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Declining rates of health problems associated with crack smoking during the expansion of crack pipe distribution… Prangnell, Amy; Dong, Huiru; Daly, Patricia; Milloy, M. J; Kerr, Thomas; Hayashi, Kanna Feb 3, 2017

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RESEARCH ARTICLE Open AccessDeclining rates of health problemsassociated with crack smoking during theexpansion of crack pipe distribution inVancouver, CanadaAmy Prangnell1,2, Huiru Dong1,2, Patricia Daly3, M. J. Milloy1,4, Thomas Kerr1,4 and Kanna Hayashi1,5*AbstractBackground: Crack cocaine smoking is associated with an array of negative health consequences, includingcuts and burns from unsafe pipes, and infectious diseases such as HIV. Despite the well-established andresearched harm reduction programs for injection drug users, little is known regarding the potential for harmreduction programs targeting crack smoking to reduce health problems from crack smoking. In the wake ofrecent crack pipe distribution services expansion, we utilized data from long running cohort studies toestimate the impact of crack pipe distribution services on the rates of health problems associated with cracksmoking in Vancouver, Canada.Methods: Data were derived from two prospective cohort studies of community-recruited people who injectdrugs in Vancouver between December 2005 and November 2014. We employed multivariable generalizedestimating equations to examine the relationship between crack pipe acquisition sources and self-reportedhealth problems associated with crack smoking (e.g., cut fingers/sores, coughing blood) among peoplereported smoking crack.Results: Among 1718 eligible participants, proportions of those obtaining crack pipes only through healthservice points have significantly increased from 7.2% in 2005 to 62.3% in 2014 (p < 0.001), while the rates ofreporting health problems associated with crack smoking have significantly declined (p < 0.001). In multivariableanalysis, compared to those obtaining pipes only through other sources (e.g., on the street, self-made), those acquiringpipes through health service points only were significantly less likely to report health problems from smoking crack(adjusted odds ratio: 0.82; 95% confidence interval: 0.73–0.93).Conclusions: These findings suggest that the expansion of crack pipe distribution services has likely served to reducehealth problems from smoking crack in this setting. They provide evidence supporting crack pipe distributionprograms as a harm reduction service for crack smokers.Keywords: Crack smoking, Crack pipe acquisition, Harm reduction* Correspondence: uhri-kh@cfenet.ubc.ca1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, UrbanHealth Research Initiative, 608-1081 Burrard Street, Vancouver, BC V6Z 1Y6,Canada5Faculty of Health Sciences, Simon Fraser University, Blusson Hall, 8888University Drive, Burnaby, BC V5A 1S6, CanadaFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Prangnell et al. BMC Public Health  (2017) 17:163 DOI 10.1186/s12889-017-4099-9BackgroundCrack cocaine use remains a significant public healthproblem in many parts of the world [1, 2]. A previousstudy documented that among 1936 persons who in-ject drugs surveyed across seven major cities inCanada, approximately 65.2% reported crack smokingin the last 6 months, and in Toronto 88.8% did so[3]. Further a significant increase in crack smokinghas been shown among persons who inject drugs inVancouver from 7.4% in 1996 to 42.6% in 2005 [4].The negative consequences that can result from cracksmoking range from extreme social marginalization toelevated morbidity and mortality [5, 6]. Of particularconcern, users suffer from high rates of infectious dis-eases, such as HCV and HIV [1, 5]. Additionally,sores on the lips and mouth from smoking crack co-caine, which are common amongst users [7], providea route for the transmission of infectious diseaseswhen users do not have access to sterile and propercrack pipes and are compelled to share a pipe withothers [8, 9]. Further exacerbating the risks of trans-mission and other health problems is the makeshiftequipment used by crack smokers when no safeequipment is available, including wire scouring padsand glass stems, both of which have concerns ofbreaking and causing cuts [10]. Brillo screens, whichare steel wool impregnated with soap, are also knownto break apart during use, allowing for the particlesto be inhaled and lead to breathing problems [11].The use of unsafe smoking equipment, also contrib-utes to the experience of pipes exploding while smok-ing, further contributing to the high reports of burnsand lesions among users [12].The Downtown Eastside (DTES) of Vancouver is hometo Canada’s largest open drug scene [13], where a rangeof harm reduction programs and addiction treatments,including a supervised injection facility, also exist [14].Beginning in 2011, in response to escalating crack smok-ing and resulting health concerns [15], the local healthauthority, Vancouver Coastal Health, implemented aSafer Smoking Pilot Project [15], which provided sterilecrack cocaine smoking paraphernalia at no cost.Through the participation of community health pro-grams and services, over 100,000 safer smoking kits weredistributed to users from December 2011 to November2012, through the coordination at over 7 distributionsites. After the initial pilot study ended, the distributionof crack pipes continued as a harm reduction programin the community.While there is substantial evidence indicating thatharm reduction strategies, including supervised injectionsites and needle exchange programs [16–18], are effect-ive in reducing the harms and improving the lives ofpeople who inject drugs [19], there is a dearth ofresearch examining the impact of crack pipe distributionprograms among non-injecting users of crack. Drawingdata from long-running prospective cohorts of peoplewho use drugs in Vancouver, we sought to determine ifthe increased availability of safe crack smoking equip-ment through various health service points was associ-ated with a decrease of health problems related to cracksmoking in this setting.MethodsStudy proceduresThe Vancouver Injection Drug Users Study (VIDUS) andthe AIDS Care Cohort to evaluate Exposure to SurvivalServices (ACCESS) are ongoing open prospective co-horts of adult drug users recruited through word ofmouth, street outreach, and referrals from communityorganizations in Vancouver, Canada. These studies havebeen described in detail previously [20]. Briefly, VIDUSenrolls HIV-negative persons who reported injecting anillicit drug at least once in the month preceding enroll-ment; ACCESS enrolls HIV-positive individuals who re-port using an illicit drug (other than, or in addition to,cannabis) in the previous month. For both cohorts, othereligibility criteria included being aged 18 years or older,residing in the greater Vancouver region and providingwritten informed consent. The study instruments andall other follow-up procedures for each study are es-sentially identical to allow for combined analyses. Atbaseline and semi-annually thereafter, participantscomplete an interviewer-administered questionnaireeliciting sociodemographic data as well as informationpertaining to drug use patterns, risk behaviors, andhealth care utilization. Nurses collect blood samplesfor HIV and hepatitis C virus serology, provide basicmedical care and arrange referrals to appropriatehealth care services if required. Participants receive a$30 (CDN) honorarium for each study visit. TheUniversity of British Columbia/Providence HealthcareResearch Ethics Board provided ethical approval forboth studies.All participants who were enrolled in the cohorts be-tween December 1, 2005 (the start date of the VIDUSand ACCESS cohorts) and November 30, 2014 (the mostrecent follow-up period available for the present ana-lysis), and who reported ever injecting drugs precedingthe baseline interview were included in the present ana-lysis. Additionally, at each follow up, the sample was re-stricted to individuals who reported smoking crackcocaine in the previous 6 months because the analysiswas focused on crack cocaine smoking.Study variablesThe primary outcome of interest was experiencinghealth problems associated with smoking crack in thePrangnell et al. BMC Public Health  (2017) 17:163 Page 2 of 7previous 6 months. As in a previous study [21], this wasdefined as reporting at least one of the following healthproblems: “Burns”, “Mouth sores”, “Cut fingers / sores”,“Raw throat”, or “Coughing blood” to the questionwithin the interviewer administered questionnaire:: “Inthe past 6 months, have you experienced any of the fol-lowing health problems from smoking crack?”The primary explanatory variable of interest was crackpipe acquisition source in the previous 6 months. Thiswas defined as reporting health service points only (e.g.needle exchange programs, health clinics, temporaryshelters) vs. a mix of health service points and othersources vs. other sources only (e.g. street, homemade,corner store), to the question: “In the past 6 months,where did you get your crack pipes?”We also considered secondary explanatory variablesthat might confound the relationship between crack pipeacquisition sources and reporting health problems fromsmoking crack. These included sociodemographic char-acteristics, including: age (per year older); biological sexat birth (female vs. male); ancestry (white vs. non-white);residing in the DTES in the previous 6 months (yes vs.no); homelessness in the previous 6 months, defined ashaving no fixed address, sleeping on the street, or stay-ing in a shelter or hostel (yes vs. no); involvement indrug dealing in the previous 6 months (yes vs. no); in-volvement in sex work in the previous 6 months (yes vs.no); educational attainment (less than high school vs.high school completion or higher). Drug-use variablesreferred to behaviours in the previous 6 months, and in-cluded: ≥ daily crack smoking (yes vs. no); ≥ daily non-injection crystal methamphetamine use (yes vs. no);binge non-injection drug use, defined as compulsivehigh-intensity non-injection drug use that exceeds nor-mal patterns of consumption (yes vs. no) [22]; sharedcrack pipe (yes vs. no); and rushed crack smoking whilein public (yes vs. no). Other exposures and health statusincluded: being a victim of violence, defined as havingbeen attacked, assaulted, or suffered violence in the pre-vious 6 months (yes vs. no); being HIV infected (yes vs.no); and incarceration in the previous 6 months (yes vs.no). All variable definitions are consistent with previousstudies [23–25].Statistical analysisAs a first step, we examined the baseline samplecharacteristics stratified by reports of experiencinghealth problems from smoking crack, using thePearson’s Chi-squared test (for binary variables) andWilcoxon Rank Sum test (for continuous variables).Fisher’s exact test was used when one or more of thecells contained expected values less than or equal tofive. First, we examined the temporal trends of crackpipe acquisition source and health problems,respectively, using univariable GEE models includingthe calendar dates of 6-month follow-up periods (perperiod later) as the independent variable.Since the analyses of experiencing health problemsincluded serial measures for each participant, we usedgeneralized estimating equations (GEE) with logit link,which provided standard errors adjusted by multipleobservations per person using an exchangeable correl-ation structure. We first used bivariable GEE analysesto examine the association between each explanatoryvariable and experiencing health problems associatedwith smoking crack. To examine the relationship be-tween crack pipe acquisition source and health prob-lems, we fit multivariable GEE models using aconservative confounding model selection approach[26]. We included all variables that were associatedwith reporting health problems in unadjusted analysesat p < 0.10 in a full multivariable model, and used astepwise approach to fit a series of reduced models.After comparing the value of the coefficient of thecrack pipe acquisition source in each reduced model,we dropped the secondary variable associated withthe smallest relative change. We continued this itera-tive process until the minimum change exceeded 5%.In order to examine if the estimates differed forwomen and men, we have also repeated the modelusing an interaction term for the primary explanatoryvariable and sex. In order to examine whether the attri-tion towards the end of the study period biased the esti-mates, we also conducted a sensitivity analysis where werepeated the analyses among those whose last study visitwas earlier than December 2013 (i.e., 1 year before theend of the study period). All p-values are two sided. Allstatistical analyses were performed using SAS softwareversion 9.4 (SAS, Cary, NC).ResultsIn total, 1718 participants were eligible for the presentstudy. Among this sample, 602 (35.0%) were women,1018 (59.3%) self-reported white ancestry and the me-dian age at baseline was 41.8 years (interquartile range[IQR] = 35.4–47.8). Overall, the 1718 individuals contrib-uted 11,034 observations to the analysis and the mediannumber of follow-up visits was 5 (IQR: 2–10) per per-son. The baseline characteristics of all participants strati-fied by reporting health problems associated with cracksmoking are presented in Table 1.As shown in Fig. 1, the proportion reporting healthproblems declined from 39.2% at baseline (December2005 – May 2006) to 20.7% during the last follow-upperiod (June 2014 – November 2014), and the decliningtrend was statistically significant (p < 0.001). Addition-ally, the proportion of those obtaining crack pipes onlythrough health service points increased significantlyPrangnell et al. BMC Public Health  (2017) 17:163 Page 3 of 7from 7.2% in 2005 to 62.3% in 2014, while the ratesobtaining from other sources only decreased signifi-cantly from 83.2% in 2005 to 31.5% in 2014 (p < 0.001).Figure 1 depicts the increase in obtaining crack pipesfrom health service points only, beginning in approxi-mately 2011 which coincides with the implementation ofthe safer crack pipe smoking distribution program bythe local health authority as described above.The results of the bivariable and multivariable GEEanalyses of reporting health problems associated withcrack smoking are presented in Table 2. As shown, inthe final multivariable model after adjusting for a rangeof potential confounders, obtaining crack pipes throughhealth service points remained significantly and nega-tively associated with reporting health problems (ad-justed odds ratio [AOR] = 0.82; 95% confidence intervalTable 1 Baseline sample characteristics, stratified by reporting health problems associated with crack smoking in the past 6 monthsamong crack smokers in Vancouver, Canada (n = 1718)Characteristic Experienced crack related health problemsa Odds Ratio(95% CI)p-valueYesn (%)587 (34.2)Non (%)1131 (65.8)Crack pipe acquisition sourceHealth service points only 74 (12.6) 167 (14.8) 0.86 (0.64–1.16) 0.318A mix of health service points and other sources 58 (9.9) 81 (7.1) 1.39 (0.97–1.98) 0.070Other sources only 455 (77.5) 883 (78.1)Female sex 235 (40.0) 367 (32.4) 1.39 (1.13–1.71) 0.002Age (median, IQR) 41 (34–47) 42 (36–48) 0.99 (0.97–1.00) 0.017Caucasian 334 (56.9) 684 (60.5) 0.86 (0.70–1.06) 0.152Completed < high school 289 (49.2) 578 (51.1) 0.93 (0.76–1.13) 0.456DTES residencya 438 (74.6) 809 (71.5) 1.17 (0.93–1.47) 0.174Homelessa 229 (39.0) 413 (36.5) 1.11 (0.91–1.37) 0.305≥ Daily crack smokinga 343 (58.4) 458 (40.5) 2.06 (1.68–2.53) <0.001≥ Daily non-injection meth usea 4 (0.7) 17 (1.5) 0.45 (0.15–1.34) 0.142Binge non-injection drug usea 225 (38.3) 290 (25.6) 1.80 (1.46–2.23) <0.001Shared crack pipea 473 (80.6) 719 (63.6) 2.37 (1.87–3.01) <0.001Rushed public crack smokinga 199 (33.9) 281 (24.8) 1.57 (1.26–1.95) <0.001Drug dealinga 255 (43.4) 368 (32.5) 1.59 (1.30–1.96) <0.001Sex worka 122 (20.8) 160 (14.1) 1.61 (1.24–2.09) <0.001A victim of violencea 188 (32.0) 218 (19.3) 1.99 (1.58–2.50) <0.001Incarcerationa 124 (21.1) 182 (16.1) 1.40 (1.09–1.81) 0.009HIV positive 240 (40.9) 458 (40.5) 1.02 (0.83–1.24) 0.876PWID People who inject drugs, CI confidence interval, IQR interquartile rangeDTES Downtown Eastsidea Denotes activities in the previous 6 monthsFig. 1 Percentages of reporting health problems associated with crack smoking and crack pipe acquisition sourcesPrangnell et al. BMC Public Health  (2017) 17:163 Page 4 of 7[CI]: 0.73–0.93), while obtaining pipes through a mix ofhealth service points and other sources was only margin-ally associated (AOR = 1.17; 95% CI: 1.00–1.36). Whenwe repeated the multivariable analysis using the inter-action term between sex and crack pipe acquisitionsource, the results were not statistically different be-tween women and men (p-value of the interactionterm =0.460).The sensitivity analysis included 431 participantswhose last study visit was earlier than December 2013.Table 2 Bivariable and multivariable GEE analyses of reporting health problems associated with crack smoking among cracksmokers in Vancouver, Canada (n = 1718)Characteristic Unadjusted AdjustedOdds Ratio(95% CI)p-value Odds Ratio(95% CI)p-valueSourceHealth service point only vs. Other sources only 0.70 (0.63–0.79) <0.001 0.82 (0.73–0.93) <0.001A mix of health source points and other sourcesvs. Other sources only1.23 (1.06–1.43) 0.006 1.17 (1.00–1.36) 0.051Age(per year older) 0.97 (0.96–0.98) <0.001 0.99 (0.98–0.99) 0.002Sex(female vs. male) 1.37 (1.20–1.56) <0.001 1.31 (1.15–1.50) <0.001Ethnicity(Caucasian vs. other) 1.00 (0.88–1.14) 0.994Less than high school diploma achieved(yes vs. no) 0.99 (0.87–1.13) 0.923DTES residencya(yes vs. no) 1.24 (1.11–1.40) <0.001 1.09 (0.96–1.22) 0.178Homelessnessa(yes vs. no) 1.34 (1.22–1.48) <0.001Daily non-injection crack smokinga(yes vs. no) 1.68 (1.53–1.84) <0.001 1.29 (1.16–1.42) <0.001Daily non-injection meth usea(yes vs. no) 1.14 (0.72–1.81) 0.582Binge non-injection drug usea(yes vs. no) 1.64 (1.51–1.79) <0.001 1.53 (1.40–1.67) <0.001Shared crack pipe a(yes vs. no) 2.07 (1.88–2.28) <0.001 1.73 (1.56–1.91) <0.001Rushed public crack smokinga(yes vs. no) 1.86 (1.66–2.08) <0.001Drug dealinga(yes vs. no) 1.66 (1.50–1.83) <0.001 1.25 (1.12–1.39) <0.001Sex worka(yes vs. no) 1.95 (1.70–2.23) <0.001A victim of violencea(yes vs. no) 1.69 (1.52–1.88) <0.001 1.47 (1.31–1.64) <0.001Incarcerationa(yes vs. no) 1.56 (1.37–1.77) <0.001HIV positive(yes vs. no) 1.06 (0.93–1.21) 0.359GEE generalized estimating equations, PWID People who inject drugs, CI confidence interval, DTES Downtown Eastsidea Denotes activities in the previous 6 monthsPrangnell et al. BMC Public Health  (2017) 17:163 Page 5 of 7The results were essentially the same as those of the pri-mary analyses. In the simple GEE analyses, the decliningtrend for reporting health problems and the increasingtrend for acquiring pipes through health service pointsonly were both significant at p < 0.001. In the multivari-able GEE analysis, obtaining crack pipes through healthservice points remained significantly and negatively asso-ciated with reporting health problems (AOR = 0.74; 95%CI: 0.55–0.99), while obtaining pipes through a mix ofhealth service points and other sources was not (AOR =0.85; 95% CI: 0.59–1.24).DiscussionWe observed that the increase in crack pipe distributionservices coincided with a corresponding increase in theuptake of crack pipes obtained through health servicepoints only. Further, rates of reporting health problemsassociated with crack smoking declined significantlyafter the crack pipe distribution program was imple-mented. In the multivariable analysis, compared toobtaining crack pipes through other non-health servicesources only, obtaining pipes through health servicepoints only was significantly and negatively associatedwith reporting health problems from smoking crack.These findings suggest that the recent expansion ofcrack pipe distributions in this setting has likely servedto reduce health problems experienced by cracksmokers, achieving the desired outcome of the program.While crack users are obtaining their safe crack smok-ing equipment from health service points, they may alsobe exposed to education around safer smoking tech-niques and practices, by being in direct contact with ser-vice providers in the community. This may also have thebenefit of exposing drug users with no connections tohealth care to available providers in their area [27]. Aprevious study of an outreach-based crack smoking kitdistribution service indicated that unsafe smoking prac-tices such as using Brillo pads and sharing crack para-phernalia remained prevalent, even after theimplementation of the service [10], suggesting the im-portance of placing such service in a continuum ofbroader health service system and ensuring the availabil-ity of smoking kits to reduce risky smoking behaviours.Our findings of a reduction of health problems, areconsistent with harm reduction programs for peoplewho inject drugs [19], including needle exchange pro-grams and supervised injection sites, where they are ef-fective in reducing overall negative health consequences.By providing users with high-quality smoking equipmentand reducing the dependence on unsafe equipment, theunintended negative consequences, including explodingpipes, burns, and inhaling brillo fragments, are furtherreduced.This study has several limitations. First, the VIDUSand ACCESS cohorts are not random samples andtherefore generalizability of the findings may be limited.Second, data used in the study, including those for theprimary explanatory and outcome variables, were solelybased on self-report and thus could be subject to report-ing bias, including socially desirable responses. Althoughefforts were made to prompt participants to report allsources of crack pipes in the past 6 months, includingopportunistic sources, the pipe sources may have beenincorrectly categorized due to self-report bias. However,self-reported behavioural data has been shown to belargely accurate among adult drug-using populations[28]. Lastly, as with any observational research, unmeas-ured confounders may exist although we sought to re-duce this bias through adjustment of statistical modelsusing key predictors of health problems associated withcrack smoking. As this was an observational study wecannot infer causation between crack pipe acquisitionand experiencing health problems. Also, while we con-ducted the sensitivity analysis for participants who werelost to follow-up in one or more years prior to the endof the study period, and showed that the resultsremained the same, it is impossible to confirm whetherattrition was random or not, and therefore there is still apossibility that attrition may have under- or over-estimated the results.ConclusionIn summary, our findings demonstrate that the uptakeof crack pipes through health service points increasedsignificantly during a period of expansion of crack pipedistribution, while the prevalence of health problemsfrom smoking crack declined significantly during thesame time period. Further, compared to obtaining pipesonly through other sources (e.g., on the street, self-made), acquiring pipes through health service pointsonly was significantly and negatively associated withreporting health problems from smoking crack. Whilewe cannot infer causation from this observational study,these findings provide support for the distribution ofsafe crack smoking kits as an effective harm reductionmeasure for crack smokers. For communities experien-cing high rates of crack cocaine smoking and the associ-ated health problems, increased safe crack smokingequipment may serve to reduce health problems andconserve health care spending.AbbreviationsDTES: Downtown Eastside; HIV: Human immunodeficiency virusAcknowledgementsThe authors thank the study participants for their contribution to theresearch, as well as current and past researchers and staff.Prangnell et al. BMC Public Health  (2017) 17:163 Page 6 of 7FundingThe study was supported by the US National Institutes of Health(U01DA038886, R01DA021525). This research was undertaken, in part, thanksto funding from the Canada Research Chairs program through a Tier 1Canada Research Chair in Inner City Medicine which supports Dr. Evan Wood(Director, Urban Health Research Initiative, BC Centre for Excellence in HIV/AIDS and Professor, Department of Medicine, University of British Columbia).Dr. Kanna Hayashi is supported by the Canadian Institutes of Health ResearchNew Investigator Award (MSH-141971). Dr. Milloy is supported in part by theUnited States National Institutes of Health (R01DA021525), a NewInvestigator award from the Canadian Institutes of Health Research, and aScholar Award from the Michael Smith Foundation for Health Research.Availability of data and materialsThe data used for this study is not publicly available. For further informationon the data and materials used in this study, please contact thecorresponding author.Authors’ contributionsTK, MJM and KH managed the cohorts during the study period. AP and KHdesigned the present study. HD conducted the statistical analyses. APdrafted the manuscript, and incorporated suggestions from all co-authors. Allauthors made significant contributions to the conception of the analyses,interpretation of the data, and drafting of the manuscript. All authors readand approved the final manuscript.Competing interestsThe authors declare that they have no competing interests. The authorsalone are responsible for the content and writing of this paper.Consent for publicationNot applicable.Ethics approval and consent to participateAll participants provided written informed consent for study participation.The cohort studies received annual ethics approval from the University ofBritish Columbia and Providence Health Care Research Ethics Board. ThePrincipal Investigators of the cohorts (Drs. Kerr, Hayashi and Milloy) grantedpermission to use the data for the present study, which was part of thelarger cohort study activities that receive annual ethics approval by theaforementioned Research Ethics Boards.Author details1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, UrbanHealth Research Initiative, 608-1081 Burrard Street, Vancouver, BC V6Z 1Y6,Canada. 2School of Population and Public Health, University of BritishColumbia, 206 E Mall, Vancouver, BC V6T 1Z9, Canada. 3Vancouver CoastalHealth, #800-601 West Broadway, Vancouver, BC V5Z 4C2, Canada.4Department of Medicine, University of British Columbia, St. Paul’s Hospital,608-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. 5Faculty of HealthSciences, Simon Fraser University, Blusson Hall, 8888 University Drive,Burnaby, BC V5A 1S6, Canada.Received: 2 November 2016 Accepted: 1 February 2017References1. DeBeck K, Kerr T, Li K, et al. 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