Scott R. McClure

Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis

OBJECTIVE To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. DESIGN Randomized controlled clinical trial. ANIMALS 253 client-owned horses with naturally occurring osteoarthritis. PROCEDURES Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. RESULTS Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.

Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses

OBJECTIVE To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. ANIMALS 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. PROCEDURES In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed. RESULTS Mean +/- SD clearance and steady-state volume of distribution of firocoxib were 40.5 +/- 14.7 mL/h/kg and 2.3 +/- 0.7 L/kg, respectively. Mean half-life was 44.2 +/- 21.6 hours and 36.5 +/- 9.5 hours for IV and oral administration, respectively. The urine concentration- time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 +/- 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance. CONCLUSIONS AND CLINICAL RELEVANCE The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.

Effect of cold compression therapy on postoperative pain, swelling, range of motion, and lameness after tibial plateau leveling osteotomy in dogs

OBJECTIVE To evaluate the effect of cold compression therapy (CCT) on postoperative pain, lameness, range of motion of the stifle joint, and swelling following tibial plateau leveling osteotomy (TPLO) in dogs. DESIGN Randomized, blinded, placebo-controlled clinical trial. ANIMALS 34 client-owned dogs with unilateral deficiency of a cranial cruciate ligament undergoing TPLO. PROCEDURES Dogs were assigned to 2 groups. Group 1 (n = 17 dogs) received CCT in the 24-hour period following TPLO. Group 2 (n = 17 dogs) received no CCT. Degree of lameness, range of motion, and circumference of the stifle joint were measured before surgery and 1,14, and 28 days after surgery. A modified composite Glasgow pain scale, visual analogue scale, and pain threshold score were used to evaluate signs of pain before surgery and 1,14, and 28 days after surgery. Logistic regression and linear regression analysis were used to compare the measured variables. RESULTS No complications were observed, and all dogs tolerated CCT. Use of CCT resulted in lower values for the visual analogue scale and Glasgow pain scale and lower pain threshold scores; lower lameness scores; less swelling; and an increased range of motion 24 hours after surgery. At 14 days after surgery, there were no significant differences between groups. At 28 days after surgery, too few data sets were available for comparison. CONCLUSIONS AND CLINICAL RELEVANCE CCT decreased signs of pain, swelling, and lameness and increased stifle joint range of motion in dogs during the first 24 hours after TPLO.

Effects of extracorporeal shock wave therapy on wounds of the distal portion of the limbs in horses

OBJECTIVE To evaluate the effects of focused, extracorporeal shock wave therapy (ESWT) on the healing of wounds of the distal portion of the limbs in horses. DESIGN Randomized controlled trial. ANIMALS 6 healthy adult horses. PROCEDURES In each horse, a 4-cm-diameter full-thickness wound that included underlying periosteum was created on the dorsomedial aspect of each metacarpus and two 3-cm-diameter full-thickness wounds that included underlying periosteum were created on the dorsomedial aspect of each metatarsus. One randomly selected metacarpal wound and a randomly selected pair of metatarsal wounds were treated once weekly with ESWT at an energy flux density of 0.11 mJ/mm(2). For metacarpal wounds, swab specimens were collected for bacterial culture on days 1, 2, and 3 and area of epithelialization and extent of wound contraction were measured at 3- to 4-day intervals. Metatarsal wounds were biopsied after 2 and 4 weeks, and immunohistochemical staining for vascular endothelial growth factor, transforming growth factor-beta1, and insulin-like growth factor-1 was performed. RESULTS Results of bacterial culture, area of epithelialization, and percentage of wound contraction did not differ between treated and untreated wounds; however, healing time for treated wounds (mean, 76 days) was significantly shorter than healing time for untreated wounds (90 days). Staining intensity of growth factors did not differ significantly between treated and untreated wounds. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that ESWT may stimulate healing of wounds of the distal portion of the limbs in horses, although the mechanism by which healing was stimulated could not be identified.

Liposome-based diclofenac for the treatment of inflammation in an acute synovitis model in horses

Lameness as a result of joint disease is a major source of decreased athletic performance in the horse. Most treatment protocols include the administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Phenylbutazone, alone or in combination with other treatments, is the most commonly and widely used NSAID, however it has the potential for serious side effects. The introduction of the liposome-based formulation of the NSAID diclofenac has shown promising effect as a safe and convenient treatment for lameness associated with osteoarthritis. The purpose of this study was to evaluate the effect of topical liposome-based diclofenac in an acute inflammation model using subjective lameness scores and objective lameness evaluation, carpal surface temperature and circumference, synovial fluid cell count and total protein content, and the biochemical markers interleukin-1 (IL-1), IL-6, and prostaglandin E(2) as determinants of inflammation. In this acute inflammation model, there was no overall difference between treatment and control groups.

Treatment of equine protozoal myeloencephalitis with nitazoxanide

Summary This report describes two horses that were diagnosed with equine protozoal myeloencephalitis (EPM) and were treated with nitazoxanide. The horses were treated once daily with 20 mg/kg nitazoxanide orally for either 28 or 42 days. Nitazoxanide improved or eliminated the clinical signs of EPM in these two horses. Neither horse relapsed following treatment during the follow-up periods noted.

Risk factors associated with cast complications in horses: 398 cases (1997–2006)

OBJECTIVE To determine the frequency of and risk factors for complications associated with casts in horses. DESIGN Multicenter retrospective case series. ANIMALS 398 horses with a half-limb or full-limb cast treated at 1 of 4 hospitals. PROCEDURES Data collected from medical records included age, breed, sex, injury, limb affected, time from injury to hospital admission, surgical procedure performed, type of cast (bandage cast [BC; fiberglass tape applied over a bandage] or traditional cast [TC; fiberglass tape applied over polyurethane resin-impregnated foam]), limb position in cast (flexed, neutral, or extended), and complications. Risk factors for cast complications were identified via multiple logistic regression. RESULTS Cast complications were detected in 197 of 398 (49%) horses (18/53 [34%] horses with a BC and 179/345 [52%] horses with a TC). Of the 197 horses with complications, 152 (77%) had clinical signs of complications prior to cast removal; the most common clinical signs were increased lameness severity and visibly detectable soft tissue damage Cast sores were the most common complication (179/398 [45%] horses). Casts broke for 20 (5%) horses. Three (0.8%) horses developed a bone fracture attributable to casting Median time to detection of complications was 12 days and 8 days for horses with TCs and BCs, respectively. Complications developed in 71%, 48%, and 47% of horses with the casted limb in a flexed, neutral, and extended position, respectively. For horses with TCs, hospital, limb position in the cast, and sex were significant risk factors for development of cast complications. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 49% of horses with a cast developed cast complications.

Therapy planning and monitoring of tissue ablation by high intensity focused ultrasound (HIFU) using imaging and simulation

High intensity focused ultrasound (HIFU) “cooks” or ablates the target tissue at the focus of the ultrasound beam by thermal and cavitation effects. The HIFU is emerging as a non-invasive method for tumor ablation. The HIFU application for tissue ablation requires tools for dosimetry therapy planning, and real-time feedback of the intended and actual target tissues. Pretreatment planning is an important step for a successful HIFU therapy outcome. Typically, the therapy planning approach involves the use of pretreatment imaging data, defining the target and surrounding tissues by manual or semiautomatic segmentation, development of a 3-D anatomy model of the region of interest from segmentation or registration with a reference dataset, simulation of the HIFU beam and thermal dosimetry around the target tissue, display and 3-D visualization of imaging and simulation data, and review of the treatment plan options. Recent developments in therapy planning using imaging are targeted for specific applications such as prostate cancer using 3-D ultrasound images and uterine fibroids using MRI. However, significant developments have been accomplished in image guidance and feedback during the delivery of HIFU treatments. This talk reviews recent work towards therapy planning and presents approaches for developing strategies for HIFU therapy. It describes general and target-specific techniques and software tools for HIFU treatment planning using pretherapy imaging, and monitoring and controlling the HIFU delivery and tissue lesion using 1D, 2D and 3D ultrasound imaging. This aids development of optimized, high-precision HIFU applications for a controlled ablation of the target tumor. It also potentially reduces the overall treatment duration and exposure to non-target tissues.

A randomized controlled field trial of a novel trimethoprim-sulfadiazine oral suspension for treatment of Streptococcus equi subsp zooepidemicus infection of the lower respiratory tract in horses

OBJECTIVE To evaluate the effectiveness of a novel trimethoprim-sulfadiazine oral suspension for the treatment of naturally acquired Streptococcus equi subsp zooepidemicus infection in horses. DESIGN Randomized, controlled field trial. ANIMALS 180 horses with S equi subsp zooepidemicus infection. PROCEDURES Horses with lower respiratory tract infections caused by S equi subsp zooepidemicus were treated with a new formulation of combined trimethoprim-sulfadiazine oral suspension at a dosage of 24 mg/kg (10.9 mg/lb) twice daily for 10 days (treatment group) or with an equivalent volume of saline (0.9% NaCl) solution (placebo group). Response to treatment, including clinical signs and fecal consistency scores, was assessed twice daily. Any adverse effects were recorded. The primary outcome variable was clinical response; the secondary outcome variable was eradication of S equi subsp zooepidemicus on study day 17 as determined by bacteriologic culture of repeated transtracheal-wash specimens. RESULTS Of the 119 horses allocated to the treatment group, 69 (58%) had a positive clinical response. A significantly smaller proportion of horses in the placebo group (9/61 [15%]) had a positive clinical response. By day 5, 25 of 61 (41%) placebo horses had been withdrawn from the study because of negative clinical response, compared with only 10 of 119 (8.4%) treated horses. By day 10, 28 of 61 (46%) placebo horses had been withdrawn because of negative clinical response, compared with only 13 of 119 (11%) treated horses. There were few adverse events associated with the trimethoprim-sulfadiazine suspension. There were no significant differences in fecal consistency scores between treatment and placebo groups. CONCLUSIONS AND CLINICAL RELEVANCE The new oral suspension administered at 24 mg/kg twice daily effectively treated the clinical signs of S equi subsp zooepidemicus lower respiratory infection in horses and eliminated the organism from the respiratory tract. Adverse effects were minimal.

Evaluation of catastrophic musculoskeletal injuries in Thoroughbreds and Quarter Horses at three Midwestern racetracks

OBJECTIVE To determine the incidence of and compare the types of catastrophic musculoskeletal injuries (CMIs) sustained in Thoroughbreds and Quarter Horses during racing at 3 Midwestern racetracks from 2000 to 2006. DESIGN Retrospective cohort study. ANIMALS 139 Thoroughbred and 50 Quarter Horse racehorses euthanized because of CMIs. PROCEDURES Veterinary officials from 3 Midwestern racing jurisdictions provided injury reports for Thoroughbreds and Quarter Horses that sustained CMIs (which required euthanasia) and the total number of race starts for each year. The number of CMIs/1,000 starts was determined for each racetrack. Past performance reports for each horse with a CMI were evaluated. RESULTS The total number of race starts (both breeds) at the 3 racetracks from 2000 through 2006 was 129,460, with an overall incidence of 1.46 CMIs/1,000 race starts. Incidences of CMIs among racetracks were similar. Of horses that sustained a CMI, the median age of Thoroughbreds at first race was 3 years, compared with a median age of 2 years for Quarter Horses. A larger proportion of Thoroughbreds sustained a CMI in a claiming race than did Quarter Horses, and a larger proportion of Quarter Horses sustained a CMI in a futurity trial than did Thoroughbreds. The most common site for CMIs in Thoroughbreds was the left forelimb (69/124 [55.6%]), whereas most CMIs in Quarter Horses involved the right forelimb (18/30 [60.0%]). CONCLUSIONS AND CLINICAL RELEVANCE Differences identified between CMIs in Thoroughbred and Quarter Horse racehorses should allow veterinarians to focus on horses and anatomic regions of greatest risk of CMI during racing.