A randomized, blinded, controlled USA field study to assess the use of fluralaner topical solution in controlling feline flea infestations.

BACKGROUND: Fleas are a common ectoparasite of domestic cats and there is a need for novel treatments that improve feline flea control. METHODS: This investigator-blinded, multi-center randomized, positive-controlled study evaluated the flea control in cats provided by a single owner-applied treatment with a fluralaner topical formulation compared with a positive control. Households with up to five healthy cats, all at least 12 weeks of age and weighing at least 1.2 kg (2.6 lb), were randomized in an approximate 3:1 ratio of fluralaner to positive control. All cats in households randomized to the positive control group were dispensed three treatments, at 4-week intervals, of a commercial formulation of fipronil/(S)-methoprene. All cats in households randomized to the fluralaner group were dispensed an initial treatment at enrollment and a second treatment at week 12 for an additional 3-week observation of treatment safety. One primary cat with at least five live fleas at enrollment was randomly selected within each household. Flea counts were performed on all primary cats at 4-week intervals through week 12. Efficacy measurement was based on reduction in flea counts from baseline. Treatment was considered effective at weeks 4, 8 and 12 if mean live flea count reductions were 90% or greater and statistically significantly different (P ≤ 0.05) from counts at enrollment. RESULTS: In 18 investigational veterinary clinics across 11 USA states, 116 households (224 cats) were randomized to receive topical fluralaner and 45 households (87 cats) were randomized to the fipronil-methoprene combination. Fluralaner was demonstrated to be effective at 4 weeks (99.1% flea count reduction), 8 weeks (99.5%), and 12 weeks (99.0%), and all reductions were significantly different from the enrollment count (all P < 0.0001). The fipronil-methoprene combination was < 90% effective at each post-treatment assessment, with peak efficacy of 75.4% at 12 weeks (all P < 0.0001). No treatment-related serious adverse events were reported in either group. CONCLUSIONS: Owner-applied fluralaner topical treatment was safe in cats and was highly effective in killing fleas over the subsequent 12 weeks.

A randomized, blinded, controlled USA field study to assess the use of fluralaner topical solution in controlling canine flea infestations.

BACKGROUND: Orally administered fluralaner effectively controls fleas and ticks on dogs for 12 weeks. This study evaluates the flea control efficacy achieved with topically applied fluralaner in dogs. METHODS: This investigator-blinded, multi-center randomized, positive controlled study evaluated flea control efficacy in dogs following a single owner-applied treatment of topical fluralaner. A positive control group received three treatments, at 4-week intervals, of a commercial formulation of fipronil/(S)-methoprene. All dogs in households randomized to the fluralaner group were dispensed an initial treatment at enrollment and a second treatment at week 12 for an additional 3-week observation of treatment safety. Households with up to five healthy dogs, all at least 12 weeks of age and weighing at least 2 kg (4.4 lb), were randomized in a ratio of 3:1 of fluralaner to positive control. Within households, one primary dog with at least 10 live fleas at enrollment was randomly selected. Flea counts were performed on all primary dogs every 4 weeks through week 12. Efficacy measurement was based on reduction from baseline flea counts. Treatment was considered effective if geometric mean live flea count reductions at weeks 4, 8, and 12 were 90% or greater and significantly different from counts at enrollment. In addition, for each time point the arithmetic mean live flea counts, the efficacy based on arithmetic means, the number and percentage of dogs with at least a 90% reduction in flea count, and the number and percentage of flea free dogs were calculated. Statistical comparisons were also made between treatment groups. RESULTS: At 12 sites, across 10 states, 121 households (221 dogs) were randomized to receive fluralaner and 44 households (100 dogs) were randomized to receive the positive control. Fluralaner was demonstrated to be significantly effective (all P ≤ 0.0001) at 4 weeks (99.8% reduction), 8 weeks (99.9%), and 12 weeks (99.9%). The positive control was significantly different from baseline (all P ≤ 0.0001) and showed a reduction of 81.2% at 4 weeks and was effective at 8 weeks (90.3%) and 12 weeks (93.0%). Arithmetic mean flea count reductions for the fluralaner group at 4, 8, and 12 weeks were 99.8, 99.9, and 99.9%, respectively. For the positive control, arithmetic mean flea count reductions were 58.8, 75.3, and 80.8% at 4, 8, and 12 weeks, respectively. No treatment-related serious adverse events were reported in either group. CONCLUSIONS: Owner-applied topical fluralaner treatment was safe in dogs and provided ≥ 99.8% flea control efficacy for 12 weeks.

A randomized, blinded, controlled USA field study to assess the use of fluralaner tablets in controlling canine flea infestations.

BACKGROUND: The novel isoxazoline molecule fluralaner provides 12 weeks activity against fleas and 8 to 12 weeks against tick infestations according to label claims. METHODS: This blinded, multi-center study in client-owned dogs evaluated the flea control provided by a single oral fluralaner treatment (25-56 mg/kg; Bravecto™, Merck Animal Health) compared to a control group administered three oral spinosad (30 - 60 mg/kg; Comfortis®, Elanco) treatments at 4-week intervals together with an amitraz collar (9%, Preventic®, Virbac). Households were randomized (3:1 ratio) to either fluralaner (224 dogs, 118 households) or control (70 dogs, 39 households). Within households, one primary dog with at least 10 live fleas at enrollment was randomly selected for whole body flea counts every 4 weeks through Week 12; all dogs were followed for safety until Week 12. Fluralaner dogs received two additional doses at Weeks 12 and 24 for further safety and palatability observations through Week 26. RESULTS: Geometric mean flea count reductions from baseline for the fluralaner group at Weeks 4, 8, and 12 were 99.7%, 99.8%, and 99.8%, respectively; and 96.1%, 99.5%, and 99.6% for the spinosad controls. Percentages of flea-free primary dogs at Weeks 4, 8, and 12 were 91.1%, 95.4%, and 95.3% for the fluralaner group; and 44.7%, 88.2%, and 84.4% for the controls; the differences were significant at Weeks 4 (P < 0.0001) and 12 (P = 0.0370). Improvements in veterinarian assessed flea allergy dermatitis (FAD) were observed in both groups. Fluralaner tablets were accepted free choice in over 90% of doses. The most common adverse event was vomiting, occurring in 7.1% of the fluralaner group and 14.3% of the controls. No treatment related serious adverse events were reported. CONCLUSIONS: A single treatment of dogs with the palatable fluralaner flavored chewable tablet provides a safe and effective option for 12 weeks of flea control at least equivalent to that of 3 sequential treatments with spinosad tablets. Linked to the high level of flea control was a substantial alleviation of associated signs of FAD.

Association of holidays, full moon, Friday the 13th, day of week, time of day, day of week, and time of year on case distribution in an urban referral small animal emergency clinic.

OBJECTIVE: To interrogate the association of variables: day of week, time of day, day of the year (major holidays, Friday the 13th, and the full moon), and month of year with the caseload of an urban academic emergency service. DESIGN: Retrospective study. SETTING: Urban small animal teaching hospital emergency clinic. ANIMALS: Cats and dogs that were presented to the emergency clinic. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The hospital computer database was searched for all visits to the Emergency Service of the Mathew J. Ryan Veterinary Hospital of the University of Pennsylvania from January 1, 1987 through December 31, 2002. Variables included in the electronic data were date of admission, time of day of admission, species (dog or cat), hospital service the case was transferred to for ongoing care and whether the case was discharged directly from the emergency service. The association of caseload with day of week, time of day, day of the year (major holidays, Friday the 13th, and the full moon), and month of year was described and statistically evaluated. Saturdays and Sundays were the busiest days of the week and significantly increased caseload was noted for the majority of holidays (except Easter Day and Thanksgiving Day) with Memorial Day being the busiest. Midweek evenings as well as Saturday and Sunday afternoons were the busiest periods of the day. There was no association with caseload and Halloween, the full moon, or Friday the 13th. CONCLUSIONS: The busiest times were midweek evenings, Saturday and Sunday afternoons, and most major holidays.

Evaluation of a contract breeding management program in Ohio dairy herds: test day summary and economic measures.

A field study was conducted to assess the impact of a contract breeding program that was offered by a breeding co-operative and featured tail chalking and daily evaluation of cows for insemination by co-operative technicians; dairy employees no longer handled estrous detection and insemination activities. From early 2002 until mid-2004, herd-level test day summary records related to production and reproduction were obtained for 32 herds identified as well-managed client herds of the breeding co-operative. Using analyses that controlled for other predictors and random herd-level effects, average days to first service were less by 13 days (P=0.0037) and estrous detection rate was greater by 12% (P=0.0011) for program than for non-program herds. Although first service conception rate was slightly less and the program herds used 0.34 more services per conception (P=0.1488) than non-program herds, the program herds averaged 16 fewer days before pregnancy (P=0.028). Test day summary information and representative estimates of feed, milk, and semen prices were used in a spreadsheet-based model to estimate a partial budget annuity value for an average cow in each herd on each test day. Value of an average cow from a contract herd did not significantly differ from a non-contract herd, even though the analyses suggested an economic benefit for the program herds; the modeling did not, however, account for costs of the program implementation. Additional analyses did not find any significant associations between technician and on days to first service, first service conception rate, estrous detection rate, services per conception, or days open.

In vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole on Malassezia organisms from dogs with otitis externa.

The purpose of this study was to evaluate the in vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole in purified water on Malassezia organisms from dogs with otitis externa. Malassezia organisms were collected from ear swab samples from the external ear canal of 19 dogs with otitis externa plus one control strain of Malassezia pachydermatis. Three test solutions were evaluated: ER (EDTA, tromethamine, benzyl alcohol), ER + keto (EDTA, tromethamine, benzyl alcohol, ketoconazole), and H2O (purified water). Ten-millilitre aliquots of each test solution was transferred into 20 tubes and inoculated with one of the isolates (1 tube per isolate: 19 clinical and 1 control strain). Samples were retrieved from each tube at five time points (0, 15, 30, 45 and 60 min), transferred to Petri dishes, mixed with Sabouraud dextrose agar supplemented with 0.5% Tween 80 and incubated. Following incubation, the plates were examined for growth and colonies counted as colony-forming units per millilitre. The data were analysed using a repeated measures analysis, with pair-wise comparisons of solution-time combinations. There was a significant reduction in Malassezia growth in ER + keto at all time points (P < 0.0001) compared to time zero. Neither ER nor H2O had any effect on the growth of Malassezia. ER + keto was significantly more effective in reducing Malassezia growth (P < 0.0001) at all time points compared to both ER and H2O. ER + keto may be useful in the treatment of Malassezia otitis externa. Future studies should be performed to evaluate the in vivo efficacy of ER + keto as treatment for otic infections caused by Malassezia.

Atrial, SA nodal, and AV nodal electrophysiology in standing horses: normal findings and electrophysiologic effects of quinidine and diltiazem.

BACKGROUND: Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. HYPOTHESES: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. ANIMALS: Fourteen healthy horses. METHODS: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during programmed electrical stimulation at baseline, after administration of quinidine gluconate (10 mg/kg IV over 30 minutes, n = 7; and 12 mg/kg IV over 5 minutes followed by 5 mg/kg/h constant rate infusion for the remaining duration of the study, n = 7), and after coadministration of diltiazem (0.125 mg/kg IV over 2 minutes repeated every 12 minutes to effect). RESULTS: Quinidine significantly prolonged the atrial effective refractory period, shortened the functional refractory period (FRP) of the AV node, and increased the ventricular response rate during atrial pacing. Diltiazem increased the FRP, controlled ventricular rate in a rate-dependent manner, caused dose-dependent suppression of the sinoatrial node and produced a significant, but well tolerated decrease in blood pressure. Effective doses of diltiazem ranged from 0.125 to 1.125 mg/kg. CONCLUSIONS AND CLINICAL IMPORTANCE: Standard electrophysiologic techniques allow characterization of drug effects in standing horses. Diltiazem is effective for ventricular rate control in this pacing model of supraventricular tachycardia. The use of diltiazem for rate control in horses with atrial fibrillation merits further investigation.

Evaluation of a contract breeding management program in selected Ohio dairy herds with event-time analysis II. Parametric frailty models.

The effect of a contract breeding program offered by a breeding co-operative was assessed using parametric frailty models with event-time analysis technique in a field study of Ohio dairies. The program featured tail chalking and daily evaluation of cows for insemination by co-operative technicians; dairy employees no longer handled estrus detection activities. Test day records were obtained between early 2002 and mid-2004 for 16,453 lactations representing 11,398 cows in 31 herds identified as well-managed client herds by the breeding co-operative. Various parametric distributions for event times available in a commercial software (Stata 9.1, College Station, TX) were tested to assess which distribution fit the calving-to-conception data best. After identifying the distribution with the best fit, a full model with potential confounders and other significant predictors of time to pregnancy was developed and then frailty terms were included in the model. Generalized gamma and log-normal distributions fit the data best, but since gamma distribution does not allow the use of frailty effects, log-normal distribution was used in further modeling. Separate accelerated failure time models with frailty terms to account for latent effects at the herd, cow, or lactation level were developed, testing both gamma and inverse Gaussian frailty distributions. In these models, potential confounders and statistically significant predictors were also controlled for, and the association between the contract breeding program and the mean time to pregnancy was characterized using time ratios. The log-normal model identified that interval to pregnancy was associated with breed, herd size, use of ovulation synchronization protocols, parity, calving season and somatic cell score (above or below 4.5) and maximum milk yield prior to pregnancy or censoring. While controlling for these factors, there was a reduction in average time to pregnancy among cows managed under the contract breeding program. All frailty terms were highly significant, regardless of whether it was an individual frailty at the lactation level or a shared frailty at the cow or herd level, suggesting that there was considerable heterogeneity within these levels. Inclusion of a frailty term at the herd level changed the estimate for the contract breeding program considerably, while a frailty term on other levels did not, indicating that herd characteristics (e.g., overall management) have a substantial impact on reproductive performance and should be accounted for in the analysis. Interpretation using time ratios with or without a shared herd frailty found that the contract breeding program was associated with a reduction of 6.5% and 14.1% in mean time to pregnancy, respectively.

Evaluation of a contract breeding management program in selected Ohio dairy herds with event-time analysis I. Cox proportional hazards models.

An observational study was conducted in order to assess the impact of a contract breeding program on the reproductive performance in a selected group of Ohio dairies using event-time analysis. The contract breeding program was offered by a breeding co-operative and featured tail chalking and daily evaluation of cows for insemination by co-operative technicians. Dairy employees no longer handled estrus detection activities. Between early 2002 and mid-2004, test-day records related to production and reproduction were obtained for 16,453 lactations representing 11,398 cows in a non-random sample of 31 dairies identified as well-managed client herds of the breeding co-operative. Of the 31 herds, 15 were using the contract breeding at the start of the data acquisition period, having started in the previous 2 years. The remaining 16 herds managed their own breeding program and used the co-operative for semen purchase. Cox proportional hazards modeling techniques were used to estimate the association of the contract breeding, as well as the effect of other significant predictors, with the hazard of pregnancy. Two separate Cox models were developed and compared: one that only considered fixed covariates and a second that included both fixed and time-varying covariates. Estimates of effects were expressed as the hazard ratio (HR) for pregnancy. Results of the fixed covariates model indicated that, controlling for breed, herd size, use of ovulation synchronization protocols in the herd, whether somatic cell score exceeded 4.5 prior to pregnancy or censoring, parity, calving season, and maximum test-day milk prior to pregnancy or censoring, the contract breeding program was associated with an increased hazard of pregnancy (HR=1.315; 95% CI 1.261-1.371). The results of the time-varying covariates model, which controlled for breed, herd size, use of ovulation synchronization protocols, somatic cell score above 4.5, parity, calving season, and testing season also found that the program was associated with an increased hazard of pregnancy (HR=1.387; 95% CI 1.327-1.451). The fixed and time-varying covariates models both found similar sets of predictors when analyzing the association of the contract breeding program with hazard of pregnancy. Both models identified a 30% or greater increase in hazard of pregnancy associated with use of the contract breeding program, suggesting that herds subscribing to the program achieved pregnancies in a more timely fashion.

Effect of medial meniscal release on tibial translation after tibial plateau leveling osteotomy.

OBJECTIVE: To evaluate the biomechanical effects of medial meniscal release (MMR) and medial, caudal pole hemimeniscectomy (MCH) on joint stability in the cranial cruciate ligament (CCL)-deficient canine stifle before and after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Experimental study. ANIMALS: Thirty-one dogs. METHODS: In experiment 1, 16 pairs of normal hindlimbs randomly assigned to an intact or transected CCL group were studied to determine the magnitude of tibial translation after MMR and MCH under 20% body weight load using radiographic imaging of radio-opaque markers. In experiment 2, 15 pairs of CCL-deficient hindlimbs were randomly assigned to a TPLO or sham TPLO group. The remainder of the experiment was performed as described for experiment 1. The effect of CCL transection, MMR, MCH and TPLO were analyzed using 2-way repeated measures ANOVA; P<.05 was considered significant. RESULTS: We found a greater effect of MMR on tibial translation in transected CCL stifles than in intact stifles (P=.0016). We found no further effect of MCH after MMR (P>.05). We found a greater effect of MMR in sham TPLO than TPLO stifles (P=.0013) but no further effect of MCH after MMR (P>.05). CONCLUSIONS: By resisting tibial translation the medial meniscus might be at greater risk of tearing in CCL-deficient stifles. TPLO may spare the medial meniscus by neutralizing the tibial thrust and eliminating the wedge effect of the medial meniscus. CLINICAL RELEVANCE: MMR may not be indicated in the CCL-deficient stifle stabilized by TPLO.

In vitro activity of an ear rinse containing tromethamine, EDTA, and benzyl alcohol on bacterial pathogens from dogs with otitis.

OBJECTIVE: To evaluate the in vitro activity of an ear rinse (ER) containing tromethamine, EDTA, and benzyl alcohol on bacterial pathogens from dogs with otitis. SAMPLE POPULATION: Organisms were collected from ear swab specimens from the external and middle ear and included Staphylococcus spp (n = 11; Staphylococcus intermedius [7] and Staphylococcus spp [4]), Pseudomonas aeruginosa (5), Proteus spp (5), beta-hemolytic streptococcus (11), and 1 control strain of each organism. PROCEDURES: 3 test solutions were evaluated including EDTA, tromethamine, and benzyl alcohol (ER); EDTA and tromethamine (ER without benzyl alcohol [ER - BA]); and purified water. Ten-milliliter aliquots of each test solution were transferred into 36 tubes and inoculated with one of the organisms. Samples were retrieved from each tube at 0, 15, 30, 45, and 60 minutes, transferred to Petri dishes, mixed with soybean-casein digest agar, and incubated. After incubation, plates were examined for growth, and the number of colonies was expressed as CFU per milliliter. RESULTS: ER significantly decreased bacterial growth in vitro of P aeruginosa and beta-hemolytic streptococcal organisms within 15 minutes, Proteus spp within 30 minutes, and Staphylococcus spp within 60 minutes. Comparatively, the presence of benzyl alcohol in ER significantly decreased bacterial growth of beta-hemolytic streptococcus and Proteus spp. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of results of this study, future studies should be performed to evaluate the in vivo efficacy of ER alone as a treatment for otic infections caused by beta-hemolytic streptococcus, P aeruginosa, and Proteus spp and of ER combined with an antimicrobial agent for otic infections caused by Staphylococcus spp.

Effects of electrostimulated acupuncture on ground reaction forces and pain scores in dogs with chronic elbow joint arthritis.

OBJECTIVE: To determine whether use of electrostimuluated acupuncture (ESA) would result in significant improvements in ground reaction forces and lameness scores in dogs with chronic elbow joint osteoarthritis secondary to elbow joint dysplasia. DESIGN: Randomized, controlled, crossover clinical trial. ANIMALS: 9 dogs with chronic forelimb lameness and radiographic evidence of elbow joint osteoarthritis. PROCEDURES: All dogs had a 3-week control acclimation period during which gait analysis was performed weekly. Dogs then received ESA once weekly for 3 weeks followed by a sham treatment once weekly for 3 weeks or received the sham treatment followed by ESA. Gait analysis was repeated prior to each treatment, and owners were asked to provide pain scores by use of a visual analog scale method. RESULTS: Treatment (control, acupuncture, or sham) did not have a significant effect on ground reaction forces for any limb. Owners of 8 of the 9 dogs were able to correctly guess the time period when ESA was delivered. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESA did not have any significant effects on severity of lameness, as determined by measurement of ground reaction forces, or severity of pain, as determined by visual analog scale pain scores, in dogs with chronic elbow joint osteoarthritis secondary to elbow joint dysplasia.

Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats.

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.