There are conflicting data regarding the relationship between the number of modifiable traditiona... more There are conflicting data regarding the relationship between the number of modifiable traditional risk factors and prognosis in acute coronary syndromes (ACS). This controversy might in part be explained by the differential use of prehospital medications. Using data from the Canadian, multicentre Global Registry of Acute Coronary Events (GRACE) (1999-2008), we stratified 13,686 ACS patients into 3 groups (0, 1-2, vs 3-4 risk factors) and compared their baseline characteristics, in-hospital treatments, and outcomes. Multivariable logistic regressions were performed to adjust for the components of the GRACE risk score and preadmission statin and acetylsalicylic acid (ASA) use. Among these patients (ST-elevation myocardial infarction 28.3%), 14.5%, 62.6%, and 22.9% had 0, 1-2, and 3-4 risk factors, respectively. Patients with fewer risk factors were less likely to be on ASA, statin, and other prehospital medications. Unadjusted in-hospital mortality was significantly different across risk factor groups (4.9%, 3.0%, and 3.1% for 0, 1-2, and 3-4 risk factor groups, respectively, P for trend = 0.002). This difference was no longer significant after adjusting for the components of the GRACE risk score (P for trend = 0.088) and further adjusting for preadmission statin and ASA use (P for trend = 0.96). For in-hospital mortality, there was no significant interaction between risk factor categories and ACS type (P = 0.26). The lower mortality observed in patients with ACS with more risk factors may be partially attributed to the protective effect of prehospital ASA and statin use. The number of risk factors does not provide incremental prognostic value beyond the validated GRACE risk score.
Journal of the American College of Cardiology, 2015
Previous studies showed gaps in prescription of evidence-based medical therapy (EBMT) for acute c... more Previous studies showed gaps in prescription of evidence-based medical therapy (EBMT) for acute coronary syndromes (ACS). We hypothesized that knowledge translation (KT) may increase EBMT's prescription.
Following percutaneous coronary intervention, 348 patients were randomized to either routine or s... more Following percutaneous coronary intervention, 348 patients were randomized to either routine or selective functional testing strategies. For the primary end point of maximal exercise endurance on a treadmill at 9 months, achievement was similar in the routine and selective groups. For the secondary end points measuring functional status and quality of life, scores were also similar. There was little difference in the rates of invasive cardiac procedures for the 2 groups at 9 months. ᮊ2004
Previous trials demonstrated the efficacy of platelet glycoprotein IIb/IIIa receptors blockade wi... more Previous trials demonstrated the efficacy of platelet glycoprotein IIb/IIIa receptors blockade with tirofiban in reducing acute ischemic events in patients with unstable angina/non-ST-elevation myocardial infarction. Little is known about the effect of tirofiban among women with acute coronary syndromes. We aimed to determine the benefit and safety of tirofiban plus heparin versus heparin alone on cardiac ischemic events among women with unstable angina/non-ST-elevation myocardial infarction. We performed a post hoc analysis of all women enrolled in the PRISM-PLUS trial. At early time points, there appeared to be a reduction of the primary composite end point of death, myocardial infarction, or refractory ischemia among women treated with tirofiban plus heparin (RR, 0.78 and 0.67) compared with women treated with heparin alone. However, at 30 and 180 days, there was no significant reduction of events with the combination therapy of tirofiban plus heparin (treatment-by-sex interactio...
We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient charac... more We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS). Admission ECGs of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) ECG substudy, and the Canadian ACS Registry I, were analysed independently at a blinded core laboratory. Multivariable logistic regression analysis was performed to assess the independent associations between LAHB on the admission ECG and in-hospital and 6-month mortality. Of the 11 820 eligible ACS patients, 692 (5.9%) patients had LAHB. The presence of LAHB on admission was associated with older age, male sex, prior myocardial infarction, prior heart failure, worse Killip class, higher creatinine level, and higher GRACE risk score (all p<0.01). Patients with LAHB less frequently underwent cardiac catheterisation, coronary revascularisation or reperfusion therapy (all p<0.05). The LAHB group had higher in-hospital (6.9% vs 3.9%, p<0.001) and 6-month mortality (12.5% vs 7.7%, p<0.001). However, after adjusting for the known predictors of mortality in the GRACE risk models, LAHB was not independently associated with in-hospital death (OR 1.07, 95% CI 0.76 to 1.52, p=0.70), or death at 6 months (OR 1.00, 95% CI 0.75 to 1.34, p=0.99). Across the broad spectrum of ACS, LAHB was associated with significant comorbidities, high-risk clinical features on presentation, and worse unadjusted outcomes. However, LAHB was not an independent predictor of in-hospital and 6-month mortality and did not carry incremental prognostic value beyond the known prognosticators in the GRACE risk models.
To examine the association between anti-Ro antibodies, namely anti-Ro60/SS-A and anti-Ro52/TRIM21... more To examine the association between anti-Ro antibodies, namely anti-Ro60/SS-A and anti-Ro52/TRIM21, together and separately, and a prolonged QT interval corrected for heart rate (QTc) in systemic sclerosis (SSc) patients. A total of 689 SSc patients enrolled in a multicenter cohort study underwent a 12-lead resting EKG at baseline. The QTc interval was measured, and a QTc ≥ 440ms was considered prolonged. Detailed clinical data and sera of these patients were collected and positivity for anti-Ro60/SS-A and anti-Ro52/TRIM21 antibodies was determined using an addressable laser bead immunoassay (ALBIA). QTc prolongation was common in this SSc cohort (25%). In a univariate analysis, Ro antibodies, together or separately, were not associated with prolongation of the QTc interval [mean difference in QTc in anti-Ro antibody positive versus negative subjects was -2.2ms (p = 0.5748), in anti-Ro60/SS-A antibody positive versus negative subjects was 1.3ms (p = 0.8616), and in anti-Ro52/TRIM21 antibody positive versus negative subjects was -3.3ms (p = 0.4106)]. In a multivariate logistic regression analysis adjusting for possible confounders, there was no association between prolonged QTc and anti-Ro antibodies [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.45, 1.22], anti-Ro60/SS-A antibodies (OR = 1.57, 95% CI: 0.72, 3.41), and anti-Ro52/TRIM21 antibodies (OR = 0.76, 95% CI: 0.46, 1.26). However, in both univariate and multivariate analyses, QTc prolongation was associated with longer disease duration, greater disease severity, and the presence of anti-RNA polymerase III antibodies. QTc prolongation is common in SSc, although anti-Ro antibodies do not seem to be associated with it as is the case in systemic lupus erythematosus. The reasons for this difference as well as the cause of abnormalities in cardiac repolarization in SSc will require additional studies.
The Canadian Journal of Neurological Sciences, 2011
... Beginning of a A New Era in Stroke Prevention David J. Gladstone, Karen M. Earl, Tammy J. Bun... more ... Beginning of a A New Era in Stroke Prevention David J. Gladstone, Karen M. Earl, Tammy J. Bungard, Jafna L. Cox, Alan Bell, Paul Dorian, Naeem Dean, Thao Huynh, Anil Chopra, John Eikelboom, Ashfaq Shuaib Can. J. Neurol. Sci. ... Connolly SJ, Ezekowitz MD, Yusuf S, et al. ...
Misalignment between evidence-informed clinical care guideline recommendations and reimbursement ... more Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guidelinebased therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes
Background: Hyperbilirubinemia is associated with increased mortality in heart failure (HF) patie... more Background: Hyperbilirubinemia is associated with increased mortality in heart failure (HF) patients. We evaluated the impact of evidence-based medical therapy, in particular beta-blocker on the survival of patients with HF and hyperbilirubinemia.
Persons with heart failure (HF) at high risk for adverse events should be followed by specialized... more Persons with heart failure (HF) at high risk for adverse events should be followed by specialized HF clinics, since follow-up by specialized HF clinics improves outcomes for HF patients. The objective was to determine whether there were disparities for gender and other factors associated with referral of patients to specialized HF clinics. In this prospective cohort study, patients with a confirmed primary diagnosis of HF were recruited by nurses at 8 hospital emergency departments (ED) in Québec, Canada. They were interviewed by telephone at 6 weeks post ED discharge and subsequently at 3 months and 6 months. Pertinent clinical variables were extracted from medical charts by trained nurses. Bivariate analysis and multiple logistic regression were used to identify whether gender and other potential factors were associated with referral to the HF clinic. We enrolled 549 patients (mean age 75.5±11.0 years; 51% males). By 6 months after their ED visit for HF, 37.6% of the cohort were referred to specialized HF clinics. Men were more likely to be referred (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.12, 3.74). Other factors associated with referral were younger age (OR 0.95; 95% CI 0.92, 0.98), and systolic dysfunction HF (left ventricle ejection fraction <40%) (OR 3.08; 95% CI 1.77, 5.46). There are disparities in referral with respect to gender, age, and type of HF. These disparities in referral need to be addressed.
Cerebral swelling after cardiopulmonary bypass might trigger a critical cerebral consequence resu... more Cerebral swelling after cardiopulmonary bypass might trigger a critical cerebral consequence resulting from intracranial spaceoccupying lesion. We experienced a 75-year-old woman who suffered from a delayed left hemiplegia after mitral valve replacement. Urgent diagnostic imaging revealed the presence of a brain tumor with perifocal cerebral edema. Fluid shifts occurring within a few days after the cardiopulmonary bypass, manifesting the focal cerebral edema, played a key role in this unique clinical course.
There are conflicting data regarding the relationship between the number of modifiable traditiona... more There are conflicting data regarding the relationship between the number of modifiable traditional risk factors and prognosis in acute coronary syndromes (ACS). This controversy might in part be explained by the differential use of prehospital medications. Using data from the Canadian, multicentre Global Registry of Acute Coronary Events (GRACE) (1999-2008), we stratified 13,686 ACS patients into 3 groups (0, 1-2, vs 3-4 risk factors) and compared their baseline characteristics, in-hospital treatments, and outcomes. Multivariable logistic regressions were performed to adjust for the components of the GRACE risk score and preadmission statin and acetylsalicylic acid (ASA) use. Among these patients (ST-elevation myocardial infarction 28.3%), 14.5%, 62.6%, and 22.9% had 0, 1-2, and 3-4 risk factors, respectively. Patients with fewer risk factors were less likely to be on ASA, statin, and other prehospital medications. Unadjusted in-hospital mortality was significantly different across risk factor groups (4.9%, 3.0%, and 3.1% for 0, 1-2, and 3-4 risk factor groups, respectively, P for trend = 0.002). This difference was no longer significant after adjusting for the components of the GRACE risk score (P for trend = 0.088) and further adjusting for preadmission statin and ASA use (P for trend = 0.96). For in-hospital mortality, there was no significant interaction between risk factor categories and ACS type (P = 0.26). The lower mortality observed in patients with ACS with more risk factors may be partially attributed to the protective effect of prehospital ASA and statin use. The number of risk factors does not provide incremental prognostic value beyond the validated GRACE risk score.
Journal of the American College of Cardiology, 2015
Previous studies showed gaps in prescription of evidence-based medical therapy (EBMT) for acute c... more Previous studies showed gaps in prescription of evidence-based medical therapy (EBMT) for acute coronary syndromes (ACS). We hypothesized that knowledge translation (KT) may increase EBMT's prescription.
Following percutaneous coronary intervention, 348 patients were randomized to either routine or s... more Following percutaneous coronary intervention, 348 patients were randomized to either routine or selective functional testing strategies. For the primary end point of maximal exercise endurance on a treadmill at 9 months, achievement was similar in the routine and selective groups. For the secondary end points measuring functional status and quality of life, scores were also similar. There was little difference in the rates of invasive cardiac procedures for the 2 groups at 9 months. ᮊ2004
Previous trials demonstrated the efficacy of platelet glycoprotein IIb/IIIa receptors blockade wi... more Previous trials demonstrated the efficacy of platelet glycoprotein IIb/IIIa receptors blockade with tirofiban in reducing acute ischemic events in patients with unstable angina/non-ST-elevation myocardial infarction. Little is known about the effect of tirofiban among women with acute coronary syndromes. We aimed to determine the benefit and safety of tirofiban plus heparin versus heparin alone on cardiac ischemic events among women with unstable angina/non-ST-elevation myocardial infarction. We performed a post hoc analysis of all women enrolled in the PRISM-PLUS trial. At early time points, there appeared to be a reduction of the primary composite end point of death, myocardial infarction, or refractory ischemia among women treated with tirofiban plus heparin (RR, 0.78 and 0.67) compared with women treated with heparin alone. However, at 30 and 180 days, there was no significant reduction of events with the combination therapy of tirofiban plus heparin (treatment-by-sex interactio...
We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient charac... more We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS). Admission ECGs of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) ECG substudy, and the Canadian ACS Registry I, were analysed independently at a blinded core laboratory. Multivariable logistic regression analysis was performed to assess the independent associations between LAHB on the admission ECG and in-hospital and 6-month mortality. Of the 11 820 eligible ACS patients, 692 (5.9%) patients had LAHB. The presence of LAHB on admission was associated with older age, male sex, prior myocardial infarction, prior heart failure, worse Killip class, higher creatinine level, and higher GRACE risk score (all p<0.01). Patients with LAHB less frequently underwent cardiac catheterisation, coronary revascularisation or reperfusion therapy (all p<0.05). The LAHB group had higher in-hospital (6.9% vs 3.9%, p<0.001) and 6-month mortality (12.5% vs 7.7%, p<0.001). However, after adjusting for the known predictors of mortality in the GRACE risk models, LAHB was not independently associated with in-hospital death (OR 1.07, 95% CI 0.76 to 1.52, p=0.70), or death at 6 months (OR 1.00, 95% CI 0.75 to 1.34, p=0.99). Across the broad spectrum of ACS, LAHB was associated with significant comorbidities, high-risk clinical features on presentation, and worse unadjusted outcomes. However, LAHB was not an independent predictor of in-hospital and 6-month mortality and did not carry incremental prognostic value beyond the known prognosticators in the GRACE risk models.
To examine the association between anti-Ro antibodies, namely anti-Ro60/SS-A and anti-Ro52/TRIM21... more To examine the association between anti-Ro antibodies, namely anti-Ro60/SS-A and anti-Ro52/TRIM21, together and separately, and a prolonged QT interval corrected for heart rate (QTc) in systemic sclerosis (SSc) patients. A total of 689 SSc patients enrolled in a multicenter cohort study underwent a 12-lead resting EKG at baseline. The QTc interval was measured, and a QTc ≥ 440ms was considered prolonged. Detailed clinical data and sera of these patients were collected and positivity for anti-Ro60/SS-A and anti-Ro52/TRIM21 antibodies was determined using an addressable laser bead immunoassay (ALBIA). QTc prolongation was common in this SSc cohort (25%). In a univariate analysis, Ro antibodies, together or separately, were not associated with prolongation of the QTc interval [mean difference in QTc in anti-Ro antibody positive versus negative subjects was -2.2ms (p = 0.5748), in anti-Ro60/SS-A antibody positive versus negative subjects was 1.3ms (p = 0.8616), and in anti-Ro52/TRIM21 antibody positive versus negative subjects was -3.3ms (p = 0.4106)]. In a multivariate logistic regression analysis adjusting for possible confounders, there was no association between prolonged QTc and anti-Ro antibodies [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.45, 1.22], anti-Ro60/SS-A antibodies (OR = 1.57, 95% CI: 0.72, 3.41), and anti-Ro52/TRIM21 antibodies (OR = 0.76, 95% CI: 0.46, 1.26). However, in both univariate and multivariate analyses, QTc prolongation was associated with longer disease duration, greater disease severity, and the presence of anti-RNA polymerase III antibodies. QTc prolongation is common in SSc, although anti-Ro antibodies do not seem to be associated with it as is the case in systemic lupus erythematosus. The reasons for this difference as well as the cause of abnormalities in cardiac repolarization in SSc will require additional studies.
The Canadian Journal of Neurological Sciences, 2011
... Beginning of a A New Era in Stroke Prevention David J. Gladstone, Karen M. Earl, Tammy J. Bun... more ... Beginning of a A New Era in Stroke Prevention David J. Gladstone, Karen M. Earl, Tammy J. Bungard, Jafna L. Cox, Alan Bell, Paul Dorian, Naeem Dean, Thao Huynh, Anil Chopra, John Eikelboom, Ashfaq Shuaib Can. J. Neurol. Sci. ... Connolly SJ, Ezekowitz MD, Yusuf S, et al. ...
Misalignment between evidence-informed clinical care guideline recommendations and reimbursement ... more Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guidelinebased therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes
Background: Hyperbilirubinemia is associated with increased mortality in heart failure (HF) patie... more Background: Hyperbilirubinemia is associated with increased mortality in heart failure (HF) patients. We evaluated the impact of evidence-based medical therapy, in particular beta-blocker on the survival of patients with HF and hyperbilirubinemia.
Persons with heart failure (HF) at high risk for adverse events should be followed by specialized... more Persons with heart failure (HF) at high risk for adverse events should be followed by specialized HF clinics, since follow-up by specialized HF clinics improves outcomes for HF patients. The objective was to determine whether there were disparities for gender and other factors associated with referral of patients to specialized HF clinics. In this prospective cohort study, patients with a confirmed primary diagnosis of HF were recruited by nurses at 8 hospital emergency departments (ED) in Québec, Canada. They were interviewed by telephone at 6 weeks post ED discharge and subsequently at 3 months and 6 months. Pertinent clinical variables were extracted from medical charts by trained nurses. Bivariate analysis and multiple logistic regression were used to identify whether gender and other potential factors were associated with referral to the HF clinic. We enrolled 549 patients (mean age 75.5±11.0 years; 51% males). By 6 months after their ED visit for HF, 37.6% of the cohort were referred to specialized HF clinics. Men were more likely to be referred (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.12, 3.74). Other factors associated with referral were younger age (OR 0.95; 95% CI 0.92, 0.98), and systolic dysfunction HF (left ventricle ejection fraction <40%) (OR 3.08; 95% CI 1.77, 5.46). There are disparities in referral with respect to gender, age, and type of HF. These disparities in referral need to be addressed.
Cerebral swelling after cardiopulmonary bypass might trigger a critical cerebral consequence resu... more Cerebral swelling after cardiopulmonary bypass might trigger a critical cerebral consequence resulting from intracranial spaceoccupying lesion. We experienced a 75-year-old woman who suffered from a delayed left hemiplegia after mitral valve replacement. Urgent diagnostic imaging revealed the presence of a brain tumor with perifocal cerebral edema. Fluid shifts occurring within a few days after the cardiopulmonary bypass, manifesting the focal cerebral edema, played a key role in this unique clinical course.
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