Bruce Carleton

Professor

Research Interests

Pharmacogenomics
Adverse drug reactions (ADRs)
Drug safety and effectiveness
Clinical pharmacology
Pharmacovigilance

Relevant Degree Programs

 

Research Methodology

genotyping, sequencing, genomic analysis, statistical genetics

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Master's students
Doctoral students
Postdoctoral Fellows
Any time / year round

There are numerous opportunities for pursuing doctoral and post-doctoral research using state of the art genotyping and sequencing platforms to identify the genetic determinants of severe adverse drug reactions (ADRs) in paediatric and adult populations. In close collaboration with the CPNDS active surveillance network, genetic association and validation studies are being performed to define ADR causal genes and to develop diagnostic tests to offer personalized therapeutic recommendations for commonly used drugs. Current pharmacogenomics and surveillance focuses are: cisplatin, anthracyclines, vincristine, warfarin, codeine, inhaled corticosteroids, 5-HT3 antagonists (antiemetics), and drugs used in the treatment of Hepatitis C. Other projects include the development of clinical practice guidelines for six drugs, and knowledge translation to implement pharmacogenomic testing in clinical practice.

I am open to hosting Visiting International Research Students (non-degree, up to 12 months).

Graduate Student Supervision

Doctoral Student Supervision (2008-2018)
Teratogenicity and perinatal outcomes associated with epilepsy and the use of antiepileptic drugs (2017)

Background and Objectives: Epilepsy complicates 0.3 – 0.7% of all pregnancies in developed countries. There is a lack of consensus on appropriate antiepileptic drug (AED) regimens, folic acid supplementation, delivery management, and breastfeeding guidance. This thesis examines how women with epilepsy in British Columbia (BC) and throughout Canada are being managed to concurrently control seizures, decrease teratogenicity and optimize obstetric and perinatal outcomes.Design and Methods: Using BC linked administrative data, I examined utilization of AEDs, teratogenicity and small for gestational age (SGA) outcomes in infants exposed to newer generation AED monotherapy in utero. Using the Canadian Community Health Survey Cycle 3.1, I compared rates of preconceptual folic acid supplementation and breastfeeding among women with and without epilepsy. Using data from the BC Perinatal Data Registry, I compared rates and indications for induction of labour and cesarean section among women with and without epilepsy.Results: Our study on the BC population demonstrates no risk for both major malformations and SGA outcomes with newer generation AED monotherapy such as gabapentin, topiramate and lamotrigine. While pregabalin was not found to increase the risk for major malformations, it is possible that it does increase the risk for SGA outcomes. Newer generation AEDs were less frequently prescribed during pregnancy than older generation AEDs. Women with epilepsy in Canada were no more likely to supplement with folic acid and were significantly less likely to breastfeed when compared to women without epilepsy. In BC, when compared to women without epilepsy, women with epilepsy were significantly more likely to deliver via cesarean section, induction of labour, assisted vaginal delivery, epidural or general anesthesia. Significant differences observed between women with and without epilepsy in the indications provided for cesarean section included breech, fetal malposition and “Other;” and “Maternal Condition” for those undergoing induction of labour.Conclusion: In women with epilepsy, pregnancy management is best implemented preconceptually. This includes planning for sufficient time to transition to the appropriate AED therapy, and to initiate folic acid supplementation. During preconceptual counselling, women with epilepsy of childbearing age should be apprised of delivery options and encouraged to attempt breastfeeding.

https://open.library.ubc.ca/collections/24/items/1.0343982

The Clinical and Pharmacogenomic Determinants of Interferon Beta Induced Liver Injury in Multiple Sclerosis (2016)

No abstract available.

Asthma drug regimen optimality and health services utilization : a population-based analysis in British Columbia (2013)

Background: Drug therapy is the mainstay medical treatment for asthma patients. Many asthma patients (up to 70%) receive suboptimal drug therapy. Inadequate use of inhaled corticosteroids (ICS) has been associated with increased emergency department (ED) visits and hospital admissions for asthma. To understand patients’ asthma drug use in British Columbia (B.C.) and improve health outcomes, this study describes the burden of asthma, identifies patients who received suboptimal asthma drug regimens according to asthma clinical practice guidelines, and examines the link between regimen optimality and health services utilization for asthma in an entire population with treated asthma in BC from 1996 to 2009.Methods: A cohort of 336,901 asthma patients between 5–55 years of age was identified using provincial health services utilization data from 1996 to 2009. Annual patient medication dispensings of short-acting bronchodilators (SABA) with or without ICS were categorized into optimal or suboptimal regimens based on the asthma clinical practice guidelines. The association between regimen optimality and health services utilization was examined in one-year, as well as during a 14-year study period, using logistic regression models and Cox Proportional regression models, respectively.Results: The prevalence (~2%) and incidence (0.7%) of asthma was stable in patients 5-55 years of age in B.C. from 1996 to 2009. Asthma-related specialist visits, ED visits and hospital admissions declined by over 50% during the study period. In 2009, patients with suboptimal regimens had significantly greater risk of using health services than patients with optimal regimens of SABA and/or ICS. Over time, switching from a suboptimal to an optimal drug regimen was associated with a 30% reduction in the use of hospital services for asthmaiii(hazard ratio (HR) 0.71; 95% CI 0.54 – 0.93), and a 50% reduction in the use of ED services for asthma (HR 0.49; 95% CI 0.33 – 0.73).Conclusions: Much of the healthcare burden associated with asthma is preventable by optimizing drug therapy, in particular, with improved ICS adherence. Identifying patients with suboptimal asthma management practices is a critical step in reducing the burden of asthma on the healthcare system and ultimately improving the quality of life of asthma patients.

https://open.library.ubc.ca/collections/24/items/1.0074010

Master's Student Supervision (2010-2017)
Pharmacogenomics of warfarin safety and effectiveness in children (2013)

No abstract available.

The pharmacogenomics of vincristine-induced neurotoxicity in paediatric cancer patients with Wilms tumor or rhabdomyosarcoma (2011)

Vincristine is one of the most effective and widely utilized antineoplastic agents.However, the clinical utility of this drug is limited by severely debilitating vincristineinducedneurotoxicities (VIN). Previous studies have associated VIN with geneticpolymorphisms in genes involved in the metabolism and transportation of vincristine,including CYP3A4, CYP3A5, and ABCB1. However, the findings of such studies have notbeen consistently reproduced. This study hypothesizes that there are specific variants ingenes involved in general drug absorption, metabolism, distribution, excretion, and toxicity(ADME-Tox) that affect the individual susceptibility to VIN in patients with Wilms tumorand rhabdomyosarcoma.Detailed clinical data was collected from 140 patients with Wilms tumor andrhabdomyosarcoma by retrospective chart review. VIN cases were characterized by type ofneurotoxicity, and severity was evaluated using a validated clinical grading system foradverse events (NCI-CTCAE v4.03). A customized Illumina GoldenGate Panel was used togenotype 4,536 single nucleotide polymorphisms (SNPs) in candidate genes involved in themetabolism and transportation pathway of vincristine, as well as in genes broadly involved inADME-Tox.None of the SNPs that were previously reported to be associated with VIN werefound to be significantly associated (p-value
https://open.library.ubc.ca/collections/24/items/1.0072033

 

Membership Status

Member of G+PS

Department(s)

 

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