Mark Crowther

McMaster University, Hamilton, Ontario, Canada

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Publications (249)1615.6 Total impact

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    ABSTRACT: This guidance document focuses on the diagnosis and treatment of venous thromboembolism (VTE). Efficient, cost effective diagnosis of VTE is facilitated by combining medical history and physical examination with pre-test probability models, D dimer testing and selective use of confirmatory imaging. Clinical prediction rules, biomarkers and imaging can be used to tailor therapy to disease severity. Anticoagulation options for acute VTE include unfractionated heparin, low molecular weight heparin, fondaparinux and the direct oral anticoagulants (DOACs). DOACs are as effective as conventional therapy with LMWH and vitamin K antagonists. Thrombolytic therapy is reserved for massive pulmonary embolism (PE) or extensive deep vein thrombosis (DVT). Inferior vena cava filters are reserved for patients with acute VTE and contraindications to anticoagulation. Retrievable filters are strongly preferred. The possibility of thoracic outlet syndrome and May-Thurner syndrome should be considered in patients with subclavian/axillary and left common iliac vein DVT, respectively in absence of identifiable triggers. The optimal duration of therapy is dictated by the presence of modifiable thrombotic risk factors. Long term anticoagulation should be considered in patients with unprovoked VTE as well as persistent prothrombotic risk factors such as cancer. Short-term therapy is sufficient for most patients with VTE associated with transient situational triggers such as major surgery. Biomarkers such as D dimer and risk assessment models such the Vienna risk prediction model offer the potential to customize VTE therapy for the individual patient. Insufficient data exist to support the integration of bleeding risk models into duration of therapy planning.
    No preview · Article · Jan 2016 · Journal of Thrombosis and Thrombolysis
  • Mark Crowther · Wendy Lim

    No preview · Article · Dec 2015 · Journal of General Internal Medicine
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    Full-text · Article · Dec 2015
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    ABSTRACT: Strategies are needed to exclude pulmonary embolism (PE) efficiently without the need for imaging tests. Although validated rules for clinical probability assessment can be combined with D-dimer testing to safely exclude PE, the rules can be complicated or partially subjective, which limits their use. To determine if PE can be safely excluded in patients with a negative D-dimer without incorporating clinical probability assessment. We enrolled consecutive outpatients and inpatients with suspected PE from four tertiary care hospitals. All patients underwent D-dimer testing using the MDA D-dimer test, a quantitative latex agglutination assay. PE was excluded in patients with a D-dimer less than 750 μg FEU/L without further testing. Patients with D-dimer levels of 750 μg FEU/L or higher underwent standardized imaging tests for PE. All patients in whom PE was excluded had anticoagulant therapy withheld and were followed for three months for venous thromboembolism (VTE). Suspected events during follow-up were adjudicated centrally. 808 patients were enrolled, among whom 99 (12%) were diagnosed with VTE at presentation. 420 (52%) patients had a negative D-dimer level at presentation and were not treated with anticoagulants; of these, one had VTE during follow-up. The negative predictive value of D-dimer testing for PE was 99.8% (95% confidence interval 98.7% to 99.9%). A negative latex agglutination D-dimer assay is seen in about one half of patients with suspected PE and reliably excludes PE as a stand-alone test. This article is protected by copyright. All rights reserved.
    Full-text · Article · Dec 2015 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: The Food and Drug Administration approval of ruxolitinib for treatment of myelofibrosis and polycythemia vera has changed the management of patients with myeloproliferative neoplasms. Yet the impact of this therapy on risk of thrombosis, a major cause of morbidity and mortality among these patients, remains unknown. The aim of this study was to evaluate the impact of ruxolitinib on the risk of thrombosis among patients with polycythemia vera or myelofibrosis. Following identification of randomized controlled trials comparing ruxolitinib to standard care or placebo, rates of thrombosis, including venous and arterial thrombosis, were analyzed using fixed effects models. Rates of thrombosis were significantly lower among patients treated with ruxolitinib [risk ratio 0.45, 95% confidence interval (CI) 0.23-0.88]. Subgroup analysis of venous and arterial thrombosis demonstrated similar risk ratios, which did not reach statistical significance (risk ratio 0.46, 95% CI 0.14-1.48 and RR 0.42, 95% CI 0.18-1.01, respectively). In conclusion, our analysis suggests that JAK2 inhibition with ruxolitinib decreases the risk of arterial and/or venous thrombosis in patients with polycythemia vera or myelofibrosis. These findings will require confirmation in a prospective study.
    No preview · Article · Nov 2015 · Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis
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    ABSTRACT: Objectives: To determine the prevalence of delayed postoperative venous thromboembolism (VTE) in patients undergoing oncologic lung resections, despite adherence to current in-hospital VTE prophylaxis guidelines. Methods: Patients undergoing lung resection for malignancy in 2 tertiary-care centers were recruited between June 2013 and December 2014. All patients received guideline-based VTE prophylaxis until hospital discharge. Patients underwent computed tomography chest angiography with pulmonary embolism (PE) protocol and bilateral lower extremity venous Doppler ultrasonography at 30 ± 5 days after surgery to determine the incidence of postoperative VTE. Univariate analysis was used to compare the VTE and non-VTE groups. Results: A total of 157 patients were included, 45.9% were men with a mean age of 66.7 years. VTE prevalence was 12.1% with a total of 19 VTE events, including 14 PEs (8.9%), 3 deep venous thromboses (DVTs) (1.9%), 1 combined PE/DVT, and 1 massive left atrial thrombus originating from the pulmonary vein stump after pulmonary lobectomy. PE events occurred in the operated lung 64% of the time and 4 patients (21.1%) were symptomatic at diagnosis. The 30-day mortality rate of VTE events was 5.2%, with 1 patient who died secondary to massive in situ ipsilateral PE following readmission to the hospital. Univariate analysis did not demonstrate significant differences between the VTE and non-VTE populations with regard to baseline characteristics. Conclusions: Despite adherence to in-hospital standard prophylaxis guidelines, VTE events are frequent, often asymptomatic, and with associated significant morbidity and mortality. More research into the potential role of predischarge screening and extended prophylaxis is warranted.
    No preview · Article · Nov 2015 · The Journal of thoracic and cardiovascular surgery
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    ABSTRACT: Background: Critically ill patients appear to be at high risk of developing deep vein thrombosis (DVT) and pulmonary embolism during their stay in the intensive care unit (ICU). However, little is known about the clinical course of venous thromboembolism in the ICU setting. We therefore evaluated, through a systematic review of the literature, the available data on the impact of a diagnosis of DVT on hospital and ICU stay, duration of mechanical ventilation and mortality in critically ill patients. We also tried to determine whether currently adopted prophylactic measures need to be revised and improved in the ICU setting. Materials and methods: MEDLINE and EMBASE databases were searched up to week 4 of June 2012. Two reviewers selected studies and extracted data. Pooled results are reported as relative risks and weighted mean differences and are presented with 95% confidence intervals (CI). Results: Seven studies for a total of 1,783 patients were included. A diagnosis of DVT was frequent in these patients with a mean rate of 12.7% (95% CI: 8.7-17.5%). DVT patients had longer ICU and hospital stays compared to those without DVT (7.28 days; 95% CI: 1.4-13.15; and 11.2 days; 95% CI: 3.82-18.63 days, respectively). The duration of mechanical ventilation was significantly increased in DVT patients (weighted mean difference: 4.85 days; 95% CI: 2.07-7.63). DVT patients had a marginally significant increase in the risk of hospital mortality (relative risk 1.31; 95% CI: 0.99-1.74; p=0.06), and a not statistically significant increase in the risk of ICU mortality (RR 1.64; 95% CI: 0.91-2.93; p=0.10). Conclusions: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including duration of ICU and hospital stay and hospital mortality. Larger, prospective studies are warranted.
    No preview · Article · Oct 2015 · Blood transfusion = Trasfusione del sangue
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    ABSTRACT: Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk. This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis. A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70–1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68–1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31–0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30–0.88, P-value = 0.01 for the cause-specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings. This competing risk analysis yields no significant treatment effect on PLDVT but a superior effect of dalteparin on PE compared with UFH in medical-surgical critically ill patients. The findings from the competing risk method are in accordance with results from the cause-specific analysis. Identifier: NCT00182143
    Full-text · Article · Sep 2015 · Medicine
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    ABSTRACT: Background Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOAC on mortality outcomes compared with warfarin remains unclear.Objective To estimate the mortality outcomes in patients treated with DOACs versus warfarin (or other vitamin K antagonist).MethodsMEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs to warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism.ResultsThirteen RCTs involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% [95% CI, 6.53-8.68, I2 = 0%] in patients taking DOACs and 11.04% [95% CI, 9.16-13.07, I2 = 33.3%] in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years [95% CI, 0.12-0.20, I2 = 36.5%]. When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53, 95% CI, 0.43-0.64, I2 = 0%), cardiovascular mortality (RR, 0.88, 95% CI, 0.82-0.94, I2 = 0%) and all-cause mortality (RR, 0.91, 95% CI, 0.87-0.96, I2 = 0%).Conclusions The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality.This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Central venous catheter-related thrombosis (CRT) is a complication seen in patients requiring long-term intravenous access. Treatment of CRT is not standardized and international guidelines for treatment are based on extrapolation of evidence from lower extremity thrombosis. We performed a systematic review of the literature to evaluate if duration of anticoagulation affects the risk of recurrent venous thrombosis, post-thrombotic syndrome, or major hemorrhage. We searched PubMed, Embase, Medline, CINAHL, Cochrane, and ACP Journal club for studies of CRT treated with anticoagulation. Of 1648 titles and abstracts, 23 studies met our inclusion criteria. No randomized trials were identified. Duration of anticoagulation varied from 8days to more than 6months. Outcomes of patients with upper extremity thrombosis due to CRT or other etiologies were often combined. The incidence of post-thrombotic syndrome varied between 0 and 75% depending on the definition used. Seven percent of patients with upper extremity thrombosis treated with anticoagulation experienced recurrent deep vein thrombosis and 2.8% experienced pulmonary embolism. Major hemorrhage was reported in 2.8-4.9% of anticoagulated patients. Prospective studies evaluating the optimal duration of anticoagulation in patients with CRT are needed.
    No preview · Article · Sep 2015 · Thrombosis Research
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    ABSTRACT: Background Dabigatran, a direct thrombin inhibitor, is effective for the treatment of venous thromboembolism and prevention of stroke and systemic embolism from atrial fibrillation. The most effective means of reversing the anticoagulant effect of dabigatran in patients who have bleeding complications is unknown.Objectives To document the clinical outcomes of patients undergoing renal replacement therapy (RRT) for dabigatran-associated bleeding.Methods We searched MEDLINE and EMBASE up to May 2015. Articles were selected if the patients presented with dabigatran-associated bleeding, underwent RRT for dabigatran removal and reported an effect on bleeding.ResultsThe search yielded 22 studies representing 35 unique patient cases. Median patient age was 74.1 years (range: 56-94). Thirteen patients (37.1%) were female and 32 (91.4%) patients received dabigatran for atrial fibrillation. Twenty-three patients (65.7%) underwent intermittent hemodialysis, 10 patients (28.6%) underwent continuous renal replacement therapy (CRRT) and 2 patients underwent both intermittent hemodialysis and CRRT. Following RRT, there were significant reductions in dabigatran concentrations (P-value=0.001). Rebound of the dabigatran concentration was reported in 12 (57.1%) patients following cessation of RRT. Hemostasis was reportedly achieved in 24 patients (70.6%) and 10 patients (29.4%) died due to bleeding.Conclusions In patients with dabigatran associated bleeding, RRT appears to be effective in reducing dabigatran concentrations and in case reports this has been associated with a reduction in duration and/or severity of bleeding. However, a rebound in concentrations may be seen following withdrawal of RRT suggesting that a prolonged course of RRT may be more effective.This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2015 · Journal of Thrombosis and Haemostasis

  • No preview · Conference Paper · Jul 2015
  • Mark Crowther · Mark A Crowther
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    ABSTRACT: The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies. © 2015 American Heart Association, Inc.
    No preview · Article · Jun 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: Gastrointestinal (GI) bleeding commonly complicates anticoagulant therapy. We aimed to systematically review the published literature to determine the risk of thromboembolism, recurrent GI bleeding and mortality for patients on long-term anticoagulation who experience GI bleeding based on whether anticoagulation therapy was resumed. We performed a systematic review of phase III randomised controlled trials and cohort studies in patients with atrial fibrillation or venous thromboembolism who received oral anticoagulant. We searched MEDLINE, EMBASE and CENTRAL (from 1996-July 2014), conferences abstracts (from January 2006-July 2014) and (up to the last week of July 2014) with no language restriction. Two reviewers independently performed study selection, data extraction and study quality assessment. A total of three studies were included in the meta-analysis. The resumption of warfarin was associated with a significant reduction in thromboembolic events (hazard ratio [HR] 0.68, 95 % confidence interval [CI] 0.52 to 0.88, p < 0.004, I²=82 %). There was an increase in recurrent GI bleeding but not statistically significant for patients who restarted warfarin compared to those who did not (HR 1.20, 95 % CI 0.97 to 1.48, p = 0.10, I² = 0 %). Resumption of warfarin was associated with significant reduction in mortality (HR 0.76, 95 % CI 0.66 to 0.88, p < 0.001, I² = 87 %). This meta-analysis demonstrates that resumption of warfarin following interruption due to GI bleeding is associated with a reduction in thromboembolic events and mortality without a statistically significant increase in recurrent GI bleeding.
    No preview · Article · May 2015 · Thrombosis and Haemostasis

  • No preview · Article · Mar 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in medline, embase, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations.
    Full-text · Article · Feb 2015
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    ABSTRACT: Integration of accepted practice standards into electronic health record systems can facilitate standardization of anticoagulation care delivery and result in improved anticoagulation safety. However, the majority of commonly used electronic health record systems are lacking the specialized features necessary for optimal anticoagulation management. The Task Force on Electronic Health Records of the New York State Anticoagulation Coalition provides such a Consensus Statement in this issue of the journal. The Anticoagulation Forum endorses these recommendations and advises the electronic health record industry and health information technology programmers at the institutional level to adopt these recommendations in a comprehensive and timely manner. © The Author(s) 2014.
    No preview · Article · Jan 2015 · Annals of Pharmacotherapy
  • A. W. Shih · E. Kolesar · S. Ning · N. Manning · D. M. Arnold · M. A. Crowther
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    ABSTRACT: Background Prothrombin complex concentrates (PCCs) can be used instead of frozen plasma (FP) transfusion to reverse the effect of warfarin. Audits have demonstrated over usage of FP transfusions even before the introduction of PCC. The objective of this study was to determine the appropriateness of current FP transfusion practice in the current era since the introduction of PCCs.MethodsA retrospective cohort study of consecutive patients receiving FP over 3 months was carried out. Each episode of FP use over a 24-h period was adjudicated independently by two reviewers as appropriate (consistent with Canadian/AABB guidelines), appropriate but inconsistent with guidelines or inappropriate. Discrepancies were resolved by a third reviewer. Use of FP to reverse warfarin was considered inappropriate. FP usage from previous years was assessed as baseline.ResultsDuring the study period, 111 FP transfusions were administered. 74·8% of FP usage occurred in the ICU. The proportion of FP transfusions that were deemed appropriate, inconsistent yet appropriate or inappropriate were 33/89 (37·1%), 16/89 (18·0%) and 40/89 (44·9%), respectively, when use of FP for therapeutic plasma exchange was excluded. The most common reasons for inappropriate use were the absence of bleeding with an increased INR or warfarin reversal.Conclusion Our study is the first to audit FP transfusions in the post-PCC era in Canada. FP usage remains inappropriately high in INR prolongation without another indication or to reverse warfarin. Targeted interventions to reduce FP usage in the future should focus on the ICU and on education about warfarin reversal.
    No preview · Article · Dec 2014 · Vox Sanguinis
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    ABSTRACT: Background The availability of Computed Tomography Pulmonary Angiography (CTPA) has led to an increase in the diagnosis of sub-segmental pulmonary embolism (SSPE). Current clinical practice guidelines do not make any treatment distinctions for SSPE, though the benefits of anticoagulation for SSPE have not been established.Objectives To review the frequency of Pulmonary Embolism and Sub-segmental Pulmonary Embolism identified through CTPA as well as their managementMethods Cross-sectional review of 2213 patient charts who underwent CTPA in three Hamilton teaching hospitals from 2009-2011. In-depth chart review of patients with SSPE was undertaken to determine the frequency with which patients received anticoagulation therapy for SSPE as well as bleeding complications and recurrent thrombosis.Results2216 CTPAs were reviewed. The frequency of PE was 24.8% (n=550). Of these, the largest pulmonary filling defects were SSPEs in 82 patients (3.9% of total scans and 15.0% of identified PEs). In 55 of these 82 SSPEs, an alternative diagnosis to PE was identified on CT to explain the patients’ symptoms. Approximately 52.4% (n=43) received anticoagulation for SSPE. Major, life-threatening bleeding complications occurred in 2 of the 43 who received anticoagulation for SSPE. There was no documented recurrent thrombosis in any patients with SSPE, with or without anticoagulation.Summary/ConclusionsA substantial proportion of patients were anti-coagulated for SSPE (52%) and two developed life-threatening bleeding complications. Randomized controlled trial data is needed to further investigate the risks and benefits of anticoagulation in patients with SSPE.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: The American Society of Hematology developed the Clinical Research Training Institute (CRTI) to address the lack of training in patient-oriented research among hematologists. As the program continues, we need to consider metrics for measuring the benefits of such a training program. This article addresses the benefits of clinical research training programs. The fundamental and key components are education and mentorship. However, there are several other benefits including promotion of collaboration, job and advancement opportunities, and promotion of work-life balance. The benefits of clinical research training programs need to be measured so that funders and society can judge if they are worth the investment in time and resources. Identification of elements that are important to program benefit is essential to measuring the benefit of the program as well as program planning. Future work should focus on the constructs which contribute to benefits of clinical research training programs such as CRTI.
    No preview · Article · Nov 2014 · Journal of Cancer Education

Publication Stats

12k Citations
1,615.60 Total Impact Points


  • 1995-2016
    • McMaster University
      • • Department of Pathology and Molecular Medicine
      • • Department of Medicine
      Hamilton, Ontario, Canada
  • 2014
    • St. Joseph's Hospital
      Savannah, Georgia, United States
  • 2002-2013
    • St. Joseph's Healthcare Hamilton
      Hamilton, Ontario, Canada
  • 2004
    • University at Buffalo, The State University of New York
      • Division of General Internal Medicine
      Buffalo, NY, United States
  • 1997
    • University of Toronto
      Toronto, Ontario, Canada