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.

 

 

 

Posted in Science-Based Veterinary Medicine | 10 Comments

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.

 

Posted in Science-Based Veterinary Medicine | 40 Comments

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.

 

 

Posted in General | 2 Comments

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!

 

 

Posted in Humor | Leave a comment

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 | 3 Comments

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

 

Posted in General | 7 Comments

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 | 6 Comments

What You Know that Ain’t Necessarily So: Pre-anesthetic Bloodwork in Dogs & Cats

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.

Pre-anesthetic Bloodwork in Healthy Animals

  1. Clinical question

P– healthy dogs & cats

I– routine cbc/chem before anesthesia

C– no bloodwork

O– mortality, complications, change plan

2. Synthetic Veterinary Literature

a. Systematic Reviews- none
b. CATs- none
c. Guidelines- none

3. Primary Veterinary Literature-

  • cbc/biochemistry profiles for 1537 dogs
  • university surgery population
  • variety of ASA stages
  • No indication in PE/Hx for labwork in 84%
  • Recategorized in ASA level- 8%
  • Procedure postponed- 0.8%
  • Additional therapy- 1.5%
  • Change in protocol- 0.2%
  • Complications in 1.9% of patients
    • Lab values normal or unrelated in 84% of these
    • 3.8% incidence with lab abnormalities
    • 1.8% incidence with normal labs (no statistical difference)

The changes revealed by pre-operative screening were usually of little clinical relevance and did not prompt major changes to the anaesthetic technique…In dogs, pre-anaesthetic laboratory examination is unlikely to yield additional important information if no potential problems are identified in the history and on physical examination.

(Alef, 2008)

  • 101 dogs
  • Private practice
  • > 7 years of age (avg=11)
  • Routine and emergent cases
  • 87% had no pre-existing conditions
  • New problem found- 29.7%
  • Anesthesia cancelled- 12.9%
  • Further tests- 5.9%
  • Euthanized- 4%
  • Procedure postponed- 1%
  • Additional therapy- 1%
  • Age did not predict abnormalities
  • Abnormalities not associated with complications

This study concluded that screening of geriatric patients important and that sub-clinical disease could be present in nearly 30 % of these patients. The value of screening before anaesthesia is perhaps more questionable in terms of anaesthetic practice but it is an appropriate time to perform such an evaluation.

(Joubert, 2007)

  • 100 cats > 6 years old
  • Not pre-anesthetic screening, just general screening
  • No know abnormalities on Hx
  • Many not normal on PE
  • Lots of abnormalities
    • 13% increased wbc
    • 29% increased creatinine
    • 15% increased BUN
    • 25% increased glucose
    • 4% increased T4
    • 6% increased ALT

Some new diagnoses

  • 14% FIV positive
  • 2% CKD
  • 1% hyperthyroidism
  • 1% UTI
  • Relevance to pre-anesthetic screening?
  • Some abnormalities were related to choice of reference interval
  • Many abnormalities were clinically irrelevant
  • Not truly screening since some had PE abnormalities

(Paepe, 2013)

4. Human Literature

a. Systematic Reviews

CBC

  • Abnormal <1% to 5%
  • Change protocol- 0.1% to 2.7%

Hemostasis

  • Abnormal 3.8-15.6%
  • Change protocol- rarely

Biochemistry

  • Abnormal <1% to 5%
  • Change protocol- rarely

Urinalysis

  • Abnormal 1-35.1%
  • Change protocol- 1% to 2.8%

The tests reviewed produce a wide range of abnormal results, even in apparently healthy individuals.

The tests lead to changes in clinical management in only a very small proportion of patients, and for some tests virtually never.

The clinical value of changes in management which do occur in response to an abnormal test result may also be uncertain in some instances.

The power of preoperative tests to predict adverse postoperative outcomes in asymptomatic patients is either weak or non-existent.

For all the tests reviewed, a policy of routine testing in apparently healthy individuals is likely to lead to little, if any, benefit.

The clinical importance of many of these abnormal results is uncertain.

(Munro, 1997)

b. Guidelines

  • Don’t obtain baseline laboratory studies in patients without significant systemic disease (ASA I or II) undergoing low-risk surgery
  • Performing routine laboratory tests in patients who are otherwise healthy is of little value in detecting disease.
  • Evidence suggests that a targeted history and physical exam should determine whether pre-procedure laboratory studies should be obtained.
  • American Society of Anesthesiologists

Bottom Line

  • If you test, you will find abnormalities
  • The clinical significance of these abnormalities is unclear
  • You will find more abnormalities if pre-test probability is high
  • Indication for test in Hx
  • Abnormality on PE
  • There is no evidence testing healthy patients reduces morbidity or mortality

What’s the harm?

  • Expense
  • Risk of testing
  • Overdiagnosis
  • Expense
  • Stress
  • Direct harm

References

Alef, M.; Praun, F. von; Oechtering, G. Is routine pre-anaesthetic haematological and biochemical screening justified in dogs? Veterinary Anaesthesia and Analgesia 2008 Vol. 35 No. 2 pp. 132-140

Munro J, et al. Routine preoperative testing: a systematic review of the evidence. Health Technol Assess. 1997;1(12):i-iv; 1-62.

Paepe D, et al. Routine health screening: findings in apparently healthy middle-aged and old cats. J Feline Med Surg. 2013 Jan;15(1):8-19.

Joubert K.E., Pre-anaesthetic screening of geriatric dogs. J S Afr Vet Assoc. March 2007;78(1):31-5.

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What You Know that Ain’t Necessarily So: ACE-I and MVD in Dogs

 

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.

  1. Clinical question

P– dogs with naturally occurring mitral valve disease (MVD)

I– angiotensin-converting enzyme inhibitor (ACE-I) before onset of congestive heart failure (CHF)

C– no ACE-I before onset CHF

O– time to CHF, survival

2. Synthetic Veterinary Literature

a. Systematic Reviews- none

b. Critically Appraised Topics (CAT)-

Best Bets for Vets
Benazepril in dogs with asymptomatic mitral valve disease
(1 study, significant weaknesses)

There is insufficient evidence to suggest that dogs with asymptomatic mitral valve disease treated with benazepril will live longer.

3. Primary Veterinary Literature

Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.

(Kvart, 2002) SVEP: Scandinavian Veterinary Enalapril Prevention Trial

Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF…Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.

  • No difference in primary endpoint (time to CHF)
  • Questionable secondary endpoint (all-cause mortality)
  • Selective exclusion of some subjects from analysis
  • Questionable selection of time points for comparisonBNZ had beneficial effects in asymptomatic dogs other than CKC and KC affected by MVD with moderate-to-severe MR.

(Atkins, 2007) VETPROOF

  • No difference overall in development of CHF or “cardiac events”
  • Questionable endpoints (all-cause mortality)
  • Differences between groups in disease severity

(Pouchelon, 2008)

4. Human Literature-

a. Systematic Reviews

CE inhibitors…reduced the RF, RV, and left ventricular size by a modest degree in chronic primary MR.. and may offer a pharmacologic treatment option to delay the deleterious hemodynamic effects of left ventricular volume overload.

(Strauss, 2012)

b. Guidelines

  • In the asymptomatic patient with chronic MR, there is no generally accepted medical therapy.
  • There has not been a consistent improvement in LV volumes and severity of MR in the small studies that have examined the effect of ACE inhibitors.
  • in the absence of systemic hypertension, there is no known indication for the use of…ACE inhibitors in asymptomatic patients with MR and preserved LV function.
  • If LV systolic dysfunction is present, primary treatment of the LV systolic dysfunction with drugs such as ACE…[has] been shown to reduce the severity of functional MR
  • (American College of Cardiology/American Heart Association, 2006)

Bottom Line

  • Research is conflicting
  • Cardiologists disagree
  • Critical review of the evidence does not suggest ACE-I
    • Delay onset of CHF
    • Prolong survival when begun before CHF

 

References

Atkins CE, et al. Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency. J Am Vet Med Assoc. 2007 Oct 1;231(7):1061-9.

Kvart C, et al. Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation. J Vet Intern Med. 2002 Jan-Feb;16(1):80-8.

Pouchelon JL, et al. Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: a retrospective study of 141 cases. J Vet Intern Med. 2008 Jul-Aug;22(4):905-14.

Strauss CE, et al. Pharmacotherapy in the treatment of mitral regurgitation: a systematic review. J Heart Valve Dis. 2012 May;21(3):275-85.

 

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