The Canadian Journal of Psychiatry / La Revue Canadienne de Psychiatrie2023, Vol. 68(11) 838‐849© The Author(s) 2023
Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/07067437231158933TheCJP.ca | LaRCP.ca
Objectives: Despite unregulated amphetamine use increasing, there are limited data on related emergency department (ED) visits in Canada. Our primary objective was to examine trends in amphetamine-related ED visits over time in Ontario, including by age and sex. Secondary objectives were to examine whether patient characteristics were associated with ED revisit within 6 months.
Methods: Using administrative claims and census data, we calculated annual patient- and encounter-based rates of amphet-amine-related ED visits from 2003 to 2020 among individuals 18+ years of age. We also performed a retrospective cohort study of individuals with amphetamine-related ED visits between 2019 and 2020 to determine whether select factors were associated with ED revisit within 6 months. Multivariable logistic regression modelling was used to measure associations.
Results: The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 (1.9/100,000 Ontarians) and 2020 (27.9/100,000 Ontarians). Seventy-five percent of individuals returned to the ED for any reason within 6 months. Psychosis and use of other substances were both independently associated with ED revisit for any reason within 6 months (psychosis: AOR = 1.54, 95% CI = 1.30–1.83; other substances: AOR = 1.84, 95% CI = 1.57–2.15), whereas having a primary care physician was negatively associated with ED revisit (AOR = 0.77, 95% CI = 0.60–0.98).
Conclusions: Increasing rates of amphetamine-related ED visits in Ontario are cause for concern. Diagnoses of psychosis and the use of other substances may serve to identify individuals who are most likely to benefit from both primary and sub-stance-specific care.
Résumé
Objectifs: Malgré la hausse de l’utilisation d’amphétamine non réglementée, les données sont limitées quant aux visites au service d’urgence (SU) qui s’y rapportent au Canada. Notre principal objectif était d’examiner les tendances des visites au SU liées aux amphétamines avec le temps en Ontario, notamment par âge et par sexe. Les objectifs secondaires étaient d’examiner si les caractéristiques du patient étaient associées à une nouvelle visite au SU dans les 6 mois.
Méthodes: À l’aide des réclamations administratives et des données du recensement, nous avons calculé les taux de rencontres annuelles et les taux basés sur les patients des visites au SU liées aux amphétamines de 2003 à 2020 chez des personnes de 18 ans et plus. Nous avons aussi mené une étude de cohorte rétrospective des personnes ayant des visites au SU liées aux amphétamines entre 2019 et 2020 pour déterminer si des facteurs sélectionnés étaient associés à une nouvelle visite au SU dans les six mois. Un modèle de régression logistique multivariable a servi à mesurer les associations.
Résultats: Le taux de visites au SU liées aux amphétamines basées dans la population s’est accru près de 15 fois entre 2003 (1,9/100,000 Ontariens) et 2020 (27,9/100,000 Ontariens). Soixante-quinze pour cent des personnes sont retournées au SU pour une raison quelconque dans les 6 mois. La psychose et l’utilisation d’autres substances étaient toutes deux indépendamment associées à une nouvelle visite au SU pour une raison quelconque dans les 6 mois (psychose : RCA = 1,54, IC à 95 % 1,30 à 1,83;) autres substances : (RCA = 1,84, IC à 95 % 1,57 à 2,15), alors qu’avoir un médecin des soins de première ligne était négativement associé à une nouvelle visite au SU (RCA = 0,77, IC à 95 % 0,60 à 0,98).
Conclusions: Les taux croissants des visites au SU reliées à l’amphétamine en Ontario sont cause de préoccupation. Les diagnostics de psychose et l’utilisation d’autres substances peuvent servir à identifier les personnes qui sont le plus susceptibles de bénéficier des soins de première ligne et des soins propres aux substances.
KeywordsOntario, amphetamines, emergency department, marginalization
Unregulated amphetamines (including methamphetamine) are a growing concern, particularly since there has been a surge in the use of these drugs in select North American regions.1–6 This may be due to factors such as greater availability and ease of access in recent years.7 Other reasons may include the use of amphetamines by populations experiencing homelessness to maintain alertness and awareness.4 Concurrent use of amphetamines with opioids may also be deliberate to achieve a specific drug effect and to combat opioid-related withdrawals.7,8 In recent years, the drug supply has unintentionally led to stimulant use alongside other unregulated substances.9 This may have adverse consequences, particularly when amphetamines are used alongside opioids, contributing to opioid-related overdoses.
Amphetamine-related healthcare visits are on the rise. Amphetamine-related hospitalizations have tripled from 55,447 to 206,180 hospitalizations in the United States between 2008 and 2015.1 In Canada, the number of Manitobans that received first-time care for methamphetamine use increased from 208 in 2013 to 1,454 in 2018.10 Moreover, amphetamine-related emergency department (ED) visits in Winnipeg increased from 10 to more than 150 visits between 2013 and 2017.11 Furthermore, hospitalizations in British Columbia and Alberta doubled from 591 to 1,210 visits, and from 217 to 460 visits, respectively, between 2012 and 2014.12 Despite these increases in amphetamine-related health visits in some Canadian regions, to date, no recent study has utilized administrative claims data to examine trends in amphetamine-related acute care visits in Ontario, the most populated province. It is important to understand amphetamine-related acute care visits because this represents one of the most severe outcomes of unregulated amphetamine use and such data may be valuable to inform future interventions.
To address knowledge gaps in unregulated amphetamine use and related ED visits in Ontario, we analyzed administrative claims data between 2003 and 2020. The primary objective of this study was to examine trends in amphetamine-related ED visits over time, including by age and sex. Our secondary objectives were to examine whether select sociodemographic and clinical factors were associated with ED revisit within 6 months.
We completed annual cross-sectional analyses to examine trends in amphetamine-related ED visits in Ontario between 2003 and 2020. Subsequently, we performed a retrospective cohort study between 2019 and 2020 to determine whether specific patient factors were associated with repeat ED visit within 6 months of an amphetamine-related visit to the ED. Ontario has a publicly funded universal singlepayer healthcare system; this allowed us to analyze all demographic and clinical data for individuals in our study using linked health administrative datasets housed at ICES. ICES is an independent, non-profit research institute whose legal status under Ontario’s health information privacy law allows it to collect and analyze healthcare and demographic data, without consent, for health system evaluation and improvement. The use of the data in this project is authorized under section 45 of Ontario’s Personal Health Information Protection Act (PHIPA) and does not require review by a Research Ethics Board. Our study complies with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) statement (Supplementary Table 1).13
The following datasets were used in our analyses: the Canadian Institute for Health Information Discharge Abstract Database (DAD), the Canadian Institute for Health Information National Ambulatory Care Reporting System (NACRS), the Ontario Drug Benefit (ODB) Claims Database, the Ontario Health Insurance Plan (OHIP) Claims Database, and the Registered Persons Database (RPDB) (Supplementary Table 2). These datasets were linked using unique encoded identifiers and analyzed at ICES.
We used International Classification of Diseases, Tenth (ICD-10-CA) Revision codes, as well as OHIP diagnostic and fee codes, to define examined diagnoses in our study; Drug Identification Numbers were used to define medications of interest. A maximum of 10 distinct ICD-10-CA codes may be recorded for each emergency department encounter, while up to 25 unique ICD-10-CA codes may be recorded and documented for inpatient stays. Diagnosis and medication definitions are provided in Supplementary Table 3.
All ED visits between January 1, 2003, and December 31, 2020, where an amphetamine-related diagnosis was identified and recorded (in any diagnostic position and irrespective of the diagnosis chiefly responsible for the visit or whether other drugs were recorded during the ED encounter) were eligible for inclusion. Visits to the ED for drug overdoses or mental health problems where amphetamine was not the primary drug of concern or cause for the problems indicated were eligible for inclusion as long as an amphetamine-related diagnosis was recorded during the encounter. We excluded ED visits: (a) where the Ontario Health Card number was missing or invalid; (b) with missing age or sex data; (c) where the patient died or had a documented death date prior to the ED visit date; and (d) that were by non-Ontario residents. We then excluded encounters by individuals less than 18 years of age, as well as encounters with missing Ontario Marginalization Index (ON-Marg) or Local Health Integration Network (LHIN; Supplementary Figure 1) data. Amphetamine-related diagnoses of interest were those attributed to unregulated drug use. Therefore, to avoid including ED visits related to the use of prescribed amphetamines, we excluded all encounters by patients that were diagnosed with attention-deficit/hyperactivity disorder and/or narcolepsy during the two preceding years.
Following the application of exclusions, we calculated the total number of unique patients that presented to the ED for at least one amphetamine-related diagnosis, as well as the total number of ED visits where an amphetamine-related diagnosis was recorded (including all repeat ED visits), for each calendar year. We then used annual provincial census data (Ontario Ministry of Health and Long-Term Care: IntelliHEALTH ONTARIO) to compute patient- and encounter-based rates of amphetamine-related ED visits from 2003 to 2020. Annual rates were stratified by age (18–24 years, 25–29 years, 30–34 years, 35–39 years, 40–44 years, 45–49 years, and 50+ years of age) and sex.
Cohort entry was defined as the date of first identified and recorded amphetamine-related ED diagnosis (any diagnostic position) for each individual between January 1, 2019, and December 31, 2020. The same exclusions utilized in our trend analyses were applied at cohort entry.
We assessed the following sociodemographic and clinical characteristics for each patient at cohort entry: age, sex, healthcare service region (Northern and Southern), marginalization (ON-Marg), select comorbidities (mood disorders, anxiety disorders, psychosis, suicide attempt, opioid use, and use of other substances), and primary care access (rostered to a family physician at cohort entry). The 2016 ON-Marg was used to report each marginalization domain (residential instability, material deprivation, dependency, and ethnic concentration).14 Overall health status during the 2-year period prior to cohort entry was estimated using the Johns Hopkins ACG® System (version 10) Aggregated Diagnosis Groups (ADGs).15
Repeat ED visits for any reason within 6 months (180 days) of cohort entry was our primary outcome. Secondary outcomes included amphetamine-related (any diagnostic position) repeat ED visit and all-cause mortality within 6 months.
Baseline sociodemographic and clinical characteristics of the analytical cohort were reported using descriptive statistics. Standardized differences were used to assess variations in baseline characteristics by outcome status, with differences of >0.10 representing imbalances.16 Unconditional logistic regression modelling was used to measure associations between baseline characteristics and ED revisit outcomes; a multivariable model was constructed for each outcome. Model covariates were selected a priori if they were imbalanced across event and nonevent groups or if, based on clinical knowledge, they were believed to be associated with examined outcomes. Alpha of 0.05 was set as the significance threshold; analyses were completed using SAS v9.4 (SAS Institute Inc., Cary, NC, US). GraphPad v8.3.1 (GraphPad Software, San Diego, CA, US) was used to graphically report ED encounter trends. Cell sizes ≤5 were suppressed to protect privacy.
We conducted analyses to assess whether examined trends and associations were representative of ED visits for amphetamine-related reasons; inclusion criteria were limited to primary diagnoses for amphetamine-related reasons within respective accrual periods.
In 2003, a total of 233 distinct patients had amphetamine-related visits to an ED; this increased to 4,146 in 2020. This represents a nearly 15-fold (1,367.9%) increase in the population-based rate of amphetamine-related ED visits between 2003 (1.9 individuals per 100,000 Ontarians) and 2020 (27.9 individuals per 100,000 Ontarians) (Figure 1A). Sex-stratified trends show that males had more amphetamine-related ED visits than females; the 2020 male ED visit rate was 2.3 times that of the rate for females (Figure 1B). Between 2015 and 2020, population-based rates of amphetamine-related ED visits increased by 217.4% and 201.5% for females and males, respectively.
Individuals <40 years of age visited the ED more frequently than older adults over time (Figure 1C). The population-based rate of amphetamine-related ED visits increased by 78.3% for individuals aged 18–24 years between 2015 and 2020 (Figure 1D), whereas this rate increased more sharply among individuals aged 25–39 years (25–29 years: 176.6%; 30–34 years: 221.8%; 35–39 years: 285.4%).
Observed trends in the annual number of distinct patients presenting to the ED for an amphetamine-related reason (Figure 2; primary diagnoses) paralleled patient trends in amphetamine-related ED visits (Figure 1). Among unique patient visits to the ED examined for each year, 68.9% had an amphetamine-related condition recorded as the primary diagnosis (most responsible for the encounter).
Trends in encounter-based amphetamine-related ED visits (Supplementary Figures 2 and 3) were similar to observed patient-based findings.
There were 9,809 ED visits between January 1, 2019, and June 30, 2020, where an amphetamine-related diagnosis was documented. After applying study-specific exclusions, 5,006 unique patients remained in our analytical cohort (Figure 3).
Nearly three-quarters (74.0%) of individuals were <40 years of age; only 8.7% were 50+ years of age (Table 1). Most individuals were male (68.0%); the majority resided in Southern Ontario (85.9%). High levels of residential instability (46.9%) and material deprivation (41.3%) were common. Almost half of all individuals were diagnosed with a mood (47.4%) or psychotic disorder (44.7%), while 70.2% experienced anxiety. Prior opioid (31.4%) and other substance use (53.4%) was common.
There were 3,736 (74.6%) individuals who revisited the ED for any reason within 6 months; 1,108 (22.1%) returned for amphetamine-related reasons. Eighty-three (1.7%) individuals died within 6 months.
After adjustment, a number of factors were associated with ED revisit (Table 2) for adults presenting to the ED with an amphetamine-related diagnosis. Compared with younger adults (age 18–24 years), individuals aged 40–44 years were significantly more likely to revisit the ED for any reason (adjusted odds ratio (AOR) = 1.36, 95% confidence interval (CI) = 1.04–1.77), but not for amphetamine-related reasons (AOR = 1.08, 95% CI = 0.83–1.42). Conversely, compared with younger adults, individuals aged 30–34 were more likely to revisit the ED for amphetamine-related reasons (AOR = 1.34, 95% CI = 1.07–1.69), but not for all causes. Geographic differences in ED revisit were not observed. Individuals with the greatest housing stability were significantly less likely (compared with least stable: AOR = 0.66, 95% CI = 0.48–0.91) to revisit the ED for amphetamine-related reasons.
Psychosis and use of other substances were both independently associated with revisiting the ED for any reason (psychosis: AOR = 1.54, 95% CI = 1.30–1.83; other substance use: AOR = 1.84, 95% CI = 1.57–2.15) and for amphetaminerelated reasons (psychosis: AOR = 1.85, 95% CI = 1.57–2.19; other substance use: AOR = 1.75, 95% CI = 1.49–2.06). Having a primary care physician was negatively associated with revisiting the ED for any reason (AOR = 0.77, 95% CI = 0.60–0.98) and amphetamine-related reasons (AOR = 0.67, 95% CI = 0.49–0.92).
Similar associations were observed in subgroup analyses restricted to index ED encounters for amphetamine-related reasons (Supplementary Table 4).
The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 and 2020. Secondary findings included: (a) males consistently presented to the ED more often than females; (b) recent increases in the rate of amphetamine-related ED visits were least pronounced among younger (18–24 years) and older (50+ years) adults; (c) psychosis and use of other substances were both positively associated with ED revisit; and (d) enrolment in primary care was negatively associated with ED revisit.
We report an alarming increase in the population-based rate of amphetamine-related ED visits in Ontario between 2003 and 2020, with the rate increasing by more than 200% since 2015. Males and individuals <40 years of age experienced the greatest rate of amphetamine-related ED visits over time, which is consistent with prior reports on amphetamine use.17,18 Additionally, we found that amphetamine-related ED visits increased at a slower rate among younger adults (18–24 years) between 2015 and 2020. It is important to note that observed differences in ED visits may not reflect actual differences in need for health services between groups. Rather, trends in amphetamine-related ED visits may be explained by differences in help-seeking behaviour, perceived need for care, and/or interaction with law enforcement.19–22 They may also be explained by changes in diagnostic and medical coding practices over time, as well as greater physician awareness of the signs and symptoms of amphetamine use. While the need for additional measures to flatten rising rates of amphetamine-related ED visits is clear, future studies should implement and assess the effectiveness of additional interventions (such as education for frontline workers on how to better manage substance-related medical and psychiatric complications).
Marked increases in amphetamine-related ED visits over time may also be partially attributed to changes in the use and availability of opioids, including synthetic opioids. Despite an almost 10% decrease in the total number of people who were prescribed opioids in Canada between 2013 and 2018, opioid-related overdose death rates considerably increased during this time. This is likely due to the increasing use of fentanyl and its analogs during this period and a rise in the concurrent use of amphetamines and other unregulated substances that may contain opioids. Polysubstance use is common among those who use unregulated substances; potential increases in the availability and affordability of amphetamines in Ontario may have contributed to the dramatic climb in amphetamine-related ED care observed in our study. In-depth information on the availability and costs of amphetamines across Ontario during our study period is however limited and should be further investigated.
Observed increases in amphetamine-related ED visits over time may be further exacerbated by the COVID-19 pandemic. Recently, a study using administrative claims data from many Canadian provinces found that the total number of ED visits for stimulant (amphetamines, such as crystal meth and ecstasy; excluding cocaine) harms increased by 29% in May 2020 compared with May 2019, whereas similar ED visits decreased by 6% in September 2020 compared with September 2019.23 The decrease in ED visits for stimulant-related harms between May and September 2020 coincided with significant increases in ED care for opioids.23 Recently observed changes in short-term trends in ED care for stimulants and other unregulated drugs are believed to be a direct result of pandemic restrictions, including physical distancing guidelines and border closures.23 In response to restrictions, individuals who use unregulated substances may change their use patterns, which may augment existing health risks. These findings highlight the importance of health services for substance use, both during and beyond the COVID-19 pandemic. Future research is also necessary to identify populations at greatest risk of stimulant-related harms, as well as on interventions that may effectively reduce barriers to accessing health services (such as having a family physician) for individuals affected by substance use.
Our findings potentially highlight an age-related shift in the reason for ED revisit, whereby younger adults revisit for amphetamine-related reasons while older adults revisit for other reasons (such as psychosis resulting from prolonged amphetamine toxicity). Individuals with significantly increased odds of ED revisit for any reason included those with psychosis and those who use other substances. Although we did not differentiate between primary and substance-induced psychotic disorders, our findings suggest that implementing interventions for individuals with psychosis, such as primary care enrolment (individuals who use substances are less likely to have a family physician)24,25 and the provision of social supports,26 may decrease avoidable ED visits. This is supported by our finding that individuals with a primary care physician had a decreased odds of ED visit. Recently, an Ontario study found that individuals who lacked primary care access (AOR = 1.68, 95% CI = 1.67–1.69) or experienced substance-related disorders (AOR = 1.66, 95% CI = 1.65-1.68) had a greater odds of the first-contact incident psychiatric ED visit.27 Similar observations were made in a study of psychiatric-related ED revisits in the United States, whereby increases in mental health services were associated with a decline in ED revisit for psychiatric-related reasons.28 Future research is required to understand barriers to accessing primary care for individuals with substance use disorders, and whether our observed baseline characteristics and/or associations are similar among other populations (such as the general public and individuals who use amphetamines but do not present to the ED). Such knowledge will greatly inform the design of future interventions aimed at reducing ED revisits, including whether such strategies should be generalized or directed towards a specific population.
There are many strengths to our study. Our study is the first to report annual trends in amphetamine-related ED visits over time in Ontario. We defined all amphetamine-related diagnoses using ICD-10-CA coding, enabling trends to be compared across many years. This is not possible in regions that have only recently implemented ICD-10 coding. We excluded individuals diagnosed with attention-deficit/hyperactivity disorder and/or narcolepsy, which increased certainty that examined ED visits were related to unregulated amphetamines. Since our analyses included all Ontarians eligible for publicly funded healthcare, reported patient- and encounter-based rates present a population-level picture of amphetamine-related ED visits over time. Our findings may be generalizable to other regions with comparable populations and a similar societal context (laws, access to health and social services, drug markets, social capital, etc.) to that of Ontario, and where amphetamine-related ED visits may be a growing concern.
Certain study limitations should be considered when interpreting our results. While our analyses are generalizable to the majority of Ontarians, they may be less applicable to individuals with publicly funded insurance other than OHIP, including First Nations People and members of the Canadian Forces. Despite excluding individuals with attention-deficit/hyperactivity disorder and/or narcolepsy from our analyses, we were unable to account for the possible misclassification of examined diagnoses, as well as ED encounters arising from the use of other stimulants. Moreover, although we utilized design and analytical approaches to minimize study biases, we could not control for all behaviours and lifestyle factors that may confound modelled associations. Nevertheless, we accounted for material deprivation and other important sociodemographic and clinical characteristics. There is no validated method for identifying amphetamine-related ED visits in Ontario; we were also unable to include individuals without an Ontario health card or individuals where amphetamine use was not clearly identified (via toxicology testing) and recorded (using appropriate ICD-10-CA codes; F15 instead of F19) in the ED. Our findings therefore underestimate the true population need for amphetamine-related ED care and highlight the importance of future research on this topic. Due to the exploratory nature of our ED revisit analyses, we did not adjust for multiple statistical comparisons. Notwithstanding, our findings establish necessary benchmark data on ED visits related to unregulated amphetamine use in Ontario.
Increasing rates of amphetamine-related ED visits in Ontario are cause for concern, particularly among males and individuals <40 years of age. Diagnoses of psychosis and/or use of other substances among individuals who present to the ED for amphetamine-related reasons may help identify those who are most likely to benefit from referrals to primary and specialty care, which in turn may reduce avoidable ED visits. Future studies should examine the actual need for amphetamine-related ED care, explore opportunities to remove healthcare barriers for marginalized populations, and develop validated approaches for detecting amphetamine use in administrative claims data.
The dataset from this study is held securely in the coded form at ICES. While legal data-sharing agreements between ICES and data providers prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS. The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.
This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions, and statements expressed in the material are those of the author(s) and not necessarily those of CIHI. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. We thank IQVIA Solutions Canada Inc. for use of their Drug Information File. This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from ©Canada Post Corporation and Statistics Canada.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
This study was funded by the Canadian Institutes of Health Research (201909MPU) and supported by ICES.
James A.G. Crispo https://orcid.org/0000-0001-9065-1170
Paul Kurdyak https://orcid.org/0000-0001-8115-7437
Supplemental material for this article is available online.
1 Collaboration for Outcomes Research and Evaluation (CORE), Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
2 Human Sciences Division, NOSM University, Sudbury, Ontario, Canada
3 ICES North, Sudbury, Ontario, Canada
4 International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada
5 Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
6 British Columbia Centre on Substance Use, St. Paul’s Hospital, Vancouver, British Columbia, Canada
7 Emergency Department, Health Sciences North, Sudbury, Ontario, Canada
8 Clinical Sciences Division, NOSM University, Sudbury, Ontario, Canada
9 ICES McMaster, Hamilton, Ontario, Canada
10 ICES, University of Toronto, Toronto, Ontario, Canada
11 Centre for Addiction and Mental Health, Toronto, Ontario, Canada
12 Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
13 Health Sciences North Research Institute, Sudbury, Ontario, Canada
14 ICES, Toronto and North, Ontario, Canada
Corresponding author:James A.G. Crispo MSc, PhD, Postdoctoral Research Fellow, Faculty of Pharmaceutical Sciences, The University of British Columbia | Vancouver Campus, Pharmaceutical Sciences Building, 2405 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3.Email: james.crispo@ubc.ca