Joanne Duncan - Academia.edu (original) (raw)

Papers by Joanne Duncan

TH Open, 2020

Introduction The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed ... more Introduction The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed a standardized perioperative management strategy in patients with atrial fibrillation who were taking a direct oral anticoagulant (DOAC) and required an elective surgery or procedure. The aim of this substudy is to analyze the safety of this management strategy across different patient subgroups, according to four presurgical variables: (1) DOAC type and dose, (2) surgery/procedure bleed risk, (3) patient renal function, and (4) age. Methods Clinical outcomes analyzed included major bleeding (MB), arterial thromboembolism, any bleeding, and any thromboembolism. We used descriptive statistics to summarize clinical outcomes, where the frequency, proportion, and 95% confidence interval were reported. Fisher's exact tests were used for testing the null hypothesis of independence between the clinical outcome and patient characteristic, where the test p-values were reported. Results There ...

Nature Medicine, 2021

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although ... more The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma...

Trials, 2021

Background Convalescent plasma has been used for numerous viral diseases including influenza, sev... more Background Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. Methods CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting pati...

Canadian Journal of General Internal Medicine, 2020

BackgroundThe sequence of second-line therapy used for the treatment of immune thrombocytopenia (... more BackgroundThe sequence of second-line therapy used for the treatment of immune thrombocytopenia (ITP) is variable. This study aimed to describe the types and sequences of second-line therapies for a large cohort of ITP patients in Canada. MethodsWe completed a retrospective cohort study of the McMaster ITP Registry. We included patients with primary or secondary ITP who had received one or more second-line therapies including any of the splenectomy, rituximab, danazol, dapsone, or thrombopoietin receptor agonists (TPO-RAs), or immunosuppressant medications. Immunosuppressant medications included azathioprine, cyclophosphamide, cyclosporine, or mycophenolate given alone or in combination. ResultsWe identified 204 ITP patients who had received one or more second-line therapies. The most common second-line therapies were immunosuppressant medications (n = 106; 52.0%), splenectomy (n = 106; 52.0%), TPO-RAs (n = 75; 36.8%), danazol (n = 73; 35.8%), and rituximab (n = 67; 32.8%). For pati...

Blood Advances, 2020

The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study prospectively evaluate... more The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study prospectively evaluated a prespecified periprocedural-interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Logistic regression analyses were performed to identify clinical parameters associated with residual DOAC levels ≥30 ng/mL or ≥50 ng/mL. Patients undergoing low-bleed-risk procedures were more likely to have residual levels of ≥30 ng/mL and ≥50 ng/mL. For low-risk procedures, age ≥75 years, female sex, a creatinine clearance (CrCl) <50 mL/min, and an interruption of <36 hours were associated with a greater likelihood of levels ≥30 ng/mL, whereas age ≥75 years, female sex, a CrCl of <50 mL/min, and standard DOAC dosing were associated with levels ≥50 ng/mL. For high-risk procedures, weight of <70 kg, CrCl <50 mL/min, and standard DOAC dosing were associated with residual levels ≥30 ng/mL, whereas female sex was associated with levels ≥50 ng/mL...

Journal of Virology, 1999

The herpes simplex virus (HSV) proteins VP16 and ICP0 play key roles in stimulating the onset of ... more The herpes simplex virus (HSV) proteins VP16 and ICP0 play key roles in stimulating the onset of the viral lytic cycle. We sought to explore the regulatory links between these proteins by studying the phenotypes of viral mutants in which the activation functions of both were simultaneously inactivated. This analysis unexpectedly revealed that truncation of the C-terminal transcriptional activation domain of VP16 (allele V422) in an ICP0-deficient background almost completely eliminated immediate-early gene expression and virus replication in Vero and HEL cells. The doubly mutant viral genome persisted in a quiescent state for at least 10 days in HEL cells infected at high multiplicity and could be reactivated by superinfection with wild-type HSV. In contrast, the in 1814 VP16 mutation produced a markedly less severe phenotype in the same ICP0-deficient background. These data demonstrate that expression of the immediate-early genes requires ICP0 when the C-terminal activation domain ...

Thrombosis and haemostasis, Dec 1, 2017

Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) f... more Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol. Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is ...

Background: It is hypothesised that complex interactions between genetic and environmental factor... more Background: It is hypothesised that complex interactions between genetic and environmental factors give rise to allergy and asthma in childhood. The Canadian Healthy Infant Longitudinal Development (CHILD) study was designed to explore these factors. Methods: CHILD is a longitudinal, general population birth cohort study following infants from mid-pregnancy to age 5 years. Over this time period, biological samples, questionnaires, clinical measures and environmental data are collected. Results: A total of 3624 families have been recruited, and many thousands of samples and questionnaires have been collected, annotated, and archived. This report outlines the rationale and methodology for collecting and storing diverse biological samples from parents and children in this study, and the mechanisms for their release for analyses. Conclusions: The CHILD sample and data repository is a tremendous current and future resource and will provide a wealth of information not only informing studies of asthma and allergy, but also potentially in many other aspects of health relevant for Canadian infants and children.

Pediatrics, 2007

BACKGROUND. A recurring epidemic of asthma exacerbations in children occurs annually in September... more BACKGROUND. A recurring epidemic of asthma exacerbations in children occurs annually in September in North America when school resumes after summer vacation. OBJECTIVE. Our goal was to determine whether montelukast, added to usual asthma therapy, would reduce days with worse asthma symptoms and unscheduled physician visits of children during the September epidemic. PATIENTS AND METHODS. A total of 194 asthmatic children aged 2 to 14 years, stratified according to age group (2–5, 6–9, and 10–14 years) and gender, participated in a double-blind, randomized, placebo-controlled trial of the addition of montelukast to usual asthma therapy between September 1 and October 15, 2005. RESULTS. Children randomly assigned to receive montelukast experienced a 53% reduction in days with worse asthma symptoms compared with placebo (3.9% vs 8.3%) and a 78% reduction in unscheduled physician visits for asthma (4 [montelukast] vs 18 [placebo] visits). The benefit of montelukast was seen both in those...

Blood, 2002

We have previously demonstrated that long-term heparin treatment causes cancellous bone loss in r... more We have previously demonstrated that long-term heparin treatment causes cancellous bone loss in rats due in part to an increase in the number of osteoclasts lining the trabecular bone surface. In the present study, we investigated this phenomenon by examining the ability of heparin to synergistically enhance interleukin-11 (IL-11)–induced osteoclast formation. Treatment of murine calvaria and bone marrow cells with IL-11 was found to induce the formation of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells (MNCs) in a dose-dependent fashion. No effect was seen when cocultures were treated with heparin alone. However, when cocultures were treated with both IL-11 and heparin, IL-11's ability to induce TRAP+ MNC formation was enhanced 6-fold. In an attempt to resolve the mechanism responsible for this effect, we examined the ability of heparin to influence IL-11 signaling using murine calvaria cells. Heparin was found to enhance both IL-11–induced STAT3-DNA ...

Journal of Allergy and Clinical Immunology, 2005

Background: Predictable peaks of asthma exacerbation requiring hospital treatment, of greatest ma... more Background: Predictable peaks of asthma exacerbation requiring hospital treatment, of greatest magnitude in children and of uncertain etiology, occur globally after school returns. Objective: We wished to determine whether asthmatic children requiring emergency department treatment for exacerbations after school return in September were more likely to have respiratory viruses present and less likely to have prescriptions for control medications than children with equally severe asthma not requiring emergent treatment. Methods: Rates of viral detection and characteristics of asthma management in 57 (of 60) children age 5 to 15 years presenting to emergency departments with asthma in 2 communities in Canada between September 10 and 30, 2001, (cases) were compared with those in 157 age-matched volunteer children with asthma of comparable severity studied simultaneously (controls). Results: Human picornaviruses were detected in 52% of cases and 29% of controls (P = .002) and viruses of any type in 62% of cases and 41% of controls (P = .011). Cases were less likely to have been prescribed controller medication (inhaled corticosteroid, 49% vs 85%; P < .0001; leukotriene receptor antagonist, 9% vs 21%; P = .04). Conclusion: Respiratory viruses were detected in the majority of children presenting to emergency departments with asthma during the September epidemic of the disease and in a significant minority of children with asthma in the community. The latter were more likely to have antiinflammatory medication prescriptions than children requiring emergent treatment. Such medication may reduce the risk of emergency department treatment for asthma during the September epidemic.