Short communication: survey of fresh cow management practices of dairy cattle on small and large commercial farms.

The objective was to conduct a survey of current fresh cow management practices that have an effect on health and diseases postpartum considering different herd sizes of commercial dairy farms. A mail survey regarding aspects of the fresh cow program including general management issues, calving, diseases, and veterinary service was conducted utilizing a convenience sample. A total of 429 survey forms were returned (12.0% response rate) and could be used for final analysis. Only 21.6% of the farms had a designated fresh cow pen. Almost every farm executed some type of fresh cow examination. Only 18.5% of farm managers documented the observations. Most of the dairy managers used more or less subjective criteria such as general appearance (97.0%) and appetite (69.7%). Only a minority of the responding dairy managers monitored their fresh cows using objective (fever 33.6%) or semiquantitative measures (subclinical ketosis 2.8%; body condition score 36.4%). On most farms, the veterinarian visited the herd only if needed (72.6%). Most cases of retained fetal membranes were treated by manual removal (72.3%) and antibiotic pills (89.5%). Several challenges and opportunities were identified to improve cow management practices.

Dirlotapide: a review of its properties and role in the management of obesity in dogs.

Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor developed specifically for canine weight reduction. MTP catalyzes the assembly of triglyceride-rich apolipoprotein-B containing lipoproteins to form chylomicrons in the intestinal mucosa and very low-density lipoproteins in the liver. Following oral administration, dirlotapide has in vivo selectivity for intestinal MTP compared with hepatic MTP. In addition to reducing intestinal fat absorption, dirlotapide also reduces food intake in a dose-dependent manner, probably via increased release of peptide YY into the circulation. The decrease in food intake is responsible for the majority of the weight reduction effect. In clinical use, it is recommended to adjust the dose according to the observed weight loss of each individual. The initial dose of 0.05 mg/kg is doubled after 14 days and then adjusted monthly, the maximum permitted daily dose is 1.0 mg/kg, although doses as high as 10 mg/kg have been administered to dogs without severe adverse experience in safety studies. Dirlotapide can be used without necessitating changes to the current feeding or exercise regimens, but it is desirable to monitor the food intake during weight-stabilization to establish revised feeding and exercise routines that will minimize the risk of weight regain post-treatment. The drug offers a novel approach that is applicable in cases where dietary management alone has proved to be unsuccessful.

Canine obesity: an overview.

Canine patients are generally regarded as being clinically obese when their body weight is at least 15% above ideal. The incidence of obesity in dogs is thought to be in the range of 20-40% of the general population and, since obesity is known to predispose or exacerbate a range of serious medical conditions, its importance cannot be overstated. Management of obesity through dietary restriction and increased exercise is often difficult to achieve and dependent upon owner compliance. Until recently there has been no authorized therapeutic medication available for weight reduction in dogs, and drugs used in people have proved unsuitable. However, with the development of microsomal triglyceride transfer protein inhibitors for canine use, such as dirlotapide, the veterinarian has a novel method with which to augment traditional weight control programmes. This approach has the additional advantage that weight loss is achieved without dietary restriction or change in exercise regimen, providing encouragement for the owner to comply with subsequent dietary and exercise recommendations, thereby increasing the likelihood for long-term success.

The safety of dirlotapide in dogs.

The safety of dirlotapide in dogs was evaluated in two studies with parallel designs. In an acute tolerance study, 24 beagles (six dogs per treatment) were treated orally once daily for 14 days with placebo or dirlotapide at 2.5, 5.0, or 10.0 mg/kg/day. In a margin-of-safety study, 38 overweight, neutered beagles were treated orally once daily for 3 months with dirlotapide at doses up to 0.5 mg/kg/day (six dogs), 1.5 mg/kg/day (12 dogs) and 2.5 mg/kg/day (six dogs). Control dogs received placebo at 0.3 mL/kg/day (10 dogs) and 0.5 mL/kg/day (four dogs). Results were similar for both studies, and no serious adverse events were observed. Dirlotapide was clinically well-tolerated in dogs at dosages up to 10 mg/kg/day for 14 days and 2.5 mg/kg/day for 3 months. Dirlotapide produced the expected decrease in food intake and body weight (up to 20-40%) without ill effects. Clinical, pathologic, and histopathologic findings were reversible and consistent with suppression of food intake and rapid weight loss produced by elevated dirlotapide dosages. In both studies, sporadic emesis and loose stools were observed in both placebo and dirlotapide-treated dogs. Incidence of emesis generally increased with dose and decreased with treatment time. Elevations in hepatic transaminase activity were seen in dogs treated with more than 1.5 mg/kg dirlotapide daily, but were not associated with clinical signs or microscopic evidence of hepatic degeneration or necrosis.

Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers.

The effects of dirlotapide on body weight (BW) reduction were investigated in overweight Labradors in two parallel-design studies. Study A involved 42 dogs randomized to 0.0, 0.025, 0.05, 0.1, 0.2 or 0.4 mg dirlotapide/kg/day orally for 4 weeks. Study B involved 72 dogs randomized to nine treatments: placebo (24 weeks); dirlotapide (24 weeks) followed by placebo (28 weeks); or dirlotapide (52 weeks); on diets containing 5%, 10% or 15% fat. Dirlotapide dose (initially 0.1 mg/kg) was adjusted monthly during 24-week weight-loss and subsequent 28-week weight-stabilization phases. Food was offered above maintenance energy requirements (MERx 1.1-1.2) based on initial BW. Body composition (body fat, lean tissue and bone mineral content) was monitored using dual-energy X-ray absorptiometry. After treatment, dogs that had received dirlotapide for 52 weeks were fed 90% of quantity consumed at week 52. In study A, BW and food intake decreased asymptotically with dose: mean weekly weight loss exceeded 1% at 0.1-0.4 mg/kg. In study B, dirlotapide resulted in significant mean weekly weight loss (>0.8%) and decreased food intake over 24 weeks compared with placebo (P = 0.0001) for all diets. Food restriction minimized post-treatment weight rebound. Dirlotapide administered daily to dogs for up to 52 weeks was clinically safe and resulted in sustained weight reduction.

An evaluation of dirlotapide to reduce body weight of client-owned dogs in two placebo-controlled clinical studies in Europe.

The clinical efficacy for weight loss and safety of dirlotapide in dogs were evaluated in two multi-centre studies with parallel designs. Overweight, adult dogs (n = 245) of various breeds were randomized to treatment with dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg/day commencing on day 0 and doubled after 14 days. Every 28 days, dogs were examined, weighed, body condition scores (BCS) were recorded, and dose was adjusted to meet weight loss targets. Each study comprised three consecutive phases: weight-loss (up to day 196); weight-stabilization (84 days); and post-treatment (28 days). pre-treatment feeding and exercise regimens were continued during treatment. Dirlotapide-treated dogs showed mean weight loss of 15.9% (study A) and 14.0% (study B) by the end of weight loss phase (up to day 196). Percentage weekly weight losses for dirlotapide were significantly greater than for placebo (P < or = 0.0002). Emesis and diarrhoea were experienced in both treatments but were more frequent with dirlotapide; resolution was spontaneous. BCS improved for 75.7-82.5% of dogs on dirlotapide treatment compared with 15.4-41.4% for placebo. Mean dirlotapide dosage at end of weight-loss phase was 0.38 (study A) and 0.29 (study B) mg/kg initial body weight/day. Dirlotapide was found to be clinically safe and effective in the reduction of body weight in overweight dogs.

Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America.

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0-112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8-14.0% compared with 3.0-3.9% for placebo (P = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.

Efficacy of doramectin injectable against Oestrus ovis and gastrointestinal nematodes in sheep in the southwestern region of France.

A study was conducted to evaluate the therapeutic efficacy of doramectin administered intramuscularly at a dose rate of 200 microg/kg to sheep harbouring naturally acquired infections of gastrointestinal nematodes and Oestrus ovis in the southwestern region of France. On day 0, 24 sheep were selected on the basis of positive faecal egg counts (>100 EPG) and positive assessment of O. ovis infection (including positive O. ovis antibody level and positive clinical score). The sheep were randomly allocated to a non-medicated control group (T1) or a doramectin-treated group (T2) of 12 animals each. On day 0, sheep in group T2 received a single intramuscular injection of doramectin (200 microg/kg), whereas those in group T1 received an intramuscular injection of saline solution (sodium chloride, 0.02ml/kg). Individual faecal egg counts were performed on days 0, 1, 2, 3, 4, 5, 6, 7, and 14. Between days 14 and 16, all sheep were slaughtered, and worm and O. ovis burdens were determined. In doramectin-treated sheep, faecal egg counts had decreased to zero by day 4 for all recovered types of nematode eggs: strongyles, Nematodirus sp., Trichuris sp., and Rhabditidae sp. For strongyles, Nematodirus sp., and Rhabditidae, the percentage reductions in faecal egg counts (geometric means) of doramectin-treated sheep, compared to the non-medicated control sheep were 100% from days 4-7. For Trichuris sp., they were 100, 99.7, 99.9, and 100% on days 4, 5, 6, and 7, respectively. On day 14, percentage reductions were 100% for Nematodirus sp. and Rhabditidae, and 99.8 and 99.1% for strongyles and Trichuris sp., respectively. At necropsy, only adult nematodes and mainly first-stage O. ovis larvae were recovered. Doramectin was highly efficacious against the adult stages of Teladorsagia circumcincta (100%), Nematodirus battus (100%), Nematodirus filicollis (99.9%), Oesophagostomum venulosum (99.8%), and Trichuris sp. (99.3%). It was also 100% efficacious against first-stage larvae of O. ovis. No abnormal clinical signs or adverse reactions in any of the sheep treated with doramectin were observed.