P S Parfrey

Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada

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Publications (309)2291.79 Total impact

  • 05/2014; 29 Suppl 3:iii47-iii48.
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    ABSTRACT: To assess hemodialysis (HD) patients' physical health, social supports, psychosocial well-being and the interrelationship among patients' experiences, demographics, illness characteristics, and biochemical indicators of health. To determine responsiveness of the Patient's Perception of Hemodialysis Scale (PPHS) to change in health status and critical events.
    04/2014; 24(2):33-44.
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    ABSTRACT: Background:Smoking is a risk factor for incident colorectal cancer (CRC); however, it is unclear about its influence on survival after CRC diagnosis.Methods:A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Smoking and other relevant data were collected by questionnaire after cancer diagnosis, using a referent period of '2 years before diagnosis' to capture pre-diagnosis information. Molecular analyses of microsatellite instability (MSI) status and BRAF V600E mutation status were performed in tumour tissue using standard techniques. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for major prognostic factors.Results:Compared with never smokers, all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95% CI: 1.04-3.06), but not for former (HR: 1.06; 95% CI: 0.71-1.59) smokers. The associations of cigarette smoking with the study outcomes were higher among patients with 40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03-2.85; disease-free survival (DFS: HR: 1.99; 95% CI: 1.25-3.19), those who smoked 30 cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22-2.67), and those with microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04-1.82 and DFS: HR: 1.32; 95% CI: 1.01-1.72). Potential heterogeneity was noted for sex (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged 60: P for heterogeneity=0.03).Conclusions:Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC.British Journal of Cancer advance online publication, 21 January 2014; doi:10.1038/bjc.2014.6 www.bjcancer.com.
    British Journal of Cancer 01/2014; · 5.08 Impact Factor
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    ABSTRACT: Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.
    The British journal of nutrition 10/2013; · 3.45 Impact Factor
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    ABSTRACT: Context:The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain.Objective:To describe (a) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and (b) the impact of cinacalcet on occurrence of severe unremitting HPT, defined by the persistence of markedly elevated parathyroid hormone (PTH) concentrations together with hypercalcemia or parathyroidectomy (PTX).Design:Randomized, double-blind, placebo-controlled clinical trial.Setting:Global, multicenter.Patients:3883 patients on hemodialysis of 5755 screened with moderate to severe sHPT.Main outcome measures:Parathyroidectomy, severe, unremitting HPT and use of commercial cinacalcet (a protocol violation).Intervention:Cinacalcet (30 to 180 mg daily) or placebo for up to 64 months.Results:In the 1935 patients randomized to placebo, 278 (14%) patients underwent PTX (median PTH 1872 pg/mL within prior 12 weeks of surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 (24%) patients. In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% CI 0.26 to 0.37). The relative hazard differed little when adjusted by baseline clinical characteristics.Conclusions:Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.
    The Journal of Clinical Endocrinology and Metabolism 10/2013; · 6.31 Impact Factor
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    ABSTRACT: Knowledge of molecular biology and genomics continues to expand rapidly, promising numerous opportunities for improving health. However, a key aspect of the success of genomic medicine is related to public understanding and acceptance. Using community consultations and an online survey, we explored public attitudes and expectations about genomics research. Thirty-three members of the general public in Newfoundland, Canada, took part in the community sessions, while 1024 Atlantic Canadians completed the online survey. Overall, many participants noted they lacked knowledge about genetics and associated research and took the opportunity to ask numerous questions throughout sessions. Participants were largely hopeful about genomics research in its capacity to improve health, not only for current residents, but also for future generations. However, they did not accept such research uncritically, and a variety of complex issues and questions arose during the community consultations and were reflected in survey responses. With the proliferation of biobanks and the rapid pace of discoveries in genomics research, public support will be crucial to realize health improvements. If researchers can engage the public in regular, transparent dialogue, this two-way communication could allow greater understanding of the research process and the design of efficient and effective genetic health services, informed by the public that will use them.
    Health expectations: an international journal of public participation in health care and health policy 08/2013; · 1.80 Impact Factor
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    ABSTRACT: Lynch Syndrome (LS) families harbor mutated mismatch repair genes,which predispose them to specific types of cancer. Because individuals within LS families can experience multiple cancers over their lifetime, we developed a progressive three-state model to estimate the disease risk from a healthy (state 0) to a first cancer (state 1) and then to a second cancer (state 2). Ascertainment correction of the likelihood was made to adjust for complex sampling designs with carrier probabilities for family members with missing genotype information estimated using their family's observed genotype and phenotype information in a one-step expectation-maximization algorithm. A sandwich variance estimator was employed to overcome possible model misspecification. The main objective of this paper is to estimate the disease risk (penetrance) for age at a second cancer after someone has experienced a first cancer that is also associated with a mutated gene. Simulation study results indicate that our approach generally provides unbiased risk estimates and low root mean squared errors across different family study designs, proportions of missing genotypes, and risk heterogeneities. An application to 12 large LS families from Newfoundland demonstrates that the risk for a second cancer was substantial and that the age at a first colorectal cancer significantly impacted the age at any LS subsequent cancer. This study provides new insights for developing more effective management of mutation carriers in LS families by providing more accurate multiple cancer risk estimates. Copyright © 2013 John Wiley & Sons, Ltd.
    Statistics in Medicine 08/2013; · 2.04 Impact Factor
  • Patrick S Parfrey, Geoff Warden, Brendan J Barrett
    American Journal of Kidney Diseases 06/2013; · 5.29 Impact Factor
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  • Glenn M Chertow, Patrick S Parfrey
    New England Journal of Medicine 05/2013; 368(19):1844-5. · 54.42 Impact Factor
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    ABSTRACT: Background The presence of Lynch syndrome (LS) can bring a lifetime of uncertainty to an entire family as members adjust to living with a high lifetime cancer risk. The research base on how individuals and families adjust to genetic-linked diseases following predictive genetic testing has increased our understanding of short-term impacts but gaps continue to exist in knowledge of important factors that facilitate or impede long-term adjustment. The failure of existing scales to detect psychosocial adjustment challenges in this population has led researchers to question the adequate sensitivity of these instruments. Furthermore, we have limited insight into the role of the family in promoting adjustment. Methods The purpose of this study was to develop and initially validate the Psychosocial Adjustment to Hereditary Diseases (PAHD) scale. This scale consists of two subscales, the Burden of Knowing (BK) and Family Connectedness (FC). Items for the two subscales were generated from a qualitative data base and tested in a sample of 243 participants from families with LS. Results The Multitrait/Multi-Item Analysis Program-Revised (MAP-R) was used to evaluate the psychometric properties of the PAHD. The findings support the convergent and discriminant validity of the subscales. Construct validity was confirmed by factor analysis and Cronbach?s alpha supported a strong internal consistency for BK (0.83) and FC (0.84). Conclusion Preliminary testing suggests that the PAHD is a psychometrically sound scale capable of assessing psychosocial adjustment. We conclude that the PAHD may be a valuable monitoring tool to identify individuals and families who may require therapeutic interventions.
    BMC Psychology. 04/2013; 1(7).
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    ABSTRACT: Genomic discoveries and technologies promise numerous opportunities for improving health. Key to these potential health improvements, however, are health-care consumers' understanding and acceptance of these new developments. We identified community groups and invited them to a public information-consultation session in order to explore public awareness, perception and expectations about genetics and genomics research. One hundred and four members of seven community groups in Newfoundland, Canada took part in the community sessions. Content analysis of participant comments revealed they were largely hopeful about genetics research in its capacity to improve health; however, they did not accept such research uncritically. Complex issues arose during the community consultations, including the place of genetics in primary care, the value of genetics for personal health, and concerns about access to and uses of genetic information. Participants unequivocally endorsed the value of public engagement with these issues. The rapid pace of discoveries in genomics research offers exciting opportunities to improve population health. However, public support will be crucial to realize health improvements. Our findings suggest that regular, transparent dialog between researchers and the public could allow a greater understanding of the research process, as well as assist in the design of efficient and effective genetic health services, informed by the public that will use them.European Journal of Human Genetics advance online publication, 17 April 2013; doi:10.1038/ejhg.2013.64.
    European journal of human genetics: EJHG 04/2013; · 3.56 Impact Factor
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    ABSTRACT: To examine the association between dietary patterns and colorectal cancer (CRC) survival. Cohort study. A familial CRC registry in Newfoundland. 529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010. Participants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates. Disease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men). The processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC.
    BMJ Open 01/2013; 3(2). · 1.58 Impact Factor
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    ABSTRACT: In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland. The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the co-dominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort. When adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04-2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15-2.76, p = 0.01), SERPINE1 -675indelG (HR: 0.52, 95%CI: 0.32-0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03-1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18-2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04-2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11-2.94, p = 0.018). In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest that the MTHFR Glu429Ala polymorphism may be an adverse prognostic marker in patients not treated with 5-FU.
    PLoS ONE 01/2013; 8(4):e61469. · 3.53 Impact Factor
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    ABSTRACT: Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) caused by mutations in mismatch repair (MMR) genes, a syndrome of unknown etiology called familial colorectal cancer type-X (FCCTX), or familial serrated neoplasia associated with the colorectal cancer (CRC) somatic BRAF mutation.
    Clinical Genetics 12/2012; · 4.25 Impact Factor
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    ABSTRACT: BACKGROUND: Sparse data are available about the natural history of hemoglobin (Hb) level trends in contemporary patients with anemia, chronic kidney disease (CKD), and type 2 diabetes mellitus. We intended to describe Hb level trends over time with no or minimal administration of erythropoiesis-stimulating agents. STUDY DESIGN: Prospective clinical trial cohort. SETTING & PARTICIPANTS: 2,019 individuals with type 2 diabetes, moderate anemia, and CKD from the placebo arm of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) followed up for 2.3 years with an average of 32 monthly Hb level determinations per patient. Darbepoetin alfa was administered only if Hb level decreased to <9 g/dL. OUTCOMES & MEASUREMENTS: Number of protocol-directed doses of darbepoetin alfa received due to an Hb level decrease to <9 g/dL. RESULTS: 1,106 (55%) placebo patients consistently maintained an Hb level ≥9 g/dL and received no protocol-directed darbepoetin alfa. The other patients received 1 (16%), 2-4 (16%), or 5 or more (13%) doses of darbepoetin alfa. Those who received no darbepoetin alfa doses had higher baseline Hb levels, higher estimated glomerular filtration rates (eGFRs), less proteinuria, and lower ferritin and transferrin saturation values. On average, Hb levels were stable or increased in all groups. Compared with individuals who received no darbepoetin alfa, those who received 5 or more doses were more likely to receive intravenous iron therapy and blood transfusions and progress to renal replacement therapy, but were not at higher risk of death. The strongest predictors of requiring 5 or more doses of darbepoetin alfa were lower baseline Hb level, lower eGFR, and higher proteinuria level. LIMITATIONS: Post hoc analysis of a clinical trial of a specific population with diabetes, anemia, and non-dialysis-dependent CKD. CONCLUSIONS: In the TREAT placebo arm, Hb levels were stable with no or minimal protocol-directed darbepoetin alfa during 2.3 years of follow-up. Most patients with moderate anemia, non-dialysis-dependent CKD, and type 2 diabetes are able to maintain a stable Hb level without implementing long-term erythropoiesis-stimulating agent therapy.
    American Journal of Kidney Diseases 11/2012; · 5.29 Impact Factor
  • New England Journal of Medicine 11/2012; · 54.42 Impact Factor
  • Patrick S Parfrey
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    ABSTRACT: Anaemia is an independent predictor of adverse outcomes in chronic kidney disease (CKD). Randomized trials using erythropoiesis-stimulating agents (ESAs) in patients with severe anaemia (baseline haemoglobin level <100 g/l) have been small, and the hypothesis that partial correction of severe anaemia may prevent cardiovascular events is tenable but unproven. Results from randomized trials of moderate anaemia correction with ESAs do not support the hypothesis that moderate anaemia is a cardiovascular risk factor. This Perspectives article discusses the idea that this finding may have been a result of the inadequate design of trials, co-intervention with high doses of ESAs or intravenous iron hiding a beneficial effect. Another idea is also discussed-that moderate anaemia is a marker of the degree of renal impairment and that its association with cardiovascular disease merely signifies that other factors are present that are pathogenic to the heart and associated with both kidney impairment and anaemia.
    Nature Reviews Nephrology 10/2012; · 7.94 Impact Factor
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    ABSTRACT: Diet and lifestyle influence colorectal cancer (CRC) risk but the molecular events that mediate these effects are poorly characterized. Several dietary and lifestyle factors can modulate DNA methylation suggesting that they may influence CRC risk through epigenetic regulation of cancer-related genes. The Wnt regulatory genes DKK1 and Wnt5a are important contributors to colonic carcinogenesis and are often silenced by promoter hypermethylation in CRC; however, the dietary contributions to these events have not been explored. To investigate the link between dietary/lifestyle factors and epigenetic regulation of these Wnt signaling genes, we assessed promoter methylation of these genes in a large cohort of Canadian CRC patients from Ontario (n = 549) and Newfoundland (n = 443) and examined associations to dietary/lifestyle factors implicated in CRC risk and/or DNA methylation including intake of vitamins, fats, cholesterol, fiber, and alcohol as well as body mass index (BMI), and smoking status. Several factors were associated with methylation status including alcohol intake, BMI, and cigarette smoking. Most significantly, however, dietary vitamin D intake was strongly negatively associated with DKK1 methylation in Newfoundland (P = 0.001) and a similar trend was observed in Ontario. These results suggest that vitamin D and other dietary/lifestyle factors may alter CRC risk by mediating extracellular Wnt inhibition.
    Nutrition and Cancer 09/2012; 64(7):919-28. · 2.70 Impact Factor
  • Tilman B Drüeke, Patrick S Parfrey
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    ABSTRACT: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline for anemia in chronic kidney disease (CKD) is designed to assist health-care providers in treating CKD patients with anemia. A guideline is not intended to define a standard of care, and should not be construed as one, nor should it be interpreted as prescribing an exclusive course of management. It is intended to provide information and to allow the practitioner to make an informed decision, based on evidence and expert judgment. Every health-care professional making use of these recommendations is responsible for evaluating the appropriateness of applying them in any particular clinical situation. Owing to the general nature of a guideline, it is sometimes difficult to translate it to an individual patient's condition. As the primary goal is to improve patient care, we have decided to focus on practical clinical aspects of the KDIGO anemia guideline.
    Kidney International 08/2012; 82(9):952-60. · 8.52 Impact Factor

Publication Stats

16k Citations
2,291.79 Total Impact Points

Institutions

  • 1988–2013
    • Memorial University of Newfoundland
      • • Division of Community Health and Humanities
      • • Faculty of Medicine
      • • Division of Nephrology
      St. John's, Newfoundland and Labrador, Canada
  • 2012
    • Stanford University
      Palo Alto, California, United States
    • Université de Picardie Jules Verne
      Amiens, Picardie, France
  • 2011
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 2010–2011
    • Brigham and Women's Hospital
      • • Center for Brain Mind Medicine
      • • Department of Medicine
      Boston, MA, United States
    • SickKids
      • Program in Genetics and Genome Biology
      Toronto, Ontario, Canada
    • The University of Calgary
      • Department of Medicine
      Calgary, Alberta, Canada
  • 1999–2011
    • University of Toronto
      • • Department of Laboratory Medicine and Pathobiology
      • • Department of Medicine
      Toronto, Ontario, Canada
  • 2009–2010
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
    • Azienda Ospedaliera di Cremona
      Cremona, Lombardy, Italy
    • McMaster University
      • Department of Clinical Epidemiology and Biostatistics
      Hamilton, Ontario, Canada
  • 2001–2009
    • University Health Network
      • • Department of Medicine
      • • Division of Nephrology
      Toronto, Ontario, Canada
  • 2008
    • Mount Sinai Hospital, Toronto
      • Department of Pathology and Laboratory Medicine
      Toronto, Ontario, Canada
  • 2007
    • Samuel Lunenfeld Research Institute
      Toronto, Ontario, Canada
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2001–2006
    • University of Manitoba
      Winnipeg, Manitoba, Canada
  • 2005
    • Newfoundland and Labrador Centre for Health Information
      St. John's, Newfoundland and Labrador, Canada
  • 2004–2005
    • Simon Fraser University
      • Department of Molecular Biology and Biochemistry
      Burnaby, British Columbia, Canada
  • 2002
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 1999–2000
    • National Heart, Lung, and Blood Institute
      • Division of Cardiovascular Sciences (DCVS)
      Maryland, United States
  • 1996
    • Florida Memorial University
      Saint John, Indiana, United States
  • 1995
    • The University of Western Ontario
      • Department of Medicine
      London, Ontario, Canada
  • 1992
    • St. John's Hospital
      Springfield, Illinois, United States