Mel Krajden

Government of British Columbia, Canada, Vancouver, British Columbia, Canada

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Publications (178)698.33 Total impact

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    ABSTRACT: Hepatitis C virus (HCV) has a naturally-occurring polymorphism Q80 K in the NS3 gene encoding the viral protease, which has been associated with reduced susceptibility to the direct-acting antiviral inhibitor Simeprevir. Q80 K is observed predominantly in genotype 1a, and seldom in other HCV genotypes; moreover, it has a markedly high prevalence in the United States. Here, we reconstruct the evolutionary history of this polymorphism to investigate why it is so highly localized in prevalence, and whether it is stably transmitted between hosts. We find the majority (96%) of HCV infections carrying Q80 K were descended from a single lineage in which a Q80 K substitution occurred around the 1940's in the United States, which implies that this polymorphism is likely highly transmissible. Furthermore, we identified two other substitutions in NS3 that may interact with Q80 K and contribute to its stability. Our results imply that the current distribution and prevalence of Q80 K are unlikely to change significantly in the short term.
    The Journal of infectious diseases. 11/2014;
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    ABSTRACT: Introduction: Individuals living in single-room occupancy (SRO) hotels constitute a socially marginalized group with exposure to multiple factors with adverse effects on neurocognition, including substance use, viral infection, psychiatric illness, and brain injury. Consequently, marked heterogeneity in neurocognitive functioning is observed. This study aimed to identify and describe distinct neurocognitive profiles within a marginally housed sample. Method: Two hundred and forty-nine (N = 249) SRO hotel residents (mean age = 43.5 years) were recruited. A battery of tests assessed neurocognition across six domains: premorbid IQ, verbal memory, attention, inhibition, mental flexibility, and decision making. Clinical examinations collected information pertaining to substance use and psychiatric diagnoses, viral infection, psychiatric symptoms, risk behaviors, and everyday functioning. Cluster analysis was used to identify subgroups of individuals with similar neurocognitive profiles and was supplemented with a discriminant function analysis. Analyses of variance and chi-square tests were used to validate the derived clusters on key clinical and functional variables. Results: A three-cluster solution was found to be optimal. Cluster 1 (n = 59) presented as overall higher functioning, whereas Cluster 3 (n = 87) exhibited overall lower functioning with a relative strength in decision-making skills. Cluster 2 (n = 103) was characterized by neurocognitive abilities that generally bisected the performance of the other groups, but with a relative weakness in decision-making skills. Discriminant function analysis indicated the six neurocognitive variables comprised two underlying dimensions that accounted for between-group variance. Clusters meaningfully differed on demographics, substance use, viral exposure, psychiatric symptoms, neurological soft signs, and risk behavior. Conclusion: Neurocognitive functioning provides the basis for identifying meaningful subgroups of marginally housed individuals, which can be reliably differentiated on key variables. This approach facilitates an understanding of the neurocognitive dysfunction and associated vulnerabilities of marginalized persons and ultimately may elucidate intervention targets.
    Journal of Clinical and Experimental Neuropsychology 11/2014; · 2.16 Impact Factor
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    ABSTRACT: This case series describes morbilliform and other rash presentations among schoolchildren during a March 2014 outbreak of influenza-like illness (ILI) in British Columbia, Canada. Multiplex nucleic acid testing of nasopharyngeal specimens and paired serologic investigations identified that influenza B, characterized as B/Massachusetts/02/2012-like (Yamagata-lineage), was the only viral aetiology and most likely cause of ILI and rash. An association between influenza B and rash has been described infrequently elsewhere, and not previously in North America. Influenza B should be considered in the differential diagnosis of febrile exanthem. Evaluation of the nature, incidence and contributing agent–host–environment interactions, and immunologic mechanisms to possibly explain influenza-associated rash is warranted.
    Influenza and Other Respiratory Viruses 11/2014; · 1.47 Impact Factor
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    ABSTRACT: Perinatal transmission of hepatitis B virus (HBV) can occur despite postexposure prophylaxis (PEP). Recent literature suggests that antiviral treatment during pregnancy when maternal HBV DNA levels are elevated can further decrease vertical transmission. However, HBV DNA screening is not routinely performed antenatally.
    Canadian journal of gastroenterology & hepatology. 11/2014; 28(10):525-8.
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    ABSTRACT: Mounting evidence affirms HPV testing as an effective cervical cancer screening tool, and many organized screening programs are considering adopting it as primary testing. HPV self-collection has comparable sensitivity to clinician collected specimens and is considered a feasible option in hard-to-reach women. We explored women's intentions to HPV self-collect for cervical cancer screening from a cohort participating in a Canadian randomized controlled cervical cancer screening trial.
    BMC Public Health 10/2014; 14(1):1060. · 2.08 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) currently infects approximately 250,000 individuals in Canada and causes more years of life lost than any other infectious disease in the country. In August 2011, new therapies were approved by Health Canada that have achieved higher response rates among those treated, but are poorly tolerated. By 2014⁄2015, short-course, well-tolerated treatments with cure rates >95% will be available. However, treatment uptake is poor due to structural, financial, geographical, cultural and social barriers. As such, 'Barriers to access to HCV care in Canada' is a crucial topic that must be addressed to decrease HCV disease burden and potentially eliminate HCV in Canada. Understanding how to better care for HCV-infected individuals requires integration across multiple disciplines including researchers, clinical services and policy makers to address the major populations affected by HCV including people who inject drugs, baby boomers, immigrants and Aboriginal and⁄or First Nations people. In 2012, the National CIHR Research Training Program in Hepatitis C organized the 1st Canadian Symposium on Hepatitis C Virus (CSHCV) in Montreal, Quebec. The 2nd CSHCV was held in 2013 in Victoria, British Columbia. Both symposia were highly successful, attracting leading international faculty with excellent attendance leading to dialogue and knowledge translation among attendees of diverse backgrounds. The current article summarizes the 3rd CSHCV, held February 2014, in Toronto, Ontario.
    Canadian journal of gastroenterology & hepatology. 10/2014; 28(9):481-487.
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    ABSTRACT: Objectives We compared a 3rd generation (gen) and two 4th gen HIV enzyme immunoassays (EIAs) to pooled nucleic acid testing (PNAT) for the identification of pre- and early seroconversion acute HIV infection (AHI). Study design 9550 specimens from males >18 years from clinics attended by men who have sex with men were tested by Siemens ADVIA Centaur® HIV 1/O/2 (3rd gen) and HIV Combo (4th gen), as well as by Abbott ARCHITECT® HIV Ag/Ab Combo (4th gen). Third gen non-reactive specimens were also tested by Roche COBAS® Ampliprep/COBAS® TaqMan HIV-1 Test v.2 in pools of 24 samples. Sensitivity and specificity of the three EIAs for AHI detection were compared. Results 7348 persons contributed 9435 specimens and had no evidence of HIV infection, 79 (94 specimens) had established HIV infection, 6 (9 specimens) had pre-seroconversion AHI and 9 (12 specimens) had early seroconversion AHI. Pre-seroconversion AHI cases were not detected by 3rd gen EIA, whereas 2/6 (33.3%) were detected by Siemens 4th gen, 4/6 (66.7%) by Abbott 4th gen and 6/6 (100%) by PNAT. All three EIAs and PNAT detected all individuals with early seroconversion AHI. Overall sensitivity/specificity for the EIAs relative to WB or NAT resolved infection status was 93.6%/99.9% for Siemens 3rd gen, 95.7%/99.7% for Siemens 4th gen and 97.9%/99.2% for Abbott 4th gen. Conclusions While both 4th gen EIAs demonstrated improved sensitivity for AHI compared to 3rd gen EIA, PNAT identified more AHI cases than either 4th gen assay. PNAT is likely to remain a useful strategy to identify AHI in high-risk populations.
    Journal of Clinical Virology 09/2014; · 3.29 Impact Factor
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    ABSTRACT: Objectives: (1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infected women, comparing HCV RNA positive to HCV RNA negative women; (2) to characterize virologic and hepatic parameters associated with HCV infection during pregnancy; and (3) to describe the rate of HCV vertical transmission. Methods: We prospectively enrolled 145 HCV-positive pregnant women across British Columbia between 2000 and 2003. Participating women were monitored during pregnancy and their infants were followed to assess them for HCV infection. Maternal HCV RNA was assessed close to delivery. Results: Seventy percent of women reported injection drug use as their primary risk factor for HCV acquisition. Observed rates of intrauterine fetal death, preterm delivery, small for gestational age, and low birth weight infants were 3.4%, 17.9%, 11.3%, and 12.5%, respectively, without a significant association with maternal HCV RNA status. The rate of cholestasis was 5.6% in the HCV RNA-positive group (6/108) and 2.8% in the HCV RNA-negative group (1/37) (P = 0.496). Serum alanine aminotransferase levels decreased significantly through pregnancy, and were significantly higher in HCV RNA-positive women than in HCV RNA-negative women after controlling for cholestasis, co-infections, and alcohol consumption. Among the HCV RNA-positive women, the median FIB-4 score was 0.67 (IQR 0.56 to 0.76) in the first trimester, 0.74 (IQR 0.52 to 1.18) in the second trimester, and 0.89 (IQR 0.52 to 1.09) in the third trimester (P = 0.02). The median HCV viral load at delivery was 424 561 IU/mL. The vertical transmission rate was 4.7% in HCV RNA-positive women, with no cases in HCV RNA-negative women. Conclusion: Because of the high rates of poor obstetrical outcomes found in this prospective cohort, population-level screening for HCV in pregnancy should be considered.
    09/2014; 36(9):785-794.
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    ABSTRACT: In light of accumulated scientific evidence of the secondary preventive benefits of antiretroviral therapy, a growing number of jurisdictions worldwide have formally started to implement HIV Treatment as Prevention (TasP) programs. To date, no gold standard for TasP program monitoring has been described. Here, we describe the design and methods applied to TasP program process monitoring in British Columbia (BC), Canada.
    Journal of acquired immune deficiency syndromes (1999). 07/2014;
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    ABSTRACT: Failure to understand the risk of false negative HIV test results during the window period results in anxiety. Patients typically want accurate test results as soon as possible while clinicians prefer to wait until the probability of a false negative is virtually nil. This review summarizes the median window periods for third-generation antibody and fourth-generation HIV tests and provides the probability of a false negative result for various days post-exposure.
    International Journal of STD & AIDS 07/2014; · 1.00 Impact Factor
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    ABSTRACT: Background. No immunogenicity data has been reported after a single dose of the quadrivalent HPV vaccine (qHPV-Gardasil®) and no data are available on co-administration of this vaccine with the HAV/HBV vaccine (Twinrix-Junior®). Two pre-licensure studies reported similar anti-HPV but lower anti-HBs titers when co-administering HPV and HBV vaccines. Objectives. To assess the immunogenicity of the qHPV and HAV/HBV vaccine when co-administered (Group-Co-adm) or given one month apart (Group-Sep) and to measure the persistence of HPV antibodies three years post-second dose of qHPV vaccine in both study groups. Methods. 416 9-10 year-old girls were enrolled. Vaccination schedule was 0-6 months. Anti-HAV and anti-HBs were measured in all subjects 6 months post-first dose and 1 month post-second dose. Anti-HPV were measured 6 months post-first dose in Group-Co-adm and in all subjects 1 and 36 months post-second dose. Results. Six months post-first dose: 100% of subjects had detectable anti-HAV and 56% and 73% had detectable anti-HBs in Group-Co-Adm and Group-Sep, respectively. In Group-Co-adm 94, 100, 99 and 96% had detectable antibodies to HPV 6, 11, 16 and 18, respectively. One month post-second dose of qHPV and HAV/HBV vaccine, in both study groups 99.5-100% of subjects had an anti-HAV titer ≥ 20IU/L, 97.5-97.6% an anti-HBs level ≥ 10IU/L, and 100% had an anti-HPV titer ≥ 3LU. Thirty-six months post-second dose of qHPV all but four subjects (99%) had antibodies to HPV18 and 100% had antibodies to HPV6, 11 and 16. The great majority (97-100%) had an anti-HPV titer ≥ 3 LU. Post-second dose administration of qHPV and HAV/HBV, no meaningful difference was observed in the immune response in the two study groups to any component of vaccines. Conclusions. The results indicate that qHPV and HAV/HBV can be given during the same vaccination session. Two doses of of qHPV and HAV/HBV vaccines induce a strong immune response. Three years post-second dose of qHPV, the great majority of subjects had antibodies to HPV types included in the vaccine. A two-dose schedule for pre-adolescents might be a reasonable alternative to the currently approved three-dose schedules.
    Human Vaccines and Therapeutics 07/2014; 10(8). · 3.64 Impact Factor
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    ABSTRACT: Little is known about factors associated with HCV transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1) and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (vs. age ≥40, adjusted odds ratio [AOR] = 1.64; 95% CI 1.03, 2.63), HIV infection (AOR = 1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR = 3.05; 95% CI 1.40, 6.66) and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36). Conclusion: In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these sub-populations.3 (Hepatology 2014;)
    Hepatology 07/2014; · 12.00 Impact Factor
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    ABSTRACT: To understand A(H1N1)pdm09 epidemic resurgence during the 2013-14 influenza season, we compared age-related cross-sectional estimates of sero-protection pre-pandemic (2009) and post-pandemic (2010 and 2013) to subsequent surveillance-based laboratory-confirmed A(H1N1)pdm09 incidence in British Columbia, Canada. Pre-pandemic sero-protection was negligible except among the very old ³80 years (80%). Conversely, post-pandemic sero-protection followed a U-shaped distribution: ∼35-45% among working-age adults but ³70% in the very old and young children, excluding children <5years in 2013 for whom sero-protection again fell below 20%. Incidence was 5-fold higher in 2013-14 than 2010-11, highest in preschool-aged children and working-age adults, following a mirror-image of sero-protection by age.
    The Journal of infectious diseases. 06/2014;
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    ABSTRACT: Objective: Test uptake and case detection trends for rubella, syphilis, HIV, and hepatitis C (HCV) were compared among the 2007 to 2011 cohort of women undergoing prenatal testing in British Columbia. Analysis involved linkage of provincially centralized laboratory and surveillance data to assess prenatal test uptake and rates of newly diagnosed versus prevalent infections. Methods: We included prenatal specimens submitted from BC women aged 16 to 45 years in 2007 to 2011. Laboratory records were linked to provincial surveillance systems to identify confirmed maternal syphilis and HIV cases. Previous positive status was determined for HIV and HCV if a prior confirmed case was identified from laboratory records. We determined rates of HIV and HCV newly identified at prenatal screening (new diagnoses per 100 000 per year). Prevalence for HIV and HCV was the sum of all new and prior diagnoses (prevalence per 100 000 per year). Results: Of 233 203 women, 96.9% were screened for rubella, 93.3% for syphilis, 93.8% for HIV, and 21.5% for HCV. From 2007 to 2011, the overall rates of new diagnoses were 15.4, 5.1, and 82.8 cases per 100 000 per year for syphilis, HIV, and HCV, respectively. The overall prevalence was 45.9 and 551.5 cases per 100 000 per year for HIV and HCV, respectively (0.05% and 0.6%). From 2007 to 2011, new diagnoses of HCV decreased 40% from 106.0 to 62.1 cases per 100 000 per year. HCV prevalence did not change and increased with maternal age. Conclusion: This study links surveillance and laboratory data to provide a provincial picture of prenatal screening test uptake and case detection, with the advantage of distinguishing new from prior diagnoses. This information can help guide prenatal communicable disease screening policy.
    06/2014; 36(6):482-490.
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    ABSTRACT: The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:34-59. · 3.08 Impact Factor
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    ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation.
    Canadian journal of gastroenterology & hepatology. 05/2014; 28(5):243-50.
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    ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:5-33. · 3.08 Impact Factor
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    ABSTRACT: The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:60-89. · 3.08 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 02/2014; 19(5). · 5.49 Impact Factor
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    ABSTRACT: Background. We estimate vaccine effectiveness (VE) against both influenza A/subtypes and B/lineages in Canada for the 2011-12 trivalent inactivated influenza vaccine (TIV) with components entirely unchanged from 2010-11 and in the context of phenotypic and genotypic characterization of circulating viruses.Methods. In a test-negative case-control study VE was estimated as [1-adjustedOddsRatio]X100 for RT-PCR-confirmed influenza in vaccinated versus non-vaccinated participants. Viruses were characterized by hemagglutination-inhibition (HI) and sequencing of antigenic sites of the hemagglutinin (HA) gene.Results. There were 1507 participants. VE against A(H1N1)pdm09 was 80%(95%CI:52-92%): circulating viruses were HI-characterized as vaccine-matched and bore just 2 amino-acid (AA) differences from vaccine. VE against A/H3N2 was 51%(95%CI:10-73%): circulating viruses were HI-characterized as vaccine-related but bore ≥11AA differences from vaccine. VE against influenza/B was 51%(95%CI:26-67%): 71%(95%CI:40-86%) for lineage-matched B/Victoria and 27%(95%CI-21-56%) for lineage-mismatched B/Yamagata. For both influenza A and B types, VE was similar among recipients of either 2010-11 or 2011-12 TIV alone, higher when vaccinated both seasons.Conclusions. Phenotypic and genotypic characterization of circulating and vaccine viruses enhances understanding of TIV performance, shown in 2011-12 to be substantial against well-conserved A(H1N1)pdm09 and lineage-matched influenza/B, suboptimal against genetic-variants of A/H3N2 and further reduced against lineage-mismatched influenza/B. With unchanged vaccine components, protection may extend beyond a single season.
    The Journal of Infectious Diseases 01/2014; · 5.85 Impact Factor

Publication Stats

4k Citations
698.33 Total Impact Points

Institutions

  • 2010–2014
    • Government of British Columbia, Canada
      Vancouver, British Columbia, Canada
    • BC Cancer Agency
      Vancouver, British Columbia, Canada
  • 2002–2014
    • University of British Columbia - Vancouver
      • • Department of Pathology and Laboratory Medicine
      • • Centre for Disease Control
      • • Department of Anesthesiology, Pharmacology and Therapeutics
      • • Department of Obstetrics and Gynaecology
      Vancouver, British Columbia, Canada
  • 2001–2014
    • BC Centre for Disease Control
      Vancouver, British Columbia, Canada
  • 2012
    • McGill University
      Montréal, Quebec, Canada
  • 2009–2012
    • Provincial Health Services Authority, British Columbia , Canada
      Vancouver, British Columbia, Canada
  • 2009–2010
    • University of New South Wales
      Kensington, New South Wales, Australia
  • 1998–2009
    • University of Toronto
      • • Institute of Health Policy, Management and Evaluation
      • • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
    • Société canadienne du sang
      Ottawa, Ontario, Canada
  • 2008
    • University of Alberta
      • Department of Medicine
      Edmonton, Alberta, Canada
  • 2005
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 1999
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 1993–1999
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 1996
    • St. Michael's Hospital
      Toronto, Ontario, Canada