Publications by authors named "Christina Osborne"

24 Publications

  • Page 1 of 1

Cognitive Dysfunction after Out-of-Hospital Cardiac Arrest: Rate of Impairment and Clinical Predictors.

Resuscitation 2021 May 12. Epub 2021 May 12.

Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Canada; School of Psychology, University of Ottawa, Ottawa, Canada.

Background: The purpose of this study was to evaluate the rate and domains of cognitive impairment in out-of-hospital cardiac arrest (OHCA) survivors, as compared to patients who experienced a myocardial infarction (MI), and to explore mechanisms and predictors of this impairment.

Methods And Results: OHCA survivors with "good" neurological recovery (i.e., Cerebral Performance Categories Scale≤2) (n=79), as well as a control group of MI patients (n=69), underwent a comprehensive neuropsychological assessment. Forty-three percent of OHCA survivors were cognitively impaired (in the lowest decile on a global measure of cognitive functioning). Rates of impairment were approximately 6 times higher in the OHCA group than the MI group. Attention, memory, language and executive function were affected. Downtime was a significant predictor of cognitive impairment; the interaction between downtime and immediate intervention was significant such that, at short downtimes, receiving cardiopulmonary resuscitation (CPR) or defibrillation within 1minute of collapse predicted less cognitive impairment.

Conclusions: OHCA survivors--even those with seemingly good neurological recovery--are at risk for cognitive impairment. Cognitive rehabilitation may be an important consideration post-OHCA.
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http://dx.doi.org/10.1016/j.resuscitation.2021.05.002DOI Listing
May 2021

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

J Pediatr 2021 02 16;229:33-40. Epub 2020 Oct 16.

Johns Hopkins Children's Center, Johns Hopkins School of Medicine, Baltimore, MD.

Objective: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US.

Study Design: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated.

Results: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided.

Conclusions: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.
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http://dx.doi.org/10.1016/j.jpeds.2020.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566788PMC
February 2021

Severe SARS-CoV-2 Infection in a Pediatric Patient Requiring Extracorporeal Membrane Oxygenation.

Case Rep Pediatr 2020 9;2020:8885022. Epub 2020 Oct 9.

Children's Hospital Colorado, Section of Emergency Medicine, Aurora, CO, USA.

The overwhelming majority of pediatric cases of SARS-CoV-2 infection are mild or asymptomatic with only a handful of pediatric deaths reported. We present a case of severe COVID-19 infection in a pediatric patient with signs of hyperinflammation and consumptive coagulopathy requiring intubation and extracorporeal membrane oxygenation (ECMO) and eventual death due to ECMO complications.
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http://dx.doi.org/10.1155/2020/8885022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547361PMC
October 2020

Temporal airway microbiome changes related to ventilator-associated pneumonia in children.

Eur Respir J 2021 Mar 18;57(3). Epub 2021 Mar 18.

Biostatistics and Informatics, University of Colorado, Colorado School of Public Health, Aurora, CO, USA.

We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children.Using a multicentre prospective study of children aged 31 days to 18 years requiring mechanical ventilation support for >72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 Centers for Disease Control and Prevention paediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case-control comparisons and unsupervised clustering.Out of 366 eligible subjects, 66 (15%) developed VAP at a median of 5 (interquartile range 3-5) days post intubation. At intubation, there was no difference in total bacterial load (TBL), but Shannon diversity and the relative abundance of , Lactobacillales and were lower for VAP subjects non-VAP subjects. However, higher TBL on each sequential day was associated with a lower hazard (hazard ratio 0.39, 95% CI 0.23-0.64) for developing VAP, but sequential values of diversity were not associated with VAP. Similar findings were observed from the matched analysis and unsupervised clustering. The most common dominant VAP pathogens included species (19%), (14%) and / (10%). and were also identified as dominant organisms in several subjects.In mechanically ventilated children, changes over time in microbial factors were marginally associated with VAP risk, although these changes were not suitable for predicting VAP in individual patients. These findings suggest that focusing exclusively on pathogen burden may not adequately inform VAP diagnosis.
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http://dx.doi.org/10.1183/13993003.01829-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979474PMC
March 2021

Foreign Body Esophageal Perforation Leading to Multifocal Brain Abscesses: A Case Report.

J Emerg Med 2020 Oct 18;59(4):e131-e135. Epub 2020 Jul 18.

Department of Emergency Medicine, Denver Health and Hospital Authority, Denver, Colorado.

Background: Among those aged 5 years or younger, foreign bodies are the fourth most common pediatric exposure reported to the American Association of Poison Control Centers. Although the majority of ingested foreign bodies pass through the gastrointestinal tract without complication, those that do not spontaneously pass can lead to a number of serious complications, such as gastrointestinal obstruction or perforation, which can be complicated by bleeding from aortoesophageal fistula, secondary mediastinitis, peritonitis, esophageal or gastrointestinal fistula formation, and abscesses.

Case Report: We present the case of a 10-month-old child who presented with new-onset focal seizure in the setting of multiple brain abscesses, ultimately found to be due to esophageal perforation from a retained, metallic esophageal foreign body. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Foreign bodies that are retained for longer than 24 h after ingestion have been associated with a higher risk of complications because they are less likely to pass spontaneously through the gastrointestinal tract. Early identification and removal of foreign bodies is necessary to prevent subsequent complications. In patients who have a subacute history of cough, gagging, vomiting, and decreased oral intake with an otherwise unknown cause, foreign-body ingestion or aspiration should be considered. In addition, central nervous system abscess and infection should be considered in patients with concerns about previous foreign body ingestion or aspiration and who are newly presenting with fever, focal neurologic changes, and irritability.
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http://dx.doi.org/10.1016/j.jemermed.2020.06.025DOI Listing
October 2020

Safety and Efficacy of Femoral Access vs Radial Access in ST-Segment Elevation Myocardial Infarction: The SAFARI-STEMI Randomized Clinical Trial.

JAMA Cardiol 2020 02;5(2):126-134

Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Importance: Among patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), a survival benefit associated with radial access compared with femoral access remains controversial.

Objective: To assess whether there is a survival benefit when radial access is used instead of femoral access among patients with STEMI referred for primary PCI.

Design, Setting, And Participants: This multicenter, open-label, randomized clinical trial was conducted at 5 PCI centers in Canada. In total, 2292 patients with STEMI referred for primary PCI were enrolled between July 2011 and December 2018, with a 30-day follow-up. The primary analyses were conducted based on the intention-to-treat population.

Interventions: Patients were randomized to radial access (n = 1136) or to femoral access (n = 1156) for PCI.

Main Outcomes And Measures: Initially, the primary outcome was bleeding, but this outcome was modified to 30-day all-cause mortality following the recommendation of the granting agency. Secondary outcomes included recurrent myocardial infarction, stroke, and Thrombolysis in Myocardial Infarction-defined major or minor bleeding.

Results: Among the 2292 patients enrolled, the mean (SD) age of the patients randomized to radial access was 61.6 (12.3) years and to femoral access was 62.0 (12.1) years, with 883 male patients in the radial access and 901 male patients in the femoral access group. The trial was stopped early following a futility analysis. Primary PCI was performed in 1082 of 1136 patients (95.2%) in the radial access group and 1109 of 1156 patients (95.9%) in the femoral access group. Bivalirudin was administered to 1001 patients (88.1%) in the radial access group and to 1068 patients (92.4%) in the femoral access group, whereas glycoprotein IIb/IIIa inhibitors were administered in only 69 patients (6.1%) in the radial access group and 68 patients (5.9%) in the femoral access group. A vascular closure device was used in 789 patients (68.3%) in the femoral group. The primary outcome, 30-day all-cause mortality, occurred in 17 patients (1.5%) assigned to radial access and in 15 patients (1.3%) assigned to femoral access (relative risk [RR], 1.15; 95% CI, 0.58-2.30; P = .69). There were no significant differences between patients assigned to radial and femoral access in the rates of reinfarction (1.8% vs 1.6%; RR, 1.07; 95% CI, 0.57-2.00; P = .83), stroke (1.0% vs 0.4%; RR, 2.24; 95% CI, 0.78-6.42; P = .12), and bleeding (1.4% vs 2.0%; RR, 0.71; 95% CI, 0.38-1.33; P = .28).

Conclusions And Relevance: No significant differences were found for survival or other clinical end points at 30 days after the use of radial access vs femoral access in patients with STEMI referred for primary PCI. However, small absolute differences in end points cannot be definitively refuted given the premature termination of the trial.

Trial Registration: ClinicalTrials.gov identifier: NCT01398254.
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http://dx.doi.org/10.1001/jamacardio.2019.4852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990931PMC
February 2020

Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study.

Lancet Infect Dis 2020 02 16;20(2):230-239. Epub 2019 Dec 16.

Section of Infectious Diseases, School of Medicine, University of Colorado, Aurora, CO, USA; Children's Hospital Colorado, Aurora, CO, USA.

Background: In May, 2018, Children's Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak.

Methods: In this retrospective observational cohort study, children (younger than 18 years) who presented to Children's Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018.

Findings: Between March 10 and Nov 10, 2018, 74 children presenting to Children's Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0-31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1-2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover.

Interpretation: This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance.

Funding: None.
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http://dx.doi.org/10.1016/S1473-3099(19)30632-2DOI Listing
February 2020

Ending student mistreatment: early successes and continuing challenges.

Med Educ Online 2020 Dec;25(1):1690846

Emergency Medicine and Medicine and Associate Dean for Faculty Affairs, University of Colorado School of Medicine, Aurora, CO, USA.

Student mistreatment represents an ongoing challenge for US medical schools. Students experiencing mistreatment may become marginalized and cynical, and they have higher rates of burnout, depression and substance use disorders. Although numerous attempts to eliminate mistreatment have been proposed, best practices remain elusive. We formed a unique student-faculty collaboration (the Ending Mistreatment Task Force) that allowed all voices to be heard and enabled identification of five interventions to reduce mistreatment. The EMTF developed and implemented five key interventions: 1) a shared mistreatment definition; 2) measures to increase faculty accountability, including adding professionalism expectations to faculty members' contracts and performance reviews; 3) a Professionalism Office to respond promptly to students' reports of mistreatment and provide feedback to faculty; 4) tools to help teachers provide authentic learning environments for students, while addressing generational misunderstandings; and 5) student-produced videos, helping faculty understand the impact of mistreatment as seen through students' eyes. These interventions occurred at one medical school where mistreatment reports were consistently above national averages. Over 6 years, the interventions helped reduce the rate of student-reported mistreatment by 36% compared with a 4% decline across all US medical schools. The collaborations between students and faculty helped each party identify unexpected misunderstandings and challenges. We learned that students want hard questions, although faculty are often afraid to challenge students for fear of offending them or being reported. We clarified differences between mistreatment and sub-optimal learning environments and openly discussed the pervasive opinion that 'some' mistreatment is important for learning. We also identified ongoing challenges, including the need to solicit residents' perspectives regarding mistreatment and develop proper responses to disrespectful comments directed at patients, family and colleagues. The collaboration reinforced students' and faculty members' shared commitment to upholding a respectful learning and clinical care environment and ending mistreatment.
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http://dx.doi.org/10.1080/10872981.2019.1690846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896410PMC
December 2020

Disseminated Histoplasmosis as an AIDS-Defining Illness Presenting as Fever of Unknown Origin in an 11-Year-Old Female.

Case Rep Pediatr 2019 13;2019:9417102. Epub 2019 May 13.

Pediatric Infectious Diseases, University of Colorado School of Medicine, 13123 East 16th Avenue, Box 055, Aurora, CO 80045, USA.

A previously healthy 11-year-old female, who emigrated from Central America four years prior, was admitted with eight days of fever, night sweats, and anorexia. Past medical history included severe bronchiolitis, varicella, and hepatitis A as a child. Upon admission, her physical exam was significant for nontender cervical lymphadenopathy, intermittent erythematous papules on the upper extremities, and mild abdominal tenderness. Initial laboratory studies revealed leukopenia, anemia, elevated inflammatory markers, and antibodies to HIV-1 in the patient's serum and cerebrospinal fluid. Computed tomography scan was remarkable for many small nodules throughout the lungs and widespread lymphadenopathy. Additional testing confirmed the diagnosis of HIV/AIDS with a CD4 count of 52 cells/mm, complicated by disseminated histoplasmosis. This case is significant because it represents a late presentation of vertically transmitted HIV with disseminated histoplasmosis in a nonendemic region as the AIDS-defining illness. This highlights the importance of maintaining a broad differential for opportunistic infections, especially among those who have spent a significant amount of time in a country where unusual pathogens may be more common. This case also considers the utility of antigen testing as a sensitive diagnostic test in immunocompromised patients.
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http://dx.doi.org/10.1155/2019/9417102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535884PMC
May 2019

Neurologic Manifestations of Influenza A(H3N2) Infection in Children During the 2016-2017 Season.

J Pediatric Infect Dis Soc 2020 Feb;9(1):71-74

Division of Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora.

Among 182 children with influenza infection in 2016-2017, 18% had neurologic manifestations of influenza (NMI), including seizures and encephalopathy; 85% of these children were infected with the H3N2 strain. Children with NMI had 3.5-times-higher odds of having a neurologic comorbidity than those without NMI and a 10-fold increased odds of hospitalization.
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http://dx.doi.org/10.1093/jpids/piy130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317155PMC
February 2020

In-hospital outcomes of STEMI patients on warfarin undergoing primary PCI.

Catheter Cardiovasc Interv 2019 01 30;93(1):41-47. Epub 2018 Sep 30.

The CAPITAL Research Group, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Objectives: We sought to describe the safety and efficacy outcomes of patients on warfarin presenting with ST-elevation myocardial infarction (STEMI).

Background: Limited data exist on the outcomes and optimal management of STEMI patients on warfarin undergoing primary percutaneous coronary intervention (PCI).

Methods: Baseline characteristics and outcomes were prospectively collected for 2,390 consecutive STEMI patients referred for primary PCI. Patients were stratified based on warfarin use at baseline. The primary safety endpoint was the rate of in-hospital bleeding (a composite of major bleeding or minor bleeding) according to the thrombolysis in myocardial infarction (TIMI) classification. Efficacy endpoints included major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, as well as intracranial bleeding, cardiogenic shock, and length of stay. Multiple logistic regression was used to determine if warfarin was independently associated with bleeding and MACE.

Results: Warfarin patients (n = 59 vs. n = 2,331) were significantly older (73.2 years vs. 61.7 years; P < 0.01), and more likely to present as Killip Class IV (13.6% vs. 2.7%; P < 0.01). TIMI major/minor bleeding occurred in 30.4% of the warfarin patients and 14.2% of the control patients (P < 0.01). After adjustment warfarin was independently associated with an increased risk of bleeding (OR 2.08; P = 0.04). Warfarin patients also had an increased frequency of MACE (20.3% vs. 5.9%; P < 0.01), though this was not significant after adjustment (OR 2.00; P = 0.10).

Conclusions: STEMI patients on warfarin referred for primary PCI are more likely to experience bleeding. New strategies are needed to optimize the management and minimize bleeding in this high-risk population.
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http://dx.doi.org/10.1002/ccd.27720DOI Listing
January 2019

Optimal mean arterial pressure in comatose survivors of out-of-hospital cardiac arrest: An analysis of area below blood pressure thresholds.

Resuscitation 2018 07 22;128:175-180. Epub 2018 Apr 22.

Department of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Aim Of The Study: To determine the optimal mean arterial pressure (MAP) during the early-to-intermediate phase care of comatose survivors of out-of-hospital cardiac arrest (OHCA).

Methods: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm. Using blood pressure-over-time plots, we calculated the area below pre-specified MAP thresholds (ABT; mmHg*hours) during the first 96 h of admission. We used incremental MAP thresholds ranging between 65 and 85 mmHg. Logistic regression analyses were used to examine the association between ABT and clinical outcomes for each MAP threshold and to adjust for age, duration of cardiac arrest, and bystander CPR. The primary outcome was severe neurological dysfunction as defined by a cerebral performance category (CPC) ≥3.

Results: We identified 122 consecutive OHCA patients meeting inclusion criteria. The rate of the primary outcome was 33%. There was a significant association between ABT and the rate of the primary outcome when MAP thresholds of 60 (p = 0.01), 65 (p < 0.01), 70 (p < 0.01), 75 (p < 0.01), and 80 mmHg (p < 0.01) were used. This association was lost once a MAP threshold of 85 mmHg was reached (p = 0.63). In the adjusted analysis, the association between ABT and the primary outcome was no longer present when the MAP threshold reached 75 mmHg.

Conclusions: In comatose survivors of OHCA with an initial shockable rhythm, higher ABT is associated with increased rates of severe neurological dysfunction when MAP thresholds <75 mmHg are used. The current findings support the hypothesis that higher MAP targets (≥75 mmHg) may be indicated in this patient population.
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http://dx.doi.org/10.1016/j.resuscitation.2018.04.028DOI Listing
July 2018

Impact of mean arterial pressure on clinical outcomes in comatose survivors of out-of-hospital cardiac arrest: Insights from the University of Ottawa Heart Institute Regional Cardiac Arrest Registry (CAPITAL-CARe).

Resuscitation 2017 04 18;113:27-32. Epub 2017 Jan 18.

Department of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address:

Aim Of The Study: We sought to assess the relationship between mean arterial pressure (MAP) and clinical outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA).

Methods: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm treated with targeted temperature management. We examined clinical outcomes in relation to mean MAP (measured hourly) during the first 96h of hospitalization. Co-primary outcomes were the rates of death and severe neurological dysfunction at discharge.

Results: In 122 patients meeting inclusion criteria, death occurred in 29 (24%) and severe neurological dysfunction in 39 (32%). Higher mean MAPs were associated with lower odds of death (OR 0.55 per 5mmHg increase; 95%CI 0.38-0.79; p=0.002) and severe neurological dysfunction (OR 0.66 per 5mmHg increase; 95%CI 0.48-0.90; p=0.01). After adjustment for differences in patient, index event, and treatment characteristics, higher mean MAPs remained associated with lower odds of death (OR 0.60 per 5mmHg increase; 95%CI 0.40-0.89; p=0.01) but not severe neurological dysfunction (OR 0.73 per 5mmHg increase; 95%CI 0.51-1.03; p=0.07). The relationship between mean MAP and the odds of death (p-interaction=0.03) and severe neurological dysfunction (p-interaction=0.03) was attenuated by increased patient age.

Conclusion: In comatose survivors of OHCA treated with target temperature management, a higher mean MAP during the first 96h of admission is associated with increased survival. The association between mean MAP and clinical outcomes appears to be attenuated by increased age.
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http://dx.doi.org/10.1016/j.resuscitation.2017.01.007DOI Listing
April 2017

Hyperglycaemia in comatose survivors of out-of-hospital cardiac arrest.

Eur Heart J Acute Cardiovasc Care 2018 Aug 3;7(5):442-449. Epub 2017 Jan 3.

Department of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Background: The optimal blood glucose target during the early hospitalisation of comatose survivors of out-of-hospital cardiac arrest (OHCA) has not been established.

Methods: In a retrospective cohort study, we examined clinical outcomes in relation to mean blood glucose during the first 96 hours of hospital admission in comatose survivors of OHCA with an initial shockable rhythm. Mean blood glucose was assessed as a continuous (primary analysis) and categorical variable: <6 mmol/L, 6 to <8 mmol/L and ⩾8 mmol/L. Co-primary outcomes were the rates of death during the index hospitalisation and severe neurological dysfunction at discharge. We used multivariable logistic regression analyses to adjust for baseline differences in patient and index event characteristics.

Results: Among 122 eligible patients, death and severe neurological dysfunction occurred in 29 (24%) and 40 (33%) patients, respectively. Higher mean blood glucose levels during the first 96 hours of admission were associated with increased odds of death (odds ratio (OR): 1.50; 95% confidence interval (CI): 1.17-1.92; p = 0.001) and severe neurological dysfunction (OR: 1.42; 95% CI: 1.11-1.80; p = 0.004). The associations between mean blood glucose and the odds of death (OR: 1.35; 95% CI: 1.04-1.76; p = 0.02) and severe neurological dysfunction (OR: 1.28; 95% CI: 1.00-1.64; p = 0.05) persisted after adjusting for age, time from cardiac arrest to return of spontaneous circulation (ROSC) and vasoactive agent use. There was no interaction between age, time from cardiac arrest to ROSC or a history of diabetes mellitus and the relationship between mean blood glucose and co-primary outcomes.

Conclusions: In comatose survivors of OHCA with initial shockable rhythms, higher mean blood glucose levels during the first 96 hours of admission are associated with increased rates of death and severe neurological dysfunction.
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http://dx.doi.org/10.1177/2048872616684685DOI Listing
August 2018

Safety and Efficacy of a Pharmacoinvasive Strategy in ST-Segment Elevation Myocardial Infarction: A Patient Population Study Comparing a Pharmacoinvasive Strategy With a Primary Percutaneous Coronary Intervention Strategy Within a Regional System.

JACC Cardiovasc Interv 2016 10;9(19):2014-2020

University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address:

Objectives: This study investigated the safety and efficacy of a pharmacoinvasive strategy compared with a primary percutaneous coronary intervention (PCI) strategy for ST-segment elevation myocardial infarction (STEMI) in the context of a real-world system.

Background: Primary PCI continues to be the optimal reperfusion therapy; however, in areas where PCI centers are not readily available, a pharmacoinvasive strategy has been proposed.

Methods: The University of Ottawa Heart Institute regional STEMI system provides a primary PCI strategy for patients presenting within a 90-km radius from the PCI center, and a pharmacoinvasive strategy for patients outside this limit. We included all confirmed STEMI patients between April 2009 and May 2011. The primary efficacy outcome was a composite of mortality, reinfarction, or stroke and the primary safety outcome was major bleeding.

Results: We identified 236 and 980 consecutive patients enrolled in pharmacoinvasive and primary PCI strategies, respectively. The median door-to-needle time was 31 min in the pharmacoinvasive group and the median door-to-balloon time was 95 min in the primary PCI group. In a multivariable model, there was no significant difference in the primary efficacy outcome (odds ratio: 1.54; p = 0.21); however, the propensity for more bleeding with a pharmacoinvasive strategy approached statistical significance (odds ratio: 2.02; p = 0.08).

Conclusions: Within the context of a STEMI system, a pharmacoinvasive strategy was associated with similar rates of the composite of mortality, reinfarction, or stroke as compared with a primary PCI strategy; however, there was a propensity for more bleeding with a pharmacoinvasive strategy.
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http://dx.doi.org/10.1016/j.jcin.2016.07.004DOI Listing
October 2016

From Coronary Care Units to Cardiac Intensive Care Units: Recommendations for Organizational, Staffing, and Educational Transformation.

Can J Cardiol 2016 10 8;32(10):1204-1213. Epub 2015 Dec 8.

Vancouver General Hospital, University of British Columbia, British Columbia, Canada.

Medical care in Canadian cardiac units has changed considerably over the past 3 decades in response to an increasingly complex and diverse patient population admitted with acute cardiac pathology. To maintain the highest level of care for these patients, there is a pressing need to evolve traditional coronary care units into contemporary cardiac intensive care units. In this article we aim to highlight the current variations in Canadian units, develop approaches to overcome logistical and infrastructural obstacles, and propose staffing and training recommendations that would allow for the establishment of contemporary cardiac intensive care units.
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http://dx.doi.org/10.1016/j.cjca.2015.11.021DOI Listing
October 2016

Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1.

J Virol 2015 Sep 17;89(17):8816-27. Epub 2015 Jun 17.

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

Unlabelled: Coronavirus spike (S) glycoproteins mediate receptor binding, membrane fusion, and virus entry and determine host range. Murine betacoronavirus (β-CoV) in group A uses the N-terminal domain (NTD) of S protein to bind to its receptor, whereas the β-CoVs severe acute respiratory syndrome CoV in group B and Middle East respiratory syndrome CoV in group C and several α-CoVs use the downstream C domain in their S proteins to recognize their receptor proteins. To identify the receptor-binding domain in the spike of human β-CoV HKU1 in group A, we generated and mapped a panel of monoclonal antibodies (MAbs) to the ectodomain of HKU1 spike protein. They did not cross-react with S proteins of any other CoV tested. Most of the HKU1 spike MAbs recognized epitopes in the C domain between amino acids 535 and 673, indicating that this region is immunodominant. Two of the MAbs blocked HKU1 virus infection of primary human tracheal-bronchial epithelial (HTBE) cells. Preincubation of HTBE cells with a truncated HKU1 S protein that includes the C domain blocked infection with HKU1 virus, but preincubation of cells with truncated S protein containing only the NTD did not block infection. These data suggest that the receptor-binding domain (RBD) of HKU1 spike protein is located in the C domain, where the spike proteins of α-CoVs and β-CoVs in groups B and C bind to their specific receptor proteins. Thus, two β-CoVs in group A, HKU1 and murine CoV, have evolved to use different regions of their spike glycoproteins to recognize their respective receptor proteins.

Importance: Mouse hepatitis virus, a β-CoV in group A, uses the galectin-like NTD in its spike protein to bind its receptor protein, while HCoV-OC43, another β-CoV in group A, uses the NTD to bind to its sialic-acid containing receptor. In marked contrast, the NTD of the spike glycoprotein of human respiratory β-CoV HKU1, which is also in group A, does not bind sugar. In this study, we showed that for the spike protein of HKU1, the purified C domain, downstream of the NTD, could block HKU1 virus infection of human respiratory epithelial cells, and that several monoclonal antibodies that mapped to the C domain neutralized virus infectivity. Thus, the receptor-binding domain of HKU1 spike glycoprotein is located in the C domain. Surprisingly, two β-CoVs in group A, mouse hepatitis virus and HKU1, have evolved to use different regions of their spike glycoproteins to recognize their respective receptors.
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http://dx.doi.org/10.1128/JVI.03737-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524053PMC
September 2015

Viral gastroenteritis in children in Colorado 2006-2009.

J Med Virol 2015 Jun 16;87(6):931-9. Epub 2015 Mar 16.

University of Colorado School of Medicine, Aurora, Colorado, 80045.

Acute gastroenteritis accounts for a significant burden of medically attended illness in children under the age of five. For this study, four multiplex reverse transcription PCR assays were used to determine the incidence of adenovirus, astrovirus, coronavirus, norovirus GI and GII, rotavirus, and sapovirus in stool samples submitted for viral electron microscopy (EM) to the Children's Hospital Colorado. Of 1105 stool samples available, viral RNA/DNA was detected in 247 (26.2%) of 941 pediatric samples (median age = 2.97 years, 54% male) with 28 (3.0%) positive for more than one virus. Adenovirus, astrovirus, norovirus GI, norovirus GII, rotavirus, and sapovirus were detected in 95 (10.0%), 33 (3.5%), 8 (0.9%), 90 (9.6%), 49 (5.2%), and 2 (0.2%) of the pediatric samples, respectively. No coronaviruses were identified. Sequencing of norovirus positive samples indicated an outbreak of norovirus strain GII.4 in 2006 with evidence of numerous circulating strains. Multiple samples from the same immunocompromised patients demonstrated symptomatic shedding of norovirus for up to 32 weeks and astrovirus for 12 weeks. RT-PCR detected 99 of 111 (89%) adenovirus-positive samples versus 12 (11%) by EM, and 186 of 192 (97%) sapovirus/astrovirus/norovirus-positive samples versus 21 (11%) by EM. Noroviruses and adenoviruses are common causes of gastroenteritis in children. Immunocompromised patients can be infected with multiple viruses and shed viruses in their stools for prolonged periods. This data support the superiority of RT-PCR compared to EM for diagnosis of viral gastroenteritis.
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http://dx.doi.org/10.1002/jmv.24022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166904PMC
June 2015

Superiority of ticagrelor over clopidogrel in patients after cardiac arrest undergoing therapeutic hypothermia.

Can J Cardiol 2014 Nov 15;30(11):1396-9. Epub 2014 Aug 15.

Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address:

Current guidelines suggest that patients undergoing percutaneous coronary intervention (PCI) receive dual-antiplatelet therapy. There are limited data on the pharmacodynamics of P2Y12 inhibitors in patients with cardiac arrest and return of spontaneous circulation (ROSC) undergoing PCI and therapeutic hypothermia (TH). Accordingly, we compared inhibition of platelet reactivity in patients undergoing TH receiving clopidogrel or ticagrelor. Notably, clopidogrel was ineffective in lowering platelet reactivity, with ticagrelor providing a more rapid (within 4 hours) and sustained reduction (6 days) in platelet reactivity. Pending outcome-based studies, ticagrelor should be used preferentially in patients who have ROSC and are undergoing PCI and TH.
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http://dx.doi.org/10.1016/j.cjca.2014.07.745DOI Listing
November 2014

Endovascular cooling catheter related thrombosis in patients undergoing therapeutic hypothermia for out of hospital cardiac arrest.

Resuscitation 2014 Oct 27;85(10):1354-8. Epub 2014 Jun 27.

Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada. Electronic address:

Background: Therapeutic hypothermia improves neurologic outcome and survival in patients following out-of-hospital cardiac arrest (OHCA). Endovascular cooling devices are commonly used to rapidly achieve and maintain hypothermia. The use of these devices may be associated with catheter related thrombosis. The objective of this study was to determine the risk of catheter related thrombosis associated with the use of an endovascular cooling catheter in patients referred for therapeutic hypothermia following OHCA.

Methods And Results: We conducted a retrospective cohort study on consecutive patients, referred for therapeutic hypothermia following OHCA, between February 2012 and May 2013. Of 80 patients initially treated with therapeutic hypothermia, 61 completed the cooling protocol using an endovascular cooling device. The primary outcome was catheter related thrombosis defined as evidence of thrombus in the inferior vena cava, deep vein thrombosis or pulmonary embolism during the index hospitalization. We further evaluated the incidence of the primary outcome between patients on dose adjusted intravenous unfractionated heparin compared to those on a subcutaneous prophylactic regimen alone. Catheter related thrombosis was observed in 9/61 (14.7%), with nine events in the prophylaxis group compared to none in the full dose unfractionated heparin group (22.0% vs. 0.0%, p=0.02).

Conclusions: The use of endovascular catheters for induction of therapeutic hypothermia is associated with a high rate of catheter related thrombosis. This risk appears to be abrogated with dose adjusted unfractionated heparin infusion.
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http://dx.doi.org/10.1016/j.resuscitation.2014.05.029DOI Listing
October 2014

Promoter methylation and tissue-specific transcription of the α7 nicotinic receptor gene, CHRNA7.

J Mol Neurosci 2012 Jun 4;47(2):389-400. Epub 2011 Nov 4.

Department of Psychiatry, University of Colorado Denver, Aurora, CO 80045, USA.

The α7 nicotinic acetylcholine receptor is known to regulate a wide variety of developmental and secretory functions in neural and non-neural tissues. The mechanisms that regulate its transcription in these varied tissues are not well understood. Epigenetic processes may play a role in the tissue-specific regulation of mRNA expression from the α7 nicotinic receptor subunit gene, CHRNA7. Promoter methylation was correlated with CHRNA7 mRNA expression in various tissue types and the role of DNA methylation in regulating transcription from the gene was tested by using DNA methyltransferase (DNMT1) inhibitors and methyl donors. CHRNA7 mRNA expression was silenced in SH-EP1 cells and bisulfite sequencing PCR revealed the CHRNA7 proximal promoter was hypermethylated. The proximal promoter was hypomethylated in the cell lines HeLa, SH-SY5Y, and SK-N-BE which express varying levels of CHRNA7 mRNA. Expression of CHRNA7 mRNA was present in SH-EP1 cells after treatment with the methylation inhibitor, 5-aza-2-deoxycytidine (5-Aza-CdR), and increased in SH-EP1 and HeLa cells using another methylation inhibitor, zebularine (ZEB). Transcription from the CHRNA7 promoter in HeLa cells was increased when the methyl donor methionine (MET) was absent from the media. Using methylation-sensitive restriction enzyme analysis (MSRE), there was a strong inverse correlation between CHRNA7 mRNA levels and promoter DNA methylation across several human tissue types. The results support a role for DNA methylation of the proximal promoter in regulation of CHRNA7 transcription.
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http://dx.doi.org/10.1007/s12031-011-9663-7DOI Listing
June 2012

Alphacoronaviruses in New World bats: prevalence, persistence, phylogeny, and potential for interaction with humans.

PLoS One 2011 May 12;6(5):e19156. Epub 2011 May 12.

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019156PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093381PMC
May 2011

Unique structure of the M loop region of β1-tubulin may contribute to size variability of platelets in the family Felidae.

Vet Clin Pathol 2010 Dec 7;39(4):417-23. Epub 2010 Oct 7.

Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.

Background: Platelet size is relatively uniform in mammals except for domestic cats. Uniform platelet production by megakaryocytes can be disrupted if microtubule assembly or dynamics is impaired. Mutations in the gene encoding β1-tubulin have been documented in dogs and people, and the resulting microtubule effects have been associated with production of large platelets.

Objectives: The objectives of this study were to evaluate morphology of platelets on feline blood smears, determine the gene sequences encoding β1-tubulin in members of the family Felidae, and compare the findings with those in other mammalian species to determine whether predicted structural differences in β1-tubulin that might affect microtubule stability or assembly were present.

Methods: At least 100 platelets/smear on blood smears from 15 domestic cats and 88 big cats were evaluated to assess platelet size variability. Platelet-derived cDNA obtained from a domestic cat and genomic DNA isolated from blood samples of domestic cats and other members of the family Felidae were analyzed by PCR using primers specific for β1-tubulin. Gene sequences obtained were compared with those of other common mammals.

Results: Two differences in gene sequence were found in a highly conserved region encoding the M loop of β1-tubulin in members of the family Felidae compared with sequences from other species. Platelet size variation was present in big cats and domestic cats. In addition, a rare amino acid change was documented in the C-terminal region encoding the H11 helix in domestic cats.

Conclusion: Members of the family Felidae have an altered M loop region in β1-tubulin compared with other mammals. This variation may contribute to the observed platelet size variability.
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http://dx.doi.org/10.1111/j.1939-165X.2010.00256.xDOI Listing
December 2010

Sebaceous adenitis in a 7-year-old Arabian gelding.

Can Vet J 2006 Jun;47(6):583-6

Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4.

A 7-year-old Arabian gelding was presented with a 9-month history of progressive patches of nonpruritic scaling, crusting, alopecia, and leukoderma of the periocular areas and muzzle, becoming generalized over time. Sebaceous adenitis was diagnosed on histopathologic examination. Lesions resolved without treatment, coinciding with regression of a sarcoid on the neck.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1461412PMC
June 2006