Faculty Perception of an Embedded Research Project in the Undergraduate Veterinary Curriculum

In this article, we describe faculty’s perception of a research project embedded in the final year of the undergraduate veterinary curriculum and look at factors associated with overall perceptions of the project. We hypothesized that faculty would have a dichotomous attitude toward the research project, with faculty viewing it either positively or negatively, and that this opinion of the project would be largely influenced by the background of the faculty member—in particular, her or his role at the Royal Veterinary College. We explored this hypothesis via a questionnaire consisting of 26 questions in categorical format, Likert-scale format, and ranking format. The questions addressed faculty demographics, faculty’s perceptions of the project, and generic skills. Faculty had an overall positive view of the project and found it to be a useful part of the undergraduate curriculum (83.3% found it to be useful or very useful). Faculty’s perception of the project was influenced by their role at the college (p = .017), the species with which they primarily work (p = .05), and their opinion on the time spent supervising the final-year project (p = .003). We concluded that faculty view research as an important and useful part of the undergraduate veterinary curriculum

Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats

The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed‐effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first‐order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip‐flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population

Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats

BACKGROUND: Hypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored. AIMS: To determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations. METHODS: Fifty‐nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response. RESULTS: Cats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response

Development and initial validation of a sensory threshold examination protocol (STEP) for phenotyping canine pain syndromes

Objective To study feasibility and test-retest repeatability of a sensory threshold examination protocol (STEP) and report quantitative sensory threshold distributions in healthy dogs. Study design Prospective, observational, cohort study. Animals Twenty-five healthy client-owned dogs. Methods Tactile sensitivity (TST) (von Frey filaments), mechanical thresholds (MT with 2, 4 and 8 mm probes), heat thresholds (HT) and responsiveness to cold stimulus (CT at 0 °C) were quantitatively assessed for five body areas (BA: tibias, humeri, neck, thoracolumbar region and abdomen) in a randomized order on three different occasions. Linear Mixed Model and Generalised Linear Mixed models were used to evaluate the effects of body weight category, age, sex, BA, occasion, feasibility score and investigator experience. Test-retest repeatability was evaluated with the Intra-class Correlation Coefficient (ICC). Results The STEP lasted 90 minutes without side effects. The BA affected most tests (p = 0.001). Higher thresholds and longer cold latencies were scored in the neck (p = 0.024) compared to other BAs. Weight category affected all thresholds (p = 0.037). Small dogs had lower MT (~1.4 N mean difference) and HT (1.1 0C mean difference) than other dogs (p = 0.029). Young dogs had higher HT than adults (2.2 0C mean difference) (p = 0.035). Gender also affected TST, MT and HT (p < 0.05) (females versus males: TST OR= 0.5, MT= 1.3 N mean difference, HT= 2.2 0C mean difference). Repeatability was substantial to moderate for all tests, but poor for TST. There was no difference in thresholds between occasions, except for CT. Test-retest repeatability was slightly better with the 2 mm MT probe compared to other diameters and improved with operator experience. Conclusions and clinical relevance The STEP was feasible, well tolerated and showed substantial test-retest repeatability in healthy dogs. Further validation is needed in dogs suffering pain

A history of antimicrobial drugs in animals: Evolution and revolution

The evolutionary process of antimicrobial drug (AMD) uses in animals over a mere eight decades (1940–2020) has led to a revolutionary outcome, and both evolution and revolution are ongoing, with reports on a range of uses, misuses and abuses escalating logarithmically. As well as veterinary therapeutic perspectives (efficacy, safety, host toxicity, residues, selection of drug, determination of dose and measurement of outcome in treating animal diseases), there are also broader, nontherapeutic uses, some of which have been abandoned, whilst others hopefully will soon be discontinued, at least in more developed countries. Although AMD uses for treatment of animal diseases will continue, it must: (a) be sustainable within the One Health paradigm; and (b) devolve into more prudent, rationally based therapeutic uses. As this review on AMDs is published in a Journal of Pharmacology and Therapeutics, its scope has been made broader than most recent reviews in this field. Many reviews have focused on negative aspects of AMD actions and uses, especially on the question of antimicrobial resistance. This review recognizes these concerns but also emphasizes the many positive aspects deriving from the use of AMDs, including the major research‐based advances underlying both the prudent and rational use of AMDs. It is structured in seven sections: (1) Introduction; (2) Sulfonamide history; (3) Nontherapeutic and empirical uses of AMDs (roles of agronomists and veterinarians); (4) Rational uses of AMDs (roles of pharmacologists, clinicians, industry and regulatory controls); (5) Prudent use (residue monitoring, antimicrobial resistance); (6) International and inter‐disciplinary actions; and (7) Conclusions

Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of robenacoxib and ketoprofen in a feline model of inflammation

Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivoIC50COX‐1/IC50COX‐2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood

Major accidents scenarios used for LUP and off-site emergency planning : importance of kinetic description

International audienceThe European States, France in particular, faced with several industrial accidents, like one of the most serious one, the AZF explosion in Toulouse (France) in 2001, which created the trauma of the stakeholders concerned by the chemical risk (industry, authorities and citizen). Learning from this experience, the French Ministry in charge of the Environment, with the help of INERIS, worked on upgrading its chemical risks knowledge and studied to improve new methods on risk assessment. In 2004, INERIS was in charge of developing a new approach to classify accidental scenarios in terms of probability, severity and response time. In this paper, INERIS proposes a prioritisation based on time of occurrence, of development of hazardous phenomena and of effects on targets. Then, INERIS shows a method enabling to integrate, as a second prioritisation criteria, the on-site and off-site response capabilities/abilities as well as the means for population protection in terms of time allowed