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Topic:NSAID

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used in horses to manage pain and inflammation. These drugs work by inhibiting enzymes involved in the inflammatory process, specifically cyclooxygenase (COX) enzymes, which play a role in the production of prostaglandins. NSAIDs are frequently administered for conditions such as musculoskeletal disorders, colic, and post-surgical pain. Common NSAIDs used in equine medicine include phenylbutazone, flunixin meglumine, and ketoprofen. While effective, the use of NSAIDs in horses requires careful management due to potential side effects, such as gastrointestinal ulceration and renal impairment. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, therapeutic applications, and safety considerations of NSAIDs in equine practice.
Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic.
Equine veterinary education    October 4, 2019   Volume 32, Issue 11 611-616 doi: 10.1111/eve.13189
Ziegler AL, Blikslager AT.Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage a wide variety of conditions in horses, including management of colic. Flunixin meglumine is by far the most commonly used drug in the control of colic pain and inflammation and has become a go-to for not only veterinarians but also horse-owners and nonmedical equine professionals. NSAID use, however, has always been controversial in critical cases due to a high risk of adverse effects associated with their potent cyclo-oxygenase (COX) inhibition. There are two important COX isoenzymes: COX-1 is generally beneficial for ...
Clinical Effects of the Extract of the Seeds of the Indian Celery-Apium Graveolens-In Horses Affected by Chronic Osteoarthritis.
Animals : an open access journal from MDPI    August 20, 2019   Volume 9, Issue 8 doi: 10.3390/ani9080585
Battaglia B, Angelone M, Vera E, Basini G, Bussolati S, Paci M, Bue MD, Aldigeri R, Grolli S, Quintavalla F, Ramoni R.The extract of the seeds from Indian celery, Apium greaveolens (CSE), tested in experimental animals (rodents), and in humans affected by chronic osteoarthritic diseases, exhibits anti-inflammatory effects that can be compared, to some degree, to those of non-steroid anti-inflammatory drugs (NSAID). In view of a potential use of CSE in the equine species, it was tested on horses affected by chronic articular pathologies. The trial was performed on 20 horses divided into three different groups, orally treated with 0 (controls), 7.0 or 30 g of CSE BID. Basic orthopedic examinations were conducte...
Effect of meloxicam treatment on movement asymmetry in riding horses in training.
PloS one    August 13, 2019   Volume 14, Issue 8 e0221117 doi: 10.1371/journal.pone.0221117
Persson-Sjodin E, Hernlund E, Pfau T, Haubro Andersen P, Holm Forsström K, Rhodin M.Quantitative gait analysis has revealed that a large proportion of horses in training, perceived as free from lameness by their owners, show movement asymmetries of equal magnitude to horses with mild clinical lameness. Whether these movement asymmetries are related to orthopaedic pain and/or pathology has yet to be further investigated. Therefore, the objective of this study was to determine whether movement asymmetries in riding horses in training are affected by anti-inflammatory treatment with meloxicam. In a crossover design, horses were treated with meloxicam or placebo for four days res...
Periovulatory administration of firocoxib did not alter ovulation rates and mitigated post-breeding inflammatory response in mares.
Theriogenology    June 29, 2019   Volume 138 24-30 doi: 10.1016/j.theriogenology.2019.06.045
Friso AM, Segabinazzi LGTM, Cyrino M, Correal SB, Freitas-Dell'Aqua CP, Teoro do Carmo M, Dell'Aqua JA, Miró J, Papa FO, Alvarenga MA.Non-steroidal anti-inflammatory drugs (NSAIDs) are a therapeutic option for the treatment of inflammation. However, negative effects of non-selective NSAIDs for treatment of mares with endometritis have been described, including delayed uterine clearance and impairment of ovulations. Firocoxib is a specific cyclooxygenase-2 (COX-2) inhibitor and has the ability to act in the uterus of mares. We investigated the effects of firocoxib on ovulation rate, numbers of polymorphonuclear neutrophils (PMNs), and COX-2 protein levels in the endometrial tissue of susceptible mares after insemination. Two ...
Daboia (Vipera) palaestinae Envenomation in 123 Horses: Treatment and Efficacy of Antivenom Administration.
Toxins    March 19, 2019   Volume 11, Issue 3 doi: 10.3390/toxins11030168
Tirosh-Levy S, Solomovich-Manor R, Comte J, Nissan I, Sutton GA, Gabay A, Gazit E, Steinman A.Envenomation by venomous snakes is life threatening for horses. However, the efficacy of available treatments for this occurrence, in horses, has not yet been adequately determined. The aim of this study was to describe the treatments provided in cases of Daboia palaestinae envenomation in horses and to evaluate the safety and efficacy of antivenom administration. Data regarding 123 equine snakebite cases were collected over four years from 25 veterinarians. The majority of horses were treated with procaine-penicillin (92.7%), non-steroidal anti-inflammatory drugs (82.3%), dexamethasone (81.4%...
Pharmacokinetics, metabolism and excretion of celecoxib, a selective cyclooxygenase-2 inhibitor, in horses.
Journal of veterinary pharmacology and therapeutics    March 19, 2019   Volume 42, Issue 5 518-524 doi: 10.1111/jvp.12757
Subhahar MB, Singh J, Albert PH, Kadry AM.Celecoxib, a nonsteroidal anti-inflammatory drug, is frequently used to treat arthritis in humans with minimal gastrointestinal side effect compared to traditional NSAIDs. The primary aim of this study was to determine the pharmacokinetic profile of celecoxib-a selective cyclooxygenase-2 (COX-2) inhibitor in horses. Six horses were administered a single oral dose of celecoxib at 2 mg/kg (body weight). After oral dosing, the drug reached a maximum concentration (mean ± SD) in blood of 1,088 ± 324 ng/ml in 4.58 hr. The elimination half-life was 13.60 ± 3.18 hr, and the area under th...
Therapeutic developments in equine pain management.
Veterinary journal (London, England : 1997)    February 28, 2019   Volume 247 50-56 doi: 10.1016/j.tvjl.2019.02.010
Mama KR, Hector RC.Many drugs and non-drug modalities are used to manage pain in horses, but evidence regarding efficacy and safety remains limited. This manuscript will first briefly review tried and tested techniques, e.g. the use of non-steroidal anti-inflammatory drugs, in the management of pain. Newer approaches to administering medications such as oral use of detomidine, which was previously only administered by injection, will also be discussed. Finally, introductory information on newer therapies, for example acupuncture and chiropractic manipulation, that the veterinarian may consider for the management...
Pharmacological Regulation in the USA and Pharmacokinetics Parameters of Firocoxib, a Highly Selective Cox-2, by Pain Management in Horses.
Journal of equine veterinary science    February 21, 2019   Volume 77 36-42 doi: 10.1016/j.jevs.2019.02.007
Rangel-Nava A, Ramírez-Uribe JM, Recillas-Morales S, Ibancovichi-Camarillo JA, Venebra-Muñoz A, Sánchez-Aparicio P.The objective of the study was to conduct a review of the pharmacological regulation and pharmacokinetic parameters of firocoxib when administered orally or intravenously in horses. A search for literature was done in SCOPUS and PubMed for studies that had to evaluate the pharmacological regulation as well as the pharmacokinetic parameters of firocoxib when administered in horses. The nonsteroidal anti-inflammatory drugs have analgesic, anti-inflammatory, antipyretics, and antiendotoxic effects. The newly developed is selective to COX2 characterized by less adverse effects in veterinary patien...
Pharmacokinetics of meloxicam after oral administration of a granule formulation to healthy horses.
Journal of veterinary internal medicine    February 15, 2019   Volume 33, Issue 2 961-967 doi: 10.1111/jvim.15433
Mendoza FJ, Serrano-Rodriguez JM, Perez-Ecija A.Nonsteroidal anti-inflammatory drugs are administered in horses for several systemic diseases. Selective cyclooxygenase-2 inhibitors are preferred because of lower risk of adverse effects. Several meloxicam formulations have been tested in horses, but a recently marketed granule oral formulation has not been studied. Objective: To characterize the pharmacokinetics of a novel granule meloxicam formulation in fasted and fed horses, and to compare pharmacokinetic features with oral suspension and tablets. Methods: Seven healthy adult horses. Methods: Meloxicam was administered at 0.6 mg/kg in fas...
Pain assessment in horses after orthopaedic surgery and with orthopaedic trauma.
Veterinary journal (London, England : 1997)    February 10, 2019   Volume 246 85-91 doi: 10.1016/j.tvjl.2019.02.001
van Loon JPAM, Van Dierendonck MC.Objective pain assessment is important to guide and tailor therapy in clinical practice. This study describes the clinical applicability and validity of two pain scales, the Composite Pain Scale (CPS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) in horses with orthopaedic trauma or after orthopaedic surgery. A cohort follow-up study was performed using 77 adult horses (n=43 with orthopaedic trauma or injury; n=34 controls). Composite and facial expression-based pain scores were assessed by direct observations of pairs of two independent observers. All horse...
Letter to the Editor: Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction.
Equine veterinary journal    February 3, 2019   Volume 51, Issue 3 422 doi: 10.1111/evj.13078
Freeman DE.No abstract available
Serum protein expression in Equine Glandular Gastric Disease (EGGD) induced by phenylbutazone.
The Journal of veterinary medical science    January 23, 2019   Volume 81, Issue 3 418-424 doi: 10.1292/jvms.18-0679
Tesena P, Yingchutrakul Y, Roytrakul S, Wongtawan T, Angkanaporn K.Equine Glandular Gastric Disease (EGGD) is a common disease in sport horses. This disease might be associated with usage of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating inflammatory diseases. Although gastroscopy has been an effective method for diagnosis, but a less invasive, and inexpensive method is preferred. This study used proteomic technology to identify candidate serum proteins that might be used as markers of NSAIDs induced EGGD. Five Thoroughbred horses were given high doses of NSAID, phenylbutazone to treat lameness. The experiment was divided into three periods: (i) P...
A prospective multicentre survey of complications associated with equine castration to facilitate clinical audit.
Equine veterinary journal    November 22, 2018   Volume 51, Issue 4 435-439 doi: 10.1111/evj.13035
Hodgson C, Pinchbeck G.Despite the regularity with which castration is performed, the types of complications and current best practice are unknown. Objective: The objective of this study was to perform a prospective audit of routine equine castrations performed in general practice to determine complication rates and factors associated with them. Methods: Multicentre, prospective audit of castrations. Methods: Data on castrations were collected on the day of surgery from 18 veterinary practices; 30-days post-operatively follow-up was obtained and complications recorded. Frequency of complications was reported, and mu...
Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses.
Equine veterinary journal    October 23, 2018   Volume 51, Issue 3 415-421 doi: 10.1111/evj.13024
Martin EM, Schirmer JM, Jones SL, Davis JL.Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. Methods: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses ...
[Use of bisphosphonates in horses – a review].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    October 19, 2018   Volume 46, Issue 5 323-333 doi: 10.15653/TPG-170804
Düsterdieck-Zellmer KF.Systemic administration of tiludronate or clodronate decreases lameness in some horses suffering from navicular syndrome within 2-6 months of treatment. In horses that fail to respond to the first treatment, a follow-up treatment may still improve the lameness. Horses with a lameness duration of less than 6 months have better odds of experiencing improvement in lameness. Bisphosphonate (BP) treatment can result in renal damage, and it is recommended to assess renal function prior to and after treatment. Horses with pre-existing renal compromise should not be treated with BP, as this may promot...
Klossiella equi infection in a Cheval Canadien Mare.
Veterinary clinical pathology    October 15, 2018   Volume 47, Issue 4 654-659 doi: 10.1111/vcp.12660
Baker RE, Schlipf JW, Brady JV, Gorman ME.A 6-year-old Cheval Canadien mare was presented for clinical signs related to acute kidney injury after receiving a course of nonsteroidal anti-inflammatory therapy. Cytologic examination of concentrated urine revealed small protozoal organisms that were later identified as Klossiella equi. Both sporocysts and free-floating sporozoites were identified in the urine, which has not been previously documented. The mare responded well to intravenous fluid therapy, and as she regained tubular function, the presence of the protozoa in the urine also abated. The mare was discharged from the hospital a...
The effect of flunixin meglumine, firocoxib and meloxicam on the uterine mobility of equine embryos.
Theriogenology    September 25, 2018   Volume 123 132-138 doi: 10.1016/j.theriogenology.2018.09.026
Okada CTC, Andrade VP, Freitas-Dell'Aqua CP, Nichi M, Fernandes CB, Papa FO, Alvarenga MA.Embryo mobility occurs as a result of prostaglandin production by the embryo and endometrium, promoting uterine smooth muscle contractions, which propels the embryonic vesicle through the lumen. Non-steroidal anti-inflammatory drugs (NSAIDs), as flunixin meglumine, are routinely used in equine medicine and can alter the conceptus mobility if applied in early pregnancy, which may impair maternal recognition of pregnancy. The objective of this study was to evaluate and compare the effect of flunixin meglumine (FM; 1.1 mg/kg IV), firocoxib (FIRO; 0.2 mg/kg PO), and meloxicam (ML; 0.6 mg/kg,...
Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction.
Equine veterinary journal    September 21, 2018   Volume 51, Issue 3 329-335 doi: 10.1111/evj.13013
Ziegler AL, Freeman CK, Fogle CA, Burke MJ, Davis JL, Cook VL, Southwood LL, Blikslager AT.Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin m...
Differential effects of selective and non-selective cyclooxygenase inhibitors on fecal microbiota in adult horses.
PloS one    August 23, 2018   Volume 13, Issue 8 e0202527 doi: 10.1371/journal.pone.0202527
Whitfield-Cargile CM, Chamoun-Emanuelli AM, Cohen ND, Richardson LM, Ajami NJ, Dockery HJ.Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in both veterinary and human medicine. Gastrointestinal injury is a frequent adverse event associated with NSAID use and evidence suggests that NSAIDs induce gastrointestinal microbial imbalance (i.e., dysbiosis) in both animals and people. It is unknown, however, whether cyclooxygenase (COX)-2-selective NSAIDs induce dysbiosis, or if this phenomenon occurs in horses administered any class of NSAIDs. Therefore, our objectives were to determine whether the composition and diversity of the fecal microbiota of adult horses were alt...
Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice.
Equine veterinary journal    August 21, 2018   Volume 51, Issue 2 147-153 doi: 10.1111/evj.12997
Duz M, Marshall JF, Parkin TD.There is little knowledge of the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and whether their prescription varies between countries. Objective: To describe prescription practices of NSAIDs in equids in the United Kingdom (UK), United States of America (USA) and Canada. Methods: Descriptive observational study. Methods: Free-text electronic medical records from 141,543 equids from 10 equine practices in the UK, 255,777 equids from 7 equine practices with 20 branches from the USA and 2 practices with 7 branches from Canada were evaluated. A validated text-mining technique was ...
Prevalence of and risk factors for equine glandular and squamous gastric disease in polo horses.
The Canadian veterinary journal = La revue veterinaire canadienne    August 15, 2018   Volume 59, Issue 8 880-884 doi: 10.1186/1751-0147-55-45
Banse HE, MacLeod H, Crosby C, Windeyer MC.The objectives of this study were to determine the prevalence rates and risk factors for equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD) in a population of 63 polo horses in competition. The prevalence of EGGD grade ≥ 1 was 69% and EGGD ≥ 2 was 31%. The prevalence of ESGD grade ≥ 1 was 54% and grade ≥ 2 was 37%. The risk factors retained in the final multivariable models were years of experience in polo competition for EGGD grade ≥ 1 and for grade ≥ 2, with decreased experience being associated with EGGD and weekly exercise duration and non-steroi...
Effect of selective versus nonselective cyclooxygenase inhibitors on gastric ulceration scores and intestinal inflammation in horses.
Veterinary surgery : VS    August 9, 2018   Volume 47, Issue 6 784-791 doi: 10.1111/vsu.12941
Richardson LM, Whitfield-Cargile CM, Cohen ND, Chamoun-Emanuelli AM, Dockery HJ.To determine whether a cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug (NSAID) would reduce gastric ulceration and gastrointestinal (GI) inflammation compared with a non-COX selective NSAID. Methods: Randomized block design. Methods: Twenty-five healthy adult horses. Methods: Horses were randomly assigned to receive placebo (n = 5), phenylbutazone (n = 10), or firocoxib (n = 10) administered daily for 10 days. Gastroscopy was performed on days 0 and 10, and both squamous and glandular ulcers were scored according to established scoring criteria. Fecal samples w...
Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model. Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA, van Weeren PR, Korthagen NM.Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple L...
Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses.
Drug testing and analysis    March 25, 2018   doi: 10.1002/dta.2378
Knych HK, Seminoff K, McKemie DS.Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the cu...
Analysis of loxoprofen in tablets, patches, and equine urine as tert-butyldimethylsilyl derivative by gas chromatography-mass spectrometry.
Archives of pharmacal research    March 23, 2018   Volume 41, Issue 4 459-466 doi: 10.1007/s12272-018-1023-5
Kim Y, Seo C, Oh S, Kwak J, Jung S, Sin E, Kim H, Ji M, Lee HS, Park HJ, Lee G, Yu J, Kim M, Lee W, Paik MJ.Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid type, which has used to treat musculoskeletal disorders in the horse racing industry. However, it has also used illicitly to mask clinical signs of inflammation and pain in racehorses. Thus, its accurate analysis has become an important issue in horse doping laboratories. In this study, an analytical method of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas chromatography-mass spectrometry (GC-MS). Characteristic fragment ions of [M-15], [M-57], and [M-139] permitted the accurate and ...
Immune Relevant Models for Ocular Inflammatory Diseases.
ILAR journal    February 24, 2018   Volume 59, Issue 3 352-362 doi: 10.1093/ilar/ily002
Gilger BC.Ocular inflammatory diseases, such as dry eye and uveitis, are common, painful, difficult to treat, and may result in vision loss or blindness. Ocular side effects from the use of antiinflammatory drugs (such as corticosteroids or nonsteroidal antiinflammatories) to treat ocular inflammation have prompted development of more specific and safer medications to treat inflammatory and immune-mediated diseases of the eye. To assess the efficacy and safety of these new therapeutics, appropriate immune-relevant animal models of ocular inflammation are needed. Both induced and naturally-occurring mode...
Diagnosis and Treatment of Undifferentiated and Infectious Acute Diarrhea in the Adult Horse.
The Veterinary clinics of North America. Equine practice    February 14, 2018   Volume 34, Issue 1 39-53 doi: 10.1016/j.cveq.2017.11.002
Shaw SD, Stämpfli H.Acute, infectious, diarrhea in adult horses is a major cause of morbidity and is associated with numerous complications. Common causes include salmonellosis, clostridiosis, Coronavirus, and infection with Neorickettsia risticii (Potomac horse fever). Treatment is empirical and supportive until results of specific diagnostic tests are available. Supportive care is aimed at restoring hydration, correcting electrolyte imbalances, and limiting the systemic inflammatory response. The mainstays of therapy are intravenous fluid therapy, electrolyte supplementation where necessary, nonsteroidal anti-i...
Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations.
Journal of veterinary pharmacology and therapeutics    November 16, 2017   Volume 41, Issue 2 239-245 doi: 10.1111/jvp.12464
Pedersen SK, Cribb AE, Read EK, French D, Banse HE.In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups....
Equine Intestinal Mucosal Pathobiology.
Annual review of animal biosciences    November 16, 2017   Volume 6 157-175 doi: 10.1146/annurev-animal-030117-014748
Blikslager A, Gonzalez L.The equine intestinal mucosa is intimately involved in maintaining homeostasis both on a systemic level by controlling extracellular fluid movement and at the local level to maintain barrier function. Horses are particularly susceptible to the clinical syndrome of colic, with the most severe cases involving strangulating obstruction that induces ischemia. Because of the mucosal vascular architecture, the mucosal epithelium is particularly susceptible to ischemic injury. The potential for reperfusion injury has been investigated and found to play a minimal role. However, inflammation does affec...
Occurrence, treatment protocols, and outcomes of colic in horses within Nairobi County, Kenya.
Veterinary world    October 22, 2017   Volume 10, Issue 10 1255-1263 doi: 10.14202/vetworld.2017.1255-1263
Gitari A, Nguhiu J, Varma V, Mogoa E.The aim of this study was to determine the treatments and their outcomes in horses with colic in Nairobi County, Kenya. Methods: This is a retrospective study to determine the occurrence, treatments, pain management, and outcomes of colic in horses in Nairobi County. Association between pain management protocols and the outcomes of colic with regard to recovery or death was also determined. Data collected from four equine practitioners were organized manually and given numerical codes as appropriate to facilitate entry into the computer. The coded data were entered into Microsoft Excel 2010 an...