The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.

BackgroundThis study evaluated the effectiveness and safety of grapiprant for treatment of pain in dogs with osteoarthritis (OA).Hypothesis/ObjectivesGrapiprant will relieve pain as measured by the owner's and veterinarian's evaluation of pain in dogs with OA. Another objective was evaluation of the safety of grapiprant.AnimalsTwo hundred and eighty‐five client‐owned dogs with OA were enrolled and treated with grapiprant or placebo with 262 cases (N = 131 in each group) evaluable for the effectiveness analysis.MethodsIn this prospective, randomized, masked, placebo‐controlled study dogs were treated daily with grapiprant (2 mg/kg) per OS or placebo. Owners completed an evaluation using the Canine Brief Pain Inventory (CBPI) on days 0, 7, 14, 21, and 28. Success was defined as improvement in the CBPI. Veterinary assessments were made on screening and days 14 and 28. Safety was evaluated by physical examination, evaluation of clinical pathology results, and owner observations.ResultsGrapiprant treatment improved pain compared to placebo on day 28 (48.1 and 31.3% treatment successes respectively; P = .0315). The pain interference score (PIS) and pain severity score (PSS) improved in the grapiprant group compared to placebo (P = .0029 and 0.0022, respectively). Veterinary assessments were significantly better in the grapiprant‐treated dogs (P = .0086). Grapiprant generally was well tolerated, but a higher percentage of treated dogs (17.02%) had occasional vomiting as compared to the placebo group (6.25%).Conclusions and Clinical ImportanceGrapiprant is an effective treatment for alleviation of pain in dogs with OA, and represents a modality of treatment that may be better tolerated than current options.

For defining the mechanism of control of sex skin colour in male rhesus macaques (Macaca mulatta) by hormones, a spectrocolorimeter was used to monitor skin redness after administration of testosterone, dihydrotestosterone (a non-aromatizable androgen), oestradiol or fadrozole (an aromatase inhibitor that blocks the conversion of testosterone to oestrogen). Skin blood flow was measured by laser doppler. Eight 9-14 kg, 5-9 year old intact male rhesus macaques were given hormone, fadrozole or vehicle treatments in a cross-over experimental design. Baseline blood flow and colour measurements were taken in four paired tattoo defined areas on the back and legs of each animal (one pair in non-sex skin, three pairs in sex skin). Colour and blood flow measurements were taken 3-4 days after the first dose and, thereafter, once a week for 3-6 weeks. Measurements taken after treatments were compared with baseline and intra-animal comparisons were made between treatment and vehicle for each animal. In all animals after administration of 4 mg testosterone kg-1 (long-acting), redness in the sex skin areas increased (P = 0.032) by day 3 and returned to baseline values by day 7. Administration of 1 mg oestradiol kg-1 day-1 for 4 days caused increased redness in all animals (P = 0.007) similar in magnitude to that caused by testosterone. Administration of 0.1 mg dihydrotestosterone kg-1 day-1 for 4 days resulted in a nonsignificant decrease in redness (P = 0.09) on days 3-7. Treatment with fadrozole (0.25-0.5 mg kg-1 day-1) for 3 weeks caused sex skin to become significantly less red during treatment (P = 0.014). There was no significant change in redness in non-sex skin areas during any treatment. Sex skin blood flow increased in animals treated with testosterone, correlating with increased redness (R = 0.906), while blood flow in non-sex skin was unchanged. Increased redness after treatment with testosterone and oestrogen, no change in redness with treatment with dihydrotestosterone and a decrease in redness after treatment with fadrozole support the conclusion that oestrogen controls sex skin redness, and testosterone acts indirectly through conversion to oestrogen to cause increased sex skin redness in male rhesus macaques.

Human prostate was used as a source of 5 alpha reductase. Compounds were incubated with an enzyme preparation and [3H]testosterone. [3H]-dihydrotestosterone production was measured to calculate 5 alpha reductase activity. IC50 values (ng/ml) were finasteride = 1; Permixon = 5,600; Talso = 7,000; Strogen Forte = 31,000; Prostagutt = 40,000; and Tadenan = 63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5 alpha reductase, while Permixon and Bazoton have neither anti-androgen nor 5 alpha reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5 alpha reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 micrograms/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5 alpha reductase.

Two questionnaires were completed by 186 presumably normal young adults. The first was a specially created Anxiety Questionnaire (AQ) that asked respondents to provide information on their current levels of anxiety, information on frequency of panic attacks, and types of symptoms experienced during a panic attack. The second questionnaire was the Hopkins Symptom Checklist (HSCL-90). The results showed that 34.4% of the subjects reported having had one or more panic attacks in the past year, and 2.2% reported having had three or more panic attacks in the past 3 weeks, a frequency that could lead to a diagnosis of panic disorder. The panic symptoms reported as being most severe were heart pounding, trembling, and sweating. When subjects who reported having had one or more panic attacks (panickers) were compared with the nonpanickers on the HSCL-90, it was found that the infrequent panickers scored significantly higher on 6 of the 10 subscales.

BackgroundThin body condition and weight loss are common in cats with chronic kidney disease (CKD). However, the time course and progression of weight loss before and after diagnosis have not been thoroughly evaluated.Hypothesis/ObjectivesTo describe weight loss in cats with CKD before and after diagnosis and its relationship to survival.AnimalsA total of 569 cats (55.5% females and 44.5% males) with CKD from 6 US veterinary practices for which International Renal Interest Society (IRIS) stage, age, date of CKD diagnosis, and at least two body weight measurements were available.MethodsBody weight measurements were analyzed by time windows and polynomial growth curve analysis. Survival analysis was performed by Kaplan–Meier curves and log‐rank tests.ResultsMedian age at diagnosis was 14.9 years (range, 5.0–22.8 years). Cats were categorized at diagnosis as IRIS stage 1 (n = 34 [6%]), stage 2 (n = 345 [61%]), stage 3 (n = 141 [25%]), and stage 4 (n = 49 [9%]). Median body weight at diagnosis was 4.2 kg (range, 1.6–9.9 kg). Cats lost a median of 8.9% of body weight in the 12 months before diagnosis, but weight loss was already present 3 years before diagnosis and accelerated after diagnosis of CKD. Cats <4.2 kg at the time of diagnosis had significantly shorter survival time compared to cats ≥ 4.2 kg at diagnosis (P < .0001).Conclusions and Clinical ImportanceWeight loss can be detected in cats before diagnosis of CKD, accelerates after diagnosis, and is associated with shorter survival. Tracking body weight may help clinicians in earlier diagnosis of CKD.

Results suggested the safety of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in the treatment of dogs with osteoarthritis needs to be evaluated in other studies.

A new anti-inflammatory drug for pain (grapiprant) was recently shown to have minimal side effects following chronic (9-month) daily oral dose of 6 or 50 mg/kg suspension. The current study compares the pharmacokinetics of the formulation used in the chronic safety study to those of the tablet formulation that will be marketed upon FDA approval. Sixteen Beagle dogs were randomized to receive single doses of either 6 or 50 mg/kg grapiprant as both suspension and table formulations within a cross-over design with a 15-day washout. Clinical observations were vomiting in one high-dose suspension dog and loose stools in two dogs, one in each 6 mg/kg formulation group. For both formulations, grapiprant reached a maximum concentration within two hours. The tablet formulation had better bioavailability, with AUC values 34% higher at 6 mg/kg and 64% higher at 50 mg/kg compared to the suspension. Results on Day 0 were similar to those reported on Day 15, suggesting little to no accumulation. Using conversion factors of 1.34 and 1.64, these findings suggest that the 6 and 50 mg/kg suspension doses are equivalent to 4.5 and 30 mg/kg tableted doses, respectively. Combining these findings with the 9-month safety study demonstrates that safety was evaluated at doses approximately 15-fold above the demonstrated therapeutic dose of 2 mg/kg and 10-fold over the 'safety dose', defined as the maximum dose a dog of any body weight could receive when dosed at 2 mg/kg with whole or half-tablets.