Preventing caesarean section wound complications: use of a silver-impregnated antimicrobial occlusive dressing.

OBJECTIVE: To investigate the role of an adherent soft silicone antimicrobial occlusive foam silver-impregnated dressing for reduction of surgical site infections (SSI) in primary low-transverse caesarean section (1°LTCS) delivery. METHOD: Women aged 18-45 years admitted to the labour and delivery or the antepartum unit undergoing a 1°LTCS were recruited. Exclusion criteria included repeat caesarean, vertical skin incision, intrapartum fever and closure with staples. Consented participants delivered by scheduled or unscheduled 1°LTCS received the silver-impregnated dressing. Those who declined to participate and were delivered by scheduled or unscheduled caesarean received a standard gauze with tape dressing (controls). Surgical preparation and preoperative antibiotics were administered as per hospital policy. RESULTS: A total of 362 participants were consented for use of the silver-impregnated dressing, with 190 participants undergoing 1°LTCS, of whom 185 were included in the final analysis. Of those who declined to participate, 190 ultimately underwent 1°LTCS during the same time period. Cases and controls were similar in demographics, body mass index, diabetes status, labour and procedure length, and tobacco use. The overall incidence of SSI was 3.7%. A 50% reduction in incidence of SSI was observed in the silver-impregnated dressing group compared with control group (2.7% versus 4.7%, respectively), but this was not statistically significant (p=0.08; odds ratio 0.55; 95% confidence interval: 0.18-1.67). CONCLUSION: Among women undergoing 1°LTCS with subcuticular closure of a transverse incision, use of a silver-impregnated dressing reduced the rate of SSI by >50% but was not statistically significant.

Pharmacokinetics of oral firocoxib in un-weaned calves.

The objective of this study was to determine the pharmacokinetics of firocoxib after oral administration in un-weaned calves. Eight Holstein calves with a mean age of 36 days and a mean weight of 55 kg were administered a single oral dose of 227 mg firocoxib. The resulting mean dosage was 4.2 mg/kg (range 3.5-5.0 mg/kg). Blood was collected prior to drug administration and at 2, 4, 6, 8, 24, 48, 72, and 96 h after treatment. Firocoxib concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Using computer software, pharmacokinetic parameters were found to fit best with a one-compartment model. Mean Cmax was 0.9 µg/ml (range 0.570-1.254), and Tmax was estimated to be 7 h (range 4-8 h). The estimated T1/2 was 15.3 h. The pharmacokinetics of firocoxib after oral dosing are similar to those in dogs, with the exception of a T1/2 that is approximately twice as long. Based on the similar pharmacokinetics, it is possible that a dose of 227 mg firocoxib orally could provide an analgesic effect in un-weaned calves.

Global health training in US obstetrics and gynaecology residency programmes: perspectives of students, residents and programme directors.

BACKGROUND: Benefits of exposure to global health training during medical education are well documented and residents' demand for this training is increasing. Despite this, it is offered by few US obstetrics and gynaecology (OBGYN) residency training programmes. OBJECTIVES: To evaluate interest, perceived importance, predictors of global health interest and barriers to offering global health training among prospective OBGYN residents, current OBGYN residents and US OGBYN residency directors. METHODS: We designed two questionnaires using Likert scale questions to assess perceived importance of global health training. The first was distributed to current and prospective OBGYN residents interviewing at a US residency programme during 2012-2013. The second questionnaire distributed to US OBGYN programme directors assessed for existing global health programmes and global health training barriers. A composite Global Health Interest/Importance score was tabulated from the Likert scores. Multivariable linear regression was performed to assess for predictors of Global Health Interest/Importance. RESULTS: A total of 159 trainees (77%; 129 prospective OBGYN residents and 30 residents) and 69 (28%) programme directors completed the questionnaires. Median Global Health Interest/Importance score was 7 (IQR 4-9). Prior volunteer experience was predictive of a 5-point increase in Global Health Interest/Importance score (95% CI -0.19 to 9.85; p=0.02). The most commonly cited barriers were cost and time. CONCLUSION: Interest and perceived importance of global health training in US OBGYN residency programmes is evident among trainees and programme directors; however, significant financial and time barriers prevent many programmes from offering opportunities to their trainees. Prior volunteer experience predicts global health interest.

Bridge to M4 (B2M4): An innovative residency application preparation curriculum.

BACKGROUND: The medical residency application process is daunting, time-consuming, and variable, making mentorship in preparation for this process important. In light of changes to the residency application process due to the COVID-19 pandemic, medical students identified a need to create a formal residency application preparation curriculum. The curriculum focused on reflection, while also furthering professional development and preparing for the nuances of the residency application cycle through structured advising. APPROACH: Bridge to M4 (B2M4) included reflective activities to help guide curriculum vitae (CV) refinement, personal and professional values clarification, residency program exploration, elevator pitch formation, personal statement development, mentor identification, guidance on requesting letters of recommendation, and virtual residency interview preparation. EVALUATION: The B2M4 elective first took place in June 2020 with 36 rising fourth year students enrolled. Perceived effectiveness of the curriculum was assessed by having student cohorts evaluate the importance of the CV, personal statement, general preparation, and residency program selection before and after the course. Student feedback was reviewed with content analysis, which highlighted the usefulness of a structured residency preparation course that was rooted in reflection and incorporated faculty mentorship and feedback. IMPLICATIONS: This student-driven, innovative curricular design provided students the opportunity to prepare for the residency application process through reflective activities including values clarification, strengths identification, and goal setting. B2M4 demonstrates a process that can be used not only during the Residency Match process, but also throughout graduate medical education and future career decisions.

Ready Day One: What Residents and Program Directors Think is Needed for a Successful Transition to Residency.

OBJECTIVE: To evaluate perceived gaps in preparedness, current on-boarding practices, and need for specialty wide resources in the transition to residency training in obstetrics and gynecology (OB/GYN) DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey of current U.S. OB/GYN residents and program directors (PDs) at the time of the resident in-training exam was conducted in 2022. Both groups provide demographic information and identified specific knowledge, skills, and abilities in need of more preparation at the start of residency. PDs were queried on perceptions of readiness for their current first year class, educational on-boarding practices, and their preference for standardized curricular materials and assessment tools. Chi-squared and Kruskal-Wallis tests were used to compare perceptions of skills deficits between PDs and residents, and the relationship of preparedness to program type and resident year in training. RESULTS: Response rates for residents and program directors were 64.9% and 72.6% respectively. A majority (115/200, 57.5%) of program directors agreed or strongly agreed with the statement, "In general, I feel that my new interns are well prepared for residency when they arrive at my program." Both groups agreed that basic suturing and ultrasound skills were deficits. Residents identified a need for better preparation in management of inpatient issues while PDs identified time management skills as lacking. There was considerable heterogeneity of program on-boarding practices across the specialty. Most PDs agreed or strongly agreed that a standardized curriculum (80.5%, 161/200) and assessment tools (75.3%, 150/199) would be helpful. CONCLUSION: OBGYN PDs feel that not all residents arrive prepared for residency and overwhelmingly support the development of standardized transition curricular and assessment tools, similar to the curriculum developed in general surgery. Based on input from PDs and residents, early curricular efforts should focus on basic surgical, ultrasound, and time management skills and on management of inpatient issues.

Analgesic drug administration and attitudes about analgesia in cattle among bovine practitioners in the United States.

OBJECTIVE: To determine current attitudes and practices related to pain and analgesia in cattle among US veterinarians in bovine practice and to identify factors associated with these attitudes and practices. DESIGN: Web-based survey. Sample-3,019 US members of the American Association of Bovine Practitioners (AABP) with e-mail addresses. PROCEDURES: Veterinarians were invited via e-mail to participate in a Web-based survey. Respondents replied to questions related to pain and analgesia and supplied personal, professional, and demographic information. Descriptive statistical analysis was performed, and associations among various factors were examined. RESULTS: 666 surveys (25.5% response rate) were analyzed. Among common procedures and medical conditions of cattle listed on the survey, castration of dairy calves < 6 months old was subjectively estimated as causing the least pain; abdominal surgery, toxic mastitis, and dehorning of calves > 6 months old were assessed as causing the greatest pain. Respondents reported not providing analgesic drugs to approximately 70% of calves castrated at < 6 months of age. The most commonly administered analgesics were NSAIDs, local anesthetics, and α(2)-adrenergic receptor agonists. Significant associations were detected among respondent characteristics and pain ratings, percentages of cattle treated, and opinions regarding analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results provide information on current attitudes and practices related to pain and analgesia in cattle among US veterinarians in bovine practice and can be considered in the development of policies and protocols for pain management in cattle. These data can be compared with those of future studies to examine changes over time.

Evaluation of the effect of bolus administration of 50% dextrose solution on measures of electrolyte and energy balance in postpartum dairy cows.

OBJECTIVE: To determine the effect of IV administration of a bolus of 50% dextrose solution on electrolyte and energy balance and effect of blood collection site on serum electrolyte values in postparturient dairy cows. ANIMALS: 24 clinically normal multiparous cows. PROCEDURES: A bolus of 50% dextrose solution (0.5 L [n=8 cows]), 50% dextrose solution (1.0 L [8]), or saline (0.9% NaCl) solution (1.0 L, control treatment [8]) was administered via jugular venipuncture 5 to 10 days after parturition. Pretreatment and posttreatment blood samples were analyzed for concentrations of calcium, magnesium, phosphorus, potassium, glucose, insulin, beta-hydroxybutyric acid (BHBA), and nonesterified fatty acids. Coccygeal vessel and jugular vein blood samples were obtained prior to treatment, and electrolyte concentrations were compared. RESULTS: Treatment with 50% dextrose decreased phosphorus concentration in serum, compared with the control treatment. Suppression of BHBA and nonesterified fatty acid concentrations following dextrose treatment lasted for <12 hours; mean BHBA concentrations in all groups were increased 24 hours after treatment. Mean serum phosphorus concentration in coccygeal vessel blood samples was 0.67 mg/dL greater than the concentration in jugular vein blood samples. CONCLUSIONS AND CLINICAL RELEVANCE: Postpartum cows treated with dextrose solution may be at risk for hypophosphatemia, and 1 treatment with 0.5 or 1 L of 50% dextrose solution is unlikely to prevent or resolve acetonemia (ketosis). The risk of hypophosphatemia may be underestimated when coccygeal vessel blood samples are used for diagnosis.

Association of Living in a Food Desert With Pregnancy Morbidity.

OBJECTIVE: To evaluate whether women living in areas deemed food deserts had higher rates of pregnancy morbidity, specifically preeclampsia, gestational hypertension, gestational diabetes, prelabor rupture of membranes, preterm labor, than women who did not live in food deserts at the time of their pregnancy and delivery. METHODS: This was a retrospective observational study in which we reviewed electronic medical records of all patients who delivered at Loyola University Medical Center in Maywood, Illinois in 2014. The Economic Research Service of the U.S. Department of Agriculture publishes the Food Access Research Atlas, which presents a spatial overview of food access indicators for low-income and other Census tracts using different measures of supermarket accessibility. A spatial join between the Food Access Research Atlas and patient coordinates was performed to identify patient point locations and determine whether each patient was located within or outside of a food desert. RESULTS: Data for 1,003 deliveries at Loyola University Medical Center in 2014 were provided by the Loyola University Chicago Clinical Research Database. Two deliveries were excluded owing to inability to map address coordinates; thus 1,001 deliveries were analyzed. Of the 1,001 patients, 195 (19.5%) women were designated to food deserts. Multivariable analysis was done by adjusting for age, race, and medical insurance class. Having at least one morbid condition was the only variable that demonstrated a significant association with the food desert in multivariable analyses (47.2% vs 35.6%) (odds ratio [OR] 1.62, 95% CI 1.18-2.22) (adjusted OR 1.64, 95% CI 1.18-2.29). CONCLUSION: The odds of having at least one of the studied morbid conditions in pregnancy were greater for patients living in a food desert. As there is an association of morbidity in pregnancy with living in a food desert, intervention trials to improve the built food environment or mitigate the effect otherwise are needed.

Deciphering Cattle Temperament Measures Derived From a Four-Platform Standing Scale Using Genetic Factor Analytic Modeling.

The animal's reaction to human handling (i.e., temperament) is critical for work safety, productivity, and welfare. Subjective phenotyping methods have been traditionally used in beef cattle production. Even so, subjective scales rely on the evaluator's knowledge and interpretation of temperament, which may require substantial experience. Selection based on such subjective scores may not precisely change temperament preferences in cattle. The objectives of this study were to investigate the underlying genetic interrelationships among temperament measurements using genetic factor analytic modeling and validate a movement-based objective method (four-platform standing scale, FPSS) as a measure of temperament. Relationships among subjective methods of docility score (DS), temperament score (TS), 12 qualitative behavior assessment (QBA) attributes and objective FPSS including the standard deviation of total weight on FPSS over time (SSD) and coefficient of variation of SSD (CVSSD) were investigated using 1,528 calves at weaning age. An exploratory factor analysis (EFA) identified two latent variables account for TS and 12 QBA attributes, termed difficult and easy from their characteristics. Inclusion of DS in EFA was not a good fit because it was evaluated under restraint and other measures were not. A Bayesian confirmatory factor analysis inferred the difficult and easy scores discovered in EFA. This was followed by fitting a pedigree-based Bayesian multi-trait model to characterize the genetic interrelationships among difficult, easy, DS, SSD, and CVSSD. Estimates of heritability ranged from 0.18 to 0.4 with the posterior standard deviation averaging 0.06. The factors of difficult and easy exhibited a large negative genetic correlation of -0.92. Moderate genetic correlation was found between DS and difficult (0.36), easy (-0.31), SSD (0.42), and CVSSD (0.34) as well as FPSS with difficult (CVSSD: 0.35; SSD: 0.42) and easy (CVSSD: -0.35; SSD: -0.4). Correlation coefficients indicate selection could be performed with either and have similar outcomes. We contend that genetic factor analytic modeling provided a new approach to unravel the complexity of animal behaviors and FPSS-like measures could increase the efficiency of genetic selection by providing automatic, objective, and consistent phenotyping measures that could be an alternative of DS, which has been widely used in beef production.

Universal tuberculosis screening in pregnancy.

We reviewed our practice of universal tuberculosis (TB) screening in an at-risk pregnant population with regards to utility and patient compliance. The Gouverneur Healthcare Services prenatal database was analyzed for compliance with TB screening. Age, ethnicity, country of origin, and education level were also analyzed. Of 4049 patients, 95.0% were compliant with their purified protein derivative (PPD) testing. Universal screening identified 1935 (50.4%) PPD+ patients, with chest X-rays (CXR) available for 95.1%. Only one patient had a CXR consistent with active TB, although sputum testing was negative for acid-fast bacilli. Asian women were more likely to be PPD-compliant (adjusted odds ratio [aOR]: 4.94, 95% confidence interval [CI]: 2.34 to 10.45). Similarly, PPD+ Asian women were more likely to be compliant with CXR (aOR: 12.67, 95% CI: 3.44 to 46.7). U.S.-born women were significantly less likely to be compliant with PPD (aOR: 0.44, 95% CI: 0.30 to 0.64) or with CXR (aOR: 0.22, 95% CI: 0.08 to 0.61). Universal prenatal TB screening is associated with excellent compliance rates and is an effective way to identify a high prevalence of latent TB, but not active disease.

Effect of endotoxic mastitis on epithelial cell numbers in the milk of dairy cows.

OBJECTIVE: To measure epithelial cell percentages and somatic cell counts (SCCs) in milk and determine whether isoflupredone acetate reduces mammary gland epithelial cell sloughing in cows with acute endotoxin-induced mastitis. ANIMALS: 13 lactating Holstein cows. PROCEDURES: Determination of SCC and flow cytometric analysis of cytokeratin-positive (epithelial) cells in milk were performed before and 12 hours after induction of mastitis via intramammary administration of bacterial endotoxin in 8 cows and at the same time points in 5 cows without mastitis. Endotoxin-treated cows received isoflupredone acetate (20 mg) or saline (0.9% NaCl) solution (n = 4/group) IV after signs of mastitis developed. RESULTS: At the 12-hour time point, mean +/- SD percentage of epithelial cells in milk increased from 2.74 +/- 1.93% to 42.11 +/- 36.21% and decreased from 5.73 +/- 4.52% to 5.31 +/- 1.93% in milk from cows with and without mastitis, respectively. Median (range) SCC in milk increased from 195,000 cells/mL (17,000 to 442,000 cells/mL) to 5,437,500 cells/mL (69,000 to 11,036,000 cells/mL) and from 19,000 cells/mL (9,000 to 125,000 cells/mL) to 51,000 cells/mL (10,000 to 835,000 cells/mL) in cows with and without mastitis, respectively. Changes in these variables were significantly greater in mastitis-affected cows. Administration of isoflupredone acetate did not affect epithelial cell percentage or SCC in milk. CONCLUSIONS AND CLINICAL RELEVANCE: During the early phase of endotoxin-induced mastitis in dairy cows, large numbers of epithelial cells were sloughed into the milk. Epithelial cell damage likely precedes an influx of immune cells into affected mammary glands and may contribute to breakdown of the blood-milk barrier.

Attitudes of Trainees in Obstetrics and Gynecology Regarding the Structure of Residency Training.

OBJECTIVE: To measure future and current resident perspectives on obstetrics and gynecology residency training structure and possible future models. METHODS: Medical students invited for obstetrics and gynecology residency interviews and residents (postgraduate year [PGY]-1-4) at the University of Colorado, the University of Washington, the University of California San Francisco, Loyola University, Saint Joseph's Hospital, and Texas A&M in 2017-2018 received a voluntary, electronic survey regarding possible models for restructuring residency training. Student and resident responses were compared using χ test for categorical and two-sample t-test for continuous items. RESULTS: Applicants (63%, 280/444) and residents (66%, 101/153) had similar response rates (overall response rate 64%). Applicants (24%) and residents (29%) reported having concerns about the current structure of residency training. The ideal residency duration was reported as 4 years by 72% of applicants and 85% of residents. Lack of gynecologic surgical volume was the most frequently reported concern among applicants (75%) and residents (72%). Fourth-year tracking (focusing on training aligned with postgraduation career path) was preferred by 90% of applicants and 77% of residents (P=.002) and 92% among respondents planning fellowship. Most applicants (68%) and residents (75%) preferred not starting fellowship training after the 3rd year of residency. DISCUSSION: The majority of learners surveyed support a 4-year training structure but likewise support individualizing training in PGY-4. It is imperative that obstetrics and gynecology leadership consider this and other feedback from learners when considering modifications to the current training paradigm.

Career Expectations of Obstetrics and Gynecology Residents and Future Residents.

OBJECTIVE: To understand contemporary fourth-year medical student and resident career expectations in obstetrics and gynecology. METHODS: Students invited for obstetrics and gynecology residency interviews and residents (postgraduate years 1-4) at the University of Colorado, University of Washington, University of California San Francisco, Loyola University, St. Joseph's Hospital, and Texas A&M in 2016-2017 received a voluntary, electronic survey regarding career expectations. Questions were compared between students and residents using a χ test for category responses and for age a two-sample t test. RESULTS: Response rates were similar between students (68% [277/409]) and residents (63% [97/153]). Residents compared with students were more frequently planning to enter private practice (43% vs 19%) and less frequently planning an academic career (19.4% vs 30.4%) or subspecialties (38% vs 51%) (P<.001). Although most respondents planned to work full-time (96% vs 94.9%), 83% (vs 94%) of residents planned to work greater than 40 hours per week (P<.001). Respondents reported greater than $150,000 in educational debt (65%) and anticipated starting salary greater than $200,000 (89%). More residents planned to retire by age 60 years (23% vs 7%) (P<.001). Thirty-eight percent of residents reported having changed career plans during residency, citing work-life balance as the most important factor (89%). DISCUSSION: Trainees' career expectations appear to evolve over time moving toward a higher likelihood to pursue private practice, work fewer hours, and retire earlier despite large educational debt. It is critical that the specialty understand these trends when planning to address national workforce needs.

Obstetricians and Gynecologists of the Future: A Survey of Medical Students Applying to Residency.

OBJECTIVE: To understand the characteristics and career goals of medical students selecting a career in obstetrics and gynecology. METHODS: In 2015-2016, medical students invited for interviews for obstetrics and gynecology residency at the University of Colorado, University of Washington, University of California San Francisco, Loyola University, and New York University received a voluntary 20-item electronic survey regarding factors influencing their choice of medical specialty. RESULTS: Two hundred twenty-six of 356 students responded (63%). Mean age was 27 years, and 88% (n=199) were women. General surgery was the most common alternate specialty (36%, n=81). The most commonly cited drawback to obstetrics and gynecology was "long hours" (66%, n=148). After residency, 157 (70%) applicants planned to complete fellowship training, 127 (56%) pursue international work, 156 (69%) seek an academic position, and 207 (92%) practice in an urban setting. One hundred twenty-four applicants (55%) planned to work 51-60 hours per week and 111 (49%) planned to take 2-3 nights of call per month. Two thirds (n=150) predicted they will have greater than $100,000 educational debt on graduation. CONCLUSION: Contemporary residency applicants have high educational debt and disproportionately plan to pursue fellowship, international work, careers in academic medicine, and work in urban centers. Based on the projected career plans among obstetrics and gynecology applicants, the workforce needs of the population may not be met.

Factors Influencing Residency Program Selection by Medical Students Pursuing Obstetrics and Gynecology.

BACKGROUND: Little is known about the factors that influence medical student selection of obstetrics and gynecology (ob-gyn) residency programs. OBJECTIVE: We assessed the factors influencing residency program selection by fourth-year medical students pursuing ob-gyn training. METHODS: A voluntary, anonymous, 19-question survey of residency selection factors was distributed to all fourth-year medical students interviewing at 1 of 5 academic ob-gyn departments for a residency position during the 2013-2014 interview season. Participants were surveyed about the relative importance (not important, somewhat important, important) of various residency selection factors, including operative experience, exposure to subspecialties, curricular experience, access to fellowships, and administrative aspects of residency, including adherence to duty hour restrictions. RESULTS: Of 322 potential respondents, 262 (81%) completed the survey. Surgical training and training in laparoscopic surgery were deemed "important" by nearly all respondents (98%, 258 of 262, and 97%, 253 of 262, respectively). Factors that were considered "not important" by a significant group of respondents included maternity/paternity leave policies (22%, 58 of 259); opportunity for international rotations/electives (20%, 51 of 259); exposure to quality and safety initiatives (13%, 34 of 259); and training in abortion (13%, 34 of 262). CONCLUSIONS: Fourth-year medical students identified surgical training as the most important factor in selecting an ob-gyn residency, a finding that is particularly relevant as decreasing and changing surgical volumes affect residency training in this specialty.

Advising and Interview Patterns of Medical Students Pursuing Obstetrics and Gynecology Residency.

OBJECTIVE: To describe the advising practices at medical schools and interview patterns among medical students pursuing obstetrics and gynecology residency training. METHODS: A voluntary, anonymous survey was distributed to all applicants interviewing for obstetrics and gynecology residency during the 2014-2015 cycle at the University of Colorado, University of Washington, University of California, San Francisco, and Loyola University. Demographic data were obtained. The survey explored student advising in the residency application process including number of applications and interviews recommended by advisors. Data are reported as percentage for each survey item and compared by select demographics using an exact χ. RESULTS: Among 315 unique possible applicants, 73% (n=230) responded. Students were most commonly advised by the obstetrics and gynecology clerkship director (33%) with recommendations to apply to 21-30 programs (48%). Thirty-four percent of students applied to 21-30 programs, 32% to 31-40 programs, and 30% to greater than 40 programs. Students were advised (70%) and planned (55%) to interview at 10-14 programs. Concern over competitiveness of the applicant pool was the most important factor (31%) in determining the number of applications. The number of programs advised to or plan to interview at was greater for those in the couples match (P<.001). CONCLUSION: Medical students pursuing obstetrics and gynecology are most likely to be advised by obstetrics and gynecology clerkship directors and concern over the competitiveness of the applicant pool results in students applying to large numbers of programs. This practice may adversely affect the obstetrics and gynecology match process for both programs and applicants through the requirements of managing additional applications and potentially needing to complete a greater number of interviews.

Effects of two anti-inflammatory drugs on physiologic variables and milk production in cows with endotoxin-induced mastitis.

OBJECTIVE: To determine the effects of 2 anti-inflammatory drugs in lactating Holstein cows with endotoxin-induced mastitis. ANIMALS: 30 multiparous Holstein cows that had been lactating for 30 to 60 days. PROCEDURE: Bacterial culture of milk samples and physical examinations established that study cows were in good health and free of mastitis. Mastitis was induced in 1 front mammary gland by intramammary administration of purified bacterial endotoxin. Cows were allocated into 1 of 3 treatment groups: untreated endotoxic mastitis (n = 9), endotoxic mastitis plus flunixin meglumine (9), and endotoxic mastitis plus isoflupredone acetate (10). Heart rate, rectal temperature, mammary surface area, and rumen motility were recorded hourly for 14 hours following endotoxin administration. Flunixin meglumine or isoflupredone acetate was administered after mammary swelling and rectal temperature > or = 40 degrees C had developed. Milk production was evaluated from 5 days before to 10 days after induction of mastitis. RESULTS: Neither drug ameliorated loss of milk production or swelling of the affected mammary gland. Both drugs reduced mean heart rate during the 14 hours following endotoxin administration, compared with untreated control cows. Cows treated with flunixin meglumine had increased rumen motility and decreased rectal temperature during the same period, compared with all other cows. CONCLUSIONS AND CLINICAL RELEVANCE: Neither drug enhanced recovery of milk production following endotoxin-induced mastitis. Flunixin meglumine decreased rectal temperature, whereas isoflupredone did not; however, it has not been established that reduction of fever is beneficial to cows with naturally occurring mastitis.

Development of a physiologically based pharmacokinetic model for flunixin in cattle (Bos taurus).

Frequent violation of flunixin residues in tissues from cattle has been attributed to non-compliance with the USFDA-approved route of administration and withdrawal time. However, the effect of administration route and physiological differences among animals on tissue depletion has not been determined. The objective of this work was to develop a physiologically based pharmacokinetic (PBPK) model to predict plasma, liver and milk concentrations of flunixin in cattle following intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) administration for use as a tool to determine factors that may affect the withdrawal time. The PBPK model included blood flow-limited distribution in all tissues and elimination in the liver, kidney and milk. Regeneration of parent flunixin due to enterohepatic recirculation and hydrolysis of conjugated metabolites was incorporated in the liver compartment. Values for physiological parameters were obtained from the literature, and partition coefficients for all tissues but liver and kidney were derived empirically. Liver and kidney partition coefficients and elimination parameters were estimated for 14 pharmacokinetic studies (including five crossover studies) from the literature or government sources in which flunixin was administered i.v., i.m. or s.c. Model simulations compared well with data for the matrices following all routes of administration. Influential model parameters included those that may be age or disease-dependent, such as clearance and rate of milk production. Based on the model, route of administration would not affect the estimated days to reach the tolerance concentration (0.125 mg kg(-1)) in the liver of treated cattle. The majority of USDA-reported violative residues in liver were below the upper uncertainty predictions based on estimated parameters, which suggests the need to consider variability due to disease and age in establishing withdrawal intervals for drugs used in food animals. The model predicted that extravascular routes of administration prolonged flunixin concentrations in milk, which could result in violative milk residues in treated cattle.