Stephen E Fremes

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Publications (215)1315.62 Total impact

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    ABSTRACT: Observational studies using propensity-score methods have been increasing in the cardiovascular literature because randomized controlled trials are not always feasible or ethical. However, propensity-score methods can be confusing, and the general audience may not fully understand the importance of this technique. The objectives of this review are to describe (1) the fundamentals of propensity score methods, (2) the techniques to assess for propensity-score model adequacy, (3) the 4 major methods for using the propensity score (matching, stratification, covariate adjustment, and inverse probability of treatment weighting [IPTW]) using examples from previously published cardiovascular studies, and (4) the strengths and weaknesses of these 4 techniques. Our review suggests that matching or IPTW using the propensity score have shown to be most effective in reducing bias of the treatment effect. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
    The Canadian journal of cardiology 05/2015; DOI:10.1016/j.cjca.2015.05.015 · 3.94 Impact Factor
  • Saswata Deb · Stephen E. Fremes
    Journal of Thoracic and Cardiovascular Surgery 03/2015; 149(6). DOI:10.1016/j.jtcvs.2015.03.014 · 3.99 Impact Factor
  • Saswata Deb · Domingos S R Souza · Stephen E Fremes
    Journal of Thoracic and Cardiovascular Surgery 02/2015; 149(2):494-5. DOI:10.1016/j.jtcvs.2014.11.046 · 3.99 Impact Factor
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    ABSTRACT: BACKGROUND: There is a paucity of data on the comparative effectiveness of percutaneous coronary intervention using contemporary drug-eluting stent (DES) compared with coronary artery bypass graft (CABG) surgery in patients with chronic kidney disease. METHODS AND RESULTS: A population-based study was performed using the Cardiac Care Network, a provincial registry of all patients undergoing cardiac catheterization in Ontario, to evaluate patients treated with either percutaneous coronary intervention using DES or CABG between October 1, 2008, and September 30, 2011. Chronic kidney disease was defined as creatinine clearance <60 mL/min. A total of 1786 propensity-matched patients from 4006 patients with chronic kidney disease undergoing index revascularization for multivessel disease with either DES or isolated CABG (n=893 each group) were analyzed. Baseline and procedural characteristics between percutaneous coronary intervention and CABG groups were well-balanced, including urgent revascularization priority, diabetes mellitus, left ventricular function, and 3-vessel disease. The 1-, 2-, and 3-year Kaplan-Meier survival analyses in propensity-matched patients favored CABG (93.2% versus 89.3%; 86.6% versus 80.3%; 80.8% versus 71.5%, respectively; P<0.001). The CABG cohort had greater 1-, 2-, and 3-year freedom from major adverse cardiac and cerebrovascular events (89.4% versus 71.2%; 81.9% versus 60.5%; 75.2% versus 51.8%, respectively; P<0.001). Cox regression analysis identified DES use to be associated with greater hazard for late mortality (hazard ratio, 1.58; 95% confidence interval, 1.32-1.90) and major adverse cardiac and cerebrovascular events (2.62; 2.28-3.01; all P<0.001). CONCLUSIONS: In this large provincial registry, CABG was associated with improved early and late clinical outcomes when compared with percutaneous coronary intervention using DES in patients with chronic kidney disease undergoing index revascularization.
    Circulation Cardiovascular Interventions 01/2015; 8(1):e001973. DOI:10.1161/CIRCINTERVENTIONS.114.001973. · 6.98 Impact Factor
  • Saswata Deb · Stephen E Fremes
    Journal of Thoracic and Cardiovascular Surgery 12/2014; 149(3). DOI:10.1016/j.jtcvs.2014.12.002 · 3.99 Impact Factor
  • Saswata Deb · Stephen E. Fremes
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    ABSTRACT: Editors Note: This invited editorial is in response to articles recently published in The Journal of Thoracic and Cardiovascular Surgery. For more in depth information on this subject, please refer to the manuscript: The long-term impact of diabetes on graft patency after coronary artery bypass grafting surgery: a substudy of the mulicenter Raidal Artery Patency Study. J Thorac Cardiovasc Surg 2014; 148:1246-1253. Copyright © 2014 Elsevier Inc. All rights reserved.
    Seminars in Thoracic and Cardiovascular Surgery 11/2014; 26(3). DOI:10.1053/j.semtcvs.2014.11.002
  • Saswata Deb · Stephen E Fremes
    Journal of Thoracic and Cardiovascular Surgery 11/2014; 149(3). DOI:10.1016/j.jtcvs.2014.11.027 · 3.99 Impact Factor
  • Saswata Deb · Stephen E Fremes
    Journal of Thoracic and Cardiovascular Surgery 10/2014; 149(2). DOI:10.1016/j.jtcvs.2014.10.063 · 3.99 Impact Factor
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    ABSTRACT: Background There is increasing demand for transcatheter aortic valve replacement (TAVR) as the primary treatment option for patients with severe aortic stenosis (AS) who are high risk surgical candidates or inoperable. We used mathematical simulation models to estimate the hypothetical effectiveness of TAVR with increasing wait-times. Methods We applied discrete event modelling, using data from the Placement of Aortic Transcatheter Valves (PARTNER) trials. We compared TAVR to medical therapy in the inoperable cohort, and compared TAVR to conventional aortic valve surgery in the high risk cohort. One-year mortality and wait-time deaths were calculated in different scenarios by varying TAVR wait-times from 10 days to 180 days, while maintaining a constant wait-time for surgery at a mean of 15.6 days Results In the inoperable cohort, the 1-year mortality for medical therapy was 50%. When the TAVR wait-time was 10 days, the TAVR wait-time mortality was 1.9% with a 1 year mortality of 31.5%. TAVR wait-time deaths increased to 28.9% with a 180-day wait, with a 1-year mortality of 41.4%. In the high risk cohort, the wait-time deaths and 1-year mortality for the surgical patients were 2.5% and 27% respectively. The TAVR wait-time deaths increased from 2.2% with a 10-day wait to 22.4% with a 180-day wait, and a corresponding increase in 1-year mortality from 24.5% to 32.6%. Mortality with TAVR exceeded surgery when TAVR wait-times exceeded 60 days. Conclusion Modest increases in TAVR wait-times have substantial impact on the effectiveness of TAVR in both inoperable patients and high risk surgical candidates.
    The Canadian journal of cardiology 10/2014; 30(10). DOI:10.1016/j.cjca.2014.03.009 · 3.94 Impact Factor
  • Canadian Medical Association Journal 09/2014; 186(18). DOI:10.1503/cmaj.131582 · 5.81 Impact Factor
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    ABSTRACT: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction. We plan a prospective, randomized double-blind, multicenter controlled trial, which will be conducted in North and South America and in Europe. In this trial we will include 1,400 high-risk patients, who are most likely to benefit from selenium supplementation. This includes patients scheduled for non-emergent combined and/or complex procedures, or with a predicted operative mortality of ≥5% according to the EuroSCORE II. Eligible patients will be randomly assigned to either the treatment group (bolus infusion of 2,000 μg sodium selenite immediately prior to surgery, followed by an additional dosage of 2,000 μg at ICU admission, and a further daily supplementation of 1,000 μg up to 10 days or ICU discharge) or to the control group (placebo administration at the same time points). The primary endpoint of this study is a composite of 'persistent organ dysfunction’ (POD) and/or death within 30 days from surgery (POD + death). POD is defined as any need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or new intermittent hemodialysis) at any time within 30 days from surgery. The SUSTAIN-CSX™ study is a multicenter trial to investigate the effect of a perioperative high dosage sodium selenite supplementation in high-risk cardiac surgical patients. Trial registration This trial was registered at Clinicaltrials.gov (identifier: NCT02002247) on 28 November 2013.
    Trials 08/2014; 15(1):339. DOI:10.1186/1745-6215-15-339 · 2.12 Impact Factor
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    ABSTRACT: Background: Much is known about the short-term risks of stroke following cardiac surgery. We examined the rate and predictors of long-term stroke in a cohort of patients who underwent cardiac surgery. Methods: We obtained linked data for patients who underwent cardiac surgery in the province of Ontario between 1996 and 2006. We analyzed the incidence of stroke and death up to 2 years postoperatively. Results: Of 108 711 patients, 1.8% (95% confidence interval [CI] 1.7%-1.9%) had a stroke perioperatively, and 3.6% (95% CI 3.5%-3.7%) had a stroke within the ensuing 2 years. The strongest predictors of both early and late stroke were advanced age ( 65 year; adjusted hazard ratio [HR] for all stroke 1.9, 95% CI 1.8-2.0), a history of stroke or transient ischemic attack (adjusted HR 2.1, 95% CI 1.9-2.3), peripheral vascular disease (adjusted HR 1.6, 95% CI 1.5-1.7), combined coronary bypass grafting and valve surgery (adjusted HR 1.7, 95% CI 1.5-1.8) and valve surgery alone (adjusted HR 1.4, 95% CI 1.2-1.5). Preoperative need for dialysis (adjusted odds ratio [OR] 2.1, 95% CI 1.6-2.8) and new-onset postoperative atrial fibrillation (adjusted OR 1.5, 95% CI 1.3-1.6) were predictors of only early stroke. A CHADS(2) score of 2 or higher was associated with an increased risk of stroke or death compared with a score of 0 or 1 (19.9% v. 9.3% among patients with a history of atrial fibrillation, 16.8% v. 7.8% among those with new-onset postoperative atrial fibrillation and 14.8% v. 5.8% among those without this condition). Interpretation: Patients who had cardiac surgery were at highest risk of stroke in the early postoperative period and had continued risk over the ensuing 2 years, with similar risk factors over these periods. New-onset postoperative atrial fibrillation was a predictor of only early stroke. The CHADS(2) score predicted stroke risk among patients with and without atrial fibrillation.
    Canadian Medical Association Journal 07/2014; 186(12). DOI:10.1503/cmaj.131214 · 5.81 Impact Factor
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    ABSTRACT: Objectives: The study objective was to determine the impact of diabetes on radial artery and saphenous vein graft occlusion and clinical outcomes more than 5 years after coronary artery bypass surgery in the multicenter Radial Artery Patency Study (NCT00187356). Methods: A total of 529 patients aged less than 80 years with triple-vessel disease undergoing coronary bypass surgery participated in this study. Angiographic follow-up occurred more than 5 years after surgery with annual clinical follow-up. The primary objective was to compare the proportion of complete graft occlusion between radial artery and saphenous vein grafts among diabetic and nondiabetic persons. Additional objectives included determining predictors of complete graft occlusion and comparison of major adverse cardiac events defined by cardiac death, late myocardial infarction, and reintervention. Results: There were 148 of 529 patients (27.8%) with diabetes; 269 patients (83/269 [30.9%] diabetic) underwent late angiography at mean of 7.7 +/- 1.5 years after surgery. In diabetic patients, the proportion of complete graft occlusion was significantly lower in the radial grafts (4/83 [4.8%]) than in the saphenous grafts (21/83 [25.3%]) (P = .0004), and this was similar in nondiabetic patients (P = .19). Multivariate modeling showed that the use of the radial artery and high-grade target vessel stenosis were protective against late graft occlusion, whereas female gender, smoking history, and elevated creatinine were associated with an increased risk; interaction between diabetic status and conduit type also was significant (P = .02). Major adverse cardiac events were higher in diabetic patients (23/148 [15.5%] vs 35/381 [9.2%], P = .04). Conclusions: The use of the radial artery should be strongly considered in diabetic patients undergoing coronary bypass surgery, especially with high-grade target vessel stenosis.
    Journal of Thoracic and Cardiovascular Surgery 07/2014; 148(4). DOI:10.1016/j.jtcvs.2014.06.057 · 3.99 Impact Factor
  • Subodh Verma · Fina Lovren · Bobby Yanagawa · Stephen Fremes
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2014; 46(6). DOI:10.1093/ejcts/ezu150 · 2.81 Impact Factor
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    ABSTRACT: Paragangliomas are catecholamine-secreting tumors external to the adrenal glands, most commonly arising in the head and neck, followed by the abdominal and thoracic cavities. The heart is a rare location for paragangliomas to originate from, with fewer than 50 cases as described in the literature. Functional paragangliomas of the right atrium are even more unusual, with only five cases reported to date. The investigations and therapies of a 41-year-old male presenting with a clinically functional cardiac paraganglioma are discussed. We performed a detailed pathology review of the primary cardiac tumor and a lung nodule to examine morphologic changes, along with an immunohistochemical profile (chromogranin A, tyrosine hydroxylase, MIB-1, and succinate dehydrogenase subunit B (SDHB)) of both tumors. Genetic testing of germline mutations in SDH genes was also completed. Both the 9.5-cm cardiac mass and 0.5-cm lung nodule were positive for chromogranin A and tyrosine hydroxylase and showed a global loss of SDHB expression. The MIB-1 labeling index of the smaller lesion and the bulk of the larger lesion was <5 %, but there were cellular foci of the larger lesion that had a labeling index of 10%. Genetic testing yielded an intronic frameshift mutation in the SDHC gene, c.IVS 5 + 1, G > A. We report the first case of a functional cardiac paraganglioma associated with an intronic frameshift SDHC gene mutation.
    Endocrine Pathology 01/2014; 25(3). DOI:10.1007/s12022-013-9296-1 · 1.64 Impact Factor
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    ABSTRACT: Neointimal hyperplasia secondary to vascular smooth muscle cell (VSMC) activation limits the long-term patency of saphenous vein grafts (SVGs). We compared markers of vascular injury and VSMC activation in SVGs harvested using the pedicled 'no-touch' (NT) vs the conventional (CON) technique. Patients undergoing coronary artery bypass surgery were enrolled in the PATENT SVG trial (clinicaltrials.gov NCT01488084). Patients were randomly allocated to have SVGs harvested with the NT technique from one leg and the CON method from the other. SVG segments underwent morphometry, histological and electron microscopy assessments and transcript measurements of VSMC activation and differentiation markers. Leg wound functional recovery and harvest site complications were assessed using a quality-of-life questionnaire. A total of 17 patients (65.3 ± 7.3 years) were enrolled. SVGs harvested using the NT vs CON technique exhibited preserved intimal, medial and adventitial architecture. CON harvest was associated with greater medial Kruppel-like factor 4 transcript levels (0.26 ± 0.05 vs 0.11 ± 0.02, P < 0.05). CON samples had significantly lower medial serum response factor (0.53 ± 0.11 vs 1.44 ± 0.50, P < 0.05) and myocardin (0.59 ± 0.08 vs 1.33 ± 0.33, P < 0.05) transcript levels. MicroRNA-145, an inhibitor of VSMC activation and differentiation, was higher in the NT vs CON samples (1.84 ± 1.03 vs 0.50 ± 0.19, P < 0.05). Leg assessment scores were worse in the NT legs at 3 months, but similar to CON scores at 12 months. SVGs harvested using the 'NT' technique exhibit an early molecular and morphological pattern consistent with decreased VSMC activation compared with CON harvesting. Functional leg recovery was similar in both groups at 12 months. Larger studies are required to corroborate these findings.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2013; 45(4). DOI:10.1093/ejcts/ezt560 · 2.81 Impact Factor
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    ABSTRACT: To identify novel predictors for coronary artery bypass grafting failure, we probed for associations with known clinical and biochemical risk factors for atherosclerosis. We also used microarray analysis to identify novel single nucleotide polymorphisms to better understand the genetics and pathogenesis of graft occlusion. The present study was a nested case-control substudy of the Radial Artery Patency Study 5-year follow-up data. From 1996 to 2001, 87 patients underwent coronary artery bypass grafting. Of these, 26 patients (29.9%) had an occluded study graft (saphenous vein or radial artery) at 8.0 ± 1.1 years. The clinical parameters, late angiography, blood biomarker levels, and surgical outcomes data were included in a multivariate analysis to determine the independent predictors of graft failure. The risk factors of graft failure were fibrinogen (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.33-11.63; P = .01), creatinine (OR, 1.06; 95% CI, 1.02-1.10; P = .006), and diabetes mellitus (OR, 5.15; 95% CI, 1.08-24.59; P = .04). High-density lipoprotein (OR, 0.74; 95% CI, 0.53-1.02; P = .06) was weakly protective; however, low-density lipoprotein and total cholesterol were not predictors. We then identified the association of several human single nucleotide polymorphisms with graft failure, including mutations in glutathione-S-transferase α3. Human coronary arteries and bypass grafts demonstrated increased protein expression of glutathione-S-transferase α3, a known cardioprotective factor, in the atherosclerotic regions and surrounding adventitial tissues. We identified diabetes as a potential clinical predictor and plasma fibrinogen, creatinine, and high-density lipoprotein as potential novel biomarkers. These might help risk stratify patients for the development of graft failure. We also demonstrated a novel association between glutathione-S-transferase α3 and graft failure.
    The Journal of thoracic and cardiovascular surgery 12/2013; 148. DOI:10.1016/j.jtcvs.2013.10.011 · 3.99 Impact Factor
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    ABSTRACT: IMPORTANCE Ischemic heart disease is the leading cause of death globally. Coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) are the revascularization options for ischemic heart disease. However, the choice of the most appropriate revascularization modality is controversial in some patient subgroups. OBJECTIVE To summarize the current evidence comparing the effectiveness of CABG surgery and PCI in patients with unprotected left main disease (ULMD, in which there is >50% left main coronary stenosis without protective bypass grafts), multivessel coronary artery disease (CAD), diabetes, or left ventricular dysfunction (LVD). EVIDENCE REVIEW A search of OvidSP MEDLINE, EMBASE, and Cochrane databases between January 2007 and June 2013, limited to randomized clinical trials (RCTs) and meta-analysis of trials and/or observational studies comparing CABG surgery with PCI was performed. Bibliographies of relevant studies were also searched. Mortality and major adverse cardiac and cerebrovascular events (MACCE, defined as all-cause mortality, myocardial infarction, stroke, and repeat revascularization) were reported wherever possible. FINDINGS Thirteen RCTs and 5 meta-analyses were included. CABG surgery should be recommended in patients with ULMD, multivessel CAD, or LVD, if the severity of coronary disease is deemed to be complex (SYNTAX >22) due to lower cardiac events associated with CABG surgery. In cases in which coronary disease is less complex (SYNTAX ≤22) and/or the patient is a higher surgical risk, PCI should be considered. For patients with diabetes and multivessel CAD, CABG surgery should be recommended as standard therapy irrespective of the severity of coronary anatomy, given improved long-term survival and lower cardiac events (5-year MACCE, 18.7% for CABG surgery vs 26.6% for PCI; P = .005). Overall, the incidence of repeat revascularization is higher after PCI, whereas stroke is higher after CABG surgery. Current literature emphasizes the importance of a heart-team approach that should consider coronary anatomy, patient characteristics, and local expertise in revascularization options. Literature pertaining to revascularization options in LVD is scarce predominantly due to LVD being an exclusion factor in most studies. CONCLUSIONS AND RELEVANCE Both CABG surgery and PCI are reasonable options for patients with advanced CAD. Patients with diabetes generally have better outcomes with CABG surgery than PCI. In cases of ULMD, multivessel CAD, or LVD, CABG surgery should be favored in patients with complex coronary lesions and anatomy and PCI in less complicated coronary disease or deemed a high surgical risk. A heart-team approach should evaluate coronary disease complexity, patient comorbidities, patient preferences, and local expertise.
    JAMA The Journal of the American Medical Association 11/2013; 310(19):2086-95. DOI:10.1001/jama.2013.281718 · 30.39 Impact Factor
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    Journal of the American College of Cardiology 10/2013; 62(18). DOI:10.1016/j.jacc.2013.08.1462 · 15.34 Impact Factor
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    ABSTRACT: Purpose: There is increasing demand for transcatheter aortic valve replacement (TAVR) as the primary treatment option for patients with severe aortic stenosis (AS) who are high risk surgical candidates or inoperable. TAVR is typically limited to centers of excellence with restricted capacity, thereby causing prolonged wait-times. Our objective was to use mathematical simulation models to estimate the hypothetical effectiveness of TAVR with increasing wait-times, when compared to either conservative medical therapy in inoperable candidates or conventional surgical aortic valve surgery in high risk candidates. Methods: We developed a fully probabilistic discrete event model, using input data from the randomized controlled Placement of Aortic Transcatheter Valves (PARTNER) trials. We evaluated two populations separately: a) in the high risk surgical cohort, we compared TAVR to conventional aortic valve surgery; b) in the inoperable cohort, we compared TAVR to conservative medical therapy. We evaluated 7 scenarios with hypothetical TAVR wait-times ranging from 10 days to 180 days. The main outcome was 1-year mortality and wait-time deaths. Results: In the inoperable cohort, the mean 1-year mortality for the conservative medical therapy arm was approximately 50%. When the TAVR wait-time was 10 days, the mean TAVR wait-time mortality was 1.9% with a 1 year mortality of 31.5%. Mean TAVR wait-time deaths increased to 28.9% with a 180-day wait, with a corresponding mean 1-year mortality of 41.4%. In the high risk cohort, the wait-time deaths and mean 1-year mortality for the surgical patients were 2.5% and 27% respectively in all scenarios. The TAVR wait-time deaths increased from 2.2% at a 10-day wait to 22.4% at a 180-day wait, with a corresponding increase in 1-year mortality from 24.5% to 32.6%. The 1-year mortality in the TAVR group exceeded that in the surgical group at wait-times greater than 60 days. Conclusion: We found that modest increases in TAVR wait-times would have substantial impact on the effectiveness of TAVR in both inoperable patients and high risk surgical candidates. In the high-risk surgical candidates, at wait-times beyond 60 days, TAVR was less effective on average compared to conventional surgery. Our results highlight the importance of aggressive wait-time management for TAVR in severe AS.
    The 35th Annual Meeting of the Society for Medical Decision Making; 10/2013

Publication Stats

5k Citations
1,315.62 Total Impact Points

Institutions

  • 1992–2015
    • Sunnybrook Health Sciences Centre
      • • Department of Critical Care Medicine
      • • Division of Cardiology
      • • Department of Medicine
      Toronto, Ontario, Canada
  • 1986–2015
    • University of Toronto
      • • Sunnybrook Health Sciences Centre
      • • Institute of Health Policy, Management and Evaluation
      • • Institute for Clinical Evaluative Sciences
      • • Department of Surgery
      • • Division of Cardiac Surgery
      Toronto, Ontario, Canada
  • 2007
    • University Health Network
      • Department of Anesthesia
      Toronto, Ontario, Canada
  • 2006
    • Women's College Hospital
      Toronto, Ontario, Canada
    • Institute for Clinical Evaluative Sciences
      Toronto, Ontario, Canada
  • 1985–2001
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 2000
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada