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Academic incentives must reward broader societal impacts.

Pharmacodynamic monitoring was used to titrate cyclosporine dosing in a dog with immune-mediated hemolytic anemia. Development of a suspected secondary infection, with subsequent discovery of an unexpectedly high level of T-cell suppression despite a relatively low cyclosporine dose, prompted an investigation into the cause of possible excessive immunosuppression. Blood cyclosporine concentrations were within expected target ranges, and the dog was determined to be heterozygous for the multidrug resistance protein 1 (MDR1; ATP-binding cassette sub family B member 1-1Δ) gene mutation. The MDR1 mutation was suspected to have contributed to the excessive immunosuppression experienced by this patient. This case highlights the need to monitor immunosuppressive therapy in the individual patient, especially when the patient is not responding to therapy at typical dosages or when secondary infections develop at dosages lower than expected to cause significant immunosuppression. Pharmacodynamic monitoring can be used to help identify unexpected excessive immunosuppression in dogs receiving cyclosporine, and MDR1 genotyping should be further explored as a potential method of predicting and preventing its occurrence.

Purpose of Review: Adolescent providers have a unique opportunity to interface with adolescents during a transformative time period. Optimizing vaccinations may protect teens against preventable but potentially deadly diseases. Healthcare providers must be aware of the evolving vaccination data and up-to-date recommendations for vaccinations., Recent Findings: In spite of the Center for Disease Control recommendations, there is a gap between the actual and desired vaccination rates of adolescents. Tetanus, diphtheria, and acellular pertussis, meningococcal against ACWY serotypes, and human papillomavirus (HPV) are vaccinations unique to the adolescent period. There has been a marked increase in pertussis cases over the last 2 decades. Either of the meningitis B vaccines may be given to 16-18 year olds and are effective in controlling college outbreaks. Increasing evidence continues to demonstrate the safety and efficacy of the HPV vaccination, although a substantial number of adolescents remain unvaccinated. Fortunately, there are proven strategies to remedy this., Summary: Adolescent providers should be aware of the increase in pertussis cases over the past 2 decades and the Category B recommendation for meningococcal B vaccine at 16-18 years, and they should work towards closing the gap between the actual and desired HPV vaccination rates.

Use of the immunosuppressant mycophenolic acid (MPA) in cats is limited because MPA elimination depends on glucuronidation, which is deficient in cats. We evaluated formation of major (phenol glucuronide) and minor (acyl glucuronide, phenol glucoside, and acyl glucoside) MPA metabolites using liver microsomes from 16 cats, 26 dogs, and 48 humans. All MPA metabolites were formed by human liver microsomes, while dog and cat liver microsomes formed both MPA glucuronides, but only one MPA glucoside (phenol glucoside). Intrinsic clearance (CLint) of MPA for phenol glucuronidation by cat liver microsomes was only 15-17% that of dog and human liver microsomes. However, CLint for acyl glucuronide and phenol glucoside formation in cat liver microsomes was similar to or greater than that for dog and human liver microsomes. While total MPA conjugation CLint was generally similar for cat liver microsomes compared with dog and human liver microsomes, relative contributions of each pathway varied between species with phenol glucuronidation predominating in dog and human liver microsomes and phenol glucosidation predominating in cat liver microsomes. MPA conjugation variation between cat liver microsomes was threefold for total conjugation and for phenol glucosidation, sixfold for phenol glucuronidation, and 11-fold for acyl glucuronidation. Our results indicate that total MPA conjugation is quantitatively similar between liver microsomes from cats, dogs, and humans despite large differences in the conjugation pathways that are utilized by these species., (© 2016 John Wiley & Sons Ltd.)

Foley catheterization (FC) is known to result in complications. Validated checklists are central to teaching/assessing procedural skills and may result in improved health care quality. The results of the first step of the validation of male and female FC checklists are described. A comprehensive literature review of articles published on FC did not yield a checklist validated by the Delphi method. A modified Delphi technique involving a panel of 7 experts was used to develop FC checklists. The internal consistency coefficients using Cronbach's α were .91 and .88, respectively, for males and females. Developing a 24-item male FC checklist and a 23-item female FC checklist for teaching/assessing FC is the first step in the validation process. For these checklists to become further validated, they should be implemented and studied in the simulation and the clinical environments.

Nasogastric (NG) tube insertion is known to result in complications. Validated checklists are central to teaching and assessing procedural skills and may result in improved health care quality. The results of the first step of the validation of an NG tube insertion checklist are described. A comprehensive literature review of articles published on NG tube insertion did not yield a checklist validated by the Delphi method. A modified Delphi technique, involving a panel of 9 interdisciplinary, interinstitutional experts, was used to develop an NG tube insertion checklist. The internal consistency coefficient using Cronbach's α was .80. Developing a 19-item checklist for teaching and assessing NG tube insertion is the first step in the validation process. For this checklist to become further validated, it should be implemented and studied in the simulation and clinical environments.

Disaster preparedness training is a critical component of medical student education. Despite recent natural and man-made disasters, there is no national consensus on a disaster preparedness curriculum. The authors designed a survey to assess prior disaster preparedness training among incoming interns at an academic teaching hospital. In 2010, the authors surveyed incoming interns (n = 130) regarding the number of hours of training in disaster preparedness received during medical school, including formal didactic sessions and simulation, and their level of self-perceived proficiency in disaster management. Survey respondents represented 42 medical schools located in 20 states. Results demonstrated that 47% of interns received formal training in disaster preparedness in medical school; 64% of these training programs included some type of simulation. There is a need to improve the level of disaster preparedness training in medical school. A national curriculum should be developed with aspects that promote knowledge retention.

Lumbar puncture (LP) is known to result in complications. Procedure skills should be taught and evaluated more effectively to improve health care quality. Validated checklists are central to teaching and assessing procedural skills. The results of the first step of the validation of an adult LP checklist are described. A comprehensive literature review of articles published on LP did not yield a checklist validated by the Delphi method. A modified Delphi technique, involving a panel of 9 experts, was used to develop a 20-item LP checklist for teaching and assessing LP, the first step in the validation process. The internal consistency coefficient using Cronbach's α was 0.79. The authors used a modified Delphi method to develop a checklist for teaching and assessing LP. For this checklist to become further validated, it should be implemented and studied in the simulation and clinical environments.

Thoracentesis is an invasive procedure known to result in complications. Procedure skills should be taught and evaluated more effectively to improve health care quality. Validated checklists are central to teaching and assessing procedural skills. The results of the first step of the validation of a thoracentesis checklist are described. A comprehensive literature review of articles published on thoracentesis did not yield a validated checklist. A modified Delphi technique, involving a panel of 8 interdisciplinary, interinstitutional experts, was used to develop a thoracentesis checklist. The internal consistency coefficient using Cronbach's α was .94. Developing the 23-item thoracentesis checklist for teaching and assessing thoracentesis is the first step in the validation process. For this checklist to become further validated, it should be implemented and studied in the simulation and clinical environments.

Paracentesis is an invasive procedure known to result in complications. Procedure skills should be taught and evaluated more effectively to improve health care quality. Validated checklists are central to teaching and assessing procedural skills. The results of the first step of the validation of a paracentesis checklist are described. A comprehensive literature review of articles published on paracentesis did not yield a validated checklist. A modified Delphi technique, involving a panel of 8 interdisciplinary, interinstitutional experts, was used to develop a paracentesis checklist. The internal consistency coefficient using Cronbach's α was .92. Developing the 24-item paracentesis checklist for teaching and assessing paracentesis is the first step in the validation process. For this checklist to become further validated, it should be implemented and studied in the simulation and clinical environments.

The cytochrome P450 (CYP) superfamily constitutes a collection of enzymes responsible for the metabolism of a wide array of endo- and xenobiotic compounds. Much of the knowledge on substrate specificity and genetic identification of the various CYP isoforms is derived from research in rodents and humans and only limited information has been captured in the dog. Currently, there exist many gaps in our knowledge of canine CYP diversity as a result of the paucity of studies focusing on canine CYPs, canine CYP polymorphisms, and the therapeutic consequences of these genetic variants. Challenges engendered by this lack of information is further amplified by inter- and intraspecies differences in the specificity and affinity of substrates and inhibitors, prohibiting a simple extrapolation of probe substances used in human CYP research. This creates a need to develop and validate canine-specific CYP probes. Failure to understand this potential metabolic and pharmacogenomic diversity can also influence the interpretation of data generated in dogs to support human drug development. It is with these objectives in mind that we provide an overview of what is currently known about canine CYPs with the hope that it will encourage further exploration into this important area of research.

Structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of segmental duplications and associated copy number variants (CNVs) in the modern domesticated dog, Canis familiaris, which exhibits considerable morphological, physiological, and behavioral variation. Through computational analyses of the publicly available canine reference sequence, we estimate that segmental duplications comprise approximately 4.21% of the canine genome. Segmental duplications overlap 841 genes and are significantly enriched for specific biological functions such as immunity and defense and KRAB box transcription factors. We designed high-density tiling arrays spanning all predicted segmental duplications and performed aCGH in a panel of 17 breeds and a gray wolf. In total, we identified 3583 CNVs, approximately 68% of which were found in two or more samples that map to 678 unique regions. CNVs span 429 genes that are involved in a wide variety of biological processes such as olfaction, immunity, and gene regulation. Our results provide insight into mechanisms of canine genome evolution and generate a valuable resource for future evolutionary and phenotypic studies.

Despite advancements in pharmacogenetics in human medicine, the incorporation of pharmacogenetics into veterinary medicine is still in its early stages of development. To date, efforts to understand the pharmacologic impact of genetic variation in veterinary species have largely focused on genes encoding for the membrane transporter, P-glycoprotein (P-gp). The emphasis on the role of P-gp is largely because of safety concerns associated with the use of some macrocyclic lactones in dogs. Because of the body of information available on this topic, we use P-gp as a platform for understanding the importance of population diversity in veterinary medicine. The impact of P-gp on drug pharmacokinetics and pharmacodynamics is considered, along with endogenous and exogenous factors that can modulate P-gp activity. The review includes discussion of how population diversity in P-gp activity can lead to susceptibility to certain diseases or alter patient response to environmental stress or pharmaceutical intervention. In addition, phenotypic diversity also needs to be considered, as demonstrated by the impact of P-gp up-regulation and drug resistance. The aim of this review was to set the stage for further exploration into the impact of genetic and phenotypic variability on drug pharmacokinetics, disease propensity, product formulation and drug response in both companion and food-producing animals.

There is limited information describing species related pharmacogenetic differences in animals. Despite the lack of genetic information in veterinary medicine, breed specific responses to endogenous and exogenous substances have been reported across many species. This finding underscores the importance of obtaining insight into the genotypic and phenotypic variation present across breeds. This article provides a summary of the literature pertaining to canine breed differences in physiology, drug response, drug pharmacokinetics, and metabolic idiosyncrasies. The existing knowledge of pedigrees and the known phenotypes and genotypes of dogs provides important information for determining mode of inheritance, penetration, and other major characteristics of heritable traits. Understanding these breed differences will improve canine population predictions (for canine drug products) and may be of value when extrapolating toxicology data from dogs to humans.

Objective: To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals., Animals: 6 healthy neonatal foals., Procedures: Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy., Results: Mean +/- SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 +/- 311 ng/mL; time to peak serum concentration, 4.3 +/- 2.0 hours; area under the serum concentration versus time curve, 40,215 +/- 8,420 ng/mL/h; mean residence time, 39.5 +/- 17.2 hours; area under the moment curve, 1,636,554 +/- 931,458 ng([h](2)/mL); and terminal half-life, 26.6 +/- 11.6 hours. The mean serum concentration of gallium at 12 hours was 756 +/- 195 ng/mL., Conclusions and Clinical Relevance: Gallium maltolate administered via nasogastric tube at a dose of 20 mg/kg to neonatal foals resulted in gallium serum concentrations considered sufficient to suppress growth or kill Rhodococcus equi in macrophages and other infected tissues.