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OBJECTIVE The aim of this study was to determine whether the pharmacokinetics of maropitant, administered SC as a commercially available maropitant-containing injectable product (Cerenia Injectable), differ when combined with lactated Ringer solution prior to administration. ANIMALS We used 6 adult spayed female Beagle dogs between 3 and 6 years of age, with a mean weight of 9.58 kg. PROCEDURES In this randomized crossover study, the dogs underwent 2 treatment protocols separated by a 14-day washout period: (1) an SC injection of 1 mg/kg of Cerenia Injectable (maropitant citrate; 10 mg/mL) and (2) 1 mg/kg of Cerenia Injectable diluted in 10 mL/kg of lactated Ringer injectable solution (LRS) given SC. Plasma maropitant concentrations were assessed by mass spectrometry. Pharmacokinetic analysis was performed using pharmacokinetic and pharmacodynamic data-analysis software to determine maximum plasma concentration (Cmax), time to reach maximum concentration, half-life, total exposure to the drug, mean residence time, clearance rate per fraction absorbed, and absorption and elimination kinetic parameters. RESULTS Cmax was reduced by 26% (P = .002), the absorption rate constant decreased 80% (P = .031), and the absorption half-life increased when Cerenia was administered diluted in LRS. CLINICAL RELEVANCE Administration of maropitant (Cerenia) diluted in LRS had a pharmacokinetic impact, resulting in a significantly reduced Cmax and slower absorption. Clinical efficacy was not assessed in this study.

International audience; BACKGROUND Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

OBJECTIVE To develop a population-derived, parsimonious, and objective risk stratification model for dogs following trauma and compare its predictive performance to the animal trauma triage (ATT) score. DESIGN Observational cohort study using data from the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma (VetCOT) trauma registry acquired between September 2013 and October 2017. SETTING Nine Level I and Level II veterinary trauma centers. ANIMALS Nine hundred eighty-four dogs assessed within 24 h of traumatic injury. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patient mortality was 10.8%. The VetCOT model was constructed based on 4 variables: plasma lactate and ionized calcium obtained within 6 h of admission, and presence or absence of clinical signs consistent with either head or spinal trauma. The VetCOT score had good discriminatory performance (AUROC = 0.87, 95% CI = 0.83-0.91) comparable to that of the 6 variable ATT score for the same population (area under the receiver operator characteristic [AUROC] = 0.87; 95% CI, 0.84-0.90). No statistical difference in discriminatory performance between the 2 scores was identified (P = 0.98). The VetCOT score showed good calibration on this population (Hosmer-Lemeshow test P = 0.93), whereas the ATT score failed to calibrate (P = 0.02) due to overprediction of mortality at low scores. Sensitivity and specificity for outcome of the VetCOT score at a risk probability cutoff of 0.5 for this population were 28.97% and 97.95%, respectively. CONCLUSIONS The VetCOT score is a more parsimonious model with comparable discriminatory performance and superior calibration to the ATT score for risk stratification in dogs following trauma. Further prospective validation studies are required to confirm the discriminatory performance of the VetCOT score.

Background Combatting antimicrobial resistance requires a One Health approach to antimicrobial stewardship including antimicrobial drug (AMD) use evaluation. Current veterinary AMD prescribing data are limited. Objectives To quantify companion animal AMD prescribing in primary care and specialty practice across 3 academic veterinary hospitals with particular focus on third‐generation cephalosporins, fluoroquinolones, and carbapenems. Animals Dogs and cats presented to 3 academic veterinary hospitals from 2012 to 2017. Methods In this retrospective study, AMD prescribing data from 2012 to 2017 were extracted from electronic medical records at each hospital and prescriptions classified by service type: primary care, specialty practice or Emergency/Critical Care (ECC). Hospital‐level AMD prescribing data were summarized by species, service type, AMD class, and drug. Multivariable logistic full‐factorial regression models were used to estimate hospital, year, species, and service‐type effects on AMD prescribing. Estimated marginal means and confidence intervals were plotted over time. Results The probability of systemic AMD prescribing for any indication ranged between 0.15 and 0.28 and was higher for dogs than cats (P

BACKGROUND The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. METHODS The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. RESULTS The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/36261

BackgroundSmall-bore wire-guided thoracostomy tubes (SBWGTT) are commonly used in small animals for management of pleural space disease. We aimed to evaluate the indications, placement locations, types of complications, and complication rate of small-bore wire-guided thoracostomy tube placements in dogs and cats in a university setting.MethodsElectronic medical records of patients that underwent SBWGTT placement were reviewed. Signalment, disease, outcome, indication for thoracostomy tube, placement location, number of attempts, diagnostic imaging, number, and type (insertional, technical, and infectious) of complications were recorded. Logistic regression analysis was performed to determine risk factors for complications.ResultsA hundred fifty-six cases were identified between 2007 and 2019. Traumatic pneumothorax (33%), pyothorax (25%), and spontaneous pneumothorax (16%) were the most common indications for placement of a SBWGTT. Complications developed in 50 cases (32%). Technical and insertional complications accounted for 21.7% and 14.1% of all cases. Infectious complications were rare with 3.1% of all cases. Pneumothorax (19%), soft tissue swelling at insertion site (14%), and kinking of the chest tube (13%) were most common. Accidental lung perforation was reported in 5/50 complications (7%). Multiple chest tube placement attempts were associated with complications (OR = 6.01 CI: 2.13 to 16.93 p = 0.0007).ConclusionsComplications of SBWGTT placement occurred in one third of cases. Serious complications such as accidental lung perforation was reported in two cases. Complications were associated with number of attempts.

Background: In humans with sepsis, hypophosphatemia is a marker of illness severity and a negative prognostic indicator. Hypophosphatemia has not been previously investigated in dogs with sepsis, however. This study aimed to estimate the prevalence of hypophosphatemia in dogs, the prevalence of presumptive sepsis in dogs with hypophosphatemia, the prevalence of hypophosphatemia in dogs with presumptive sepsis and the association between outcome and hypophosphatemia in dogs with presumptive sepsis.Methods: Electronic medical records of the Cornell University Hospital for Animals from 2008–2018 were queried to identify all dogs with hypophosphatemia and all dogs with presumptive sepsis. Hypophosphatemia was defined as a serum phosphate concentration U test. Differences in frequency between categorical variables were analyzed using contingency tables, calculation of Fisher's exact test or Chi2 and estimation of odds ratios.Results: In the study period, 47,992 phosphate concentration measurements from 23,752 unique dogs were identified. After eliminating repeat analyses, the period prevalence of hypophosphatemia on a per dog basis over the 11-year study period was 10.6% (2,515/23,752). The prevalence of presumptive sepsis within dogs with hypophosphatemia was 10.7% (268/2,515). During the 11-year study period, 4,406 dogs with an infection were identified, of which 1,233 were diagnosed with presumptive sepsis and had a contemporaneous phosphate concentration. Hypophosphatemia was more prevalent in dogs with presumptive sepsis than in dogs without 21.7 vs. 10.2%; OR 2.44 [95% CI 2.12–2.81]; P < 0.0001. The mortality rate was greater in dogs with hypophosphatemia and presumptive sepsis than in dogs with hypophosphatemia without presumptive sepsis (15.3 vs. 3.1%; OR 5.70 [95% CI 3.76–8.52]; P < 0.0001), however hypophosphatemia was not associated with outcome in dogs with presumptive sepsis OR 0.87 [95% CI 0.60–1.26]; P = 0.518.Conclusions: In dogs with hypophosphatemia, a presumed diagnosis of sepsis was associated with increased mortality compared to other associated disease processes. In dogs with presumptive sepsis, hypophosphatemia was not associated with outcome.

International audience; Background: Antimicrobial use contributes to emergence of antimicrobial resistance. It was hypothesized that antimicrobial prescribing behavior varies between the emergency (ER) and critical care (CC) services in a veterinary teaching hospital. This study aimed to: (i) describe antimicrobial prescribing patterns in the ER and CC services; (ii) assess adherence to stewardship principles; (iii) evaluate the prevalence of multidrug resistant (MDR) bacterial isolates.Methods: Institution electronic medical records were queried for all antimicrobial prescriptions from the ER and CC services between 1/1/2017 and 12/31/2017. Prescriptions were manually reviewed, and the following data recorded: drug, dosage, duration, diagnosis, outcome, hospitalization duration, culture submission, and susceptibility results.Results: There were 5,091 ER visits, of which 3,125 were not transferred to another service. Of these emergency visits, 516 (16.5%) resulted in 613 antimicrobial drug prescriptions. The most commonly prescribed drugs for the ER were amoxicillin/clavulanate (n = 243, 39.6%), metronidazole (n = 146, 23.8%), and ampicillin/sulbactam (n = 55, 9.0%). The most common reasons for antimicrobial prescriptions were skin disease (n = 227, 37.0%), gastrointestinal disease (n = 173, 28.2%), and respiratory disease (n = 50, 8.2%). For ER patients 18 cultures were submitted, equivalent to a 3.5% submission rate. The CC service managed 311 case visits for 822 patient days. Of these, 133 case visits (42.7%) resulted in 340 prescriptions. The most commonly prescribed drugs for the CC service were ampicillin/sulbactam (n = 103, 30.3%), enrofloxacin (n = 75, 22.1%), and metronidazole (n = 59, 17.4%). The most common reasons for antimicrobial prescriptions were gastrointestinal disease (n = 106, 31.2%), respiratory disease (n = 71, 20.9%), and sepsis (n = 61, 17.9%). On the CC service, 46 patients had >= 1 culture submitted, equivalent to a 34.6% submission rate. Of patients prescribed antimicrobials, 13/38 (34%) with urinary tract disease, 2/28 (7%) with pneumonia, 1/11 (9%) with canine infectious respiratory disease complex and 2/8 (25%) with feline upper respiratory infection were compliant with published guidelines.Conclusions: Antimicrobial prescription was common in both ER and CC services and followed similar patterns. Adherence to published guidelines for urinary and respiratory infections was poor.

Within continental lithosphere, widespread seismic evidence suggests a sharp discontinuous downward decrease in seismic velocity at 60–160 km depth. This midlithospheric discontinuity (MLD) may be due to anisotropy, melt, hydration, and/or mantle metasomatism. We survey global seismologic observations of the MLD, including observed depths, velocity contrasts, gradients, and locales across multiple seismic techniques. The MLD is primarily found in regions of thick continental lithosphere and is a decrease in seismic shear velocity (2–7% over 10–20 km) at 60–160 km depth, the majority of observations clustering at 80–100 km. Of xenoliths in online databases, 25% of amphibole-bearing xenoliths, 90% of phlogopite-bearing xenoliths, and none of carbonate-bearing xenoliths were formed at pressures associated with these depth (2–5 GPa). We used Perple_X modeling to evaluate the elastic moduli and densities of multiple petrologies to test if the MLD is a layer of crystallized melt. The fractional addition of 5–10% phlogopite, 10–15% carbonate, or 45–100% pyroxenite produce a 2–7% velocity decrease. We postulate this layer of crystallized melt would originate at active margins of continents and crystallize in place as the lithosphere cools. The concentration of mildly incompatible elements (Y, Ho, Er, Yb, and Lu) in xenoliths near the MLD is consistent with higher degrees of melting. Thus, we postulate that the MLD is the seismological signature of a chemical interface related to the paleointersection of a volatile-rich solidus and progressively cooling lithosphere. Furthermore, the MLD may represent a remnant chemical tracer of the lithosphere-asthenosphere boundary (LAB) from when the lithosphere was active and young.

Some individuals with chronic combat-related posttraumatic stress disorder do not benefit from standard psychotherapies and often drop out of treatment. Innovative treatment techniques, such as virtual-reality, may be useful to help address treatment goals by promoting presence and overcoming cognitive avoidance to improve ability to reconsolidate the traumatic memory. This pilot study examined the effect of a new virtual-reality therapy (Motion-Assisted, Multi-Modal Memory Desensitization and Reconsolidation) on symptoms of posttraumatic stress disorder in Canadian Armed Forces service members. Meaningful reductions in posttraumatic stress disorder symptoms were observed as well as notable improvements in social functioning. These preliminary findings demonstrated that our service members can benefit from this new virtual-reality therapy.

Background: Cimicoxib is a coxib recently licensed in Europe for pain and inflammation associated with osteoarthritis (OA), and the management of perioperative pain due to orthopaedic or soft tissue surgery. Purpose: This prospective study was to complete the product information for the end users by providing additional scientific data obtained after a thirty-day treatment course of cimicoxib in dogs with OA, and to collect owners’ feedback. Data were collected from nine European countries with 492 client owned dogs recruited to the trial. Dogs were treated once daily with 2 mg/kg cimicoxib orally. Immediately before, at Day (D) 15 and D30 after the start of treatment veterinarians and owners scored body condition, appetite, locomotion, lameness, pain on palpation and manipulation of the joint and joint effusion (veterinarians) and dog demeanor and well being (owners). In a subset of dogs, serum urea (n = 191), creatinine (n = 184), AST (n = 141) and ALT (n = 174) were measured at day (D) 0 and D30. Statistical tests were carried out to detect significant changes in the clinical parameters with time. Results and Discussion: Veterinary and owner assessments were analysed from 236 and 215 dogs respectively. Improvements in locomotion, mobility, pain scores and dog demeanor and body condition were identified; outcome measures assessed by veterinarians continued to improve after 15 days of treatment up to the 30-day time point. At D30 a significantly higher number of dogs had an urea concentration superior to the upper limit of the reference range. However, there was no significant difference for creatinine, ALT and AST. Conclusions: A 30-day treatment course with cimicoxib improved locomotion and decreased pain scores in dogs with OA, with minimal adverse effects. These data, support pre-clinical data in dogs receiving cimicoxib and are useful for veterinarians making decisions about which NSAID to administer to dogs that require pain management for OA.

Objective – To report the surgical repair, case management, and outcome of a dog with sepsis and severe intraabdominal trauma secondary to a penetrating stick injury. Case or Series Summary – A 1.5-year-old, spayed female, mixed-breed dog was presented to the emergency service after incurring a small laceration on the medial aspect of the left pelvic limb while running in the woods. The wound was surgically explored and a primary closure achieved. The patient was discharged the same day with oral antimicrobial therapy. The following morning the dog was represented to the emergency service for acute vomiting. Abdominal radiographs were performed and demonstrated loss of serosal detail and pneumoperitoneum. An emergency celiotomy was performed and revealed distal colonic perforation, left ureteral laceration, and lacerations of the left common iliac vein. Ureteronephrectomy, as well as primary closure of the distal colonic perforation and left common iliac vein lacerations, were performed. The patient recovered and was ultimately discharged from the hospital 5 days later. Follow-up 1 year later revealed no significant physical exam or biochemical abnormalities. New or Unique Information Provided – A seemingly benign penetrating stick injury initially deemed to be superficial in nature was later demonstrated to have resulted in sepsis following severe intraabdominal trauma that included lacerations of the distal colon, left ureter, and left common iliac vein in a dog. Successful surgical management and intensive care led to a full recovery without any residual impairment noted a year later.

This preliminary study examined the impact of aerobic exercise as an adjunctive intervention to regular care in reducing obsessive compulsive disorder (OCD) symptoms in a clinical sample. Fifteen patients (53% male; mean age = 44.4 years) receiving behavioral therapy and/or pharmacotherapy for OCD and who still demonstrated clinically significant OCD symptoms (i.e., Yale-Brown obsessive compulsive scale, Y-BOCS scores above 16) were enrolled in a 12-week moderate-intensity exercise intervention. Measures of OCD symptom severity were obtained at baseline, end of treatment, and at 3- and 6-week, and 6-month follow-up. Study findings at the end of this 12-week aerobic exercise intervention point to a beneficial effect (Cohen's d = 1.69) on reduction in OCD symptom severity. Further, reductions in OCD symptom severity appear to persist 6 months later. Lastly, improvement in overall sense of well-being was observed after the 12-week intervention. Results of this study suggest that a randomized clinical trial evaluating the efficacy of this 12-week aerobic exercise intervention is warranted.