ORCID Profile
0000-0002-4485-4054
Current Organisations
Provincial Health Services Authority
,
University of British Columbia
,
University of Victoria
,
Vancouver Coastal Health Research Institute
,
BC Children's Hospital
,
Child and Family Research Institute
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Publications
Activated protein C as disease-modifying therapy in antenatal preeclampsia: An open-label, single arm safety and efficacy trial
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.PREGHY.2018.05.009
Abstract: Preecl sia is characterized by maternal systemic inflammation and coagulation activation, akin to the sepsis syndrome. Recombinant human activated protein C (rhAPC drotrecogin alfa [activated]) may modify disease progression to safely prolong pregnancies and improve perinatal outcomes. Both maternal and perinatal risks are highest remote from term. Open-label, single arm safety and efficacy trial of rhAPC in consenting pregnant women with severe early-onset preecl sia. Disease severity-matched rhAPC-naïve controls were identified from an existing database. An additional six women were recruited as biomarker controls. Primary safety outcome: incidence of peripartum bleeding primary efficacy outcome: duration of pregnancy after enrolment. Twelve (31.6%) of 38 eligible women consented 3 did not receive the infusion due to staffing. Therefore, 9 women received rhAPC (24 μg/kg/hr for ≤96 h antenatally). No safety issues were identified. There was a marginal prolongation in eligibility-to-delivery intervals for women receiving rhAPC (Mantel-Cox p = 0.052 Gehan-Breslow-Wilcoxon p = 0.049). Compared with both the pre-infusion phase in the rhAPC-treated women themselves and with fullPIERS rhAPC-naïve women, rhAPC was associated with increased urine output during the infusion (6/9 vs 1/9 had urine output >100 mL/h during the infusion, Fisher's exact p = 0.003). These data support further investigation of APC in women with severe early-onset preecl sia recombinant and purified human APC is available. In addition, these data will inform the design and implementation of randomized controlled trials aiming to modify and/or moderate the proinflammatory and proacoagulant state of preecl sia.
SJS/TEN 2019: From science to translation
Publisher: Elsevier BV
Date: 04-2020
SJS/TEN 2017: Building Multidisciplinary Networks to Drive Science and Translation
Publisher: Elsevier BV
Date: 2018
Sildenafil citrate therapy for severe early-onset intrauterine growth restriction
Publisher: Wiley
Date: 11-03-2011
DOI: 10.1111/J.1471-0528.2010.02879.X
Abstract: Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011 :624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9 95% confidence interval (CI), 1.3, 126 compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.
Fifty years of pediatric asthma in developed countries: How reliable are the basic data sources?
Publisher: Wiley
Date: 08-09-2012
DOI: 10.1002/PPUL.21537
Abstract: Given the difficulties in diagnosing, or even defining, asthma in children, claims of a pediatric asthma epidemic in Canada and other developed countries are accepted with surprisingly little critical examination. We reviewed a broad range of data sources to understand how the epidemic evolved during the last 50 years and also to assess the reliability of the conclusions drawn from that data. We obtained Canadian National and Provincial data from Statistics Canada National Population Health Survey, and the British Columbia Ministry of Health respiratory database. International data were obtained by extensive review of pediatric asthma epidemiological surveys published during the last 50 years. In many developed countries, there have been three separate epidemics involving different aspects of pediatric asthma during the last 50 years: a double peaked mortality epidemic (1960s and 1980s), a hospital admission epidemic (peaked around 1990) and a steadily growing epidemic of children who report asthmatic symptoms on questionnaires. Canadian pediatric rates for asthma mortality (1-2/million/year) and hospital admission (1-2/thousand/year) are low and have fallen for the last 20 years. Rates based on questionnaire studies are high (10-15/hundred) and rose steadily over the same period. Objective reductions in asthma deaths and hospital admission likely reflect improved education and treatment programmes. Current claims of an epidemic based largely on subjective self-reported symptoms require more careful analysis. The possibility that symptom misperception, disease fashions, and poor recall, may be part of the explanation for the current high levels of self-reported symptoms deserves more attention.
Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-12-2017
DOI: 10.1212/WNL.0000000000004853
Abstract: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. We report an association between a rare variant in the complement factor H–related 4 ( CFHR4 ) gene and phenytoin-induced MPE in Europeans ( p = 4.5 × 10 –11 odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H ( CFH ) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.
RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy
Publisher: Elsevier BV
Date: 12-2021
Related Organisations
Related Funding Activities
No related grants have been discovered for Bruce Carleton.