Achieving temperature stability for storage of biological samples in an autodefrost freezer.

OBJECTIVE: To assess the temperature stability of an autodefrost freezer commonly used in veterinary practices, whether the use of a Styrofoam cooler within the freezer provides temperature stability, and the ease of use of a remote monitoring system for the notification of temperature elevations. ANIMALS: None. METHODS: Temperature in the freezer and 2 Styrofoam coolers were assessed with remote monitoring thermometers every 15 minutes. Temperature values were monitored from October 11 to December 18, 2023 (for a 68-day period). Data analysis focused on temperatures for the freezer exceeding 0 °C and the elevations in temperatures within the coolers relative to the freezer. RESULTS: The freezer had an increase in temperature approximately every 16 hours. Over 68 days, the freezer had a temperature greater than 0 °C 27 times, representing 26 separate elevations. The Styrofoam coolers within the freezer never registered a temperature higher than -5 °C. Elevations in temperature within the freezer were larger in magnitude than temperature elevations within the coolers, which showed smaller-magnitude changes in temperature. CLINICAL RELEVANCE: The temperature stability provided by the Styrofoam cooler would avoid potential freeze-thaw cycles of any stored biological samples. Additionally, the remote temperature monitoring system is easy to install and monitor, providing peace of mind to practice management.

Sample Sizes Using Hochberg's Procedure for Two Comparisons with Three Different Study Designs.

When simultaneous comparisons are performed, a procedure must be employed to control the overall level (also known as the Type I Error rate). Hochberg's stepwise testing procedure is often used and here determination of the sample size needed to achieve a specified power for two pairwise comparisons when observations follow a normal distribution is addressed. Three different scenarios are considered: subsets defined by a baseline criterion, two treatments compared to a control, or one set of subjects nested within the other. The solutions for these three scenarios differ and are examined. The sample sizes for the differences in success probabilities for binomial distributions are presented using the asymptotic normality. The sample sizes and power using Hochberg's procedure are compared to the corresponding results using the Bonferroni approach.

Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial.

Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child-Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49-1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45-1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51-1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.

Environmental Impact and Relative Invasiveness of Free-Roaming Domestic Carnivores-a North American Survey of Governmental Agencies.

A survey of the United States and Canadian governmental agencies investigated the environmental impact and relative invasiveness of free-roaming domestic non-native carnivores-dogs, cats, and ferrets. Agencies represented wildlife, fish, game, natural or environmental resources, parks and recreation, veterinary and human health, animal control, and agriculture. Respondents were asked to document the number and frequency of sightings of unconfined animals, evidence for environmental harm, and the resulting "degree of concern" in their respective jurisdictions. Results confirmed the existence of feral (breeding) cats and dogs, documenting high levels of concern regarding the impact of these animals on both continental and surrounding insular habitats. Except for occasional strays, no free-roaming or feral ferrets were reported; nor were there reports of ferrets impacting native wildlife, including ground-nesting birds, or sensitive species. This is the first study to report the relative impact of free-roaming domestic carnivores. Dogs and cats meet the current definition of "invasive" species, whereas ferrets do not. Differences in how each species impacts the North American environment highlights the complex interaction between non-native species and their environment. Public attitudes and perceptions regarding these species may be a factor in their control and agency management priorities.

Treatment of Plaque-Type Psoriasis With Oral CF101: Data from a Phase II/III Multicenter, Randomized, Controlled Trial.

BACKGROUND: CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
OBJECTIVE: To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
METHODS: This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
RESULTS: CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
CONCLUSIONS: Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.

J Drugs Dermatol. 2016;15(8):931-938.

Gender differences in salary and practice ownership expectations of matriculating veterinary students.

OBJECTIVE: To examine gender differences in initial and long-term salary and practice ownership expectations among first-year veterinary students. DESIGN: Survey. SAMPLE: First-year veterinary students at the North Carolina State University College of Veterinary Medicine during 2000 through 2003 and 2005 through 2009. PROCEDURES: A 1-page survey was distributed to students during orientation exercises or on the first day of a first-year course on ethics and jurisprudence. Students were asked to indicate their expected salary at graduation and in 5-year increments after graduation and to indicate whether they expected to own a practice after graduation. RESULTS: Responses were obtained from 567 female and 120 male students. There was no significant difference in initial salary expectations between male and female students. However, men had higher expectations for salary increases over the course of their career, so that expected salary was significantly higher for men than for women 5 years after graduation and beyond. A significantly greater percentage of men (69/93 [74.2%]) than women (242/499 [48.5%]) indicated they expected to own a practice. CONCLUSIONS AND CLINICAL RELEVANCE: Although male and female veterinary students had similar expectations with regard to initial salaries, the male students had higher long-term salary expectations and were more likely to indicate an expectation to become a practice owner. Differences in expectations may lead to differences in behavior when those expectations are or are not met.

Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial.

OBJECTIVE: To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. DESIGN: Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. PARTICIPANTS: Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. INTERVENTION: Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. MAIN OUTCOME MEASURES: An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. RESULTS: A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CONCLUSIONS: CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Assessing clinical competency: reports from discussion groups.

This report describes proposed new models for assessment of eight of the nine clinical competencies the American Veterinary Medical Association Council on Education requires for accreditation. The models were developed by discussion groups at the Association of American Veterinary Medical Colleges' Clinical Competency Symposium. Clinical competencies and proposed models (in parentheses) are described. Competency 1: comprehensive patient diagnosis (neurologic examination on a dog, clinical reasoning skills); Competency 2: comprehensive treatment planning (concept mapping, computerized case studies); Competency 3: anesthesia, pain management (student portfolio); Competency 4: surgery skills (objective structured clinical examination, cased-based examination, "super dog" model); Competency 5: medicine skills (clinical reasoning and case management, skills checklist); Competency 6: emergency and intensive care case management (computerized case study or scenario); Competency 7: health promotion, disease prevention/biosecurity (360 degrees evaluation, case-based computer simulation); Competency 8: client communications and ethical conduct (Web-based evaluation forms, client survey, communicating with stakeholders, telephone conversation, written scenario-based cases). The report also describes faculty recognition for participating in clinical competency assessments.

Introduction and evaluation of virtual microscopy in teaching veterinary cytopathology.

Virtual microscopy (VM) uses a computer to view digitized slides and is comparable to using a microscope to view glass slides. This technology has been assessed in human medical education for teaching histology and histopathology, but, to the authors' knowledge, no one has evaluated its use in teaching cytopathology in veterinary medical education. We hypothesize that students will respond positively to the use of VM for viewing cytopathology preparations and that the technology can be successfully used for student assessment. To test this hypothesis, we surveyed students regarding their level of satisfaction with features of the VM system, their preference for use of VM in the curriculum, and the potential influence virtual slides may have on student study habits; student performance on a traditional cytopathology practical examination and a similar exam using VM was evaluated. Our results show that student perception of the VM system is generally very positive, with some concerns about resolution and the need for continued exposure to traditional microscopy. Within the curriculum, students indicated a preference for the option of using virtual slides for studying and take-home exercises. Overwhelmingly, students wanted either hybrid laboratory sessions or sessions using glass slides with virtual slides available for study and review. Students identified many VM test-taking features as advantageous compared with traditional glass-slide practical exams as traditionally administered. However, students indicated a strong preference for continued use of traditional microscopy for graded practical exams. Students may be more likely to study slides in preparation for practical examinations if virtual slides are available. Results also indicate that VM can be used successfully for assessment purposes, but students should receive training in using virtual slides if the technology will be used for assessment.

Skin grafts and skin flaps in the horse.

Although most equine wounds can be easily treated and heal without consequence, there are many that present special challenges. Skin grafts area valuable part of the veterinarian's armamentarium for treatment of complicated wounds, particularly limb wounds. Attention to preparation of the recipient site and proper aftercare are critical to successful grafting. With better understanding of equine wound and graft physiology and the promise foretold by advances in human skin grafting, the outcome of treatments of difficult equine wounds should continue to improve in the future.

Superior safety in noninferiority trials.

Noninferiority of a new treatment to a reference treatment with respect to efficacy is usually associated with the superiority of the new treatment to the reference treatment with respect to other aspects not associated with efficacy. When the superiority of the new treatment to the reference treatment is with respect to a specified safety variable, it may be necessary to perform the between-treatment comparisons. The efficacy and safety comparisons may be considered separately or simultaneous comparisons may be performed. Here techniques are discussed for the simultaneous consideration of both aspects.

N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: II. in vivo characterization in rat models of inflammatory and neuropathic pain.

The vanilloid receptor 1 (VR1) is a cation channel expressed predominantly by nociceptive sensory neurons and is activated by a wide array of pain-producing stimuli, including capsaicin, noxious heat, and low pH. Although the behavioral effects of injected capsaicin and the VR1 antagonist capsazepine have indicated a potential role for VR1 in the generation and maintenance of persistent pain states, species differences in the molecular pharmacology of VR1 and a limited number of selective ligands have made VR1 difficult to study in vivo. N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropryazine-1(2H)-carbox-amide (BCTC) is a recently described inhibitor of capsaicin- and acid-mediated currents at rat VR1. Here, we report the effects of BCTC on acute, inflammatory, and neuropathic pain in rats. Administration of BCTC (30 mg/kg p.o.) significantly reduced both mechanical and thermal hyperalgesia induced by intraplantar injection of 30 micro g of capsaicin. In rats with Freund's complete adjuvantinduced inflammation, BCTC significantly reduced the accompanying thermal and mechanical hyperalgesia (3 mg/kg and 10 mg/kg p.o., respectively). BCTC also reduced mechanical hyperalgesia and tactile allodynia 2 weeks after partial sciatic nerve injury (10 and 30 mg/kg p.o.). BCTC did not affect motor performance on the rotarod after administration of doses up to 50 mg/kg p.o. These data suggest a role for VR1 in persistent and chronic pain arising from inflammation or nerve injury.

Using alumni research to assess a veterinary curriculum and alumni employment and reward patterns.

RATIONALE FOR THE STUDY: The purpose of the study was to obtain an outcomes assessment of the professional degree program of a veterinary college and to determine whether recently published national gender differences were true for a program that has always been predominantly female. METHODOLOGY: A survey was developed and mailed to all alumni of the veterinary degree program at North Carolina State University. Anonymous responses were collected by an independent organization for summation. Results were expressed numerically where possible, although the survey included numerous opportunities for textual responses. Responses were stratified by year of graduation, in five-year increments, and by gender of the respondents. RESULTS: Sixty-one percent of graduates remained within North Carolina. While most of the prerequisite courses were considered useful preparation for the curriculum, physics and calculus were exceptions. Over half the alumni thought time allocations to specific courses were appropriate. However, there were substantial differences between courses. The alumni were satisfied with most aspects of the training program, although there were differences between various components. There were substantial gender differences in length of first employment, salaries, species treated, practice ownership and type of ownership, and career satisfaction. Most alumni work in small animal private clinical practice. Ninety-four percent were employed within three months of graduating. Ninety-five percent did no work with the state's predominant agricultural species. Nineteen percent of alumni were either unsure, probably would not, or definitely would not become a veterinarian if they could choose again. CONCLUSION: The survey was a tremendously valuable source of information. Results provided support for curricular revision. The survey also provided comparative data in relation to national norms, where such norms were available. Unfortunately, few reports of this type are available, making inter-institutional comparisons difficult. The Association of American Veterinary Medical Colleges could assist with standardizing the process of outcomes assessment.

Changes in fecal flora and comparative multiple-dose pharmacokinetics of ceftibuten, cefpodoxime proxetil and amoxycillin/clavulanate.

OBJECTIVE: To investigate changes in fecal flora and multiple-dose pharmacokinetics with the oral antibiotics ceftibuten 400 mg daily and cefpodoxime proxetil (CPX) 200 mg every 12 h, compared to amoxycillin/clavulanate 500/125 mg every 8 h during and following 1 week of medication. METHODS: In an open randomized triple crossover design, 18 (nine female, nine male) healthy volunteers received each drug for 7 days, followed by a 'washout' period of 4 weeks. Serum and urine levels of the substances were determined by bioassay, and for ceftibuten isomers by high-pressure liquid chromatography. Statistical analysis of quantitative aerobic and anaerobic cultures of feces was performed, and beta-lactamase activity was determined. RESULTS: Ceftibuten showed a mean Cmax of 18.9 (SD 3.0) mg/L, a terminal half-life of 2.89 h, and an AUCtot of 100 (21.8) mg.h/L; protein binding was 63.7 (5.1)%, and accumulation was marginal. Cefpodoxime proxetil had a Cmax of 1.92 (0.61) mg/L, a terminal half-life of 1.97 (0.42) h and an AUCtot of 10.8 (3.3) mg.h/L; no accumulation was seen. Amoxycillin and clavulanate had Cmax values of 7.15 (2.16) mg/L and 3.39 (1.31) mg/L, terminal half-life values of 1.03 (0.15) h and 0.93 (0.17) h, AUCtot values of 20.0 (4.2) mg.h/L and 8.87 (3.10) mg.h/L, and there was no accumulation. Statistical analysis for ech microorganism in fecal samples showed significant differences between amoxycillin/clavulanate and the two third-generation cephalosporins, but virtually no differences between ceftibuten and cefpodoxime proxetil. Eleven of 12 volunteers reported loose stools (days 2-7, mean duration 4.4 (SD 2.7) days) with amoxycillin/clavulanate, but nobody during ceftibuten administration and one volunteer during cefpodoxime proxetil administration. CONCLUSIONS: Ceftibuten showed excellent and cefpodoxime favorable pharmacokinetic properties, with significantly less pronounced fecal flora changes and intestinal side effects compared to amoxycillin/clavulanate. The multiple crossover design allows powerful microbiological statistical analysis and pharmacokinetic parameter comparisons.