, and other complications compared with standard techniques.29-30

Finally, surgical or laparoscopic vasectomy is sometimes recommended as a means of sterilizing male dogs and cats without neutering.26 Both approaches are effective at achieving this outcome. There have been no direct published comparisons between surgical and laparoscopic vasectomy. One small study comparing laparoscopic vasectomy with surgical castration in dogs found few differences except for a subjectively greater level of post-operative discomfort in the surgical patients.31

REFERENCES

  1. New JC. Characteristics of shelter-relinquished animals and their owners compared with animals and their owners in U.S. pet-owning households. Journal of Applied Animal Welfare Science 2000;3(3):179–201.
  2. McKenzie B. Evaluating the benefits and risks of neutering dogs and cats. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources. 2010;5(45):1-18. Updated version available at: https://goo.gl/pWCKYl
  3. May S. The flank cat spay: eminence-driven fashions in veterinary surgery. Veterinary Record. 2012;170:460-461.
  4. Howe LM. Surgical methods of contraception and sterilization. Theriogenology. 2006 Aug;66(3):500-9.
  5. Berzon JL. Complications of elective ovariohysterectomies in the dog and the cat at a teaching institution: clinical review of 853 cases. Veterinary Surgery. 1967;8:89–91.
  6. Burrow R. Batchelor D. Cripps P. Complications observed during and after ovariohysterectomy of 142 bitches at a veterinary teaching hospital. Veterinary Record 2005;157:829–833
  7. Kiani FA. Kachiwal AB. Shah MG. et al. Comparative Study on Midline and Flank Approaches for Ovariohystrectomy in Cats. Journal of Agriculture and Food Technology. 2014;4(2):21-31
  8. Coe RJ. Grint NJ. Tivers MS. et al. Comparison of flank and midline approaches to the ovariohysterectomy of cats. Veterinary Record. 2006;159(10):309-313
  9. Oliveira JP. Mencalha R. dos Santos Sousa CA. et al. Pain assessment in cats undergoing ovariohysterectomy by midline or lateral celiotomy through use of a previously validated multidimensional composite pain scale. Acta Cirúrgica Brasileira. 2014;29(10):633-38.
  10. Burrow R. Wawra E. Pinchbeck G. et al. Prospective evaluation of postoperative pain in cats undergoing ovariohysterectomy by a midline or flank approach. Veterinary Record. 2006;158(19):657-60.
  11. Janssens LA. Janssens GH. 1991. Bilateral flank ovariectomy in the dog—surgical technique and sequelae in 72 animals. Journal of Small Animal Practice. 32: 249– 252.
  12. Van Goethem B. Schaefers-Okkens A. Kirpensteijn J. Making a rational choice between ovariectomy and ovariohysterectomy in the dog: a discussion of the benefits of either technique. Veterinary Surgery. 2006;35(2) 136-143.
  13. DeTora M. McCarthy R. J. 2011. Ovariohysterectomy versus ovariectomy for elective sterilization of female dogs and cats: is removal of the uterus necessary? Journal of the American Veterinary Medical Association. 239: 110
  14. Okkens AC. Kooistra HS. Nickel RF. Comparison of long-term effects of ovariectomy versus ovariohysterectomy in bitches. Journla of Reproduction and Fertility Suppl 1997;51:227–31.
  15. Lee SS. Lee SY. Park S. et al. Comparison of ovariectomy and ovariohysterectomy in terms of postoperative pain behavior and surgical stress in dogs. Journal of Veterinary Clinics. 2013 30 3 166-171
  16. Peeters ME. Kirpensteijn J. Comparison of surgical variables and  short-term postoperative complications in healthy dogs undergoing ovariohysterectomy or ovariectomy. Journal of the American Veterinary Medical Association. 2011:238;189-194.
  1. Davidson EB. Moll HD. Payton ME. Comparison of laparoscopic ovariohysterectomy and ovariohysterectomy in dogs. Veterinary Surgery. 2004;33:62–69.
  2. Ataide MW. de Brun MV. Barcellos LJ. et al. Laparoscopic-assisted or open ovariohysterectomy using Ligasure AtlasTMin dogs. Ciência Rural. 2010;40(9):1974-1979.
  3. Gower S. Mayhew P. Canine laparoscopic and laparoscopic assisted ovariohysterectomy and ovariectomy. Compendium of Continuing Education for the Practicing Veterinarian. 2008;30:430–440.
  4. Case JB. Boscan PL. Monnet EL. et al Comparison of surgical variables and pain in cats undergoing ovariohysterectomy, laparoscopic-assisted ovariohysterectomy, and laparoscopic ovariectomy. Journal of the American Animal Hospital Association. 2015;51(1):1-7.
  5. Phypers C. In Cats and Dogs Does Laparoscopic Ovariectomy Offer Advantages Over Open Ovariectomy for Postoperative Recovery?. Veterinary Evidence. 2017; 2(2). doi:http://dx.doi.org/10.18849/ve.v2i2.59
  6. Grier RL. Tubal ligation-alternative sterilization operation. Iowa State University Veterinarian. 1973;35(2):49-50
  7. Belfield WO. Partial spay (hysterectomy). Veterinary Medicine. 1972;1223-1224.
  8. Hamilton KH. Henderson ER. Toscano M. et al. Comparison of postoperative complications in healthy dogs undergoing open and closed orchidectomy. J Small Anim Pract. 2014 Oct;55(10):521-6.
  9. Woodruff K. Rigdon-Brestle K. Bushby, PA. et al. Scrotal castration versus prescrotal castration in dogs. Vet Med. 2015;110(5):131-135.
  10. Howe LM. Surgical methods of contraception and sterilization. Theriogenology. 2006 Aug;66(3):500-9. Epub 2006 May 23.
  11. Karen Maciel de Oliveira, Leonardo Augusto Lopes Muzzi, Bruno Benetti Junta Torres, et al. A comparative study among three open orchiectomy techniques in cats. Acta Scientiae Veterinariae. 2010;38(2):177-183.
  12. Okwee-Acai J. Omara R. Onyait JS. et al. evaluation of pinhole castration as an alternative technique for dog population control in resource-poor communities. Bulletin of Animal Health and Production in Africa An. 2013;61(3):337-345.
  13. Baba MA, Fazili MR, Athar H, et al. Pinhole castration technique: an alternative to orchiectomy in stray dogs. Anim Reprod Sci. 2013;137(1-2):113-8.
  14. Abd-el-Wahed RE. Korritum AS. Abu-Ahmed HM.et al. Evaluation of pinhole castration technique compared with traditional method for castration in dogs. Alexandria Journal of Veterinary Sciences. 2014;42:90-98.
  15. Anburaja Mahalingam; Naveen Kumar; Maiti S.K. et al. Laparoscopic sterilization vs. open method sterilization in dogs: a comparison of two techniques. Turkish Journal of Veterinary & Animal Sciences. 2009;33(5):427-436.

 

OVE, OVH, OMG: Pragmatic Review of Surgical Neutering Techniques Slides

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Presentation on Cannabis for Pets

I recently gave a presentation for veterinarians on Cannabis as a potential source of medical therapies for veterinary patients.  There haven’t been many new studies in veterinary species since my last post on the subject in 2016, but that is about to change. A number of veterinary schools have studies in progress, one pharmacokinetic study has already been reported, and a study of CBD for arthritis in dogs has reportedly been completed but not yet published. There has also been a recent article on CBD for refractory epilepsy in children, and this product looks likely to be approved by the FDA very soon.

Hopefully, this wave of evidence will come soon, and we will start to better understand the potential in Cannabis-based treatments.  In the meantime, here is the summary and the slides from my recent presentation on the subject.

INTRODUCTION
Medical marijuana for humans has been a hot topic for many years. Much of the debate about it has focused on ethical and legal issues that aren’t directly answerable through scientific research. Participants in these debates often gravitate towards ideological extremes. For some, any use of marijuana, medical or recreational, is immoral and dangerous. For those at the other extreme, marijuana is a perfect, risk-free cure for anything from depression to cancer.

In the last several years, these debates have migrated to veterinary medicine, with both extremes well represented. It has grown easier and more common for animal owners to provide their pets with cannabis-based remedies, both marijuana itself and products specifically produced for companion animals.

Insufficient attention, however, is generally given to the critical scientific question, “What are the risks and benefits of medicinal use of cannabis-based products?” Any consideration of the medical use of cannabis should be based on rational, objective evaluation of the scientific evidence concerning risks and benefits, uninfluenced by the surrounding ethical and legal debates.

RISKS AND BENEFITS: WHAT’S THE EVIDENCE?
Cannabis sativa contains a bewildering variety of chemical compounds. Some have been shown to have significant effects on many different body systems, from the CNS to the GI tract to the immune system. Different varieties of Cannabis have different concentrations of various cannabinoids as well THC, the compound responsible for the psychotropic effects of marijuana and humans and the toxic effects in some animal species. This variation makes it likely that medical and recreational products will differ significantly in their constituency and effects.

In vitro and lab animal research shows a variety of promising effects for some of the many compounds in Cannabis as well as multifaceted and complex potential physiologic effects. There is, therefore, good reason to believe cannabis-derived medicine could have real benefits, as well as real risks, in veterinary patients. However, the vast majority of compounds which appear promising in pre-clinical studies never prove safe or effective in actual clinical patients, so such evidence only provides potential avenues for clinical research, not a validation of claims for real-world effects.

Unfortunately, so far there is no reliable clinical research evidence for the use of cannabis-based remedies in small animal patients. That means we cannot say with confidence what the benefits or risks of any such remedy might be. We can hypothesize, based on the pharmacology of cannabis compounds or on anecdotal evidence. We can also extrapolate from studies in lab animals or humans. However, we have no direct, reliable evidence to support any claim about any veterinary medical marijuana treatment.

This lack of research is primarily due to strict laws regulating the availability of marijuana, for research purposes as well as medical or recreational use. Hopefully, as these laws change, more data will be produced. For now, the best we can do is look at what we know about the risks of marijuana in veterinary species, as well as the risks and benefits identified in humans.

A recent comprehensive literature review has been produced by the National Academies of Science, Engineering, and Medicine.7 This review evaluates those risks and benefits of cannabis-based therapies that have been studied in humans, and classifies them using a straightforward system. The strength of evidence is rated as insufficient to draw a conclusion, limited, moderate, substantial, or conclusive.

Here are the conditions for which moderate or better evidence exists in humans for a beneficial effect and which might be relevant to veterinary patients:

  • In adults with chemotherapy-induced nausea and vomiting, oral cannabinoids are effective anti-emetics.
  • In adults with chronic pain, patients who were treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms.

For these conditions the effects of cannabinoids are modest; for all other conditions evaluated there is inadequate information to assess their effects.

While it is encouraging that some Cannabis-derived products have validated clinical benefits for these indications in humans, this still leaves us far from having reasonable evidence to support veterinary use. Our patients often respond quite differently to medicinal compounds than humans, and extrapolation across species is a risky proposition.

With any medical intervention that has benefits, there are certainly going to be risks, and these must be identified and understood in order to balance risks and benefits in the context of specific patients. Many of the risks identified for humans may not be relevant to veterinary patients (such as the risk of impaired driving). However, cannabis use has been associated with increased risk of schizophrenia and other psychoses and with some anxiety disorders in a dose-dependent relationship in people, and this raises the possibility of adverse behavioral effects in veterinary patients.

It is clear that marijuana exposure can have toxic effects on dogs and cats.1-2 These range from mild to severe, though exposure is rarely fatal. There is also evidence that the greater availability of marijuana associated with legalization for human medical or recreational use can increase the incidence of marijuana toxicosis in pets in some areas.3 These effects are likely due to products which contain relatively high levels of THC, and it is likely, though unproven, that products with little THC and higher levels of other cannabinoids might be safer for veterinary patients.

There are many cannabis-based products on the market specifically for use in animals. Unfortunately, there is virtually no information on the safety of any of these products. Assessment of both benefits and risks is entirely based on anecdote, which is a very unreliable form of evidence. One survey of owners using such products, for example, did report low rates of undesirable effects, as well as some perceived benefits.4 However, history is full of medical products for which anecdotal evidence has proven a poor guide to the true risks and benefits.

There is also concern about the consistency and labeling accuracy of medical cannabis products. Some states that allow medical marijuana use in humans have standards for labeling and quality control testing. However, there is evidence cannabis products are frequently inconsistent in composition and labeling despite these regulations.5-6 Given the complete absence of regulation or testing for veterinary cannabis-derived remedies, it is impossible to evaluate the consistency or labeling of these products, but they are likely to be at least as unreliable as products intended for human use. Even if the safety and clinical benefits for some Cannabis compounds is validated in veterinary patients, veterinarians and animal owners cannot rely on specific products having the appropriate type and amount of these compounds with no regulatory oversite or objective quality assurance mechanisms in place.

THE FUTURE
Ideally, changing attitudes towards cannabis will allow more clinical research to be done and the true risks and benefits for veterinary patients will be determined. Cannabis have many active chemical compounds., and it is likely some will turn out to have beneficial therapeutic effects. There is substantial evidence for only a couple of uses in humans, including pain and chemotherapy-induced nausea. There is no direct evidence for any use of cannabis in dogs and cats, though there is clear evidence for the toxicity of marijuana. All veterinary cannabis products are unregulated, and most have not been tested for safety or quality control, much less clinical benefits. Until further research is available, use of cannabis in dogs and cats is entirely experimental and based only on anecdote, and it is most likely illegal for veterinarians to provide or recommend any of these products.

REFERENCES

  1. Janczyk, P. Donaldson, C. W. Gwaltney, S. Two hundred and thirteen cases of marijuana toxicosis in dogs. Vet and Human Toxicol 2004 46 1 19-21
  2. Donaldson, C. Marijuana exposure in animals.Vet Med. 2002;97(6):437-439.
  3. Meola SD, Tearney CC, Haas SA, et al. Evaluation of trends in marijuana toxicosis in dogs living in a state with legalized medical marijuana: 125 dogs (2005-2010). J Vet Emerg Crit Care (San Antonio). 2012 Dec;22(6):690-6.
  4. Kogan, LR. Hellyer, PW. Robinson, NG. et al. Consumer perceptions of hemp products for animals. J Amer Holistic Vet Med Assoc. 2016;42:40-48.
  5. Vandrey, R. Raber, J. C., Raber, ME. Et al. Cannabinoid dose and label accuracy in edible medical cannabis products. 2015;313:2491–2493.
  6. Thomas, BF. Pollard, GT. Preparation and Distribution of Cannabis and Cannabis-Derived Dosage Formulations for Investigational and Therapeutic Use in the United States. Frontiers in Pharmacol. 2016;7:285.
  7. National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. Accessed on April 30, 2017 at https://www.nap.edu/read/24625/chapter/1

Confused About Cannabis Presentation Slides

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Actually, Raw Chicken Likely Can Lead to Paralysis in Dogs.

I recently reported on a study out of Australia that found an association between feeding raw chicken, infection with the bacterium Campylobacter, and a serious neurologic disease call Acute Polyradiculoneuritis (APN). Not surprisingly, advocates of raw diets are desperate to find ways to dismiss this study so they can continue to claim raw diets are as safe, or safer than commercial cooked pet foods. Cognitive dissonance, the discomfort that one feels when confronted with evidence that one’s beliefs about something may be wrong, is a powerful force, and it can lead even smart, educated people to engage in extreme mental gymnastics to dismiss such evidence and preserve cherished beliefs.

Many of the criticisms of the Australian study are simplistic and obviously wrong or irrelevant. It is sometimes dismissed as ”just one study.” This would be a fair criticism if it were true and if there were substantial evidence of benefits to feeding raw that balanced the potential risks, but unfortunately neither of these is the case. There is abundant and robust evidence that raw meat poses a greater risk for infectious disease and parasites than cooked meat, both in terms of studies of contamination of raw pet foods (1,2,3,4,5,6) and the overwhelming evidence in humans that handling and eating raw meat increases these risks and cooking reduces them. It is simply a fact that raw meat is more dangerous than cooked meat, and there is no good argument or evidence that this is not true for pets as it is for people.

A more complex attempt to dismiss the APN findings, and one which is getting some attention online, comes from a raw feeding advocate (and perhaps not surprisingly a marketer of raw foods and other alternative health products), Dr. Conor Brady.

Dr. Brady has a PhD in animal behavior and states that is research focus involved nutrition, so one would expect him to at least present a scientifically reasonable argument. Any study has limitations, and the Australian APN study is no exception, so a science-based critique would be a normal and welcome part of the scientific process.

Sadly, this is not what Dr. Brady offers. Instead, he lurches from scientifically sloppy arguments to cherry-picking of evidence to empty ad hominem attacks on the pet food industry. What he fails to do is provide any real reason to doubt the findings of the APN study.

What Does the Australian Study Actually Say?

Let’s start by looking at what the APN study actually says. The core of the argument made in the study is this:

  1. Up to 40% of Guillain-Barre Syndrome (GBS) cases in humans may be triggered by the bacterium Campylobacter.
  2. Most Campylobacter infections in humans come from eating or handling raw poultry.
  3. APN is believed to be a canine version of GBS, so the study sought to see whether there was an association between APN, Campylobacter, and eating raw chicken.
  4. APN did turn out to be associated with Campylobacter. 48% of dogs with APN had this bacterium while only 23% of healthy digs did. When looking at recent Campylobacter infections, which would be the most likely to serve as a trigger for autoimmune diseases like APN, three times as many APN dogs had it compared with control dogs.
  5. APN was also associated with feeding raw chicken. 96% of APN dogs were fed raw chicken while only 26% of control dogs were. Only 1 APN case was not fed raw chicken, and this dog had daily contact with live poultry.

Give these clear associations, it is likely that Campylobacter acquired from raw chicken is a trigger for some APN cases, as it is a trigger for GBS in humans. There are likely other triggers as well, but in this population of dogs feeding raw chicken seems a clear risk factor which would be easily eliminated. If there were clear and proven benefits to feeding raw chicken that outweighed this risk, it might still make sense to do so, but no such benefits have ever been demonstrated.

Dr. Brady’s Attempted Rebuttal

So now let’s turn to Dr. Brady’s comments on this study. He begins reasonably enough by acknowledging that Campylobacter is a serious infectious organism and that raw chicken is a common source for it:

Raw chicken is certainly a source of Campylobacter and a lot of raw dog foods are based on raw chicken. What’s more, Campylobacter is well known to put you on your ass, or at least pooing a lot out of it. It is the most common bacterial cause of enteric disease worldwide, with two million American cases reported annually.

From there, though, he goes through a series of objections which range from reasonable but misleading to completely ridiculous. Let’s take each in turn.

  1. Do most dogs have Campylobacter in their intestines regardless of what they are fed?

The prevalence of Campylobcater in healthy dogs varies. Some studies show rates from 25-58%, as Dr. Brady claims, but others show much lower rates (such as this study in Poland with infection rates < 5%). Dr. Brady is being misleading, however, in suggesting that the rate in the Australian APN study was irrelevant because it was “normal” or the same as in normal dogs in Australia. The only other study looking and Campy in Australian used mostly stray dogs, which obviously have different diets and health status from owned pet dogs.

Certainly, not all dogs with Campylobacter will get sick, and not all varieties of Campylobacter are pathogenic. However, that has little to do with the results of the APN study. The dogs with APN still had Campy at a much higher rate than the dogs without APN, and this difference doesn’t magically go away just because other dogs in other places have had Campylobaxcter without having APN. As Dr. Brady acknowledges, Campylobacter is a potentially serious infection often acquired by exposure to raw chicken, and this remains true even if some strains are worse than others and not all dogs exposed to it get sick.

  1. There are many potential triggers for GBS and APN.

So what? If Campy from eating raw chicken is a risk factor (potentially causing 40% of human GBS cases), shouldn’t we do what we can to eliminate this and reduce the risk? Dr. Brady’s argument is like saying that because some people die in car crashes from reasons other than not wearing a seatbelt, we can ignore the fact that not wearing a seat belt is a major reason people do die in car wrecks. Medicine and public health are about reducing risk where we can, not creating a risk-free world. Until there is evidence of benefit from feeding raw meat (and right now there isn’t!), doing so despite the risk of diseases like Campy and APN makes no sense.

Dr. Brady makes a number of misleading or false statements in this section of his post. For one, he cites a paper that found no association between APN and Campylobacter to suggest this contradicts the Australian study. What he ignores is the fact that the paper he cites studied an entirely different population of dogs in another part of the world, it used less reliable measures of Campylobacter infection (serology rather than culture and PCR), and none of the dogs in that study were fed raw meat. In implying that this paper undermines the conclusion of the Australian study, Dr. Brady is either being disingenuous or showing a lack of understanding of basic principles in science and epidemiology.

Interestingly, the study he cites here implicated a different pathogen, Toxoplasma, as a potential trigger for APN. Since this parasite is also mostly acquired in humans from eating undercooked meat, this would actually provide another reason to avoid feeding raw meat to dogs. Dr. Brady cherry picks not only the studies he cites but the parts of them he refers to.

Brady also mentions vaccinations as a potential trigger for APN. In doing so, he cites a case report, which is a much lower level of evidence than the Australian case-control study he is dismissing here. He chooses which evidence to accept and which to reject based primarily on what agrees with his beliefs, not objective scientific criteria for the strength of the evidence.

Even more ridiculous is Dr. Brady’s reference to a study he suggest shows that APN can occur in dogs not even being fed “real food” but still nursing (how mother’s milk is not “real food” isn’t made clear). The study he cites, however, is actually a case report of dogs with a protozoal parasite invading their brains and causing neurologic symptoms, which is not even the same disease as the immune-mediated APN in the Australian study. This fast-and-loose approach to scientific evidence is another example of how Brady seeks only to legitimize his existing beliefs with reference to cherry-picked or misconstrued research, not to really listen to the evidence.

  1. Was the study too small or poorly done?

The short answer is, “No.” Sample size is always an issue in veterinary research, especially when studying uncommon diseases like APN. Most of the time, too small a sample either leads to false negative results due to low statistical power (that is, not finding something that is actually true because you didn’t have enough examples to get a statistically significant result). The other problem with small samples is that random variation between individuals can more easily lead to the appearance of differences between groups that don’t really exist. If you measure the height of five people to determine the average height in the entire country, a sample that includes only men or only NBA basketball players is likely to give you a result that doesn’t accurately reflect the whole population.

A larger sample would certainly strengthen the results of the APN study, but the results were quite consistent and distinctive even with the numbers used. The results were also consistent with the existing evidence regarding the link between Campy and eating raw chicken as well as the link between Campy and GBS in humans. To borrow a phrase from Dr. Brady, it is “extremely unlikely” that the results of this study are due to chance effects from a small sample population.

His second criticism is less reasonable and betrays a surprising lack of understanding of research methods for someone with a PhD. He complains that the control group was not selected “randomly.” He is correct that it was not, but he is confusing this study, which was a case-control study, with a randomized clinical trial, which is a very different design with different methods.

In a case control study, you start by collecting patients with the disease you are interested in. This is commonly done for rare diseases because simply studying a bunch of patients at random would likely never give you enough cases to learn anything from. Once you have your cases, you select controls that are matched to your cases so that they are likely to be representative of the same group that the cases came from. That means deliberately looking for patients with similarities to the patients with the disease such as age, sex, race, etc. This is not a mistake, it is a core feature of the type of study being done.

Dr. Brady then makes a bunch of comments about how the case selection method invalidates the results which illustrate that he doesn’t understand very well the research methods he is critiquing. He complains that selecting staff pets means they aren’t comparable to the APN dogs because they were less likely to be fed raw chicken. However, the fact that dogs without APN are less likely to be fed raw than dogs who are eating raw meat is exactly the thing being studied. If the control dogs and the APN dogs were all eating raw, there would be no way to tell if this was a risk factor or not!

Similarly, Brady complains that the dogs were not matched on weight, implying again this invalidates the results. But once again, this was a deliberate part of the design to allow the investigation of weight as a potential risk factor, as is actually explained in the published study report: “Very coarse frequency matching by dog size (so that this variable could still later be analyzed for associations with case-control status).” It turned out that weight wasn’t a risk factor associated with APN anyway, but breed size category was. Small breeds were more likely to be APN cases that larger breeds.

Now, the authors hypothesized this might be because small breeds were more likely to be fed raw chicken and get Campylobacter, which are the main risk factors associated with APN in this study. Dr. Brady seems to agree that small breeds are more likely to be fed raw chicken, but he makes the odd conclusion that instead of this leading to Campy infection which triggers APN, small dogs are more likely to get APN for some other reason and the fact they eat raw chicken more often is unrelated.

If this is true, then of course we have to ignore all the evidence of association between Campy and GBS and between raw chicken and Campy and just assume there is some other reason small breed dogs get more APN. This is not supported by any reasoning or evidence. It is ultimately just a guess intended to deflect any potential acknowledgement of the risks of raw feeding.

4. Couldn’t Campy in APN dogs be due to something else? Anything else?! ANYTHING BUT RAW!!

At this point, Dr. Brady loses even basic coherence in his argument. He asks the rhetorical question “Might there be another reason dogs with APN shed Campylobacter” and proceeds to admit he doesn’t know, but he is willing to speculate wildly so long as the reason is anything but feeding raw meat. All the evidence that eating raw meat is associated with Campy in humans and other animals is ignored as he grasps at straws to find another answer more compatible with his faith in raw feeding.

He meanders into unsubstantiated musings about reverse causality, suggesting APN weakens the immune system which leads to Campy infection. This is clearly nonsense since APN is an inappropriate immune system reaction, not a weakened immune system, and the overwhelming majority of Campy is associated with eating raw meat in people and dogs without APN.

Brady then launches into a tirade about the evil of feeding dogs carbohydrates that has absolutely nothing to due with Campy, APN, and the Australian study. This is simply hand-waving to distract from the lack of a coherent explanation for the study findings. He also turns the lack of evidence for raw feeding on its head, suggesting that the lack of any research evidence showing health benefits to feeding raw rather than conventional diets is actually a reason to choose raw diets. Talk about smoke and mirrors! The decades of research on conventional diets is casually dismissed by reference to “industry,” which is not only silly but hypocritical for someone who makes his living selling unproven supplements, diets, and dietary advice.

Finally, he launches into a lofty rhetorical assault on the pet food industry, full of sound and fury but also full of bullshit and woefully lacking in facts. Here is a brief sample:

Lacking any evidence to support the use of their junk food products over fresh ingredients, all they have left to convince you to hand over €5 per kilo for what is Weetabix with cows toenail and crushed centrum tablet in it, is smoke and mirrors. And the best smoke is fear. Fear you will do it wrong. Fear they will get sick. Fear you will get sick. Fear your kids will get sick.

…as cereal-based dry food sales stutter and fall worldwide, to be replaced by more natural, raw dog food products not yet owned by them, the multi-billion industry is not going to go down without a fight. The notion of fear and danger will keep coming up, more and more in the future. ..while raw dog food is yet to kill a dog or harm a single human, dry food cannot say the same in either instance. Injury aside, dry foods’ body count from chemical and microbiological contamination is absolutely shocking.

There isn’t a dry-versus-raw debate guys, any more than there is a global warming debate. There is only skewed, industry nonsense and everyone else. Fear is their weapon. Truth is their enemy. The really scary bit is that what is true and what is industry-nonsense will become harder and harder to detect.

Actually, I find the really scary bit to be the ability of a smart, scientifically educated person like Dr. Brady to ignore and distort evidence to preserve his beliefs at any cost. One can speculate on the financial motives that might influence his thinking, as he clearly believes it influences the thinking of anyone who dares to disagree with him, but I actually doubt that’s a major factor. I think he is simply a true believer who fancies himself a brave warrior against the Evil Empire and is unable to accept any facts that might undermine that belief. The real scary bit is that people might belief the rhetoric and the distortions and suffer for it. Despite his bold claim to the contrary, raw food can harm your pets and you and, yes, your children. Here is just one recent example:

The Minnesota Department of Health reports that two children in a single household were exposed to contaminated Raws for Paws product, which was used to feed the family dog. One child’s illness resulted in septicemia (blood infection) and osteomyelitis, a painful and serious bone infection.

Testing performed by the Minnesota Department of Health and the Minnesota Department of Agriculture demonstrated that the same strain of S. Reading found in the ill children was also found in four samples of Raws for Paws Ground Turkey Food for Pets that was used to feed the family pet.

Dr. Brady can call me a dupe or lackey of Big Pet Food if he wants (and I suspect he will). The truth is, I am open to the idea that fresh food, even raw food, might have health benefits. However, the evidence is clear that raw has risks, and it is up to the proponents of raw diets to prove there are benefits that make these risks worth taking. Not with anecdotes, faulty logic about what is “natural,” rhetorical assaults on the pet food industry, or mere passion. They should prove it with data, with reliable evidence derived from appropriate scientific research. Until they do so, there is no reason for pet owners to take the risks they deny exist for ourselves, our pets, or our families.

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