Today's Veterinary Practice, May 2017 by davidpsu

IN THIS ISSUE 28 LIVER FUNCTION TESTING 40 DENTAL RADIOGRAPHY: NORMAL VS ABNORMAL 60 CHALLENGING CHRONIC OTITIS

Behavior Issues Separation Anxiety Medication Choices

MAY/JUNE 2017 VOLUME 7, NUMBER 3

BECAUSE OF VETMEDIN For 10 years, VETMEDIN has given dogs with CHF the opportunity for better days and longer lives.1 With ongoing research and innovative support tools, we’re determined to keep making a difference. See the stories and join the celebration at DecadeOfVetmedin.com.

LIN D A AN D B UF F Y 12 YEARS CON N ECT ED

IMPORTANT SAFETY INFORMATION: Use only in dogs with clinical evidence of heart failure. The safety of VETMEDIN has not been established in dogs with asymptomatic heart disease or in heart failure caused by etiologies other than atrioventricular valvular insufficiency or dilated cardiomyopathy. Please refer to the package insert for complete product information or visit www.vetmedin.com. Reference: 1. Lombard CW, Jöns O, Bussadori CM; for the VetSCOPE Study. Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc. 2006;42(4):249–261.

MAY/JUNE 2017

VOLUME 7, NUMBER 3

An Official journal of the

An official journal of the NAVC, Today’s Veterinary Practice is the trusted source for peer-reviewed clinical information in small animal veterinary medicine. Our goal is to enhance knowledge and encourage confidence, inspiring the highest quality of veterinary care. As an NAVC publication, our audience has access to world-class continuing professional development developed for the global veterinary health care community. Subscriptions (only): 630.739.0900, CDS/Today’s Veterinary Practice 440 Quadrangle Drive, Suite E, Bolingbrook, IL 60440. Email subscription form to subscriptions@CDS1976.com or fax to 630.739.9700 Free subscriptions only to qualifying subscribers.* For a new subscription, confirmation, or renewal, please visit tvpjournal.com to fill out an online form. For updates, please include your subscription ID from label. To have a form emailed or faxed to you, please contact us at our 800 number or email above and provide email or fax number. Change Name/Address or Cancel: Please use online form at tvpjournal.com or contact us by phone, fax, or email subscriptions@CDS1976.com. Please provide the ID number (directly above your name on label) for positive identification. If the ID number is not available or legible, provide name and address as it appears on the label to allow identification of the subscription. *Qualifying Subscribers: Veterinarians, members of the veterinary health care team, veterinary school faculty, veterinary students, and other professionals allied to the field. Eastern States Veterinary Association, Inc (NAVC) reserves the right to determine eligibility for a free subscription. WARRANTIES, LIMITATIONS. Except as expressly set forth herein, Eastern States Veterinary Association, Inc (NAVC) makes no warranties whatsoever, express, implied, or statutory. NAVC specifically disclaims any implied warranty of merchantability or fitness for a particular purpose. In no event will NAVC be liable to you or any third party for any indirect, punitive, special, incidental, or consequential damages (including loss of profits, use, data, or other economic advantage), however it arises, even if NAVC has previously been advised of the possibility of such damage. All rights reserved. No part of this publication may be reproduced in any form without written permission from the publisher. Entire contents ©2017 Eastern States Veterinary Association, Inc (NAVC).

Editor in Chief Simon R. Platt, BVM&S, MRCVS, DACVIM (Neurology), DECVN University of Georgia College of Veterinary Medicine SRPlatt@NAVC.com

Chief Executive Officer, NAVC Thomas M. Bohn, MBA, CAE TBohn@NAVC.com

Laura C.S. Walker Senior Vice President of Sales & Publishing LWalker@NAVC.com Nick Paolo, MS, MBA, Publisher NPaolo@NAVC.com Robin Henry, Executive Editor RHenry@NAVC.com Jackie D’Antonio, Managing Editor JDantonio@navc.com Renee Luttrell, Director of Sales RLuttrell@NAVC.com, 610.558.1819 Sondra Reynolds, Director of Audience Development SReynolds@NAVC.com

Editorial Advisory Board P. Jane Armstrong, DVM, MS, MBA, DACVIM, (Small Animal Internal Medicine) University of Minnesota, College of Veterinary Medicine Mark Cofone, VMD, DACVS Veterinary Specialty Center, Wilmington, Delaware

Michelle Taylor, Senior Art Director MTaylor@NAVC.com David Beagin, Art Director DBeagin@NAVC.com Julie Butler, Assistant Editor Megan Cox, Staff Writer Cheryl Hobbs, Staff Editor Suzanne B. Meyers, Staff Editor Lisa Wirth, VMD, Staff Editor

NAVC Board of Directors President Gail Gibson, VMD

Sheila Grosdidier, RVT, PHR Veterinary Management Consultation Evergreen, Colorado

Garret Pachtinger, VMD, DACVECC Veterinary Specialty & Emergency Center Levittown, Pennsylvania Michael Schaer, DVM, DACVIM, DACVECC University of Florida College of Veterinary Medicine

Immediate Past President Melinda D. Merck, DVM President-Elect K. Leann Kuebelbeck, DVM, DACVS Vice President Cheryl Good, DVM Treasurer Laurel Kaddatz, DVM Directors Paige Allen, MS, RVT Harold Davis, Jr, BA, RVT, VTS (Emergency & Critical Care) (Anesthesia & Analgesia) Sally Haddock, DVM Bob Lester, DVM

FEATURES 28 RACE-APPROVED CE CREDIT ARTICLE

Liver Enzyme Interpretation and Liver Function Tests Brigitte B. McAtee, DVM, and Jonathan A. Lidbury, BVMS, MRCVS, PhD, DACVIM, DECVIM-CA Early diagnosis of liver disease often relies on serum biochemical testing, which may prompt further diagnostics, including liver function testing. This article reviews the interpretation of serum liver enzyme activities and commonly used liver function tests.

RACE-APPROVED CE CREDIT ARTICLE

Imaging Essentials: Interpretation of Dental Radiographs in Dogs and Cats Santiago Peralta, DVM, DAVDC, and Nadine Fiani, BVSc, DAVDC This article is the second of two articles that focus on interpretation of dental radiographs in dogs and cats. It includes normal dental variations and pathologic findings that can be viewed on dental radiographs.

FEATURE

Separation-Related Disorders: The Differences Between Dogs and Cats Lisa Radosta, DVM, DACVB, and Ariel Fagen, DVM Separation-related disorders are well recognized in dogs, but they are less understood in cats. This article addresses the clinical signs, predisposition factors, diagnosis, and treatment of these disorders in dogs and cats.

6 10 14 73

ADVERTISER INDEX TODAY’S VETERINARY NEWS INSIDE NAVC SPECIAL SECTION: FOCUS ON NUTRITION

Today’s Veterinary Practice does not, by publication of ads, express endorsement or verify the accuracy and effectiveness of the products and claims contained therein. The publisher, Eastern States Veterinary Association, Inc (NAVC), disclaims any liability for any damages resulting from the use of any product advertised herein and suggests that readers fully investigate the products and claims prior to purchasing. The opinions stated in this publication are those of the respective authors and do not necessarily represent the opinions of the NAVC nor its Editorial Advisory Board. NAVC does not guarantee nor make any other representation that the material contained in articles herein is valid, reliable, or accurate; nor does the NAVC assume any responsibility for injury or death arising from any use, or misuse, of same. There is no implication that the material published herein represents the best or only procedure for a particular condition. It is the responsibility of the reader to verify the accuracy and applicability of any information presented and to adapt as new data becomes publicly available. Today’s Veterinary Practice (ISSN 2162-3872 print and ISSN 2162-3929 online) is published bi-monthly (Jan/Feb, Mar/Apr, May/June, Jul/Aug, Sept/ Oct, Nov/Dec; 6x per year) by North American Veterinary Conference, 37 Paul Lane, Glen Mills, PA 19342. Periodicals postage paid at Glen Mills, PA 19342 and additional mailing offices. POSTMASTER: Send all UAA to CFS (See DMM 507.1.5.2); NON-POSTAL AND MILITARY FACILITIES: send address corrections to CDS/Today’s Veterinary Practice, 440 Quadrangle Drive, Ste E, Bolingbrook, IL 60440.

TABLE OF CONTENTS

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A Strength for Every Dog AVAILABLE IN 5 MG, 10 MG, 30 MG, 60 MG AND 120 MG CAPSULES

Come learn how to diagnose and treat Cushing’s disease in Dechra Academy • 2 Separate Modules – Learn at your own pace • Free – Just sign up or use your existing Dechra login • RACE Approved

www.dechra-us.com/CE VETORYL Capsules offers a full range of sizes from 5 mg up to 120 mg, so you don’t have to rely on compounders to provide the dose that’s right for the patient, regardless of how small or how large. VETORYL Capsules are the only FDA veterinary-approved treatment for pituitary-dependent and adrenaldependent hyperadrenocorticism in dogs (Cushing’s syndrome). They contain the active ingredient trilostane, which blocks the excessive production of cortisol. As with all drugs, side effects may occur. In field studies and post-approval experience, the most common side effects reported were: anorexia, lethargy/depression, vomiting, diarrhea, elevated liver enzymes, elevated potassium with or without elevated sodium, elevated BUN, decreased Na/K ratio, hypoadrenocorticism, weakness, elevated creatinine, shaking, and renal insufficiency. In some cases, death has been reported as an outcome of these adverse events. VETORYL Capsules are not for use in dogs with primary hepatic or renal disease, or in pregnant dogs. Refer to the prescribing information for complete details or visit www.Dechra-US.com. 24 Hour Technical Support:

866-933-2472 | www.dechra-us.com | support@dechra.com

NADA 141-291, Approved by FDA CAUTION: Federal law restricts this drug to use by or on the order of licensed veterinarian. 1 http://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/ucm049823.htm Vetoryl is a registered trademark of Dechra Limited. Dechra is a registered trademark of Dechra Pharmaceuticals PLC. ©2015, Dechra Ltd

COLUMNS 7 EDITOR’S NOTE

The Doctor Will See You Now! Simon R. Platt, BVM&S, MRCVS, DACVIM (Neurology), DECVN

GUEST EDITORIAL

Now Is Not the Time

PRACTICAL TOXICOLOGY

Tremorgenic Mycotoxin Intoxication in Dogs

Julie Stafford, DVM

Kirsten Waratuke, DVM, DABT

VET REPORT VITALS

How Often Does Treatment Follow the Guidelines?

Nathaniel Spofford, BA, MPH, and Molly McAllister, DVM, MPH

PRACTICAL PARASITOLOGY

The Flea-Infested Pet: Overview of Current Products Cherie M. Pucheu-Haston, DVM, PhD, DACVD

AHS HEARTWORM HOTLINE

Heartworm Education: It Takes a Team

Chris Duke, DVM, and Kathleen Williston

FOCUS ON PHARMACOLOGY

Behavior Medications: Which Medication, Which Patient? Karen L. Overall, MA, VMD, PhD, DACVB

DERMATOLOGY DETAILS

The Challenge of Chronic Otitis in Dogs— From Diagnosis to Treatment

106

HOW I TREAT…

Mammary Carcinoma An Interview With Dr. Annette Smith

Sandra Koch, DVM, MS, DACVD

Erratum

Atkins CE. Heartworm disease: the science, the practice and the future. Today’s Veterinary Practice 2017;7(1):87-92. The author regrets that there were errors in Figure 1 in the January/February 2017 AHS Heartworm Hotline. Below, please find a corrected version of the table and its legend.

tests performed well with overall (n = 150 samples) sensitivity/ specificity of 91%/99% for SNAP RT and 97/96% for Witness HW. Test results from 10 dogs with discordant results and retested (result in parentheses) after heat treating plasma. Results in red (+ or -) indicate a false- positive or -negative result. Dog

Initial test result

DiroCHEK

Witness HW

SNAP RT

+ (+)

− (*vol)

+ (+)

− (+)

+ (−)**

− (−)

+ (+)

− (+)

+ (+)

− (+)

+ (+)

− (+)

Neg

− (−)

+ (−)

− (−)

− (+)

+ (+)

− (+)

+ (+)

− (*vol)

− (−)

+ (−)

Figure 1. Data for heartworm test results are shown for 10 field samples, submitted to Auburn University, as part of a larger group of 150 plasma samples. All were tested with DiroCHEK (zoetisus.com), Witness HW (zoetisus.com), and SNAP RT (idexx.com) commercial heartworm tests, following the manufacturer’s directions or the laboratory protocol. These 10 samples demonstrated discordant results between the 3 diagnostic tests. All were tested again, using the same 3 tests, after heat treatment of the plasma. This was done to break down antigen–antibody complexes, which have been associated with false-negative results. The results shown represent findings after heat treatment of plasma and are considered to be the true test result. Heat treatment of samples yielded complete concordance* among all three assays.

*Insufficient volume postheating precluded the testing of 2 samples on the SNAP RT [displayed as *vol in the table], however, postheating results are displayed for the DiroCHEK and Witness HW.

Each assay had a small number of false-positive and falsenegative results. Nevertheless, compared to the DiroCHEK, both

**This sample tested positive prior to heat treatment and is considered a false-positive, as all 3 assays tested negative following heat treatment of this sample.

TABLE OF CONTENTS

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VETORYL® CAPSULES (trilostane)

5 mg, 10 mg, 30 mg, 60 mg and 120 mg strengths Adrenocortical suppressant for oral use in dogs only. BRIEF SUMMARY (For Full Prescribing Information, see package insert.) CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: VETORYL Capsules are an orally active synthetic steroid analogue that blocks production of hormones produced in the adrenal cortex of dogs. INDICATION: VETORYL Capsules are indicated for the treatment of pituitary- and adrenal-dependent hyperadrenocorticism in dogs. CONTRAINDICATIONS: The use of VETORYL Capsules is contraindicated in dogs that have demonstrated hypersensitivity to trilostane. Do not use VETORYL Capsules in animals with primary hepatic disease or renal insufficiency. Do not use in pregnant dogs. Studies conducted with trilostane in laboratory animals have shown teratogenic effects and early pregnancy loss. WARNINGS: In case of overdosage, symptomatic treatment of hypoadrenocorticism with corticosteroids, mineralocorticoids and intravenous fluids may be required. Angiotensin converting enzyme (ACE) inhibitors should be used with caution with VETORYL Capsules, as both drugs have aldosterone-lowering effects which may be additive, impairing the patient’s ability to maintain normal electrolytes, blood volume and renal perfusion. Potassium sparing diuretics (e.g. spironolactone) should not be used with VETORYL Capsules as both drugs have the potential to inhibit aldosterone, increasing the likelihood of hyperkalemia. HUMAN WARNINGS: Keep out of reach of children. Not for human use. Wash hands after use. Do not empty capsule contents and do not attempt to divide the capsules. Do not handle the capsules if pregnant or if trying to conceive. Trilostane is associated with teratogenic effects and early pregnancy loss in laboratory animals. In the event of accidental ingestion/overdose, seek medical advice immediately and take the labeled container with you. PRECAUTIONS: Hypoadrenocorticism can develop at any dose of VETORYL Capsules. A small percentage of dogs may develop corticosteroid withdrawal syndrome within 10 days of starting treatment. Mitotane (o,p’-DDD) treatment will reduce adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an interval of at least one month should elapse before the introduction of VETORYL Capsules. The use of VETORYL Capsules will not affect the adrenal tumor itself. Adrenalectomy should be considered as an option for cases that are good surgical candidates. The safe use of this drug has not been evaluated in lactating dogs and males intended for breeding. ADVERSE REACTIONS: The most common adverse reactions reported are poor/reduced appetite, vomiting, lethargy/dullness, diarrhea, elevated liver enzymes, elevated potassium with or without elevated sodium, elevated BUN, decreased Na/K ratio, weakness, elevated creatinine, shaking, and renal insufficiency. Occasionally, more serious reactions, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis or adrenal necrosis/rupture may occur, and may result in death.

(florfenicol, terbinafine, mometasone furoate) Otic Solution

Antibacterial, antifungal, and anti-inflammatory For Otic Use in Dogs Only CAUTION: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: CLARO® contains 16.6 mg/mL florfenicol, 14.8 mg/mL terbinafine (equivalent to 16.6 mg/mL terbinafine hydrochloride) and 2.2 mg/mL mometasone furoate. Inactive ingredients include purified water, propylene carbonate, propylene glycol, ethyl alcohol, and polyethylene glycol. INDICATIONS: CLARO® is indicated for the treatment of otitis externa in dogs associated with susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Staphylococcus pseudintermedius). DOSAGE AND ADMINISTRATION: Shake before use. CLARO® should be administered by veterinary personnel. Administer one dose (1 dropperette) per affected ear. The duration of effect should last 30 days. 1. Clean and dry the external ear canal before administering the product. 2. Verify the tympanic membrane is intact prior to administration. 3. Remove single dose dropperette from the package. 4. While holding the dropperette in an upright position, remove the cap from the dropperette. 5. Turn the cap over and push the other end of the cap onto the tip of the dropperette. 6. Twist the cap to break the seal and then remove cap from the dropperette. 7. Screw the applicator nozzle onto the dropperette. 8. Insert the tapered tip of the dropperette into the affected external ear canal and squeeze to instill the entire contents (1 mL) into the affected ear. 9. Gently massage the base of the ear to allow distribution of the solution. 10. Repeat with other ear as prescribed. Cleaning the ear after dosing may affect product effectiveness. CONTRAINDICATIONS: Do not use in dogs with known tympanic membrane perforation (see PRECAUTIONS). CLARO® is contraindicated in dogs with known or suspected hypersensitivity to florfenicol, terbinafine hydrochloride, or mometasone furoate. WARNINGS: Human Warnings: Not for use in humans. Keep this and all drugs out of reach of children. In case of accidental ingestion by humans, contact a physician immediately. In case of accidental skin contact, wash area thoroughly with water. Avoid contact with eyes. Humans with known hypersensitivity to florfenicol, terbinafine hydrochloride, or mometasone furoate should not handle this product. PRECAUTIONS: Do not administer orally. The use of CLARO® in dogs with perforated tympanic membranes has not been evaluated. The integrity of the tympanic membrane should be confirmed before administering the product. Reevaluate the dog if hearing loss or signs of vestibular dysfunction are observed during treatment. Use of topical otic corticosteroids has been associated with adrenocortical suppression and iatrogenic hyperadrenocorticism in dogs (see ANIMAL SAFETY). Use with caution in dogs with impaired hepatic function (see ANIMAL SAFETY). The safe use of CLARO® in dogs used for breeding purposes, during pregnancy, or in lactating bitches has not been evaluated. ADVERSE REACTIONS: In a field study conducted in the United States (see EFFECTIVENESS), there were no directly attributable adverse reactions in 146 dogs administered CLARO®. To report suspected adverse drug events and/or obtain a copy of the Safety Data Sheet (SDS) or for technical assistance, contact Bayer HealthCare at 1-800-422-9874. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth. PHARMACOLOGY: CLARO® Otic Solution is a fixed combination of three active substances: florfenicol (antibacterial), terbinafine (antifungal), and mometasone furoate (steroidal anti-inflammatory). Florfenicol is a bacteriostatic antibiotic which acts by inhibiting protein synthesis. Terbinafine is an antifungal which selectively inhibits the early synthesis of ergosterol. Mometasone furoate is a glucocorticosteroid with anti-inflammatory activity. MICROBIOLOGY: The compatibility and additive effect of each of the components in CLARO® solution was demonstrated in a component effectiveness and non-interference study. An in vitro study of organisms collected from clinical cases of otitis externa in dogs enrolled in the clinical effectiveness study determined that florfenicol and terbinafine hydrochloride inhibit the growth of bacteria and yeast commonly associated with otitis externa in dogs. No consistent synergistic or antagonistic effect of the two antimicrobials was demonstrated. The addition of mometasone furoate to the combination did not impair antimicrobial activity to any clinically significant extent. In a field study (see EFFECTIVENESS), at least 10 isolates from successfully treated cases were obtained for S. pseudintermedius and M. pachydermatis. EFFECTIVENESS: In a well-controlled, double-masked field study, CLARO® was evaluated against a vehicle control in 221 dogs with otitis externa. One hundred and forty six dogs were treated with CLARO® and 75 dogs were treated with the vehicle control. All dogs were evaluated for safety. Treatment (1 mL) was administered once on Day 0 to the affected ear(s). Prior to treatment, the ear(s) was cleaned with saline. The dogs were evaluated on Days 0, 7, 14, and 30. Blood work and urinalysis were obtained on Day 0 pre-treatment and Day 30 at study completion. Four clinical signs associated with otitis externa were evaluated: erythema, exudate, swelling, and ulceration. Success was based on clinical improvement at Day 30. Of the 183 dogs included in the effectiveness evaluation, 72.5% of dogs administered CLARO® solution were successfully treated, compared to 11.1% of the dogs in the vehicle-control group (p=0.0001). ANIMAL SAFETY: In a target animal safety study, CLARO® was administered aurally to 12-week-old Beagle puppies (4 dogs/sex/group) at 0X, 1X, 3X, and 5X the recommended dose once every 2 weeks for a total dosing period of 28 days (3 times the treatment duration). No clinically relevant treatment-related findings were noted in hearing tests, body weight, weight gain, or food consumption. CLARO® administration was associated with post-treatment ear wetness or clear aural exudate, increased absolute neutrophil count, decreased absolute lymphocyte and eosinophil counts, suppression of the adrenal cortical response to ACTH-stimulation, decreased adrenal weight and atrophy of the adrenal cortex, increased liver weight with hepatocellular enlargement/cytoplasmic change, and decreased thymus weight. Other potentially treatment-related effects included mild changes to AST, total protein, inorganic phosphorus, creatinine, and calcium. STORAGE INFORMATION: Store between 20ºC-25ºC (68ºF-77ºF), excursions permitted 15ºC-30ºC (59ºF-86ºF). HOW SUPPLIED: CLARO® solution is supplied in a single-use dropperette in a blister. Each dropperette contains one 1 mL dose. CLARO® is available in cartons of two, ten, or twenty dropperettes. NADA 141-440, Approved by FDA. Bayer, the Bayer Cross and CLARO are registered trademarks of Bayer. ©2016 Bayer HealthCare, LLC. Distributed by: Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201

ADVERTISER INDEX AAHA My Veterinary Career . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 myveterinarycareer.com Advanced Veterinary Ultrasound Ultrasound equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 advancedveterinaryultrasound.com Antech Diagnostics Lab diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 antechdiagnostics.com Bayer Claro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5, 6 bayerdvm.com/claro Quellin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Front cover quellinsoftchew.com Seresto . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 bayerdvm.com Shampoos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 bayerdvm.com Boehringer Ingelheim Vetmedin . . . . . . . . . . . . . . . . . . . . . . . . . . . inside front cover, 9 vetmedin.com Dechra Otic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 dechra-us.com Vetoryl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3,6 dechra-us.com Elanco Duramune Lyme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 elanco.com Trifexis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104, 105 elanco.com Exelint International Syringes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 exelint.com Masterfoods USA Royal Canin Feline Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 royalcanin.com Royal Canin Nutritional Solutions . . . . . . . . . . . . . . . . 36 royalcanin.com Merial Heartgard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 heartgard.com NexGard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108, back cover nexgardfordogs.com Midmark Midmark products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 midmarkanimalhealth.com NAVC Discovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 navc.com/discovery Live . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 navc.com/live VMX 2018 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 navc.com Nestlé Purina NeuroCare Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 purinaproplanvets.com Nutramax Laboratories Proviable-Forte . . . . . . . . . . . . . . . . . . . . . . . . . inside back cover proviable-forte.com Pet Health Pharmacy Pharmacy services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 pethealthpharmacy.com PRN Pharmacal University of PRN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 universityprn.com VetFolio VetFolio @ Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 vetfolio.com

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TABLE OF CONTENTS

Vetoquinol Zylkene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 vetoquinolusa.com

AD INDEX

Simon R. Platt , BVM&S, MRCVS, DACVIM (Neurology), DECVN University of Georgia

EDITOR’S NOTE

The Doctor Will See You Now!

“ We must always tell what we see. Above all, and this is more difficult, we must always see what we see.”

Charles Peguy

We may fear the future that technology can bring into our daily lives, but what is already here is probably around to stay. It’s been roughly 40 years since telemedicine was introduced into human healthcare, and for many purposes, its exponential progress has been embraced and accepted. Its role in veterinary medicine has been slower to evolve, partly because of some different challenges when using remoteaccess capabilities in daily practice. An advisory panel for the AVMA recently released a report on telemedicine; however, at this stage, the report is for informational purposes, not a policy statement.1 So what is this technology, and should we embrace it or fear it? The American Telemedicine Association briefly defines telemedicine as “the remote delivery of healthcare services and clinical information using telecommunications technology [that] includes a wide array of clinical services using internet, wireless, satellite, and telephone media.”2 This broadly encompasses much of what we already do and accept: telephone consultations with colleagues, telephone updates with owners, and remote imaging3 and ECG interpretation services, to name a few. The AVMA advisory panel defines telemedicine as “the use of medical information exchanged from one site to another via electronic communications to improve a patient’s clinical health status.”1 Based on these definitions, we could simplistically divide telemedicine into consultation services

(teleconsulting), which assist us with decisions about diagnosis and care, and diagnostic services, which at the extreme can directly offer a medical diagnosis from a remote situation. The former is widely accepted—for example, a consultant may provide advice about a particular case. The latter seems fraught with complications and lacks the “handson” approach that so many of us feel uncomfortable without. Surely just “seeing” is not enough to believe? Many feel certain that the correct use of telemedicine can enhance animal health by facilitating communication, diagnostics, treatment, and education.4–7 In the field of human medicine, telemedicine has become successful because of its convenience and accessibility, enabling the provision of healthcare in remote, underserved areas. Some healthcare plans now even include access to a doctor via video call; however, there are some very clear guidelines and laws defining this interaction. The healthcare provider must be licensed in the state where the patient resides; an established doctorpatient relationship must exist; and it must be clear to the patient that the healthcare provider is indeed qualified! All of these requirements are included in the AVMA’s advisory panel recommendations. The question that the use of videoconferencing prompts is, can an accurate diagnosis can ever be achieved “over the phone”? In human medicine, videoconferencing has intuitive benefits, including convenience, reduced costs, and improved access to specialists. Long-term study of these benefits is limited, but it is suggested that outcomes are at least as good as those achieved through traditional models of healthcare delivery.8 So why do we fear this technology? Possibly we fear where it all could lead. The fast growth of telemedicine has legal and ethical standards EDITOR’S NOTE continued on page 12

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TVPJOURNAL.COM

GUEST EDITORIAL

Julie Stafford, DVM Wasilla Veterinary Clinic, Wasilla, Alaska

GUEST EDITORIAL

Now Is Not the Time et’s work together to achieve better L mental health and wellness for the veterinary profession.

Unless you’ve been living under a rock in the United States for the past 2 or 3 years, you’ve likely heard about the push for veterinary wellness in our profession. Work-life balance, compassion fatigue, burnout, substance abuse, depression, suicide—we see these terms and statistics in our publications and online forums, from our veterinary medical associations, and even in mainstream media. With the onslaught of negative information regarding mental health and wellness it is easy to turn the page, to let it be someone else’s battle, to turn your back on a problem plaguing so many veterinarians. Now is not that time.

Now is not that time because this problem isn’t new. The mental health factors leading to depression and suicide within our profession are not new. This is a problem that has existed for quite some time. Speak with a veterinarian of almost any age and they will know of someone in our profession who committed suicide. Veterinarians who have been around longer know of more victims, but these tragedies don’t occur during a single period in time or single stage of our veterinary careers. Whether we are exhausted veterinary students, nervous new grads, deep in the trenches, or struggling with an exit strategy, we are all at risk. Our profession has been and will continue to be at risk until we create greater awareness, gain stronger support, and facilitate better avenues for improved mental health and wellness.

GUEST EDITORIAL

Now is not the time because this problem doesn’t just affect us. This is a problem of veterinarians worldwide. In Colombia, at the WSAVA Congress, I was able to discuss our professional mental health with veterinarians from around the world. Attendees from Mexico, Denmark, Colombia, Thailand, Australia, and many other countries all recognized the same problem. Some veterinarians live in countries where mental health is not readily recognized or treated because of education or cultural boundaries. Some do not have the financial or even physical means to seek professional mental health care due to economic factors or rural geography. But these veterinarians still deserve help and support. Let us use our exposure to these issues for the greater good. Let’s reach out to others to educate and support. Let’s collaborate with one another to find preventive measures and treatments.

Now is not the time because we haven’t developed a solution. Awareness is the beginning of anything, but we still need more information about these issues. We need to understand why our profession struggles with work-life imbalance, compassion fatigue, burnout, depression, and suicide. We need to reach out to other healthcare professionals, experts in mental healthcare and wellness, to obtain more research and information so we can better diagnose this disease of our profession and find ways to both treat and prevent it. Many veterinary groups and associations around the globe are striving to produce or facilitate this information. Associations such as the WSAVA, AVMA, and CVMA have online wellness resources readily available, as do many state veterinary medical associations. In November 2016, the Association of American Veterinary Medical Colleges held a

GUEST EDITORIAL

090340591/0 NADA 141-273, Approved by FDA

Vetmedin®(pimobendan) Chewable Tablets Cardiac drug for oral use in dogs only

ur profession has been and will O continue to be at risk until we create greater awareness, gain stronger support, and facilitate better avenues for improved mental health and wellness.

Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Description: Vetmedin (pimobendan) is supplied as oblong half-scored chewable tablets containing 1.25, 2.5, 5 or 10 mg pimobendan per tablet. Pimobendan, a benzimidazole-pyridazinone derivative, is a non-sympathomimetic, non-glycoside inotropic drug with vasodilatative properties. Pimobendan exerts a stimulatory myocardial effect by a dual mechanism of action consisting of an increase in calcium sensitivity of cardiac myofilaments and inhibition of phosphodiesterase (Type III). Pimobendan exhibits vasodilating activity by inhibiting phosphodiesterase III activity. The chemical name of pimobendan is 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3(2H)-pyridazinone. Indications: Vetmedin (pimobendan) is indicated for the management of the signs of mild, moderate, or severe (modified NYHA Class IIa, IIIb, or IVc) congestive heart failure in dogs due to atrioventricular valvular insufficiency (AVVI) or dilated cardiomyopathy (DCM). Vetmedin is indicated for use with concurrent therapy for congestive heart failure (e.g., furosemide, etc.) as appropriate on a case-by-case basis. a

wellness summit to explore these pressing issues; many veterinary schools, such as the University of Tennessee, have developed health and wellness into a part of their curricula. There are online support groups such as “Not One More Vet,” a private Facebook page dedicated to supporting veterinarians. Even companies such as Zoetis and VetGirl have informative online resources on mental health.

A dog with modified New York Heart Association (NYHA) Class II heart failure has fatigue, shortness of breath, coughing, etc. apparent when ordinary exercise is exceeded.

A dog with modified NYHA Class III heart failure is comfortable at rest, but exercise capacity is minimal.

A dog with modified NYHA Class IV heart failure has no capacity for exercise and disabling clinical signs are present even at rest.

Contraindications: Vetmedin should not be given in cases of hypertrophic cardiomyopathy, aortic stenosis, or any other clinical condition where an augmentation of cardiac output is inappropriate for functional or anatomical reasons. Warnings: Only for use in dogs with clinical evidence of heart failure. At 3 and 5 times the recommended dosage, administered over a 6-month period of time, pimobendan caused an exaggerated hemodynamic response in the normal dog heart, which was associated with cardiac pathology. Human Warnings: Not for use in humans. Keep this and all medications out of reach of children. Consult a physician in case of accidental ingestion by humans. Precautions: The safety of Vetmedin has not been established in dogs with asymptomatic heart disease or in heart failure caused by etiologies other than AVVI or DCM. The safe use of Vetmedin has not been evaluated in dogs younger than 6 months of age, dogs with congenital heart defects, dogs with diabetes mellitus or other serious metabolic diseases, dogs used for breeding, or pregnant or lactating bitches. Adverse Reactions: Clinical findings/adverse reactions were recorded in a 56-day field study of dogs with congestive heart failure (CHF) due to AVVI (256 dogs) or DCM (99 dogs). Dogs were treated with either Vetmedin (175 dogs) or the active control enalapril maleate (180 dogs). Dogs in both treatment groups received additional background cardiac therapy. The Vetmedin group had the following prevalence (percent of dogs with at least one occurrence) of common adverse reactions/new clinical findings (not present in a dog prior to beginning study treatments): poor appetite (38%), lethargy (33%), diarrhea (30%), dyspnea (29%), azotemia (14%), weakness and ataxia (13%), pleural effusion (10%), syncope (9%), cough (7%), sudden death (6%), ascites (6%), and heart murmur (3%). Prevalence was similar in the active control group. The prevalence of renal failure was higher in the active control group (4%) compared to the Vetmedin group (1%).

So don’t turn the page, or your back, on yourself or your colleagues that need you. Continue to stress the importance of mental health and wellness within our profession. Get involved at a local, state, or national level or even hop online and learn a little more about why veterinarians are at risk. Don’t let this issue pass you by without making a difference. Now is not that time.

Adverse reactions/new clinical findings were seen in both treatment groups and were potentially related to CHF, the therapy of CHF, or both. The following adverse reactions/new clinical findings are listed according to body system and are not in order of prevalence: CHF death, sudden death, chordae tendineae rupture, left atrial tear, arrhythmias overall, tachycardia, syncope, weak pulses, irregular pulses, increased pulmonary edema, dyspnea, increased respiratory rate, coughing, gagging, pleural effusion, ascites, hepatic congestion, decreased appetite, vomiting, diarrhea, melena, weight loss, lethargy, depression, weakness, collapse, shaking, trembling, ataxia, seizures, restlessness, agitation, pruritus, increased water consumption, increased urination, urinary accidents, azotemia, dehydration, abnormal serum electrolyte, protein, and glucose values, mild increases in serum hepatic enzyme levels, and mildly decreased platelet counts. Following the 56-day masked field study, 137 dogs in the Vetmedin group were allowed to continue on Vetmedin in an open-label extended-use study without restrictions on concurrent therapy. The adverse reactions/new clinical findings in the extended-use study were consistent with those reported in the 56-day study, with the following exception: One dog in the extended-use study developed acute cholestatic liver failure after 140 days on Vetmedin and furosemide. In foreign post-approval drug experience reporting, the following additional suspected adverse reactions were reported in dogs treated with a capsule formulation of pimobendan: hemorrhage, petechia, anemia, hyperactivity, excited behavior, erythema, rash, drooling, constipation, and diabetes mellitus. Effectiveness: In a double-masked, multi-site, 56-day field study, 355 dogs with modified NYHA Class II, III, or IV CHF due to AVVI or DCM were randomly assigned to either the active control (enalapril maleate) or the Vetmedin (pimobendan) treatment group. Of the 355 dogs, 52% were male and 48% were female; 72% were diagnosed with AVVI and 28% were diagnosed with DCM; 34% had Class II, 47% had Class III, and 19% had Class IV CHF. Dogs ranged in age and weight from 1 to 17 years and 3.3 to 191 lb, respectively. The most common breeds were mixed breed, Doberman Pinscher, Cocker Spaniel, Miniature/Toy Poodle, Maltese, Chihuahua, Miniature Schnauzer, Dachshund, and Cavalier King Charles Spaniel. The 180 dogs (130 AVVI, 50 DCM) in the active control group received enalapril maleate (0.5 mg/kg once or twice daily), and all but 2 received furosemide. Per protocol, all dogs with DCM in the active control group received digoxin. The 175 dogs (126 AVVI, 49 DCM) in the Vetmedin group received pimobendan (0.5 mg/kg/day divided into 2 portions that were not necessarily equal, and the portions were administered approximately 12 hours apart), and all but 4 received furosemide. Digoxin was optional for treating supraventricular tachyarrhythmia in either treatment group, as was the addition of a β-adrenergic blocker if digoxin was ineffective in controlling heart rate. After initial treatment at the clinic on Day 1, dog owners were to administer the assigned product and concurrent medications for up to 56±4 days.

Julie Stafford, DVM

Dr. Stafford is the 2016 WSAVA Hill’s Next Generation Award winner and a 2014–2015 AVMA Future Leader. The Next Generation Award acknowledges the work of a veterinarian who has graduated within the past 10 years and who has contributed significantly to the betterment of companion animals, the veterinary profession, and society at large. Winners are active in continuing education, have a strong record in community service, and work to bridge the gap between their generation and others. The 2014–2015 AVMA Future Leaders class developed resources on wellness and peer assistance that can be found on avma.org.

The determination of effectiveness (treatment success) for each case was based on improvement in at least 2 of the 3 following primary variables: modified NYHA classification, pulmonary edema score by a masked veterinary radiologist, and the investigator’s overall clinical effectiveness score (based on physical examination, radiography, electrocardiography, and clinical pathology). Attitude, pleural effusion, coughing, activity level, furosemide dosage change, cardiac size, body weight, survival, and owner observations were secondary evaluations contributing information supportive to product effectiveness and safety. Based on protocol compliance and individual case integrity, 265 cases (134 Vetmedin, 131 active control) were evaluated for treatment success on Day 29. At the end of the 56-day study, dogs in the Vetmedin group were enrolled in an unmasked field study to monitor safety under extended use, without restrictions on concurrent medications. Vetmedin was used safely in dogs concurrently receiving furosemide, digoxin, enalapril, atenolol, spironolactone, nitroglycerin, hydralazine, diltiazem, antiparasitic products (including heartworm prevention), antibiotics (metronidazole, cephalexin, amoxicillin-clavulanate, fluoroquinolones), topical ophthalmic and otic products, famotidine, theophylline, levothyroxine sodium, diphenhydramine, hydrocodone, metoclopramide, and butorphanol, and in dogs on sodium-restricted diets. Manufactured for: Boehringer Ingelheim Vetmedica, Inc. St. Joseph, MO 64506 U.S.A. Vetmedin® is a registered trademark of Boehringer Ingelheim Vetmedica GmbH licensed to Boehringer Ingelheim. Copyright © 2017 Boehringer Ingelheim or an affiliated company. All Rights Reserved. 448005-00 Revised 01/2017

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TODAY’S VETERINARY NEWS

Check out the

Tech Champions!

The maker of HEARTGARD Plus is continuing its Tech Champions program in 2017 with events and education sessions for veterinary technicians focused on flea and tick control, dental health, heartworm disease prevention, and intestinal parasite treatment. Now in its third year, the Tech Champions program was formed by the maker of HEARTGARD Plus and the National Association of Veterinary Technicians in America (NAVTA) to demonstrate commitment to and appreciation for veterinary technicians. Tech Champions are a coalition of selected veterinary technicians who serve as a rotating council of advocates for preventive health for pets, traveling to conferences and Tech Fest events around the country to reach as many veterinarians, technicians, and related professionals as possible. iscover more at ■D heartgardclinic.com/education.

Janet McConnell (left) and Rebecca Rose (right), two Tech Champions, behind the scenes.

LOOKING FOR LEADERS Do you know a veterinary technician or veterinary nurse with a talent for leadership who would like to attend the 2018 VMX (formerly the NAVC Conference) on a leadership scholarship? Here’s their chance! Last year, the NAVC said a final farewell to Dr. Earl H. Rippie, Jr, former past president and secretary–treasurer, and a champion of veterinary technicians. He believed that veterinary technicians bring unparalleled value to the health and wellbeing of animals. The new Dr. Earl H. Rippie Veterinary Technician Leadership Scholarship honors Dr. Rippie’s memory and his appreciation for veterinary technicians. or more information visit ■F navc.com/scholarships. The deadline is July 1, 2017.

TODAY’S VETERINARY NEWS

NEW BLOOD GLUCOSE MONITORING SYSTEM The iPet PRO blood glucose monitoring system is specifically designed to measure blood glucose in dogs, cats, and horses. The meter analyzes both venous and capillary blood samples, making it an effective tool for clinic or home use. The advanced technology detects and corrects sources of error for improved accuracy, exceeding the minimum acceptable criteria specified in ISO 15197:2013. The iPet PRO’s advanced system offers the latest technology in pet glucose monitoring to help improve the lives of pets living with diabetes. earn more at ulticare.com/ ■L pet-blood-glucose-monitoring.

30 Years of Prevention.

THANK YOU FOR MAKING US A PART OF YOUR TEAM.

TODAY’S VETERINARY NEWS

NEW VETERINARY MONITOR PROMOTES FEAR-FREE VISITS

CHECK OUT THE PET EFFECT CAMPAIGN

Midmark Animal Health has introduced the Cardell Insight Veterinary Monitor. Featuring veterinary-specific algorithms that quickly provide accurate and consistent readings, the Insight is useful in all areas of a veterinary practice, including examination, treatment, surgery, and recovery. Designed to be compact, lightweight, and durable, the Insight can also monitor patients should they need to be transferred within the hospital or be used for field monitoring. The Insight is noninvasive, supporting a fear-free environment for pets.

Zoetis has launched the Pet Effect campaign, which aims to raise awareness about how pets make people healthier and how, by extension, veterinary professionals are key contributors to human and public health. Zoetis has partnered with the Human Animal Bond Research Institute (HABRI) to publicize this research. The numerous health benefits of pet ownership include lower blood pressure, reduced risk of heart disease, stress reduction, and decreased rates of anxiety and depression. Research also shows that being exposed to pets can help prevent allergies in children and build immunity. The campaign features humorous videos, smart social media posts, and other assets that veterinarians can share with their clients to explain the health benefits of the human–animal bond.

or more information, ■F call 1-800-MIDMARK or visit midmarkanimalhealth.com.

EDITOR’S NOTE continued from page 7 EDITOR’S NOTE

struggling to catch up. This is where we need to be careful—the rules of the game don’t change because a consultation occurs electronically rather than face to face. The standards of care and laws of healthcare provision stay the same, but with appropriate oversight, the continued advancement, implementation, and acceptance of this technology could help veterinary medicine augment animal health and welfare. We will see! References 1. AVMA Practice Advisory Panel. Final Report on Telemedicine. January 13, 2017. Accessed April 2017. avma.org/KB/Resources/ Reports/Documents/Telemedicine-Report-2016.pdf. 2. American Telemedicine Association. Q&A. Accessed April 2017. americantelemed.org/main/about/about-telemedicine/telemedicine-faqs. 3. Poteet BA. Veterinary teleradiology. Vet Radiol Ultrasound 2008;49 (1 Suppl 1):S33-S36. 4. Mazan MR, Kay G, Souhail ML, et al. Patients without borders: using telehealth to provide an international experience in veterinary global health for veterinary students. J Vet Med Educ 2016 Sep 30:1-8.

o learn more about The Pet Effect ■T and download the campaign materials to share with others, visit ThePetEffect.org/veterinarian.

NEW LINE OF DISINFECTANTS LAUNCHED Neogen has introduced its line of COMPANION disinfecting products specifically formulated for the effective cleaning and disinfection of veterinary practices, animal care facilities, and animal laboratories. Neogen’s new line of disinfecting products includes COMPANION Cleaner-Disinfectant, Hand Sanitizer, and Disinfectant Wipes. When used in combination, the products can help safeguard the health of animal facility patients, clients, and staff by limiting the spread and impact of infectious agents. or more information, visit ■F animalsafety.neogen.com.

5. Sims MH, Howell N, Harbison B. Videoconferencing in a veterinary curriculum. J Vet Med Educ 2007;34(3):299-310. 6. Mtema Z, Changalucha J, Cleaveland S, et al. Mobile phones as surveillance tools: implementing and evaluating a large-scale intersectoral surveillance system for rabies in Tanzania. PLoS Med 2016 Apr 12;13(4). 7. Mars M, Auer RE. Telemedicine in veterinary practice. J S Afr Vet Assoc 2006;77(2):75-78. 8. Taqui A, Cerejo R, Itrat A, et al. Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis. Neurology 2017;88(14):1305-1312.

TODAY’S VETERINARY NEWS

REDUCES SEIZURES IN EPILEPTIC DOGS

WHEN FED AS AN ADJUNCT TO VETERINARY THERAPY

Epilepsy can make your clients feel powerless – but now, you can offer them an additional way to help their dogs. Purina® Pro Plan® Veterinary Diets NeuroCare is formulated with medium chain triglyceride oil to help nutritionally manage dogs with epilepsy along with their current medication. Give your clients the power of nutrition to help their dogs in a new way, every day.

IET LY DANAGE N O M & * LLY

T IONA SY P IT F I RS UTR PILE TO N WITH E S DOG

TO L E A R N M O R E A B O U T N E U RO CA R E , V I S I T PURINAPROPLANVETS.COM. Law TH, Davies ES, Pan Y, et al. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr. 2015 Nov 14;114(9):1438-47 Purina trademarks are owned by Société des Produits Nestlé S.A. Printed in USA.

*as an adjunct to veterinary therapy

INSIDE NAVC

Matt Winter, DVM, DACVR Executive Vice President of Veterinary Education

INSIDE NAVC

Educational Journeys Education is the facilitation of learning and the acquisition of knowledge. A proverb says, “Tell me and I’ll forget; show me and I may remember; involve me and I will understand.” This simple statement embodies the complexities of learning and the stimulating challenges of designing lasting educational experiences. At NAVC, our mission is to provide world-class continuing professional development for the global veterinary healthcare community. We continually strive to create programs that give veterinary professionals the opportunity to learn and teach through contact and engagement; to grow through interaction with the community; and to retain skills and information for future use and dissemination. Many veterinary professionals have experienced the NAVC Conference, now VMX—the Veterinary Meeting & Expo. Hundreds of speakers, experts in their fields, head to Orlando to provide thousands of hours of continuing education lectures and handson laboratories on topics that cover the many facets of our amazingly diverse profession. Attendees from every part of the veterinary profession converge at this meeting to learn, collaborate, and grow. But there are many other opportunities to learn with us.

NAVC Institute The NAVC Institute provides deep dives into focused areas—behavior, cardiology, and ophthalmology, to name a few—during weeklong courses designed around small groups and intensive, hands-on sessions. These intimate courses foster close communications with instructors and peers and allow development of novel, complex skill sets that can be brought to your practice. This level of involvement in didactic, laboratory, and discussion sessions ensures a memorable experience and improves retention of material and skills.

INSIDE NAVC

NAVC Discovery Building on the model of the NAVC Institute, NAVC Discovery takes some of our most popular courses—including Small Animal Abdominal Ultrasound and Soft Tissue Surgery—on the road to Buffalo, New York. Here, we combine the engaging small-group learning environment with a destination that boasts great food, craft beer, Lake Erie, and Niagara Falls. Discovery will also feature an innovative approach to teaching and learning surgical techniques as we introduce SynDaver synthetic canine cadavers to the soft tissue surgery lab. These complex models, designed in partnership with the University of Florida, replace canine cadaveric tissue with synthetic tissues that more closely mimic living tissue. The synthetic organs are perfused, have pulsatile synthetic blood flow, and have lesions that must be identified and resected completely, with vascular ligation. This is the future of veterinary medical education.

NAVC LIVE: Portland While sitting in a 50-minute continuing education lecture, have you ever thought that your cases never present as cleanly as the ones in the session? Have you ever wondered what the session case was really like from beginning to end? How was client interaction and communication handled? Have you pondered how the complexities of case management would have affected the outcome of that case? NAVC LIVE: Portland is designed to explore cases more fully by incorporating Veterinary Case Theater presentations. These sessions feature complete interactions with “clients,” the use of improv techniques, and tips and tricks that fuse the art of practice with the science of veterinary medicine.

INSIDE NAVC

NAVC Learning Academy As our careers progress, we often find that we gravitate to a specific area of interest. While residencies afford an opportunity to practice a particular aspect of veterinary medicine while earning specialist credentials, many veterinary professionals would like to seek more specialized training while still engaging in general practice. The NAVC Learning Academy will be introducing robust and rigorous certification programs in a variety of areas, providing in-depth coursework and instruction in topics such as the human– animal bond, teaching and learning, veterinary business, and more. These certifications will be provided through a combination of live and online materials, in partnership with experts in each field. Mastery of these materials must be demonstrated through an examination or project, and credentials must be kept current through maintenance of certification. As each of these certifications grows, new information will be introduced and developed, fostering collaborative communities and driving innovation.

“Tell me and I forget, teach me and I may remember, involve me and I learn.”

—Benjamin Franklin

Education is the red thread of our profession, tying us all together and advancing the art and science of veterinary medicine. As veterinary professionals, we have embarked on a lifelong journey of professional development. Aristotle is credited with the phrase “Education is the best provision for old age.” We also know that education keeps us young and knowledge is our greatest tool. With it, we solve problems daily for the love of animals, for the love of people, and for the love of the planet.

—Matt Winter, DVM, DACVR, Executive Vice President of Veterinary Education

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VET REPORT VITALS

How Often Does Treatment Follow the Guidelines? Nathaniel Spofford, BA, MPH Molly McAllister, DVM, MPH Banfield Pet Hospital, Portland, Oregon shutterstock.com/Soloviova Liudmyla

VET Report Vitals focuses on the results of the groundbreaking Banfield Veterinary Emerging Topics (VET) Report™ “Are We Doing Our Part to Prevent Superbugs? Antimicrobial Usage Patterns Among Companion Animal Veterinarians.” This report, a collaboration between the NAVC and Banfield Pet Hospital, aims to promote prudent antimicrobial use among companion animal practitioners by providing a baseline of antimicrobial usage data that can contribute to the discussion on how to achieve better concordance with published guidelines. This article presents data from the report as well as findings from industry research exploring practitioner’s current attitudes toward antimicrobial resistance (AMR). Future articles will explore the implications of AMR for veterinary practitioners and discuss strategies for improving guideline concordance in daily practice.

PRACTITIONERS’ ATTITUDES TOWARD ANTIMICROBIAL RESISTANCE Antimicrobials are a cornerstone of treatment for many conditions, and their use can be critical for patient quality of life and survival. As

VET REPORT VITALS

such, antimicrobial resistance (AMR) not only affects the provision of safe and effective care, but also represents a critical and growing threat to public health. Evidence suggests that AMR is an important concern for many companion animal practitioners, with 59% of respondents to a survey of clinical veterinarians at a veterinary teaching hospital1 and 45% of respondents to an American Veterinary Medical Association (AVMA) survey of self-identified companion animal practitioners2 indicating they were strongly concerned about antimicrobial-resistant infections. Despite these concerns, awareness of available resources, such as guidelines for judicious use and disease-specific treatment recommendations, remains low. Most respondents to the AVMA survey indicated that they would like additional guidance regarding the choice of antimicrobials for various infections (77%) and the duration of antimicrobial treatment (83%), yet 88% were unaware of the existence of antimicrobial usage guidelines created by veterinary professional associations (Figure 1). Given this low level of awareness, poor concordance of usage patterns with guideline recommendations might be expected.

VET REPORT VITALS

CONCORDANCE OF CURRENT USAGE PATTERNS WITH GUIDELINE RECOMMENDATIONS The availability of population-based data on antimicrobial use in companion animals from the electronic medical records of Banfield Pet Hospital provides an excellent snapshot of current usage patterns in general practice. This year’s edition of the VET Report™ explored antimicrobial usage patterns among companion animal practitioners to help inform voluntary adjustments that could result in a better balance between patient care and public health.

Methodology The report looked at antimicrobial usage patterns from the electronic medical records of dogs evaluated for urinary tract infections (UTIs) or respiratory tract infections (RTIs) at any of 926 general-practice Banfield Pet Hospitals over the course of a calendar year (January 1, 2015–December 31, 2015). Usage patterns were evaluated for concordance with recommendations for antimicrobial treatment (drug, dosage, frequency, and duration) of UTIs and RTIs published by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases (ISCAID).3,5 Because the primary aim was to evaluate concordance with current first-line treatment guidelines, only episodes in which a single antimicrobial was dispensed were included in the analysis.

Antimicrobial Use in Urinary Tract Infections There were 24,801 episodes of canine UTI treated with a single antimicrobial at Banfield Pet Hospitals in 2015 (Table 1). Episodes were

further classified as recurrent or nonrecurrent based on whether the patient had experienced 2 or more UTIs in the preceding 12 months. Of the 24,801 episodes evaluated, 95% were determined to be nonrecurrent in nature, whereas 5% were preceded by 2 or more UTIs in the previous year. The most recently published guidelines for care of nonrecurrent UTIs recommend initial treatment with amoxicillin (11–15 mg/kg PO q8h) or trimethoprim–sulfonamide (15 mg/kg PO q12h) for a duration of 7 days.3 Amoxicillin– clavulanate (12.5–25 mg/kg PO q8h) is described as an acceptable option, but not recommended owing to lack of evidence of the need for clavulanic acid. Based on these criteria, 9% of nonrecurrent UTI episodes received a guideline-concordant antimicrobial, although that number increases to 67% if amoxicillin– clavulanate is considered an acceptable option. For recurrent UTIs, guidelines recommend that providers consider waiting for culture and susceptibility (C&S) results before instituting therapy. In cases where immediate treatment is warranted, the same recommendations as for nonrecurrent UTIs apply, with the additional recommendations that antimicrobial therapy be given for a duration of 4 weeks and that an alternative drug class to the one used for treatment of the previous UTI be dispensed. For recurrent infections, 7% of episodes received a guideline-concordant drug, increasing to 44% if amoxicillin–clavulanate is considered concordant. Information about dosage, frequency, and duration was unavailable as structured data, so a utilization snapshot was obtained by conducting a manual

TABLE 1 Concordance With Drug Guidelines for Treatment of UTIs and RTIs

Recurrent UTIs Nonrecurrent

RTIs

CIRD Bacterial bronchitis

NUMBER OF EPISODES

CONCORDANCE NOT INCLUDING AMOXICILLIN–CLAVULANATE

CONCORDANCE INCLUDING AMOXICILLIN–CLAVULANATE

23,561 (95%)

2120 (9%)

15,786 (67%)

1240 (5%)

87 (7%)

546 (44%)

23,182 (95%)

5796 (25%)

18,546 (80%)

122 (5%)

29 (22%)

n/a

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VET REPORT VITALS

AWARENESS AMONG VETERINARIANS CAN BE INCREASED

45%

62%

88%

are concerned about antimicrobial-resistant infections2

feel that antimicrobials in small animal practice impact AMR2

are unaware of the 3 existing sets of antimicrobial use guidelines: urinary infections,3 superficial bacterial folliculitis,4 and respiratory infections5

PRESCRIPTION PATTERNS CAN BE IMPROVED In 2015, guideline-recommended first-line antimicrobials were not prescribed for6:

32.9%

55.8%

20.4%

78.3%

of canine nonrecurrent urinary infections

of canine recurrent urinary infections

of canine infectious respiratory disease episodes

of canine bronchitis episodes

FIGURE 1. Data about AMR awareness and antimicrobial use in veterinary medicine.

review of the medical notes from a random sample of 500 UTI episodes: 250 for which amoxicillin was dispensed and 250 for which amoxicillin– clavulanate was dispensed. For amoxicillin, 34% of the reviewed prescriptions were concordant with the ISCAID recommended dosage and 14% were concordant with both the recommended frequency and duration. For amoxicillin–clavulanate, 78% of reviewed prescriptions were concordant with the recommended dosage, <1% with the recommended frequency, and 28% with the recommended duration.

Antimicrobial Use in Respiratory Tract Infections There were 24,402 episodes of guideline-related canine respiratory disease treated with a single antimicrobial at Banfield Pet Hospitals in 2015, 95% of which were classified as canine

infectious respiratory disease complex (CIRD) and 5% as bacterial bronchitis (Table 2). Fifteen of 17 reviewers in ISCAID’s recently published guidelines for treatment of RTI recommended firstline treatment of the bacterial component of CIRD with doxycycline (5 mg/kg PO q12h or 10 mg/kg PO q24h) for a duration of 7 to 10 days.5 Amoxicillin– clavulanate (11 mg/kg PO q12h) was considered a suitable alternative by 13 of 17 reviewers. For bacterial bronchitis, doxycycline (5 mg/kg PO q12h or 10 mg/kg PO q24h) was recommended by 16 of 17 reviewers as the preferred empirical choice while waiting for results of C&S testing. Based on these criteria, 25% of CIRD episodes were treated with a guideline-concordant antimicrobial—increasing to 80% if amoxicillin–clavulanate is considered a suitable alternative—while 22% of bronchitis episodes received a guideline-concordant drug.

TABLE 2 Concordance With Dosage, Frequency, and Duration Guidelines for Treatment of UTIs and RTIs NUMBER OF RECORDS REVIEWED

RECOMMENDED DOSAGE GIVEN

RECOMMENDED FREQUENCY GIVEN

RECOMMENDED DURATION GIVEN

Amoxicillin

250

85/250 (34%)

34/250 (14%)

Amoxicillin–clavulanate

250

194/250 (78%)

1/250 (<1%)

69/250 (28%)

Doxycycline

250

72/250 (29%)

250/250 (100%)

115/250 (46%)

Amoxicillin–clavulanate

250

14/250 (6%)

250/250 (100%)

128/250 (51%)

UTIs

RTIs

VET REPORT VITALS

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VET REPORT VITALS

The medical notes from a random sample of 500 RTI episodes were reviewed to obtain information on the dosage, frequency, and duration of antimicrobial use: 250 for which doxycycline was dispensed and 250 for which amoxicillin–clavulanate was dispensed. For doxycycline, 29% of reviewed prescriptions were concordant with the ISCAID recommended dosages, 100% with the recommended frequency, and 46% with the recommended duration. For amoxicillin–clavulanate, 6% of reviewed prescriptions were concordant with the ISCAID recommended dosage, 100% with the recommended frequency, and 51% with the recommended duration.

CLINICAL BOTTOM LINE Antimicrobial usage data from 926 general-practice hospitals throughout the United States indicate that there is room for improved concordance with existing guidelines. Evidence suggests that low concordance may be driven by a lack of awareness

References 1.

Jacob ME, Hoppin JA, Steers N, et al. Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections. JAVMA 2015;247:938-944.

2. AVMA Task Force for Antimicrobial Stewardship in Companion Animal Practice. Understanding companion animal practitioners’ attitudes toward antimicrobial stewardship. JAVMA 2015;247:883-884. 3. 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. 4. Hillier A, Lloyd DH, Weese JS, et al. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Vet Dermatol 2014;25:163-175, e142-163. 5. Lappin MR, Blondeau J, Boothe D, et al. Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med 2017;31:279-294. 6. Banfield Pet Hospital/North American Veterinary Community. Veterinary Emerging Topics Report: Are We Doing Our Part to Prevent Superbugs? Antimicrobial Usage Patterns among Companion Animal Veterinarians. Portland, OR: Banfield Pet Hospital; 2016.

Nathaniel Spofford, BA, MPH

Nate Spofford is a Senior Research Specialist on Banfield’s Applied Research & Knowledge (BARK) team. He received his bachelor of arts degree from the University of Puget Sound and his master of public health degree from Portland State University. Before joining Banfield, Nate worked in clinical, behavioral, and public health research at Oregon Health & Science University. Nate is dedicated to conducting population-based research to support the practice of evidence-based medicine. He currently lives in Portland, Oregon, with his wife Kenzin, daughter Madeleine, and cat Smallie.

Molly McAllister, DVM, MPH

Dr. Molly McAllister is the Director of Research for the Banfield Applied Research and Knowledge (BARK) team at Banfield Pet Hospital. She is a graduate of Oregon State University College of Veterinary Medicine and subsequently earned her master of public health degree from the University of Minnesota. Dr. McAllister is passionate about the role of preventive and proactive care in the health and quality of life of our pets, as well as the intersection of human, animal, and environmental health. She lives with her family and 4 pets in Vancouver, Washington, where they spend as much time outdoors as possible.

of available resources. As such, strategies are needed to make the transition from publication of guidelines to incorporation of guidelines into practice. Upcoming VET Report Vitals articles will explore the implications of AMR for veterinary practitioners and discuss strategies for improving guideline concordance in daily practice.

VET REPORT VITALS

Banfield has always been dedicated to using its extensive data to provide insights to the profession on topics that can improve veterinary care for pets. The first annual Banfield Veterinary Emerging Topics (VET) Report, supported by the collaborative educational efforts of the NAVC, focuses on a critical topic: antimicrobial resistance. It is titled “Are We Doing Our Part to Prevent Superbugs? Antimicrobial Usage Patterns Among Companion Animal Veterinarians.” “We are proud to team up with the NAVC on the 2017 VET Report to raise awareness about the critical topic of antimicrobial resistance in companion animal practice and how veterinarians can address it in their own practices,” said Dr. Karen Faunt, Vice President of Medical Quality Advancement at Banfield Pet Hospital. The full report is available at Banfield.com/VETReport or VetFolio.com/VETReport.

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HEARTWORM HOTLINE

AHS HEARTWORM HOTLINE

Heartworm Education: It Takes a Team Chris Duke, DVM, and Kathleen Williston Bienville Animal Medical Center, Ocean Springs, Mississippi shutterstock.com/atiger

The Heartworm Hotline column is presented in partnership between Today’s Veterinary Practice and the American Heartworm Society (heartwormsociety.org). The goal of the column is to communicate practical and timely information on prevention, diagnosis, and treatment of heartworm disease, as well as highlight current topics related to heartworm research and findings in veterinary medicine.

Heartworm disease is one of the most important diseases threatening companion animals. According to the American Heartworm Society (AHS), disease caused by Dirofilaria immitis has been diagnosed in all 50 states, and, as most veterinarians and veterinary technicians are aware, it can affect both dogs and cats. Veterinary professionals have a wealth of effective, Food and Drug Administration– approved products, including oral, topical, and injectable formulations, that make heartworm disease preventable. One goal of veterinarians and technicians should be to ensure that every pet is protected from heartworm disease for 12 months each year. The key to realizing this goal is effective client education.

AHS HEARTWORM HOTLINE

MAKING HEARTWORM PREVENTION A PRIORITY Given the veterinary profession’s understanding of the importance of heartworm prevention, it’s easy to overestimate how seriously clients take this disease. Our practice, along with 46 other veterinary practices, recently participated in a client compliance survey. While we expected that most of our dogs and at least half of our cats would be receiving year-round heartworm prevention, the survey showed that just 58% of dogs and 30% of cats met this profile. Moreover, on average, the survey showed that dogs received heartworm preventives just 4.7 months of the year and cats only 3 months annually. Our profession—and our clients—can do much better.

CLIENT EDUCATION Each client represents an opportunity for heartworm education or reeducation. The discussion can come about naturally, within the course of any preventive care annual or semiannual visit. In our practice, all puppies and kittens begin receiving heartworm prevention at the time of

HEARTWORM HOTLINE

their second visit. Although there are similarities and differences in heartworm lifecycles (Figure 1), testing procedures, preventive products, and treatment methods between dogs and cats, what is most important is to simply start the discussion.

Another way to frame the discussion of cost of prevention is as follows: If you break the $100 per year cost down to a daily figure, it is $0.28 per day. On a monthly basis, that amounts to approximately $8.40. The value is unquestionable.

COSTS OF PREVENTION

THE HEARTWORM CONVERSATION

Heartworm prevention is not just an investment in an effective medication for the pet; it is an insurance policy against a preventable, potentially lethal disease. For an average-sized dog (20–30 lb), prevention costs around $50 for 6 months, or $100 a year. For small dogs and cats, the cost is even lower. On average, the cost of heartworm prevention is a just a fraction of the cost of heartworm treatment for dogs (Figure 2)—even without consideration of the health risks associated with heartworm infection in dogs. Meanwhile, there is no approved adulticide product for cats, making heartworm prevention essentially priceless.

In the world of marketing, there is a principle called the “Rule of 7,” which refers to the premise that consumers must hear a message approximately 7 times before they will buy or accept a product or service. A single voice—technician or veterinarian— explaining the importance of heartworm prevention is not sufficient. However, not every repetition of the message needs to be verbal. Posters, brochures, videos, and social media posts can all be used to support the message. The waiting room is a prime area to begin the education process. Display heartworm brochures

Heartworm-infected Dog

FIGURE 1. Canine and feline heartworm lifecycles. Reproduced with permission from the American Heartworm Society.

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HEARTWORM HOTLINE

so clients can read about the disease before they even enter the examination room. Posters and videos in the waiting area are also useful. Once the client and pet are in the examination room, the veterinary technician takes the lead in discussing heartworm prevention. This discussion should not be overly technical, but rather a common-sense approach to explaining a life-threatening disease, and it can fit into the intake process. In our practice, the technician asks questions about diet, weight trends, lifestyle changes, and parasite prevention. We use a series of exam stickers (Figure 3) to make recording this information easier. One simple way to begin the heartworm prevention conversation is for the technician to simply ask clients if they have ever seen mosquitoes around their home. If the client says yes—and in almost every instance they will—the technician can explain that the mosquito is the vector in the transmission of heartworm disease. We tell clients, “We can’t kill every mosquito around your home, but we can prevent against the heartworm larvae that any given mosquito can infect your pet with.” The veterinarian can then restate the practice’s heartworm and flea control recommendations while

FIGURE 2. Cost comparison between heartworm treatment and prevention. Reproduced with permission from the American Heartworm Society.

AHS HEARTWORM HOTLINE

summarizing the findings from the intake discussion. If an annual heartworm test is conducted during the visit, both the veterinarian and technician can again reinforce the importance of prevention, as well as explain why the test is needed even if the pet is receiving year-round prevention. In our practice, if the results of the heartworm test are positive, the veterinarian will discuss those results. At checkout, the receptionist can provide one last point of heartworm education, supporting the recommendations of the veterinarian and technician and explaining the value of the recommended products the client is purchasing. Consistent positive affirmation of heartworm prevention, from pet intake to pet discharge, is powerful. By keeping the “Rule of 7” in mind, the veterinary team can remind themselves of the value of repetition.

CLIENT RELUCTANCE Some clients refuse to purchase heartworm prevention products—sometimes because of cost and sometimes for other reasons. Pet owners may rationalize that their pets are at low risk because they live indoors or have limited time outside. Others mistakenly believe that a holistic approach will be effective. Still others are concerned about the safety of heartworm preventives. Every one of these objections presents an educational opportunity. Veterinarians can share stories of heartworm cases with tragic outcomes—or display an infected heart in a jar of formalin to prove the reality of heartworms. Although our practice’s philosophy leans toward positive education, both approaches can work.

FIGURE 3. Chart label used in authors’ practice to track recommendations for and use of heartworm prevention.

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HEARTWORM HOTLINE

If heartworm prevention or a heartworm test is declined, this should be noted in the clinic record. If the pet later becomes infected, the opportunity for reeducation is always there.

BOX 1. A Tale of Two Heartworm-Positive Cases A principle of adult learning is the use of narrative: people learn through stories. In our clinic, telling stories of past patients is one of the most effective ways to emphasize the importance of heartworm prevention, testing, and treatment. Owners who are concerned about adopting a heartworm-positive rescue dog might be inspired to learn about Maya. Those who are questioning the importance of year-round prevention or whose buying history indicates lapses in compliance likewise may benefit from hearing how Rock’s unfortunate outcome might have been averted. Maya Maya was a 4-year-old mixed-breed rescue dog. When she was spayed at a local shelter, she was tested for heartworms and diagnosed with asymptomatic heartworms. She was then referred to our hospital for treatment. The hospital staff promptly started her on a course of doxycycline for 30 days and a monthly dose of ivermectin, following the AHS heartworm treatment protocol. Maya was placed in foster care for the next 2 months, then brought back for melarsomine therapy. She completed the treatment without complications. Shortly after treatment ended, a foster group asked to have her shipped from the Gulf Coast to Connecticut. Maya is now happily settled in her new home, with a new veterinarian. She is now receiving year-round heartworm prevention to avoid a repeat episode. Rock Rock was a 10-year-old neutered male bulldog whose owners had discontinued use of heartworm prevention. At diagnosis of heartworm infection, he presented clinically with heavy, labored breathing, pale gums, and ascites on his abdomen and had been anorectic for 3 days. The staff worked valiantly to improve his condition through supportive IV fluids, antibiotics, and other drugs; however, after watching Rock’s condition deteriorate over 3 days in the hospital, the owner elected to have him euthanized. It was too late for Rock to be helped. This outcome was preventable. There are many ways to share anecdotes such as these. Tell stories of successful heartworm treatment and rescue dog turnarounds on your Facebook page (if the owner/foster volunteer consents). Feature stories on your clinic website. Share them on Twitter. The goal is to turn these compelling stories into messages that reinforce the importance of heartworm prevention, testing, and treatment.

REMINDER SYSTEMS For the Veterinary Practice Every time a heartworm prevention product is sold, it should be linked to a refill reminder to be e-mailed, texted, or delivered via traditional postal service. A simple reminder is one of a practice’s strongest compliance enhancers. In our practice, annual heartworm tests are commonly performed in conjunction with annual examinations, but resale or renewal opportunities for prevention products often coincide with semiannual visits at 6-month intervals. In some veterinary clinics, a team member calls the client with a reminder on a given date. Regardless of the products stocked or the communication method used, the main objective is to compel the client to return to the clinic for more heartworm preventives—and to use them. Free and convenient resources are available. All the major pharmaceutical manufacturers that sell heartworm preventives provide incentives, discounts, or rebates to help market their products. These offers can be used to help educate your clients and distribute the product.

For Clients Once your clients have purchased heartworm medication, they must be encouraged to administer it. Enhancing client compliance at home is as important as getting clients to the clinic. Consider two useful approaches: 1. Clients who use a smartphone can add a reminder to alert them when their pet requires dosing. The app used by our practice generically reminds clients that heartworm and flea prevention should be administered on the first of the month, whether a monthly, every-3months, or every-6-months product is used. 2. Clients can use their at-home calendar to remind them when doses are due or can use the check-off panels on the prescription boxes if applicable. It is important to improve compliance on heartworm prevention with an electronic or more traditional reminder system within the comfort zone of the client. HEARTWORM HOTLINE continued on page 95

AHS HEARTWORM HOTLINE

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LIVER ENZYME INTERPRETATION

CONTINUING EDUCATION

Liver Enzyme Interpretation and Liver Function Tests Brigitte B. McAtee, DVM Jonathan A. Lidbury, BVMS, MRCVS, PhD, DACVIM, DECVIM-CA Texas A&M University

Hepatobiliary disease is an important cause of morbidity and mortality in dogs and cats and can present a diagnostic challenge for two main reasons. First, patient signalment varies because liver disease and dysfunction can occur in cats and dogs of any age, sex, or breed (see Case Studies). Despite this, the patientâ&#x20AC;&#x2122;s signalment can sometimes give important clues because certain breeds have disease predispositions; for example, Labrador retrievers are predisposed to copper-associated chronic hepatitis. Second, elevations of serum liver enzyme activities are commonly encountered in small animal practice but are not specific for primary liver disease. However, early in the course of liver diseases, such as chronic hepatitis, patients may have no or only subtle, nonspecific clinical signs, such as intermittent anorexia or lethargy. In these patients, increased liver enzyme activities may be the first indicator of a problem. More liver-specific clinical signs, such as icterus, ascites, edema, polyuria/ polydipsia, and hepatic encephalopathy, tend to occur late in the course of disease, when

it is often too late to prevent its progression. Therefore, early diagnosis of liver disease often relies on serum biochemical testing, which may prompt further diagnostics, including liver function testing. This article reviews the interpretation and limitations of serum liver enzyme activity and liver function tests.

BACKGROUND The liver has a wide variety of metabolic functions (Box 1). Because of these diverse metabolic roles, liver dysfunction is associated with a variety of sequelae and clinicopathologic abnormalities. The liver is unique in that it receives much of its blood supply (75%) from the portal venous system, which drains abdominal organs, such as the gastrointestinal (GI) tract, spleen, and pancreas.1,2 This means that diseases of the pancreas and GI tract can secondarily affect the liver. The liver also metabolizes and/or excretes a variety of exogenous substances (ie, drugs and toxins) that may cause secondary liver injury.

LIVER DISEASE AND DYSFUNCTION can occur in cats and dogs of any age, sex, or breed.

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HEPATIC ENZYMOLOGY Serum liver enzymes are sensitive but not necessarily specific markers of primary hepatobiliary disease. They are not direct markers of liver function. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular damage, whereas alkaline phosphatase (ALP) and gammaglutamyltransferase (GGT) are markers of cholestasis.3 Each individual enzyme can provide information on whether liver disease is present and may provide clues as to the most likely differential diagnosis.

Alanine Aminotransferase ALT is a cytoplasmic enzyme found mainly in hepatocytes. However, it is also found in other cells, such as skeletal muscle, renal, and red blood cells, in smaller amounts. ALT is released into the circulation when there is hepatocyte necrosis or increased cell membrane permeability and therefore is a sensitive marker of hepatocellular injury. ALT is the most liver specific of the liver enzymes,

BOX 1 Metabolic Functions of the Liver 1 Protein metabolism • Synthesis of plasma proteins (albumin, globulins, coagulation proteins) • Deamination of amino acids • Conversion of ammonia to urea • Amino acid synthesis • Interconversion of amino acids Lipid metabolism •β -oxidation of fatty acids • Synthesis of cholesterol • Synthesis of lipoproteins • Synthesis of fatty acids from proteins and carbohydrates Carbohydrate metabolism • Storage of glycogen • Conversion of galactose and fructose into glucose • Gluconeogenesis • Synthesis of many compounds from carbohydrates

LIVER ENZYME INTERPRETATION

but occasionally severe muscle damage or ex vivo hemolysis may increase ALT activity.4 Concurrent evaluation of creatine kinase activity may help discriminate between muscle disease and liver disease because creatine kinase activity is expected to increase with muscle damage. ALT activity can also be increased in patients with extrahepatic diseases that secondarily affect the liver (eg, feline hyperthyroidism). The reported half-life of ALT has been reported to be about 60 hours in dogs and 3.5 hours in cats.3 These relatively short half-lives are useful when monitoring recovery after acute liver injury. Conditions that can cause an increase in ALT activity include those listed in Table 1.

Aspartate Aminotransferase AST is a cytoplasmic and mitochondrial enzyme found in hepatocytes and other cells. Reversible or irreversible damage to the liver causes release of the cytoplasmic AST; however, only irreversible damage to the cell will cause release of mitochondrial AST. These two sources of AST are not distinguishable by measuring serum AST activity on a routine biochemistry panel. Increases in AST activity generally parallel those of ALT. However, AST is less specific for liver injury than ALT because increases in activity of AST may also be due to cardiac or skeletal muscle injury4 or ex vivo hemolysis. The half-life of AST is about 22 hours in dogs and 80 minutes in cats.3 The shorter half-life compared with ALT means that AST activity decreases and returns to normal before that of ALT in patients with acute liver injury. Conditions that can cause an increase in AST activity include those listed in Table 1.

Alkaline Phosphatase ALP is an enzyme found in hepatocytes that line the bile canaliculi. It is released into the circulation during intra- or extrahepatic cholestasis. This enzyme is sensitive for hepatobiliary disease in dogs (80%), but because of the possible contributions of bone and glucocorticoid-induced isoenzymes to serum ALP activity, its specificity is low (51%).5 In young, growing animals, ALP activity is normally increased because of the bone isoenzyme, with 71%

CONTINUING EDUCATION

of dogs younger than 1 year having ALP activity >150 U/L.6 Bone ALP may also be elevated in patients with osteomyelitis or osteosarcoma. Dogs with hyperadrenocorticism and those receiving glucocorticoids can be expected to have increased ALP activity due to the glucocorticoid-induced isoenzyme. Conditions that can cause an increase in ALP activity include those listed in Table 1.

The highest activities of ALP have been reported with conditions such as cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis.7 This lack of tissue specificity can make increases in activity of ALP hard to interpret. The half-life of ALP is approximately 70 hours in dogs and 6 hours in cats.3 In cats, which lack the glucocorticoid-induced isoenzyme with a

TABLE 1 Causes of Increased Liver Enzyme Activity ALT/AST

ALP

Metabolic/endocrine

Hepatic lipidosis (cats), diabetes mellitus, hyperthyroidism (cats), hypothyroidism (dogs), hyperadrenocorticism

Hepatic lipidosis (cats), diabetes mellitus, hyperadrenocorticism, hypothyroidism (dogs)

Hypoxic

Hepatic congestion, thrombosis, anemia, sepsis, seizures

Neoplastic

Lymphoma, metastatic neoplasia (eg, mast cell tumor), hepatocellular carcinoma

Bile duct carcinoma, pancreatic carcinoma, lymphoma

Inflammatory

Acute/chronic hepatitis, cholangitis, cholangiohepatitis, cholecystitis, pancreatitis, enteritis

Infectious

Leptospirosis, histoplasmosis, feline infectious peritonitis, schistosomiasis, ascending bacterial infections, toxoplasmosis

Can cause increases in ALP activity, but they are less consistent and not as marked as those of ALT

ENDOGENOUS CAUSES

• E xtrahepatic bile duct obstruction: gallbladder, • Steroid hepatopathy (caused

Other

by endogenous or exogenous glucocorticoids) • B enign nodular hyperplasia • M uscle injury (AST > ALT): myositis, muscular dystrophy, trauma • Hemolysis

mucocele, pancreatic neoplasia, choledocholithiasis •B enign nodular hyperplasia • Increased osteoblastic activity: osteosarcoma,

fracture repair, rickets, hyperparathyroidism • B enign familial hyperphosphatemia (Siberian

huskies) •V acuolar hepatopathy • G rowth (young dogs)

EXOGENOUS CAUSES

Medications

Tetracyclines, carprofen, phenobarbital, azathioprine, antifungal medications (ketoconazole/itraconazole), trimethoprim–sulfadiazine, lomustine, amiodarone, diazepam (cats), griseofulvin, zonisamide

Corticosteroids (dogs), phenobarbital, primidone

Toxins

Cycads, xylitol, zinc, aflatoxin, amanita mushroom, blue-green algae, heavy metals, carbon tetrachloride

Can cause increases in ALP activity, but they are less consistent and not as marked as those of ALT

Trauma

Yes

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Case Studies CASE 1

CASE 2

Signalment and Presentation A 3-month-old female intact Irish wolfhound presents for stunted growth and episodes of intermittent lethargy and disorientation.

Signalment and Presentation An 8-year-old male neutered Labrador retriever presents for a 3-month history of decreased appetite and weight loss.

Results of Diagnostic Testing A serum biochemistry panel is performed, with the results in Table A. The fasted ammonia concentration is 175 mcg/dL (normal range, 0–50 mcg/dL). Preprandial and postprandial (2-hour) SBA are 40 mcmol/L (normal, 0–8 mcmol/L) and 102 mcmol/L (normal, 0–30 mcmol/L), respectively.

TABLE A Case 1 Serum Biochemistry Results ANALYTE

VALUE

NORMAL RANGE

BUN

3 mg/dL

7–27 mg/dL

Total protein

5.0 g/dL

5.2–8.2 g/dL

Albumin

2.0 g/dL

2.4–4 g/dL

Cholesterol

79 mg/dL

110–220 mg/dL

Glucose

118 mg/dL

74–140 mg/dL

ALT

50 U/L

10–130 U/L

AST

15 U/L

10–34 U/L

ALP

180 U/L

24–147 U/L

GGT

<10 U/L

0–25 U/L

Total bilirubin

0.1 mg/dL

0–0.8 mg/dL

Interpretation The combination of hypoalbuminemia, decreased BUN, and hypocholesterolemia suggests decreased hepatic synthetic capacity. The ALT and AST activities are within normal limits, making hepatocellular damage unlikely; the ALP activity is only mildly elevated, probably because the dog is growing.

Results of Diagnostic Testing A serum biochemistry panel is performed, with the results in Table B. The fasted ammonia concentration is <15 mcg/dL (normal range, 0–50 mcg/dL). Preprandial and postprandial (2-hour) bile acids are 2.9 mcmol/L (normal, 0–8 mcmol/L) and 14.5 mcmol/L (normal, 0–30 mcmol/L), respectively.

TABLE B Case 2 Serum Biochemistry Results ANALYTE

VALUE

NORMAL RANGE

BUN

13 mg/dL

7–27 mg/dL

Total protein

6.2 g/dL

5.2–8.2 g/dL

Albumin

3.3 g/dL

2.4–4 g/dL

Cholesterol

179 mg/dL

110–220 mg/dL

Glucose

110 mg/dL

74–140 mg/dL

ALT

550 U/L

10–130 U/L

AST

50 U/L

10–34 U/L

ALP

198 U/L

24–147 U/L

GGT

<10 U/L

0–25 U/L

Total bilirubin

0.2 mg/dL

0–0.8 mg/dL

Interpretation The ALT activity is 2.4 times the upper limit of the reference interval, while the ALP activity is only 1.3 times the upper limit of the reference interval. This, along with the increased serum AST activity, is consistent with a hepatocellular damage pattern.

The ammonia concentration and SBA results suggest portosystemic shunting and/or hepatic insufficiency.

The ammonia concentration and SBA results rule out portosystemic shunting and do not support the presence of severe liver dysfunction. However, hepatobiliary disease is not excluded and further testing is indicated.

Given the patient’s signalment, clinical findings, and laboratory abnormalities, a congenital portosystemic shunt is likely and imaging (ultrasonography and/or computed tomography) is warranted.

Abdominal ultrasonography would be a logical next step. If the ALT is persistently increased and no evidence supports the presence of extrahepatic disease, liver biopsy would be indicated.

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shorter half-life, increases of serum ALP activity are more specific for hepatobiliary disease than in dogs and are generally clinically relevant.

Gamma-Glutamyltransferase GGT is associated with the cell membranes of hepatocytes that form the bile canaliculi and bile ducts, as well as periportal hepatocytes. It is a marker of intrahepatic (eg, feline hepatic lipidosis) or extrahepatic (eg, bile duct obstruction) cholestasis. In dogs, it has a higher specificity (87%) and lower sensitivity (50%) for hepatobiliary disease compared with ALP.7 In general, GGT is a more sensitive marker of feline hepatobiliary disease than ALP. However, in cats with feline hepatic lipidosis, GGT is generally only mildly elevated.8 No definitive studies determining the half-life of GGT have been performed in cats or dogs. However, serum GGT and ALP activities decrease after liver injury at a similar rate in dogs, suggesting that they have a similar half-life.9

Interpreting Liver Enzyme Elevations The degree of the increase in hepatocellular-damage enzyme activities may help stratify disease severity as follows5:

• Mild: 2- to 3-fold elevation in activity • Moderate: 5- to 10-fold elevation in activity • Marked: >10-fold elevation However, such increases do not always correlate with severity of disease. This is true in dogs and cats with portosystemic shunting and dogs with end-stage chronic hepatitis, in which hepatocytes are replaced by fibrous tissue. Therefore, the degree of liver enzyme increase should be interpreted with caution. Because the liver has a large regenerative capacity, the degree of liver enzyme elevation should also not be used to indicate prognosis. For example, a dog with acute liver injury may have severely increased serum ALT activity but can still make a full recovery. Longitudinal monitoring trends in liver enzyme activities can help in determining chronicity and monitoring disease progression and/or response to treatment.

In evaluating liver enzymes, it is important to determine what type of elevation pattern is present (ie, hepatocellular damage versus cholestasis). A relatively greater increase in ALT and AST activity indicates hepatocellular damage, while a greater increase in ALP and GGT activity indicates cholestasis, which could be intrahepatic or extrahepatic. Establishing the pattern may help narrow the differential diagnosis. However, some liver diseases can display a mixed pattern (eg, cholangitis, phenobarbital hepatopathy).

LIVER FUNCTION TESTING Routine biochemical testing can give clinicians an insight into many liver functions. Box 2 presents common abnormal results of biochemical tests that can have liver-related causes as well as important differential diagnoses to consider for these test results. However, because of the liver’s functional reserve capacity, these tests are not sensitive for liver insufficiency. Abnormal results can also be caused by other conditions and thus also lack specificity. It is important for clinicians to not only look for analytes that are flagged as being outside their respective reference intervals but also look at their actual values. For example, serum albumin, cholesterol, and blood urea nitrogen (BUN) concentrations toward the lower limit of the reference interval suggest hepatic insufficiency or portosystemic shunting. Monitoring trends in these values over time can also be informative. Because of the limited sensitivity and specificity of biochemical tests, patients with confirmed or suspected liver disease sometimes require additional liver function testing to better characterize their disease.

Serum Bile Acids Measurement of the total concentrations of serum bile acids (SBA) aids in the diagnosis of patients with portosystemic shunts and in the assessment of hepatic function. Potential indications for SBA measurement include:

• Suspicion for portosystemic shunting (eg, seizures, other signs of encephalopathy) • Persistently increased liver enzyme activities, especially ALT

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• Severe hypoalbuminemia (<2.0 g/dL) in dogs • Unexplained ammonium urate urolithiasis

BOX 2 Biochemical Test Results That Can Indicate Hepatic Disease and Important Differential Diagnoses Severe hypoalbuminemia (<2.0 g/dL) •D ecreased hepatic synthesis (portosystemic shunting, hepatic parenchymal disease) •D ifferential diagnoses: protein-losing nephropathy and protein-losing enteropathy Hypocholesterolemia •D ecreased hepatic synthesis (portosystemic shunting, hepatic parenchymal disease) •H ypoadrenocorticism •M alassimilation •S tarvation Hypercholesterolemia •C holestasis (intrahepatic, extrahepatic) •D ifferential diagnoses: endocrine disease (diabetes mellitus, hyperadrenocorticism, hypothyroidism), nephrotic syndrome, postprandial Hypoglycemia •S everely decreased functional hepatic mass (<75% of normal5) •D ifferential diagnoses: sepsis, hypoadrenocorticism, toy breeds/puppies, insulinoma/other neoplasia, starvation, polycythemia, leukemia Hyperbilirubinemia • Cholestasis (intrahepatic, extrahepatic) • Differential diagnosis: hemolysis (in vivo, ex vivo) Decreased BUN •D ecreased hepatic synthesis (portosystemic shunting, hepatic parenchymal disease) •D ifferential diagnosis: polyuria (eg, fluid therapy, polydipsia) Increased SBA • Portosystemic shunting •M icrovascular dysplasia (portal vein hypoplasia without portal hypertension) • Hepatic parenchymal disease • Extrahepatic bile duct obstruction • Differential diagnosis: small intestinal dysbiosis (possibly)

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• Hyperbilirubinemia when hemolysis cannot be definitely diagnosed/excluded (uncommon) In a healthy patient, SBA are synthesized from cholesterol. In dogs, bile acids are conjugated to glycine or taurine and then stored in the gallbladder, whereas in cats they are conjugated almost exclusively with taurine.10 After a meal, the gallbladder contracts because of secretion of cholecystokinin, emptying bile into the duodenum. Bile acids are absorbed in the ileum. They are transported via the portal circulation to the liver, where they are subsequently reabsorbed. Normally this process is about 95% to 98% efficient. The enterohepatic recirculation of bile acids is impeded in dogs without gallbladders and patients with ileal disease or that have had ileal resection, causing a decrease in SBA concentration. Other conditions that can cause decreased SBA concentrations include GI malabsorption and decreased gastric motility.2 Causes of increased total SBA concentrations are listed in Box 2. Diseases that cause intrahepatic cholestasis (lipidosis, diabetes mellitus, lymphoma, histoplasmosis, cirrhosis) or extrahepatic cholestasis (cholangitis, bile duct carcinoma, liver flukes, cholelithiasis, pancreatitis) can cause decreased bile acid excretion, despite no decrease in functional hepatic mass. In patients with hyperbilirubinemia, once hemolysis has been ruled out, measuring SBA is not indicated because their concentration will be predictably increased. Compared with plasma ammonia, SBA are easy to measure and do not not require special sample handling. Paired preprandial and 2-hour postprandial SBA measurements are usually performed to increase the sensitivity of this test (Box 3). While SBA measurement is arguably the best test of liver function and portosystemic shunting in dogs and cats, increased concentrations are not specific for any single hepatobiliary disease. Therefore, this test can be helpful for evaluating the likelihood of hepatobiliary disease; however, it cannot definitively determine the underlying liver disease. Additionally, this test does not provide a truly quantitative assessment of hepatic function. Because of the hepatic reserve capacity, it is possible for dogs with normal SBA concentrations to have hepatobiliary disease; therefore, this test

CONTINUING EDUCATION

Blood ammonia concentration can be increased because of portosystemic shunting, severe hepatic insufficiency, or urea cycle enzyme deficiencies (Box 4).12 Potential indications for plasma ammonia measurement include:

of urea and proteins in the large bowel. Therefore, blood coming from the splanchnic circulation is rich in ammonia.13 The liver detoxifies ammonia through two pathways: (1) the urea cycle, which converts ammonia into urea and (2) consumption of ammonia during glutamine synthesis by hepatocytes. In animals with portosystemic shunting or severe hepatic dysfunction, the liver is unable to synthesize sufficient glutamine or urea, leading to hyperammonemia. Because ammonia freely passes across membranes, including the blood–brain barrier, hyperammonemia contributes to the development of clinical signs of hepatic encephalopathy.

• Suspicion for portosystemic shunting (eg, seizures, other signs of encephalopathy)

Fasting Ammonia Measurement

should not be used to screen patients for hepatobiliary disease. However, the sensitivity of SBA measurement for portosystemic shunts (congenital and acquired) is high and in one study was reported to be 93% and 100% for dogs and cats with congenital portosystemic shunt, respectively.11

Ammonia

• Suspicion for urea cycle enzyme deficiency (eg, cat with feline hepatic lipidosis) • Unexplained ammonium urate urolithiasis Ammonia is mainly produced by catabolism of glutamine by enterocytes and bacterial degradation

BOX 3 Bile Acid Challenge Test Procedure 1. Withhold food for 12 hours and collect a blood sample in serum tube (preprandial sample). 2. Feed a meal containing protein and fat (canned food) to encourage gallbladder contraction. 3. Collect a blood sample 2 hours after the meal (postprandial sample)

Ammonia testing requires heparinized tubes, transfer of the sample on ice, and urgent separation of plasma and is ideally performed within 30 minutes of sample collection. These requirements can make this diagnostic assay difficult to perform in private practice. Increased serum ammonia is a sensitive marker for congenital and acquired portosystemic shunts, with a reported sensitivity of 83% to 98%.11,14 However, in the absence of portosystemic shunting, ammonia is not a sensitive test of liver disease. Ammonia Tolerance Test

When ammonia is administered orally or rectally to a normal dog, it should be efficiently extracted from the portal circulation by the liver. However, dogs with a portosystemic shunt or decreased

Interpretation of Results • Fasting bile acids should be <5 mcmol/L in normal dogs and cats. asting bile acid concentrations >20 mcmol/L •F and postprandial bile acids >25 mcmol/L are considered specific for hepatobiliary disease. Preprandial values of 5 to 20 mcmol/L are considered equivocal. ccasionally, the fasting SBA concentration •O may be higher than the postprandial concentration because of early gallbladder contraction, alterations in gastrointestinal transit, or decreased response to cholecystokinin.

BOX 4 Causes of Hyperammonemia • Portosystemic shunts (congenital or acquired) • Diffuse hepatocellular disease • Urea cycle enzyme deficiencies (congenital or acquired) •U rinary infection with urease-containing bacteria and concurrent urethral obstruction • Renal failure • Ammonium chloride administration (per os or per rectum)

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hepatic functional mass cannot extract the additional ammonia, leading to an excessive increase in plasma ammonia concentration. The main indication for this test is concern for hepatic insufficiency that is not supported by routine laboratory testing. This test is unnecessary for dogs with increased baseline ammonia, in addition to posing a risk for hepatic encephalopathy in these patients. Disadvantages of oral ammonia administration include15:

• Absorption depends on gastric emptying. • Vomiting can occur. • It is stressful to the patient. • The taste of the ammonium chloride is unpleasant. The rectal ammonia tolerance test avoids these problems (Box 5).16 However, we do not routinely perform either test in dogs or cats. Postprandial Venous Ammonia Tolerance Test

The postprandial ammonia tolerance test involves a procedure similar to that of the oral or rectal ammonia tolerance test except that digested food provides the ammonia challenge and the disadvantages of oral administration are avoided. The patient is fed a commercial diet containing about 30% protein to provide 33 kcal/kg, and a blood sample is collected 6 hours after feeding. This test was reported to have 91% sensitivity for the detection of portosystemic shunting, but in

BOX 5 Rectal Ammonia Tolerance Test16 Procedure 1. Fast animal for 12 hours and collect a blood in a heparin anticoagulant tube (immediately place in an ice bath, separate plasma as soon as possible, and run assay within 30 minutes of collection). 2. Give ammonium chloride rectally (5% solution; 2 mL/kg) through a catheter inserted 20 to 35 cm into the colon. 3. Collect blood samples 20 and 40 minutes after ammonium chloride administration. Interpretation of Results • The preadministration to postadministration increase of blood ammonia concentration in normal dogs should be about 2- to 2.5-fold. • Dogs with severe ammonia concentration increases of 3- to 10-fold likely have hepatobiliary disease and/or portosystemic shunting.

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the absence of portosystemic shunts it is not as sensitive for detecting hepatic insufficiency.17

Protein C Protein C is an anticoagulant protein produced by the liver. Measurement of protein C provides information regarding liver function and perfusion. In one study,18 dogs with congenital and acquired portosystemic shunts, hepatic failure, and chronic hepatitis had decreased levels of protein C, which distinguished them from dogs with microvascular dysplasia (portal vein hypoplasia) and those without hepatobiliary disease. With use of a cutoff value of 70% activity, protein C could distinguish dogs with congenital portosystemic shunt from those with microvascular dysplasia with a sensitivity of 93% and a specificity of 88%.

Measuring SBA or ammonia concentrations provides a more accurate assessment of liver function, but it is important to be aware that patients with normal liver function test results can still have liver disease. Although these laboratory tests play an important role in diagnosing canine and feline liver disease, definitive diagnosis usually requires a combination of diagnostic imaging and cytologic or histologic assessment of liver tissue. REFERENCES 1. Hall JE, Guyton AC. Guyton and Hall Textbook of Medical Physiology, 12th ed. Philadelphia: Saunders/Elsevier; 2011. 2. Allison RW. Laboratory evaluation of the liver. In: Thrall M, Weiser, G, Allison RW, Campbell TW (eds): Veterinary Hematology and Clinical Chemistry, 2nd ed. Oxford: John Wiley & Sons; 2012:401-424. 3. Lidbury JA, Steiner JM. Diagnostic evaluation of the liver. In: Washabau RJ, Day MJ, eds: Canine & Feline Gastroenterology. St. Louis, MO: Elsevier Saunders; 2013:863-875.

CONCLUSIONS

4. Valentine BA, Blue JT, Shelley SM, et al. Increased serum alanine aminotransferase activity associated with muscle necrosis in the dog. J Vet Intern Med 1990; 4(3):140-143.

Increased liver enzyme activities are common results in small animal practice and can suggest patterns of liver disease, including hepatocellular damage, cholestasis, or both. Liver enzymes, especially ALP, are not specific for primary liver disease. To evaluate their clinical significance, a combination of history, clinical signs, physical examination, diagnostic imaging, and other liver function test results must be considered. Changes such as hypocholesterolemia or hypoalbuminemia can suggest hepatic dysfunction.

5. Webster CRL, Cooper JC. Diagnostic approach to hepatobiliary disease. In: Bonagura J, Twedt D, eds. Kirkâ&#x20AC;&#x2122;s Current Veterinary Therapy, 15th ed. St. Louis, MO: Elsevier; 2014:569-575. 6. Comazzi S, Pieralisi C, Bertazzolo W. Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples. J Small Anim Pract 2004; 45(7):343-349. 7. Center SA, Slater MR, Manwarren T, et al. Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (19801990). JAVMA 1992; 201(8):1258-1264. 8. Center SA, Baldwin BH, Dillingham S, et al. Diagnostic value of serum gamma-glutamyl transferase and alkaline phosphatase activities in hepatobiliary disease in the cat. JAVMA 1986; 188(5):507-510. 9. Kaneko JJ, Harvey J, Bruss ML. Diagnostic enzymology of domestic animals. In: Clinical Biochemistry of Domestic Animals, 6th ed. St. Louis, MO: Elsevier; 2008:358-361. 10. Rabin B, Nicolosi RJ, Hayes KC. Dietary influence on bile acid conjugation in the cat. J Nutr 1976; 106(6):1241-1246.

Brigitte B. McAtee

Brigitte B. McAtee received her DVM from Auburn University. She is currently a second-year internal medicine resident at Texas A&M University in College Station, Texas. Her clinical and research interests include infectious and immune-mediated diseases.

Jonathan A. Lidbury

Jonathan A. Lidbury graduated from the University of Glasgow and completed his internal medicine residency at Texas A&M University. Jonathan is an assistant professor of small animal internal medicine and the associate director for clinical services of the Gastrointestinal Laboratory at Texas A&M University. His clinical interests are small animal hepatology and gastroenterology, and he is involved in a wide range of research in these fields.

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11. Ruland K, Fischer A, Hartmann K. Sensitivity and specificity of fasting ammonia and serum bile acids in the diagnosis of portosystemic shunts in dogs and cats. Vet Clin Pathol 2010; 39(1):57-64. 12. Center SA, ManWarren T, Slater MR, et al. Evaluation of twelvehour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs. JAVMA 1991; 199(2):217-226. 13. Lidbury JA, Cook AK, Steiner JM. Hepatic encephalopathy in dogs and cats. J Vet Emerg Crit Care (San Antonio) 2016; 26(4):471487. 14. Gerritzen-Bruning MJ, van den Ingh TS, Rothuizen J. Diagnostic value of fasting plasma ammonia and bile acid concentrations in the identification of portosystemic shunting in dogs. J Vet Intern Med 2006; 20(1):13-19. 15. Meyer DJ, Strombeck DR, Stone EA, et al. Ammonia tolerance test in clinically normal dogs and in dogs with portosystemic shunts. JAVMA 1978; 173(4):377-379. 16. Rothuizen J, van den Ingh TS. Rectal ammonia tolerance test in the evaluation of portal circulation in dogs with liver disease. Res Vet Sci 1982; 33(1):22-25. 17. Walker MC, Hill RC, Guilford WG, et al. Postprandial venous ammonia concentrations in the diagnosis of hepatobiliary disease in dogs. J Vet Intern Med 2001; 15(5):463-466. 18. Toulza O, Center SA, Brooks MB, et al. Evaluation of plasma protein C activity for detection of hepatobiliary disease and portosystemic shunting in dogs. JAVMA 2006; 229(11):1761-1771.

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Interpretation of Dental Radiographs in Dogs and Cats Part 2: Normal Variations and Abnormal Findings Santiago Peralta, DVM, DAVDC, and Nadine Fiani, BVSc, DAVDC Cornell University

REVIEWING DENTAL RADIOGRAPHS CE TEST To view the CE test for this article, please visit tvpjournal.com.

As described in Part 1, Principles & Normal Findings (January/February 2017), dental radiography in dogs and cats constitutes an essential component of a comprehensive diagnostic plan.1-4 Part 1 also described appropriate mounting and display of radiographic films/ plates for reviewing purposes, explained a recommended workflow to review radiographs and record findings, and presented radiographic examples of normal relevant structures. This article focuses on interpretation of normal anatomic variations as well as congenital and pathologic abnormal findings on dental radiographs in dogs and cats (Box 1). Both articles assume the reader is familiar with basic dental radiographic acquisition techniques, concepts, and skills.

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Teeth Abnormally Present and/or Absent Persistent deciduous teeth with the permanent counterpart present (Figures 1A and 1B) are considered a pathologic condition of suspected genetic origin that predisposes the

BOX 1. Definitions: Normal Versus Abnormal • Normal radiographic findings are defined as those consistent with what is considered typical, average, or expected and are free of any indicators of disease. Normal variations are defined as radiographic • findings that deviate from what is considered typical, average, or expected but do not otherwise indicate any preventive or therapeutic medical or surgical intervention, monitoring, or maintenance recommendations. Abnormal radiographic findings are any • findings considered pathologic.

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involved permanent teeth to periodontitis and malocclusion. This is a common condition in dogs, especially toy breeds, but uncommon in cats. The treatment of choice is extraction of the persistent deciduous teeth. Although the initial diagnosis is clinical, radiographs are necessary to document the orientation of the root relative to the permanent counterpart and/or other teeth in the immediate vicinity, as well as the degree of root resorption (if present). This information is essential to minimize potential collateral damage when extracting a persistent deciduous tooth. Persistent deciduous teeth without a permanent counterpart (Figures 1C and 1D) are usually smaller and slightly more radiolucent than the contralateral, adjacent, and/ or opposing permanent teeth.

Clinicians should keep in mind that the morphology of a persistent deciduous premolar resembles that of the permanent tooth immediately distal to it (eg, the deciduous fourth premolar resembles the permanent first molar) to it but is significantly smaller. Clinicians should be also familiar with normal deciduous tooth exfoliation times and know which teeth have a deciduous predecessor (ie, deciduous dental formula).5,6 Retained (unerupted or embedded) teeth (Figures 2A and 2B) are important because they can result in dentigerous cyst formation (see Jaw Lesions of Developmental Origin)7 and are, therefore, considered pathologic. Although deciduous teeth may be retained, most retained teeth are permanent.

The cause of tooth retention is not always apparent. If a physical barrier (eg, bone, another tooth) did not allow the tooth to erupt, the tooth can be referred to as impacted. Retention of the first premolar tooth appears to be relatively common in brachycephalic dogs, suggesting possible genetic mechanisms.7 In some cases, historical or radiographic

findings may suggest a traumatic origin (eg, local trauma during odontogenesis); some retained teeth may be dysplastic. As retained teeth are not visible clinically, radiographs are necessary to establish a diagnosis. Dental radiographs are indicated whenever there are missing teeth with no obvious cause (eg, previous tooth loss, extraction). Congenitally missing teeth (Figure 2B) are considered an incidental finding. The term

FIGURE 1. Persistent deciduous teeth. FIGURE 1A shows a persistent right maxillary deciduous canine tooth in a 7-month-old dog; the permanent counterpart is present. FIGURE 1B shows a persistent right maxillary deciduous canine tooth in a 6-month-old cat; the permanent counterpart is present. FIGURE 1C shows a persistent deciduous left maxillary second premolar tooth in a 1-year-old dog; the permanent counterpart is not present. FIGURE 1D shows a persistent deciduous left mandibular fourth premolar tooth in the same dog as Figure 1C; the permanent counterpart is not present.

FIGURE 2. Retained (unerupted or embedded) teeth. FIGURE 2A shows a retained right mandibular first premolar tooth in a 6-year-old dog. FIGURE 2B shows retained left and right mandibular canine teeth in a 4-year-old dog. Note that the left and right mandibular premolar teeth are missing; based on history and breed, the absence of these teeth was considered congenital in origin.

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hypodontia is applied when several teeth are absent; the term oligodontia is a relative term that can be used when only a few teeth are present.8 Congenitally missing teeth should be suspected if dental radiographs do not show retained and/or resorbing roots, unerupted teeth, or vacated and/or remodeling alveoli.

Supernumerary teeth (polydontia) (Figure 3B) can be present at any location in the dental arches. More than one supernumerary tooth can be present in the same area. Other than creating a plaqueretentive area and, therefore, predisposing the animal to periodontal disease, supernumerary teeth are usually considered a normal anatomic variation.

Crowding and rotation (Figure 3A) may be considered normal or part of the standard in certain breeds (eg, brachycephalic dogs). Teeth present in severely crowded areas may be rotated owing to the lack of space; this is particularly common with the maxillary third premolar tooth of dogs with maxillary brachygnathia. Teeth that are in close proximity represent a plaqueretentive area and may therefore predispose an animal to focal periodontitis. Although crowding and rotation can be appreciated clinically, dental radiographs are useful to document the periodontal status of the teeth involved (Box 2).

Malformations

FIGURE 3. Crowding and supernumerary teeth. FIGURE 3A shows crowding of premolars with rotation and palatoversion of the right maxillary third premolar tooth in a 6-year-old dog. FIGURE 3B shows a supernumerary right maxillary first premolar tooth, as well as crowding of premolars with rotation and palatoversion of the right maxillary third premolar tooth in a 3-year-old dog.

Enamel hypoplasia (Figures 4A and 4B) is considered pathologic; affected areas are plaque retentive and predispose affected teeth to caries and periodontal disease. The defects can be seen clinically and radiographically as irregularities in the enamel. Teeth with enamel hypoplasia can also have dysplastic roots that are only detectable radiographically.9 Dysplasia (odontodysplasia) (Figure 5A) of the crowns of erupted teeth is evident clinically; however, malformation of roots or of unerupted teeth is only detectable radiographically. If only one or a group of adjacent teeth are malformed, local trauma or infection during odontogenesis is suspected as the cause. If odontodysplasia is generalized or semigeneralized, systemic acquired or congenital causes are suspected.

BOX 2. Determining Periodontal Status Radiographs are useful to establish the severity of periodontitis. In general, periodontitis is classified as: • Mild if <25% of alveolar bone has been lost • Moderate if 25% to 50% of alveolar bone has been lost • Severe if >50% of alveolar bone has been lost

FIGURE 4. Enamel hypoplasia. FIGURE 4A shows the clinical appearance of enamel hypoplasia affecting the maxillary incisors and canine teeth in a 7-month-old dog. FIGURE 4B is a lateral projection of the left maxillary canine tooth on the same dog; note the defective enamel at the mesial aspect of the cusp.

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In many cases, the severity and extent of periodontitis on radiographs determine prognosis and treatment choice (ie, extraction, periodontal surgery, or conservative treatment). As a general rule, if severe periodontitis is present, extraction of the affected tooth is indicated.

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Dens-in-dens (dens invaginatus; Figure 5B) is a rare malformation in which the enamel and underlying dentin invaginate towards the pulp cavity, sometimes resulting in a direct or indirect communication and, in some cases, secondary endodontic disease. The malformation may or may not be clinically evident. Radiographically, it may appear as a small tooth-like structure within the pulp cavity, and endodontic disease (see Endodontic Findings) is often present. Double teeth (Figures 6A and 6B) appear to have two crowns due to gemination or fusion. Gemination occurs when two crowns originate from a single root; fusion occurs when the roots of two independent teeth fuse. Clinically, these conditions are indistinguishable; radiographs are necessary to determine if double teeth are due to gemination or fusion. Regardless, double teeth are most often an incidental finding. Concrescent or fused roots (Figure 7A) represent nonpathologic anatomic variations of clinical relevance because they may affect the surgical approach if a tooth requires extraction. The roots of multirooted teeth are usually slightly divergent with alveolar bone in between. However, in some cases, concrescence occurs when the roots of a tooth converge and are only separated by cementum. In other cases, actual fusion of the roots occurs. Dilacerated roots (Figure 7B) have an acute angulation at their apical third. Although this is considered a developmental abnormality, it is not usually of clinical significance, unless the tooth has to be extracted for any reason. The extraction may require additional root exposure to avoid fracturing the tooth. Peg teeth are relatively small, permanent mandibular premolar teeth with only one root (Figure 8). These are usually considered an anatomic variation of little or no clinical significance.

Jaw Lesions of Developmental Origin Dentigerous cysts, by definition, are associated with unerupted teeth. The most commonly

associated tooth is the first mandibular or maxillary premolar in dogs7; dentigerous cysts have not been reported in cats. The cystic lesion is usually visible radiographically as an area of geographic bone loss (see Jaw Lesions) of varying size; in some cases the lesion involves adjacent teeth (Figure 9A).

FIGURE 5. Odontodysplasia and dens-in-dens. FIGURE 5A shows a dysplastic root of the right maxillary canine tooth in a 9-year-old dog. Periodontitis of varying severity is present at the incisors, canine, and premolar teeth, as well as external inflammatory tooth resorption at the second premolar. FIGURE 5B shows dens-in-dens affecting the right mandibular first molar tooth of a 5-year-old dog; note the abnormal appearance of the crown just above the furcation area and extending mesially.

FIGURE 6. Double teeth. FIGURE 6A is a clinical image of a right maxillary first incisor tooth in a 4-year-old dog with seemingly two crowns. FIGURE 6B shows the occlusal radiograph of the same dog; note that the double maxillary incisor corresponds to fusion.

FIGURE 7. Fused and dilacerated roots. FIGURE 7A shows fused roots at the left mandibular second molar tooth in a 5-year-old dog. FIGURE 7B shows dilacerated roots at the left mandibular first molar tooth in another 5-year-old dog.

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Mandibular radiopacities are round or oval welldefined radiopacities observed along the caudal or midmandibular body (Figure 9B). In the absence of clinical signs or anatomic proximity to an endodontically diseased tooth, the finding can be considered incidental and is likely the result of sclerotic bone.10

Periodontal Findings Calculus deposits, when thick, can be visible radiographically (Figure 10) because of their mineralized nature. However, the amount of calculus accumulation visible clinically and radiographically should not be used as an indicator of the severity or extent of periodontal disease. Alveolar bone loss by definition is pathologic. Namely, if alveolar bone loss is present, a diagnosis of periodontitis is established. Of the 4 tissues that

compose the attachment apparatus of teeth (the periodontium), alveolar bone is the only one that is directly visible on radiographs. In general, alveolar bone loss can follow a vertical or a horizontal pattern. Vertical bone loss is when the defect is perpendicular to the cementoenamel junction (CEJ; Figures 11A, 11B, and 11C); horizontal bone loss is when the defect is parallel to the CEJ. A combined pattern can also occur. The pattern of bone loss is clinically relevant as it can affect therapeutic options. Buccal bone expansion is an alveolar bone loss pattern that seems to be unique to cats. Buccal bone expansion appears radiographically as bulbous and/or thickened alveolar bone with varying degrees of vertical bone loss, primarily on the buccal aspect of canine teeth (Figure 11D). More than one tooth can be affected. Furcation defects can occur at a very early stage of periodontitis because the furcation area is very close to the alveolar margin. Furcation involvement is used to describe bone loss that is observed at the furcation but does not appear to communicate all the way through (Figure 11C). In contrast, furcation exposure refers to through-and-through defects (Figures 11A and 11C). If furcation exposure is detected, the long-term periodontal prognosis is poor, and extraction is most often indicated, regardless of severity of periodontitis. Periodontalâ&#x20AC;&#x201C;endodontic lesions may be detectable radiographically if alveolar bone loss

FIGURE 8. Peg tooth. The radiograph shows an abnormally small and single-rooted left mandibular third premolar tooth in a 6-year-old cat.

FIGURE 9. Jaw lesions. FIGURE 9A shows an unerupted right mandibular first molar tooth with an associated dentigerous cyst in an 8-year-old dog. FIGURE 9B shows a caudal mandibular radiopacity just rostral to the mesial root of the right mandibular first molar tooth in a 6-year-old dog.

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FIGURE 10. Calculus. Heavy calculus deposits are visible radiographically over the left maxillary fourth premolar tooth in an 8-year-old dog.

CONTINUING EDUCATION

(ie, periodontitis) has allowed bacteria to enter the pulp cavity via the apical delta or accessory canals, with ensuing apical periodontitis. The radiographic characteristics usually include some degree of alveolar bone loss and periapical lucency around the root(s) (Figure 12). The prognosis of periodontal–endodontic lesions is poor.

(it is determined clinically). The loss of crown integrity (Figure 13A) should alert and encourage clinicians to look for radiographic indicators of

Endodontic Findings Crown integrity may be lost because of traumatic fractures. Tooth fractures are visible radiographically, although pulp exposure cannot be reliably diagnosed on a radiograph

FIGURE 12. Periodontal–endodontic lesions. This radiographs shows a right mandibular first molar tooth in a 7-year-old dog. There is moderate to severe combined horizontal and vertical bone loss and welldefined periapical lucencies at both roots.

FIGURE 11. Alveolar bone loss. FIGURE 11A shows moderate horizontal bone loss with furcation exposure affecting the left mandibular fourth premolar and first and second mandibular teeth of a 10-year-old-dog. The first molar tooth also has vertical bone loss at the mesial aspects of both roots. Note the inflammatory root resorption affecting the distal root of the second molar tooth. FIGURE 11B shows near-total loss of attachment due to severe horizontal bone loss at the left mandibular first and second incisors in the same dog and left and right mandibular canine teeth. Note the inflammatory root resorption at the apical area of the first incisor tooth; also note the calculus deposits on the crowns of the canine teeth. Figure 11C shows moderate horizontal bone loss with furcation exposure at the right mandibular fourth premolar and first molar teeth in a 15-year-old cat; note the inflammatory root resorption at the furcation areas. FIGURE 11D shows buccal bone expansion affecting the right maxillary canine tooth more than the left in a 9-year-old cat; note the inflammatory root resorption affecting the right canine tooth; note also the retained roots present at the incisor area.

FIGURE 13. Endodontic disease. FIGURE 13A shows an occlusal maxillary radiograph of a 5-year-old dog; note the fractured crown of the right maxillary canine tooth and the relatively wide pulp cavity when compared with the contralateral tooth. FIGURE 13B shows a fractured middle cusp of the left mandibular first molar tooth in a 6-year-old dog; note the welldefined periapical lucencies at both roots. FIGURE 13C shows the occlusal maxillary radiograph of a 9-year-old dog with severe abrasion of several incisors; note the relatively wide pulp cavity of the right maxillary first incisor tooth and the associated well-defined periapical lucency. FIGURE 13D shows pulp stones at the mesial and middle pulp horns of the left mandibular first molar tooth in a 4-year-old dog; the tooth is otherwise periodontally and endodontically sound.

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endodontic disease (see Apical periodontitis and Relatively wide pulp cavities) because the most common cause of endodontic disease is trauma. Apical periodontitis is inflammation of the periapical tissues that invariably occurs in the presence of untreated endodontic disease (eg, inflamed or necrotic pulp). This inflammatory process is detectable radiographically after enough lysis of the associated bone has occurred (Figure 13B). Typically, the lesion appears as an ill- or well-defined round, lucent area that encompasses the apical portion of the root(s). Lack of radiographically detectable periapical lucency does not rule out apical periodontitis. Relatively wide pulp cavitiesâ&#x20AC;&#x201D;when compared with contralateral, opposing, or adjacent teethâ&#x20AC;&#x201D; may indicate a longstanding nonvital pulp (Figures 13A and 13C). Clinicians should be aware that a lack of discrepancy in pulp cavity width does not rule out endodontic disease, especially in cases of endodontic disease of relatively short duration (a few days or weeks).

cavity on dental radiographs, sometimes in otherwise clinically and radiographically healthy teeth (Figure 13D). In the event endodontic intervention is required for unrelated causes, pulp stones may interfere with root canal instrumentation. Chevron signs are widened periodontal ligament spaces in the apical areas of endodontically sound teeth, often in the shape of a chevron, resembling radiographic signs of apical periodontitis (Figure 14). This occurs most frequently at the maxillary incisors, canines, and mandibular first molar teeth. It is believed these areas are normal anatomic variations and possibly correspond to vascular channels in the bone.11 A chevron sign is suspected in the absence of clinical and radiographic signs of endodontic disease; in some cases, however, it is very difficult to differentiate between a chevron sign and pathologic changes.

Pulp stones are considered incidental findings that appear as mineralized structures within the pulp

FIGURE 14. Chevron sign. This radiograph is the lateral view of the right maxillary canine tooth in an 8-year-old dog. Note the wide lucent space at the apex. The lesion is not bulbous, round, or encompassing of the entire apical area, and the lamina dura appears intact. Given the lack of other radiographic indicators of endodontic disease, and in the absence of clinical signs, this finding should not necessarily be considered pathologic.

IMAGING ESSENTIALS

FIGURE 15. Tooth resorption. FIGURE 15A shows advanced inflammatory tooth resorption affecting the left mandibular fourth premolar and first molar teeth in an 8-year-old cat. FIGURE 15B shows advanced replacement resorption affecting the left and right mandibular canine teeth in a 14-year-old cat. FIGURE 15C shows replacement resorption affecting both roots of the left mandibular fourth premolar and mesial root of the mandibular first molar in a 7-year-old dog; note the loss of periodontal ligament space and sclerotic alveolar bone around the affected roots. FIGURE 15D shows inflammatory root resorption secondary to apical periodontitis at the left mandibular canine tooth in a 7-year-old dog; note the irregular and relatively short apical third of the tooth compared to the contralateral.

VETFOLIO WORK Sherri O’Brien, DVM VetFolio User Since 2015

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See how Sherri puts VetFolio to work: Getting Started “We as veterinarians are good at multitasking. I can cook dinner, fold laundry or work out on my exercise bike while I listen to a class. I can even listen to a podcast while I am driving to an alumni event. The education comes to you!” Staying Fresh “Our profession is constantly changing, and VetFolio allows you to engage in this change. If you have recently graduated, there are surgery videos and classes on the subjects you may have not covered deeply in school. If you have been out of school for over five years, VetFolio can help you stay current and academically fresh. We are never too old to learn!” Becoming a Pro “Everyone has their own way that they prefer to learn. There are surgery videos, short podcasts, longer lectures, and articles at your fingers. You can choose how you take your educational adventure.”

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Continuing the Experience “I use the information learned on VetFolio daily. There are a variety of topics that I incorporate into my daily discussions with clients, technicians and rescue groups. Whether it has to deal with the pros and cons of early spay/neuter or the life expectancy of a dog with splenic HSA, the classes offer information that can be used in real-life practice. VetFolio also allows one to stay medically current and have access to the newest products coming out on the market!” Making #Goals I truly try to obtain 100 hours of CE a year. At least 40 are at conferences. I look forward to going to the NAVC Conference every year.

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Other Dental Findings Tooth resorption may be secondary to inflammatory processes (ie, inflammatory root resorption) or of unknown origin (Figures 15A through 15D).12 Although tooth resorption is often clinically detectable, radiographs are necessary to reveal the actual extent, severity, and radiographic pattern of resorption. The pattern and stage of tooth resorption help determine the surgical approach (ie, extraction or coronectomy), the level of surgical difficulty, and possible complications.13 Caries have not been described in cats, and the prevalence of caries is relatively low in dogs compared to humans. The radiographic appearance of a caries lesion depends on the stage of disease. Very early caries lesions may or not be detectable radiographically. Advanced caries lesions involving the dentin appear as cup-shaped cavitated lesions that may or may not extend into the pulp cavity (Figure 16). Abrasion and attrition are wearing of teeth due to contact with an external object or surface (abrasion) or another tooth (attrition). Radiographically, abrasion and attrition usually appear as even or smooth loss of tooth surfaces of varying severity, often affecting multiple teeth (Figures 17A and 17B). Wear of dental structures can result in damage to the pulp; therefore,

clinicians should be attentive to radiographic signs of endodontic disease (see Endodontic Findings).

Jaw Structures Jaw lesions appear on dental radiographs as areas of bone loss of inflammatory, cystic, or neoplastic origin. The bone loss can have a geographic, permeative, or moth-eaten pattern.14 A geographic pattern is characterized by an area of bone loss that is uniform in appearance and has well-defined borders (Figure 18A). In contrast, a permeative pattern of bone loss is an area with poorly defined borders (Figure 18B). Multiple contiguous areas of bone loss with poorly defined borders characterize a moth-eaten pattern. Maxillomandibular fractures may be detected on dental radiographs (Figure 19). However, patients that have sustained maxillofacial trauma often have multiple injuries that are not detectable radiographically; therefore, computed tomography

FIGURE 17. Abrasion and attrition. FIGURE 17A shows wear of the occlusal surface of the right mandibular second and third molar teeth in a 6-year-old dog. FIGURE 17B shows mild wear of the distal aspect of the right mandibular canine tooth in a 6-year-old dog, consistent with cage-biting behavior.

FIGURE 16. Caries lesion. An advanced caries lesion affecting the left maxillary first molar tooth in a 5-yearold dog; note the loss of crown integrity and apical periodontitis secondary to pulp involvement.

IMAGING ESSENTIALS

FIGURE 18. Bone loss jaw lesions. FIGURE 18A shows a multilocular lesion of geographic bone loss involving the right mandibular third and fourth premolar teeth in a 5-year-old dog. FIGURE 18B shows extensive permeative bone loss affecting both rostral mandibles in a 15-year-old cat.

CONTINUING EDUCATION

(CT) is the imaging modality of choice to detect mandibular and/or maxillary fractures.15 Symphyseal separation may be observed if the fibrocartilaginous fibers at the symphysis have been stretched or torn as a result of trauma. The symphyseal space may appear wider than usual and an occlusal discrepancy between the right and left incisor teeth may be observed (Figure 20).

Limitations of Dental Radiography Dental radiographs have some limitations and disadvantages compared with other modalities. For instance, unlike advanced imaging modalities (eg, CT, cone-beam CT), dental radiographs represent 2-dimensional images of 3-dimensional structures. Given the anatomic complexity of certain areas (eg, caudal maxilla) and the level of superimposition of dental and related structures, radiographs may fail to reveal lesions depending on their nature, location, extent, and severity. Moreover, dental radiographs are useful only for imaging teeth and associated structures in the immediate vicinity. They have little or no value for imaging other maxillofacial structures. In cases of maxillofacial trauma, temporomandibular joint disorders, and neoplasia of the head and neck (including oral tumors), CT (multislice or conebeam CT) may be indicated.14â&#x20AC;&#x201C;16 If a CT scan of the head is already available, dental radiographs may not be

FIGURE 19. Mandibular fracture. This radiograph shows a comminuted mid-body fracture between the left mandibular third and fourth premolar teeth in an 8-year-old dog.

necessary to detect radiographic signs of periodontitis or endodontic disease.17 Cone-beam CT has been proposed as a valid imaging modality for the diagnosis of dental disease in animals, but its precise clinical applications and limitations have not been systematically investigated.18 Dental radiography has traditionally been, and still is, considered the gold standard for the diagnosis of dental disease in dogs and cats. In a general practice setting, its diagnostic value and the relatively low cost of required equipment make dental radiography the most practical imaging modality. References 1.

Eisner ER. Standard of care in North American small animal dental service. Vet Clin North Am Small Anim Pract 2013;43:447-469.

2. Holmstrom SE, Bellows J, Juriga S, et al. 2013 AAHA dental care guidelines for dogs and cats. JAAHA 2013;49:75-82. 3. Verstraete FJ, Kass PH, Terpak CH. Diagnostic value of full-mouth radiography in dogs. Am J Vet Res 1998;59:686-691. 4. Verstraete FJ, Kass PH, Terpak CH. Diagnostic value of full-mouth radiography in cats. Am J Vet Res 1998;59:692-695. 5. Shabestari L, Taylor G, Angus W. Dental eruption pattern of the beagle. J Dent Res 1967;46:276-278. 6. Wiggs RB, Lobprise HB. Veterinary Dentistry: Principles and Practice. Lippincott-Raven Publishers, 1997. 7. Verstraete FJ, Zin BP, Kass PH, et al. Clinical signs and histologic findings in dogs with odontogenic cysts: 41 cases (1995-2010). JAVMA 2011;239:1470-1476. 8. Fulton AJ, Fiani N, Verstraete FJ. Canine pediatric dentistry. Vet Clin North Am Small Anim Pract 2014;44:303-324.

FIGURE 20. Symphyseal separation. This radiograph shows an abnormally wide space at the symphysis of a 2-year-old dog consistent with symphyseal separation.

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PEER REVIEWED 9. Fiani N, Arzi B. Diagnostic imaging in veterinary dental practice. JAVMA 2009;235:271-273. 10. Carle DS, Shope BH. Diagnostic imaging in veterinary dental practice. JAVMA 2012;241:1283-1285.

Santiago Peralta

Santiago Peralta, DVM, DAVDC, is an assistant professor of dentistry and oral surgery at Cornell University College of Veterinary Medicine. His clinical and research interests include the microbial pathogenesis of dental diseases, comparative aspects of maxillofacial birth defects, comparative aspects of maxillofacial imaging, and molecular mechanism of oral tumor formation in dogs and cats. Dr. Peralta received his DVM from Universidad de La Salle in Bogota, Colombia, and completed a 3-year residency in dentistry and oral surgery at the University of California, Davis.

11. DuPont GA, DeBowes LJ, eds. Atlas of Dental Radiography in Dogs and Cats. St. Louis, MO: Saunders Elsevier; 2009. 12. Peralta S, Verstraete FJ, Kass PH. Radiographic evaluation of the types of tooth resorption in dogs. Am J Vet Res 2010;71:784-793. 13. Peralta S, Verstraete FJ, Kass PH. Radiographic evaluation of the classification of the extent of tooth resorption in dogs. Am J Vet Res 2010;71:794-798. 14. Amory JT, Reetz JA, Sanchez MD, et al. Computed tomographic characteristics of odontogenic neoplasms in dogs. Vet Radiol Ultrasound 2014;55:147-158. 15. Bar-Am Y, Pollard RE, Kass PH, et al. The diagnostic yield of conventional radiographs and computed tomography in dogs and cats with maxillofacial trauma. Vet Surg 2008;37:294-299. 16. Arzi B, Cissell DD, Verstraete FJ, et al. Computed tomographic findings in dogs and cats with temporomandibular joint disorders: 58 cases (2006-2011). JAVMA 2013;242:69-75.

Nadine Fiani

Nadine Fiani, BVSc, DAVDC, is an assistant clinical professor of dentistry and oral surgery at Cornell University College of Veterinary Medicine. She has an interest in education and a clinical interest in endodontics and zoo dentistry. Dr. Fiani received her veterinary degree from the University of Sydney and completed a rotating internship followed by a 3-year residency in dentistry and oral surgery at the University of California, Davis. Before her current position, Dr. Fiani spent 3 years in private referral practice in Sydney.

17. Campbell RD, Peralta S, Fiani N, Scrivani PV. Comparing intraoral radiography and computed tomography for detecting radiographic signs of periodontitis and endodontic disease in dogs: an agreement study. Front Vet Sci 2016;3. 18. Soukup JW, Drees R, Koenig LJ, et al. Comparison of the diagnostic image quality of the canine maxillary dentoalveolar structures obtained by cone beam computed tomography and 64-multidetector row computed tomography. J Vet Dent 2015;32:80-86. 19. Tsugawa AJ, Verstraete FJ. How to obtain and interpret periodontal radiographs in dogs. Clin Tech Small Anim Pract 2000;15:204-210. 20. Lommer MJ, Verstraete FJ, Terpak CH. Dental radiographic technique in cats. Compend Contin Educ Pract Vet 2000;22:107-116. 21. Floyd MR. The modified Triadan system: nomenclature for veterinary dentistry. J Vet Dent 1991;8:18-19.

Notes on Images All radiographic images provided are representative examples that support the explanations presented in the article. They are displayed based on labial mounting and considered to be of diagnostic quality. Some of the images have been cropped, but the structures of interest have not been altered or enhanced.

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All images were acquired following standard technique for small animals19,20 using a commercially available dental radiography unit (Heliodent DS, Sirona, Bensheim, Germany) and a computerized radiographic processor using phosphor plates of size 0, 2, or 4 with corresponding software (CS7600, Carestream, Rochester, NY). Due to space limitations, most radiographs shown are from dogs. In case some readers are unfamiliar with other accepted systems (ie, modified Triadan), anatomic dental nomenclature is used here. 21 For more information, interested readers are encouraged to consult a more specialized source.

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The College of Veterinary Medicine at Cornell University (CVM) owns and retains the copyrights to all images. The CVM grants permission to use the provided images within the context of the articles titled Interpretation of Dental Radiographs in Dogs & Cats – Part 1: Principles & Normal Findings and Interpretation of Dental Radiographs in Dogs & Cats – Part 2: Normal Variations and Abnormal Findings.

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Separation-Related Disorders: The Differences Between Dogs and Cats Lisa Radosta, DVM, DACVB Florida Veterinary Behavior Service Ariel Fagen, DVM Florida Veterinary Behavior Service Veterinary Behavior Consultations of Colorado

SIGNALMENT AND PREDISPOSITIONS

Separation-related disorders1 are characterized by physiologic and emotional distress occurring only when the patient anticipates or experiences an actual or virtual (eg, person present but not accessible) absence from a person with whom the pet is socially bonded.

Clinical signs in cats and dogs may develop at any age, in any breed, and in either sex. There is evidence that 55% of affected dogs exhibit clinical signs before 3 years of age8 and that cats older than 7 years may be predisposed.2 Known predisposing factors in dogs include neutering,9 absence of obedience training,8–10 and adoption from a shelter or rescue or being a found stray.8,9,11 Predisposing factors in both dogs and cats include daily extended periods of time without the owner, change in schedule or family makeup, and

Separation-related disorders are well recognized in dogs, but they are less understood in cats because of a lack of representation in the literature.2,3 Prevalence in dogs presented to a behavior specialist ranges from 14% to 50%4–7 compared with 19% in cats.2 These disorders are probably underreported in cats.

SYMPTOMS OF A SEPARATION-RELATED DISORDER can include destructive acts, such as destroying household objects, chewing furniture, and frantic scratching at door frames and window sills.

shutterstock.com/Michelle D. Milliman

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single-owner households.3,9 There may also be a hereditary predisposition in both dogs and cats.3,12

CLINICAL SIGNS Onset of clinical signs in dogs and cats may occur with life events, lifestyle changes, or development of medical or other behavioral disorders (Box 1).3,13,14 Dogs with separation-related disorders can be divided into three classes: A, B, and C.1 Dogs in class A may show initial signs in puppyhood and display hyperattachment1 to one person by following them and soliciting attention and physical interaction.1,3,9,13,16,17 Dogs in class B display signs triggered by a change in schedule or lifestyle or by aging and often show distress only when left completely alone.1,14 Dogs in class C show clinical signs after a fearful experience and do not show hyperattachment.1 Clinical signs in both cats and dogs may start in anticipation of the owner’s departure.2,3,16 Dogs may exhibit aggression in an apparent attempt to keep the owner from departing3,8,12 or appear apathetic and withdrawn. Some dogs avoid participating in morning routines.8 Particular signs reported in cats include urination on the owner’s bed and destruction; these signs are more common among males than females.2,3

DIAGNOSIS Step 1: Collect a Targeted History Even in affected dogs, as few as 13% of owners may seek assistance.17 A simple behavior questionnaire with questions such as “Has your pet urinated or defecated in your house since your last visit?” or “Does your pet act differently as you get ready for work?” can decrease the time invested in the examination room. Signs of anxiety with departure cues strongly support a diagnosis of separation anxiety.13 Behaviors that indicate13 a diagnosis other than separation anxiety are those that:

• Do not occur consistently and exclusively with departures • Occur only in conjunction with other environmental events (eg, storms) • Occur only when the pet is confined

Step 2: Perform a Physical Examination and Appropriate Diagnostic Testing Complete a full examination. In dogs, monitor for caudal wear of the canines, a marker of crate chewing.14 Complete blood count, blood chemistry, urinalysis, and thyroid testing should be performed to screen for underlying medical

BOX 1 Clinical Signs of Separation Anxiety in Dogs and Cats2,8,9,13–16 • Vocalizationa

• Attempts to escape

• Rearranging the owner’s things

• D estructiona

• Pacing

• I ncreased motor activity

• Eliminationa

• Aggression

• Trembling

• Anorexia

• Withdrawal

• Inability to settle

• Lethargy

• E xcessive licking or groominga

• Diarrheaa

• Tachypnea

•R itualized circling

• Hypersalivation

• S elf-mutilation

• Compulsive behaviors

• D epressiona

• Freezing

• Fearful postures

• Tachycardia

• E xaggerated greetings

• Inactivitya

• Vomiting

Reported in cats. 2,16

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causes of the clinical signs and serve as a baseline before medication use.8,13 Conditions that can cause discomfort or pain can present similarly to anxiety.18 Depending on clinical presentation, initial diagnostics, and examination findings, additional diagnostics may be warranted.

Step 3: Rule Out Behavioral Contributors or Differentials As many as 30% to 60% of dogs have comorbid noise and storm phobias.9,15,19 Confinement distress could be the sole cause of anxiety or a very large contributor.3,8,13 Testing the dog’s distress level with confinement when the owners are present13 and no confinement when the owners are not present can rule this out. Other diagnostic differentials to consider are listed in Box 2. Video recording is helpful13 because many signs are “silent,” with no evidence of the behavior upon the owner’s return. In addition, video can confirm the diagnosis, provide a baseline, have treatment implications, and help monitor for treatment success. There are many ways to inexpensively record video, including smartphones, apps, and home security systems.

TREATMENT Step 1: Educate Owners may have preconceived ideas of the cause of their pet’s disorder. The owner should understand that his or her pet is not acting this way out of spite or anger; that the owner didn’t cause the behavior by loving the pet too much, spoiling it, or not being dominant; and that the pet is not bored and getting another pet will not help.1,9,13

Step 2: Avoid and Manage Distress Immediately As quickly as possible, put into place strategies and treatments to decrease or ameliorate the distress. This will ease owner stress and improve the pet’s quality of life while long-term treatments are instituted. Avoid departures in the initial stages of treatment14 through use of daycare, boarding, house sitters, or bringing the pet along when the owner departs. Confinement can prevent destruction but also can increase anxiety13,14 and is generally avoided because of the comorbidity with confinement anxiety. If

BOX 2 Differential Diagnoses for Separation Anxiety in Dogs and Cats3,8,13,14 DOGS and CATS

DOGS

CATS

• Storm phobia

• Overactivity

itterbox aversion •L

• N oise phobia

•S ocially facilitated

•L itterbox preference

•C onfinement distress

• D rive to roam

•S ubstrate aversion

•P anic disorder

• Play

• S ubstrate preference

• Cognitive dysfunction

• N ormal puppy behavior

• N ormal scratching behavior

• M arking

• L ack of enrichment/stimulation

• Fear • E xcitement shutterstock.com/zossia

• Reaction to external stimuli • Territorial aggression • L ack of house training •L ack of opportunity to reach elimination areas

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crated, the pet should not wear a collar because of strangulation risk with escape attempts.14 Block off areas most likely to be damaged and clean soiled areas of the residence13 with a bacterial/enzymatic cleaner, like Anti-IckyPoo (MisterMax Quality Products) or other cleaners such as Urine Off or Zero Odor.20 Play the radio, white noise, or music to prevent the pet from retriggering to external stimuli.13 Instruct the owners to avoid punishment, such as yelling, hitting, and shock collars. These types of treatments are contraindicated13,16 because they can increase anxiety and make the course of treatment longer. Be sure to remind clients that their pet is suffering from an emotional disorder and no amount of punishment will fix it. Pair owner departures with positive things by setting up food-searching games and food toys3,13 before the first signs of distress. Adjust the pet’s feeding schedule to increase the likelihood of eating when the owner is gone,8 and use enticing food. Recommend that the owner keep departures and returns low-key.13 A regular and predictable routine should be provided.16 Consider medication. Medications can directly decrease anxiety and panic.14 Situational medications that take effect within 1 to 2 hours of administration can be essential in the treatment of separation anxiety and should be considered at the first appointment. Ideally, the medication would take effect before the patient shows clinical signs. Benzodiazepines (avoid diazepam in cats), trazodone, gabapentin, and clonidine can be used to reduce anxiety quickly.13,14 Acepromazine is not a good anxiolytic so should not be used alone, but it can be used at low dosages as an adjunct if additional sedation is needed.13

Step 3: Institute Behavior Modification So the Pet Can Learn to Stay Calm for Departures Proper implementation of behavior modification maximizes the likelihood of a long-term positive outcome. In our experience, behavioral treatments increase the probability that medication doses can be reduced over time, if that is a goal of treatment,

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and decrease the likelihood of relapse. Ideally, a veterinary behavior technician within the practice would conduct behavior modification sessions in clear communication with the veterinarian so the plan and medications can be adjusted efficiently. All treatments should focus on conditioning the pet to feel calm and happy during departures by using things the pet likes. Independence and relaxation exercises are a cornerstone of treatment.8,13 Examples include food-searching games at an increasing distance from the owner,10 relaxation exercises, and rewarding calm behavior.16 Treatment can be made simple in some cases by using food toys and remote treat-dispensing devices. Structured interactions between the pet and the owner through positive reinforcement (eg, cueing the pet to sit before the pet receives attention) can promote consistency and predictability in the pet’s life.13,14 Adequate exercise and enrichment should be given to meet the pet’s general needs.13,16 Additional behavioral modification includes uncoupling departure cues and desensitization and counterconditioning to departures.13,14 Dogs can be taught to be comfortable with confinement if that is a goal of the owner or helps the dog feel safe.13 Caution should be exercised when recommending this because it can take months for often little yield. As a warning, if pets are pushed too fast through these protocols, these methods can backfire and actually sensitize the pet to departures, making the patient worse.14 If you do not feel comfortable enacting these treatments and do not have a behavior technician on whom to rely, refer your patient to a board-certified veterinary behaviorist. If such a specialist is not available in your area, try the American Veterinary Society of Animal Behavior (avsab.org) to find someone qualified.

Step 4: If Indicated, Prescribe Longer-Acting Pharmaceuticals Longer-acting pharmaceuticals may be indicated if owners have a difficult time predicting departures (making situational medications difficult to implement) or if situational medications

PEER REVIEWED 3. Schwartz S. Reference point: separation anxiety syndrome in dogs and cats. JAVMA 2003;222(11):1526-1532.

Lisa Radosta

Lisa Radosta, DVM, DACVB, is the owner of Florida Veterinary Behavior Service in West Palm Beach, Florida. She completed a residency in behavioral medicine at the University of Pennsylvania, where she received two national research awards. She has authored textbook chapters, produced continuing education podcasts for VetGirl, published research papers on thyroid disease and clinician–client communication, and lectured across the country and internationally. She is the behavior section editor for Small Animal Advances in Medicine and Surgery and has sat on the American Animal Hospital Association Behavior Management Guidelines Task Force and the Fear Free Executive Council.

Ariel Fagen

Ariel Fagen, DVM, is an American College of Veterinary Behavior resident in private practice. She works at Florida Veterinary Behavior Service with Dr. Lisa Radosta and at Veterinary Behavior Consultations of Colorado with Dr. E’Lise Christensen. She graduated from the Tufts University Cummings School of Veterinary Medicine and completed a small animal rotating internship at Wheat Ridge Animal Hospital in Colorado.

4. Bradshaw JW, McPherson JA, Casey RA, Larter S. Aetiology of separation-related behaviour in domestic dogs. Vet Rec 2002;151(2):43-46. 5. Voith VL, Borchelt PL. Separation anxiety in dogs. In: Voith VL, Borchelt PL, eds. Readings in Companion Animal Behavior. Yardley, PA: Veterinary Learning Systems; 1996:124-139. 6. Denenberg S, Landsberg GM, Horwitz D. A comparison of cases referred to behaviorists in three different countries. In: Mills D, Levine E, Landsberg GM, et al (eds). Current Issues and Research in Veterinary Behavioral Medicine. West Lafayette, Indiana: Purdue University Press; 2005:56-62. 7. Landsberg G. The most common behavior problems in older dogs. Vet Med 1995;90(suppl):16-24. 8. Horwitz DF, Neilson JC. Blackwell’s Five-Minute Veterinary Consult Clinical Companion Canine & Feline Behavior. Ames, Iowa: Blackwell Publishing; 2007. 9. Flannigan G, Dodman NH. Risk factors and behaviors associated with separation anxiety in dogs. JAVMA 2001;219(4):460-466. 10. Clark GI, Boyer WN. The effects of dog obedience training and behavioural counselling upon the human-canine relationship. Appl Anim Behav Sci 1993;37(2):147-159. 11. Blackwell E, Twells C, Seawright A, Casey R. The relationship between training methods and the occurrence of behavior problems, as reported by owners in a population of domestic dogs. J Vet Behav 2008;3:207-217. 12. Simpson BS. Separation anxiety in dogs. Compend Contin Educ Pract Vet 2008;30(1):27-42. 13. Landsberg GM, Hunthausen W, Ackerman L (eds.). Fears, phobias, and anxiety disorders. In: Behavior Problems of the Dog & Cat. 3rd ed. Philadelphia: Saunders; 2013:181-208. 14. Overall KL. Abnormal canine behaviors and behavioral pathologies not primarily involving pathological aggression. In: Manual of Clinical Behavioral Medicine for Dogs and Cats. St. Louis: Mosby; 2013:231-309. 15. Palestrini C, Minero M, Cannas S, Rossi E, Frank D. Video analysis of dogs with separation-related behaviors. Appl Anim Behav Sci 2010;124(1):61-67. 16. Seksel K. Separation anxiety in dogs and cats with reference to homeostasis. In: Proceedings. Veterinary Behavior Chapter. Science Week 2013. 2013:22-26.

are insufficient. Some patients may need polypharmacy.14 Tricyclic antidepressants and selective serotonin reuptake inhibitors can be helpful in easing anxiety over time. Substantial evidence supports use of clomipramine21–23 (Clomicalm, Novartis.com) and fluoxetine24,25 for separation anxiety in dogs. Clomicalm is the only drug on the market with a Food and Drug Administration label for separation anxiety in dogs older than 6 months.26 Other daily options to consider include sertraline or paroxetine.13,14 Supplements (Zylkene [vetoquinolusa.com], Solliquin [nutramaxlabs.com]), prescription diets (Royal Canin CALM [royalcanin.com]), and pheromone therapy can be considered.8,14,16,23 References 1. Appleby D, Pluijmakers J. Separation anxiety in dogs: the function of homeostasis in its development and treatment. Vet Clin North Am Small Anim Pract 2003;33:321-344. 2. Schwartz S. Separation anxiety syndrome in cats: 136 cases (19912000). JAVMA 2002;220(7):1028-1033.

SEPARATION-RELATED DISORDERS

17. Simpson BS. Canine separation anxiety. Compend Contin Educ Pract Vet 2000;22:328-338. 18. Frank D. Recognizing behavioral signs of pain and disease: a guide for practitioners. Vet Clin Small Anim 2014;44(3):507-524. 19. Ogata N. Review: Separation anxiety in dogs: what progress has been made in our understanding of the most common behavioral problems in dogs? J Vet Behav 2016;16:28-35. 20. Melese P. Detecting and neutralizing odor sources in dog and cat elimination problems. Appl Anim Behav Sci 1994;39:188-189. 21. King JN, Simpson BS, Overall KL, et al. Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. Appl Anim Behav Sci 2000;67:255-275. 22. King JN, Overall KL, Appleby D, et al. Results of a follow-up investigation to a clinical trial testing the efficacy of clomipramine in the treatment of separation anxiety in dogs. Appl Anim Behav Sci 2004;89:233-242. 23. Gaultier E, Bonnafous L, Bougrat L, et al. Comparison of the efficacy of a synthetic dog-appeasing pheromone with clomipramine for the treatment of separation-related disorders in dogs. Vet Rec 2005;156(17):533-538. 24. Landsberg GM, Melese P, Sherman BL, et al. Effectiveness of fluoxetine chewable tablets in the treatment of canine separation anxiety. J Vet Behav 2008;3:11-18. 25. Simpson BS, Landsberg GM, Reisner IR, et al. Effects of Reconcile (fluoxetine) chewable tablets plus behavior management for canine separation anxiety. Vet Ther 2007;8(1):18-31. 26. US Food and Drug Administration. Clomicalm FOIA Drug Summary. Available at: fda.gov/downloads/AnimalVeterinary/Products/ ApprovedAnimalDrugProducts/FOIADrugSummaries/ucm117165. pdf. Accessed March, 2017.

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The Challenge of Chronic Otitis in Dogsâ&#x20AC;&#x201D; From Diagnosis to Treatment Sandra Koch, DVM, MS, DACVD College of Veterinary Medicine, University of Minnesota shutterstock.com/135 pixels

Canine chronic and recurrent otitis externa can be extremely challenging to treat and require multifactorial, step-by-step strategic plans. Understanding otitis and its associated causes and contributing factors is an important initial step toward successful diagnosis and treatment.

UNDERSTANDING OTITIS: CAUSE AND PATHOGENESIS Understanding the multifactorial nature of otitis and paying attention to the different causes and contributing factors, not just the infection, is critical because the infection is usually only part of the problem (Figure 1). The most recently proposed classification for otitis includes primary and secondary causes and predisposing and perpetuating factors (Table 1).1â&#x20AC;&#x201C;3

by the owner or even the veterinarian until a secondary complicating factor arises. Most cases have a primary cause. In a retrospective study3 of 100 dogs with acute (37%) and chronic-recurrent (63%) otitis externa, the most common primary cause of otitis was allergic dermatitis (43/100 dogs; Figure 2), followed by grass awns (12/100) and otoacariasis (7/100). No primary factor could be identified in 32 of 100 cases. Allergic and hormonal diseases can be associated with

Primary Causes Primary disorders initiate the inflammatory process within the ear canal and alter the aural environment, allowing secondary complicating factors, such as infections, to develop. The primary cause may be very subtle and often is unrecognized

DERMATOLOGY DETAILS

FIGURE 1. Pathologic cycle for chronic otitis externa.

DERMATOLOGY DETAILS

TABLE 1 Causes and Factors Associated With Otitis Externa in Dogs CAUSE

EXAMPLES

PRIMARY CAUSES: ACTUAL CAUSE OF OTITIS EXTERNA IN A NORMAL EAR Parasites

Ear mites (Otodectes cynotis), demodicosis, sarcoptic mange, ticks

Dermatophytes

Microsporum canis, Trichophyton mentagrophytes

Hypersensitivity disorders

Environmental allergy, food allergy, flea allergy, contact allergy, drug reactions

Keratinization disorders

Idiopathic seborrhea, abnormal cerumen production

Endocrine disorders

Hypothyroidism, hypercortisolism, sex hormone imbalances

Foreign bodies

Plant material, hair, sand, hardened medication

Autoimmune disorders

Pemphigus complex, lupus erythematosus

Glandular disorders

Ceruminous, sebaceous, and apocrine gland hyperplasias; ceruminous cystomatosis

Benign tumors

Ceruminous gland adenoma, basal cell tumor, papilloma

Malignant tumors

Ceruminous gland adenocarcinoma, squamous cell carcinoma

Non-neoplastic growths

Inflammatory polyps

Primary otitis media

More common in brachycephalic breeds, such as Cavalier King Charles spaniel

Idiopathic

No identified cause despite attempt

SECONDARY CAUSES: CONTRIBUTE TO OR CAUSE DISEASE ONLY IN AN ABNORMAL EAR Bacteria

Various species: most common are Staphylococcus and Pseudomonas species

Fungus/yeast

Malassezia pachydermatis, Candida albicans (rare)

PREDISPOSING FACTORS: INCREASE RISK FOR DEVELOPMENT AND PERSISTENCE OF OTITIS EXTERNA Conformation

Pendulous pinna, congenital stenosis, excessive hairs in ear canal

Breed disposition

Cocker spaniel, German shepherd, poodle, basset hound

Excessive moisture

Swimmer’s ear

Immunosuppression

Medications, immunosuppressive diseases

Overtreatment

Excessive cleaning and moisture, physical trauma (eg, cotton swabs)

Respiratory viral diseases

More common in cats and common cause of otitis media

PERPETUATING FACTORS: RESULT FROM INFLAMMATION AND INFECTION AND PREVENT RESOLUTION OF OTITIS Progressive pathologic changes

Altered epithelial migration, proliferation, hyperplasia, stenosis, and calcification

Otitis media

Infectious, sterile, proliferative, cholesteatoma, osteolysis, osteomyelitis

Abnormal tympanic membrane

Opacity, scarring, diverticulum, rupture, myringitis

unilateral or bilateral otitis, but bilateral otitis is more common. Foreign bodies, neoplasia, and polyps are usually associated with unilateral otitis; however, bilateral problems have been reported.3

Secondary Causes

FIGURE 2. Otitis externa secondary to allergies.

Secondary causes occur in combination with primary causes or predisposing factors. The most common secondary causes are infections.1–3 Generally, secondary causes of otitis externa are easy to eliminate once identified. When they are chronic and difficult to treat, it is MAY/JUNE 2017

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usually because primary causes or perpetuating factors have not been adequately addressed.

Predisposing Factors Predisposing factors alone do not cause otitis externa, but they facilitate inflammation by permitting the external ear canal microenvironment to be altered, thereby allowing pathogenic or opportunistic bacteria or yeast to become established.1,2 In conjunction with primary or secondary causes, these factors become a significant problem. It is important to eliminate as many of these factors as possible while realizing that some, such as ear conformation, cannot be changed.

Perpetuating Factors Perpetuating factors sustain and aggravate the inflammatory process and prevent resolution of, or worsen existing, otitis externa.1,2 Once present, they accentuate or permit the development of secondary causes, such as infection, by providing favorable environments and microscopic niches. In many cases, perpetuating factors prevent the resolution of otitis externa when treatments are directed only at primary and secondary causes. These factors may be subtle at first but can develop into the most severe component of chronic ear disease. They are not disease specific and are most commonly seen in chronic cases. Perpetuating factors are the most common reasons for surgical intervention.

IMPORTANT DIAGNOSTIC STEPS

or surgery (total ear canal ablation with or without bulla osteotomy) is the best treatment. If the patientâ&#x20AC;&#x2122;s ears are painful, sedation or general anesthesia may be necessary before otoscopic examination. Regular (ie, handheld) otoscopes should have a strong light and power source. If available, fiberoptic video-enhanced otoscopy (eg, videootoscope [Figure 3]) is extremely helpful in improving diagnosis and therapy because it not only allows visualization of fine details that may not be seen with regular otoscopes but also facilitates proper flushing of the ears, determination of disease extent, and discovery of indications for additional diagnostics and treatment (eg, myringotomy, otitis media). However, because of the expense to purchase and maintain this equipment, referral to a dermatologist may be necessary.

Physical Examination Performing a complete physical examination, including a detailed dermatologic examination, can help in identifying an underlying or primary cause. In patients with otitis media and/or otitis interna, concurrent neurologic abnormalities (eg, facial paralysis, nystagmus, ataxia, head tilt) may be present; therefore, a detailed neurologic examination is indicated.

Otic Cytology Otic cytology establishes whether an infection is present in the ears and assists with the selection

History A detailed and complete history is essential to help investigate the underlying cause and associated factors.

Otic Examination The ear examination allows the clinician to evaluate the amount and type of exudate in the ear canals; estimate the amount of otic inflammation; identify hyperplasia (along with palpation of the horizontal and vertical ear canals), masses, and foreign bodies; and determine the status of the tympanic membrane (eg, changes in structure or rupture). These findings help in determining whether medical management

DERMATOLOGY DETAILS

FIGURE 3. Video otoscopic examination.

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of topical therapy. Cytologic samples should be collected gently from the horizontal canal. Exudate samples can be smeared onto a slide with mineral oil to look for mites. The most common type of coccoid bacteria found in the ears of dogs with otitis externa is Staphylococcus pseudintermedius, and the most common type of rod bacteria is Pseudomonas aeruginosa.1–6 Malassezia species are also common organisms1–5 (Figure 4). It is important to describe the presence of any inflammatory or neoplastic cells as well as quantify each type of bacteria and yeast per oil immersion field (100×) to establish severity and allow monitoring at future visits. In one study, mean bacterial counts per high-power dry field of ≥25 and mean Malassezia counts per high-power dry field of ≥5 were considered abnormal in the external ear canals of dogs.5 Leukocytes are always abnormal, and bacteria in the presence of leukocytes signal infection.

one study,7 however, cytologic results agreed with culture results only 68% of the time. The same study7 showed that different bacterial organisms were isolated from the same ear in 20% of the

FIGURE 4. Cytologic appearance of Malassezia species (high-power oil immersion field 100× objective).

Bacterial Culture and Sensitivity Culture and sensitivity (C/S) may be useful in identifying specific otic pathogens and assisting with treatment decisions; however, a limitation is that antibiotic sensitivity data reflect the serum level needed systemically and may not predict true susceptibility of otic topical antibiotics. Typical indications for bacterial C/S include the following1–4:

• Chronic otitis associated with bacteria (cocci [Figure 5] and/or rods) seen on cytology

FIGURE 5. Cytologic appearance of degenerate neutrophils and cocci (high-power oil immersion field 100× objective).

• Rods seen on cytology (Figure 6) • Suspected or confirmed cases of otitis media (systemic therapy may be indicated) • History of multidrug-resistant bacteria • History of long-term oral or topical antibiotic therapy • Bacteria persisting on cytology despite apparently appropriate therapy Cytology should always be performed before aerobic C/S to assist with interpretation of results and identification of concurrent problems. In

FIGURE 6. Cytologic appearance of degenerate neutrophils and rods (high-power oil immersion field 100× objective).

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cases; therefore, it is important to remember that ear cytology or a single swab submitted for C/S may not reveal the total population of organisms truly present in the ear canal. This might explain why, in some cases, sensitivity results (in vitro) and response to topical therapy (in vivo) do not always correlate. This study poses questions regarding the true benefit of C/S for selecting antimicrobials for otic infections; therefore, clinicians should be careful and critical when interpreting otic cytologic and culture results. Clinicians should sample the middle ear separately if otitis media is confirmed when the tympanic membrane is intact. The types and sensitivity pattern of bacteria isolated from the middle ear may differ from those of bacteria isolated from the external canal.8 In one study, different organisms were cultured from the middle and external ear, and even when Pseudomonas species were cultured twice from the same ear, different strains were suspected on the basis of the sensitivity pattern exhibited.8 Culture results should be interpreted

with caution because mixed bacterial flora and light commensal and contaminant bacteria might be present and may not be relevant as pathogens.

Diagnostic Imaging Techniques Dogs with chronic, recurrent, and severe otitis and those with neurologic signs (eg, vestibular signs or facial nerve paralysis), para-aural swelling, or pain on opening the mouth usually require diagnostic imaging to help identify contributing problems, such as middle ear disease (eg, otitis media, neoplasia) and otitis interna, that cannot be identified with regular otoscopy (Table 2). Patients with an apparently normal tympanic membrane may also have otitis media. Although otitis interna is uncommon in dogs with chronic otitis externa, otitis media is common, with a reported incidence of 50% to 88.9%.8 In dogs with recurrent ear infections of 6 months or longer, up to 89% may have concurrent otitis media; about 70% have an intact but abnormal tympanic membrane.8

TABLE 2 Advantages and Disadvantages of Diagnostic Imaging Techniques DIAGNOSTIC IMAGING TECHNIQUES

ADVANTAGES

DISADVANTAGES

•H as limited value in identifying soft tissue

changes •C an detect mineralization and neoplasia in the Radiography

ear canal and bony changes in the bulla wall •U sually does not require sedation, general

anesthesia, or intravenous contrast material

•C annot rule out otitis media •C annot distinguish between fluid and tissue in

the middle ear •N ot as sensitive as CT and MRI for predicting

presence and severity of middle ear disease, such as otitis media

Ultrasonography

•R elatively quick and noninvasive •C an detect thickening and fluid in tympanic bulla •U sually does not require sedation or general

•C annot distinguish between fluid and tissue in

the middle ear

anesthesia •P rovides excellent images of bony structures CT

and can differentiate bony changes in bullae from soft tissue reactions •C an detect presence of fluid in tympanic bulla (ie, otitis media) •C an detect otitis interna, tumors, and meningitis

•R equires general anesthesia and administration

of intravenous contrast material •N ot as sensitive for identifying otitis interna,

tumors, and meningitis compared with MRI •E xpensive

•B etter for assessing soft tissue structures

MRI

of external ear, inner ear, adjacent neural structures, and brain •C an detect fluid in tympanic bulla (ie, otitis media) and otitis interna •C an detect tumors and their specific location, as well as meningitis

CT, computed tomography; MRI, magnetic resonance imaging.

DERMATOLOGY DETAILS

•M ay not identify mineralization of the external

canals unless it is severe •R equires general anesthesia and administration

of intravenous contrast material •E xpensive

DERMATOLOGY DETAILS

Deep Ear Flushing This procedure is very helpful not only as a diagnostic tool but also as part of the treatment plan.9 A short course (2 to 3 weeks) of an anti-inflammatory dose of oral and/or topical glucocorticoids may be needed before deep ear flush in order to decrease inflammation and stenosis of the ear canals. This procedure should be performed under general anesthesia so that the ear can be completely cleaned and the ear canal and tympanic membrane examined. Anesthesia also allows the placement of an endotracheal tube, which precludes the aspiration of fluids that may pass through the middle ear into the auditory tube and then into the posterior pharynx. Ideally, computed tomography of the tympanic bulla should be performed before the flush to stage ear disease and help make the decision to perform myringotomy if otitis media is present. Several techniques to clean and flush the ears exist.9 Follow-up visits after flushing are very important to monitor response to therapy and evaluate the status of the tympanic membrane. If myringotomy is performed, the tympanic membrane usually heals within 30 days after the procedure. Deep ear flush and myringotomy are best performed by experienced practitioners with a videootoscope; therefore, referral to a dermatologist might be ideal. For a description of one deep ear flush technique, please visit tvpjournal.com.

therapy. The amount of medication applied is important. Generally, the recommendation is to use about 0.5 to 1 mL (10 to 20 drops) per ear, depending on the size of the dog. Ear Cleaners

Ear cleaners should be used at home as part of most treatment protocols initially (once daily to twice weekly depending on the severity of the otitis and amount of discharge present) and as maintenance therapy (usually once to twice weekly) to help prevent future infections once the otitis and infection are resolved.10–13 Removal of debris and purulent material greatly improves the efficacy of topical antimicrobials, especially aminoglycosides and polymyxin B. However, overcleaning should be avoided because it can contribute to maceration and ear disease. Clients should be educated on the proper technique to clean the ears and to avoid using cotton balls and cotton swabs inside the ears. Available ear cleaners include drying agents, antiseptics, ceruminolytics, and combination products. For a table listing these cleaners, please visit tvpjournal.com. Acaricidals

TREATMENT

Many different acaricidal products may be used to treat infections caused by Otodectes cynotis (ear mites) and, less commonly, Demodex species.10–13 Veterinary acaricidal products for label and extralabel use include ivermectin, milbemycin, selamectin, fipronil, monosulfiram, permethrin, piperonyl butoxide, pyrethrins, thiabendazole, and rotenone.13

There are 5 general goals of otitis externa treatment:

Antimicrobials

1. Resolve discomfort and pain. 2. Remove debris and discharge. 3. Eliminate infection from the external and middle ears. 4. Reverse chronic pathologic changes, when possible. 5. Identify and treat the primary cause of the otitis.

Topical Therapy In most cases of otitis externa, topical therapy alone is sufficient and is preferred when possible. In contrast, chronic, severe cases of otitis externa and otitis media often require additional systemic

It is important to always use higher volumes or concentrations of topical antibiotics because they may prove efficacious, even when resistance has been suggested on a susceptibility panel. With topical drugs, concentrations 100 to 1000 times superior to the minimum inhibitory concentration may be reached.13 Antimicrobials should be used until 1 week past negative cytologic results for most bacterial and/or yeast otic infections.10-13 Twicedaily applications are usually recommended. For Pseudomonas (Figure 7) and multidrug-resistant infections, I recommend treating the patient until 1 week past negative cytologic and culture results. MAY/JUNE 2017

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Antibacterial agents: These products are indicated when infection is present and cleansing solutions are insufficient. Most topical antibacterial products also contain glucocorticoids and antifungals.

• First-line antibiotics most commonly used include products containing neomycin alone or in combination with other agents (Tresaderm, us.merial.com) and gentamicin (Gentocin Otic; Otomax, merck-animal-health-usa.com; Mometamax, merck-animal-health-usa.com). Ototoxicity is reported with all gentamicin topicals. However, as with chlorhexidine, this concern may be overstated. One study showed no vestibulotoxic or ototoxic effects from 21 days of otic gentamicin applied q12h to ears with ruptured tympanic membranes.13,14 Polymyxin B (Surolan, elanco.com) can also be a highly effective topical antibiotic and often is effective in many Pseudomonas infections; however, polymyxin can be inactivated by purulent exudates. • Second-line antibiotics include tobramycin (Tobrex ophthalmic solution, alcon.com), injectable amikacin mixed with saline at a final concentration of 25 mg/mL, and ticarcillin– clavulanate potassium, which may be ordered at compounding pharmacies. Care needs to be used with certain topical aminoglycosides because ototoxicity, based on brainstem auditory evoked response testing, was recently seen to occur more commonly in dogs treated with amikacin- and tobramycin-based topicals.13,14

• Third-line antibiotics include mupirocin and fluoroquinolones, ideally based on C/S. Mupirocin should be saved for multidrugand methicillin-resistant Staphylococcus infections; the product is mixed as 1 tube of product (30 g) to 30 mL of sterile saline. Enrofloxacin and silver sulfadiazine (Baytril Otic, bayerdvm.com) is often ineffective in chronic severe cases. Injectable formulations of enrofloxacin (Baytril injectable) are preferable in many different extralabel recipes, such as a 25% mixture of injectable enrofloxacin (22.7 mg/mL diluted with water, saline, or other active agents with variable concentrations of dexamethasone, not exceeding 0.1% to 1%). Posatex (merck-animal-health-usa.com) contains orbifloxacin, posaconazole, and prednisone and may be used against multidrug-resistant infections, such as Staphylococcus and Pseudomonas infections. • Antifungal agents: These may be used in any otitis case associated with yeasts, such as Malassezia or Candida species.10–13 Many available products contain glucocorticoids and antibiotics; however, products containing only antifungals can be found. Usually effective antifungals include clotrimazole (Otomax, Mometamax), miconazole (Conofite, merck-animal-health-usa.com), thiabendazole (Tresaderm), acetic acid (MalAcetic Otic, dechra-us.com), and TrizEDTA and ketoconazole flush (TrizUltra+Keto, dechra-us.com). Glucocorticoids

FIGURE 7. Chronic Pseudomonas otitis.

DERMATOLOGY DETAILS

Numerous topical preparations of variable potencies are available for use in the external ear canal.10–13 The frequency of use varies from q6h to q24h, depending on the product and the severity of the otitis. Most cases of chronic otitis externa benefit from topical glucocorticoids. Glucocorticoids have antipruritic, anti-inflammatory effects and decrease exudation and swelling, thereby helping to reduce pain and discomfort. In addition, they cause sebaceous atrophy and decrease glandular secretions. Glucocorticoids may reduce scar tissue and proliferative changes, which helps to promote

DERMATOLOGY DETAILS

drainage and ventilation. Most ear products contain various combinations of glucocorticoids, antibiotics, antifungals, and parasiticides.

• Otic products containing betamethasone (Otomax) and dexamethasone (Tresaderm) are usually effective but can be absorbed systemically and cause adrenal suppression with long-term use, so they should be used cautiously. In one study, a more potent yet “soft” glucocorticoid, mometasone (Mometamax), showed no adrenal suppression after 1 week of therapy.12 In cases of allergic otitis externa, long-term topical glucocorticoids may be required with careful monitoring for adrenal suppression or local side effects, such as pinnae hair loss. Products with weakerstrength glucocorticoids should be used in these situations, such as those containing 1.0% or 0.5% hydrocortisone (Zymox HC, zymox.com). I often recommend fluocinolone and dimethyl sulfoxide (Synotic, zoetisus.com), with great results for many chronic, hyperplastic, and stenotic otitis cases. New Food and Drug Administration– Approved Single-Dose Antimicrobial and Steroid Otic Solutions

Two new veterinarian-administered products containing florfenicol, terbinafine, and mometasone furoate (Claro, bayerdvm.com) and florfenicol, terbinafine, and betamethasone acetate (Osurnia, osurnia.com) are indicated as single-dose treatments for canine otitis externa associated with susceptible strains of yeast (Malassezia pachydermatis) and bacteria (S pseudintermedius). The duration of effect is 30 days for Claro and 7 days for Osurnia. Ears should not be cleaned at home after application. The recommendation is for use in the clinic after ear cleaning, and only with intact tympanic membranes. These are great options for patients that do not allow topical therapy at home and to improve compliance, with potential benefit for acute or mild otitis cases. Their use in chronic severe otitis cases is limited because severe hyperplasia and stenosis preclude ear cleaning and evaluation of the tympanic membrane.

Systemic Therapy Indications for systemic therapy include the following:

• Otitis externa that is severe and unresponsive to topical therapy alone • Concurrent otitis media • Owner unable to medicate with topical therapy • Topical therapy precluded by adverse reactions • Marked proliferative chronic changes Antibiotics

These drugs may be used in animals with otitis media, moderate or marked proliferative changes with suspected otitis media, or no response to appropriate topical therapy and cleansing. I usually recommend C/S before a systemic antibiotic is selected. Usually, higher doses are recommended to achieve good penetration in the middle ear. Treatment duration may vary; however, I usually treat for 1 month after resolution of clinical signs and healing of the tympanic membrane (from spontaneous perforation or myringotomy). Fluoroquinolones may be prescribed when Pseudomonas species, other relevant gram-negative organisms, or very resistant gram-positive bacteria are isolated and susceptibility is confirmed after culture. Higher doses than usually recommended may be needed. Oral fluoroquinolones that may be used include enrofloxacin (Baytril) at 10 to 20 mg/kg q24h, marbofloxacin (Zeniquin, zoetisus.com) at 5 to 10 mg/kg q24h, or orbifloxacin (Orbax, merck-animal-health-usa.com) at 10 mg/kg q24h. Ciprofloxacin should be avoided in dogs because oral absorption is inconsistent and low (58.4%) with oral tablets,15 potentially leading to inefficacy and bacterial resistance. In rare cases, injectable antimicrobials, such as aminoglycosides, carbapenems, and ceftazidime sodium, may be required to treat multidrug-resistant otitis cases. Potential side effects with these therapies need to be considered. Referral of these cases to a dermatologist should be considered, particularly when treatment options are limited.

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Antifungals

Antifungal agents can sometimes be used in severe cases of Malassezia otitis or cases with poor response to topical agents alone. Oral antifungals commonly used include ketoconazole (Nizoral, nizoral.com), fluconazole (Diflucan, pfizer.com), and itraconazole (Sporanox, janssen.com). All are dosed at 5 to 10 mg/kg q24h or q12h (divided). Terbinafine (Lamisil, lamisilat.com) may also be used at 30 mg/kg q24h. Glucocorticoids

Glucocorticoids are usually indicated in cases of markedly inflamed and painful otitis with chronic pathologic changes, such as marked hyperplasia and stenosis of the canal. Oral anti-inflammatory dosages of prednisone or prednisolone (0.5 to 1 mg/kg q24h) can be used initially and then tapered to the minimum alternate-day dosage that controls the clinical signs. I typically recommend oral glucocorticoids for cases of Pseudomonas otitis and for dogs that have undergone deep ear flushing. Oral glucocorticoids can also be helpful to reduce pain and discomfort, particularly a few days before the owners clean and medicate the ears. I

FIGURE 8. End-stage otitis.

often combine opioids, such as oral tramadol at 2 to 4 mg/kg q84 to q12h, with oral glucocorticoids in severely painful cases. When longer-term treatment is expected, alternate-day glucocorticoid therapy may be indicated, with careful monitoring for adverse effects. Cyclosporine

Oral cyclosporine (Atopica, us.atopica.com) may be considered a medical option for dogs with severe proliferative otitis externa when surgery is not an

TABLE 3 Surgical Techniques for Chronic Otitis and Otic Masses/Tumors9 SURGERY

Lateral ear canal resection

INDICATIONS

COMMENTS

•C ongenital ear canal stenosis •R esection of masses located in the

•A ssociated with frequent failures for

vertical ear canal •F acilitation of medical management •P ossible improvement of local environment factors and facilitation of topical treatment

treatment of chronic otitis externa, particularly with chronic pathologic changes to the ear canal or failure to control the underlying cause of otitis •F ailure rates are higher in cocker spaniels •N ot recommended for chronic proliferative

Vertical ear canal resection

•D isease limited to the vertical canal, such

as masses or neoplasia

cases involving horizontal canal and middle ear •L ess invasive than TECA-BO •N ot recommended for chronic proliferative

Ventral bulla osteotomy

•D iseases, such as tumors or polyps,

present in bulla •S evere chronic end-stage otitis externa/

TECA-BO

media •C hronic recurrent otitis externa/media unresponsive to long-term proper medical therapy •M asses or neoplasia of ear canal and/ or bulla that cannot be removed by alternative methods

TECA-BO, total ear canal ablation + lateral bulla osteotomy.

DERMATOLOGY DETAILS

cases involving horizontal canal and middle ear •L ess invasive than TECA-BO •M ost commonly recommended by

dermatologists •A ssociated with highest success rate and

best prognosis of all surgical procedures for chronic severe otitis • I deally should be performed by a boardcertified surgeon to minimize potential surgical complications

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PEER REVIEWED

option. In a pilot study,16 5 client-owned dogs were treated with cyclosporine at 5 mg/kg q12h for a minimum of 12 weeks. All dogs were evaluated clinically every 4 weeks to monitor progress; they all showed significant clinical improvement based on owner and clinical assessments. Individual owners also commented on improved disposition, hearing, and quality of life. I have seen limited benefits with oral cyclosporine in end-stage disease (Figure 8), but the drug may be considered in cases when surgery cannot be performed.

Sandra Koch

Sandra Koch is an associate professor of veterinary dermatology at the College of Veterinary Medicine, University of Minnesota. She is primarily involved with clinical service and teaching. Dr. Koch’s special interests include allergic and infectious skin diseases, particularly multidrug- and methicillinresistant Staphylococcus skin and ear infections and dermatologic therapies. She is the primary author of a therapeutic drug book, Canine and Feline Dermatology Drug Handbook.

CLIENT EDUCATION AND FOLLOW-UP VISITS It is very important to talk to clients about the lengthy process of managing otitis, including the need for proper home therapy and frequent followup visits, pain management, quality of life, longterm prognosis, and medical costs. Clients must also be taught how to clean the ears and place ear medications. Dogs with otitis should be reevaluated with otic examination and cytology every 2 to 4 weeks, depending on severity, to assess response to therapy. It is important to treat ear infections until 1 week past clinical improvement and negative ear cytologic results for most bacterial and yeast infections. For multidrug-resistant and Pseudomonas ear infections, I usually recommend treatment until 1 week past negative cytologic and culture results.

MAINTENANCE/PREVENTIVE EAR CARE AT HOME

References 1.

Harvey RG, Patterson S. Otitis Externa: An Essential Guide to Diagnosis and Treatment. Boca Raton, FL: CRC Press; 2014.

2. Gotthelf LN. Small Animal Ear Diseases: An Illustrated Guide. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2004. 3. Saridomichelakis MN, Farmaki R, Leontides LS, et al. Aetiology of canine otitis externa: a retrospective study of 100 cases. Vet Dermatol 2007;18(5):341-347. 4. Griffin CE. Otitis externa and media. In: Griffin CE, Kwochka KW, MacDonald JM, eds. Current Veterinary Dermatology, The Science and Art of Therapeutics. St Louis, MO: Mosby–Year Book; 1993:245-262. 5. Ginel P, Lucena R, Rodriguez JC, Ortega J. A semiquantitative cytological evaluation of normal and pathological samples from the external ear canals of dogs and cats. Vet Dermatol 2002;13(3):151-156. 6. Defalque V, Rosser EJ Jr, Peterson AD. Aerobic and anaerobic bacterial microflora of the middle ear cavity in normal dogs. 20th Proc North Am Vet Dermatol Forum 2005:159. 7. Graham-Mize CA, Rosser EJ. Comparison of microbial isolates and susceptibility patterns from the external ear canal of dogs with otitis externa. JAAHA 2004;40(2):102-108.

Some type of maintenance otic therapy is usually required, such as a cleaning and drying agent (to keep the ear canal free of wax buildup), antimicrobial ear cleaners (eg, for recurrent ear infections), and sometimes topical glucocorticoids (for severe hyperplasia or stenosis, when surgery is not an option).

8. Cole L, Kwochka KW, Kowalski JJ, Hillier A. Microbial flora and antimicrobial susceptibility patterns of isolated pathogens from the horizontal ear canal and middle ear in dogs with otitis media. JAVMA 1998;212(4):534-538.

SURGICAL MANAGEMENT

12. Paterson S. Topical ear treatment—options, indications and limitations of current therapy. J Small Anim Pract 2016;57(12):1-11.

Surgical management may be recommended (Table 3), particularly in cases of otic tumors and chronic end-stage otitis, when all medical therapeutic attempts are made, after detailed discussion of potential benefits, risks, and postsurgery complications. Histopathology and bacterial culture of

removed tissue or masses should always be performed. Advanced imaging before surgery is ideal.

DERMATOLOGY DETAILS

9. Patterson S, Tobias KM. Atlas of Ear Diseases of the Dog and Cat. Ames, IA: Wiley-Blackwell; 2012. 10. Rosychuk RAW. Management of otitis externa. Vet Clin North Am Small Anim Pract 1994;24(5):921-952. 11. White PD. Medical management of chronic otitis in dogs. Compend Contin Educ Pract Vet 1999;21:716-722.

13. Koch SN, Torres MF, Plumb DC. Canine and Feline Dermatology Drug Handbook. Ames, IA: Wiley-Blackwell; 2012. 14. Patterson S. Ototoxicity. Proc WCVD 6 2008:227-230. 15. Papich MG. Ciprofloxacin pharmacokinetics and oral absorption of generic ciprofloxacin tablets in dogs. Am J Vet Res 2012;73(7):10851091. 16. Hall J. Oral cyclosporine in the treatment of end state ear disease: a pilot study. Proc 18th Annu Meeting Am Acad Vet Dermatol Am Coll Vet Dermatol 2003:217.

A solution for every ear. Dechra Veterinary Products is one of the leaders in innovative solutions for ear conditions in pets. Some of our original formulations relied on TrizEDTA, which chelates minerals in bacterial cell walls thereby increasing their susceptibility to active ingredients in topical products. Other enhancements in some formulas were the addition of Ceramides. Ceramides aid in moisturizing, repairing and restoring damaged skin. We now have built a portfolio of products listed below that can help you address many common ear conditions.

DECHRA OTIC OR FLUSH

Condition Present in the Ear & Benefits of the Dechra Otic Yeast

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Dechra Veterinary Products US and the Dechra D logo are registered trademarks of Dechra Pharmaceuticals PLC. Caution is recommended when using chlorhexidine in the ear when the status of the tympanic membrane is unknown.

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Nutrition A special section to Today’s Veterinary Practice May/June 2017

BEHAVIOR

RESEARCH

PREVENTION

Behavior Monitoring Taking Pet Healthcare to a New Level

Neurologic Breakthrough in Canine Nutrition

Nutritionists’ View: OTC Versus Therapeutic Veterinary Diets

S. Dru Forrester | Page 3

Jason Gagné | Page 5

Donna Raditic & Joe Bartges | Page 8

A special section to Today’s Veterinary Practice

May/June

INTRO

A Hand-in-Hand Approach to Pet Nutrition W

elcome to our special nutrition section, designed to bring you some of the latest developments in nutrition news, science, and innovative products. Today’s Veterinary Practice is also dedicated to helping veterinarians and staff keep up-to-date on important topics in this area by providing peer-reviewed articles in a partnership with the American College of Veterinary Nutrition. Recently we covered… D iets

and the Dermis: Nutritional Considerations in Dermatology March/April 2017 F eaturing Fiber: Understanding Types of Fiber & Clinical Uses January/February 2017 T o Feed or Not to Feed? Controversies in the Nutritional Management of Pancreatitis November/December 2016 CONTENTS Introduction . . . . . . . . . . . . . . . . . . 2 Behavior . . . . . . . . . . . . . . . . . . . . . . 3 Behavior Monitoring Taking Pet Healthcare to a New Level

Research . . . . . . . . . . . . . . . . . . . . . 5 Neurologic Breakthrough in Canine Nutrition

Prevention . . . . . . . . . . . . . . . . . . . . 8 Nutritionists’ View: Over-theCounter Versus Therapeutic Veterinary Diets

Many more topics are available under the “Nutrition” clinical topic on the tvpjournal.com website. Nutrition continues to grow as a critical area of service for the veterinary practice. Clients seek advice and prescription diets for many different medical concerns and conditions, and veterinarians now have more solutions available to them than ever before. In this section, we offer articles on the following topics:  B ehavior

Monitoring in Nutrition Plans Breakthrough in Canine

 N eurologic

Nutrition  O ver-the-Counter

Versus Therapeutic

Veterinary Diets

The opinions expressed in this special section are those of the authors and do not necessarily reflect the opinions of the publisher. Articles in this section have not been peer reviewed. Product mentions in this section do not imply product endorsement by the publisher.

A special section to Today’s Veterinary Practice

May/June

BEHAVIOR

Behavior Monitoring Taking Pet Healthcare to a New Level S. Dru Forrester, DVM, MS, DACVIM

Technology provides actionable insights to improve patient care and enhance client communication and compliance

ecause pets lack the ability to describe their clinical signs or explain how they feel, the veterinary healthcare team is at a disadvantage when it comes to successfully diagnosing and treating patients. The limited time with patients in the examination room means that diagnosis relies heavily on perceptions and observations of pet owners, who may not recognize or may misinterpret important signs. For example, clients with an overweight dog on a recommended exercise plan might think that their dog is active, but can they measure how many minutes per day the dog spends resting versus running or walking? And what about dogs with allergic skin disease or otitis that are home alone for much of the day—is it possible to know

how many minutes per day they spend scratching or head shaking? Today’s technology can help close this information gap, and veterinarians are taking note. “Advances in technology continue to provide veterinarians with tools to deliver higher-quality care to their patients. Remote monitoring of a dog’s activity and movement can actually assist the veterinarian to fine-tune treatment choices, while at the same time providing the client with objective information about just how well their dog is responding to a care plan. This is a win–win for all involved,” said Robin Downing, DVM, MS, DAAPM, DACVSMR, CVPP, CCRP, of the Downing Center for Animal Pain Management in Windsor, Colorado.

ABOUT THE AUTHOR

S. Dru Forrester, DVM, MS, DACVIM

GATHERING DATA

shutterstock.com/Ilike

The limited time with patients in the examination room means that diagnosis relies heavily on perceptions and observations of pet owners, who may not recognize or may misinterpret important signs.

S. Dru Forrester is director of Global Scientific Affairs for Hill’s Pet Nutrition. Dr. Forrester was invited by Today’s Veterinary Practice to author this column. Dr. Forrester received her DVM from Auburn University. She completed an internship and residency in internal medicine and received a Master of Science degree at Texas A&M University. Dr. Forrester was a faculty member in the Department of Small Animal Clinical Sciences at the Virginia-Maryland Regional College of Veterinary Medicine for 13 years and a professor at the Western University College of Veterinary Medicine in southern California for 2 years. She has received many awards in recognition of teaching excellence, including the national Carl Norden/ Pfizer Distinguished Teacher Award in 2004. Dr. Forrester is also an adjunct faculty member in the Department of Clinical Sciences at Kansas State University. Her professional interests include urology and nephrology.

A special section to Today’s Veterinary Practice

May/June

shutterstock.com/pinbox77

BEHAVIOR

“ As veterinary dermatologists, we ask pet parents how itchy their dogs are, but they don’t know because they’re not home for most of the day.” — DR. JOEL GRIFFIES

THE TECHNOLOGY A number of lightweight sensors that can attach to a dog’s collar and collect a variety of data are available. The best systems go beyond basic activity tracking to provide more advanced behavior monitoring. These devices can provide continuous (24/7), detailed, and actionable insights to the veterinary healthcare team to help inform veterinarians as they recommend treatment options and provide valuable behavioral information related to pets’ underlying health conditions. For example, AGL’s Vetrax™ system captures multidimensional, highfrequency data, which is then processed by cloud-based algorithms developed by scientists at Georgia Tech. The algorithms can match waves of energy, which are the pets’ movements detected by the sensor, to a database of identified behaviors. Specific actions, such as resting, walking, running, scratching, and head shaking, can then be quantified, informing the veterinary healthcare team of the amount of time per day the dog exhibits each behavior. Going beyond the ability to collect and process data, advances in software design now allow the entire veterinary healthcare team to effectively and efficiently analyze this information and clearly present their findings to clients. Web portals serve as the hub of information where veterinary healthcare team members can see a dashboard with infographics that visually summarize an overview for all patients. The team members can also access a detailed view of data for individual patients and set goals to help manage the pet’s underlying conditions. For example, through the Vetrax portal, the veterinary healthcare team can schedule reminders, send questions to pet owners, or request photos or videos between visits to the hospital. This provides an opportunity to enhance communication with clients and increase productivity and quality of each hospital visit. Clients can view progress and communications through a smartphone app, which provides a vehicle to see measurable changes from their veterinarian’s treatment plan and can improve compliance.

NUTRITION INTEGRATION With the ability to monitor and quantify specific behaviors, technology can help play a vital role in gauging the effectiveness of a nutrition therapy plan for a healthcare team. This year, Hill’s Pet Nutrition announced the launch of Hill’s® SmartCare, a combination of the Vetrax behavioral monitoring system and Prescription Diet nutrition available exclusively through veterinarians. With this program, dogs wear the Vetrax sensor on their collars as part of a veterinarian-prescribed plan, which includes therapeutic nutrition to help manage dermatologic disorders (allergic skin disease, otitis), obesity, or osteoarthritis. Through the online portal and smartphone app, the veterinary healthcare team and owner can monitor the dog’s behaviors (eg, scratching, head shaking, sleep quality) and have a more objective measurement to show the benefits of therapeutic nutrition. Dr. Joel Griffies, DACVD, has used the Hill’s SmartCare and Vetrax technology with his patients at the Animal Dermatology Clinic in Marietta, Georgia. “As veterinary dermatologists, we ask pet parents how itchy their dogs are, but they don’t know because they’re not home for most of the day. Now, Hill’s SmartCare powered by Vetrax helps bridge the communication gap by giving us an objective measurement, rather than relying on human observation,” Dr. Griffies said. With new technology, veterinarians will be able to extend their care beyond in-office consultations and monitor effects of their recommendations in real time. Access to quantitative data provides a new level of understanding about how a veterinarian’s treatment plan affects patient behaviors and, ultimately, helps transform the lives of dogs with common conditions, including dermatologic disorders, obesity, and osteoarthritis. The availability of a behavioral monitoring system allows veterinarians and clients to partner like never before and maximize effectiveness of a pet’s healthcare program. Moving forward, technology will advance to be able to recognize and track additional behaviors and provide veterinarians with even more powerful tools to help transform the lives of pets. 

A special section to Today’s Veterinary Practice

May/June

RESEARCH

Neurologic Breakthrough in Canine Nutrition J ason Gagné, DVM, DACVN Director, Veterinary Technical Marketing | Purina Pro Plan Veterinary Diets

eterinarians in companion animal practice are familiar with canine idiopathic epilepsy, a neurologic condition that affects an estimated 1 in 111 dogs.1 Companion animal practitioners are also familiar with the shortcomings of current therapeutic approaches, which include medication side effects and breakthrough seizures. While the precise cause of canine idiopathic epilepsy is unknown, the effect in the brain has been documented as a rapid, uncontrolled discharge of neurons within the brain’s cerebral cortex that leads to seizures.2 Epilepsy appears to be a heritable condition in dogs; while any dog of any breed can develop the condition, some breeds are predisposed. These include Labrador retrievers, Belgian shepherds, petit Basset

Griffon vendeens, boxers, Irish wolfhounds, English springer spaniels, vizslas, Bernese mountain dogs, standard poodles, border collies, Australian shepherds, and border terriers.3 The condition is also more common in males than females, with neutering having no effect on this predisposition.2 Anti-epilepsy drugs (AEDs) such as phenobarbital and potassium bromide are commonly used for canine epilepsy.2 Patients typically have their first seizure between 1 and 3 years of age4 and begin treatment with one of these medications, with others added if and when treatment results are unsatisfactory (a 50% reduction in seizures is considered a successful response5). The challenge: two-thirds of affected dogs continue to suffer from seizures in spite of medication,6 and 20% to 30% remain poorly controlled.7–9 Meanwhile, AEDs themselves are associated with side effects, including

ABOUT THE AUTHOR

Jason Gagné, DVM, DACVN

A HERITABLE CONDITION

shutterstock.com/Garry Quinn

While any dog of any breed can develop epilepsy, some breeds are predisposed: boxers, Labrador retrievers, Belgian shepherds, petit Basset Griffon vendeens, Irish wolfhounds, English springer spaniels, Australian shepherds, Bernese mountain dogs, standard poodles, border collies, and border terriers.

Dr. Jason Gagné is a boardcertified veterinary nutritionist employed by Nestlé Purina as a Director, Veterinary Technical Marketing. Jason works closely with innovation and renovation, development of clinical trials, and the Sales and Marketing departments of the Purina® Pro Plan® Veterinary Diets Brand. Prior to, and throughout his residency at Cornell, he served as an Associate Veterinarian in a small animal practice in Syracuse, New York. Jason has authored a number of publications in veterinary journals and textbooks, given scientific presentations at the regional and national level, taught a series of courses at Cornell, and serves as a scientific reviewer for leading journals.

A special section to Today’s Veterinary Practice

May/June

RESEARCH

polyphagia, polydipsia, polyuria, restlessness, lethargy, and ataxia, leading veterinarians to walk a narrow line between achieving medication benefits and causing harm. As a result, only 4% of veterinarians surveyed are “totally” or “mostly” satisfied with current treatment options.1

While the precise cause of canine idiopathic epilepsy is unknown, the effect in the brain has been documented as a rapid, uncontrolled discharge of neurons within the brain’s cerebral cortex that leads to seizures.

DIETARY THERAPY: A NEW APPROACH TO MANAGING DOGS WITH EPILEPSY? Traditional ketogenic diets, which are designed to force the body to burn fat instead of carbohydrate and put the body into a state of ketosis, have been used for decades in children whose seizures are not controlled with medication.10 The rationale is that brain glucose metabolism, which allows for production of adenosine triphosphate (ATP) as well as substrates for the generation of neurotransmitters,11 is disrupted in epileptic patients, creating a need for alternative sources of brain energy.11–16 While high-fat, low-carbohydrate diets utilizing long-chain triglycerides have been used and studied in children, this type of diet has yet to be shown to significantly improve seizure control in dogs.17 In addition, such diets also are unsatisfactory from a nutrient and palatability standpoint for dogs requiring lifelong therapy. Fortunately, dogs can metabolize mediumchain triglycerides (MCTs) to produce ketones,18 and experts believe that dietary MCTs may also have direct antiseizure effects via blocking the alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain.19 Diets supplemented with MCT oil for dogs can also be formulated with lower amounts of fat and higher proportions of protein and carbohydrates than traditional ketogenic diets—an important factor when a diet needs to be fed for the remainder of a dog’s life. EPILEPSY STUDY EXAMINES THE EFFECTS OF TEST DIET WITH MCT OIL ON SEIZURES Neurologic researchers at the Royal Veterinary College (RVC), in partnership with Purina, recently investigated the potential role of diet in the nutritional management of dogs whose seizures were not being well controlled with AEDs. While achieving complete remission was not considered realistic for many patients, the

goal was to reduce seizure frequency in epileptic dogs on chronic AED therapy. A total of 21 dogs with idiopathic epilepsy that had experienced at least 3 seizures in the 3 months prior to enrollment completed a 6-month, randomized, placebo-controlled, double-blinded crossover study at the RVC. The study demonstrated for the first time that a test diet with MCT oil can have positive effects on reduction of seizure frequency when fed as an adjunct to veterinary therapy.18 Dogs in the 2 groups were fed either a test diet containing MCT oil or a placebo diet for a period of 3 months—then switched to the other diet. In the study, the following results were noted: 7 1% of dogs showed a reduction in seizure frequency 4 8% of dogs showed a 50% or greater reduction in seizure frequency 1 4% of dogs achieved complete seizure freedom DIET HELPS NUTRITIONALLY MANAGE DOGS WITH EPILEPSY AS AN ADJUNCT TO VETERINARY THERAPY The results of this study inspired Purina to develop the Purina® Pro Plan® Veterinary Diets NC NeuroCare™ diet, which is formulated with MCT oil to help nutritionally manage dogs with epilepsy that are also being administered AEDs. The diet is enhanced with a unique blend of nutrients—eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, antioxidants, and B vitamins, as well as MCT oil—to promote cognitive health and help nutritionally manage dogs with cognitive dysfunction syndrome.  REFERENCES 1. 2016 Veterinary Landscape Dashboard. 2. Bollinger-Schmitz, K, Kline, K. An overview of canine idiopathic epilepsy for the small animal practitioner. Iowa State University Veterinarian Publication 2000;62(1). 3. Berendt M, Farquhar RG, Mandigers PJJ, et al. International veterinary epilepsy task force consensus report of epilepsy definition, classification and terminology in companion animals. BMC Vet Res 2015;11:182. 4. Skerritt G. Canine epilepsy. In Pract 1988;10:27-30. 5. Packer RMA, Shihab NK, Torres BBJ, et al. Responses to successive anti-epileptic drugs in canine idiopathic epilepsy. Vet Rec 2015;176(8):203. 6. Arrol L, Penderis J, Garosi L, et al. Aetiology and longterm outcome of juvenile epilepsy in 136 dogs. Vet Rec 2012;170:335. 7. Podell M, Fenner W. Bromide therapy in refractory canine idiopathic epilepsy. J Vet Intern Med 1993;7:318-327. 8. Trepanier L, Schwark W, Van Schoick A, et al. Therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide alone or in combination with

A special section to Todayâ&#x20AC;&#x2122;s Veterinary Practice

May/June

RESEARCH

NUTRITIONAL SUPPORT

shutterstock.com/Halfpoint

A properly planned diet can help nutritionally manage dogs with epilepsy as a supplement to veterinary therapy.

10.

11.

12.

13.

14.

other anticonvulsants: 122 cases (1992-1996). JAVMA 1998;213:1449-1453. Schwartz-Porsche D, Loscher W, Frey H. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J Vet Pharmacol Ther 1985;8:113-119. Neal EG, Chaffe H, Schwartz RH, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 2009;50:1109-1117. Viitmaa R, Haaparanta-Solin M, Snellman M, et al. Cerebral glucose utilization measured with high resolution positron emission tomography in epileptic Finnish Spitz dogs and healthy dogs. Vet Radiol Ultrasound 2014;55:453-461. Jokinen TS, Haaparanta-Solin M, Viitmaa R et al. FDG-PET in healthy and epileptic Lagotto Romagnolo dogs and changes in brain glucose uptake with age. Vet Radiol Ultrasound 2014;55:331-341. Eom KD, Lim CY, Gu SH et al. Positron emission tomography features of canine necrotizing meningoencephalitis. Vet Radiol Ultrasound 2008;49:595-599. Kang BT, Kim SG, Lim CY et al. Correlation between fluorodeoxyglucose positron emission tomography and

15.

16.

17.

18.

19.

magnetic resonance imaging findings of non-suppurative meningoencephalitis in 5 dogs. Can Vet J 2010;51:986-992. Kim YK, Lee DS, Lee SK, et al. Differential features of metabolic abnormalities between medial and lateral temporal lobe epilepsy: quantitative analysis of 18F-FDG PET using SPM. J Nucl Med 2003;44:1006-1012. Galazzo IB, Mattoli MV, Pizzini FB, et al. Cerebral metabolism and perfusion in MR-negative individuals with refractory focal epilepsy assessed by simultaneous acquisition of 18F-FDG PET and arterial spin labeling. NeuroImage Clinical 2016;11:648657. Patterson EE, Munana KR, Kirk CA, et al. Results of a ketogenic food trial for dogs with idiopathic epilepsy. J Vet Int Med 2005;19:421. Law TH, Davies ES, Pan Y, et al. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr 2015;114(9):1438-1447. Chang, PS, Augustin K, Boddum K, et al. Seizure control by decanoic acid through direct AMPA receptor inhibition. Brain 2015;25:1-13.

A special section to Today’s Veterinary Practice

May/June

PREVENTION

ABOUT THE AUTHORS

Donna Raditic, DVM, DACVN

Nutritionists’ View: Over-the-Counter Versus Therapeutic Veterinary Diets onna Raditic, DVM, DACVN D Joe Bartges, DVM, PhD, DACVN, DACVIM

Dr. Raditic received a BS in Animal Science at Cornell University and her DVM at Cornell’s College of Veterinary Medicine. She has been a professor of nutrition and integrative medicine at the University of Tennessee College of Veterinary Medicine. Dr. Raditic is an author and coauthor of textbooks and research in nutrition and integrative therapies. Her interests are nutritional therapies in small animal diseases, supplements, integrative therapies in disease states, metabolomics, translational research, and One Health. Based in Athens, Georgia, she currently does consulting on nutrition and integrative veterinary medicine.

ith so many brands and types of foods available (pet food sales exceed $24 billion in the United States, with Nestle Purina PetCare, Mars PetCare Inc, Big Heart Pet Brands, Hill’s Pet Nutrition, Diamond Pet Foods, and Blue Buffalo accounting for approximately 70% of the market), owners, veterinarians, and veterinary nurses can have difficulty interpreting ingredient labels, assessing the quality of diets, and understanding pet food regulations. As a result, members of the veterinary healthcare team may be reluctant to make specific recommendations. Veterinary healthcare teams are familiar with recommending veterinary therapeutic diets (VTD) for management of chronic

disease states, but many of these diets are suitable for adult maintenance and growth. VTD have accessible information on caloric and nutrient profiles, may address inflammation with specific nutrients, and have higher digestibility and less contamination than over-the-counter (OTC) diets. DIFFERENCES BETWEEN OTC DIETS AND VTD The term “therapeutic diet” has no legal definition; however, the Food and Drug Administration has guidelines for the labeling and marketing of canine and feline diets intended to diagnose, cure, mitigate, treat, or prevent diseases (BOX 1). These

Joe Bartges, DVM, PhD, DACVN, DACVIM CONSTANT CRAVING Calories consumed per day is the best common measure across all diets.

shutterstock.com/Sidarta

Dr. Bartges earned his DVM at the University of Georgia College of Veterinary Medicine and PhD at the University of Minnesota. He has served as an interim department head at the University of Tennessee as well as an internist and nutritionist at Cornell University Veterinary Specialists. Currently, Dr. Bartges is Professor of Medicine and Nutrition at the University of Georgia College of Veterinary Medicine. He is on the editorial boards of 5 journals, a consultant for the Urinary and Nutrition boards with Veterinary Information Network, and a member of the Blue Buffalo Veterinary Advisory Board.

A special section to Today’s Veterinary Practice

May/June

PREVENTION

BOX 1

TABLE 1

AAFCO Statements for VTD

Online Resources College of Veterinary Nutrition (acvn.org)

AAFCO ADULT MAINTENANCE*

AAFCO GROWTH*

Hill’s i/d Purina EN Purina DRM Purina HA Vegetarian Purina JM Royal Canin GI Puppy Royal Canin HP

Yes Yes Yes Yes Yes No Yes

Yes Yes Yes Yes Yes Yes Yes

Royal Canin Select Protein PV

Yes

Yes Yes Yes

Yes

 American

CANINE DRY VTD

 Food and Drug Administration: FDA’s Regulation

of Pet Food (fda.gov/animalveterinary/ resourcesforyou/ucm047111.htm)

guidelines came about because such diets were historically distributed only through veterinarians; however, some of these diets are now available to consumers through Internet or store purchase with a veterinary prescription. VTD are usually considered for managing specific medical conditions, such as kidney disease or osteoarthritis.1,2 Their ingredients and/or composition differ from OTC pet foods for a specific purpose, but this does not always preclude recommending these diets for healthy patients. Additionally, the quality control of their manufacture is often more stringent than that of OTC diets. Although some may carry statement reading “use under supervision of a veterinarian,” many VTD have AAFCO nutritional adequacy statements for adult and sometimes growth life stages (TABLE 1). For these reasons, we often recommend VTD for healthy pets to provide better nutrition and to aid in prevention of common disease states.

Blue Buffalo GI FELINE DRY VTD Hill’s i/d Purina EN Purina HA Royal Canin High Energy GI Royal Canin Select Protein PV *According to current product guides.

BENEFITS OF VTD VTD are formulated to assist in managing medical conditions based on known physiologic and nutritional differences between healthy individuals and those with a disease, or to contain nutrients that may have a functional role in managing a particular medical condition. For instance, VTD used for gastrointestinal (GI) disease

TABLE 2

Select Nutritional Profiles for Select Canine VTD and OTC Diets* CRUDE PROTEIN

CRUDE FAT

CRUDE FIBER

CALCIUM

PHOSPHORUS

CA:P RATIO

CANINE GI VTD 26.5

14.8

2.3

1.18

0.9

1.3:1

27.17 23.3

15.22 10

2.72 3.8

1.52 0.8

1.2 0.68

1.3:1 1.2:1

Purina EN CANINE OTC DIETS

27.67

13.09

1.02

1.45

1.5:1

Orijen Nature’s Variety Wellness Ziwi Solid Gold

43 42 37.8 44 45.6

20.4 22 17.8 34 22.2

4.5 4.4 4.4 2 4.4

2.16 2.56 2.22 2.41 NA

1.23 0.91 1.59 1.56 1.4

1.8:1 2.8:1 1.4:1 1.5:1 NA

Taste of the Wild AVERAGES

16.7

1.2

26.16 40.73

13.28 22.18

2.46 4.12

1.24 2.34

0.95 1.32

1.3:1 1.8:1

Hill’s i/d Blue Buffalo Natural GI Royal Canin Mod Calorie GI

VTD OTC Diet

*All amounts are given on a percentage dry matter basis.

The Food and Drug Administration has guidelines for the labeling and marketing of canine and feline diets intended to diagnose, cure, mitigate, treat, or prevent diseases.

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PREVENTION

PREVENTING OBESITY

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Caloric density is important in determining accurate feeding plans for pets at risk for becoming overweight/obese.

Prescribing VTD with known kcal/kg density along with exact feeding plans can be used to help prevent excess weight gain in at-risk pets.

are moderate in fat, calcium, and phosphorus. OTC diets often have more variable nutrient profiles and higher calcium:phosphorus ratios (TABLE 2). VTD may also contain anti-inflammatory nutrients, as inflammation is a component of many disease states. Formulated with omega-3 fatty acids,3 antioxidants,4 and other special nutrients, these diets attempt to modulate inflammation in GI, dermatologic, orthopedic, and urologic disease states. Digestibility of VTD has also been reported to be higher than that of OTC diets, and according to ELISA testing, VTD are not contaminated with soy or with a protein source not listed on the label.5â&#x20AC;&#x201C;7 When choosing diets to recommend for their patients, practitioners can access the complete nutrient profiles of VTD more easily than for many OTC diets. Caloric density in kcals/kg, kcals/cup, and kcals/can3 is available on websites and product guides; beginning in 2017, this information is required on all pet food labels. Caloric density is important in determining accurate feeding plans for pets

at risk for becoming overweight/obese. Information regarding the use of VTD is also available from manufacturers and Diplomates of the American College of Veterinary Nutrition (ACVN), who routinely use VTD. THE PRICING DIFFERENCE VTD are often perceived as expensive compared to OTC diets. TABLE 3 shows average costs of therapeutic and OTC diets, based on information obtained via the Internet. Compared with human food packaging, pet food bag and can sizes vary greatly. This variability makes it difficult to TABLE 3

Average Cost of Select VTD and OTC Diets DIET GI VTD Hydrolyzed VTD OTC Grocery Brands OTC Pet Store

COST (USD/100 KCAL) CANINE FELINE 0.19 0.27 0.21 0.08 0.31

0.38 0.08 0.40

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PREVENTION

compare costs on a “per bag or can” basis. We determined the costs of both VTD and OTC diets on a per 100 kcal basis for comparison, because calories consumed per day is the best common measure across all diets. VTD can be competitively priced when compared per 100 kcal. We suggest, however, that comparisons be simplified across the pet food industry by employing common bag and can sizes. PREVENTION, NOT JUST TREATMENT It has been reported that >50% of the US pet population is overweight.8 Prescribing VTD with known kcal/kg density along with exact feeding plans can be used to help prevent excess weight gain in at-risk pets. We recommend owners use a gram scale for weighing canned and dry foods, similar to human weight management plans, to deliver exact daily caloric intake. This also allows precise intake adjustments as the pet grows, is neutered, and ages (BOX 2). We also use VTD, especially those formulated for GI disease, orthopedic disease, and adverse food reactions, for patients who are “at risk” for chronic disease states. For instance, we have used VTD in breeds of dogs at risk for developmental orthopedic disease, obesity, and immunologic adverse food reactions. We use VTD in cats at risk for obesity and urinary tract disease because of neutering and environmental conditions (eg, indoor versus outdoor, single cat versus multicat household). As VTD have more similar, moderate, and complete and known nutrient profiles along with company support, we encourage practitioners to recommend these diets for adult maintenance and growth. In our opinion, better quality control, fatty acid balance, and reported higher digestibility of VTD make these diets better nutrition for pets.  REFERENCES 1. Polzin DJ. Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats. J Vet Emerg Crit Care (San Antonio) 2013;23:205-215. 2. Bartges JW, Budsberg SC, Pazak HE, et al. Effects of different n6:n3 fatty acid ratio diets on canine stifle osteoarthritis. Orthopedic Research Society 47th Annual Meeting 2001. 3. Bauer JE. Therapeutic use of fish oils in companion animals. JAVMA 2011;239:1441-1451. 4. Sparkes AH. Feeding old cats—an update on new nutritional therapies. Top Companion Anim Med 2011;26:37-42. 5. Raditic DM, Remillard RL, Tater KC. ELISA testing for common food antigens in four dry dog foods used in

dietary elimination trials. J Anim Physiol Anim Nutr (Berl) 2011;95:90-97. 6. Willis-Mahn C, Remillard R, Tater K. ELISA testing for soy antigens in dry dog foods used in dietary elimination trials. JAAHA 2014;50:383-389. 7. Parr JM, Remillard RL. Common confounders of dietary elimination trials contain the antigens soy, pork, and beef. JAAHA 2014;50:298-304. 8. Larsen JA, Villaverde C. Scope of the problem and perception by owners and veterinarians. Vet Clin North Am Small Anim Pract 2016;46:761-772. 9. Bartges JW, Kirk CA, Lauten S. Calculating a patient's nutritional requirements. Vet Med 2004;99:632. 10. Root MV, Johnston SD, Olson PN. Effect of prepuberal and postpuberal gonadectomy on heat production measured by indirect calorimetry in male and female domestic cats. Am J Vet Res 1996;57:371-374. 11. Jeusette I, Daminet S, Nguyen P, et al. Effect of ovariectomy and ad libitum feeding on body composition, thyroid status, ghrelin and leptin plasma concentrations in female dogs. J Anim Physiol Anim Nutr (Berl) 2006;90:12-18. 12. Bermingham EN, Thomas DG, Cave NJ, et al. Energy requirements of adult dogs: a meta-analysis. PLoS One 2014;9:e109681. 13. Morrison R, Penpraze V, Greening R, et al. Correlates of objectively measured physical activity in dogs. Vet J 2014;199:263-267.

BOX 2

Example of Lifetime Change in Nutritional Requirements Puppy (4.5 kg)  Resting  Diet:

energy requirement (RER)9: 218 kcal × 1.6 (growth) = 349 kcal/day

Dry GI VTD containing 3594 kcal/kg (3.6 kcal/g)

 Amount

to feed: 349 kcal/3.6 kcal/g = 97 g/day

 Feeding

plan: Feed 32 g of dry GI VTD 3 times/day

Neutered adult (11 kg)*  RER:

423 kcal × 1.2 (adult maintenance) = 508 kcal/day

 Diet:

Dry GI VTD containing 3594 kcal/kg (3.6 kcal/g)

 Amount

to feed: 508 kcal/3.6 kcal/g = 141 g/day

 Feeding

plan: Feed 70 g of dry GI VTD 2 times/day

Overweight (BCS 6/9) neutered adult (13 kg) maintained on dry GI VTD**  RER:

479 kcal × 1 = 479 kcal/day

 Diet:

Dry GI VTD containing 3594 kcal/kg (3.6 kcal/g)

 Amount

to feed: 479 kcal/3.6 kcal/g = 133 g/day

 Feeding

plan: Feed 66 g of dry GI VTD 2 times/day

Overweight (BCS 8/9) neutered adult (13 kg) switched to dry weight-loss VTD**  RER:

479 kcal × 0.8 = 383 kcal/day

 Diet:

Dry weight-loss VTD containing 3000 kcal/kg (3.0 kcal/g)

 Amount

to feed: 479 kcal/3.0 kcal/day = 127 g/day

 Feeding

plan: Feed 64 g of dry weight-loss VTD 2 times/day

*Caloric intake will need to be adjusted with growth and then again when a pet is neutered.10,11 **Weight increase may be related to breed risk or individual inactivity.12,13

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PRACTICAL TOXICOLOGY

Tremorgenic Mycotoxin Intoxication In Dogs Kirsten Waratuke, DVM, DABT ASPCA Animal Poison Control Center, Urbana, Illinois shutterstock.com/Grigorita Ko

Welcome to Practical Toxicology, brought to you in partnership between Today’s Veterinary Practice and the ASPCA Animal Poison Control Center (APCC) (aspcapro.org/poison). This column provides practical clinical information about diagnosing and treating pets that have been exposed to potentially harmful substances. The APCC: rovides 24-hour diagnostic and treatment •P recommendations by specially trained veterinary toxicologists rotects and improves animal lives through toxicology •P education, consulting services, and case data review eveloped and maintains AnTox, an animal toxicology •D database system that identifies and characterizes toxic effects of substances in animals orks closely with human poison control centers to •W provide animal poisoning information ffers extensive veterinary •O toxicology consulting to organizations in industry, government, and agriculture. If treating a patient that requires emergency care for poisoning, call the APCC at 888-426-4435.

Tremorgenic mycotoxins are metabolites produced by fungi that cause neurotoxicosis in dogs. While several fungal metabolites may cause this intoxication, current research supports penitrem A as the primary mycotoxin involved. The fungi most commonly associated with penitrem A, Penicillium species, grow on meat, cereals, nuts, cheese, eggs, fruits, processed/ refrigerated food, refuse, and compost.1,2 Small animal veterinarians most commonly treat dogs for penitrem A intoxication; however, rats, mice, rabbits, guinea pigs, hamsters, and calves have also been affected.3 There are no published reports of penitrem A toxicosis in cats. Based on the current understanding of the toxin’s mechanism of action, there is no reason to believe cats could not be affected by penitrem A; most likely, the absence of feline cases is explained by the more discerning eating habits of cats.

CLINICAL SIGNS Muscle tremors are the hallmark clinical sign of tremorgenic mycotoxin intoxication (Box 1).

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Aspiration has been reported and is a worrisome complication; when heavy sedation is necessary to control tremors, the risk of aspiration increases.4,5

Baseline laboratory tests should include a complete blood cell count (CBC), blood chemistry, electrolytes, and urinalysis.

Since patients may present with an unknown exposure history, considering other diagnostic differentials is important. These differentials may include pyrethroids, metaldehyde, bromethalin, strychnine, organophosphates/ carbamates, paintballs, methylxanthines (caffeine, theophylline, theobromine), ivermectin, macadamia nuts, cocaine, amphetamines, ethylene glycol, and some heavy metals.7

Elevations in liver and kidney values as well as creatine kinase have been noted.2 Penitrem A has been isolated from the liver and kidney in an intoxicated dog, but the role it plays in the liver and kidneys is not known.2 Other potential causes of elevations in liver and kidney values include significant muscle activity and adverse effects of drugs used to control clinical signs.2

Nontoxic diagnostic differentials may include steroid-responsive tremor syndrome (idiopathic tremor syndrome), cerebellar disease, idiopathic episodic tremors, metabolic disorders (eg, hypoglycemia), hypocalcemia, and hepatic encephalopathy. Infectious diseases such as distemper and rabies should also be included under nontoxic differentials.7

Patients may develop dehydration and electrolyte changes secondary to vomiting and diarrhea. Additionally, disseminated intravascular coagulopathy may occur secondary to severe hyperthermia.

MECHANISM OF ACTION

DIAGNOSTICS

DIAGNOSIS In many cases, a presumptive diagnosis of tremorgenic mycotoxin toxicity is made based on clinical signs and a history including access to compost piles, moldy food, or roaming behavior. A more definitive diagnosis may be made through testing suspected foodstuffs, stomach ingesta, or vomitus for the presence of penitrem A or another metabolite, roquefortine C, which is often found in tandem with penitrem A.6 On necropsy, penitrem A has been isolated from the liver, kidney, and brain.2

As with many toxins, the exact mechanism of action of penitrem A is not known. However, it is known that its primary site of action is the central nervous system. Most likely, penitrem A has dual roles affecting both inhibitory and excitatory neurotransmission.8 Penitrem A appears to be rapidly absorbed, with onset of clinical signs starting as soon as 15 minutes after exposure up to several hours later. The dose of penitrem A may affect how quickly clinical signs occur. In one study, mice administered larger doses of penitrem A had faster onset of clinical signs.8 In most patients, signs resolve within 24 to 48 hours; however, there are rare reports of signs lasting longer. In one patient, mild signs persisted for 7 months, and another patient had signs still present 3 years later.2

BOX 1. Clinical Signs Associated With Tremorgenic Mycotoxin Intoxication

TREATMENT

• Muscle tremors

• Diarrhea

There are two important goals when treating toxicosis:

• Ataxia

• Hyperesthesia

1. Prevent absorption of the toxin (decontamination).

• Seizures

• Nystagmus

• Vomiting

• Hyperthermia

2. Treat the clinical effects of the intoxication. Induction of emesis, gastric lavage, and administration of activated charcoal have all been

PRACTICAL TOXICOLOGY

used to address tremorgenic mycotoxin toxicity. Because of the rapid absorption of penitrem A and rapid onset of clinical neurologic signs, the window of opportunity to safely induce emesis and administer activated charcoal is generally limited.4,9 As the ability to safely induce emesis and/ or give activated charcoal may be limited, gastric lavage may provide some benefit. Patients presenting with severe signs (eg, notable hyperthermia, severe muscle tremors, seizures) may require heavy sedation or even anesthesia to control clinical signs. Once clinical signs are appropriately controlled, patient size and time of toxin exposure become important factors in deciding whether gastric lavage should be performed. Radiographs may be useful to assess how much material is in the stomach. The size of the patient dictates the bore of orogastric tube that can be used; recovering food material through a small-bore tube may prove futile.5 Instilling activated charcoal after gastric lavage via stomach tube may be considered but should be weighed against risk for aspiration.9

The patient’s temperature should be monitored closely for hyperthermia. Management of muscle tremors will help address the cause of hyperthermia, but other cooling measures may be warranted, such as wetting the patient, fans, and IV fluids; in severe cases, cold packs or running the IV fluid line through cool water may be warranted. Cooling measures should be discontinued when the temperature reaches 102.5°F to prevent rebound hypothermia.12

Intravenous Lipid Emulsion Therapy Intravenous lipid emulsion (ILE) therapy is a newer therapy that is gaining popularity in veterinary medicine. Although initially designed to treat local anesthetic overdoses in humans, its use has been expanded to include a variety of lipophilic drug overdoses in both humans and veterinary species. The mechanism of action of ILE therapy is not known; however, it likely includes a “lipid sink” or “lipid shuttle,” where lipid-soluble drugs are transiently sequestered in intravenous liposomes, as well as direct cardiovascular effects.13

Symptomatic Care Control of tremors is paramount (Box 2); however, this may be a challenge. While diazepam and barbiturates are advised, they may not always be effective (eg, diazepam). Heavy sedation also places the pet at risk for aspiration. Methocarbamol has been used with success. Other drugs used to control tremors include propofol and gas anesthesia. IV fluids should be administered to all patients that do not have physical contraindications to fluid therapy. Benefits of IV fluids include correction of electrolyte abnormalities and fluid loss secondary to vomiting or diarrhea, cooling (in patients with hyperthermia), and minimizing the risk of kidney injury from myoglobinuria secondary to rhabdomyolysis. Antiemetics should be used in vomiting patients to limit risk of aspiration, dehydration, and electrolyte abnormalities.

BOX 2. Drugs Used to Control Tremors •M ethocarbamol*: 55−220 mg/kg IV; administer half the estimated dose ≤2 mL/min, wait until the patient starts to relax, and then continue to administer to effect10 •D iazepam: 0.5−1 mg/kg IV; 0.1-2 mg/kg/h CRI10 •M idazolam: 0.07−2 mg/kg IV or IM; 0.05−0.5 mg/kg/h CRI10 •P henobarbital: 2−20 mg/kg IV: administer 2−5 mg/kg IV bolus q20min to effect11 •P ropofol: 6 mg/kg IV followed by 0.1−0.6 mg/kg/min CRI 10

*Extra-label dosing for methocarbamol: Consider initial IV bolus followed by constant-rate infusion (CRI) or multiple IV boluses, titrating dose and frequency to effects. The labeled maximum dosing of 330 mg/kg/d can be exceeded, if necessary, but monitoring for central nervous system depression, seizures, and hypotension is warranted.10

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IN SUMMARY Kirsten Waratuke

Kirsten Waratuke, DVM, DABT, received her degree in biology and doctorate of veterinary medicine from the University of Illinois. After working at a small animal practice and emergency clinic, she joined the ASPCA Animal Poison Control Center (APCC) as a consulting veterinarian in clinical toxicology. In addition to answering calls on the APCC hotline, Dr. Waratuke also co-authors the Tox Insider, a monthly e-newsletter for veterinarians and veterinary staff, and has published several papers and book chapters. She received her Diplomate of the American Board of Toxicology credential in 2016.

Because many dogs have indiscriminate eating habits, tremorgenic mycotoxicosis is an intoxication small animal veterinarians may see in practice. Ingestion of moldy foods may not be witnessed; therefore, it is important for veterinarians to be familiar with clinical signs and differential diagnoses commonly associated with tremorgenic mycotoxin intoxication. In addition, because of the potential for rapid onset and potentially life-threatening signs, prompt care may affect the outcome in these cases. References

Penitrem A is believed to be a lipid-soluble compound, making it a potential candidate for ILE therapy. However, information regarding the use of ILE with tremorgenic mycotoxin intoxication is limited.14,15 ILE therapy may be indicated in patients with a lipophilic toxicosis that does not respond to standard therapy and when signs are serious or life-threatening.

Evaluation of liver, pancreas, and kidney functions, as well as correction of any electrolyte abnormities, is best done before administration of ILE.15-17 Adverse effects of and contraindications to ILE therapy include:

6. Tiwary AK, Puschner B, Poppenga RH. Using roquefortine C as a biomarker for penitrem A intoxication. J Vet Diagn Invest 2009;21(2):237-239.

• Allergic or anaphylactoid reactions to components in the lipid emulsion • Inability or decreased ability to clear lipids from the bloodstream • Volume overload

2. Eriksen GS, Jaderlund KH, Moldes-Anaya A, et al. Poisoning of dogs with tremorgenic Penicillium toxins. Med Mycol 2010;48(1):188-196. 3. Arp LH, Richard JL. Intoxication of dogs with the mycotoxin penitrem A. JAVMA 1979;175(6):565-566. 4. Boysen SR, Rozanski EA, Chan DL, et al. Tremorgenic mycotoxicosis in four dogs from a single household. JAVMA 2002;221(10):14411444. 5. Lowes NR, Smith RA, Beck BE. Roquefortine in the stomach contents of dogs suspected of strychnine poisoning in Alberta. Can Vet J 1992;33(8):535-538.

7. Barker AK, Stahl C, Ensley SM, Jeffery ND. Tremorgenic mycotoxicosis in dogs. Compend Contin Educ Vet 2013;35(2):E2. 8. Moldes-Anaya A, Rundberget T, Faeste CK, et al. Neurotoxicity of Penicillium crustosum secondary metabolites: tremorgenic activity of orally administered penitrem A and thomitrem A and E in mice. Toxicon 2012;60(8):1428-1435. 9. Crandell D. Toxicological emergencies. In: Mathews KA, ed. Veterinary Emergency and Critical Care Manual. 2nd ed. Guelph: Lifelearn Publishers; 2006:630-640. 10. Plumb DC. Plumb’s Veterinary Drug Handbook. 8th ed [online]. plumbsveterinarydrugs.com. Accessed February 2017. 11. Plumb DC. Plumb’s Veterinary Drug Handbook. 7th ed. Ames: Wiley-Blackwell; 2011. 12. Mathews KA. Hyperthermia, heatstroke, and malignant hyperthermia. In: Mathews KA, ed. Veterinary Emergency and Critical Care Manual. 2nd ed. Guelph: Lifelearn Publishers; 2006:297-303.

• Pancreatitis • Hemolysis • Interference with common laboratory testing • Interference with other treatment modalities (the “lipid sink” is not selective and may affect lipophilic drugs as well as toxins) • Recurrence of clinical signs if lipid emulsion is eliminated prior to the toxin

Evans TJ, Gupta RC. Tremorgenic mycotoxins. In: Gupta RC, ed. Veterinary Toxicology Basic and Clinical Principles. 2nd ed. San Diego: Elsevier; 2012:1231-1237.

PRACTICAL TOXICOLOGY

13. Fettiplace MR, Weinberg G. Past, present and future of lipid resuscitation therapy. J Parenter Enteral Nutr 2015;39(1 Suppl):72S83S. 14. Eriksen GS, Moldes-Anaya A, Faeste CK. Penitrem A and analogues: toxicokinetics, toxicodynamics including mechanism of action and clinical significance. World Mycotoxin J 2013;6(3):263-272. 15. Robben JH, Dijkman MA. Lipid therapy for intoxications. Vet Clin North Am Small Anim Pract 2016;47(2):435-450. 16. Gwaltney-Brant S, Meadows I. Use of intravenous lipid emulsions for treating certain poisoning cases in small animals. Vet Clin North Am Small Anim Pract 2012;42(2):251-262. 17. Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg 2009;108(4):1344-1346.

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PRACTICAL PARASITOLOGY

The Flea-Infested Pet: Overview of Current Products Cherie M. Pucheu-Haston, DVM, PhD, DACVD Louisiana State University School of Veterinary Medicine shutterstock.com/Elwynn

Dealing with flea-infested pets has never been easier—or more complicated. At this time, at least 20 active ingredients are commonly used in prescription flea control products in the United States, with numerous other ingredients appearing in various over-the-counter products. Despite this wealth of options, providing practical and effective suggestions for flea control to clients can still be a frustrating and overwhelming experience. This article provides an overview of some of the clinically relevant features of currently available flea control agents (Table 1). A subsequent article will discuss how to use client and patient information to help select an optimal treatment control program.

PYRETHRIN AND PYRETHROIDS These are the oldest flea control products currently in common use. Both pyrethrin and pyrethroids work by disrupting insect nerve sodium channels.1 They are active against adult fleas but have no efficacy against immature stages. Pyrethrin is derived from the chrysanthemum plant.2 It is generally very safe when applied properly, even in young cats.1 Pyrethrin has a very quick “knock-down” effect but minimal residual activity. It is readily removed

PRACTICAL PARASITOLOGY

by water exposure. Pyrethrin products are often formulated to include a synergist, such as piperonyl butoxide. These synergists are typically well tolerated in dogs and cats when used at label doses. However, pyrethrins and many synergists may be highly toxic to other pet species, such as fish and amphibians.2,3 Pyrethroids are synthetic pyrethrins. Compared with pyrethrin, these products have a slightly slower onset of action but significantly better residual and repellent effects. Examples of this class include permethrin and cyphenothrin. Pyrethroids are often combined with other agents to take advantage of the pyrethroids’ repellent effects and efficacy against ticks. Examples of these products include K9 Advantix (bayerdvm.com), Certifect, Vectra 3D (vectrapet.com), and Activyl Tick Plus (us.activyl.com). As a general rule, pyrethroids have relatively poor resistance to water exposure. Unfortunately, most pyrethroids are extremely toxic to cats.1 Notable exceptions include flumethrin and etofenprox, which appear to be well tolerated by most cats. Signs of pyrethroid intoxication include depression, coma, seizures, hypersalivation, muscle twitching or tremors, and hyperthermia. Severe or

PRACTICAL PARASITOLOGY

untreated intoxication may be fatal.4 Many cases of pyrethroid intoxication come from mistaken or intentional application of dog-only flea control formulations. However, a few cases of toxicity have been reported in cats that came into contact with treated dogs soon after application.5 For this reason, client education is critical when dispensing pyrethroid-containing products to households that include cats. Alternatively, these products may be avoided completely for dogs that live with cats or as environmental treatments in homes with cats.4

Resistance to pyrethrins and pyrethroids has been reported in both colonized flea strains and wildcaught fleas.6,7 Resistance may be associated with mutations in a gene coding for neural sodium channels.8 These mutations, which are commonly referred to as kdr (knockdown resistance) or super kdr mutations, are widely distributed throughout flea colonies and in field-collected fleas.9 As a result, the effectiveness of this class of compounds may be reduced in some areas, especially when they are not combined with other therapeutic agents.

TABLE 1 Overview of Current Products ACTIVE INGREDIENT

CLASS

TRADE NAMES

SPECIES

Imidacloprid

Neonicotinoid

Advantage II Advantage Multi K9 Advantix

Dogs Cats (except K9 Advantix, which includes permethrin)

Fipronil

Phenylpyrazole

Frontline, many others

Dogs, cats

Selamectin

Avermectin

Revolution

Dogs, cats

Indoxacarb

Oxadiazine

Activyl Activyl Tick Plus

Dogs Cats (except Activyl Tick Plus, which includes permethrin)

Pyrethrin

Many

Dogs, cats

Permethrin

Pyrethroid

Many

Dogs only

Flumethrin

Pyrethroid

Seresto

Dogs, cats

Dinotefuran

Neonicotinoid

Vectra Vectra 3D

Dogs Cats (except Vectra 3D, which includes permethrin)

Spinetoram

Neonicotinoid

Cheristin

Cats only

Fluralaner

Isoxazoline

Bravecto topical

Dogs, cats

Spinosad

Neonicotinoid

Comfortis Trifexis

Dogs, cats

Nitenpyram

Neonicotinoid

Capstar

Dogs, cats

Afoxolaner

Isoxazoline

NexGard

Dogs Not labeled for cats, but OK in households with treated dogs

Fluralaner

Isoxazoline

Bravecto

Dogs Not labeled for cats, but OK in households with treated dogs

Sarolaner

Isoxazoline

Simparica

Dogs Not labeled for cats, but OK in households with treated dogs

TOPICAL

ORAL

INSECT GROWTH REGULATORS Lufenuron

Chitin synthesis inhibitor

Sentinel

Dogs, cats

Methoprene

Juvenile hormone analog

Many

Dogs, cats

Pyriproxyfen

Juvenile hormone analog

Many

Dogs, cats

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NEONICOTINOIDS

Dinotefuran

This class of agents acts by binding to insect acetylcholine receptor sites.1 This induces inhibition of insect nervous system function, with subsequent paralysis and death.

This agent is primarily active against adult fleas.1 It is available in a spot-on formulation in combination with an insect growth regulator either with (Vectra 3D) or without (Vectra) permethrin. It is labeled for application once monthly. This agent has moderate to good resistance to water, although it is suggested that the pet not be bathed or allowed to swim for several hours after application.15 Nonetheless, it is probably not ideal for a dog that swims or is bathed very frequently.

Imidacloprid This product has a rapid onset of action.10,11 It primarily targets adult fleas, and it is often combined with an insect growth regulator to provide efficacy against immature flea stages.1 Imidacloprid is available as a spot-on product, either by itself or in combination with permethrin (K9 Advantix), flumethrin (Seresto collar; seresto.com), or moxidectin (Advantage Multi; bayerdvm.com). Imidacloprid is generally very well tolerated by most individuals. Products containing imidacloprid alone (or imidacloprid/insect growth regulator alone) can be applied up to once weekly for aggressive flea control.1 In my experience, imidacloprid has poor water resistance and must be reapplied after bathing or water immersion. The imidacloprid/flumethrin collar appears to replenish the product on the pet, making this product better suited for patients that are bathed or swim regularly.12 However, this does shorten the expected lifespan of the collar. The efficacy of the collar is generally very good, which represents a substantial improvement over most older flea collars (typically containing organophosphates), which demonstrated low efficacy.13,14

Nitenpyram This agent is available as a nonflavored oral tablet (Capstar). It has a very rapid onset of activity against adult fleas but a short duration of action (approximately 24 to 48 hours).1 Because of the speed of onset, it is well suited for rapid decontamination of animals before or after hospitalization or boarding or after trips to areas such as dog parks. The short duration of action makes it poorly suited for use as a primary flea control agent, but it can be used as often as daily if desired.1 For this reason, it is sometimes used daily for a short period to get a â&#x20AC;&#x153;head startâ&#x20AC;? on flea depopulation in heavily contaminated environments. It has no larvicidal or ovicidal properties.1

PRACTICAL PARASITOLOGY

Spinosad/Spinetoram These two products are closely related. Spinosad is a naturally occurring mixture of spinosyns A and D, which are produced by Saccharopolyspora spinosa, a soil-dwelling actinomycete bacterium.16 It is available as a flavored (pork) tablet. It should be given with food.16 The same formulation (Comfortis; comfortis.com) is used in cats and dogs, although the feline version reflects the need for a higher dose per body weight than in dogs (50 mg/kg vs 30 mg/kg, respectively). It is labeled for once-monthly administration. The major side effect in both species is vomiting, which can be treatment limiting in some individuals.16 Spinosad should be administered with caution (or avoided entirely) in dogs with preexisting seizure disorders because seizures have been associated with administration of this drug in these dogs.16 However, this effect has not been reported in cats. Spinosad should not be given with extralabel doses of ivermectin because coadministration has been associated with seizures, ataxia, twitching, and other neurologic signs.16 Spinetoram is a semisynthetic insecticide produced by chemical modification of the naturally occurring spinosyns J and L.17 It is labeled for use in cats only (Cheristin; cheristin4cats.com).18 It is provided as a spot-on formulation, which may be easier for some clients to administer than oral tablets. It is normally well tolerated, although it may be associated with vomiting in some cats. Applicationsite dermatitis has been reported, although this is less common than with the older formulation.18,19

PRACTICAL PARASITOLOGY

ISOXAZOLINES These products selectively inhibit insect gammaaminobutyric acid (GABA)- and glutamate-gated chloride channels. This induces hyperexcitation and uncontrolled central nervous system activity, resulting in death of the insect.1 There are currently three agents in this category: afoxolaner, fluralaner, and sarolaner. Because the agents are very similar in many respects, they will be discussed together. Afoxolaner (NexGard; nexgardfordogs.com), fluralaner (Bravecto; us.bravecto.com), and sarolaner (Simparica; simparica.com) are all available as flavored chewable oral tablets labeled for dogs only; fluralaner is also available in a topical formulation for both cats and dogs.20–22 Afoxolaner and sarolaner are given monthly, whereas fluralaner is given every 3 months.20–22 Because these tablets are flavored with food-based ingredients (soy or pork), they are not suitable for administration during food allergy elimination diet trials, and they may or may not be tolerated by food-allergic individuals. However, because of fluralaner’s extended duration of action, it may be given at the beginning of an elimination diet, with efficacy expected to continue through the 10- to 12-week duration of the trial. Afoxolaner and sarolaner may be given with or without food, but the bioavailability of fluralaner is best when the agent is given with food.20 All 3 agents have very good efficacy against adult fleas and may also have clinically significant inhibition of flea reproduction. They are also efficacious against many species of ticks, including Ixodes scapularis, Dermacentor variabilis, Rhipicephalus sanguineus, and Amblyomma americanum.20–22 However, fluralaner must be given every 2 months for maximal efficacy against A americanum.20 Sarolaner also has efficacy against A maculatum.22 All of the agents appear to have very good efficacy against canine demodicosis.23–25 Evidence shows that they are also effective against Sarcoptes, although whether this is reliable enough to permit diagnostic therapy remains to be

seen.26–28 Sarolaner has also been demonstrated to be efficacious against Otodectes species.25 Overall, the 3 agents are well tolerated, with vomiting being the most common adverse effect.20–22 Afoxolaner should be given with caution in animals with preexisting seizure disorders, as breakthrough seizures have been reported.21 Seizures, ataxia, and trembling have been reported with sarolaner and with topical (but not oral) fluralaner in dogs.20,22 Similar reactions have not been reported in cats with topical fluralaner. The oral formulations of all agents are expected to be waterproof. Topical fluralaner is expected to be very water resistant after 3 hours.20

MISCELLANEOUS ACTIVE INGREDIENTS Selamectin This agent is an avermectin, similar to ivermectin.1,29 It activates insect glutamategated chloride channels, which causes paralysis and eventual death of the fleas. It is marketed as a spot-on product for both cats and dogs. It is primarily used for its heartworm preventive and flea control properties but also has label claims against Otodectes, Dermacentor, and Sarcoptes species in dogs and Otodectes, Toxocara, and Ancylostoma species in cats.29 It inhibits development of immature flea stages.30 Unlike some other avermectins, selamectin can be administered to ivermectin-sensitive dogs (although salivation and ataxia have been reported with extralabel dose administration in these breeds).29 Selamectin is systemically absorbed and is essentially waterproof after 2 hours.

Fipronil This agent belongs to the phenylpyrazole class.1 Like the isoxazolines, it acts by blocking GABAand glutamate-gated chloride channels, causing hyperexcitation and death. It is available as both a spray and a spot-on. Fipronil is available in numerous formulations, many of which include other agents (such as permethrin or amitraz). It

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Cherie Pucheu-Haston

Cherie Pucheu-Haston, DVM, PhD, is an associate professor of veterinary dermatology and immunology at Louisiana State University School of Veterinary Medicine. She received her DVM from Louisiana State University and completed her residency at North Carolina State University (NCSU). She worked as a specialist in private practice for 7 years, then returned to NCSU to pursue a PhD in immunology. She is serving as the American co-chair of the International Committee on Allergic Diseases in Animals. Her interests include the immunology of allergic skin and pulmonary diseases, as well as the immune response to fungal infections.

is labeled for once-monthly use. Fipronil kills adult fleas and is typically formulated with an insect growth regulator. Some reports suggest that this agent may be losing efficacy, at least against certain strains of fleas.31 Fipronil is somewhat water resistant but may not hold up if the patient requires frequent bathing or swims frequently.

CONCLUSIONS Todayâ&#x20AC;&#x2122;s veterinary practitioner has more choices than ever before when it comes to flea control. Nonetheless, there is still no single product that is ideal for use under all circumstances. Effective formulation of a flea control program requires a thorough understanding of the available products and of the individual client and patient situation. In the next article, I will discuss key factors that will allow the practitioner to select the right product for the patient. References 1.

Plumb DC. Plumb's Veterinary Drug Handbook. Stockholm, WI: PharmaVet, 2015.

2. Pyrethrins. Covallis, OR: National Pesticide Information Center, 2014: 1-4.

Indoxacarb

3. Piperonyl butoxide. Covallis, OR: National Pesticide Information Center, 2000: 1-4.

This agent belongs to the oxadiazine pesticide class. It is considered a pro-insecticide because it requires activation by insect enzymes to become effective.1 Once activated, it blocks sodium channels, resulting in flea paralysis and death. Indoxacarb has good water resistance but may not be sufficient in patients that require very frequent bathing or swim frequently. Indoxacarb is available as a spot-on formulation, both on its own (Activyl) and with permethrin (Activyl Tick Plus). This product is normally well tolerated, but there have been anecdotal reports of seizures, neurologic signs, and occasional application-site dermatitis (of varying severity) in both cats and dogs.

Insect Growth/Development Regulators Two classes of insect growth/development regulators have been registered for use as flea control products: juvenile hormone analogs (methoprene, pyriproxyfen) and chitin synthesis

inhibitors (lufenuron).1 These agents have no adulticidal effects but prevent the development or maturation of immature flea stages. They are not well suited for use as sole flea control products but are commonly added to formulation of agents with adulticidal therapy to provide broad, multiâ&#x20AC;&#x201C;life stage control.

PRACTICAL PARASITOLOGY

4. Wisner T. Feline toxins: recognition, diagnosis, treatment. In: Little SE, ed. August's Consultations in Feline Internal Medicine. St. Louis, MO: Elsevier; 2016:798. 5. Malik R, Ward MP, Seavers A, et al. Permethrin spot-on intoxication of cats Literature review and survey of veterinary practitioners in Australia. J Feline Med Surg 2010;12(1):5-14. 6. Bossard RL, Dryden MW, Broce AB. Insecticide susceptibilities of cat fleas (Siphonaptera: Pulicidae) from several regions of the United States. J Med Entomol 2002;39(5):742-746. 7. Lemke LA, Koehler PG, Patterson RS. Susceptibility of the cat flea (Siphonaptera: Pulicidae) to pyrethroids. J Econ Entomol 1989;82(3):839-841. 8. Bass C, Schroeder I, Turberg A, et al. Identification of mutations associated with pyrethroid resistance in the para-type sodium channel of the cat flea, Ctenocephalides felis. Insect Biochem Mol Biol 2004;34:1305-1313. 9. Rust MK, Vetter R, Denholm I, et al. Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci. Parasitol Res 2015;114(1):7-18. 10. Vo DT, Hsu WH, Abu-Basha EA, Martin RJ. Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals. J Vet Pharmacol Ther 2010;33(4):315-322. 11. Arther RG, Cunningham J, Dorn H, et al. Efficacy of imidacloprid for removal and control of fleas (Ctenocephalides felis) on dogs. Am J Vet Res 1997;58(8):848-850. 12. Stanneck D, Kruedewagen, EM, Fourie JJ, et al. Efficacy of an imidacloprid/flumethrin collar against fleas, ticks, mites and lice on dogs. Parasit Vectors 2012;5(1):102-108. 13. Dryden MW, Smith V, Davis WL, et al. Evaluation and comparison of a flumethrin-imidacloprid collar and repeated monthly treatments of fipronil/(s)-methoprene to control flea, Ctenocephalides f. felis, infestations on cats for eight months. Parasit Vectors 2016;9(1):287.

HEARTWORM HOTLINE

PRACTICAL PARASITOLOGY 14. Dantas-Torres F, Capelli G, Giannelli A, et al. Efficacy of an imidacloprid/flumethrin collar against fleas, ticks and tick-borne pathogens in dogs. Parasit Vectors 2013;6(1):245.

HEARTWORM HOTLINE continued from page 26

15. Vectra 3D product label. Lenexa, KS: Ceva Animal Health; 2013.

Finding and telling stories

16. Comfortis prescribing information. Indianapolis, IN: Elanco Animal Health; 2014. 17. Sparks TC, Crouse GD, Dripps JE, et al. Neural network-based QSAR and insecticide discovery: spinetoram. J Comput Aided Mol Des 2008;22(6):393401. 18. Cheristin product label. Indianapolis, IN: Elanco Animal Health, 2014. 19. Credille KM, Thompson LA, Young LM, et al. Evaluation of hair loss in cats occurring after treatment with a topical flea control product. Vet Dermatol 2013;24(6):602-605. 20. Bravecto prescribing information. Madison, NJ: Merck Animal Health; 2016. 21. NexGard prescribing information. Duluth, GA: Merial, Inc; 2015. 22. Simparica prescribing information. Kalamazoo, MI: Zoetis, Inc; 2015. 23. Beugnet F, Halos L, Larsen D, de Vos C. Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis. Parasite 2016;23:14-21. 24. Fourie JJ, Liebenberg JE, Horak IG, et al. Efficacy of orally administered fluralaner (BravectoTM) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs. Parasite Vectors 2015;8(1):187-193. 25. Six RH, Becskei C, Mazaleski MM, et al. Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp. and Otodectes cynotis. Vet Parasitol 2016;222:62-66.

OTHER RESOURCES One of the most effective client education tools is the real-life stories of other pet owners and pets the practice has seen (Box 1 on page 26). AHS resources

The AHS offers members and nonmembers many nonbranded client education materials at heartwormsociety.org. Brochures, videos, infographics, and heartworm preventive waivers are among the numerous tools available to help busy practitioners. Educational websites

Clients desiring links to informational websites may be directed to heartwormsociety.org, avma.org/ public/PetCare/Pages/Heartworm-Disease.aspx, or capcvet.org. PetMD.com also has a very practical, informative page on heartworm disease and prevention. Educating and re-educating clients about heartworm disease can be challenging. A team approach to heartworm education not only helps lighten the load but also ensures the message breaks through.

26. Beugnet F, de Vos C, Liebenberg J, et al. Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei. Parasite 2016;23:26-37. 27. Taenzler J, Liebenberg J, Roepke RKA, et al. Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs. Parasite Vectors 2016;9(1):392-396. 28. Becskei C, De Bock F, Illambas J, et al. Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica), for the treatment of sarcoptic mange in dogs. Vet Parasitol 2016;222:56-61. 29. Revolution prescribing information. Kalamazoo, MI: Zoetis, Inc., 2014. 30. McTier TL, Shanks DJ, Jernigan AD, et al. Evaluation of the effects of selamectin against adult and immature stages of fleas (Ctenocephalides felis felis) on dogs and cats. Vet Parasitol 2000;91(3– 4):201-212. 31. Dryden MW, Payne PA, Smith V, et al. Evaluation of indoxacarb and fipronil (s)methoprene topical spot-on formulations to control flea populations in naturally infested dogs and cats in private residences in Tampa FL. USA. Parasites Vectors 2013;6(1):366-372.

Chris Duke

Chris Duke, DVM, is co-owner of Bienville Animal Medical Center in Ocean Springs, Mississippi. He is a 34-year veterans of veterinary practice. He is a member of the American Society of Veterinary Journalists and writes weekly columns for South Mississippi media. He is also a board member of the American Heartworm Society. He is a graduate of the College of Veterinary Medicine at Auburn University.

Kathleen Williston

Kathleen Williston is completing her fifth year as a certified veterinary technician at Bienville Animal Medical Center in Ocean Springs, Mississippi. A graduate of the CVT program at Hinds Community College, Kathleen has special interests in behavioral management and client education.

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Behavior Medications: Which Medication, Which Patient? Karen L. Overall, MA, VMD, PhD, DACVB University of Pennsylvania shutterstock.com/Anna Hoychuk

The best treatment approaches in veterinary behavioral medicine are often multimodal. At the core of state-of-the art multimodal treatment is smart, rational, and effective use of behavioral medication. Which medication do you choose for which condition, how do you know if it is working, what are the risks, and what advantages might you gain for your patient by combining medications?

to recognize and quantify behavioral signs and to do so as part of routine evaluation. As for all other conditions in veterinary medicine, the best and most successful treatment is early treatment. The earlier appropriate behavioral medication is prescribed, the less the patient will suffer from fear, anxiety, or aggression and the cognitive and social changes that result from these pathologic conditions.

The keys to effective treatment of behavioral problems are no different than for somatic medical problems:

A helpful approach to understanding the thought process involved in choosing medications is to consider practical diagnostic examples, review the signs exhibited in these examples and the regions of the brain involved, and review effects of medications on those regions and on neurochemicals affecting these regions. An advantage of this approach is that the clinical signs provide a baseline against which targeted signs can be assessed for response to medication and other treatment.

• Identify the constellation of relevant signs/changes. • Nest these within a diagnosis or diagnoses. • Understand the factors that contribute to the development and maintenance of the diagnosis. • Use your treatment to modulate these factors in a manner that can be measured and tracked by alterations in the clinical signs and profile. Unfortunately, practitioners often feel helpless in the face of behavioral complaints because the signs seem so nonspecific. As is true in internal medicine, relevant clinical signs in behavioral medicine are not specific, but too few veterinarians are taught

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RECOGNIZING CLINICAL SIGNS AND COMORBID CONDITIONS Consider patients with 2 common behavioral diagnoses: separation anxiety and noise reactivity/

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phobia. These are commonly comorbid conditions,1 as is the rule among anxiety disorders.2,3 Because the development of both conditions ranges from subtle to explosive, veterinarians should screen for them at each appointment using a standardized clinical assessment tool4 to identify and treat them early. Results of these routine clinical assessments should be recorded and evaluated to determine whether they meet diagnostic criteria (Box 1). Signs of distress should be evaluated in currency and terminology that are meaningful for the individual patient because the most commonly reported behaviors (elimination, destruction, excessive vocalization) are only the most readily apparent and easily recognizable signs of anxiety for the clients and veterinary team. Drooling, panting, freezing, withdrawal, and cognitive signs of anxiety are less commonly diagnosed because they are less apparent to people, but dogs displaying them may be even more profoundly affected than dogs that show more obvious signs (Box 2 lists signs of anxiety). Dogs that are distressed when exposed to noises or storms but do not meet the criteria for a noise phobia may best be classified as “reactive” and assessed for treatment. The risk for worsening in these dogs is nontrivial. Even the mildest signs should be treated if a dog has any history of reacting to noises.6 Clients may insist that they can simply hold the dog while it pants and shakes or that the dog calms itself by hiding in the closet. In fact, these patients are suffering and need behavioral medication. Video is a powerful tool for accurate diagnosis and an even better way to assess response to medication and other treatment.

CHOOSING MEDICATIONS ACCORDING TO PATIENT PRESENTATION When choosing medication for patients with separation anxiety, noise reactivity, or both, practitioners should be guided by expected changes in relevant signs, regions of the brain that may be affecting those signs, and distributions of

neurochemical receptors in the regions that may be affected by the medication chosen. Some dogs show suites of correlated behaviors; for example, salivation appears to be more common in dogs that freeze and become immobile. If we alter the salivation, do we alter any part of the feedback system that maintains the anxiety? In fact, by

BOX 1. Diagnostic Criteria for Common Behavioral Disorders5 Separation anxiety Behavioral condition resulting in the following signs of distress exhibited by the patient only in the absence of, or lack of access to (a virtual absence), the client: • Physical (injury, uneven nail wear, scored teeth) • Physiologic (salivation, increased heart rate) •B ehavioral, cognitive, or emotional (social withdrawal, agitation, lack of focus) Noise phobia • Behavioral abnormality resulting in profound, nongraded, extreme response to noise, manifested as intense avoidance, escape, or anxiety, associated with sympathetic nervous system signs. • Dogs can shut down and freeze or run without caution. •D ecreased sensitivity to pain or social stimuli is often concomitant. nce established, repeated exposure results in an •O invariant pattern of response, but not all dogs show a full-blown invariant response. Panic disorder/panic • Behavioral abnormality resulting in a sudden, all-ornothing, profound, abnormal response that results in extremely fearful behaviors (catatonia, mania, escape) where the provocative stimulus may be unknown/ unclear, situational, internal, and/or generalized. iffers from conditions involving phobias, where the •D provocative stimulus is more discrete and identifiable, and where the level of distress characteristic of panic may not be achieved. he term panic disorder should be restricted to a •T described pattern of like events. • A panic event is a singular or infrequent event where the patient exhibits these behaviors, but the data are insufficient to determine whether the consistent pattern exists as required for panic disorder. he risk that a patient will experience another panic •T event after having had one is great.

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affecting salivation we may affect related regions of the amygdala associated with distress.7

anticholinergic effects. Table 2 indicates the relative effects of these medications on receptor classes.

Medications commonly used to treat fears, anxieties, and aggression in dogs are listed in Table 1. Many other medications used to treat some aspect of behavioral abnormalities are beyond the scope of this article and so are not discussed here (but see Overall 2013 5).

CONSIDERING RISK FACTORS

Table 1 compares many of these medications, by class, with respect to their effects on noradrenaline/norepinephrine (NA/NE) and serotonin (5-HT) receptors and sedation and

Because so many behavioral conditions are comorbid or have wildly different behavioral presentations within a diagnosis (eg, dogs with noise phobia can freeze and hide or may run and destroy in panic), the best approach is probably one that allows combination of medications to address the neurochemical profile of the behavioral abnormality but minimizes somatic risk. Box 3 provides a general model for such an approach.

BOX 2. Common Nonspecific Signs of Anxiety5 • Urination

• Inability to meet a direct gaze

• Defecation

• Staring at some middle distance

• Anal sac expression

•B ody posture lower (in fear, the body is extremely lowered and tail tucked)

• Panting • Increased respiration and heart rates • Trembling/shaking • Muscle rigidity (usually with tremors) • Lip licking • Nose licking • Grimace (retraction of lips) • Head shaking

• Mydriasis • Scanning •H ypervigilance/hyperalertness (may be noticed only when dog or cat is touched or interrupted; animal may hyperreact to stimuli that otherwise would not elicit this reaction) • Shifting legs

• Smacking or popping lips/jaws together • Salivation/hypersalivation

• Lifting paw in an intention movement • Increased closeness to preferred associates

•V ocalization (excessive and/or out of context); often frequent repetitive sounds (including high-pitched whines, like those associated with isolation)

• Decreased closeness to preferred associates

• Immobility/freezing or profoundly decreased activity

•P rofound alterations in eating and drinking (acute stress is usually associated with decreases in appetite and thirst; chronic stress is often associated with increases)

• Pacing and profoundly increased activity

• Increased grooming, possibly with self-mutilation

• Hiding or hiding attempts

• Decreased grooming

• Escaping or escape attempts

•P ossible appearance of ritualized or repetitive activities

• Yawning

•B ody language of social disengagement (turning head or body away from signaler) • Lowering of head and neck

ars lowered and possibly droopy because of changes •E in facial muscle tone

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hanges in other behaviors, including increased •C reactivity and increased aggressiveness (may be nonspecific)

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TAILORING THERAPY: CLINICAL EXAMPLES

Most of these medications are metabolized through the cytochrome P-450 system. Table 3 lists inducers and inhibitors that affect how these behavioral compounds are metabolized. Understanding such P-450 enzyme system interactions allows medication adjustment to minimize adverse events. Although most available information is for humans, some studies have measured CYP effects for dogs,11–14 with particularly strong conservation for CYP 1A enzymes. Isoforms are sufficiently similar between humans and dogs that inference from human information may serve as a good precaution.

Applying an approach that seeks to tailor treatment in behavioral medicine to specific presentations and targeted signs is not difficult but does require thought.

Separation Anxiety A dog with separation anxiety that involves salivation will benefit from any anticholinergic agent because the undesirable effect may be part of a reinforcing feedback cycle. Medications classified as anticholinergics are not used in

TABLE 1 Relative Effects of Medications on Noradrenaline/Norepinephrine and Serotonin Receptors and for Sedation or Anticholinergic Effects8–10 NA/NE

5-HT

POTENTIAL FOR SEDATION

POTENTIAL FOR ANTICHOLINERGIC EFFECTS

+++

Moderate

Amitriptyline

High

Nortriptyline

Moderate

Clomipramine

+++

High

+++

Moderate

Low

High

+++

Moderate

Fluvoxamine

+++

Moderate

Citalopram

+++

Moderate

High

Low

PARENT COMPOUND

TCAs Imipramine

SSRIs Fluoxetine Paroxetine Sertraline

SARIs Trazodone Benzodiazepines Alprazolam

Low to moderate

Lorazepam

Low to moderate

Diazepam Clonazepam

High Moderate

α-Agonists Clonidine OTM dexmedetomidine

Moderate Low

+, some effect; ++, moderate effect; +++, large effect; 5HT, 5-hydroxytryptamine (serotonin); NA/NE, noradrenaline/norepinephrine; OTM, oral transmucosal; SARI, serotonin antagonist/reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

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veterinary medicine; however, many medications have anticholinergic effects as part of their pharmacologic profile. Anticholinergic effects are common for many tricyclic antidepressants (TCAs), and although they have the potential for undesirable events, in this example, a medication with some anticholinergic effect may be beneficial. Additionally, a region in the central nucleus of the amygdala contributes to salivation, suggesting that medications that affect serotonin and norepinephrine regulation will be useful.

intermediate metabolites, and affects a wide range of receptor types. It may be a good choice here. If the dog is vocalizing or blocks or destroys doors through which clients leave, the behaviors are associated with affiliation and social needs and loss. A medication that has a profound effect on 5HT receptors, especially the 5-HT1A receptors that are involved in social anxieties, may benefit the patient. Unfortunately, medication costs and formulations change frequently. What do we do if clients cannot afford or obtain any formulation of clomipramine, a particular problem in the United States in the past few years? By reverting to the idea that distress about absences lies at the core of separation anxiety, pick a selective serotonin reuptake inhibitor (SSRI) affecting the 5-HT1A receptor because this receptor

Accordingly, amitriptyline or clomipramine may be rational choices, but clomipramine comes in a canine form (Clomicalm) with scored tablets, is a relatively more specific compound because of its

TABLE 2 Relative Medication Effects on Most Common Receptors (Antagonist Role Unless Otherwise Specified)8–10 PARENT COMPOUND

5-HT 1A

5-HT 1B

5HT1D

5HT2A

5-HT 2B

5-HT 2C

5-HT 3

α1A

α 1B

α 2B

H1 a

ACh

TCAs Imipramine

+++

Amitriptyline

+++

Nortriptyline

+++

+ +

+++

Clomipramine

SSRIs Fluoxetine

+++

Paroxetine

+++

Sertraline Fluvoxamine

+++

Citalopram

+++

SARIs Trazodone

+++

α-Agonists +

+++

Propranolol

Pindolol

Clonidine OTM dexmedetomidine

+ +++

β -blockers/antagonists

+, some effect; ++, moderate effect; +++, large effect; ACh, acetylcholine; SARI, serotonin antagonist/reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. a Potency at the H1 receptor correlates with weight gain in humans.9 b Primarily affects transporters.

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has been widely experimentally associated with social anxieties. If broader coverage is needed, combine it with a less specific TCA (amitriptyline, nortriptyline) and lower the dosage of both.

or sedative effect of a behavioral medication, but with long-term use benzodiazepines can disrupt natural sleep rhythms. This is not a major concern for short-term treatment.

Separation Anxiety Plus Noise Reactivity

Anxious dogs likely have interrupted sleep cycles; clients often say they notice that once the dog begins to respond to medication, the dog sleeps longer or more deeply. Good, restorative sleep should be a treatment goal. In contrast, excessive sedation, including persistent cognitive impairment, lack of motor coordination, or paradoxical excitement, is an undesired effect. The key with benzodiazepines is finding the right dose for the patient; these medications have highly variable effects. Having clients test benzodiazepines for adverse events, such as excessive sedation or paradoxical excitation, when no stimulation is expected is an important step. If no adverse effects are observed, clients should then help test and record the effects of increasing dosages to see if they can find one that provides relief.

What are the concerns if the patient also reacts badly to noises? Here, we need to distinguish between panicking and being distressed (Box 1). If the dog is distressed, any of the benzodiazepines may lower its reactivity level by providing central inhibition of responses. Benzodiazepines can be calming agents, antianxiety agents, or sedative and analgesic agents, depending on dose, route, and choice of medication. Alprazolam is considered the only truly “panicolytic” benzodiazepine. These compounds should not be used to treat patients in households where humans have addiction or substance abuse difficulties. Dogs that are distressed about noise or departures may respond to lorazepam and become calmer, while others may need longer-lasting benzodiazepines (diazepam, clonazepam), which may also make them sleep more. Additional and deeper sleep may not always be an adverse

Clonidine, an α2 agonist, may also aid distressed dogs by decreasing both central and peripheral signs of sympathetic arousal. At higher dosages, clonidine can be both sedative (impairing cognition) and hypotensive (rendering patients

BOX 3. Sample Combinations of Medications That May Allow Dosage of Each to Be Lowered With Enhanced Efficacy5 • Amitriptyline (TCA) [anxiety-related diagnosis] + fluoxetine (SSRI) [anxiety-related diagnosis] •A mitriptyline (TCA) [anxiety-related diagnosis] + fluoxetine (SSRI) [anxiety-related diagnosis] + alprazolam (BZD) [panic/phobia/severe distress with known trigger] • Amitriptyline (TCA) [anxiety-related diagnosis] + alprazolam (BZD) [panic/phobia] • Fluoxetine (SSRI) [anxiety-related diagnosis] + alprazolam (BZD) [panic/phobia] • Clomipramine (TCA, relatively specific) [anxiety-related diagnosis] + alprazolam (BZD) [panic/phobia] •C lomipramine (TCA, relatively specific) [anxiety-related diagnosis] + diazepam (BZD) [panic/phobia]—could be fairly sedating • Amitriptyline (TCA) [anxiety-related diagnosis] + diazepam (BZD) [panic/phobia]—could be fairly sedating • Paroxetine (SSRI) (social anxiety) + alprazolam (BZD) [panic/appetite stimulation in cats] BZD, benzodiazepine; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

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TABLE 3 Behavioral Medications That Act as Substrates to Inhibit or Induce the CYP Enzyme in Humans P-450 ENZYME

CYP 1A2

SUBSTRATE

INHIBITOR

INDUCER

TCAs Fluvoxamine Mirtazapine Duloxetine

Fluvoxamine Fluoxetine Paroxetine Sertraline Some TCAs Fluoroquinolonesa

Phenobarbitala Carbamazepinea Phenytoina

CYP 2A6

Barbituratesa

CYP 2B6

Phenobarbitala

2 CYP C9/ CYP 2C9/10

Sertraline Fluoxetine Amitriptyline

Fluvoxamine Fluoxetine Sertraline Fluconazolea Sulfaphenazolea

Carbamazepinea Phenobarbitala Phenytoina

2C19/CYP 2C19

Citaprolam Sertraline Clomipramine Imipramine

Fluvoxamine Fluoxetine Sertraline Omeprazolea

Carbamazepinea

Fluoxetine Fluvoxamine Citalopram Duloxetine Paroxetine Venlafaxine Trazodone Nefazodone TCAs

Duloxetine Fluoxetine Paroxetine Norfluoxetine Citalopram Sertraline Some TCAs

Nefazodone Sertraline Venlafaxine Trazodone TCAs

Fluvoxamine Norfluoxetine TCAs, barbiturates Dexamethasone/long-term glucocorticoids Phenytoin St. Johnâ&#x20AC;&#x2122;s wortb Flucloxacillin Nefazodonea Fluconazolea Ketoconazolea Cimetidinea Macrolides: clarithromycin, erythromycina Propofol

CYP 2D6

CYP 2E1

CYP 3A4

Carbamazepinea Barbituratesa Dexamethasone/long-term glucocorticoidsa Phenytoina St. Johnâ&#x20AC;&#x2122;s worta,b Flucloxacillina

Inducers slow the rate at which the substrate medication is available and lower the amount available. Inhibitors increase the rate at which the substrate medication is available and increase the amount available. There are few detailed studies for dogs, but the patterns identified to date do not deviate from these, so consideration should be given to monitoring patients carefully when medications from these classes are combined. TCA, tricyclic antidepressant. Adapted from Overall.5 a Medications used for nonbehavioral conditions. b Hyperforin is the compound that is the inducer.

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unstable on stairs or as they move through complex environments). If these effects appear, lowering the dose may ameliorate them. Trazodone, a serotonin antagonist/reuptake inhibitor (SARI), may help the dog to calm its activity level because the main effect of this drug is a slightly sedative one— trazodone increases sleep time,15–17 and its receptor profile (5-HTA/B antagonist, partial 5-HT1A agonist) is consistent with this.

Panic If the dog is panicking, there are 2 additional suitable choices. The first, alprazolam, can be given before or during the distressing event. In fact, if it is given regularly (usually q12h but up to q6h) before anticipated events, it can raise the threshold for reaction but provide central inhibitory effects, as well as peripheral effects on muscle tension that may accompany and provide a positive feedback response associated with panic. The second choice is dexmedetomidine, which has anxiolytic, sedative, analgesic, and sympatholytic properties.18 As an oral transmucosal (OTM) gel (Sileo; zoetisus.com), it has no first-pass effects; instead, it directly exerts agonist effects on presynaptic α2 receptors in the locus ceruleus. The locus ceruleus is the region of the brainstem that gives rise to all NA/NE brain tracts and is where sympathetic arousal may originate and is modulated. In essence, this region is the source of anticipatory anxiety and arousal. Accordingly, without involving the CYP 450 enzyme system, OTM dexmedetomidine may have profound panicolytic effects and may prevent and/or modulate the arousal that makes it so difficult for humans to use any behavioral or environmental management strategies or for dogs to use any operant or cognitive-behavior management skills they may have learned.

Nausea With both separation anxiety and noise phobia/ reactivity, dogs may feel nauseous. Distressed dogs cannot eat because of antagonism of

parasympathetic effects due to sympathetic arousal. However, the distress itself may contribute to nausea. For dogs that retch, salivate, chew on nonfood substances, have diarrhea before or after the event, stop eating before the event, and take a long time to eat after the event, we should consider whether maropitant (Cerenia; cereniadvm.com), the neurokinin 1 receptor antagonist/substance P blocker, could be beneficial. This compound may have a role in directly treating aspects of depression, fear, and anxiety19 but may be helpful for the more immediate gastrointestinal effects that may be associated with distress. In dogs with combined abnormalities that cause them to react to noise and absences, medications from 2 to 4 classes may need to be combined to achieve maximal resolution of signs. As to be expected from the patterns of receptor response, when medications that share a direct mechanism of action and/or a potential adverse effect are combined (eg, sedation, shared CYP 450 enzymes), dosages should be lowered. Occasionally, frequencies may be altered, rather than dosages lowered, depending on the dog’s response. If 2 medications that are combined both affect serotonin, reduce the dose of both to minimize the risk for serotonin syndrome. This condition is rare and usually idiopathic, and data in dogs are lacking; however, it can be tragic. Although not discussed here, monoamine oxidase inhibitors (eg, selegiline) should not be combined with TCAs, SSRIs, or SARIs.

SUMMARY Behavioral medicine and neuroscience are about pattern recognition. This brief introduction to thinking in a neurobehavioral mechanistic manner is intended to introduce clinicians to how to recognize and use relevant patterns for the benefit of the patients. We are learning more about genetic and functional patterns daily, and new applications for medications may result. By using the tables in this article to inform medication choice and to become comfortable with a few different treatment combinations, clinicians can make great improvements in their patients’ mental health and in everyone’s quality of life. MAY/JUNE 2017

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PEER REVIEWED

Karen L. Overall

Karen L. Overall, MA, VMD, PhD, DACVB, is a senior research scientist in the Biology Department at the University of Pennsylvania. She received her VMD degree from the University of Pennsylvania and her PhD from the University of Wisconsin-Madison. She did her residency training in veterinary behavioral medicine at the University of Pennsylvania. She has served on the faculties of both the veterinary and medical schools at the University of Pennsylvania and ran the Behavior Clinic at Penn Vet. Dr. Overall has been named the North American Veterinary Conference Small Animal Speaker of the Year. Her research focuses on neurobehavioral genetics of dogs, the development of normal and abnormal behaviors, and how behavior is assessed, especially as concerns working dogs.

References 1.

Overall KL, Dunham AE, Frank D. Frequency of nonspecific clinical signs in dogs with separation anxiety, storm/thunderstorm phobia, and noise phobia, alone or in combination. JAVMA 2001;219(4):467-473.

2. Tiira K, Lohi H. Early life experiences and exercise associate with canine anxieties. PLoS One 2015;10(11):e0141907. 3. Tiira K, Sulkama S, Lohi, H. Prevalence, cormorbidity, and behavioral variation in canine anxiety. J Vet Behav Clin Appl Res 2016;16:36-44. 4. Hammerle M, Horst C, Levine E, et al. AAHA 2015 Canine and Feline Behavior Management Guidelines. aaha.org/professional/resources/behavior_management_ guidelines.aspx. Accessed November 2016. 5. Overall KL. Manual of Clinical Behavioral Medicine for Dogs and Cats. St, Louis, MO: Elsevier; 2013. 6. Overall KL, Tiira K, Broach D, Bryant D. Genetics and behavior: a guide for practitioners. Vet Clin North Am Small Anim Pract 2014;44(3):483-505. 7. Davis M. Neurobiology of fear responses: the role of the amygdala. J Neuropsychiatry Clin 1997;9(3):382-402. 8. Cusack B, Nelson A, Richelson E. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl) 1994;114(4):559-565. 9. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 2007;151(6):737-748. 10. Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997;340(2-3):249-258. 11. Martignoni M, Groothuis GMM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and inductions. Expert Opin Drug Metab Toxicol 2006;2(6):875-894. 12. Bogaards JJP, Bertrand M, Jackson P, et al. Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica 2000;30(12):1131-1152. 13. Turpeinene M, Ghiciuc C, Opritoui M, et al. Predictive value of animal models for human cytochrome P450 (CYP)-mediated metabolism: a comparative study in vitro. Xenobiotica 2007;37(12):1367-1377. 14. Van Beusekom CD, Schipper L, Fin-Gremmels J. Cytochrome P450-mediated hepatic metabolism of new fluorescent substrates in cats and dogs. J Vet Pharmacol Ther 2010;33(6):519-527. 15. Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging 1994;4(4):331-55. 16. Gruen ME, Sherman BL. Use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders: 56 cases (1995-1997). JAVMA 2008;233(12):1902-1907. 17. Gilbert-Gregory SE, Stull JW, Rice MR, Herron ME. Effects of trazodone on behavioral signs of stress in hospitalized dogs. JAVMA 2016;249(11):1281-1291. 18. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedativeanalgesic agent. BUMC Proc 2001;14:13-21. 19. Varty GB, Cohen-Williams ME, Hunter JC. The antidepressant-like effects of neurokinin NK1 receptor antagonists in a gerbil tail suspension test. Behav Pharmacol 2003;14(1):87-95.

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Your 3-in-1 and

DONE recommendation every month

More pet owners recommend Trifexis than any other brand1

Talk to your Elanco sales representative about 3-in-1 protection

Indications Trifexis is indicated for the prevention of heartworm disease (Dirofilaria immitis). Trifexis kills fleas and is indicated for the prevention and treatment of flea infestations (Ctenocephalides felis), and the treatment and control of adult hookworm (Ancylostoma caninum), adult roundworm (Toxocara canis and Toxascaris leonina) and adult whipworm (Trichuris vulpis) infections in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater.

Important Safety Information Serious adverse reactions have been reported following concomitant extra-label use of ivermectin with spinosad alone, one of the components of Trifexis. Treatment with fewer than three monthly doses aﬅer the last exposure to mosquitoes may not provide complete heartworm prevention. Prior to administration of Trifexis, dogs should be tested for existing heartworm infection. Use with caution in breeding females. The safe use of Trifexis in breeding males has not been evaluated. Use with caution in dogs with pre-existing epilepsy. The most common adverse reactions reported are vomiting, lethargy, pruritus, anorexia and diarrhea. To ensure heartworm prevention, dogs should be observed for one hour aﬅ er administration. If vomiting occurs within one hour, redose. Puppies less than 14 weeks of age may experience a higher rate of vomiting. For product information, including complete safety information, see page 104. Brand Experience Tracker Research, March 2016.

Trifexis®, Elanco™, and the Diagonal Bar™ are trademarks owned by or licensed to Eli Lilly and Company, its subsidiaries or aﬃliates. © 2017 Eli Lilly and Company, its subsidiaries or aﬃliates. USCACTFX00947

shutterstock.com/InBetweentheBlinks

HOW I TREAT

How I Treat… Mammary Carcinoma AN INTERVIEW WITH DR. ANNETTE SMITH

Today’s Veterinary Practice “How I Treat” column is based on the popular How I Treat sessions presented at the annual NAVC Conference in Orlando, Florida (navc.com/conference). This column features interviews with leading veterinary specialists on pertinent clinical topics, with the goal of bringing practitioners essential information on therapeutic approaches. Annette Smith, DVM, MS, DACVIM Auburn University

In this How I Treat column, Annette Smith, DVM, MS, DACVIM, answers our questions on diagnosing and treating mammary carcinoma in dogs.

Q. What is the estimated incidence of mammary carcinoma in dogs, and what risk factors are associated with its development? A. Mammary tumors are the most common tumor in intact female dogs, occurring in approximately 25% of this population, with the risk increasing with age. However, because of the incidence of early neutering in the United States, we see fewer cases in veterinary practice. Spaying

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before the first estrus cycle has been reported to decrease the incidence to approximately 0.5%, and spaying before the second estrus cycle remains protective, with an incidence of approximately 8%. Besides hormonal exposure, obesity at the time of puberty and ingestion of red meat and homemade diets have also been reported to be risk factors for mammary cancer development. Q. What diagnostic plan should you follow to get a definitive and staged answer? A. Mammary tumors require pathology after tumor removal for a definitive diagnosis, although

HOW I TREAT

we usually attempt to rule out other tumor types with fine-needle aspiration and cytology before surgery. These tumors can spread to local lymph nodes and the lungs, so sampling of local lymph nodes, if palpable, and chest radiography and abdominal ultrasonography are recommended. Computed tomography (CT) can be used to detect smaller lesions in the lungs, but its role in routine staging for mammary cancer has not been determined. The increased expense of CT and requirement for anesthesia may not be cost effective for most patients. Q. What is the current recommended treatment and its prognosis for dogs with mammary carcinoma? A. Surgery is the mainstay of treatment for dogs with mammary carcinoma, with the extent of surgery dependent on the extent of disease. The goal is to remove all existing masses, along with any local, easily accessible lymph nodes. Multifocal disease is common, occurring in more than half of patients. The role of ovariohysterectomy is somewhat controversial, but many oncologists recommend spaying at the time of tumor removal to remove any hormonal influence on tumor progression, as well as to eliminate the risk of ovarian and uterine diseases, which are also common in older dogs. Radiation therapy has not found a role in the management of canine mammary carcinoma, although it is a frequent treatment modality in treating breast cancer in people. Chemotherapy has also not been proven to extend survival in veterinary patients in most studies, but it is used frequently in dogs with tumors that have the potential to be aggressive. Doxorubicin, carboplatin, 5-fluorouracil/cyclophosphamide, and toceranib phosphate are some of the more commonly recommended chemotherapeutics. Hormonal modulation therapy (eg, tamoxifen) is not currently recommended in veterinary patients.

ammary tumors are the most common M tumor in intact female dogs, occurring in approximately 25% of this population, with the risk increasing with age.

tumors are usually associated with survival times measured in years after complete tumor removal. Q. How would a genetic blood test change the diagnosis and treatment for this disease? A. MicroRNAs (miRs) are small, noncoding RNA molecules that can be detected in the blood of cancer patients. If we can identify which miRs are specifically associated with the presence of mammary carcinomas, we may be able to make a diagnosis on the basis of a simple blood test, possibly very early in the course of disease. If we can identify markers associated with more aggressive types and perhaps predict response to treatment, it will inform veterinariansâ&#x20AC;&#x2122; decisionmaking about how to manage these patients.

BOX 1. Malignant Versus Benign Tumors About half of mammary tumors are benign, and half are malignant. Of those that are malignant, approximately half are likely to metastasize. Large-breed dogs appear to be more predisposed to malignant tumors. A few mutations have been identified in certain breeds and lines of dogs that are similar to mutations found in people, such as in the BRCA1 and BRCA2 genes, which have been shown to increase the incidence of breast and ovarian cancer.

Prognosis is most influenced by tumor type, size, and evidence of metastatic disease (Box 1). Lower-stage disease (<3 cm, no lymphatic invasion or distant metastasis) and well-differentiated

MAY/JUNE 2017

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HOW I TREAT CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Description: NexGard® (afoxolaner) is available in four sizes of beef-flavored, soft chewables for oral administration to dogs and puppies according to their weight. Each chewable is formulated to provide a minimum afoxolaner dosage of 1.14 mg/lb (2.5 mg/ kg). Afoxolaner has the chemical composition 1-Naphthalenecarboxamide, 4-[5- [3-chloro-5-(trifluoromethyl)-phenyl]-4, 5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl. Indications: NexGard kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of Black-legged tick (Ixodes scapularis), American Dog tick (Dermacentor variabilis), Lone Star tick (Amblyomma americanum), and Brown dog tick (Rhipicephalus sanguineus) infestations in dogs and puppies 8 weeks of age and older, weighing 4 pounds of body weight or greater, for one month. Dosage and Administration: NexGard is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg). Dosing Schedule: Body Weight 4.0 to 10.0 lbs. 10.1 to 24.0 lbs. 24.1 to 60.0 lbs. 60.1 to 121.0 lbs. Over 121.0 lbs.

BOX 2. MicroRNA: Evolving Research For more details on microRNAs and their potential application in cancer diagnosis, see the Auburn University press release “Researchers Using Innovative Blood Testing in Breast Cancer Detection.” Information on other Auburn University clinical oncology trials is also available on the Clinical Trials page.

Afoxolaner Per Chewables Chewable (mg) Administered 11.3 One 28.3 One 68 One 136 One Administer the appropriate combination of chewables

NexGard can be administered with or without food. Care should be taken that the dog consumes the complete dose, and treated animals should be observed for a few minutes to ensure that part of the dose is not lost or refused. If it is suspected that any of the dose has been lost or if vomiting occurs within two hours of administration, redose with another full dose. If a dose is missed, administer NexGard and resume a monthly dosing schedule. Flea Treatment and Prevention: Treatment with NexGard may begin at any time of the year. In areas where fleas are common year-round, monthly treatment with NexGard should continue the entire year without interruption. To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea control product. Tick Treatment and Control: Treatment with NexGard may begin at any time of the year (see Effectiveness). Contraindications: There are no known contraindications for the use of NexGard. Warnings: Not for use in humans. Keep this and all drugs out of the reach of children. In case of accidental ingestion, contact a physician immediately. Precautions: The safe use of NexGard in breeding, pregnant or lactating dogs has not been evaluated. Use with caution in dogs with a history of seizures (see Adverse Reactions). Adverse Reactions: In a well-controlled US field study, which included a total of 333 households and 615 treated dogs (415 administered afoxolaner; 200 administered active control), no serious adverse reactions were observed with NexGard. Over the 90-day study period, all observations of potential adverse reactions were recorded. The most frequent reactions reported at an incidence of > 1% within any of the three months of observations are presented in the following table. The most frequently reported adverse reaction was vomiting. The occurrence of vomiting was generally self-limiting and of short duration and tended to decrease with subsequent doses in both groups. Five treated dogs experienced anorexia during the study, and two of those dogs experienced anorexia with the first dose but not subsequent doses. Table 1: Dogs With Adverse Reactions. Treatment Group Afoxolaner

Vomiting (with and without blood) Dry/Flaky Skin Diarrhea (with and without blood) Lethargy Anorexia

N1 17 13 13 7 5

% (n=415) 4.1 3.1 3.1 1.7 1.2

I am grateful that the American College of Veterinary Internal Medicine Foundation has funded work in this exciting area and to be part of it! We are continuing to collect samples to investigate the utility of this approach in dogs with mammary carcinoma. More information is available on the Auburn University website (Box 2).

Oral active control

N2 25 2 7 4 9

% (n=200) 12.5 1.0 3.5 2.0 4.5

1 Number of dogs in the afoxolaner treatment group with the identified abnormality. 2 Number of dogs in the control group with the identified abnormality. In the US field study, one dog with a history of seizures experienced a seizure on the same day after receiving the first dose and on the same day after receiving the second dose of NexGard. This dog experienced a third seizure one week after receiving the third dose. The dog remained enrolled and completed the study. Another dog with a history of seizures had a seizure 19 days after the third dose of NexGard. The dog remained enrolled and completed the study. A third dog with a history of seizures received NexGard and experienced no seizures throughout the study. To report suspected adverse events, for technical assistance or to obtain a copy of the MSDS, contact Merial at 1-888-6374251 or www.merial.com/NexGard. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth. Mode of Action: Afoxolaner is a member of the isoxazoline family, shown to bind at a binding site to inhibit insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking preand post-synaptic transfer of chloride ions across cell membranes. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. The selective toxicity of afoxolaner between insects and acarines and mammals may be inferred by the differential sensitivity of the insects and acarines’ GABA receptors versus mammalian GABA receptors. Effectiveness: In a well-controlled laboratory study, NexGard began to kill fleas four hours after initial administration and demonstrated >99% effectiveness at eight hours. In a separate well-controlled laboratory study, NexGard demonstrated 100% effectiveness against adult fleas 24 hours post-infestation for 35 days, and was ≥ 93% effective at 12 hours post-infestation through Day 21, and on Day 35. On Day 28, NexGard was 81.1% effective 12 hours post-infestation. Dogs in both the treated and control groups that were infested with fleas on Day -1 generated flea eggs at 12- and 24-hours post-treatment (0-11 eggs and 1-17 eggs in the NexGard treated dogs, and 4-90 eggs and 0-118 eggs in the control dogs, at 12- and 24-hours, respectively). At subsequent evaluations post-infestation, fleas from dogs in the treated group were essentially unable to produce any eggs (0-1 eggs) while fleas from dogs in the control group continued to produce eggs (1-141 eggs). In a 90-day US field study conducted in households with existing flea infestations of varying severity, the effectiveness of NexGard against fleas on the Day 30, 60 and 90 visits compared with baseline was 98.0%, 99.7%, and 99.9%, respectively. Collectively, the data from the three studies (two laboratory and one field) demonstrate that NexGard kills fleas before they can lay eggs, thus preventing subsequent flea infestations after the start of treatment of existing flea infestations. In well-controlled laboratory studies, NexGard demonstrated >97% effectiveness against Dermacentor variabilis, >94% effectiveness against Ixodes scapularis, and >93% effectiveness against Rhipicephalus sanguineus, 48 hours post-infestation for 30 days. At 72 hours post-infestation, NexGard demonstrated >97% effectiveness against Amblyomma americanum for 30 days. Animal Safety: In a margin of safety study, NexGard was administered orally to 8 to 9-week-old Beagle puppies at 1, 3, and 5 times the maximum exposure dose (6.3 mg/kg) for three treatments every 28 days, followed by three treatments every 14 days, for a total of six treatments. Dogs in the control group were sham-dosed. There were no clinically-relevant effects related to treatment on physical examination, body weight, food consumption, clinical pathology (hematology, clinical chemistries, or coagulation tests), gross pathology, histopathology or organ weights. Vomiting occurred throughout the study, with a similar incidence in the treated and control groups, including one dog in the 5x group that vomited four hours after treatment. In a well-controlled field study, NexGard was used concomitantly with other medications, such as vaccines, anthelmintics, antibiotics (including topicals), steroids, NSAIDS, anesthetics, and antihistamines. No adverse reactions were observed from the concomitant use of NexGard with other medications. Storage Information: Store at or below 30°C (86°F) with excursions permitted up to 40°C (104°F). How Supplied: NexGard is available in four sizes of beef-flavored soft chewables: 11.3, 28.3, 68 or 136 mg afoxolaner. Each chewable size is available in color-coded packages of 1, 3 or 6 beef-flavored chewables.

Annette Smith

Annette Smith, DVM, MS, DACVIM, graduated with honors from Texas A&M’s College of Veterinary Medicine. After her internship at the University of Illinois, she joined Auburn University’s residency program, where she became certified in both small animal internal medicine and oncology and completed a master’s degree in biomedical sciences. She has served on the Auburn University faculty since 1999 and is currently the Robert & Charlotte Lowder Distinguished Professor in Oncology. She coordinates Auburn University’s oncology program, which focuses on a multidisciplinary team approach to each patient.

NADA 141-406, Approved by FDA Marketed by: Frontline Vet Labs™, a Division of Merial, Inc. Duluth, GA 30096-4640 USA Made in Brazil. ®NexGard is a registered trademark, and TMFRONTLINE VET LABS is a trademark, of Merial. ©2015 Merial. All rights reserved. 1050-4493-03 Rev. 1/2015

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IMPORTANT SAFETY INFORMATION: NexGard® is for use in dogs only. The most frequently reported adverse reactions included pruritus, vomiting, dry/flaky skin, diarrhea, lethargy, and lack of appetite. The safe use of NexGard in pregnant, breeding, or lactating dogs has not been evaluated. Use with caution in dogs with a history of seizures. For more information, see full prescribing information or visit www.NexGardForDogs.com.