The response of Canada's clinical health research ecosystem to the COVID-19 pandemic.

BACKGROUND: The response of Canada's research community to the COVID-19 pandemic provides a unique opportunity to examine the country's clinical health research ecosystem. We sought to describe patterns of enrolment across Canadian Institutes of Health Research (CIHR)-funded studies on COVID-19. METHODS: We identified COVID-19 studies funded by the CIHR and that enrolled participants from Canadian acute care hospitals between January 2020 and April 2023. We collected information on study-and site-level variables from study leads, site investigators, and public domain sources. We described and evaluated factors associated with cumulative enrolment. RESULTS: We obtained information for 23 out of 26 (88%) eligible CIHR-funded studies (16 randomized controlled trials [RCTs] and 7 cohort studies). The 23 studies were managed by 12 Canadian and 3 international coordinating centres. Of 419 Canadian hospitals, 97 (23%) enrolled a total of 28 973 participants - 3876 in RCTs across 78 hospitals (median cumulative enrolment per hospital 30, interquartile range [IQR] 10-61), and 25 097 in cohort studies across 62 hospitals (median cumulative enrolment per hospital 158, IQR 6-348). Of 78 hospitals recruiting participants in RCTs, 13 (17%) enrolled 50% of all RCT participants, whereas 6 of 62 hospitals (9.7%) recruited 54% of participants in cohort studies. INTERPRETATION: A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and provides information for multiple key partners to consider ways to realize the full research potential of Canada's health systems.

Defining sepsis in small animals.

OBJECTIVE: To discuss the definitions of sepsis in human and veterinary medicine. DESIGN: International, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine. SETTING: Veterinary private practice and university teaching hospitals. ANIMALS: Dogs and cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis is a life-threatening condition associated with the body's response to an infection. In human medicine, sepsis has been defined by consensus on 3 occasions, most recently in 2016. In veterinary medicine, there is little uniformity in how sepsis is defined and no consensus on how to identify it clinically. Most publications rely on modified criteria derived from the 1991 and 2001 human consensus definitions. There is a divergence between the human and veterinary descriptions of sepsis and no consensus on how to diagnose the syndrome. This impedes research, hampers the translation of pathophysiology insights to the clinic, and limits our abilities to optimize patient care. It may be time to formally define sepsis in veterinary medicine to help the field move forward. In this narrative review, we present a synopsis of prior attempts to define sepsis in human and veterinary medicine, discuss developments in our understanding, and highlight some criticisms and shortcomings of existing schemes. CONCLUSIONS: This review is intended to serve as the foundation of current efforts to establish a consensus definition for sepsis in small animals and ultimately generate evidence-based criteria for its recognition in veterinary clinical practice.

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. Results: 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. Conclusion: In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. Trial registration: CTRI/2020/03/024371. How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, et al. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023;27(12):910-916.

Noninvasive sampling of the small intestinal chyme for microbiome, metabolome and antimicrobial resistance genes in dogs, a proof of concept.

BACKGROUND: The gastrointestinal microbiome and metabolome vary greatly throughout the different segments of the gastrointestinal tract, however current knowledge of gastrointestinal microbiome and metabolome in health and disease is limited to fecal samples due to ease of sampling. The engineered Small Intestinal MicroBiome Aspiration (SIMBA™) capsule allows specific sampling of the small intestine in humans. We aimed to determine whether administration of SIMBA™ capsules to healthy beagle dogs could reliably and safely sample the small intestinal microbiome and metabolome when compared to their fecal microbiome and metabolome. RESULTS: Eleven beagle dogs were used for the study. Median transit time of capsules was 29.93 h (range: 23.83-77.88). Alpha diversity, as measured by the Simpson diversity, was significantly different (P = 0.048). Shannon diversity was not different (P = 0.114). Beta diversity results showed a significant difference between capsule and fecal samples regarding Bray-Curtis, weighted and unweighted unifrac (P = 0.002) and ANOSIM distance metric s (R = 0.59, P = 0.002). In addition to observing a statistically significant difference in the microbial composition of capsules and feces, distinct variation in the metabolite profiles was seen between the sample types. Heat map analysis showed 16 compounds that were significantly different between the 2 sampling modes (adj-P value ranged between 0.004 and 0.036) with 10 metabolites more abundant in the capsule than in the feces and 6 metabolites more abundant in the feces compared to the capsules. CONCLUSIONS: The engineered Small Intestinal MicroBiome Aspiration (SIMBA™) capsule was easy and safe to administer to dogs. Microbiome and metabolome analysis from the capsule samples were significantly different than that of the fecal samples and were like previously published small intestinal microbiome and metabolome composition.

Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. Objective: To determine whether vitamin C improves outcomes for patients with COVID-19. Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy. Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).

Prevalence of antibiotic use for dogs and cats in United States veterinary teaching hospitals, August 2020.

BACKGROUND: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU). OBJECTIVES: To estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection. ANIMALS: Medical record data were collected from dogs and cats examined at 14 VTHs. METHODS: Data were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed. RESULTS: Of 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use. CONCLUSIONS AND CLINICAL IMPORTANCE: Collaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

Dilution of maropitant (Cerenia) in lactated Ringer solution prolongs subcutaneous drug absorption and reduces maximum plasma concentration.

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.

When does exposure to daily negative acts frustrate employees' psychological needs? A within-person approach.

Based on self-determination theory, this two-sample study investigates the effects of negative acts on psychological need frustration in greater depth using a within-person perspective. More specifically, through two distinct diary studies, we aim to contribute to the dearth of research on the daily effects of bullying by investigating the daily relationship between exposure to negative acts and need frustration as well as the moderating role of perceived emotional support at work in this relationship. Overall, results from both studies show that employees experience greater need frustration (perceptions of rejection, oppression, and incompetence) on days they are confronted with negative acts and that daily emotional support buffers the impact of direct negative acts (humiliation, physical intimidation) on frustration of the needs for competence and relatedness at the daily level. As such, the results of the present two-sample study provide a better understanding of the boundary conditions under which exposure to negative acts may result in psychological costs by identifying emotional support as a key resource in the workplace that can offset the immediate harmful effects of certain negative behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

How Work-Family Guilt, Involvement with Children and Spouse's Support Influence Parents' Life Satisfaction in a Context of Work-Family Conflict.

Work-family guilt (WFG) is sometimes perceived as an adaptive characteristic, since it has been found to encourage working parents to engage in more activities with their children in off-work time (Cho & Allen, 2012). However, while it may be an adaptive characteristic for the parent-child relationship, the same may not be true for parents' psychological health. Using insights from the work-home resources model (W-HR), this study aims to determine WFG's influence on parents' life satisfaction. This study also investigates if parents' belief regarding the investment of their spouse in recreational activities with their children is a resource that could foster their life satisfaction. A cross-sectional design was used with a sample of 289 working parents with at least one child aged between 5 and 10. A path analysis shows a significant moderated mediation model. Parent-child activities were found to partially mediate the relationship between strain-based work interference with family and parents' life satisfaction. Furthermore, WFG moderated this mediation. Specifically, it worsened the detrimental effect of doing fewer parent-child activities on parents' life satisfaction. Results also show that a spouse's investment in activity with their child is a resource that motivates parents to invest more in their children and directly contributes to parents' life satisfaction.

Effect of antimicrobial administration on fecal microbiota of critically ill dogs: dynamics of antimicrobial resistance over time.

BACKGROUND: Multidrug resistance in companion animals poses significant risks to animal and human health. Prolonged antimicrobial drug (AMD) treatment in animals is a potential source of selection pressure for antimicrobial resistance (AMR) including in the gastrointestinal microbiota. We performed a prospective study of dogs treated for septic peritonitis, pyometra, or bacterial pneumonia and collected repeated fecal samples over 60 days. Bacterial cultures and direct molecular analyses of fecal samples were performed including targeted resistance gene profiling. RESULTS: Resistant Escherichia coli increased after 1 week of treatment (D1:21.4% vs. D7:67.9% P < 0.001) and returned to baseline proportions by D60 (D7:67.9% vs D60:42.9%, P = 0.04). Dogs with septic peritonitis were hospitalized significantly longer than those with pneumonia or pyometra. Based on genetic analysis, Simpson's diversity index significantly decreased after 1 week of treatment (D1 to D7, P = 0.008), followed by a gradual increase to day 60 (D1 and D60, P = 0.4). Detection of CTX-M was associated with phenotypic resistance to third-generation cephalosporins in E. coli (OR 12.1, 3.3-68.0, P < 0.001). Lincosamide and macrolide-resistance genes were more frequently recovered on days 14 and 28 compared to day 1 (P = 0.002 and P = 0.004 respectively). CONCLUSION: AMR was associated with prescribed drugs but also developed against AMDs not administered during the study. Companion animals may be reservoirs of zoonotic multidrug resistant pathogens, suggesting that veterinary AMD stewardship and surveillance efforts should be prioritized.

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

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.).

Serial evaluation of thoracic radiographs and acute phase proteins in dogs with pneumonia.

BACKGROUND: Acute phase proteins (APP) may guide treatment of pneumonia in dogs but correlations with radiographic abnormalities are poorly characterized. OBJECTIVES: Develop a thoracic radiographic severity scoring system (TRSS), assess correlation of radiographic changes with APP concentrations, and compare time to APP and radiograph normalization with duration of antimicrobials treatment. ANIMALS: Sixteen client-owned dogs, 12 with aspiration pneumonia, and 4 with community-acquired pneumonia. METHODS: Concentrations of C-reactive protein (CRP), serum amyloid A (SAA), and haptoglobin were measured on days 1, 3, 7, 14, 28, and 60 and orthogonal 2-view thoracic radiographs were obtained on days 1, 7, 14, 28, and 60. Treatment was clinician-guided and blinded to APP concentrations. Radiographic severity scores were assigned by blinded, randomized retrospective review by 2 board-certified radiologists with arbitration by a third radiologist. RESULTS: Median (interquartile range [IQR]) time to normalization of CRP (7 days [7-14]) and SAA concentrations (7 days [7-14]) were shorter than antimicrobial treatment duration (17.5 days [14.5-33.5]; P = .001 and .002, respectively) and TRSS normalization (14 days [8.8-52], P = .02 and .02, respectively). The CRP and SAA concentrations were positively correlated with TRSS (CRP rs , 0.643; SAA rs , 0.634; both P < .0001). Both CRP and SAA identified normal thoracic radiographs area under the curve (AUC) 0.873 and 0.817, respectively, both P < .0001. Interobserver agreement for TRSS assignment was moderate (κ, .499; P < .0001). CONCLUSION AND CLINICAL IMPORTANCE: Concentrations of CRP and SAA normalized before radiographic resolution and before clinicians discontinued antimicrobial treatment. The CRP and SAA concentrations may guide duration of antimicrobial treatment for dogs with pneumonia.

Retrospective Evaluation of the Use and Complications of Small-Bore Wire-Guided Thoracostomy Tubes in Dogs and Cats: 156 Cases (2007-2019).

Background: Small-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. Methods: Electronic 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. Results: A 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). Conclusions: Complications 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.

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

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 IDENTIFIER (IRRID): DERR1-10.2196/36261.

Serial analysis of blood biomarker concentrations in dogs with pneumonia, septic peritonitis, and pyometra.

BACKGROUND: Prolonged antimicrobial drug (AMD) treatment is associated with antimicrobial resistance development. Biomarker measurement may aid treatment decision-making. OBJECTIVES: Investigate temporal changes in blood biomarker concentrations in dogs undergoing treatment for pulmonary and intra-abdominal infections; compare time to biomarker concentration normalization with duration of clinician-directed AMD treatment. ANIMALS: Forty-two client-owned dogs with pneumonia (n = 22), septic peritonitis (n = 10), or pyometra (n = 10). METHODS: Plasma concentrations of C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, procalcitonin, nucleosomes, cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), CC-motif chemokine ligand-2 (CCL2), CXC-motif chemokine ligand-8 (CXCL8), and keratinocyte chemoattractant-like (KC-Like) were quantitated in samples collected on days 1, 3, 7, 14, 28, and 60. Treatment was directed by clinicians blinded to biomarker concentrations. RESULTS: Concentrations of CCL2, CRP, and KC-Like were maximal on D1, concentrations of SAA, cfDNA, HMGB1, and nucleosomes were maximal on D3 and haptoglobin concentrations were maximal on D7. These maximal concentrations were significantly different from those on D60. Concentrations of CRP and SAA decreased by 80% from peak and into respective reference intervals before AMDs were discontinued. For CRP, the median (interquartile range [IQR]) times to 20% peak and normal were 7 (6-9) and 7 (6-12) days, respectively, and for SAA they were 4 (4, 5) and 6 (5-8) days, respectively, compared to a median (IQR) duration of AMD prescribing of 16 (12-23) days (all P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Biomarker concentrations normalized within 7 to 14 days. Serial measurements of CRP and SAA might aid identification of disease resolution and could help guide AMD prescription decision-making.

Development of a veterinary trauma score (VetCOT) in canine trauma patients with performance evaluation and comparison to the animal trauma triage score: A VetCOT registry study.

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.

A Diary Study on When and With Whom Recovery Experiences Modulate Daily Stress and Worry During a COVID-19 Lockdown.

In April 2020, almost six out of 10 people around the world were in lockdown due to the COVID-19 pandemic. Being locked down usually has a deleterious effect on the confined individual's mental health. In this exceptionally challenging context, finding ways to minimize negative mood about the pandemic is essential. Pandemic-related negative states ("negative mood") and recovery experiences were investigated in a sample of 264 individuals who completed daily surveys four times per day over 7 consecutive days. MSEMs analyses revealed that negative mood persisted from moment-to-moment through the day, thus showing a response lag effect. Further analyses revealed that when someone experienced pandemic-related psychological detachment, relaxation, mastery, control, pleasure, or relatedness at specific periods of the day, mood had improved at the next measured time period, suggesting a protective effect. However, the pattern displayed by singles with dependents suggests that some recovery experiences at specific periods during the day seem to have a backfiring effect and worsen subsequent mood. These findings bring new insight into the role of recovery experiences during lockdowns and suggest that many could benefit from such experiences throughout the day when self-isolating. However, for individuals with multiple risk factors such as being single with dependents, some recovery experiences, at specific periods during the day, might not bring the desired outcome and future research is needed to examine if guilt or domestic burden may explain this finding. Results contribute to our understanding of how to take care of one's mental health during the current pandemic, and concrete recommendations adapted to individual contexts are provided.

Patterns of antimicrobial drug use in veterinary primary care and specialty practice: A 6-year multi-institution study.

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 < .05) apart from 2017 at hospital 1. Animals presented to primary care were least likely to receive AMDs (dogs 0.03-0.15, cats 0.03-0.18). The most commonly prescribed AMD classes were aminopenicillins/ß-lactamase inhibitors (0.02-0.15), first-generation cephalosporins (0.00-0.09), fluoroquinolones (0.00-0.04), nitroimidazoles (0.01-0.06), and tetracyclines (0.00-0.03). Among the highest priority classes, fluoroquinolones (dogs 0.00-0.09, cats 0.00-0.08) and third-generation cephalosporins (dogs 0.00-0.04, cats 0.00-0.05) were most frequently prescribed. CONCLUSIONS AND CLINICAL IMPORTANCE: Antimicrobial drug prescribing frequencies were comparable to previous studies. Additional stewardship efforts might focus on fluoroquinolones and third-generation cephalosporins.

Hypophosphatemia in Dogs With Presumptive Sepsis: A Retrospective Study (2008-2018).

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 <2.7 mg/dL. Sepsis was presumed where ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria were satisfied associated with a documented or highly suspected infection. Variables were assessed for normality using the D'Agostino-Pearson test. Continuous variables were compared between groups using the Mann-Whitney 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.