SkeptVet Visits The Pet Doctor Podcast- Are we seeing more cancer in pets?

In October, I wrote a column for Veterinary Practice News (VPN) on the question of whether or not cancer is more common in dogs and cats now than it used to be. This is a core argument in the Truth About Pet Cancer propaganda video series I debunked HERE and HERE. The VPN article caught the attention of Dr. Bernadine Cruz, who asked me to visit her podcast to discuss the subject. Enjoy!

The Pet Doctor Podcast- Are we seeing more cancer in pets.

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Crowdfunding Quackery

One of the most heartbreaking things we all see on social media are appeals for financial help to fund medical treatment. Especially here in the U.S., where healthcare is less readily available to low-income people than in most developed countries, it has become common to see crowdfunding campaigns raising money for medical care. It is inspiring that people are so often willing to help strangers with medical expenses, but it is sad and wrong that patients have to rely on such ad hoc methods for funding the care they need.

As sad as this inherently is, it becomes depressing and infuriating when these crowdfunding campaigns are intended to pay for unproven or quack therapies. Crowdfunding provides a new venue for people to be misled and exploited by proponents of untested, ineffective, and dangerous medical treatments, Now, not only the desperation of patients and their families are taken advantage of, but also compassion of well-meaning strangers who contribute to these campaigns.

Two recent studies have been published in the Journal of the American Medical Association (JAMA) investigating this issue, and these have been publicized through reporting by NPRand other media outlets.

Vox F, Folkers KM, Turi A, Caplan AL. Medical Crowdfunding for Scientifically Unsupported or Potentially Dangerous TreatmentsJAMA. 2018;320(16):1705–1706. doi:10.1001/jama.2018.10264

This study looked at homeopathyand naturopathyfor cancer, hyperbaric oxygen therapy,stem cell treatmentfor brain and spinal cord injury, and long-term antibiotics for Chronic Lyme Disease. All. But the last will be familiar to readers as examples of methods that are dubious or simply don’t work. The study found:

More than 1000 medical crowdfunding campaigns for 5 treatments that are unsupported by evidence or potentially unsafe raised more than $6.7 million… These results reveal that a wide scope of cam- paigns for unsupported, ineffective, or potentially dangerous treatments are moderately successful in obtaining funding. Assuming that the funds raised are spent to pay for these treatments, donors indirectly contributed millions of dollars to practitioners to deliver dubious, possibly unsafe care. 

Snyder J, Turner L, Crooks VA. Crowdfunding for Unproven Stem Cell–Based Interventions. JAMA.2018;319(18):1935–1936. doi:10.1001/jama.2018.3057

The second study focused specifically on stem cell therapies and found similarly large amounts of money committed to campaigns for questionable treatment and also misleading appeals to donors:


Our search identified 408 campaigns seeking donations for stem cell interventions advertised by 50 individual businesses. These campaigns requested $7?439?308 and received pledges for $1?450?011 from 13?050 donors.

Crowdfunding campaigns for unproven stem cell–based interventions underemphasize risks and exaggerate the efficacy of these interventions. These findings suggest that medical crowdfunding campaigns convey potentially misleading messages about stem cell–based interventions. These claims may be especially powerful when embedded within compelling personal narratives. 

As usual, there are no similar studies looking at how much crowdfunding there is for unproven and quack veterinary therapies, but it takes little time and effort to find such campaigns online:

Chi Chi’s Recent Medical Expenses

Chi Chi has an integrated treatment plan that includes both traditional and holistic treatments…Chi Chi takes a number of traditional and Chinese medications to manage her medical conditions… and regular Hyperbaric Oxygen Treatments

Help Give Cayman a Fighting Chance!

extensive therapies including laser, acupuncture

Paralyzed Rescue Dog – Pani

water therapy and laser therapy… cranberry supplements and probiotics…has also been recommended joint supplements

Grace’s Health Treatment?

the best course of treatment for quality of life and longevity is to go a TCM (Traditional Chinese Medicine) route.  With a combination of a fully holistic/organic diet, herbal supplements, chinese medicine and an aggressive 3-day Vitamin drip protocol

Of course, I don’t believe the people making these appeals are doing anything wrong. They desperately want to help the animals they love, and they are willing to ask for help even when that may be difficult for them to do. And those who donate to these campaigns are illustrating the best qualities of the human spirit, compassion and concern for not only friends and family but complete strangers. Most of the appeals I have seen, including those that\ mention alternative therapies, do describe appropriate, science-based medical care, so hopefully these animals are getting the real treatment they need to get well.

Unfortunately, the fact remains that these animal owners and the good Samaritans who help them are paying for treatments that are at best questionable and, in many cases, clearly do not and cannot work. Though the practitioners offering them likely do so believing they are helping, at some point being a healthcare provider should mean knowing better and being required to provide effective treatment. It is hard not to wonder how many pets are harmed by the false belief in these therapies, and how much effective medical care could be paid for with the money that goes to unsupported or quack therapies.

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Evidence Update: Grain-free and other “BEG” Diets Associated with Heart Disease in Dogs

I have been following with great interest the emerging evidence about grain-free and exotic protein diets as a possible risk factor for heart disease in dogs. I first raised the subject in response to several cases of dilated cardiomyopathy (DCM) I saw in my practice, and which became part of a study which has recently been published looking at the issue in this breed. There have been several other papers recently published touching on the relationship between diet and DCM in dogs, and I want to quickly discuss each of them

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 Dec 1;253(11):1390-1394. doi: 10.2460/javma.253.11.1390.

This is an excellent summary of what we know and don’t know about this issue so far. The bottom line is that a suspicious number of cases of DCM have been appearing in dogs eating what have been called BEG diets- boutique, exotic protein, grain-free. What this means is that diets without grains, diets with a high proportion of legumes, and diets with animal proteins that have not been traditionally used in dog food, and which consequently have not been studied as thoroughly in terms of their nutrient content and other factors, have been associated with DCM in a variety of breeds. This is not proof that the diets, or any particular characteristic of them, is causing this disease. Such proof will require different kinds of research studies. However, this is a potential warning sign that deserves to be acknowledged and followed up with appropriate research.

In some cases, the diets and disease has also been associated with a deficiency in the amino acid taurine. This is an amino acid that dogs do not normally require in the diet since they can make as much as they need. However, in some breeds there appear to be genetic factors that make individuals more susceptible to taurine deficiency, and associated heart disease. These may include reduced production of taurine, increased loss of taurine, or increased need for taurine. Certain diets that have low levels of the ingredients from which taurine is made or that contain substances, such as legumes and some types of. Fiber that make reduce absorption or synthesis of taurine and its precursors or that encourage taurine loss make act in con cert with these genetic factors to lead to deficiency and disease in some dogs. Many of the details in this hypothetical series of steps remain to be understood. 

An example of how this problem may work comes from another recent paper looking at golden retrievers with DCM, including several of my patients.

Kaplan JL, Stern JA, Fascetti AJ, Larsen JA, Skolnik H, et al. (2018) Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. PLOS ONE 13(12): e0209112. 

In this study, the dogs with DCM had taurine deficiency, and most were eating BEG diets. Changing the diet and supplementing taurine, along with other treatments, seemed to improve or cure the disease in most, but not all of the dogs.  Again, this was not a study designed to determine if the diets caused the taurine deficiency or the DCM, but the fact that all the dogs were on the diets that we are concerned about, and the fact that changing the diet and adding taurine, among other interventions, seemed to help most of these dogs, does make looking more closely at these diets worthwhile. It also makes it reasonable to consider avoiding these diets in golden retrievers, and perhaps other breeds known to have a higher-than-average risk of taurine deficient DCM even if we are not certain if the diets are the cause or, if so, how exactly that works.

It is important, however, not to get too fixated on taurine. Many of the dogs seen with DCM and eating BEG diets are not taurine deficient, so golden retrievers appear to be experiencing a different problem than these other breeds. It is possible that other aspects of these diets besides their effects on taurine levels could be a risk factor for DCM, and we know even less about how this might work.

This is illustrated by the third new study, which looked at dogs with DCM and evaluated the differences between those on grain-free diets and those on grain-based diets. 

DarcyAdin, Teresa C.De Francesco, BruceKeene, SandraTou, KathrynMeurs, ClarkeAtkins, BrentAona, KariKurtz, LaraBarron, KorinnSaker. Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type.J Vet Cardiol. 2019;21:1-9.

In this group of dogs, grain-free diets were associated with some signs of more severe heart disease than that exhibited by dogs on diets containing grains, though the differences did not appear in all measures of heart disease severity. None of the dogs in this group were taurine deficient, so whatever the relationship between diet and DCM here, it had nothing to do with taurine.

The great deal we don’t know about DCM and diet is frustrating to all of us. We have to try and resist the temptation, however, to substitute our own beliefs and theories for the missing facts. Proponents of grain-free and other unconventional diets will point to the gaps in our knowledge as evidence that we can’t really blame these diets and that there is no need to change what they feed. While it is true that we can’t be certain what role, if any, such diets are playing in causing heart disease, the fact that they are consistently associated with DCM in several different groups of dogs is, at the least, reason for concern and further research. What is more, none of the claims for the health benefits of grain-free and other unconventional diets have any compelling scientific support, so there is no good reason to choose such diets even if the evidence for their potential risks are still very preliminary.

Bottom Line
We cannot say with certainty that BEG diets cause heart disease. We can only say that they have been associated with DCM in both golden retrievers with taurine deficiency and in other breeds without taurine deficiency. We can also say that changing diets appears to have benefitted some of these dogs, though many other treatments were employed at the same time, which limits out ability to know how important a factor this diet change was in the dogs’ recovery. 

We can also say that none of the claims for health risks from grains in pet foods, or for health benefits from grain-free or other BEG diets, are supported by any reasonable scientific evidence. Certainly, the evidence for such diets is weaker than even the very limited evidence against them. 

As pet owners and veterinarians, we need to proportion our confidence in any conclusions to the strength of the available evidence and be willing to change our minds as new evidence emerges. We also need to make our decisions now, even before we have perfect evidence. Right now, there is no solid reason to think grain-free diets have any health advantages, and there is weak evidence to suggest they might have health risks for some dogs. If you have a golden retriever, it seems reasonable to avoid the diets that have been associated with taurine deficiency and DCM in this breed. Even if you don’t have a golden, you should at least give some thought to why you might want to feed or avoid BEG diets. The evidence can’t make the decision for you, but it should certainly be considered.

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New Report on Complication Rates for Neutering Surgery in Dogs and Cats

I have written extensively about the subject of neutering (spaying and castrating male and female dogs and cats). The bulk of the discussion and debate about this procedure centers on the health effects. It is generally recognized to be a pretty safe procedure, though of course no surgery is entirely without risk. The scientific literature has limited information on the specific risks of the neutering surgery procedure itself and how often they occur.

Total complication rates for routine castration or spaying have been reported from 2.6%-33% of cases.The majority of these complications are minor and require no treatment. Complication rates vary considerably from practice to practice and are generally reported to be higher in studies of surgeries performed by students in training. Reported death rates are less than 0.1%.1-5

A new source of data on this subject has recently become available which represents the type of “Big Data” so popular these days. The Royal College of Veterinary Surgeons (RCVS) charity arm RCVS Knowledge,  has a program in place that collects information from practices around the country in a central database. The goal is to encourage clinical audit, a quality improvement process in which veterinary practices can investigate the outcomes for their patients and compare these with those of other practices or with an established “gold standard.” This facilitates recognizing processes that aren’t working as well as they could and improvement in patient care.

The RCVS has recently released the results of data collection on complications of neutering. Though not the result of a controlled, prospective research process, this audit report is based on over 30,000 individual surgeries, so it at least represents a potentially powerful source of data. The specific variables that affect outcome of neutering surgery in individual animals can’t be identified, and there is the problem of patients who can’t be followed and whose outcome is unknown. However, this type of data complements the research evidence already available and gives us a general sense of the complication rates in the UK for these common procedures.

Routine Neuter Complication Rates

The outcomes measured were cases with no complications, those with minor complications not needing treatment, problems needing medical treatment, problems needing surgical treatment, and fatalities. About 8% of the cases in the database were not available for followup, and these were not included in the calculation of complication rates.

Total Overall Complications

Outcome Frequency Percent Cum Percent
Abnormal but no treatment necessary 2795 9.3% 9.3%
Abnormal requiring medical treatment 2254 7.5% 16.8%
Abnormal requiring surgical intervention 341 1.1% 17.9%
Fatality of animal 29 0.1% 18.0%
No abnormality present 24627 82.0% 100.0%
Total 30046 100.0% 100.0%

 

Complications for Male Cats

Outcome Frequency Percent Cum Percent
Abnormal but no treatment necessary 56 1.4% 1.4%
Abnormal requiring medical treatment 53 1.3% 2.7%
Abnormal requiring surgical intervention 23 0.6% 3.3%
Fatality of animal 3 0.1% 3.4%
No abnormality present 3885 96.6% 100.0%
Total 4020 100.0% 100.0%

 

Complications for Male Dogs

Outcome Frequency Percent Cum Percent
Abnormal but no treatment necessary 977 11.4% 11.4%
Abnormal requiring medical treatment 796 9.3% 20.6%
Abnormal requiring surgical intervention 61 0.7% 21.3%
Fatality of animal 6 0.1% 21.4%
No abnormality present 6763 78.6% 100.0%
Total 8603 100.0% 100.0%

 

Complications for Female Cats

Outcome Frequency Percent Cum Percent
Abnormal but no treatment necessary 616 7.0% 7.0%
Abnormal requiring medical treatment 385 4.4% 11.4%
Abnormal requiring surgical intervention 163 1.9% 13.3%
Fatality of animal 5 0.1% 13.3%
No abnormality present 7596 86.7% 100.0%
Total 8765 100.0% 100.0%

 

Complications for Female Dogs

Outcome Frequency Percent Cum Percent
Abnormal but no treatment necessary 1146 13.2% 13.2%
Abnormal requiring medical treatment 1020 11.8% 25.0%
Abnormal requiring surgical intervention 94 1.1% 26.1%
Fatality of animal 15 0.2% 26.3%
No abnormality present 6383 73.7% 100.0%
Total 8658 100.0% 100.0%

 

These results are broadly similar to previously reported numbers, though lower than sometimes seen in studies in which inexperienced veterinary students are performing the procedures. They confirm that the procedure is very safe, that most complications are minor and do not require much, if any, treatment, and that mortality rates are very low. Females experience more complications because the surgery is necessarily more invasive. These data don’t tell us anything about the differences between specific neutering procedures, breeds, ages of patients, and many other factors, so they don’t let us predict the precise risk for individual patients. But they provide a general background that help us in making decisions about neutering.

 

References

  1. Pollari FL, Bonnett BN, Bamsey SC, Meek AH, Allen DG.Postoperative complications of elective surgeries in dogs and cats determined by examining electronic and paper medical records. Journal of the American Veterinary Medical Association 1996;208(11):1882-6.
  2. Howe LM. Short-term results and complications of prepubertal gonadectomy in cats and dogs. Journal of the American Veterinary Medical Association 1997;211(1):57-62.
  3. Pollari FL, Bonnettt B.N. Evaluation of postoperative complications following elective surgeries of dogs and cats at private practices using computer records. Canadian Veterinary Journal 1996;37:672-8.
  4. Burrow R, Batchelor D, Cripps P. Complications observed during and after ovariohysterectomy of 142 bitches at a veterinary teaching hospital. Veterinary Record 2005;157(26):829-33.
  5. Root Kustritz MV. Effects of surgical sterilization on canine and feline health and on society. Reprod Domest Anim. 2012 Aug;47 Suppl 4:214-22.

 

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Hair and Saliva Test for Allergies are Worthless Pseudoscience

There is a lot of mythology out there about food allergies. The recent concern about the potential risks of grain-free diets is only an issue at all because such diets became wildly popular with no evidence that grains were a problem in the first place. A lot of folks blame grains for allergies and other health problems, but there’s no real evidence this is true, and these ingredients probably play a fairly minor role in food allergies in dogs and cats.

Other myths about food allergies include the idea that changing diets can cause them (actually, prolonged exposure is usually needed to develop a sensitivity), that raw foods are less allergenic (nope, only more likely to give you a food-borne illness), and that you can use blood, hair, or saliva tests to diagnose food allergies (sorry, a limited ingredient diet trial is the only way to do this). This last misconception is perpetuated despite evidence from human medicine that it is not true because, quite frankly, it makes people money.

I’ve previously discussed an example of this quackery, Jean Dodds’ Nutriscan allergy testing system. In her book, Dr. Dodds provides many citations to support her claim that this is a legitimate test, but a cursory look at these shows they don’t make that case at all. And there are unpublished reports from at least one allergy specialist that suggest the test is not merely inaccurate but completely useless nonsense:

One veterinary dermatologist has performed her own uncontrolled test of Nutriscan, with Dr. Dodds’ knowledge and permission, and found it entirely unreliable. Twelve samples were submitted for testing in a blind manner, from dogs with known food sensitivities based on dietary testing, dogs with environmental allergies, dogs without allergic disease, and one sample of tap water. All samples including tap water, environmental allergy dogs, and normal dogs showed reactivity to beef, corn, milk and wheat. Some samples showed reactivity to soy. In some cases, these obviously false results would have led to recommendations against diets which actually helped these dogs.

Granted, this is essentially an unpublished anecdote, so while it counters the anecdotes Dodds and others put forward for Nutriscan, it is not published scientific research. Now, however, a different allergy test, using saliva and hair samples to identify allergies, has failed the same test as spectacularly as Nutriscan purportedly did.

Coyner K, Schick A. Hair and saliva test fails to identify allergies in dogs. J Small Anim Pract. October 2018. doi:10.1111/jsap.12952

Our study demonstrates that hair and saliva testing fails not only to identify allergic dermatitis in dogs, but fails to differentiate between animal and non-animal samples, providing essentially identical results, regardless of the origin of the sample.

These authors submitted not only hair and saliva from dogs with known allergies and dogs without allergies, but also fake hair samples from stuffed animals and water (in place of saliva). All of the samples tested positive for some allergies, and there was essentially no difference between the results and random chance.

Bottom Line
Saliva and hair tests for food allergies are a scam and a waste of time and money.

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Evidence Update: Prolotherapy

Back in 2011 I wrote about a therapy popular with alternative practitioners called prolotherapy. I try to check in from time to time to see if there is any new evidence for the treatments I consider, and in doing so I did find some new evidence. First, here’s my conclusion from the previous review:

Prolotherapy is a purported treatment for connective tissue and joint pain and disability. It involves injecting substances which induce inflammation and other chemical and cellular reactions into affected tissues. These reactions are theorized to relieve pain and improve function. The logic of this theory is questionable, and no clear mechanism for beneficial effects from prolotherapy has been described, but it is possible that the theory could be valid.

The clinical research on prolotherapy in humans is generally of low quality and results have been mixed. There is great variation in the techniques used by different investigators, so it is difficult to compare or generalize between studies.

There is virtually no controlled research investigating prolotherapy in companion animals, and all claims made for safety and efficacy in these species are based solely on anecdotal evidence.

The use of proltherapy in pets should be viewed as experimental with unknown risks and benefits. Such treatments should be reserved for patients that have significant symptoms that have failed to respond or cannot be treated by conventional means.

What Is It?
Prolotherapy involves injecting substances into joints or musculoskeletal tissue to treat pain and dysfunction. The particular substances used vary. Some are clearly useless (e.g. homeopathic remedies), but the evidence is growing that others may have some beneficial clinical effects. The most common substance currently used is dextrose, a form of sugar, but there are many others, and of course each substance has to be evaluated individually for specific uses.

Does It Work?
The in vitro and lab evidence suggests some potentially useful effects on joint tissues and in lab animals, but of course this level of evidence frequently turns out to be unreliable in predicting the actual effects in patients. At the time of my previous article, most systematic reviews were inconclusive, and the quality of the clinical trial evidence in humans was weak. There is still significant differences of opinions in different reviews, and all call for better quality evidence, but there is an emerging consensus that dextrose prolotherapy may be useful for arthritis in people. Other uses are still not supported by very convincing evidence. Here are some samples of the systematic review literature:

Limited evidence from low-quality studies indicates a beneficial effect of prolotherapy for OA management. The number of participants in these studies was too small to provide reliable evidence…Current data from trials about prolotherapy for OA should be considered preliminary, and future high-quality trials on this topic are warranted.1

Although anecdotal clinical success guides the use of prolotherapy for many conditions, clinical trial literature supporting evidence-based decision-making for the use of prolotherapy exists for low back pain, several tendinopathies, and osteoarthritis.2

This systematic review suggests that ST and PT may be effective treatment options for AT and that they can be considered safe. Long-term studies and RCTs are still needed to support their recommendation.3

Within the limitations of the study, dextrose prolotherapy may cause significant reduction in mouth opening and pain associated with TMJ hypermobility. Conclusions with regard to reduction of episodes of subluxation/dislocation cannot be drawn. There is a need of more high-quality RCTs with larger sample size and homogenous prolotherapy protocol to draw stronger conclusions on the effect of dextrose prolotherapy in patients with TMJ hypermobility.4

Dextrose injections decreased pain in osteoarthritis patients but did not exhibit a positive dose-response relationship following serial injections. Dextrose prolotherapy was found to provide a better therapeutic effect than exercise, local anesthetics, and probably corticosteroids when patients were retested 6 months following the initial injection.5

Use of dextrose prolotherapy is supported for treatment of tendinopathies, knee and finger joint OA, and spinal/pelvic pain due to ligament dysfunction. Efficacy in acute pain, as first-line therapy, and in myofascial pain cannot be determined from the literature.6

Moderate evidence suggests that prolotherapy is safe and can help achieve significant symptomatic control in individuals with OA. Areas for developing research Future research should focus on larger sample size, standardization of treatment protocol and basic science evidence.7

Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.8

Systematic review, including meta-analysis, and randomized controlled trials suggest that prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy. Although the mechanism of action is not well understood and is likely multifactorial, a growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who are refractory to conservative therapy and deserves further basic and clinical science investigation for the treatment of osteoarthritis and tendinopathy.9

Unfortunately, the same proliferation of research evidence has not happened in veterinary medicine. To date, there is only one study of this treatment in dogs10 and none in cats.

Sherwood JM, Roush JK, Armbrust LJ, Renberg WC. Prospective Evaluation of Intra-Articular Dextrose Prolotherapy for Treatment of Osteoarthritis in Dogs. J Am Anim Hosp Assoc. 2017;53(3):135-1

This was a small but very high-quality study with appropriate blinding, randomization, control groups, and a mix of subjective and objective outcome measures. That’s the good news. The bad news is there was no significant difference between prolotherapy and placebo in any measure, so the therapy clearly didn’t work. This is only one study, and given the encouraging evidence in humans, it is possible that further studies will find some forms of prolotherapy helpful in veterinary patients.

Bottom Line
There are a variety of theories behind prolotherapy, some more plausible than others, but there is not yet a clearly established general mechanism. The clinical trial research in humans is mixed and not robust, but there is moderate evidence supporting the effectiveness of prolotherapy for arthritis. There has only been one small animal study, a clinical trial in dogs for elbow and knee arthritis, and it found no benefit.

References

  1. Krsti?evi? M, Jeri? M, Došenovi? S, Jeli?i? Kadi? A, Puljak L. Proliferative injection therapy for osteoarthritis: a systematic review. Int Orthop. 2017;41(4):671-679. doi:10.1007/s00264-017-3422-5
  2. Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care. 2010;37(1):65-80. doi:10.1016/j.pop.2009.09.013
  3. Morath O, Kubosch EJ, Taeymans J, et al. The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy-a systematic review including meta-analysis. Scand J Med Sci Sports. 2018;28(1):4-15. doi:10.1111/sms.12898
  4. Nagori SA, Jose A, Gopalakrishnan V, Roy ID, Chattopadhyay PK, Roychoudhury A. The efficacy of dextrose prolotherapy over placebo for temporomandibular joint hypermobility: A systematic review and meta-analysis. J Oral Rehabil. 2018;45(12):998-1006. doi:10.1111/joor.12698
  5. Hung C-Y, Hsiao M-Y, Chang K-V, Han D-S, Wang T-G. Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis. J Pain Res. 2016;Volume 9:847-857. doi:10.2147/JPR.S118669
  6. Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:CMAMD.S39160. doi:10.4137/CMAMD.S39160
  7. Hassan F, Trebinjac S, Murrell WD, Maffulli N. The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review. Br Med Bull. 2017;122(1):91-108. doi:10.1093/bmb/ldx006
  8. Sit RW, Chung VC, Reeves KD, et al. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis. Sci Rep. 2016;6(1):25247. doi:10.1038/srep25247
  9. Rabago D, Nourani B. Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review. Curr Rheumatol Rep. 2017;19(6):34. doi:10.1007/s11926-017-0659-3
  10. Sherwood JM, Roush JK, Armbrust LJ, Renberg WC. Prospective Evaluation of Intra-Articular Dextrose Prolotherapy for Treatment of Osteoarthritis in Dogs. J Am Anim Hosp Assoc. 2017;53(3):135-142. doi:10.5326/JAAHA-MS-6508
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Evidence Update: Associations between Environmental Chemical Exposure and Hyperthyroidism in Cats

One of the great mysteries of veterinary medicine if hyperthyroidism in cats. Benign tumors of the thyroid glad in older cats can produce excessive amount of thyroid hormone, and this can lead to a host of clinical symptoms. Fortunately, the disease is relatively easily treated by various methods. However, the condition seems to be more common than it used to be a few decades ago (though there are no reliable statistics, and it could just as easily be that vets were less likely to diagnose this problem in the past), so this begs the question of what might be the cause of the apparent increase in cases.

There are many theories, and environmental toxins of one kind of another are a popular focus of blame for this disease. In 2015 I wrote about the claim that certain flame retardant chemicals, known as PBDEs, might be associated with thyroid disease in cats, and I provided an update on the literature about this in 2017. At this point, the best we can say is that there has been some association between PBDE levels and thyroid disease in cats, but it is based on very weak data involving few animals, and no strong evidence yet exists to label this as a causal factor.

I recently ran across a new article by the same research group who looked at PBDEs and thyroid disease in 2016, this time suggesting there might be a connection with a different class of environmental chemicals, known as per- and polyfluoroalkyl substances (PFASs for short).

Miaomiao Wang, Weihong Guo, Steve Gardner, Myrto Petreas, June-Soo Park. Per- and polyfluoroalkyl substances in Northern California cats: Temporal comparison and a possible link to cat hyperthyroidism. Environmental Toxicology and Chemistry, 2018; DOI:

This paper appears to be using blood samples from the same groups of cats discussed in the previous paper, 26 sampled between 2008 and 2010, and 22 sampled between 2012 and 2013. The conclusions are similar but even more tentative than those regarding PBDEs. Levels of the chemicals declined between the earlier sampling period and the later (in humans as well as cats), likely due to the phasing out of these chemicals in industrial use.

There was a statistical associated between PFAS levels and thyroid disease in the latter period, but not in the earlier period. However, there was tremendous individual variation and very few cats in the two groups (those with thyroid disease and those without), so it is impossible to identify a clearly meaningful difference. Whether these chemicals even could be a potential cause for hyperthyroidism is unclear. While some lab animal studies have shown that PFASs can affect thyroid hormone levels, the direction of this effect (towards higher or lower levels) and the real-world significance are not at all clear in ab animals or humans.

Interestingly, there was no apparent association between levels of PFASs and PBDEs in these cats. That means that while PBDEs may have been associated with hyperthyroidism, and PFASs may have been associated with hyperthyroidism, there was no association between PBDEs and PFASs. That doesn’t make a lot of statistical sense, and it is likely an example of the limitations of such a small sample of cats.

While papers like these are interesting, they don’t yet add up to any clear or compelling evidence for a causal role of either of these classes of chemicals in feline hyperthyroidism. If anything, they may suggest such a role is unlikely since the levels of both PFASs and PBDEs seem to be going down over the last 10 years, yet there is no sign that thyroid disease is becoming any less common.

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Evidence Update: Still no Convincing Scientific Evidence for any Benefits from Veterinary Hyperbaric Oxygen Therapy

It’s been a few years since I covered the subject of hyperbaric oxygen therapy (HBOT), a treatment that involves placing patients in a sealed chamber and raising the air pressure and oxygen levels above those in the normal atmosphere at sea level. Back in 2013, I summarized the available evidence and reached this conclusion:

HBOT is a biologically plausible therapy with substantial in vitro and animal model research to support possible benefits in a variety of conditions. There is, however, almost no clinical trial evidence to support its use in companion animal species. Justification of veterinary use of HBOT comes only from extrapolation from basic principles, pre-clinical research, anecdote, and extrapolation from research in humans, so this should be viewed as an unproven, experimental veterinary therapy.

There are a few indications for which the human clinical trial research provides at least a moderate degree of confidence that HBOT is effective. There are many others for which there is only limited and low-quality evidence and no clear conclusion can be drawn. Not all uses validated in humans are relevant to veterinary use, and most veterinary applications have not been directly studied in people. Overall, the evidence is strongest for adjunctive use of HBOT to facilitate healing of chronic wounds not resolving with standard therapies.

HBOT is generally quite safe, but there are both minor and serious potential adverse effects, and there is some risk associated with the use of the equipment.

I followed this article with a brief report of warnings from the FDA about unsupported and exaggerated claims for HBOT in humans and a report on a human study showing no benefits for treatment of concussion. Given that I last looked at the literature 5 years ago, I thought it worthwhile to check for any new evidence on this treatment in veterinary patients. Unfortunately, there hasn’t been very much research published since 2013.

A 2017 review by two authors supportive of HBOT concluded:

There is a paucity of data about use of HBOT in veterinary medicine, and no randomized, controlled clinical trials for any condition have been published… HBOT holds therapeutic promise in animals and deserves clinical and research attention. However, the therapy is not benign, and understanding the basics of HBOT and possible complications is critical. Because the clinical information, apart from expert opinion and research experiments with small numbers, remains minimal, research is essential to expand information about the physiology behind the modality, condition-specific treatment parameters, and appropriate and efficacious indications for use in veterinary patients.

Since then, there have been two published veterinary reports. One study evaluated the safety of HBOT by recording any adverse effects noticed during 230 treatments in 12 cats and 78 dogs. Though this was only an observational study of short-term treatment, and there were a few other limitations, no serious adverse effects were seen. Minor effects, suggesting some discomfort and possible inner ear problems, were seen in some patients at a modest rate. This certainly doesn’t rule out the possibility of any more serious harm, and cases of significant injury have been reported in humans. However, this study supports the general findings in the limited veterinary literature that adverse effects of HBOT seem uncommon and typically minor. The only known fatality reported in veterinary HBOT involved an explosion which killed both the patient and the operator at an equine therapy facility in 2012.

There has been one study of HBOT in dogs published since my last review:

Latimer CR, Lux CN, Roberts S. Effects of hyperbaric oxygen therapy on uncomplicated incisional and open wound healing in dogs. Vet Surg. 2018 Aug;47(6):827-836.

This was an experimental study, not a clinical study. Ten lab beagles were given surgical wounds, and then given the same wound care (suturing, bandaging, pain control, etc.) except that 5 were given a series of HBOT treatments as well. Blinded observers evaluated wound healing scores, and biopsies of the wounds were examined. No effect of HBOT was seen, and the wounds healed the same regardless of whether the dogs got HBOT or not.

There are a number of limitations to this study, including the small number of dogs and the use of lab dogs with artificial wounds rather than a real-world population of dogs with the kinds of wounds that would typically be treated with HBOT. Nevertheless, the study certainly suggests there is no dramatic benefit to HBOT in the healing of routine, uncomplicated wounds.

Bottom Line
The literature since 2013 has not provided any reason to alter my original conclusions. While HBOT appears to have promise based on theoretical reasoning, lab animal studies, and some validated uses in humans, there is still no convincing evidence to support any claims of benefits to veterinary patients. While the risks appear to be minimal, there is only weak and unreliable evidence of any benefits. The use of a complex, expensive, and potentially harmful treatment in the absence of any strong evidence for benefits is not the best way to use limited resources in veterinary medicine or to provide the best care to patients. Advocates for HBOT, especially those selling it as part of their practice, ought to focus on supporting rigorous and objective clinical studies to identify what real benefits, if any, there are from this therapy.

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FDA Webinar Discussing Dietary Risk Factors for Dilated Cardiomyopathy

The FDA has recently held a webinar with a representative of the agency, a nutritionist, and a representative of the pet food industry to provide an update on the state of the ongoing investigation of certain diets and possible heart disease risk. Here is the link to the recording along with my summary notes.

Martine Hartogensis– FDA
Cardiologists reported ~ 150 cases dilated cardiomyopathy (DCM) in atypical breeds to FDA

FDA noted ~ 30 case reports had been filed with them with dogs on grain-free and legume/tubers containing diets.

FDA followed up on 30 cases and did not see low taurine in the foods but did find low taurine in some of patients

Now total of 160 dogs reported with DCM (149 case reports), 39 deaths, mostly from 2017-2018

8 cats reported (in 4 cases) with 1 death, these are from 2015-16

90% of dog cases had grain-free/legume/tuber-containing diet history

Prospective study ongoing checking foods and dogs for cysteine/methionine/taurine

Lisa Freeman– Tufts
DCM 2nd most common canine heart disease after valvular disease

A variety of different diets and breeds linked to taurine deficiency/DCM over the years

Dr. Sterns at UC Davis has been looking at taurine-deficient DCM in Golden Retrievers for about 3 years

Some dogs with DCM on grain-free or legume-containing diets are taurine deficient but even those that aren’t sometimes improve on taurine supplementation

Roughly 3 groups of dogs-

  1. Typical breed primary DCM cases (Boxers, Dobermans, etc.)
  2. Taurine-deficiency DCM in both typical and atypical breeds
  3. Diet-associated DCM with normal taurine levels in either typical or atypical breeds. These are not just grain-free but also “boutique” and exotic protein diets (“BEG” diets). The majority of DCM cases on these BEG diets have NOT been taurine deficient.

May be deficient in taurine or precursors, decreased absorption, increased elimination, other variables

Recommendations-
All DCM cases should have full diet history, screen for taurine, supplement taurine whether low levels or not, change to more typical diet

Greg Aldrich– KSU/Industry
Lots of manufacturers are now adding taurine to diets even though it is not clear this is the answer

Grain-free diets are ~ 25% of the dog food market, so not going away
Even with a large supply of relevant amino acids in meat meal, if the bioavailability is not high enough there may not be enough on an as-fed basis

Legume seeds/pulses lower in methionine than traditional cereals and lower bioavailability. They also have some soluble fibers in them which can influence bacterial fermentation in the colon which can deplete taurine.

Potatoes don’t really contribute to the protein in a diet, so unclear how any association with taurine levels might work

Q&A
Hartogensis-
FDA uses cat taurine levels as guideline since likely to be higher than dogs need, so in foods identified as not deficient this means they meet the cat requirement

Number of reports has, of course, increased since FDA announced it is investigating this, and many do not appear to be genuinely related to this issue; The 160 dogs mentioned are confirmed DCM diagnoses by echocardiogram.

Even though most notable association has been legumes/tubers/boutique diets the FDA is looking at other possible causal factors but so far no other clear signals. No clear pattern related to particular protein source in diets.

Freeman-
BEG Diets= boutique (small manufacturers but not willing to define specifically), exotic ingredient, grain-free diets. Reiterated majority of DCM cases on these diets have not been taurine deficient.

Aldrich-
Worth bearing in mind that < 200 animals known to be affected out of ~100 million pet dogs, so scale of the problem does not yet appear very large

Aldrich/Freeman-
Bear in mind taurine may not be the whole story so adding taurine to foods or supplementing individual dogs may not be appropriate if it turns out some of these cases are associated with other risk factors

Hartogensis/Freeman-
Recommendation to pet owners is to speak with veterinarian about nutrition since a lot of the information and advice people seek and use to guide feeding comes from marketing, pet food stores, and other sources without necessarily a sound, science-based approach.

Freeman-
Very few reports from countries outside the U.S. at this point.

Resources-
Petfoodology

The Science Dog

 

Posted in Nutrition | 20 Comments

Herbal Medicine Will not be a Recognized Medical Specialty

For over a year now, I have been covering the petition from the American College of Veterinary Botanical Medicine (ACVBM) seeking recognition as a medical specialty from the American Board of Veterinary Specialties (ABVS). I have argued that the discipline does not yet have adequate scientific evidence to support this status and that the ACVBM is dominated by proponents of Traditional Chinese Medicine and other pseudoscientific folk practices and cannot be trusted to take a truly scientific approach to herbal medicine when the leadership ignores or rejects scientific methods and relies primarily on tradition and personal belief in their own herbal prescribing.

The ABVS has apparently rejected the ACVBM petition, though the only indication of this comes from a brief statement on the ACVBM website:

Unfortunately [the ABVS] rejected our petition to be a stand alone college as we are a relatively new entity to them, but did open the door for us to apply under a currently existing college, specifically the College of Clinical Pharmacology.  At the ACVIM in June, representatives of the ACVBM will be meeting with representatives of the College of Clinical Pharmacology to discuss what being under their ‘wing’ will entail.

I have asked the ABVS if they intend to make their decision or the outcome of their review of the ACVBM petition public in any form, but they have not yet responded.

A subspecialty status under the American College of Veterinary Clinical Pharmacology (ACVCP) has some advantages over an independent specialty status in that the ACVCP is a soundly scientific organization and would, hopefully, hold herbalists to a higher, more scientific standard of evidence than they would require of themselves. It is still problematic, however, in that it creates the impression of scientific legitimacy for herbal prescribing practices before they have done the work of validating specific treatments for specific conditions or even demonstrated the validity of most basic theoretical principles underlying the discipline.

The inclusion of unproven or clearly ineffective methods under the auspices of otherwise legitimate specialty areas is not unusual. The American College of Veterinary Sports Medicine and Rehabilitation (ACVSMR), for example, includes chiropractic, acupuncture, herbal medicine and even the quintessential quackery of homeopathy as 3-6% of the content of the examination for board-certification under the Trojan Horse label of “Integrative Medicine.” I’ve discussed many times before how such a concept is a dangerous opening for unproven and useless therapies to weasel their way into mainstream medicine without going through the process of demonstrating true safety and efficacy via legitimate scientific methods. It would not surprise me if subspecialty status for herbal medicine under the ACVCP exacerbated this problem. I will have to see, of course, the details of any such application before I can draw any conclusions about whether it might serve to make herbal medicine a truly scientific discipline or give a patina of legitimacy to mystical folk medicine practices.

For now, I will wait with interest to see if the ABVS makes any additional information available and how the potential integration of herbalism into the ACVCP proceeds.

Addendum 8/21/2018- The ABVS has responded to my inquiry and will only indicate that they recommended the ACVBM seek recognition as a subspecialty under an existing specialty college. Apparently, no additional information about the process or the decision will be made public.

Addendum 9/2/2018-
One of the members of the ACVBM petition organizing committee directed me to a recent newsletter from the World Association of Traditional Chinese Veterinary Medicine (WATCVM) for more information about the ABVS response to the petition:

Additional tentative ‘Big News’, Herbal medicine including TCVM, has a potential ‘door opened’ as The American College of Veterinary Botanical Medicine’s petition to be recognized as a boarded veterinary specialty was not rejected, but not accepted. The ACVBM was told that although the petition was impressive and complete, the ABVS feels unwilling to have the ACVBM as a stand-alone college. So the petition to be a stand-alone college was not accepted. But, the ABVS instructed the ACVBM to resubmit the petition under the ‘wings’ of a pre-existing college, specifically the College of Clinical Pharmacology. I am sure all are aware of the irony of this, as drug therapy is a molecular perversion of herbal medicine.

The ACVBM will start exploring this route being clear that the ACVBM must retain its autonomy and ability to hold true to the herbal traditions that are the foundation of herbal medicine. The ACVBM will need to re-submit its petition by November of 2018.

I have to wonder how eager the College of Clinical Pharmacology will be to accept as a subsidiary specialty a group whose leadership views their discipline as “a molecular perversion of herbal medicine?”

Posted in Herbs and Supplements | 6 Comments