Sex differences in the neural and behavioral effects of acute high-dose edible cannabis consumption in rats.

The consumption of D9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (6 males, 7 females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Rats were provided access to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg) for 10 minutes, during which they voluntarily consumed all of the provided Nutella and THC mixture. Cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24-h after exposure. In another cohort (16 males, 15 females), we examined the effects of AHDECC on learning and prepulse inhibition, and serum and brain THC and 11-hydroxy-THC concentrations. AHDECC resulted in higher brain and serum THC and 11-hydroxy-THC levels in female rats over 24 h. AHDECC also produced: 1) Cg, dHipp, and NAc gamma power suppression, with the suppression being greater in female rats, in a time-dependent manner; 2) hypolocomotion, hypothermia, and anti-nociception in a time-dependent manner; and 3) learning and prepulse inhibition impairments. Additionally, most neural activity and behavior changes appear 2 h post-ingestion, suggesting that interventions around this time might be effective in reversing/reducing the effects of AHDECC. Significance Statement The effects of high-dose edible cannabis on behaviour and neural circuitry are poorly understood. We found that the effects of acute high-dose edible cannabis consumption, which include decreased gamma power, hypothermia, hypolocomotion, analgesia, and learning and information processing impairments, are time- and sex-dependent. Moreover, these effects begin 2 h after AHDECC and last for at least 24 h, suggesting that treatments should target this time window in order to be effective.

Depletion of dexamethasone in cattle: Food safety study in dairy and beef cattle.

Dexamethasone is approved for cattle in Canada for several conditions, but no withdrawal times are currently provided on the approved labels. Recently, the list of Maximum Residues Limits for Veterinary Drugs in Foods in Canada was amended to include dexamethasone. The objectives of this study were to determine the residue depletion profile of dexamethasone after an extra-label dosage regimen in milk of healthy lactating dairy cattle (n = 18) and in edible tissues of healthy beef cattle (n = 16) and to suggest withdrawal intervals. Dexamethasone was administered intramuscularly at 0.05 mg/kg daily for 3 days. Milk samples were collected prior to treatment and every 12 h up to 96 h post-dose. Muscle, liver, kidney, and peri-renal fat tissues were collected from beef cattle at 3, 7, 11, or 15 days post-dose. Dexamethasone analysis was performed by liquid chromatography/mass spectrophotometry. Dexamethasone residues were detected in milk samples up to 36 h. Muscle and fat had no detectable dexamethasone residues while kidney and liver had detectable residues only on day 3 post-dose. A withdrawal interval of 48 h for milk in Canadian dairy cattle and 7 days for meat in Canadian beef cattle are suggested for the dexamethasone treatment regimen most commonly requested to CgFARAD™.

Improving Methods of Identifying Anaphylaxis for Medical Product Safety Surveillance Using Natural Language Processing and Machine Learning.

We sought to determine whether machine learning and natural language processing (NLP) applied to electronic medical records could improve performance of automated health-care claims-based algorithms to identify anaphylaxis events using data on 516 patients with outpatient, emergency department, or inpatient anaphylaxis diagnosis codes during 2015-2019 in 2 integrated health-care institutions in the Northwest United States. We used one site's manually reviewed gold-standard outcomes data for model development and the other's for external validation based on cross-validated area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and sensitivity. In the development site 154 (64%) of 239 potential events met adjudication criteria for anaphylaxis compared with 180 (65%) of 277 in the validation site. Logistic regression models using only structured claims data achieved a cross-validated AUC of 0.58 (95% CI: 0.54, 0.63). Machine learning improved cross-validated AUC to 0.62 (0.58, 0.66); incorporating NLP-derived covariates further increased cross-validated AUCs to 0.70 (0.66, 0.75) in development and 0.67 (0.63, 0.71) in external validation data. A classification threshold with cross-validated PPV of 79% and cross-validated sensitivity of 66% in development data had cross-validated PPV of 78% and cross-validated sensitivity of 56% in external data. Machine learning and NLP-derived data improved identification of validated anaphylaxis events.

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats.

Trazodone and gabapentin are common oral sedatives in cats, used alone or combined, but no pharmacokinetic studies exist for trazodone in this species. The objective of this study was to determine the pharmacokinetics of oral trazodone (T) alone, or in combination with gabapentin (G) in healthy cats. Cats (n = 6) were randomly allocated to receive T (3 mg/kg) intravenously (IV), T (5 mg/kg) orally (PO), or T (5 mg/kg) and G (10 mg/kg) PO with a 1-week washout period between treatments. Heart rate, respiratory rate, indirect blood pressure, and level of sedation were assessed, and venous blood samples were collected serially over 24 h. Analysis of plasma trazodone concentration was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral T administration resulted in a bioavailability of 54.9(7-96)%, and 17.2(11-25)% when administered with G. Tmax 0.17 (0.17-0.5) and 0.17 (0.17-0.75) h; Cmax 1.67 ± 0.91 and 1.22 ± 0.54 µg/mL, AUC 5.23 (2.0-18.76) and 2.37 (1.17-7.80) h*µg/mL; T1/2 5.12 ± 2.56 and 4.71 ± 1.07 h; for T and TG, respectively. Sedation was significant when compared to baseline in all groups from 20 or 45 min to 8 h indicating some lag between peak plasma concentration and sedative effects. Physiological variables remained within normal limits. This study concludes that oral trazodone is rapidly absorbed in healthy cats. Addition of gabapentin did not result in more profound sedation, showing no clinical advantage of combining these drugs in this study population.

Pharmacokinetics of combined administration of iron dextran with meloxicam or flunixin meglumine in piglets.

Objective: The objective was to evaluate the pharmacokinetics of compounding non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam or flunixin meglumine with iron dextran (ID) in piglets. Animal: Forty piglets (8 d of age) were randomly allocated into 5 groups (8 piglets/group) and received 1 intramuscular injection in the neck of the following treatments: flunixin meglumine (2.2 mg/kg) administered alone (F) or mixed with ID (F+ID); or meloxicam (0.4 mg/kg) administered alone (M) or mixed with ID (M+ID); or ID alone. Procedure: Blood samples were collected via indwelling jugular catheters at pre-dose, and 10, 20, 30, 45, and 60 min, and 2, 4, 8, 12, 24, 36, 48, and 72 h post-treatment to determine plasma NSAIDs concentrations using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters for plasma meloxicam and flunixin meglumine concentration-time profiles were determined for each piglet using noncompartmental analysis approaches. Statistical analyses were performed using SAS software with significance set at P < 0.05. Results: The AUC0-tlast, AUC0-∞, Cmax, and relative bioavailability values in the M+ID and F+ID groups were lower than corresponding M and F groups. The M+ID group elimination half-life was lower, whereas λz and tmax values were greater than the corresponding M group. Conclusion: Relative bioavailability of meloxicam and flunixin meglumine were reduced when compounded with ID in the same bottle and administered to piglets. Clinical relevance: Further research is warranted to evaluate if decreased NSAID exposure when compounded with ID alters analgesic efficacy or drug residue depletion.

Objectif: L'objectif était d'évaluer la pharmacocinétique de la combinaison d'anti-inflammatoires non stéroïdiens (NSAID) méloxicam ou flunixine méglumine avec du fer dextran (ID) chez les porcelets. Animal: Quarante porcelets (âgés de 8 jours) ont été répartis au hasard en cinq groupes (8 porcelets/groupe) et ont reçu une injection intramusculaire dans le cou des traitements suivants : flunixine méglumine (2,2 mg/kg) administrée seule (F) ou mélangée avec ID (F+ID); soit du méloxicam (0,4 mg/kg) administré seul (M) ou en mélange avec ID (M+ID); ou du ID seul. Procédure: Des échantillons de sang ont été prélevés via des cathéters jugulaires à demeure à la pré-dose, et 10, 20, 30, 45 et 60 min, et 2, 4, 8, 12, 24, 36, 48 et 72 h après le traitement pour déterminer la concentration plasmatique de NSAID par chromatographie liquide-spectrométrie de masse en tandem. Les paramètres pharmacocinétiques des profils concentration-temps du méloxicam et de la flunixine méglumine plasmatiques ont été déterminés pour chaque porcelet à l'aide d'approches d'analyse non compartimentale. Les analyses statistiques ont été effectuées à l'aide du logiciel SAS avec un seuil de signification fixé à P < 0,05. Résultats: Les valeurs AUC0­tlast, AUC0­∞, Cmax et de biodisponibilité relative dans les groupes M+ID et F+ID étaient inférieures à celles des groupes M et F correspondants. La demi-vie d'élimination du groupe M+ID était plus faible, tandis que les valeurs λz et tmax étaient supérieures à celles du groupe M correspondant. Conclusion: La biodisponibilité relative du méloxicam et de la méglumine de flunixine était réduite lorsqu'ils étaient combinés avec ID dans le même flacon et administrés aux porcelets. Pertinence clinique: Des recherches supplémentaires sont nécessaires pour évaluer si une diminution de l'exposition aux NSAID lorsqu'elle est associée à une ID modifie l'efficacité analgésique ou l'épuisement des résidus de médicaments.(Traduit par Dr Serge Messier).

Pharmacokinetics and pharmacodynamics of doxycycline in a Streptococcusequi subsp. zooepidemicus infection model in horses.

The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration (Cmax ) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean Cmax /MIC was 1.30, and mean AUClast /MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model.

Pharmacokinetics and bioavailability of ketoprofen when compounded with iron dextran for use in nursing piglets.

In Canada, piglets receive analgesia to control pain after surgical castration. There is interest in examining the potential to mix non-steroidal anti-inflammatory drugs with iron dextran prior to injection to minimize piglet handling and labor. The objective of this study was to compare pharmacokinetics and the relative bioavailability of ketoprofen given alone (3.0 mg/kg IM) versus the same dose of ketoprofen mixed with iron dextran (52.8 mg/kg IM) (ketoprofen + iron dextran) before injection in piglets. Piglets 8 to 11 d old were allocated into 2 treatment groups (n = 8/group). Plasma drug concentrations were measured using mass spectrometry at 13 time points after injection. No significant differences were detected between the 2 groups when examining pharmacokinetic parameters (e.g., Cmax, Tmax, AUC) or relative bioavailability for either S- or R-ketoprofen enantiomers (P > 0.05). However, pain control efficacy and food safety studies of these formulations are required to further examine this practice.

Pharmacocinétique et biodisponibilité du kétoprofène lorsque mélangé avec du fer dextran pour utilisation chez les porcelets allaitants. Au Canada, les porcelets reçoivent une analgésie pour diminuer la douleur après une castration chirurgicale. Il y a un intérêt à examiner la possibilité de mélanger des anti-inflammatoires non stéroïdiens avec du fer dextran avant l'injection afin de minimiser la manipulation des porcelets et le travail. L'objectif de cette étude était de comparer la pharmacocinétique et la biodisponibilité relative du kétoprofène administré seul (3,0 mg/kg IM) par rapport à la même dose de kétoprofène mélangé à du fer dextran (52,8 mg/kg IM) (kétoprofène + fer dextran) avant l'injection des porcelets. Des porcelets âgés de 8 à 11 jours ont été répartis en deux groupes de traitement (n = 8/groupe). Les concentrations plasmatiques de médicament ont été mesurées par spectrométrie de masse à 13 moments dans le temps après l'injection. Aucune différence significative n'a été détectée entre les deux groupes lors de l'examen des paramètres pharmacocinétiques (par ex., Cmax, Tmax, AUC) ou de la biodisponibilité relative pour les énantiomères S- ou R-kétoprofène (P > 0,05). Cependant, des études sur l'efficacité de la diminution de la douleur et la sécurité alimentaire de ces formulations sont nécessaires pour examiner de manière plus approfondie cette pratique.(Traduit par Dr Serge Messier).

Pharmacokinetics of imidocarb dipropionate in white-tailed deer (Odocoileus virginianus) after single intramuscular administration.

This study was designed to investigate the pharmacokinetics of imidocarb, a carbanilide derivative, in white-tailed deer (Odocoileus virginianus). The pharmacokinetic properties of a single intramuscular (IM) dose of imidocarb were determined in 10 deer. A single IM injection of 3.0 mg/kg imidocarb dipropionate was administered, and blood samples were collected prior to, and up to 48 hr after imidocarb administration. Plasma imidocarb concentrations were determined by high-performance liquid chromatography with ultraviolet detection. The disposition of plasma imidocarb was best characterized by a two-compartment open model. The mean ± SE maximal imidocarb concentration in deer was 880.78 ± 81.12 ng/ml at 38.63 ± 5.30 min postinjection. The distribution phase had a half-life (t1/2α ) of 25.90 ± 10.21 min, and plasma imidocarb concentration declined with a terminal elimination half-life (t1/2ß ) of 464.06 ± 104.08 min (7.73 ± 1.73 hr). Apparent volume of distribution based on the terminal phase (VZ /F) was 9.20 ± 2.70 L/kg, and apparent total body clearance (Cl/F) was 15.97 ± 1.28 ml min-1  kg-1 .

Reconstruction of a subtotal septorhinectomy defect with a chimeric paramedian-pericranial forehead flap.

The nose is a complex structure important for aesthetic appearance, social interaction, and respiration. Full thickness nasal defects with resection of the septum pose a significant challenge to the reconstructive surgeon due to the lack of local tissues to replace the nasal lining and significant risk of nasal collapse owing to the paucity of rigid infrastructure. The purpose of this paper is to present a unique case of nasal reconstruction utilizing a bilaminar paramedian forehead flap (combined pericranial flap and forehead flap) with embedded cantilever rib graft in a patient who underwent resection for an intranasal malignancy involving the septum and soft tissue envelope. This case serves to demonstrate the great utility in using chimeric flaps based on a single pedicle given the low patient morbidity, predictable results, and rapid recovery period.

Pharmacokinetics of midazolam and its major metabolite 1-hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations.

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1-hydroxymidazolam were determined by the use of high-performance liquid chromatography tandem-mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half-lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration-time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady-state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr-1  kg-1 , and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1-hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1-hydroxymidazolam following IC administration.

Tissue residue depletion of fenbendazole after oral administration in turkeys.

The objectives of this study were to determine tissue depletion of fenbendazole in turkeys and estimate a withdrawal interval (WDI). Forty-eight 9-week-old turkeys were fed fenbendazole at 30 mg/kg of feed for 7 consecutive days. Three hens and 3 toms were sacrificed every 2 days from 2 to 16 days post-treatment, and tissues were collected to determine fenbendazole sulfone (FBZ-SO2) concentrations using mass spectrometry. At all timepoints, FBZ-SO2 concentrations in liver and skin-adherent fat were above the limit of quantification (1 ppb), with higher concentrations than those in kidney and muscle. Two turkeys had detectable FBZ-SO2 concentrations in kidney at 16 days. No detectable FBZ-SO2 concentrations were found in muscle at 14 and 16 days. Fenbendazole residues depleted very slowly from the liver and a WDI of at least 39 days should be observed under the conditions of this study, in order to comply with Canadian regulatory agencies.

Déplétion du fenbendazole pour les résidus tissulaires après l'administration orale chez les dindons. Les objectifs de cette étude consistaient à déterminer la déplétion du fenbendazole dans les tissus chez les dindons et d'estimer un délai d'attente (DA). Du fenbendazole a été administré à quarante-huit dindons âgés de 9 semaines, à raison de 30 mg/kg d'aliments pendant 7 jours consécutifs. Trois dindes et 3 dindons ont été sacrifiés tous les deux jours pendant les jours 2 à 16 après le traitement et les tissus ont été prélevés pour déterminer les concentrations de fenbendazole sulfone (FBZ-SO2) en utilisant la spectrométrie de masse. À tous les moments de prélèvement, les concentrations de FBZ-SO2 dans le foie et le gras adhérent à la peau étaient supérieures à la limite de quantification (1 ppm), avec des concentrations supérieures à celles présentes dans les reins et les muscles. Deux dindes avaient des concentrations de FBZ-SO2 détectables dans les reins à 16 jours. Aucune concentration détectable de FBZ-SO2 n'a été trouvées dans les muscles à 14 et à 16 jours. Les résidus de fenbendazole se résorbaient très lentement du foie et un DA d'au moins 39 jours devrait être observé conformément aux conditions de cette étude afin de satisfaire aux exigences des agences réglementaires canadiennes.(Traduit par Isabelle Vallières).

Perioperative analgesic use by Ontario veterinarians, 2012.

The objectives of this study were to describe the routine use of analgesics by Ontario veterinarians for common surgeries in dogs and cats, and to compare routine use of analgesics between species and surgeries, using Chi-square analyses. In total, 239 veterinarians responded to the questionnaires; a response rate of 13.1%. Fifty-two percent to 79% of veterinarians used meloxicam for both species and all surgeries. Approximately 9% of veterinarians did not use analgesics for dog ovariohysterectomy and castration, while 16% to 22% did not use analgesics for these surgeries in cats. Veterinarians used and dispensed analgesics to dogs more often than to cats (P < 0.05). Many (60% or more) veterinarians administered analgesics pre-emptively to both dogs and cats for all surgeries. Continuing education for veterinarians needs to focus on understanding of pre-emptive analgesia, preventive analgesia, and the importance of dispensing analgesic drugs after surgery for all surgeries.

Utilisation de l'analgésie péri-opératoire par les vétérinaires de l'Ontario, 2012. Les objectifs de cette étude consistaient à décrire l'utilisation routinière de l'analgésie par les vétérinaires de l'Ontario pour les chirurgies courantes chez les chiens et les chats et à comparer l'utilisation routinière de l'analgésie entre les espèces et les chirurgies en utilisant des analyses du chi-carré. Au total, 239 vétérinaires ont répondu aux questionnaires, pour un taux de réponse de 13,1 %. De cinquante-deux à 79 % des vétérinaires avaient recours au méloxicam pour les deux espèces et toutes les chirurgies. Environ 9 % des vétérinaires n'ont pas utilisé d'analgésie pour l'ovario-hystérectomie et la castration canines, tandis que de 16 % à 22 % n'ont pas eu recours à l'analgésie pour ces chirurgies chez les chats. Les vétérinaires utilisaient et distribuaient des analgésiques aux chiens plus souvent qu'aux chats (P < 0,05). Plusieurs vétérinaires (60 % ou plus) ont administré des analgésiques de manière préventive aux chiens et aux chats pour toutes les chirurgies. La formation continue des vétérinaires doit continuer de se concentrer sur la compréhension de l'analgésie préventive et sur l'importance d'administrer des analgésiques après la chirurgie pour toutes les chirurgies.(Traduit par Isabelle Vallières).

Code Grey: Stained Surgical Instruments and Their Impact on One Canadian Health Authority.

In 2016, NL's largest RHA was faced with serious challenges stemming from the discovery of stained surgical instruments at its two largest hospitals. This discovery prompted a series of postponed surgeries, an extensive internal mobilization of labour and the purchase of millions of dollars of new equipment. In tackling these challenges, the organization not only acquired a better understanding of its surgical tools, but it also gained renewed appreciation for the resilience of its human resources. By describing this incident and the lessons learned, we hope to offer insight to providers in similar circumstances.

Disparities in the Use of Internet and Telephone Medication Refills among Linguistically Diverse Patients.

BACKGROUND: Health systems are increasingly implementing remote telephone and Internet refill systems to enhance patient access to medication refills. Remote refill systems may provide an effective approach for improving medication non-adherence, but more research is needed among patients with limited English proficiency with poor access to remote refill systems. OBJECTIVE: To compare the use of remote medication refill systems among limited-English-proficiency (LEP) and English-proficient (EP) patients with chronic conditions. METHODS: Cross-sectional survey in six languages/dialects (English, Cantonese, Mandarin, Korean, Vietnamese, and Spanish) of 509 adults with diabetes, hypertension, or hyperlipidemia. Primary study outcomes were self-reported use of 1) Internet refills, 2) telephone refills, and 3) any remote refill system. LEP was measured by patient self-identification of a primary language other than English and a claims record of use of an interpreter. Other measures were age, gender, education, years in the U.S., insurance, health status, chronic conditions, and number of prescribed medications. Analyses included multivariable logistic regression weighted for survey non-response. RESULTS: Overall, 33.1 % of patients refilled their medications by telephone and 31.6 % by Internet. Among LEP patients (n = 328), 31.5 % refilled by telephone and 21.2 % by Internet, compared with 36.7 % by telephone and 52.7 % by Internet among EP patients (n = 181). Internet refill by language groups were as follows: English (52.7 %), Cantonese (34.9 %), Mandarin (17.4 %), Korean (16.7 %), Vietnamese (24.4 %), and Spanish (12.6 %). Compared to EP patients, LEP patients had lower use of any remote refill system (adjusted odds ratio [AOR] 0.18; p < 0.001), CONCLUSIONS: LEP patients are significantly less likely than EP patients to use any remote medication refill system. Increased reliance on current systems for remote medication refills may increase disparities in health outcomes affecting LEP patients with poor access to telephone and Internet medication refills.

Effects of acepromazine or dexmedetomidine on fentanyl disposition in dogs during recovery from isoflurane anesthesia.

OBJECTIVE: To describe fentanyl pharmacokinetics during isoflurane anesthesia and on recovery from anesthesia with concurrent administration of acepromazine, dexmedetomidine or saline in dogs. STUDY DESIGN: Experimental blinded, randomized, crossover study. ANIMALS: Seven adult hound dogs. METHODS: Dogs were administered intravenous (IV) fentanyl as a bolus (5 µg kg(-1)) followed by an infusion (5 µg kg(-1) hour(-1)) for 120 minutes during isoflurane anesthesia and emergence from anesthesia, and for 60 minutes after extubation during recovery from anesthesia. At the time of extubation, dexmedetomidine (2.5 µg kg(-1)), acepromazine (0.05 mg kg(-1)) or saline were administered IV. Venous blood was sampled during the maintenance and recovery periods. Fentanyl plasma concentrations were measured using high-performance liquid chromatography-mass spectrometry and population pharmacokinetic analyses were performed. RESULTS: Mean fentanyl plasma concentrations were 1.6-4.5 ng mL(-1) during isoflurane anesthesia and 1.6-2.0 ng mL(-1) during recovery from anesthesia. Recovery from isoflurane anesthesia without sedation was associated with an increase in the volume of the central compartment from 0.80 to 1.02 L kg(-1). After administration of acepromazine, systemic clearance of fentanyl increased from 31.5 to 40.3 mL minute(-1) kg(-1) and the volume of the central compartment increased from 0.70 to 0.94 L kg(-1). Administration of dexmedetomidine did not significantly change fentanyl pharmacokinetics. Inter-individual variability for fentanyl parameter estimates in all treatments ranged from 2.2% to 54.5%, and residual error ranged from 6.3% to 13.4%. CONCLUSIONS AND CLINICAL RELEVANCE: The dose rates of fentanyl used in this study achieved previously established analgesic plasma concentrations for the duration of the infusion. Despite alterations in fentanyl pharmacokinetics, differences in fentanyl plasma concentrations among treatments during recovery from anesthesia were small and were unlikely to be of clinical significance.

Survey of Ontario veterinarians' knowledge and attitudes on pain in dogs and cats in 2012.

Appropriate management of animal pain is a critical component of optimal animal welfare in small animal veterinary clinics. An online convenience survey was used to examine the knowledge and attitudes of practicing veterinarians in Ontario about pain in dogs (n = 100) and cats (n = 139). Veterinarian participants showed strong agreement with the need for appropriate animal pain relief, and low agreement with lack of analgesic use due to cost or side effects. All of the surgical procedures included in the survey were ranked as being moderately to highly painful, but female veterinarians had higher median rankings. Importantly, 78% of veterinarians thought their knowledge about pain recognition was sufficient. Selection bias might have resulted in overestimates of attitudes about pain in comparison to the general veterinary population. However, these results suggest that knowledge and attitudes related to pain assessment and treatment in dogs and cats have improved since the last similar survey in 2001.

Sondage sur les connaissances et les attitudes des vétérinaires de l'Ontario à propos de la douleur chez les chiens et les chats en 2012. La gestion appropriée de la douleur animale est une composante critique du bien-être animal dans les cliniques vétérinaires pour petits animaux. Un sondage de convenance en ligne a été mené pour examiner les connaissances et les attitudes des vétérinaires praticiens en Ontario à propos de la douleur chez les chiens (n = 100) et les chats (n = 139). Les participants vétérinaires se sont dits fortement en accord avec le besoin d'analgésie appropriée pour soulager la douleur des animaux et très peu en accord avec l'absence d'utilisation des analgésiques en raison du coût ou des effets secondaires. Toutes les interventions chirurgicales incluses dans le sondage étaient classées comme étant modérément à très douloureuse, mais les femmes vétérinaires présentaient des classements moyens supérieurs. Fait important, 78 % des vétérinaires croyaient que leurs connaissances à propos de la reconnaissance de la douleur étaient suffisantes. Le biais de sélection pourrait s'être traduit par des surestimations des attitudes à propos de la douleur comparativement à la population vétérinaire en général. Cependant, ces résultats suggèrent que les connaissances et les attitudes se rapportant à l'évaluation de la douleur et au traitement des chiens et des chats se sont améliorées depuis le dernier sondage semblable réalisé en 2001.(Traduit par Isabelle Vallières).

Relationship between cardiovascular risk and lipid testing in one health care system: a retrospective cohort study.

BACKGROUND: The US Preventive Services Taskforce (USPSTF) recommends routine lipid screening beginning age 35 for men [1]. For women age 20 and older, as well as men age 20-34, screening is recommended if cardiovascular risk factors are present. Prior research has focused on underutilization but not overuse of lipid testing. The objective is to document over- and under-use of lipid testing in an insured population of persons at low, moderate and high cardiovascular disease (CVD) risk for persons not already on statins. METHODS: The study is a retrospective cohort study that included all adults without prior CVD who were continuously enrolled in a large integrated healthcare system from 2005 to 2010. Measures included lipid test frequency extracted from administrative data and Framingham cardiovascular risk equations applied using electronic medical record data. Five year lipid testing patterns were examined by age, sex and CVD risk. Generalized linear models were used to estimate the relative risk for over testing associated with patient characteristics. RESULTS: Among males and females for whom testing is not recommended, 35.8 % and 61.5 % received at least one lipid test in the prior 5 years and 8.4 % and 24.4 % had two or more. Over-testing was associated with age, race, comorbidity, primary care use and neighborhood income. Among individuals at moderate and high-risk (not already treated with statins) and for whom screening is recommended, between 21.4 % and 25.1 % of individuals received no screening in the prior 5 years. CONCLUSIONS: Based on USPSTF lipid screening recommendations, this study documents substantial over-testing among individuals with low CVD risk and under-testing among individuals with moderate to high-risk not already on statins. Opportunity exists to better focus lipid screening efforts appropriate to CVD risk.

Effects of acute transmural pressure elevation on endothelium-dependent vasodilation in isolated rat mesenteric veins.

BACKGROUND/AIMS: The vascular regulatory function of the endothelium can be impaired by increases in transmural pressure (TMP). We tested the hypothesis that increasing TMP impairs the endothelial dilator function of rat mesenteric small veins (MSVs). METHODS: In PGF2α-preconstricted MSVs, bradykinin (BK), sodium nitroprusside (SNP) and S-Nitroso-N-acetylpenicillamine (SNAP) concentration-response curves were generated at intermediate (6 mm Hg) and high (12 mm Hg) pressures. BK-induced vasodilation was examined in the absence and presence of nitric oxide synthase inhibitor [N(ω)-nitro-L-arginine (L-NNA), 100 µM], cyclooxygenase inhibitor (indomethacin, 1 µM), and large (BKCa, paxilline, 500 nM) and small (SKCa, apamin, 300 nM) conductance Ca(2+)-activated K(+) channel blockers. RESULTS: BK, SNP and SNAP responses were not altered by TMP increases. BK-induced vasodilation was significantly reduced by L-NNA, indomethacin, apamin and paxilline at 6 mm Hg and L-NNA at 12 mm Hg, and was further reduced by coapplication of apamin and/or paxilline with L-NNA compared with responses obtained with either blocker. Endothelium removal completely abolished BK-induced vasodilation. CONCLUSION: Venous endothelial dilator function is not affected by TMP elevation. BK-induced vasodilation is completely dependent on the presence of functional endothelial cells and mediated in part by nitric oxide, BKCa and SKCa channels, while the participation of prostacyclin may be important at intermediate pressures.

Intra-articular pharmacokinetics of a gentamicin impregnated collagen sponge in the canine stifle: an experimental study.

OBJECTIVE: To investigate local and systemic pharmacokinetics of gentamicin after intra-articular implantation of a gentamicin impregnated collagen sponge (GICS) in the inflamed canine joint. STUDY DESIGN: Descriptive repeated measures experimental study. ANIMALS: Dogs (n = 9). METHODS: Stifle joint inflammation was caused by urate injection. Twenty-four hours later a GICS (gentamicin dose, 6 mg/kg) was arthroscopically implanted. Synovial fluid and plasma gentamicin concentrations were measured for 14 days after implantation, and pharmacokinetic parameters modeled using statistical moment analyses. RESULTS: Intra-articular gentamicin concentrations fell to sub-MIC for Staphylococcus sp. (4 µg/mL) by 22.4 hours (95% CI: 18.6-26.2) after sponge implantation. Cmax synovial was 2397 µg/mL (95%CI: 1161-3634 µg/mL) at 1.2 hours (95%CI: 0.5-1.8 hours). Plasma gentamicin concentrations achieved levels of Cmax plasma = 8.0 µg/mL (95%CI: 6.1-10.0 µg/mL) at 1.5 hours (95%CI: 0.8-2.1) after GICS placement and fell below target trough of 2.0 µg/mL by 5.6 hours (95%CI: 4.7-6.5 hours) after GICS placement. CONCLUSIONS: Intra-articular gentamicin concentration after GICS placement at an IV-equivalent dose reached high levels and declined rapidly. The maximum plasma levels attained were ∼1/3 of the recommended sub-toxic target for people after parenteral gentamicin administration.