Evidence Update- Ocu-GLO for Prevention of Cataracts in Diabetic Dogs

About a year ago, I wrote a review of Ocu-GLO, an oral supplement marketed for a variety of purposes:

Ocu-GLO Rx™ is needed when your dog is showing any of the following signs:

– Diminished vision at night or in dim conditions – Diminished vision at all times – Cloudy appearance to eyes – Pupils that do not constrict – Obvious cataracts Or… -Your dog is generally healthy, but you want him or her to be placed on an excellent lifetime antioxidant supplement to help support and enhance ocular health and also general health.

We (Drs. Carmen Colitz and Terri McCalla) are also dispensing Ocu-GLO Rx™ for patients predisposed to primary glaucoma (having lost their first eye to glaucoma) and that already have glaucoma; for Golden Retrievers with pigmentary uveitis (also called “Golden Retriever Uveitis” or GRU); for diabetic dogs in which cataracts are immature or have not yet formed; for dogs with senile retinal degeneration; for dogs post-cataract surgery to help reduce the incidence of PCO and ACO (Posterior Capsular Opacity and Anterior Capsular Opacity) and for any dogs for which owners want to provide the best nutritional support for their pet’s eyes.

At the time, I concluded that the theoretical premise behind the product and the specific ingredients included was plausible but supported only by weak evidence, and there was little direct clinical research in humans, and virtually none in dogs, showing actual benefits. Therefore, no firm conclusion about the safety and efficacy of the product was possible.

I also noted that:

Unlike the marketing for many supplements pitched to pet owners, the claims made by this company are pretty measured and reasonable in light of the limited available evidence…Hopefully, the ophthalmologists behind the product will pursue appropriate research efforts to determine if, in fact, the product has the benefits they suspect and what, if any, risks are associated with its use.

I was pleased, therefore, to see a clinical trial investigating Ocu-GLO published this month which adds to the evidence regarding this product.

Williams, D. Fitchie, A. Colitz, C. An Oral Antioxidant Formulation Delaying and Potentially Reversing Canine Diabetic Cataract: A Placebo-controlled Double-masked Pilot Study. Int J Diabetes Clin Res 2015, 2:1

This trial targeted a specific disease, cataracts developed by diabetic dogs. The process of cataract formation in diabetics is well understood, and there is reason to expect at least some of the ingredients in Ocu-GLO might influence this process, so again there is a plausible potential mechanism here that is consistent with established science.

The study involved giving either the supplement or a control containing antioxidant vitamins but not several of the other ingredients in Ocu-GLO, to 15 dogs each and monitoring them for changes in their lenses that would indicate cataract formation. It was not considered ethical to allow actual cataract development, so once such signs appeared, the treatment was identified and dogs who had been getting the control vitamins were switched to the supplement.

The results were quite impressive.

Mean time without change in lens opacification at the time of writing was 278±184 days with Ocu-GLO Rx™ and 77 ± 40 days in the placebo group. Median duration without lens change was 261 and 84 days, respectively, this difference being statistically significant at p=0.0003.

Twelve of the 15 dogs (80%) taking the placebo developed significant lens changes while on the study protocol. Five of 15 dogs (33%) taking Ocu-GLO Rx™ developed significant cataract, in three of these animals Ocu-GLO Rx™ was not being given as directed…

These differences between the groups is not only statistically significant but, far more important, they are clinically relevant. While the supplement did not absolutely prevent lens changes in treated dogs, it appeared to dramatically delay these changes. In one subject who was switched from the control supplement to the test product, it appeared that the product even reversed changes that had already begun.

Like all research, there are flaws and limitations to this study which require some skepticism about even such dramatic results. To begin with, several key methodological factors were not mentioned in the published report. This is unfortunately extremely common in veterinary research. However, I contacted Dr. Williams, the lead author, and he was kind enough to answer a few questions and provide at least some of this missing information.

There is no mention in the paper of how the subjects were assigned to the two groups. Random assignment, and a process which prevent anyone from intentionally or unconsciously influencing the selection and assignment of patients, is a critical component to reducing bias and error in clinical trials. According to Dr. Williams, the subjects were individually randomized to the two groups. It is not entirely clear, though, how this process was protected from being unintentionally influenced by study personnel or how the exact balance in number between the groups was achieved.

Blinding of investigators and owners to the treatment assignment is another critical element of an effective clinical trial. It appears that investigators were effectively blinded to the treatment each patient received. This is especially important because the outcome being measured was subjective and not very precisely defined as “significant progression of lens opacity, as documented photographically.” It is not clear if the owners could distinguish the two treatments, but this would be less likely to have a significant impact on the results since owners were not involved in assessing the outcome.

A number of other potential limitations exist in this study, including minimal comparison of the two groups before treatment to ensure there were no relevant differences and a small number of subjects, but in general the design and execution seem quite good.

One of the authors, Dr. Colitz, is affiliated with the company marketing Ocu-GLO. This raises the potential of unconscious or overt bias, but this is likely mitigated by the blinding, randomization, and other typical bias-control aspects of the study. Dr. Williams also indicated that there was no financial support of the study from the manufacturer, reducing the risk of any funding bias.

The issue of adverse effects was not specifically addressed in the published report. The company has previously indicated that some unpublished data exist demonstrating the product is safe, and there is no specific evidence to suggest any risk, though unintended effects with long-term use or in particular patients cannot be completely ruled out. With the limited evidence currently available, there seems to be little risk to the use of this product.

I have previously discussed the Decline Effect, which is a well-recognized phenomenon in which small, early studies of a scientific hypothesis give dramatic results which diminish, and sometimes disappear entirely, in subsequent research with better control for bias, confounding, and other sources of error. So it is important to remember that no single study ever definitively proves or disproves a scientific hypothesis. As the researchers themselves acknowledge, further research is not only desirable but necessary to allow confidence in these findings and this treatment.

Bottom Line

This is a small but well-executed clinical trial with a large, clinically relevant difference in the progression of changes in the lens clarity of dogs with diabetes treated with Ocu-GLO compared with a control supplement. The trial is not perfect, of course, and no single trial should ever be viewed as definitive. And this study applies only to the issue of using this supplement to slow the development of cataracts in diabetic dogs. It does not provide good evidence that the supplement can completely prevent or cure cataracts or that it is effective for other uses.

As always in veterinary medicine, however, we must make decisions on the basis of the imperfect evidence we have, while still pursuing more and better evidence. Though the evidence is still limited at this point, I believe it is good enough to recommend the use of this supplement for cataract prevention in diabetic dogs.

 

 

 

 

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What Do Holistic Vets Say About Science and Evidence-based Medicine?

I’ve written several times about how proponents of alternative therapies appear to view science and evidence-based medicine. (1, 2, 3)  I think it is critical in evaluating these practices, as pet owners or  veterinarians, to understand the philosophy and approach behind them. Alternative medicine advocates will frequently talk about their respect for science, and will laud studies that appear to support their claims. But in many cases, they are fundamentally not convinced that science is superior to personal experience or faith as a method of evaluating medical therapies, and they are virtually never willing to abandon a practice they believe they have seen work no matter how clear the evidence against it is. If people wish to apply such practices, of course they are free to make that choice. But they should be fully and honestly informed when they are being asked to choose belief and opinion over science and evidence.

The following are comments veterinarians who are advocates for alternative veterinary therapies and critics of conventional medicine. These illustrate some of the views that should concern those of us committed to a scientific approach to evaluating the treatments we use for our patients and animal companions. I will be adding to this collection of comments over time, just to have examples available of the kinds of misconceptions those of us committed to a science-based approach to medicine need to address in our efforts to educate and to promote evidence-based medicine.

Evidence-based Medicine
“Remember evidence based science is last to know.”

“#AHVMF strongly supports scientific process, but in seeking real answers we recognize that scientific practice is last to know. #pioneers”

“Since evidence based medicine can’t know what hasn’t been studied, a false separation of proven vs unexamined data fields arises.”

“Evidence based medicine is being miss used according to its creators. It was about integrative informed decision processes.”

“The evidence said the case would die, the people felt otherwise. They tried, they lived, they danced together & finally all died. Life! :-)”

“Evidence should inform decision making but not limit treatment options. Combining experience and evidence is called evidence based practice, an excellent model for advancing veterinary care in areas with less evidence. Patients need access to all options and guardians and clinicians want to know.”

Placebo
“At the root a healing from placebo IS real healing from the person. How do we improve self healing? Can we align w/ Nature simply powerfully.”

“Perhaps love is the basis of placebo. In that case let’s fill the world and to hell with the research. Ascendant mindfulness finds healing.”

Anecdotes/Stories
“Stories have an important place in discovery of new approaches and therapies in medicine. No cure? Find the stories and follow those paths.”

“Narrative medicine allows the telling of a story, the discovery of truth, its sharing and consequences. Help write a happy ending.”

Leading integrative veterinarian Richard Palmquist will describe how he went from skeptic to champion of integrative veterinary medicine through witnessing miraculous outcomes from integrative approaches, after conventional options were exhausted.

“I suggested we apply a dose of Caulophyllum 30c…about 45 minutes later a live calf was eased into the world.

I readily accept this is not a scientific experiment that would satisfy the cynically minded, but when one saw this repeatedly over a period of 15 years it held much greater sway for us than any scientific experiment.”

“As a veterinarian now practicing homeopathy and chiropractic almost exclusively,  I have all the proof I need every day in my practice to justify these modalities.”

Science
“It might take science >100-1000 years to categorize and understand some basic healing principles. Pioneers go first, science comes later.”

#RealSearch is actual scientific pursuit of truth without interference in design or reporting of data. It seeks causal discovery. Support it. We don’t look because we believe, we believe because we have seen so many people and animals benefit from integrative therapies. Did you know the word believe means we find truth in or feel affection for an area? It’s an interesting word when we consider its origin. When we find something true, we love. When we love we find truth. These go hand in hand with healing, too. First we look, then we test, then we believe. THEN we LIVE. BE LIVE!”

“Universities exist to provide a circle for the exploration & perfection of love. At their core each subject, each expert is examining this.”

“Pearls of wisdom handed down through the generations, scientific studies, and Chinese terminology bring together knowledge that is most certainly true. Modern science and the trend toward evidence based medicine has many pitfalls, whereas the “tried and true” passed through centuries holds as much truth for me.”

“Science is powerful and wonderful and so important. We must not lose ourselves in the game of science while ignoring healing.”

Alternative Medicine
“Holistic medicine addresses the patient as a whole – body, mind, and SPIRIT. There is a level of reality beyond, and yet enmeshed in, the physical, material universe. If I did not have an appreciation of the spiritual aspects of my patients and their caregivers, they and I would become little more than robots.

Don’t settle for treatment by a robot.”

“There is evidence-based research that holistic medicine works, but many people are quick to dismiss it because the studies are not funded by pharmaceutical companies,” she says, “the research is there if people would just do it.”

“If your veterinarian (or medical doctor for that matter) is relying strictly on published medical information for his prescribed treatment options, then his therapy will be 90% flawed. In other words, he will get it right 10% of the time.”

“Lack of ‘adequate’ research is why alternative medicine is considered alternative and is excluded from EBM. This lack of “evidence” is also an excuse for the rejection and criticism of many helpful alternative therapies by well-meaning, conventional practitioners. This attitude may lead your veterinarian astray.”

“Critics of homeopathy like to throw up the term “evidence based medicine”, as if to suggest that pharmaceutical drugs are more scientifically arrived at. If they are evidence based, why are they always being withdrawn after causing injury and death? Let’s explore the actual evidence.

Bottom line: Drug companies commit fraud in drug testing, lie about drug effectiveness and safety, publish positive articles in peer reviewed journals and then sell those drugs to the public. The FDA redacts the wrong doing from their reports.

Now you know…. pharmaceutical drugs are NOT evidence based… period.”

“How does acupuncture work? We know that it does work from thousands of years of experience.”

“Traditional Chinese Veterinary Medicine (TVCM) has been used in China for about 3000 years. Originally the practice was handed down from father to son and you were only paid if you made your patient well. So you either got good at it or your family line died out. “

“Holistic practitioners believe that vital life energy is the most important factor in the health of the patient…Because medical science has defined itself on a strictly physical basis, it is true that vitalism is unscientific. By definition, vitalism embraces a concept about a nonphysical force that can never be understood within the current scientific, medical paradigm.”

 

 

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Evidence Update- Neutering and Cancer Risk in Danish Dogs

One of the “hot topics” in veterinary medicine right now is the balance of risk and benefits to neutering. Even though I completed an extensive review of this subject in 2010, and updated it just last year, the new evidence is rolling in at brisk pace. The latest tidbit I have come across specifically touches on the specific issue of cancer risk.

M.M.E. Larsen, B. Børresen, A.T. Kristensen.  Neuter status and risk of cancer in a Danish dog population.

…From August 2005 to March 2014, 3801 canine neoplasms were reported to the Danish Veterinary Cancer Registry…The overall distribution of malignant neoplasia was 481 (38%) intact male dogs, 157 (12.5%) neutered male dogs, 404 (32%) intact female dogs and 220 (17.5%) neutered female dogs. The distribution was even between male and female dogs (50.5% and 49.5%). Compared to a known standard population of dogs, there was an overall statistically significant association of malignant neoplasia with neuter status in both sexes. For both genders this was significant for lymphoma, mast cell tumors and osteosarcomas. For neutered females, but not males, there was increased risk of hemangiosarcoma, squamous cell carcinoma and malignant melanoma. These findings indicate that there might be an association between neuter status and development of malignant neoplasia but larger prospective studies are needed to evaluate the risk of non-sex hormone dependent cancers in neutered dogs.

This was published as an abstract of a presentation at the European Society of Veterinary Oncology, so the full details of the study are not available. In particular, the breed and age of the dogs involved are factors which have proven critical to evaluating any link between neutering and cancer risk in previous studies. Hopefully, more data will become available in a full-length publication.

This study is in general agreement with some of the previous research in suggesting neutering may increase the risk of some specific cancers, and that this increase will differ between males and females. The tables below summarize previous studies on neutering and lymphoma, mast cell tumors, osteosarcoma, and hemangiosarcoma, so these data can be put in context.

As always, it is critical to evaluate the importance of any change in cancer risk with other health effects, including potential benefits. There is, for example, evidence that mammary cancer rates are decreased by neutering. And there is also some evidence that neutered animals live longer than intact animals, and if this is true it would certainly influence any decision about what action to take based on the new data about neutering and cancer risk. The subject is complex, and simple rules of thumb are unlikely to be very useful in making decisions about what to do for individual pets. Fortunately, as more and more data become available, we should be able to do a better job of making informed decisions about neutering in particular patients.

 

 

Table 1: Cited reports examining the relationship between neuter status and risk of osteosarcoma in dogs

Study More Common Neutered More Common Intact No Difference Comments
Ru, G. 1998 OverallOR=2.2 Purebred dogs only, case-control study
Cooley, D. 2002 Males neutered <1yrRR=3.8

(95% CI=1.5-9.2)

 

Females neutered <1yr

RR=3.1

(95% CI=1.1-8.3)

Males neutered 1-3.5yrsRR=1.7

(95% CI=0.7–4.3)

 

Males neutered >3.5yrs

RR=1.4

(95% CI=0.6–3.5)

 

Females neutered 1-5yrs

RR=1.4

(95% CI=0.5–3.8)

 

Females neutered >5yrs

RR=1.2

(95% CI=0.4–3.2)

Rottweilers only, retrospective cohort
Hoffman, J.M. 2013 Overall Multiple breeds/mixed-breeds, retrospective cohort

 

This study found an increased risk with neutering for both males and females, but no information on age at neutering or breed was provided.
Table 2: Cited reports examining the relationship between neuter status and risk of hemangiosarcoma in dogs

Study More Common Neutered More Common Intact No Difference Comments
Prymak, C. 1988 FemalesOR=2.2

(95% CI=1.2-4.1)

 

Males Splenic HSA only, retrospective cohort
Ware, W. 1999 FemalesRR=5.33

(95% CI=3.96-7.19)

 

Males

RR=1.55

(95% CI=1.21-1.98)

Differences not found for all breeds, retrospective cohort, cardiac HSA only
Torres de la Riva, G. 2013 Females neutered >12mosRR=6.1

(95% CI=1.18-31.37)

MalesFemales neutered <12mos Golden retrievers only, retrospective cohort
Hart, B.L. 2014 All groups Golden retrievers & Labrador retrievers, retrospective cohort
Zink, M.C. 2014 Males neutered >12mosOR=5.3

(95% CI=1.5-18.2)

 

Females overall

OR=9.0

(95% CI=2.8-29.4)

 

Females neutered >12mos

OR=11.5

(95% CI=3.5-38.5)

 

Females neutered <6mos

OR=6.0

(95% CI=1.7-21.3)

Males overallOR=0.6

(95% CI=0.3-1.4)

 

Males neutered <6mos

OR=2.0

(95% CI=0.6-7.3)

Viszlas only, online owner survey

 

This study found an increased risk with neutering for females and not for males, but no information on age at neutering or breed was provided.

 

 

Table 3: Cited reports examining the relationship between neuter status and risk of lymphosarcoma in dogs

Study More Common Neutered More Common Intact No Difference Comments
Villamil, JA. 2009 Intact Female OR=0.69(95% CI=0.63-0.74) Intact MaleOR=1.32

(95% CI=1.24-1.41)

 

Neutered Male

OR=0.91

(95% CI=0.85-0.97)

Neutered FemaleOR=1.02 (95% CI=0.96-1.08) Multiple breeds, matched case-control study, OR is for development of lymphoma in each sex category
Torres de la Riva, G. 2013 Males neutered <12mos FemalesMales neutered >12mos Golden retrievers only, retrospective cohort
Hoffman, J.M. 2013 Overall Multiple breeds/mixed-breeds, retrospective cohort
Hart, B.L. 2014 Male & Female Goldens neutered 6-11mos  Males and Female Goldens neutered <6mos and >1year 

All Labradors

Golden retrievers & Labrador retrievers, retrospective cohort
Zink, M.C. 2014 OverallOR= 4.3

(95% CI=1.9-9.7)

 

Neutered <6mos

OR=3.5

(95% CI=1.3-9.6)

 

Neutered 7-12mos

OR=3.1

(95% CI=1.0-9.4)

 

Neutered >12mos

OR=5.2

(95% CI=2.2-12.0)

Viszlas only, online owner survey, OR reference category is intact animals

 

This study found an increased risk with neutering for both males and females, but no information on age at neutering or breed was provided.

 

Table 4: Cited reports examining the relationship between neuter status and risk of mast cell neoplasia in dogs

Study More Common Neutered More Common Intact No Difference Comments
White, CR. 2011 FemalesOR=4.11

(95% CI=2.19–7.69)

MalesOR=1.37

(95% CI=0.90–2.09)

Case/control study, multiple breeds
Hoffman, J.M. 2013 Overall Multiple breeds/mixed-breeds, retrospective cohort
Torres de la Riva, G. 2013 Females2.3% of neutered <12mos

5.7% of neutered >12mos

No cases in intact

Males1.7% of neutered <12mos

4.2% of neutered >12mos

2.8% of intact

Golden retrievers only, retrospective cohort
Hart, B.L. 2014 Female Goldensneutered <6mos & >1yr All Golden MalesAll Labradors Golden retrievers & Labrador retrievers, retrospective cohort
Zink, M.C. 2014 OverallOR=3.5

(95% CI=2.3-5.4)
Neutered <6mos

OR=2.8

(95% CI=1.6-5.0)

 

Neutered 7-12mos

OR=2.0

(95% CI=1.1-3.9)

 

Neutered >12mos

OR=4.5

(95% CI=2.9-7.0)

Viszlas only, online owner survey, OR reference category is intact animals

 

This study found an increased risk with neutering for both males and females, but no information on age at neutering or breed was provided.

 

 

 

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Longevity & Causes of Death in Pet Cats

Basic epidemiological research, identifying the most common diseases and causes of death and risk factors for these, is the foundation of preventative medicine. Unfortunately, such research is often scarce in veterinary medicine. Collecting data on a large population of animals over an extended period of time is expensive and time-consuming, and since there is generally no direct economic incentive for doing so and little private or government funding for such research, studies like this are seldom done.

Some longitudinal data have been collected by insurance companies, large corporate practices, and some non-profit organizations supporting veterinary research. A recent paper has reported some information from another source, VetCompass. This is an effort of the Royal Veterinary College to collect clinical data from private veterinary practices and use this data to improve our understanding of health and disease in veterinary patients. This is a potentially rich source of information, and such efforts could contribute significantly to the evidence base needed to improve healthcare for our pets.

O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Longevity and mortality of cats attending primary care veterinary practices in England. J Feline Med Surg. 2015 Feb;17(2):125-33. doi: 10.1177/1098612X14536176. Epub 2014 Jun 12.

A brief version of the results can be found on the VetCompass site. The study used data from over 100,000 cats at 90 different practices in England, which allowed for some pretty robust statistical analysis. A random sample of cats who had died was used to investigate longevity and causes of death

A couple of interesting patterns emerged from these. The median longevity was 14 years, but this did vary quite a bit by breed, and there were two peaks in mortality—one at 1 year of age and another at 16 years of age (Figure 1). This suggests that cats pass through a period of relative high risk at about 1 year, but those who get through this time have a could chance of living well into their teens.

longevity chart

The leading cause of death is listed as trauma, which I initially found surprising (Table 2). However, when causes of death are broken down by age group, this is the #1 cause for cats under 5 years of age. It is still #6 for cats over 5, which suggests a higher proportion of outdoor cats than I typically see in my area. For the young cats, trauma accounted for 47% of the death (half of these from road accidents), far more than the second-leading cause of death, viral infectious disease, which accounted for only 6.6%.This is a reminder of why an outdoor lifestyle is a very risky one for domestic cats.

For cats over 5 years of age, kidney disease was the leading cause of death, accounting for 13.6% of the deaths evaluated. Unfortunately, the second-leading cause was the rather uninformative category of “non-specific illness.”

mortality cats

The study also used a linear regression analysis to evaluate factors associated with longevity. In addition to finding that mixed-breed lived longer than purebred cats, the data did show a longevity benefit to neutering. Neutered female cats lived roughly six months longer than intact female cats. Intact male cats, however, died nearly two years younger than neutered male cats. The reasons for this difference are likely multiple. While neutering has been associated with greater longevity in a variety of species, and there seems to be some underlying physiological factor that contributes to greater longevity in neutered individuals. However, there are also likely other differences that have more to do with husbandry than biology. If, for example, neutered male cats are less likely to be allowed outside than intact male cats, which is almost certainly the case, then the risk of being an outdoor cat will confound any apparent effect of neuter status on longevity.

There are, as always, limitations to this study. The accuracy of causes of death could not be independently verified, and many were lumped under the vague heading of “non-specific illness.” The evidence that comes out of retrospective studies of medical records is only as good as the information that goes into the records, so there is always a significant risk of error when dealing with a large and diverse group of clinicians who haven’t all been trained in the same way to use the same record-keeping practices.

The results of this study also apply only to the population studies, which means cats of this particular mix of breeds, lifestyles, and those with similar husbandry and environmental circumstances. The results likely would be different in some significant respects from, for example, an urban U.S. cat population. Nevertheless, the accumulation of such information from different sources over time provides valuable knowledge about the factors that influence health, disease, and longevity in our pet cats, and more such research is critical to improving the care we provide and the health of our pets.

 

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What You Know that Ain’t Necessarily So: Antibiotics, Endocarditis, & Dentistry

I recently gave a lecture at the Western Veterinary Conference called “What You Know that Ain’t Necessarily So.” The purpose of this was to take some common or controversial beliefs and practices in veterinary medicine and discuss the scientific evidence pertaining to these. This was not intended as a definitive, “final word” on these subjects, but as an illustration of how weak and problematic the evidence often is even behind widely held beliefs. In some cases, these practices or ideas may actually be valid, but without good quality scientific evidence, we should always be cautious and skeptical about them.

Eventually, I will post recordings of the presentations themselves, but for now I am posting a summary of each topic.

Each starts with a focused clinical question using the PICO format.

P- Patient, Problem Define clearly the patient in terms of signalment, health status, and other factors relevant to the treatment, diagnostic test, or other intervention you are considering. Also clearly and narrowly define the problem and any relevant comorbidities. This is a routine part of good clinical practice and so does not represent “extra work” when employed as part of the EBVM process.

I- Intervention Be specific about what you are considering doing, what test, drug, procedure, or other intervention you need information about.

C- Comparator What might you do instead of the intervention you are considering? Nothing is done in isolation, and the value of most of our interventions can only be measured relative to the alternatives. Always remember that educating the client, rather than selling a product or procedure, should often be considered as an alternative to any intervention you are contemplating.

O- Outcome What is the goal of doing something? What, in particular, does the client wish to accomplish. Being clear and explicit, with yourself and the client, about what you are trying to achieve (cure, extended life, improved performance, decreased discomfort, etc.) is essentially in evidence-based practice.

This is then followed by a summary of the evidence available at each of the levels in the following pyramid (which is a pragmatic reinterpretation of the classical pyramid of evidence that is a bit more useful for general practice veterinarians).

evidence pyramid

Finally, I list the Bottom Line, which is my interpretation of the evidence.

Antibiotics, Endocarditis, & Dentistry

  1. Clinical question

P- dogs & cats with periodontal disease

I- prophylactic antibiotics with dentistry

C- no antibiotics with dentistry

O- incidence of bacterial endocarditis

2. Synthetic Veterinary Literature

a. No systematic reviews:
b. No critically appraised topics

c. Guidelines-

…use of a systemically administered antibiotic is recommended to reduce bacteremia for animals that are immune compromised, have underlying systemic disease (such as clinically-evident cardiac, hepatic, and renal diseases) and/or when severe oral infection is present.

American Veterinary Dental College

3. Primary Veterinary Literature

Retrospective review of records for ~59,000 dogs with periodontal disease

periodontal disease was associated with cardiovascular-related conditions, such as endocarditis and cardiomyopathy.

  • Concerns about diagnostic criteria
  • Many data inconsistent with previous findings
  • Study design not appropriate to establish causal relationship

Glickman, L.T. (2009)

  • Retrospective case (70)/control(80) study
  • No association between dental disease or Tx and endocarditis

Peddle, G.D. (2009)

4. Human Literature

a. Systematic Reviews

There remains no evidence about whether antibiotic prophylaxis is effective or ineffective against bacterial endocarditis in people at risk who are about to undergo an invasive dental procedure. It is not clear whether the potential harms and costs of antibiotic administration outweigh any beneficial effect.

Glenny, A.M. (2013)

b. Clinical Practice Guidelines

Today, antibiotics before dental procedures are only recommended for patients…who have:

  • A prosthetic heart valve or who have had a heart valve repaired with prosthetic material.
  • A history of endocarditis.
  • A heart transplant with abnormal heart valve function
  • Certain congenital heart defects

American Heart Association

Antibiotic prophylaxis against infective endocarditis is not recommended:

  • for people undergoing dental procedures
  • for people undergoing non-dental procedures at the following sites:
  • upper and lower gastrointestinal tract
  • genitourinary tract
  • upper and lower respiratory tract

Chlorhexidine mouthwash should not be offered as prophylaxis against infective endocarditis to people at risk of infective endocarditis undergoing dental procedures.

National Institute for Health & Care Excellence

Bottom Line

  • Endocarditis is rare
  • Dental treatment is probably not a major risk factor for endocarditis
  • Antibiotics with dentistry are probably not useful in preventing endocarditis

Fun Fact!

  • Antibiotics with dentistry are probably not useful in preventing endocarditis
  • Overall bacteremia in 6 blood samples-
  • Extraction + amoxicillin- 56%
  • Extraction + placebo- 80%
  • Toothbrushing- 32%

Although amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction, given the greater frequency for oral hygiene, toothbrushing may be a greater threat for individuals at risk for infective endocarditis.

Lockhart, P.B. (2008)

References
Glenny AM, et al. Antibiotics for the prophylaxis of bacterial endocarditis in dentistry. Cochrane Database Syst Rev. 2013 Oct 9;10:CD003813.

Lockhart, PB. et al. Bacteremia Associated With Toothbrushing and Dental Extraction. Circulation. 2008; 117: 3118-3125.

Peddle GD, et al. Association of periodontal disease, oral procedures, and other clinical findings with bacterial endocarditis in dogs. J Am Vet Med Assoc. 2009 Jan 1;234(1):100-7.

Glickman LT, et al. Evaluation of the risk of endocarditis and other cardiovascular events on the basis of the severity of periodontal disease in dogs. J Am Vet Med Assoc. 2009 Feb 15;234(4):486-94.

 

 

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Jimmy Kimmel Gets Hate Mail (I feel your pain, Jimmy)

I review my own hate mail here from time to time (I’m actually overdue for another summary, so stay tuned). I totally get what Jimmy’s dealing with here!

 

 

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Jimmy Kimmel–oh, and some Doctors–Talk About Vaccination

I think we need a veterinary version of this video. Who’s with me?!

 

 

Posted in Humor | 37 Comments

Can Your Vet Diagnose a Seizure from Your Home Video?

The age of ubiquitous cell phone cameras is upon us, and it appears to be double-edged sword. On the one hand, moments historically understood to be private can, often without the participants’ permission, become worldwide entertainment. On the other hand, widespread video capability also has advantages. It may, for example, make it easier to catch the perpetrators of crimes. And in veterinary medicine, the ability to make videos of unusual and infrequent behaviors allows owners to more clearly show their vet what is happening with their pets, which may improve our ability to diagnose and treat some problems.

A recent study, the first of its kind, has begun the process of looking scientifically at the potential usefulness of one kind of video evidence often presented to vets– paroxysmal episodes which may be seizures, fainting spells, or other manifestations of disease.

Packer RMA, et al. Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists. BMC Veterinary Research (2015) 11:39.

The purpose of this study was to see if veterinarians, both neurology specialists and general practitioners, would agree on whether an event they saw on video was or was not a seizure. The study also looked in detail at agreement on specific ways of describing the events and at differences between specialists and non-specialists. There was no gold standard test to identify the right answer, so the purpose was not to see how well vets could identify seizures, but just to see if vets can even agree among themselves as to what is or is not a seizure. This is useful primarily in helping to refine and improve how we define and describe such events to make our diagnostic criteria better and our ability to use video evidence more accurate.

The image below shows some of the main data from this study.

video seizure identification

The results found generally only fair agreement about whether an event witnessed was or was not a seizure. On average, there was only 29% agreement between observers for each video as to whether or not the event witnessed was a seizure. Agreement was even lower with respect to the type of seizure or whether the animal in the video had impairment of consciousness. Agreement was generally better about the presence or absence of specific motor movements.

Interestingly, specialists were less likely to classify an event as a seizure than non-specialists, possibly because they were better able to recognize unusual events that mimic seizures but that non-specialists don’t get to see very often.

Overall, the study shows us that we need to put in some work to improve how we characterize seizures and events that can resemble seizures so that we can have a consistent classification system for describing what we see in the videos our clients bring us and a better ability to incorporate this kind of evidence into our diagnostic process.

Here is what the authors of this study concluded:

In conclusion, this study has demonstrated that there were relatively low levels of agreement of seizure presence, type and semiologies reported by veterinary neurology specialists and non-specialists, highlighting the need for ongoing debate regarding the descriptive terminology used for seizure semiology in veterinary medicine, and the need for further training in focussed areas.

Although the use of videos to diagnose seizure activity may be increasingly common, the results presented here demonstrate that it should not be solely relied upon, with existing diagnostics always supplementing videos, and new diagnostics such as EEG more widely used for more objective, definitive diagnoses.

 

Posted in Science-Based Veterinary Medicine | Leave a comment

What You Know that Ain’t Necessarily So: Vaccination & Autoimmune Diseases

I recently gave a lecture at the Western Veterinary Conference called “What You Know that Ain’t Necessarily So.” The purpose of this was to take some common or controversial beliefs and practices in veterinary medicine and discuss the scientific evidence pertaining to these. This was not intended as a definitive, “final word” on these subjects, but as an illustration of how weak and problematic the evidence often is even behind widely held beliefs. In some cases, these practices or ideas may actually be valid, but without good quality scientific evidence, we should always be cautious and skeptical about them.

Eventually, I will post recordings of the presentations themselves, but for now I am posting a summary of each topic.

Each starts with a focused clinical question using the PICO format.

P- Patient, Problem Define clearly the patient in terms of signalment, health status, and other factors relevant to the treatment, diagnostic test, or other intervention you are considering. Also clearly and narrowly define the problem and any relevant comorbidities. This is a routine part of good clinical practice and so does not represent “extra work” when employed as part of the EBVM process.

I- Intervention Be specific about what you are considering doing, what test, drug, procedure, or other intervention you need information about.

C- Comparator What might you do instead of the intervention you are considering? Nothing is done in isolation, and the value of most of our interventions can only be measured relative to the alternatives. Always remember that educating the client, rather than selling a product or procedure, should often be considered as an alternative to any intervention you are contemplating.

O- Outcome What is the goal of doing something? What, in particular, does the client wish to accomplish. Being clear and explicit, with yourself and the client, about what you are trying to achieve (cure, extended life, improved performance, decreased discomfort, etc.) is essentially in evidence-based practice.

This is then followed by a summary of the evidence available at each of the levels in the following pyramid (which is a pragmatic reinterpretation of the classical pyramid of evidence that is a bit more useful for general practice veterinarians).

evidence pyramid

Finally, I list the Bottom Line, which is my interpretation of the evidence.

Immune-mediated Blood Disease & Vaccination

  1. Clinical question

P- healthy dogs & cats

I- routine vaccinations

C- no vaccination (fewer)

O- incidence of Immune-mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (ITP)

  1. Synthetic Veterinary Literature
    a. No systematic reviews:
    b. No CATs
  2. Primary Veterinary Literature
  • Case/control study
  • Cases more likely to be vaccinated in previous month (26%) than controls (7%)
  • Did not r/o pre-existing disease

Duval, D. (1996)

  • 10% of cases vaccinated within 1 month
  • No difference between cases and controls in time from vaccination to presentation

Carr, A.P. (2002)

  • Proportion of dogs vaccinated within 2 months of onset not different between cases and controls
    • Cases- 16.1%
    • Controls- 44.4%

Davidow, E.B. (2004)

  • Proportion of dogs vaccinated within 42 days of onset not different between cases and controls-
    • Cases- 8%
    • Controls- 14%

Huang, A.A. (2012)

  • 4% vaccinated within 2 weeks
  • Not primary purpose of study

Reimer, M.E. (1999)

  • 2.4% vaccinated within 2 weeks
  • Not primary purpose of study

Klag, A.R. (1993)

3. Human Literature
a. Systematic Reviews

  • Database of 4.2 million children
  • 55 cases of IMHA reported 1991-2001
  • No association with vaccination

Naleway, A.L. (2009)

  • ITP only associated with MMR
  • 1-3 children per 100,000 doses
  • This is lower than the rate of ITP caused by the diseases MMR prevents! (1:3000 to 1:6000 cases)

Cecinati, V. (2013)

Bottom Line

  • Little evidence vaccination causes IMHA/ITP
  • No consistent temporal association
  • Data are weak
  • Overwhelming majority of vaccinated animals do not develop these diseases
  • Infection can be a greater risk for IMHA/ITP than vaccination
  • Don’t vaccinate more than necessary
  • Don’t vaccinate less than necessary
  • Don’t avoid vaccination out of fear of IMHA/ITP

Reference

Carr AP, et al. Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: A retrospective study of 72 dogs. J Vet Internal Med.2002;16:504-509.

Cecinati V. Hum Vaccin Immunother. Vaccine administration and the development of immune thrombocytopenic purpura in children. 2013 May;9(5):1158-62.

Davidow EB, et al. Risk factors for development of IMHA-A prospective case-control study. Abstract. VECCS 2004.

Duval D et al. Vaccine-associated immune-mediated hemolytic anemia in the dog. J Vet Internal Med. 1996;10:290-295.

Huang AA, et al. Idiopathic immune-mediated thrombocytopenia and recent vaccinations in dogs. JVIM 2012; 26: 142-148.

Klag AR, et al. Idiopathic immune-mediated hemolytic anemia in dogs: 42 cases (1986-1990). J Am Vet Med Assoc. 1993;202:783-788.

Naleway AL. et al. Risk of immune hemolytic anemia in children following immunization. Vaccine. 2009 Dec 9;27(52):7394-7.

Reimer ME, Troy GC, Warnick LD. Immune-mediated hemolytic anemia: 70 cases (1988-1996). J Am Anim Hosp Assoc. 1999;35:384-391

 

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The Best Acupuncture Study EVER!

I have previously discussed in detail the reasons why, despite a fairly large and often positive research literature, I believe the evidence is strong that acupuncture works almost entirely as a placebo. Shortly after posting my most recent discussion of this issue, I ran across a paper which illustrates the phenomenon in an unusual and unexpected way. Steven Novella has already reviewed this paper on his blog, so I won’t go through it in detail, but I did want to call attention to this odd and interesting bit of evidence.

Chae Y, Lee IS, Jung WM, Park K, Park HJ, Wallraven C. Psychophysical and neurophysiological responses to acupuncture stimulation to incorporated rubber hand. Neurosci Lett. 2015 Feb 11;591C:48-52. doi: 10.1016/j.neulet.2015.02.025. [Epub ahead of print]

The researchers in this paper used a process called “incorporation,” a bit of psychological sleight-of-hand (pun intended) that allowed them to create in their subjects the sensation that a rubber model of a hand was actually part of their own body. In brief, then hand subjects sit with one hand hidden from view below a table and with a rubber hand positioned where their own hand would be if it was rested on the table. They then stroked the rubber hand and the subjects’ own hand simultaneously, creating the sensory illusion that the rubber hand belonged to the subject’s body.

This is weird enough, and says some interesting things about how our brains work and how they don’t always interpret the world around us correctly. But in this experiment, the incorporation was just the first step. The investigators then performed acupuncture on the rubber hand and measured responses in a couple of ways. They asked patients about signs of what is called DeQi, a sensation associated with acupuncture that is sometimes used in acupuncture studies as a marker of treatment effects. They also looked at activity in the subjects’ brains using a functional MRI unit.

What they found was that performing acupuncture on a rubber hand that one had been tricked by a visual and tactile illusion into seeing as one’s own hand had the same kinds of effects on the subject as acupuncture practices on their real body.

The findings of the present study clearly demonstrate that acupuncture stimulation to a rubber hand resulted in the expe-rience of the DeQi sensation when the rubber hand was fully incorporated into the body.

The present study also demonstrated that acupuncture stimu-lation to the incorporated rubber hand was associated with brain activations in the DLPFC, insula, SII, and MT visual area. These findings are consistent with those of previous studies which found that acupuncture stimulation leads to common brain activations inthe sensorimotor cortical network, including the insula and SII Although acupuncture stimulation was only applied to the incor-porated rubber hand in the present study, the stimulation clearly produced similar brain activations as does acupuncture to the realhand.

Interestingly, this is not the first study showing that so-called phantom acupuncture can mimic real acupuncture, though what “real” means in this context is unclear.

Though I am certain acupuncturists will disagree, what does seem clear is that if you can induce the sensations and brain activity associated with acupuncture by using needles in places not considered “real” acupuncture points, fake needles that don’t penetrate the skin, toothpicks, and now even needles poked into a fake hand not even connected to a subject’s body, the sensations and brain activity you are invoking come from the mind of the subject, not the acupuncture. What clearer definition of a placebo is there than a treatment that exerts its effects entirely through the beliefs of the subject without ever having to actually be applied to their body?

 

 

Posted in Acupuncture | 2 Comments