Placebos for Pets? The Truth About Alternative Medicine in Animals

As I hinted a few months ago, I have had a book in the works for several years. Written for pet owners, but heavily researched and referenced so as to be a useful reference for veterinary professionals as well, the book is a comprehensive review of the claims and evidence for alternative therapies in veterinary patients.

The book will be officially released on November 1, 2019. It is currently available for pre-order on Amazon and at Barnes and Noble. If you have found this blog at all interesting or useful, you will find much more depth and detail in the book on many of the subjects discussed here. The goal is to provide not only a review of specific therapies but a strategy for rational, evidence-based evaluation of medical therapies offered for you pets and patients. Readers will learn how science works as a method for evaluating medical treatments as well as what the current best evidence says about popular alternative veterinary therapies.

I hope this will be useful for veterinarians, veterinary technicians, and pet owners, and I look forward to hearing your impressions of the book when it comes out!

Posted in Presentations, Lectures, Publications & Interviews | 20 Comments

CellBIO: Another Dubious Lab Test from Hemopet and Dr. Jean Dodds

Dr. Jean Dodds
I have, unfortunately, had to write about Dr. Jean Dodds many times over the years. She has undergone a depressing transformation from a pioneer in transfusion medicine to a shameless promoter of dubious or bogus alternative medical ideas. She is particularly known for promoting diagnostic tests that claim to be revolutionary breakthroughs but which are based on questionable theories and little to no evidence. Here are some previous articles related to Dr. Dodds’ activities:

Canine Nutrigenomics by Dr. Jean Dodds: Science as Windowdressing
This is a comprehensive review of Dr. Dodds’ book Canine Nutrigenomics. Like so much of what she produces, the book is a mixture of fact and fiction, science and pseudoscience, plausible ideas and outright nonsense. Overall the work is deeply misleading. It has little at all to do with nutrigenomics or epigenetics, despite the title and claims to the contrary, and it uses real science primarily to give an aura of legitimacy or authority to claims which are unproven or outright false. The book is a collection of opinions, some plausible and some not, supported in most cases by very little evidence and in some cases clearly contradicted by this evidence. The references employed are often simply other people’s opinions or, in some cases, Dr. Dodds’ own opinions reprinted elsewhere.

The recommendations made for and against specific feeding practices and dietary supplements are typical for proponents of alternative medicine, and they stem from ideology and philosophical beliefs rather than scientific evidence. Occasionally, such claims turn out to be true, in the manner of a broken clock which happens to be right twice a day but this has little to do with the underlying principles. And while there are a few evidence-based claims here and there in the book, and some recommendations I would agree with, overall Canine Nutrigenomics is misleading, misguided, and in conflict with the best evidence and expert consensus in veterinary nutrition.

Hair and Saliva Test for Allergies are Worthless Pseudoscience
Dr. Dodds’ proprietary test for food allergies using saliva has beenshown not to work(along with similar tests by other companies), and yet she continues to promote and sell it. Charging pet owners hundreds of dollarsfor a bogus allergy test is unethical and should not be allowed regardless of whether or not Dr. Dodds refuses to accept the verdict of the evidence against the test. 

What’s the Right “Dose” of a Vaccine for Small-Breed Dogs?
Evidence Update: Dodds’ Study on Vaccine Dose in Small Breed Dogs
Dr. Dodds is, if not outright anti-vaccine, certainly an alarmist about vaccine safety, and she promotes the unscientific and unproven notion that arbitrary reductions in the volume of vaccines given to dogs and cats will reduce the risks of adverse effects from vaccination. 

Quack “Documentary” about Pet Cancer
Dr. Dodds was interviewed for a propaganda film about cancer in pets, which I have evaluated in detail, and she contributed an impressive variety of pseudoscientic nonsense to the project, ranging from claims about vaccines and GMO ingredients in pet foods to praise for animal psychics.

Dr. Dodds has also been involved in promoting questionable claims about thyroid disease in animals which are not accepted by experts in veterinary endocrinology, in suing a pet food manufacturer for the exclusive right to use the term “nutrigenomics” (1,2), in legal wrangling with the state of Californiaover the taxes owned by her company Hemopet, and in legal and ethical controversies over Hemopet’s blood bank operations.

CellBio- Salivary Isoprostane
The latest questionable test Dr. Dodds is marketing through Hemopet is promoted this way:

CellBIO is a novel biomarker test for cellular oxidative stress in pets using saliva and measures Cellular Oxidative Stress (inflammation, injury) and Microbiome Health.

The new easy saliva collection device with a volume indicator offers non-invasive sampling of saliva by veterinary clinic of pet owner— this is a patented test. Positive results occur with inflammation, infections, obesity and cancers (dysbiosis). Functional beneficial foods and supplements are given to re-balance the Microbiome and restore health.

The marketing then lists a hodgepodge of foods and supplements supposed to undo the damage detected by the test:

Alpha-Lipoic acid
Co-Enzyme Q-10
Ginger
Green tea
Licorice Root
Milk thistle
Garlic (in moderation)
Honey (not for young puppies)
Resveratrol (as a natural supplement or as food like blueberries and cranberries)
Soybeans
Tomatoes
Turmeric (curcumin) – without black pepper for pets
Vitamin E

These claims fall under the general concept Oxidation=Bad and Antioxidants=Good. I have written about this idea before, and the decades of research based on it have not been encouraging. Like most things in biology, reality has turned out to be more nuanced and complex than our simplistic ideas about good and bad. Oxidation can, in some cases, be beneficial, and antioxidants have failed to show dramatic benefits and have even been harmful for some patients, so the general principle is shaky to begin with. 

In more specific terms, the explicit and implied value of the CellBIO test involve three core claims which must be proven for the test to be worthwhile:

  1. The test accurately identifies oxidative damage in dogs and cats.
  2. The test results accurately predict the risk of disease.
  3. Interventions based on using the test, such as supplements or foods, reduce both oxidative damage and, more importantly, risk of disease.

Does the Test Work?
There is no published research evidence demonstrating the validity of the specific test Dr. Dodds is selling. The test fails the most basic criteria for a legitimate laboratory test, which is proof that it accurately and consistently measures what it is supposed to measure. Given the demonstrable failure of Hemopet’s Nutriscansalivary food allergy test, it is not reasonable to expect the veterinary profession or the public to take the company’s word for the validity of this new test.

There is plenty of research in humans and laboratory animals showing that isoprostanes are accurate indicators of lipid peroxidation, a chemical process that indicates active oxidation and oxidative stress.1There is some limited research in dogs and cats investigating the measurement of isoprostanes, but the significance of the findings is not at all clear.2–4Typically, these compounds are measured in blood or urine, and there is less support for the accuracy of saliva as a sample for measuring systemic oxidative stress. All of this evidence illustrates how far we are from being able to support the claim that a salivary isoprostane test is accurate or useful in dogs and cats. 

Do the Test Results Predict Disease?
Even with other tests in humans that have been shown to accurately measure oxidative stress, it is not always clear that doing so allows us to predict health problems. Isoprostane levels have been associated with some diseases in some studies, and they have not been reliable indicators in other studies.1The idea that measuring isoprostanes could predict the chances of specific diseases is a reasonable hypothesis, but it is still being investigated in humans, and it is almost entirely untested in pets. A couple of studies have explored the measurement of isoprostanes in dogs and cats with various health conditions, but no clear conclusions about the predictive value of such testing have been reached.2–4Dr. Dodds is extrapolating well beyond the bounds of the available evidence—in other words, she is guessing.

Does Antioxidant Treatment Based on the Test Reduce Disease?
Once again, there is absolutely zero published evidence that using this specific test to guide the use of antioxidant therapy has any benefit at all. The claim is based entirely on speculation and anecdote.

Extensive testing of a variety of antioxidants over several decades in humans has been profoundly disappointing. The evidence not only hasn’t found that consistent health benefits can be achieved in healthy or ill people with the use of such supplements, there have even been studies in which antioxidants actively harmed patients.5–11Antioxidants can have some benefits in specific circumstances, but they are not a universally safe and effective treatment, and in many cases they do nothing or cause harm. Using such supplements should be based on specific and compelling evidence for their safety and effectiveness in treating or preventing disease, and there is little of this available for most of the things Dr. Dodds recommends.

There is little research evidence on the use of antioxidant supplements in animals. A handful of studies show some potentially promising effects on markers of oxidative damage, and a couple seem to show some clinical benefits, but the evidence is scant and weak.12–21The harmful effects

of antioxidant supplementation in humans has only emerged with studies of large numbers of individuals over periods of time far longer than typical veterinary trials, so while few specific safety risks are known for common antioxidants, the assumption of safety in pets is not justified for most. 

The bottom line is that most of the claims concerning the benefits of antioxidants are based on theory or indirect and limited evidence. The specific antioxidant given, the form in which it is given, the other components of the diet, the species, health status, and individual makeup of each animal, and many other factors all influence the effects of antioxidants. Whether such effects are strong enough to be clinically significant, and whether they are beneficial or harmful if they do have a real effect, is a complicated question, and simplistic, strong claims are not justified. 

Using antioxidant supplements in your pets or patients is a roll of the dice. You might protect them, you might put them at risk, and you probably won’t ever be able to tell which you are doing because the complexity of biology makes individual cases unreliable predictors of the true benefits and risks of such products. The claim that using this test can reliably tell you whether antioxidants will benefit a patient or pet is simply not supported by any evidence.

Bottom Line
Dr. Dodds has a long history of promoting questionable and unproven tests and treatments. Real experts in veterinary endocrinology, nutrition, immunology, and other relevant fields rarely agree with Dr. Dodds beliefs or claims. Some of her recommendations are unproven (e.g. her beliefs about thyroid testing), others are demonstrably false (e.g. the Nutriscan food allergy test). 

The CellBIO saliva test for inflammation and oxidative stress is another unproven idea being sold well before it is properly tested. There is no specific published research showing the test is accurate, that its results are clincally useful, or that the treatments Dr. Dodds recommends based on using the test have any value. All of the claims for this test are based on theory, dramatic extrapolation from complex research evidence in humans and lab animals, or anecdote. 

Both the details of the claims made for this product, and Dr. Dodds track record, should inspire significant skepticism about the value of this test. Perhaps this will be the exception, a test Dr. Dodds promotes that is one day actually validated with strong research evidence, but based on the past I am not optimistic that this will happen, and I would not recommend using this test in the meantime.

References
1.          Milne GL, Dai Q, Roberts LJ, II. The isoprostanes–25 years later. Biochim Biophys Acta. 2015;1851(4):433-445. doi:10.1016/j.bbalip.2014.10.007

2.        Whitehouse W, Quimby J, Wan S, Monaghan K, Robbins R, Trepanier LA. Urinary F 2-Isoprostanes in Cats with International Renal Interest Society Stage 1-4 Chronic Kidney Disease. J Vet Intern Med. 2017;31(2):449-456. doi:10.1111/jvim.14634

3.        Kendall A, Woolcock A, Brooks A, Moore GE. Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary F2- Isoprostanes as Markers of Oxidative Stress in Anemic Dogs. J Vet Intern Med. 2017;31(6):1700-1707. doi:10.1111/jvim.14847

4.        Viviano KR, VanderWielen B. Effect of N-acetylcysteine supplementation on intracellular glutathione, urine isoprostanes, clinical score, and survival in hospitalized ill dogs. J Vet Intern Med. 2013;27(2):250-258. doi:10.1111/jvim.12048

5.        Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements and mortality. Curr Opin Clin Nutr Metab Care. 2013;17(1):1. doi:10.1097/MCO.0000000000000009

6.        Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention. JAMA. 2007;297(8):842. doi:10.1001/jama.297.8.842

7.        Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364(9441):1219-1228. doi:10.1016/S0140-6736(04)17138-9

8.        Bjelakovic G, Gluud LL, Nikolova D, Bjelakovic M, Nagorni A, Gluud C. Antioxidant supplements for liver diseases. Cochrane Database Syst Rev. 2011;(3):CD007749. doi:10.1002/14651858.CD007749.pub2

9.        Sesso HD, Buring JE, Christen WG, et al. Vitamins E and C in the Prevention of Cardiovascular Disease in Men. JAMA. 2008;300(18):2123. doi:10.1001/jama.2008.600

10.      Paulsen G, Cumming KT, Holden G, et al. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol. 2014;592(8):1887-1901. doi:10.1113/jphysiol.2013.267419

11.      Schürks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702. doi:10.1136/BMJ.C5702

12.      Piercy RJ, Hinchcliff KW, DiSilvestro RA, et al. Effect of dietary supplements containing antioxidants on attenuation of muscle damage in exercising sled dogs. Am J Vet Res. 2000;61(11):1438-1445. http://www.ncbi.nlm.nih.gov/pubmed/11108194. Accessed December 11, 2018.

13.      Freeman LM. Focus on nutrition: antioxidants in cancer treatment: helpful or harmful? Compend Contin Educ Vet. 2009;31(4):154-158. http://www.ncbi.nlm.nih.gov/pubmed/19517407. Accessed December 11, 2018.

14.      Hall JA, Chinn RM, Vorachek WR, et al. Influence of dietary antioxidants and fatty acids on neutrophil mediated bacterial killing and gene expression in healthy Beagles. Vet Immunol Immunopathol. 2011;139(2-4):217-228. doi:10.1016/j.vetimm.2010.10.020

15.      Milgram NW, Head E, Zicker SC, et al. Learning ability in aged beagle dogs is preserved by behavioral enrichment and dietary fortification: a two-year longitudinal study. Neurobiol Aging. 2005;26(1):77-90. doi:10.1016/j.neurobiolaging.2004.02.014

16.      Plevnik Kapun A, Salobir J, Levart A, Tav ar Kalcher G, Nemec Svete A, Kotnik T. Vitamin E supplementation in canine atopic dermatitis: improvement of clinical signs and effects on oxidative stress markers. Vet Rec. 2014;175(22):560-560. doi:10.1136/vr.102547

17.      Barrouin-Melo SM, Anturaniemi J, Sankari S, et al. Evaluating oxidative stress, serological- and haematological status of dogs suffering from osteoarthritis, after supplementing their diet with fish or corn oil. Lipids Health Dis. 2016;15(1):139. doi:10.1186/s12944-016-0304-6

18.      Snigdha S, de Rivera C, Milgram NW, Cotman CW. Effect of mitochondrial cofactors and antioxidants supplementation on cognition in the aged canine. Neurobiol Aging. 2016;37:171-178. doi:10.1016/j.neurobiolaging.2015.09.015

19.      Sechi S, Fiore F, Chiavolelli F, Dimauro C, Nudda A, Cocco R. Oxidative stress and food supplementation with antioxidants in therapy dogs. Can J Vet Res. 2017;81(3):206-216. http://www.ncbi.nlm.nih.gov/pubmed/28725111. Accessed December 11, 2018.

20.      Head E, Murphey HL, Dowling ALS, et al. A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer’s Disease. J Alzheimer’s Dis. 2012;32(4):1029-1042. doi:10.3233/JAD-2012-120937

21.      Hesta M, Ottermans C, Krammer-Lukas S, et al. The effect of vitamin C supplementation in healthy dogs on antioxidative capacity and immune parameters. J Anim Physiol Anim Nutr (Berl). 2009;93(1):26-34. doi:10.1111/j.1439-0396.2007.00774.x

Posted in Miscellaneous CAVM | 5 Comments

Canned or Dry Food: Which is Better for Cats?

Introduction
Among the timeless questions that are debated endlessly from generation to generation, such as “What is the meaning of life?” and “Does the refrigerator light go off when the door is closed?” is one that veterinarians and cat owners are particularly familiar with: “Is feeding canned or dry food better for cats?” Cat lovers, and many vets, often have strong and absolute opinions on this question, and disagreements on the subject tend to be about as amicable as disagreements about politics and religion. 

The most widely held belief seems to be that canned foods are healthier for cats than dry diets. This is predicated on two key arguments:

  1. As obligate carnivores, cats cannot thrive on dietary carbohydrates, and canned diets are low-carb compared with kibble. Therefore, dry diets are more likely to lead to obesity and diabetes mellitus (DM), two common and important feline health problems.1–5

  2. Cats eating dry food don’t drink enough water, and this increases the risk of chronic kidney disease (CKD) and lower urinary tract diseases, such as feline interstitial cystitis (FIC) and urolithiasis. Feeding canned foods will maintain better hydration and promote dilute urine, and this will reduce the risk of these diseases.4,6,7

These are plausible and logically sound arguments, but the history of medicine is full of plausible hypotheses that turned out to be wrong. It is not enough to make a good argument based on general principles. To know what is really best for our patients, we must test such arguments experimentally and follow the evidence, whether or not it supports seemingly obvious, “common sense” beliefs. 

The question of whether cats are healthier when fed canned or dry food is, unfortunately, far more complicated that it seems. There are many nutritional variables which affect health and disease and which are not determined solely by whether the food is dry or canned. 

Macronutrient content can vary dramatically between diets, and while dry foods are typically higher in carbohydrates than canned diets, they can be higher or lower than canned foods in fat or protein. The micronutrient content of a diet is also critical, as the consequences of feeding taurine deficient diets to cats illustrates. Other variables, such as calorie density, the amount of food fed, and the feeding pattern (e.g. number of meals per day) can have as much or more impact on health than the general form of the diet.

Even the basic assumptions of the arguments in favor of canned diets are not always as clear as they might seem. Cats certainly process carbohydrates differently from more omnivorous species, but that doesn’t translate into a simple equation that ”carbohydrates = bad for cats.” The type and relative amount of carbohydrates fed make a great deal of difference. And while canned food unquestionably contains more water than dry food, the idea that cats eating canned food are better hydrated and have more dilute urine turns out not to be consistently true. 

Cats and Carbs
The debate about the effect of dietary carbohydrates on cats has raged for decades. A couple of reviews have recently summarized the evidence, and simplistic, general conclusions are difficult to justify.1,8It is clear that cats do metabolize carbohydrates differently than dogs and humans. However, the type of carbohydrate (simple or complex) and the feeding pattern both have significant effects of postprandial glucose levels and other measures. Cats can utilize carbohydrates as an energy source, and they can adapt metabolically to different macronutrient ratios in the diet, so the simplistic notion of carbohydrates as “toxic” to cats isn’t supported.

Research evidence generally shows no adverse effects on resting glucose or insulin sensitivity in cats fed typical types and levels of dietary carbohydrates. Diets with greater than 50% of calories from carbohydrates, especially when fed once daily rather than ad libor as multiple meals, can generate higher and more prolonged spikes in blood glucose, but even this does not appear to achieve levels associated with harm in experimental studies.

Though there is some inconsistency among studies, most research has failed to find that dietary carbohydrates is a significant risk factor for DM in cats.1,8One study even found cats who developed diabetes were less likely to be fed dry foods than cats without DM.9There is evidence that reduced-carbohydrate diets may be useful in management of feline DM, though such diets can be counterproductive and promote obesity if they are very high in fat.1,10

Cats and Water
Cats can produce more highly concentrated urine than dogs and have lower weight-specific water requirements.6It has been argued that dry diets are associated with less overall water intake and that they promote dehydration and may increase the risk of CKD and other urinary tract diseases.4Some research has found that cats will drink less water when eating low-moisture diets.4,6However, other studies contradict this finding and identify no difference in water turnover and intake or body water content between cats fed dry and canned diets.6There are many factors that affect water intake in cats other than the form of the food, including the protein and mineral content and the energy density, so simply feeding a canned diet is not guaranteed to increase water intake or reduce urine specific gravity.6

Some studies have identified consumption of dry diets as a risk factor for FIC and urolithiasis while others have not confirmed this link.6Other research has even found that cats who develop FIC are morelikely to be fed canned food than control cats, suggesting canned foods could increase FIC risk in some cases.11Similarly, while dry diets are often cited as a risk factor for the development of CKD, research has consistently failed to support this purported association.6,12,13And while canned diets certainly have a role in the management of CKD and urolithiasis, moisture content is not the only relevant variable, and dry diets can have benefits in patients with these conditions as well.6,14

Higher moisture diets are typically less calorie-dense than lower-moisture diets, and it has been suggested that canned diets may help prevent or treat obesity in cats. Other factors are clearly also relevant, of course, such as the specific composition of the diet, the amount fed, and the feeding pattern. It is clearly possible to maintain cats in a lean body condition with dry foods and to develop and perpetuate obesity while feeding canned diets. Overall, however, it is likely that high-moisture diets, including canned foods or dry diets with added water, may be beneficial in preventing and managing feline obesity.6

Conclusions
Regular readers will not be surprised to see that the simple answer, canned foods are better/worse than dry foods for cats, is not the true answer. “It depends” is a much less satisfying response to questions about the relative merits of canned food and kibble, but it is more likely to lead us to the best dietary strategy for individual patients. 

Overall, concerns about the health effects of dietary carbohydrates in cats are typically exaggerated, and dry diets should not be avoided on the basis of the idea that they have too much carbohydrate and promote obesity and DM. The specific nutrient and calorie content of the diet is more important than the form it comes in.

Canned diets are higher in moisture than dry foods, and while it is unclear how much impact this has on the risk of urinary tract disease, it does seem likely this characteristic may help owners control calorie intake and weight in their cats. 

So when our clients ask whether they should feed canned or dry food to their cats, rather than giving a satisfying, simple answer that is probably wrong, we should be prepared to discuss the evidence and the nuances of the issue in the context of the individual pet. This is the essence of evidence-based practice. 

References

1.        Verbrugghe A, Hesta M. Cats and Carbohydrates: The Carnivore Fantasy? Vet Sci. 2017;4(4):55. doi:10.3390/vetsci4040055

2.        Rand JS, Fleeman LM, Farrow HA, Appleton DJ, Lederer R. Canine and feline diabetes mellitus: nature or nurture? J Nutr. 2004;134(8 Suppl):2072S-2080S. http://www.ncbi.nlm.nih.gov/pubmed/15284406. Accessed June 14, 2019.

3.        Buffington CAT. Dry foods and risk of disease in cats. Can Vet J = La Rev Vet Can. 2008;49(6):561-563. http://www.ncbi.nlm.nih.gov/pubmed/18624064. Accessed June 14, 2019.

4.        Zoran DL. The carnivore connection to nutrition in cats. J Am Vet Med Assoc. 2002;221(11):1559-1567. doi:10.2460/javma.2002.221.1559

5.        Gomez-Mejias Y. Does Grain Actually Predispose Our Cats to Gain Weight? Vet Evid. 2019;4(2). doi:10.18849/ve.v4i2.201

6.        Larsen JA. The role of water in disease management. In: 2018 ACVIM Forum. Seattle, WA; 2018.

7.        Markwell PJ, Buffington CT, Smith BHE. The Effect of Diet on Lower Urinary Tract Diseases in Cats. J Nutr. 1998;128(12):2753S-2757S. doi:10.1093/jn/128.12.2753S

8.        Laflamme D. Cats and carbohydrates: Why is this still controversial? In: 2018 ACVIM Forum. Seattle, WA; 2018.

9.        Sallander M, Eliasson J, Hedhammar A. Prevalence and risk factors for the development of diabetes mellitus in Swedish cats. Acta Vet Scand. 2012;54(1):61. doi:10.1186/1751-0147-54-61

10.      Nguyen PG, Dumon HJ, Siliart BS, Martin LJ, Sergheraert R, Biourge VC. Effects of dietary fat and energy on body weight and composition after gonadectomy in cats. Am J Vet Res. 2004;65(12):1708-1713. http://www.ncbi.nlm.nih.gov/pubmed/15631038. Accessed June 14, 2019.

11.      Lund HS, Sævik BK, Finstad ØW, Grøntvedt ET, Vatne T, Eggertsdóttir A V. Risk factors for idiopathic cystitis in Norwegian cats: a matched case-control study. J Feline Med Surg. 2016;18(6):483-491. doi:10.1177/1098612X15587955

12.      Finch NC, Syme HM, Elliott J. Risk Factors for Development of Chronic Kidney Disease in Cats. J Vet Intern Med. 2016;30(2):602-610. doi:10.1111/jvim.13917

13.      Bartlett PC, Van Buren JW, Bartlett AD, Zhou C. Case-control study of risk factors associated with feline and canine chronic kidney disease. Vet Med Int. 2010;2010. doi:10.4061/2010/957570

14.      Roudebush P, Polzin DJ, Ross SJ, Towell TL, Adams LG, Forrester SD. Therapies for Feline Chronic Kidney Disease. J Feline Med Surg. 2009;11(3):195-210. doi:10.1016/j.jfms.2009.01.004

Posted in Nutrition | 15 Comments

Neutered Dogs Live Longer than Intact Dogs

I’ve written extensively over the years about the risks and benefits of neutering. It’s a complicated subject that tends to draw a lot of passion even in the absence of robust scientific evidence. Variable such as sex, breed, age at neutering, and the particular procedure performed all influence the risk, and there are few conditions for which we can make absolute predictions in an individual dog or cat. The best we can say is that a few conditions are clearly much more common in intact animals (e.g. uterine infections, breast cancer), some are more common in neutered animals (e.g. obesity), and many, many conditions are influence subtly by neutering and also by many other variables.

The overall outcome for any individual is affected by so many factors that it is effectively unpredictable. Strident claims that neuteringmustbe done or should notbe done or that the age at which it is done is crucial conflict with the much more nuanced and complex reality evidence in the scientific research on the subject. A balanced, rational approach is to recognize that some risks increase and others decrease with neutering and that the best we can do is make tentative recommendations for individual pets based on the population literature. As the evidence changes, new research can shift our estimate of the risks and benefits, though radical revisions in practice are rarely justified. A new piece of evidence recently published strengthens one claim that has been tentatively made based on previous research; neutered dogs appear to live longer on average than intact dogs.

A number of studies in dogs (as well as other species, including humans) have found greater longevity in neutered animals than in those left intact.1-9Not all studies agree, and there are significant differences in longevity between breeds. There are also potential differences in other factors, such as the quality of husbandry and medical care received by intact versus neutered animals, especially in countries in which neutering is the norm. Generalizations about the effect of neutering on lifespan may not apply to every individual, but overall the pattern in the research literature has been for neutered animals to live longer than intact animals.

A recent retrospective study looking at records from a chain of hospitals across the U.S. evaluated lifespan in a cohort of over 2 million dogs seen at these clinics during a two-year period. 

Silvan R. Urfer, Mansen Wang, Mingyin Yang, Elizabeth M. Lund, and Sandra L. Lefebvre (2019) Risk Factors Associated with Lifespan in Pet Dogs Evaluated in Primary Care Veterinary Hospitals. Journal of the American Animal Hospital Association: May/June 2019, Vol. 55, No. 3, pp. 130-137.

The results showed statistically significant differences in lifespan associated with neuter status and breed size. The figures below illustrate the key findings.

Neuter Status and Lifespan
Breed Size and Lifespan

These data agree with the majority of the results of previous studies, which suggests that the relationship between neutering a longevity is real. This does not, of course, explain what this relationship is. Differences in breed, husbandry and medical care, specific causes of death, and many other factors are involved in determining lifespan. However, it is at least clear that broad claims neutering shortens lifespan are not consistent with the evidence.

This study also provides a good example of a problem common in the interpretation of scientific literature, which is the difference between statistical and real-world significance. It is possible to find differences between groups which are statistically significant, especially if you include a very large number of subjects, but these differences can be effectively meaningless in the real world. In this study, for example, the difference between the median lifespan of neutered and intact male dogs was 0.06 years (about three weeks). This is clearly not a meaningful difference in the life of an actual male dog.

The difference between spayed and intact females, in contrast, was 0.58 years (about 7 ½ months). This is a more significant difference in terms of real life, though still small as a portion of the overall lifetime of a dog. 

Breed size had a much larger effect, with giant breed dogs (over 90 lbs adult weight) living almost four years less than small-breed dogs (under 20 lbs adult weight). This too is consistent with previous research though again it doesn’t explain the cause for this difference.

Bottom Line
This study strengthens the claim that neutered dogs live longer than those that are not neutered. Longevity is affected by breed, sex, care, and many other factors, and the reason for this difference is unclear. The magnitude of the difference in lifespan between intact and neutered dogs varies among studies, and the difference is not always large enough to be of any real-world significance. However, these results clearly contradict broad claims about the overall negative effect of neutering on health and longevity in dogs.

References

  1. Michell AR. Longevity of British breeds of dog and its relationship with sex, size, cardiovascular variables, and disease. Veterinary Record 1999;145(22):625-9.
  2. Bronson RT. Variation in age at death of dogs of different sexes and breeds. American Journal of Veterinary Research 1982;43(11):2057-9.
  3. Moore GE, Burkman KD, Carter MN, Peterson MR. Causes of death or reasons for euthanasia in military working dogs: 927 cases (1993-1996). Journal of the American Veterinary Medical Association 2001;219(2):209-14.
  4. Drori D, Folman Y. Environmental effects on longevity in the male rat: exercise, mating, castration and restricted feeding. Experimental Gerontology 1976;11(1-2):25-32.
  5. Greer KA, Canterberry SC, Murphy KE. Statistical analysis regarding the effects of height and weight on life span of the domestic dog. Research in Veterinary Science 2007;82:208-14.
  6. Kraft W. Geriatrics in canine and feline internal medicine. European Journal of Medical Research 1998;3:3-41.
  7. Waters DJ, Shen S, Glickman LT. Life expectancy, antagonistic pleiotropy, and the testis of dogs and men.Prostate 2000;1:43(4);272-7.
  8. Hoffman JM, Creevy KE, Promislow DEL. Reproductive Capability Is Associated with Lifespan and Cause of Death in Companion Dogs. PLoS ONE. 2013;8(4): e61082. doi:10.1371/journal.pone.0061082
  9. Cooley DM, Beranek BC, Schlittler DL, Glickman NW, Glickman LT, Waters DJ. Endogenous gonadal hormone exposure and bone sarcoma risk. Cancer Epidemiology, Biomarkers, and Prevention 2002;11:1434-40.

Posted in Science-Based Veterinary Medicine | 10 Comments

Vegetarian Diets for Dogs & Cats

Pet owners frequently project their beliefs about human health onto their companion animals. Anxieties about purported harms from vaccines in children, for example, have spurred an anti-vaccination movement among vets and pet owners.1–4Beliefs in alternative medical therapies for people, such as herbal medicine and acupuncture, may motivate pet owners to seek such treatments for their animals. But perhaps the most common example of this phenomenon is the translation of dietary beliefs and fads from human nutrition to animal feeding practices.5

This projection of human dietary practices onto pets takes many forms. On the heels of a wave of hysteria about gluten and the health effects of grains in humans, we saw the rise in popularity of grain-free pet foods, which now make up close to half of commercial diets for dogs and cats.6Organic ingredients are often marketed to pet owners as having health benefits based on the belief that this is true for people, despite the lack of real evidence for this in humans or in other animals.7And among those who minimize or avoid animal products in their own diet, there is significant interest in feeding such vegetarian or vegan diets to their pets.8

People may avoid meat or other animal products in their diet for a variety of reasons, including concerns about food animal welfare, beliefs about the health effects of plant-based and animal-based foods, and religious dietary restrictions. Surveys of pet owners indicate that those who follow a vegan diet (eating no animal-based foods) or other vegetarian diets (limited consumption of some types of animal-based foods) sometimes feel discomfort at violating their own dietary rules in the feeding of their dogs and cats, especially if their own food choices are driven by religious or ethical concerns.8–11They have a clear interest and motivation to feed vegetarian or vegan diets to their pets, but many do not because of concerns about the health effects of such diets on their pets.8

Beliefs about the nutritional requirements of dogs and cats are often based on the notion that whatever wild canids and felids eat must be a “natural,” and thus a healthy diet for our pets. However, wild carnivores often suffer from malnutrition, parasitism, and other ills associated with their diet, so it is a mistake to imagine that the diet available to them in the wild is perfectly suited to optimize their health.12–23Natural history does have an influence the nutritional requirements of a species, but these requirements are not always best met by feeding a diet identical to that eaten by the wild ancestors of modern animals. This is especially true for animals that have been domesticated, a process which induces significant changes to the anatomy and physiology of domestic species.

Dogs have been dramatically impacted by their long association with humans. Some of these changes are obvious, and their relevance to the concept of a “natural” diet like that of wolves and wild dogs is clear. It is unlikely that a pack of feral pugs or French bulldogs will even be seen running down and savaging an elk or antelope, and the idea that this would be an optimal diet for them is clearly ridiculous. However, even breeds with a more typically canine anatomy have undergone changes in morphology and physiology that reflect their adaptation to human foods. From their dentition to their ability to digest starches and taste sweetness, dogs have been shaped by domestication, and they are well-suited to an omnivorous diet.24–27

In theory, then, dogs should be able to thrive on vegetarian or vegan diets. However, there have been few studies demonstrating this, and such diets can still be problematic. A vegan diet must be properly and carefully formulated to meet the nutritional needs of dogs, and there is less room for error than with diets containing animal ingredients. Numerous studies of commercial vegan and vegetarian pet foods have found formulation errors and inadequacies in essential nutrients.9,28Some studies have also found mammalian DNA in such diets, suggesting they may not even be accurately labeled as vegetarian or vegan.29

Even diets which appear adequate on paper or in laboratory testing, however, may not support normal health under real-world conditions. Most commercial grain-free diets, for example, should be nutritionally complete for dogs, yet recent reports of cardiomyopathy in dogs eating such diets suggest a serious health risk for some individuals fed these diets.30–32At present, there are only short-term studies and uncontrolled, low-quality case series evaluating the health of dogs fed vegan or vegetarian diets.9,33Such limited evidence leaves significant uncertainty about the risks and benefits of such diets for domestic dogs.

Cats have been more lightly touched by domestication and artificial selection than dogs, and they are clearly still obligate carnivores.34,35This does not mean they are healthiest when fed only raw birds and small mammals, and in fact the evidence indicates this is not the safest or healthiest diet for domestic cats.36,37However, domestication has had limited effects on the physiology of cats, and their dietary requirements are unlikely to be effectively met by plant-only diets. The need for preformed vitamin A, taurine and other specific amino acids lacking in plant-based foods, and other specific and known dietary requirements of cats makes it unlikely that long-term feeding of vegan diets will support good health in this species.35,38

There are few studies evaluating the health effects of plant-based diets on cats. Some research on cats fed commercial vegetarian diets by their owners have found deficiencies in some nutrients in some cats, but the evidence is limited and of low quality, so no robust conclusions can be drawn.9,39–41

Bottom Line

There is no evidence that vegetarian diets have health benefits for dogs and cats, and no real reason to believe they should based on the physiology and nutritional requirements of these species. Pet owners may choose to feed such diets due to their philosophical or religious beliefs, but veterinarians should make it clear that any potential health benefits of vegetarianism for humans likely do not apply to our dogs and cats.

Dogs are omnivores shaped by domestication to be able to eat both plant and animal foods, and in theory they should be able to thrive on vegetarian or vegan diets. However, these diets must be carefully formulated, and many commercial vegetarian dog foods do not appear to be nutritionally adequate. There is also little reliable research evidence showing that dogs can remain healthy fed only a vegan diet. Given the unexpected health problems seen with theoretically adequate grain-free diets, we should be cautious about the potential risks of vegetarian diets for dogs until there is better evidence showing their long-term health effects.

Cats are clearly obligate carnivores with nutritional requirements that are unlikely to be effectively met by vegan diets. Such diets offer only risks and no benefits for cats and should be avoided.

References

1.        Clifton J. Stop the Shots!?: Are Vaccinations Killing Our Pets?New York, NY: Foley Square Books; 2007.

2.        Duan N. Inside the World of Pet Anti-Vaxxers. The Awl.com. January 2018.

3.        Kluger J. Some Anti-Vaxxers Aren’t Getting Their Pets Vaccinated. Here’s Why That’s So Dangerous. Time.com. March 2019.

4.        Ducharme J. Veterinary Group: Dogs Can’t Get Autism, So Please Keep Vaccinating Them. Time.com. 2018.

5.        Walet E. Are trends in Human Food reflected in Pet Food Purchase? 2015. https://dspace.ou.nl/bitstream/1820/6538/1/Walet E scriptie.pdf. Accessed December 20, 2018.

6.        Phillips-Donaldson D. Are grain-free pet foods truly healthy and sustainable? Pet Food Ind. 2017.

7.        Smith-Spangler C, Brandeau ML, Hunter GE, et al. Are Organic Foods Safer or Healthier Than Conventional Alternatives? Ann Intern Med. 2012;157(5):348. doi:10.7326/0003-4819-157-5-201209040-00007

8.        Dodd SAS, Cave NJ, Adolphe JL, Shoveller AK, Verbrugghe A. Plant-based (vegan) diets for pets: A survey of pet owner attitudes and feeding practices. Suchodolski JS, ed. PLoS One. 2019;14(1):e0210806. doi:10.1371/journal.pone.0210806

9.        Knight A, Leitsberger M, Knight A, Leitsberger M. Vegetarian versus Meat-Based Diets for Companion Animals. Animals. 2016;6(9):57. doi:10.3390/ani6090057

10.      Rothgerber H. A meaty matter. Pet diet and the vegetarian’s dilemma. Appetite. 2013;68:76-82. doi:10.1016/j.appet.2013.04.012

11.      Wakefield LA, Shofer FS, Michel KE. Evaluation of cats fed vegetarian diets and attitudes of their caregivers. J Am Vet Med Assoc. 2006;229(1):70-73. doi:10.2460/javma.229.1.70

12.      Tidière M, Gaillard J-M, Berger V, et al. Comparative analyses of longevity and senescence reveal variable survival benefits of living in zoos across mammals. Sci Rep. 2016;6:36361. doi:10.1038/srep36361

13.      Mukherjee S, Heithaus MR. Dangerous prey and daring predators: a review. Biol Rev. 2013;88(3):550-563. doi:10.1111/brv.12014

14.      Woodroffe R, Davies-Mostert H, Ginsberg J, et al. Rates and causes of mortality in Endangered African wild dogs Lycaon pictus: lessons for management and monitoring. Oryx. 2007;41(02):215. doi:10.1017/S0030605307001809

15.      Mech LD. Productivity, Mortality, and Population Trends of Wolves in Northeastern Minnesota. J Mammal. 1977;58(4):559-574. doi:10.2307/1380004

16.      Young TP. Natural Die-Offs of Large Mammals: Implications for Conservation. Conserv Biol. 1994;8(2):410-418. doi:10.1046/j.1523-1739.1994.08020410.x

17.      Holmes JC, Podesta R. The helminths of wolves and coyotes from the forested regions of Alberta. Can J Zool. 1968;46(6):1193-1204. doi:10.1139/z68-169

18.      Bosch G, Hagen-Plantinga EA, Hendriks WH. Dietary nutrient profiles of wild wolves: insights for optimal dog nutrition? Br J Nutr. 2015;113(S1):S40-S54. doi:10.1017/S0007114514002311

19.      Choquette LPE, Gibson GG, Kuyt E, Pearson AM. Helminths of wolves, Canis lupusL., in the Yukon and Northwest Territories. Can J Zool. 1973;51(10):1087-1091. doi:10.1139/z73-158

20.      Amanda A. Parasites of the African painted dog (Lycaon pictus) in captive and wild populations: Implications for conservation. 2011. http://researchrepository.murdoch.edu.au/id/eprint/10519/2/02Whole.pdf.

21.      Berentsen AR, Becker MS, Stockdale-Walden H, Matandiko W, McRobb R, Dunbar MR. Survey of gastrointestinal parasite infection in African lion ( Panthera leo), African wild dog ( Lycaon pictus) and spotted hyaena ( Crocuta crocuta) in the Luangwa Valley, Zambia. African Zool. 2012;47(2):363-368. doi:10.1080/15627020.2012.11407561

22.      Fuchs B. Sarcoptic mange in the Scandinavian wolf population. 2014. https://brage.bibsys.no/xmlui/bitstream/handle/11250/222199/Boris Fuchs.pdf?sequence=1. Accessed December 28, 2018.

23.      Benson JF, Mills KJ, Loveless KM, Patterson BR. Genetic and environmental influences on pup mortality risk for wolves and coyotes within a Canis hybrid zone. Biol Conserv. 2013;166:133-141. doi:10.1016/J.BIOCON.2013.06.018

24.      Vilà C, Maldonado JE, Wayne RK. Phylogenetic relationships, evolution, and genetic diversity of the domestic dog. J Hered. 90(1):71-77. http://www.ncbi.nlm.nih.gov/pubmed/9987908. Accessed October 27, 2018.

25.      Serpell J, Barrett P. The Domestic Dog?: Its Evolution, Behavior and Interactions with People. Second edition.; 2017. https://www.worldcat.org/title/domestic-dog-its-evolution-behavior-and-interactions-with-people/oclc/987274028&referer=brief_results. Accessed October 27, 2018.

26.      Axelsson E, Ratnakumar A, Arendt M-L, et al. The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature. 2013;495(7441):360-364. doi:10.1038/nature11837

27.      Reiter T, Jagoda E, Capellini TD. Dietary Variation and Evolution of Gene Copy Number among Dog Breeds. 2016. doi:10.1371/journal.pone.0148899

28.      Kanakubo K, Fascetti AJ, Larsen JA. Assessment of protein and amino acid concentrations and labeling adequacy of commercial vegetarian diets formulated for dogs and cats. J Am Vet Med Assoc. 2015;247(4):385-392. doi:10.2460/javma.247.4.385

29.      Kanakubo K, Fascetti AJ, Larsen JA. Determination of mammalian deoxyribonucleic acid (DNA) in commercial vegetarian and vegan diets for dogs and cats. J Anim Physiol Anim Nutr (Berl). 2017;101(1):70-74. doi:10.1111/jpn.12506

30.      Adin D, DeFrancesco TC, Keene B, et al. Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type. J Vet Cardiol. 2019;21:1-9. doi:10.1016/J.JVC.2018.11.002

31.      Kaplan JL, Stern JA, Fascetti AJ, et al. Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. Loor JJ, ed. PLoS One. 2018;13(12):e0209112. doi:10.1371/journal.pone.0209112

32.      Freeman LM, Stern JA, Fries R, Adin DB, Rush JE. Diet-associated dilated cardiomyopathy in dogs: what do we know? J Am Vet Med Assoc. 2018;253(11):1390-1394. doi:10.2460/javma.253.11.1390

33.      Brown WY, Vanselow BA, Redman AJ, Pluske JR. An experimental meat-free diet maintained haematological characteristics in sprint-racing sled dogs. Br J Nutr. 2009;102(09):1318. doi:10.1017/S0007114509389254

34.      MacDonald ML, Rogers QR, Morris JG. Nutrition of the Domestic Cat, a Mammalian Carnivore. Annu Rev Nutr. 1984;4(1):521-562. doi:10.1146/annurev.nu.04.070184.002513

35.      Morris JG. Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptations. Nutr Res Rev. 2002;15(01):153. doi:10.1079/NRR200238

36.      Glasgow A, Caver N, Marks S, Pedersen N. Role of Diet in the Health of the Feline Intestinal Tract and in Inflammatory Bowel Disease.; 2002. http://www.vetmed.ucdavis.edu/ccah/530-752-7295. Accessed December 28, 2018.

37.      Schlesinger DP, Joffe DJ. Raw food diets in companion animals: a critical review. Can Vet J = La Rev Vet Can. 2011;52(1):50-54. http://www.ncbi.nlm.nih.gov/pubmed/21461207. Accessed October 27, 2018.

38.      Weeth L, Chandler M. Vegetarian Diets. Clin Br. 2015;(January):61-63. https://www.cliniciansbrief.com/article/vegetarian-diets. Accessed April 29, 2019.

39.      Leon A, Bain SA, Levick WR. Hypokalaemic episodic polymyopathy in cats fed a vegetarian diet. Aust Vet J. 1992;69(10):249-254. http://www.ncbi.nlm.nih.gov/pubmed/1359869. Accessed April 29, 2019.

40.      Wakefield L, Michel KE. Taurine And Cobalamin Status of Cats Fed Vegetarian Diets. J Anim Physiol Anim Nutr (Berl). 2005;89(11-12):427-428. doi:10.1111/j.1439-0396.2005.00611_2.x

41.      Gray CM, Sellon RK, Freeman LM. Nutritional adequacy of two vegan diets for cats. J Am Vet Med Assoc. 2004;225(11):1670-1675. http://www.ncbi.nlm.nih.gov/pubmed/15626215. Accessed April 29, 2019.

Posted in Nutrition | 6 Comments

FDA Update on Grain-free Diets and Heart Disease in Dogs

The FDA has released a new update about the ongoing investigation into dogs developing the dilated cardiomyopathy (DCM), a serious heart disease, which appears to be associated with the use of grain-free or exotic protein diets. The agency has received reports of 560 dogs and 14 cats with DCM, and of these 199 dogs and 5 cats have died from the condition.

The agency has also released a list of all the diets being fed to these pets:

Brands reported fed in at least 10 reported cases of DCM: 

The specific relationship between diet and DCM in these cases is not yet understood, so it is impossible to say if the food is a primary cause of DCM and, if so, how this is happening. However, the common thread among the diets involved seems to be the use of legumes or pulses (e.g. peas, lentils) in place of grains in the diet.

While many of the diets contain common protein sources (e.g. chicken and lamb), a surprisingly high proportion have unusual and uncommon meats as their main protein source. Again, the significance of this is not yet clear.

There is a concentration of cases among golden retrievers, though dogs of many other breeds have been affected as well.

Further data collection and research will be necessary to determine the precise relationship between diet and DCM in these cases. There are likely multiple factors involved, including the ingredients in the diet, the genetics or particular breeds and individuals, and others we may not yet know about. Pet owners feeding these diets don’t need to panic, since far more dogs on these diets do NOT have DCM than do. However, if you are feeding one of these foods, or a diet similar in composition, and especially if you are feeding this to a golden retriever, it would be a good idea to talk to your vet about screening your pet for DCM and considering a change in diet.

Posted in Nutrition | 48 Comments

Happy 10th Blogiversary to Me!

Hard to believe, but my first post, What is Open-Mindendess?, appeared June 4, 2009. Lots of things have changed in the ten years since I began this blog. My subjects and the tone of my writing are often different from the early days. And I have been fortunate to have the opportunity to share my enthusiasm for evidence-based medicine and my skepticism in a wide variety of other venues, from veterinary conferences and journal articles to media interviews and my monthly column in Veterinary Practice News. It’s impossible to know what the impact of this work is, but despite the steady trickle of hate mail it generates, I get a lot of support from folks in the veterinary field and also animal owners who find the ideas and information I share useful. I shared some of this positive feedback on my 5th Blogiversary post, and I will continue the tradition with some examples below.

I also want to celebrate the occasion with an announcement. As a further contribution to the cause of rational, evidence-based veterinary medicine and the health of our animal companions, I have spent a lot of time over the last few years working on a special project, and I happy to say that this work will finally come to fruition later this year in the form of a book for pet owners and veterinary professionals.

I can’t provide a lot more detail at this point, but my hope is that this will become a useful reference and an introduction to science-based veterinary medicine in the way that some of my favorite books, such as Don’t Believe Everything You Think and Trick or Treatment, have been for science-based human medicine.

Finally, thank you all for reading and for sharing the ideas information I pass along here. If we can help just a few people and their animals make sound, science-based decisions about healthcare for pets, we have done something worthwhile!

SkeptVet

My dogs and cats appreciate the work you do. Alt med, and woo hucksters in general, don’t typically have a great moral compass. As skeptics, if we could shut off the ethical side of our brains, we could make loads of money.

@SkeptVetyou are fantastic, and any ridiculous insinuation that you have anything to do with the mental health crisis in the vet med world is entirely ludicrous. Thank you for all that hard work that you do! Please – keep it up!

Thank you for your truth and insight on various subjects. I have worked in the veterinarian field for over 20 years, and live in the same city as Rodney Habib. When I would question a few of his claims, he would block or ban me. As I was being respectful and professional in my questioning. I can only surmise he didn’t have evidence to back up his claims. We have seen many sick animals on the type of nutrition he preaches. He is a social media celebrity that is very slick with the smoke and mirror show when it comes to fear mongering pet owners against conventional and science based medicine. Too bad so many people listen to him, as he does give out much misinformation.

[SkeptVet] is one of the most knowledgeable, capable, thoughtful, insightful, thorough, caring, intelligent vet/person that I’ve had the pleasure of knowing and working with ever.

They believe what they want to believe no matter the evidence to the contrary. Thank-you so much for this article skeptvet…This saved my partner from wasting money & getting hopes up for nothing. … It upsets me to discover so many trying to profit off of others… creating false hopes from folks who’ll do just about anything to help their pet.

Thank you so much!…I really appreciate you taking the time to address my concerns and provide me with reliable –evidence based, and hallelujah for that!…I also appreciate you taking the time and effort to provide factual info in a world where “belief” grows ever more important than evidence….and being willing to take the attacks that arise because of your efforts.
sincerely,

Great response doctor
So proud of you as a fellow veterinarian

Thank you so much for this article and the associated comments. 

As a fellow veterinarian I applaud you for publishing true science and facts in the face of a continued stream of ignorance and hatred. Ours is an exhausting profession involving (in my case at least) ten years of university and two professional degrees. How anyone can insinuate that we are uneducated is beyond me. Carry on with the great work!

So pleased to discover this. Very interesting…I am so grateful for the time you take to write your opinions. Thanks.

Thank you SkeptVet for all the time and energy it must require to compose your thoughtful and well written blogs. I am trained as a pharmacist however I now work with horses, mostly training. I often feel very alone in my skepticism as horse people in general seem to be very susceptible to all kinds of blarney. I am also dismayed to find that a lot of folks have only a vague idea of how bodies function much less the realities of chemistry and physics. Your blogs have touched on things I come across all the time in the horse world and I often feel like the Lone Ranger in my skepticism or outright challenge of certain modalities that are accepted with no question. I try to be circumspect because alienating people does not advance my cause. But maybe I throw out a comment or two that might spark some investigation (e.g. most folks have no idea what homeopathy is, they think it is herbs or home remedies). Most of the time this goes nowhere but on rare occasions I can change someone’s thinking. So thanks for letting me know I’m not alone.

Absolutely! Positively! I couldn’t agree more. Thank you, skeptvet, for writing this piece, and thank you, Veterinary Practice News, for also publishing it!

After reading the kind of response you get from those who disagree with the importance of skepticism in medicine, I appreciate the work you do even more so. I am about to head into a small animal internship, and the value of science based medicine when available can’t be any more important. I take this into account with my own health and medicine too. Thank you for your inspiration!

Sorry you are the target of so much rage and outrage. I must admit, it’s puzzling to me, too, why so many people who don’t agree with you get so upset and vicious about it.

As a counterpoint, let me say that I GREATLY appreciate all the research and time you put into creating this blog–it’s a wonderful and unique resource for those of us who value evidence-based medicine. I never realized how little it’s actually being practiced out there til I started reading your articles. I really rely on your analyses and only wish you could cover even more topics!

Wow. I am not skimmed a few, and found them pretty strange and not great reading. I admire you for your balanced viewpoint and for remaining courteous – not something most of your detractors manage, I see. Thank you for writing and thinking.

As I have said before I really appreciate the effort you put into this blog, when you could no doubt be doing far more entertaining things or even just sleeping. I also appreciate that you manage to maintain a polite tone, while I love me some Respectful Insolence the field of sceptical scientific bloggers is small enough that we still need all of the straight analytical posters we can get. So once again THANK YOU!!!!!!

Wow, that’s some heavy stuff. I applaud you for expressing enough clear opinion to piss people off. 

Thank you for your quick and helpful response!

Hello there. I *really* admire and enjoy your blog posts. I have forwarded a link to this latest one to several more junior colleagues who are very interested in this topic…I find your work on this blog outstandingly good and very enjoyable.

I really appreciate this blog.

Excellent commentary, as usual.

I appreciate your blog and I am so glad that I found it several years ago. You provide a great service, especially for pet owners such as myself. The articles you have published have helped me have informed opinions about different alternative treatments. Plus, your discussions about EBM approaches in conventional medical care have helped me understand how to better discuss and interact with our vets when we seek care for our poodles.

I love this blog and check it often…Thanks for all your writing, time and assistance.

I love this blog. You have no idea how much. I’m a retired pharmacist and I like my medicine evidence based and my science peer reviewed. You are a rare voice in the blogosphere these days but a badly needed one. I am constantly getting in heated discussions over woo. I recently saw someone suggest a person nebulize their sick puppy with colloidal silver. I nearly swallowed my tongue but I could not keep quiet in the face of such insane ideas. I often think we are totally losing the battle for common sense and good judgement. I would be even more depressed if not for your blog.

I just came across your blog as my husband asked me to look at an herbal product being marketed for Cushing’s. Our 14 year old mixed breed dog has this. She is on Vetoryl. I am a retired psychologist who knows the value of relying on good scientific research. I just wanted to tell you that I appreciate your good advice and will be following your blog. I may be asking for some of your advice in the future.

Someone recommended ozone therapy for my dog who is having repeating diarrhea episodes…It sounded like homeopathic/holistic nonsense to me from the description I read so I thought “where can I get some reliable info on this?” Of course I came to you first. Thank you for providing facts and reliable information on these types of subjects so those of us who shun all the hocus pocus inflicted on our animals in the name of healing can make informed decisions and feel better about telling well-meaning people “no, thanks!”

I appreciate your website and insightful comments, and I agree that a few individual cases do not amount to proof…Thank you!

Thank you so much for the information provided on your website. I have been working for an Internal Medicine Practice for 12 years under 3 Dip. ACVIM doctors. On currently practicing for 47 years. As time goes by more and more of our clients are being stooped into believing non-science based information they read online. Most recently, Glacier Peak Holistic Pet Life Scan. I have provided my client with your review of their rubbish. Thanks again!!!

We need more vets like you fighting for veterinary medicine to be based on the same requirement for evidence that human medicine is.

I just want to say I am really enjoying the site and I am learning lots which is always good

Thank you. Your reply has done more good than you may realize. ?? Compassion and science – a powerful medicine.

Your website is invaluable for accurate information.   Thank-you!  

Excellent article, thank you for your efforts.

If I had an animal, you would be my vet.

Just found this in a Google search on standard process. I love the thoughtful analysis.

I really, really wish I’d found this post–or something similar, lol–5 years ago. Thanks.

Thank you so much! There are so many anecdotal stories about these products (and everything dog related) online, which as you point out, does not constitute evidence. I sincerely appreciate such a considered post. You are doing great work, it’s often difficult to separate marketing from real science when dealing with a pup with behavioural issues and I’m so glad to see someone working to address this.

Since I found this blog a while ago I’ve been a fan. The main problem I have is that a lot of veterinarians will advertise “acupuncture”, “traditional Chinese medicine” or “holistic” (which generally has acquired a different meaning than just “considering all aspects”). It seems to be not easy to actually find a veterinarian who tells you that they are doing science based medicine. It leaves me as a pet owner to try to check up on the vet (refused to buy glucosamin supplements from 3 different vets so far) and trying to figure out what aspects of their medical practice I can trust and which I can’t. I tend to come here to check.

Dear Skeptvet
I too was happy to stumble on your blog via the NPR article , while browsing “News” on my phone. Having spent 13 years in scientific research before becoming a vet, I was originally shocked by the idea that medicine was NOT entirely evidence based. I just assumed it would be. But after ten years in practice I am getting worn down by the lack of rigorous data
And scientific information, pressure of colleagues, pressure of pet owners to practice unproven methods left and right. It is great to have your reasoned voice out there. I hope more pet owners will come across your blog.

I came to your blog after a friend posted your interview. I have now book marked your blog! Keep advocating for science based medicine – my dogs thank you for it.!

I just found your blog through the NPR interview and have been impressed while perusing it. Thanks for the enormous amount of time, effort, etc. you’ve devoted to this fantastic resource. As a pet owner (2 cats) with longtime professional expertise in research synthesis — mainly meta-analysis — and personal interest in scientific skepticism, I’m heartened to see this sort of critical thinking emphasized for the well-being of creatures who depend heavily on their vets and owners to make responsible healthcare choices.

I can say that it would have been extremely helpful to have had the benefit of this blog at the time we were weighing our options. Thank you for this site, which does an excellent job of providing fact based information to assist in making critical choices about the care and well being of cherished members of our family.

I am new here. I appreciate what you do. Found out about you on NPR. Thank you for taking the time to do this.

P.s. love your site, as usual. Many hours slip away from me some days perusing and reperusing your very entertaining and thoughtful analyses :b

As a professional, you are always one of my first choices to take care of my pets or someone that I refer others to take their pets to. Your open mindedness, willingness to look at the whole picture and willingness to listen to the client about their concerns makes you very competent in my eyes. Screw this tool who doesn’t even know you.


And to @Skeptvet, I just came across your site today in trying to do research on this product as it was prescribed for one of my patients. I am impressed with what I have read, and if this is any indication of the rest of your site, bravo to you for such a thoughtful, helpful and fact-based approach to the problems many owners confront. Keep up the good work.

I am so glad I found this site. Keep it up! Many more clients asking about ‘Veterinary naturopaths’ these days.– a concerned DVM student

Thanks for your clear explanations, skeptvet.

On another note, thanks for your blog, @skeptvet. I consult it frequently to help me keep my eye on the ball when it comes to the care of my digestively challenged, highly allergic white boxer/staffie angel. 

Thank you for this article, I am very glad I stumbled across you.

As another evidence-inspired practitioner, I am grateful for the time and effort Skeptvet puts forth in this continuing discussion.

This is EXACTLY what I needed as we try to understand what’s happening with her kidneys, and as we look to exhaust all of the options that are both within our financial reach and that are most likely to have a positive impact on her health. Thank you.

I want to thank you for doing this.

Not everyone can contact a friend and have her go to a friend who is a knowledgeable veterinary researcher. I am glad your site exists. There’s so much trash out there, it’s good to have a voice of reason.

I love this skepticism! People need to see a balance of ideas and decide for themselves what resonates with them.

Thanks,.
I just wanted to check, is it okay if I quote you from time to time? I would always provide the link to the article and your website.
I have been doing this, but wanted to know if it was okay?

Your site has been very helpful . Thanks For sharing information.

Thank you so much for taking the time to provide clear thought and information on these topics, Skeptvet. I just learned of your site from a friend’s post and I can’t stop reading. I appreciate all the work you have done to lay out the evidence and arguments, with explanations of how the scientific process works, and how to evaluate information. We need science more than ever!

Thanks for your blog! I’m a pet owner, and I’ve noticed that a number of local vets are into various practices that I’m sceptical of. (I’m from Canada; that’s how we spell sceptic.) Despite my doubts, I just tried hemp oil for my dog’s chronic rhinitis; no effect. Back to proven Western meds.
It was great to see you quoting the Cochrane folks! Carry on!

I want to thank you also; your website provides good information and helps me avoid quackery. 

Thank you for doing this. I hope you have something that works to ‘clean’ your brain after going through so much dross.

I, too, thank you. A few months ago, before finding your website, I would have watched the series and believed it all: anti-vaccine, anti-preventative, raw food, holistic. Now i’m using Dog Food Logic to try to figure out what kibble to feed our new dog. Where do I send the Scotch??

Hopefully people are drawn to your blog since it’s extremely well researched and presented. Thanks again for everything you do!

Hi there. I reguarly seek refuge in your blog when I’m bombarded by client questions on homeopathy, natural remedies, and, the product do jour, CDB oil.

I just discovered your blog tonight. Thanks so much for this! Wow — what a tremendous amount of work you put in to helping people make informed decisions in a confusing world of real and bogus (or at least, unbacked) treatments. Much appreciated!

Thank you for your refreshing blog. I am constantly frustrated by  clients who insist various non-sense treatments work, as opposed to my science based treatments. Of course, their perception is that I am just out to make money (aren’t all veterinarians? because we went into this field to make money??)

Thank you for helping me verbalize these ideas to my clients.

I am a physician and much appreciate your fine web site. Keep up the great work!!

Skeptvet, Firstly I’d like to thank you for your efforts in advocating for science based veterinary medicine. I’ve been a big fan of Dr Steven Novella and his efforts in human medicine and one of the few people I trust for good information. Your blog has become my go to source for advice regarding my dogs.

Thank you for getting back to me, and for spending so much time and effort helping to promote good, evidence-based medicine and stamping out quackery.

I love your blog by the way.  Its nice to read pet/animal information that is presented in a factual and scientific way instead of all the bogus stuff on the internet that essentially tries to tell you that you are killing your dog/cat if you are/aren’t doing “xyz”.  No research, no trials, no really any information to back it up with, just people spouting what they think.

Keep up the good work!

Thank you for this site! I’m a bit of a helicopter cat mom and have read so many articles debating certain ingredients in cat foods—namely carrageenan and menadine sodium bisulfate complex. I recently added weruva to my kitty’s rotational diet and kicked myself for feeding him something MSD in it after seeing it on the label until I read this!! Thanks so much for putting my mind at ease.

Your extremely articulate writing and your views are a breath of fresh air amidst what I sometimes feel is pure insanity. You are not alone, although even within the vet community it sometimes feels that way.

I just want to say “thank you.” Finding your blog fills me with relief – that I have someone to go to who uses critical thinking skills to produce relevant, science-based information about veterinary medicine…Screw those critics. Rock on.

Just want to say thank you for producing such amazingly educating contents with scientific rigor and empirical prudence. In this crazy milieu teeming with paranoiac pet parents and cultish advocates (with all due respect to those who aren’t), it is hard to find a public platform like yours with a voice so scientifically careful yet reassuringly informative. Keep up the good work!

I’m a PHD chemist, and I get a lot of questions from my friends about woowoo stuff. You blog is a REAL breath of fresh air. You focus on the science, you do not condemn (despite that fact that I would want to slap some commenters silly). Keep doing what you are doing. It really is appreciated.

Posted in General | 13 Comments

Should I Worry About Bacteria in My Pet’s Urine? Well, It Depends….

Veterinarians and pet owners are highly motivated to find discrete, fixable problems when pets are unwell. Owners want the reassurance and sense of control that comes with knowing what the problem is and taking action. Vets want to help our patients, and we want to satisfy our clients, who often expect us to offer some clear preventative or therapeutic intervention, which can justify their time and expense coming to see us and reassure them about their pets’ condition. Finally, our medical training often emphasizes diagnosis and treatment as the core responsibility for a doctor, and the importance of knowing when not to take action is frequently underemphasized.1,2

Such inherent bias towards finding and treating problems creates discomfort and resistance when scientific evidence suggests we should avoid some tests or treatments. Though there is widespread awareness of the risks of overdiagnosis and overtreatment in human medicine, these are relatively new and controversial concepts in the veterinary field.3,4My own efforts in this column and elsewhere, to suggest that we might sometimes do better not to run a test (e.g. pre-anesthetic bloodwork)5or prescribe a treatment (e.g. lysine)6have generated the kind of pushback that often greets such suggestions. 

Nevertheless, we have a responsibility to heed the evidence and recognize when inaction may serve our patients better than intervention. One example of this that is beginning to gain some attention in veterinary medicine is subclinical or asymptomatic bacteriuria (AB).7This is most simply defined as the presence of bacteria in urine without clinical signs compatible with a urinary tract infection (UTI).8–10The definition of AB may also include a threshold quantity of bacteria grown on culture and repeated positive urine cultures, to distinguish AB from transient bacteriuria and contamination of the urine sample.11,12

In humans, the presence of bacteria without symptoms of UTI is quite common, though the prevalence varies with sex, age, and many other factors. Less than 5% of healthy, pre-menopausal women have AB, whereas 100% of people with chronic indwelling urinary catheters will have bacteriuria even when no symptoms of UTI are present. Prevalence is higher in the elderly, diabetics, and people with some other causes of immunocompromise.8,12

Despite this high prevalence, there is substantial research showing most people with AB do not benefit from antibiotic therapy.8,12–14Even in diabetics, the elderly, and other individuals with potentially compromised immune function, AB does not seem to increase the risk of negative outcomes, and treatment with antibiotics provides no benefit and may even cause harm.12,14Antibiotic treatment for humans with AB appears to be beneficial for only a very limited set of circumstances, such as in pregnancy and prior to transurethral resection surgery.11

Clinical practice guidelines for physicians recommend against screening and treatment for AB in most patient populations.11,12Despite this, many physicians will still prescribe antibiotics when they diagnose AB, particularly if pyuria or other findings are present that they believe indicate UTI even when the evidence does not support this practice.  Education programs have been employed to reduce this inappropriate antibiotic use because it can increase patient morbidity and antibiotic resistance.8

It is less clear how common AB in dogs and cats. Studies have found highly variable prevalence, from 28% to less than 1% of samples in cats15–20and from 25% to 0% of samples in dogs.9,10,21The occurrence of AB appears to vary with many factors, including species, sex, age, body condition score, and presence of potentially predisposing diseases.7,10,15,17–19,21,22Morbidly obese dogs, for example, appear more likely to have AB than dogs with less extreme body conditions scores.21Females are often reported to have AB more frequently than males.17,23

Interestingly, some studies have failed to find any association between potentially immunosuppressive drug treatment and AB even though such medications have been reported to increase the risk of urinary tract infections.20,24–26An increased risk in the presence of chronic kidney disease (CKD) has been seen in some reports but not others.9,17

Unfortunately, most of the studies in veterinary patients have evaluated small numbers of patients, and they have varied methods and numerous limitations which it challenging to compare studies or have much confidence in the results. Sufficient detail is lacking to clearly identify associations between specific patient characteristics and the prevalence and risk of AB. This makes it more difficult to challenge the reflexive urge many of us have to treat bacteriuria whenever we see it despite the strong evidence in humans that this may not always be best for the patient.

The limited veterinary evidence available does suggest that AB is not likely to be a predictor or cause of subsequent disease.10,19However, this conclusion must be viewed as tentative given the strength of the evidence. The most recent guideline from The International Society for Companion Animal Infectious Diseases offers the following recommendation:27

“Treatment may not be necessary in animals that have no clinical signs of UTI and no evidence of UTI based on examination of urine sediment. 

In some circumstances, treatment may be considered if there is concern that there is a particularly high risk of ascending or systemic infection (e.g., immunocompromised patients, patients with underlying renal disease) or that the bladder may be a focus of extra-urinary infection.”

This is necessarily a far more tentative recommendation than guidelines for physicians due to the paucity of high-quality research evidence. Nevertheless, it reflects a growing awareness that treatment of AB is likely to be unnecessary in at least some veterinary patients and, as in humans, it may lead to increased antibiotic resistance and poorer clinical outcomes. 

There is also research in humans showing that colonization of the urinary tract with non-virulent bacteria can protect against more virulent, and more antibiotic-resistant varieties. Such bacteria have been used clinically to reduce the risk of symptomatic UTI and more serious sequelae, such as pyelonephritis.12,28AB was once considered a probable cause of pyelonephritis, but it is now recognized as benign or even a potentially protective condition.12

Research has been conducted to evaluate this potential prophylactic use of non-pathogenic organisms in dogs.29–31In one study, instillation of  an E. colistrain obtained from an individual with AB into dogs appeared to have no significant risks, and it may have been effective in treating and preventing some naturally occurring UTIs. The study was small and uncontrolled, so further research will be needed to confirm the safety and efficacy of this practice.

Bottom Line
In the absence of conclusive evidence for veterinary species, individual clinicians must decide how to manage apparent cases of bacteriuria. While extrapolation from human medicine is not always reliable, it is a common starting point for making clinical decisions in veterinary patients. In cases when bacteriuria is identified and when there are no apparent clinical signs of UTI and no special circumstances (such as advanced age, immunosuppressive disease or medical treatment, etc.), it is reasonable for veterinarians to choose not to provide antibiotic therapy. We must, of course, explain to clients the reasoning for this choice, including the goal of avoiding harm from unnecessary treatment, in the form of medication side-effects and potentially more dangerous and drug-resistant UTIs. 

When treating AB or uncomplicated UTI, we should also bear in mind that 3-5 days of treatment is the standard in human medicine.32–34Though again the evidence is not yet conclusive in veterinary patients,35it is likely that longer treatment only increases complications and reduces compliance without improving outcomes for our patients.

References

1.        Vandeweerd J-M, Vandeweerd S, Gustin C, et al. Understanding Veterinary Practitioners’ Decision-Making Process: Implications for Veterinary Medical Education. J Vet Med Educ. 2012;39:142-151. doi:10.3138/jvme.0911.098R1

2.        McKenzie BA. Veterinary clinical decision-making: Cognitive biases, external constraints, and strategies for improvement. J Am Vet Med Assoc. 2014;244(3). doi:10.2460/javma.244.3.271

3.        McKenzie BA. Overdiagnosis.J Am Vet Med Assoc. 2016;249(8). doi:10.2460/javma.249.8.884

4.        Welch H, Schwartz L, Woloshin S. Overdiagnosed: Making People Sick in Pursuit of Health. Boston, MA: Beacon Press; 2011.

5.        McKenzie B. Why do we run diagnostic tests? Vet Pract News. February 2018:38.

6.        McKenzie B. Lysine: A therapeutic zombie? Vet Pract News. May 2018:26-28.

7.        Senior DF. Subclinical Bacteriuria. Clin Br. November 2018:61-64.

8.        Flokas ME, Andreatos N, Alevizakos M, Kalbasi A, Onur P, Mylonakis E. Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2017;4(4):ofx207. doi:10.1093/ofid/ofx207

9.        Foster JD, Krishnan H, Cole S. Characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease. J Am Vet Med Assoc. 2018;252(10):1257-1262. doi:10.2460/javma.252.10.1257

10.      Wan SY, Hartmann FA, Jooss MK, Viviano KR. Prevalence and clinical outcome of subclinical bacteriuria in female dogs. J Am Vet Med Assoc. 2014;245(1):106-112. doi:10.2460/javma.245.1.106

11.      Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005;40(5):643-654. doi:10.1086/427507

12.      Nicolle LE. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria. Pathog (Basel, Switzerland). 2016;5(2). doi:10.3390/pathogens5020038

13.      Bigotte Vieira M, Alves M, Costa J, Vaz-Carneiro A. Análise da Revisão Cochrane: Antibióticos Destinados ao Tratamento da Bacteriúria Assintomática. Cochrane Database Syst Rev. 2015;4:CD009534. Acta Med Port. 2018;31(2):76. doi:10.20344/amp.10077

14.      Köves B, Cai T, Veeratterapillay R, et al. Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel. Eur Urol. 2017;72(6):865-868. doi:10.1016/j.eururo.2017.07.014

15.      Litster A, Moss S, Platell J, Trott DJ. Occult bacterial lower urinary tract infections in cats—Urinalysis and culture findings. Vet Microbiol. 2009;136(1-2):130-134. doi:10.1016/j.vetmic.2008.10.019

16.      Teichmann-Knorrn S, Reese S, Wolf G, Hartmann K, Dorsch R. Prevalence of feline urinary tract pathogens and antimicrobial resistance over five years. Vet Rec. 2018;183(1):21-21. doi:10.1136/vr.104440

17.      Puchot ML, Cook AK, Pohlit C. Subclinical bacteriuria in cats: prevalence, findings on contemporaneous urinalyses and clinical risk factors. J Feline Med Surg. 2017;19(12):1238-1244. doi:10.1177/1098612X16688806

18.      Eggertsdóttir A V, Sævik BK, Halvorsen I, Sørum H. Occurrence of Occult Bacteriuria in Healthy Cats. J Feline Med Surg. 2011;13(10):800-803. doi:10.1016/j.jfms.2011.07.004

19.      White JD, Cave NJ, Grinberg A, Thomas DG, Heuer C. Subclinical Bacteriuria in Older Cats and its Association with Survival. J Vet Intern Med. 2016;30(6):1824-1829. doi:10.1111/jvim.14598

20.      Lockwood SL, Schick AE, Lewis TP, Newton H. Investigation of subclinical bacteriuria in cats with dermatological disease receiving long-term glucocorticoids and/or ciclosporin. Vet Dermatol. 2018;29(1):25-e12. doi:10.1111/vde.12480

21.      Wynn SG, Witzel AL, Bartges JW, Moyers TS, Kirk CA. Prevalence of asymptomatic urinary tract infections in morbidly obese dogs. PeerJ. 2016;4:e1711. doi:10.7717/peerj.1711

22.      Koutinas AF, Heliadis N, Saridomichelakis MN, Leontides L, Terpsidis K, Christodoulou C. Asymptomatic bacteriuria in puppies with canine parvovirus infection: a cohort study. Vet Microbiol. 1998;63(2-4):109-116. http://www.ncbi.nlm.nih.gov/pubmed/9850991. Accessed January 7, 2019.

23.      White JD, Cave NJ, Grinberg A, Thomas DG, Heuer C. Subclinical Bacteriuria in Older Cats and its Association with Survival. J Vet Intern Med. 2016;30(6):1824-1829. doi:10.1111/jvim.14598

24.      Simpson AC, Schissler JR, Rosychuk RAW, Moore AR. The frequency of urinary tract infection and subclinical bacteriuria in dogs with allergic dermatitis treated with oclacitinib: a prospective study. Vet Dermatol. 2017;28(5):485-e113. doi:10.1111/vde.12450

25.      Torres SMF, Diaz SF, Nogueira SA, et al. Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment. J Am Vet Med Assoc. 2005;227(2):239-243. http://www.ncbi.nlm.nih.gov/pubmed/16047659. Accessed January 20, 2019.

26.      Ihrke PJ, Norton AL, Ling G V, Stannard AA. Urinary tract infection associated with long-term corticosteroid administration in dogs with chronic skin diseases. J Am Vet Med Assoc. 1985;186(1):43-46. http://www.ncbi.nlm.nih.gov/pubmed/3965423. Accessed January 20, 2019.

27.      Weese JS, Blondeau JM, Boothe D, et al. Antimicrobial use guidelines for treatment of urinary tract disease in dogs and cats: antimicrobial guidelines working group of the international society for companion animal infectious diseases. Vet Med Int. 2011;2011:263768. doi:10.4061/2011/263768

28.      Darouiche RO, Hull RA. Bacterial interference for prevention of urinary tract infection: an overview. J Spinal Cord Med. 2000;23(2):136-141. http://www.ncbi.nlm.nih.gov/pubmed/10914355. Accessed January 20, 2019.

29.      Thompson MF, Schembri MA, Mills PC, Trott DJ. A modified three-dose protocol for colonization of the canine urinary tract with the asymptomatic bacteriuria Escherichia coli strain 83972. Vet Microbiol. 2012;158(3-4):446-450. doi:10.1016/j.vetmic.2012.03.012

30.      Thompson MF, Totsika M, Schembri MA, Mills PC, Seton EJ, Trott DJ. Experimental colonization of the canine urinary tract with the asymptomatic bacteriuria Escherichia coli strain 83972. Vet Microbiol. 2011;147(1-2):205-208. doi:10.1016/j.vetmic.2010.06.007

31.      Segev G, Sykes JE, Klumpp DJ, et al. Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI. J Vet Intern Med. 2018;32(1):267-273. doi:10.1111/jvim.14851

32.      Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257

33.      Kang C-I, Kim J, Park DW, et al. Clinical Practice Guidelines for the Antibiotic Treatment of Community-Acquired Urinary Tract Infections. Infect Chemother. 2018;50(1):67. doi:10.3947/ic.2018.50.1.67

34.      American Academy of Family Physicians. R, Williams M. American Family Physician.Vol 84. American Academy of Family Physicians; 1970. https://www.aafp.org/afp/2011/1001/p771.html. Accessed January 28, 2019.

35.      Jessen LR, Sørensen TM, Bjornvad CR, Nielsen SS, Guardabassi L. Effect of antibiotic treatment in canine and feline urinary tract infections: A systematic review. Vet J. 2015;203(3):270-277. doi:10.1016/j.tvjl.2014.12.004

Posted in Science-Based Veterinary Medicine | 3 Comments

What are Screening Tests, and Should You Use them?

What is Screening?
Screening is the use of diagnostic tests in apparently healthy individuals with no clinical symptoms.1-2The purpose is to detect asymptomatic disease with the presumption that this allows earlier, more effective intervention and will reduce suffering and delay or prevent death. 

Screening is widespread in human medicine, though it is increasingly a subject of controversy and debate.3Large-scale programs in human medicine to promote testing for specific diseases have been widely used, such as prostate-specific antigen (PSA) testing for prostate cancer and mammography for detection of asymptomatic breast cancer. These are examples of screening programs which are now being questioned and scaled back in light of better evidence concerning their risks and benefits.4-5

However, any diagnostic test employed in an individual with no clinical symptoms of illness is a screening test. In veterinary medicine, there are few large-scale, coordinated screening programs, but routine well-pet exams are a common screening practice. There are also calls for more extensive and intensive screening efforts, such as the recent guideline from the American Animal Hospital Association (AAHA) and the large diagnostic laboratory IDEXX promoting routine lab testing for nearly all pets.6

How Does Screening Benefit Patients?
Most veterinarians understand the potential benefits of screening. Individual patients will benefit if a disease is identified which can be treated more effectively when asymptomatic than at a later stage. Some diseases can be delayed or even cured if treated at an early stage which cannot be so effectively managed if not detected until there are clinical symptoms. Identifying IRIS Stage 2 Chronic Kidney Disease and instituting dietary therapy is an example of effective screening and intervention.7-8This is what most of us assume all screening accomplishes.

True negative results might be considered beneficial as well in that they provide reassurance and, depending on the tests involved, potentially a baseline value that can be used for diagnostic purposes in the future, even though they don’t directly impact morbidity or mortality.

When Is Screening Not Beneficial to Patients?
Screening is of no benefit if it fails to detect disease that is present (false negative results), if it detects disease that is not present (false positive results), if it detects disease that is indolent and would not ever cause clinical symptoms (overdiagnosis), and if it detects disease for which treatment is not effective or no more effective than it would be if the disease had not been identified until the symptomatic stage.

When Does Screening Harm Patients?
Screening is harmful when patients are given an incorrect diagnosis. False positive results create anxiety and discomfort and often incur risk and cost from additional testing or treatment for a disease which does not exist. False negative results provide reassurance when there actually is a disease present, which can delay truly beneficial diagnosis and treatment. 

Even correct diagnoses can cause harm.9-10The distress associated with a diagnosis of cancer in an asymptomatic patient, for example, is not counterbalanced by any benefit if there is no effective treatment. The patient simply lives longer knowing they have an illness they cannot treat. And overdiagnosis, the correct identification of disease that is non-progressive and does not lead to illness, exposes patients and owners to the risks and costs of the initial diagnosis and any further testing and treatment without any potential benefit from intervention. Patients may perceive a benefit from false positive results or from knowing about and treating indolent disease, but objectively this can only cause harm.11-13

How Do We Evaluate the Risks and Benefits of Screening?
It is rarely possible to know if screening has been beneficial or harmful for a particular individual because the outcome in the absence of testing cannot be known. Patients, pet owners, and clinicians nearly always feel as if testing is worthwhile even when not objective benefit can be demonstrated. True negative and false negative results are always reassuring, and if disease develops later there is rarely any recognition that these results may have delayed identification and treatment of it. Even if a false positive test is later shown to be false by further evaluation, many people experience such relief at the eventual result that they are grateful for the screening even though objectively the cost and discomfort associated with it have no possible benefit. Subjective evaluation of screening, then, nearly always supports it, but this is a limited and unreliable measure of the value of such testing.

Statistical evaluation of specific tests can be useful. The well-known parameters of sensitivity and specificity tell us something about the reliability of tests. However, the parameters of positive and negative predictive (PPV and NPV) value are arguably more important clinically. These are a function not only of the tests but of the prevalence of the disease we are testing for. If the majority of the population does not have the disease (as is usually the case with screening of asymptomatic individuals), the PPV will be quite low and most positive results will be false positives. Since most patients diagnosed through screening don’t actually have that disease they are tested for, the overall risks and costs of screening and follow-up testing or treatment may outweigh the benefits even if some individual patients are helped.14

The most accurate way to determine whether more patients benefit or are harmed by screening is through epidemiologic data regarding specific diseases and the outcome of screening and treatment.1-3,10-11,15Data on large populations has shown, for example, that most prostate cancer detected by PSA testing is nonprogressive. While some individuals do benefit from early detection, statistically many more undergo psychological distress (including a rise in heart attacks and suicide) and physical harm (such as incontinence, impotence, and even death) due to testing and treatment. PSA screening is no longer recommended as widely as it once was because such evidence shows the practice does more harm than good.4,9-10Similar evidence has led to reduced use of mammography and many other screening tests in humans.5, 9-10

Unfortunately, there is little data and awareness of this issue in veterinary medicine, and screening is widely viewed as an unqualified good. For example, the recent AAHA/IDEXX effort to encourage more laboratory testing of asymptomatic individuals never mentions overdiagnosis and suggests that even normal results or abnormal findings of no clinical significance should be “celebrated” and treated as useful information.6Screening is frequently promoted as a marker of high-quality, effective medicine.16-19The financial benefits of screening, to veterinary practices and companies that provide testing services, are also often mentioned as a benefit,6without any discussion about the issue of veterinary healthcare costs and the potential impact of this on availability of care.20-21

There is little evidence that screening improves outcomes such as quality of life or mortality in veterinary patients for most conditions. Research shows that testing of asymptomatic individuals often finds abnormalities and that some of these lead to potentially beneficial intervention.6,9However, few studies have looked at costs and risks of screening or gathered objective data on the balance between these and the potential benefits.

Bottom Line
“All screening programmes do harm; some do good as well, and, of these, some do more good than harm at reasonable cost.” (Gray et al, 2008)22The challenge for veterinary medicine is to recognize the potential harms of screening and to actively collect evidence to identify the risks and benefits of specific tests in specific populations. The current approach of assuming the theoretical benefits of screening must apply and that harms are negligible is not consistent with the evidence from human medicine and not a cost-effective, evidence-based approach for improving the welfare of our patients.

 The Power of Stories
Anecdotes are the primary justification for screening in veterinary medicine. The AAHA/IDEXX protocol, for example, includes a section called “The Power of Stories” which provides anecdotes of patients who benefitted from screening tests. Apart from not being an objective measure of the balance between risks and benefits, anecdotes can just as easily be used to challenge screening as to defend it. Here are two brief examples. 

Case Example: 10 Year-old Whippet
The patient presented for an annual examination and was offered a CBC and chemistry panel. Thrombocytopenia was identified, as well as mild neutropenia, elevated amylase, and decrease AST and CPK. Follow-up testing confirmed thrombocytopenia, and the patient was referred for further testing. Tick-borne disease panel, abdominal ultrasound, and thoracic radiographs were unremarkable. A subsequent CBC was unchanged, and pathology review concluded the findings were likely normal for the individual and breed. Despite the lack of any preceding or subsequent clinical illness, the owner experienced great distress at the possibility of serious illness in her pet, and the patient was exposed to the discomfort of numerous diagnostic procedures at a total cost of $924. 

Case Example: 5 Year-old Labrador Retriever
The patient presented with acute-onset lameness in the left hind leg and no other symptoms. Physical examination identified acute cranial cruciate ligament rupture. Pre-anesthetic chemistry panel revealed moderate elevation of ALT. Abdominal ultrasound identified mildly hypoechoic, indistinct nodular foci in the liver. Ultrasound-guided biopsy identified benign nodular hyperplasia. The patient died of hemorrhage following the biopsy. 

References
1. Wilson JMG. Jungner G. (1968) Principles and practice of screening for disease. World Health Organization Public Health Papers #34. Geneva, Switzerland.

2. Speechley M. Kunnilathu A. Aluckal E. et al. Screening in Public Health and Clinical Care: Similarities and Differences in Definitions, Types, and Aims – A Systematic Review. Journal of Clinical and Diagnostic Research. 2017;11(3):LE01-LE04.

3. Bulliard JL. Chiolero A. Screening and overdiagnosis: Public health implications. Public Health reviews. 2015:36(8). 

4. Tabayoyong W, Abouassaly R. Prostate Cancer Screening and the Associated Controversy. Surg Clin North Am. 2015 Oct;95(5):1023-39. 

5. Berry DA. Breast cancer screening: controversy of impact. Breast. 2013 Aug;22 Suppl 2:S73-

6. American Animal Hospital Association. Promoting preventative care protocols: Evidence, enactment, and economics. 2018. Accessed September 21, 2018. Available at: https://www.aaha.org/public_documents/professional/resources/promoting_preventive_care_protocols.pdf

7. International Renal Interest Society. IRIS staging of CKD. 2017. Accessed September 21, 2018. Available at: http://www.iris-kidney.com/pdf/IRIS_2017_Staging_of_CKD_09May18.pdf

8. Ross SJ, Osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc. 2006 Sep 15;229(6):949-57.

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

10. Welch HG, Schwartz LM, Woloshin S. Overdiagnosed: mak­ing people sick in pursuit of health. Boston: Beacon Press, 2011.

11. Raffle AE. Gray JAM. Screening: Evidence and Practice. Oxford: Oxford University Press, 2007. 

12. Boone D. Mallett S. Zhu S. et al. Patients’ & Healthcare Professionals’ Values Regarding True- & False-Positive Diagnosis when Colorectal Cancer Screening by CT Colonography: Discrete Choice Experiment. PLoS ONE 2017;8(12): e80767. 

13. Brodersen J, Siersma VD. Long-Term Psychosocial Consequences of False-Positive Screening Mammography. Annals of Family Medicine. 2013;11(2):106-115.

14. Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhalation Toxicology. 2014;26(13):811-828. 

15. Gates TJ. Screening for cancer: concepts and controversies. Am Fam Physician. 2014 Nov 1;90(9):625-31.

16. Lewis HB. Healthy pets benefit from blood work. Ban­field Data Savant. Accessed September 21, 2018. Available at: www.banfield.com/getmedia/1216c698-7da1-4899-81a3-24ab549b7a8c/2_1-Healthy-Pets-benefit-from-blood-work.

17. Irwin J. Do tests first: pre-surgical blood work may eliminate variety of surprises. DVM 360 Nov 1, 2003.

18. IDEXX Laboratories. Preanesthetic testing: don’t compro­mise—change happens fast. Accessed September 21, 2018. Available at: www.idexx.com.au/smallanimal/inhouse/preanesthetic-testing.html

19. Ward E. Ask the expert: preanesthetic testing in private prac­tice. NAVC Clinician’s Brief. January 2010. Accessed September 21, 2018. Available at: https://www.cliniciansbrief.com/article/preanesthetic-testing-private-practice

20. LaVallee E, Mueller MK, McCobb E. A Systematic Review of the Literature Addressing Veterinary Care for Underserved Communities. J Appl Anim Welf Sci. 2017 Oct-Dec;20(4):381-394.

21. Stull JW. Shelby J. Bonnett B. et al. Broadening access to veterinary care: Barriers and next steps to providing a spectrum of effective healthcare to our patients. J Amer Vet Med Assoc. 2018. In press

22. Gray JAM, Patnick J, Blanks RG. Maximising benefit and minimising harm of screening. British Medical Journal. 2008;336(7642):480-483.

Posted in Science-Based Veterinary Medicine | 28 Comments

Should we be Vaccinating Dogs at Acupuncture Points?

A couple of recent articles by acupuncturists have suggested that giving vaccines at acupuncture points may be more effective than giving them in other locations. This is clearly an attempt to demonstrate the serious, scientific legitimacy of acupuncture. However, there are a number of serious problems with these claims and with the studies used to support them. 

Study 1
Jin H, Xu Y, Shi F, Hu S. Vaccination at different anatomic sites induces different levels of the immune responses.Res Vet Sci. 2019;122:50-55. doi:10.1016/j.rvsc.2018.11.005

The Study
This study vaccinated rats with a live attenuated combination vaccine for dogs containing antigens for canine distemper, canine parvovirus, canine parainfluenza, canine adenovirus, and rabies. The rats were injected at several different anatomic locations (see Figure 1). A group of 10 female Rottweiler puppies between 32-36 days old were also vaccinated twice, three weeks apart, first with a modified live distemper/parvo vaccine and then with a modified-live vaccines for distemper, parvovirus, adenovirus, and parainfluenza. These vaccines were given at different locations in different dogs (see Figure 1). 

Figure 1

The study measured blood antibody levels as a marker of vaccine response. The rats were vaccinated twice, 2 weeks apart, and blood was collected at 2, 4, and 6 weeks after the second vaccination. The dogs were vaccinated twice, with different vaccines, three weeks apart. Blood was collected from the dogs 2, 4, and 6 weeks after the second vaccination. The levels of antibodies detected at each time period following vaccination at the different locations in the rats and dogs are shown in Figures 2 and 3.

Figure 2
Figure 3

Analysis of the Study
Methodologically, this study lacks a number of important features to control for error and bias. There was no randomization of subjects, no blinding of investigators or caregivers to the different treatments, and only a small number of dogs of one sex and breed were included. Such controls are especially important given that the study was funded by a veterinary acupuncture group with a clear interest in the outcome. It is also unclear what relevance the immune response of rats to injection with canine vaccines might have to the effect of those vaccines in protecting dogs from infectious diseases.

The dogs in the study were initially vaccinated at about 4 weeks of age, which is earlier than recommended because most puppies will have maternal antibodies at this age that interfere with the effect of vaccination. The second vaccine they received was at about 7 weeks of age, which is still slightly earlier than typically recommended. It is unclear whether these puppies had nursed or had maternal antibodies to begin with, but generally vaccination is done repeatedly between 8 and 16-20 weeks to ensure an adequate immune response. 

It is also unclear whether the differences in antibody levels have any real-world significance. With only a couple of exceptions, the levels were above or below the cutoff for all dogs in all groups at each time point. All dogs achieved antibody levels above the cutoff by about 11 weeks of age, well before the end of the usual vaccine series, so there is little reason to think the differences measured have any implications for susceptibility to disease, which is the import thing in any immunization program. There were also no adverse events for any of the dogs, so there is no reason to think the location of vaccination influences safety or effectiveness of immunization. 

The fact that antibody levels different with the site of vaccination is interesting. There has been some research in humans suggesting that the anatomic location of vaccination can influence the strength of the response.1-2This is suspected to be due to differences in blood supply, fat density, presence of immune surveillance cells, and other such factors. However, what, if anything, this has to do with acupuncture is a different question. For one thing, as I have discussed in detail in the past, there is little compelling evidence that acupuncture points exist at all as distinctive anatomic or functional locations. There is also significant variation in where acupuncturists locate such points, suggesting the concept is more a metaphor than a biological reality. 

In this study, the highest antibody levels were detected at the huohaiacupuncture point (also known as GV 1). This is a sensitive spot between the dorsal edge of the anus and the ventral tail base (see Figure 1). There likely are differences in the activity of the immune system between such a protected spot located close to an obvious source of bacteria and a location like the nape of the neck, a spot fortified against attack with thick skin and subcutaneous fat, little blood supply, and far from any excretory organs. There are plenty of distinctions between such locations that are far more plausible than the mystical notions of energy channels, Ch’i, Yin and Yang, and the other ideas that form the theoretical structure of Traditional Chinese Medicine. Any difference that might be found between the immune response at these spots does not require us to accept the reality of such folk mythology as the only explanation.

Study 2
Perdrizet JA, Shiau D-S, Xie H. The serological response in dogs inoculated with canine distemper virus vaccine at the acupuncture point governing vessel-14: A randomized controlled trialVaccine. 2019;37(13):1889-1896. doi:10.1016/j.vaccine.2018.10.076

The Study
100 client-owned dogs were randomly assigned (though by an odd method with some potential for umasking) to be vaccinated with a modified-live vaccine containing antigens for canine distemper, adenovirus, parvovirus, and parainfluenza at either the side of the neck or at the GV-14 acupuncture point (dorsal midline cranial to the dorsal spinous process of T1). Antibody titers for canine distemper were measured at the time of vaccination and 2 weeks later for all dogs.

Analysis of the Study
The dogs in both groups were vaccinated about a year after previous vaccination, which is earlier than the 3-5 years typically recommended, and both groups had both measurable antibody levels before vaccination and an increase in these levels after vaccination. There was tremendous individual variation in antibody titers and response to vaccination (Figures 4 and 5). Whether there is a consistent and meaningful effect of location of immune response is difficult to tease out of this background variation. The authors did some transformations and various statistical manipulation of the data to identify a statistically significant difference. Whether this is a true difference or a function of the particular study and the methods used is unclear.

Figure 4. Antibody responses to vaccination in different sites
Figure 5. Change in antibody titers after vaccination in different sites.

It is also unclear if there is any real-world difference in the protection against disease between these groups, a fact the authors acknowledge. Even if the location of vaccination predictably influences the magnitude of immune response, most dogs will be protected either way and a small proportion will not be protected either way, so is there any meaningful difference in the chances of dogs becoming ill? That is not a question this study can answer, but given how effective current vaccination is for core infectious diseases, it seems unlikely that changing the location in which we vaccinate is going to protect more dogs.

The authors imply that one reason to determine if vaccination at supposed acupuncture points might be worthwhile is that we could reduce the risks of vaccination if we generated a stronger or more durable response and, presumably, could then vaccinate less. This is implausible. For one thing, the disease they suggest result from vaccination, such as immune-mediated destruction of platelets or red blood cells, have not been consistently or convincingly associated with vaccines.And if we were able to trigger a stronger immune response by vaccinating in a particular location, there is no reason to believe this would not also increase any risks associated with the vaccination response. No adverse events were reported for either group in this study (not surprisingly, since such reactions are uncommon, though it is also possible that dogs with a history of vaccine reactions simply were not included in the study since they may no longer be receiving vaccines). 

General Issues 
These studies do not make a convincing case for vaccinating dogs in supposed acupuncture points. The reasons for this include the following:

  1. The principles of Traditional Chinese Medicineare unscientific folk mythology, and there is no reason to believe any practice guided by these ideas is going to be equal to or superior to practices based on scientific principles.

  2. Despite thousands of years of use, and decades of research, it has not been convincingly shown that so-called acupuncture points exist at all, except as metaphorical concepts. Acupuncturists in different sects identify very different points, and studies show acupuncturists are highly variable and imprecise in their localization of points. No consistent evidence indicates that acupuncture points in general, or the specific points in these studies, have distinctive and relevant anatomic or functional differences from other locations not designated as “points” by the TCM mythology.

  3. The variability in antibody levels and immune response may well be influenced by the location of vaccination. However, any such effect is more likely to be explained by objective and conventional anatomic and functional features of these locations, not by their status as special locations in terms of folk metaphors.

  4. There is great individual variation in antibody levels and immune response to vaccination, and it is unclear whether the statistical differences identified in these studies represent real differences, study artefacts, or normal variability. There is a growing recognition that statistical significance testing is misused in medical research and readily creates the impression of meaningful biological difference where none exists. This awareness has led to calls from statisticians and researchers to abandon the practice and emphasize more meaningful measures of effect in research studies.

  5. Even if it were established that there were true differences between the groups in these studies, from whatever cause, it has yet to be established that these have any real-world significance in terms of protection from disease or safety. Current vaccination practice are incredibly safe and effective, and while improvement is always desirable, the small differences seen in these studies are unlikely to have any implications for the actual health of patients. Certainly, nothing in this research suggests the locations chosen by the authors are safer or more effective at presenting disease than current locations typically used.

  6. From the practical perspective of a clinician actually treating dogs, I can tell you that vaccinating routinely at GV-1 (just above the anus) is going to be far more painful and difficult than current locations. Without a large, proven benefit to doing so, it makes no sense to subject patients or staff to this practice. 

Interestingly, the least antibody response seen in the Jin study was at a location very close to the GV-14 point used in the Perdrizet study. While I’m sure the authors would argue that these points are not comparable because of the precise localization of acupuncture point, again the research indicates that such points are in fact quite variable and imprecise, so to a small extent these studies actually contradict one another in terms of the effect of vaccination over the shoulders.

Bottom Line
There is no plausible reason to think that vaccinating dogs at supposed acupuncture points, if these even exist, will improve the protection from disease conveyed by vaccination or will reduce the risks of vaccinating.

References

  1. Jin H, Xu Y, Shi F, Hu S. Vaccination at different anatomic sites induces different levels of the immune responses. Res Vet Sci. 2019;122:50-55. doi:10.1016/j.rvsc.2018.11.005

  2. Shaw FE, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine. 1989;7(5):425-430. http://www.ncbi.nlm.nih.gov/pubmed/2530717. Accessed April 8, 2019.
Posted in Acupuncture | 6 Comments