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Establishing the Melbourne injecting drug user cohort study (MIX): rationale, methods, and baseline and… Horyniak, Danielle; Higgs, Peter; Jenkinson, Rebecca; Degenhardt, Louisa; Stoové, Mark; Kerr, Thomas; Hickman, Matthew; Aitken, Campbell; Dietze, Paul Jun 21, 2013

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RESEARCH Open AccessEstablishing the Melbourne injecting drug usercohort study (MIX): rationale, methods, andbaseline and twelve-month follow-up resultsDanielle Horyniak1,2*, Peter Higgs1,3,4, Rebecca Jenkinson1,2, Louisa Degenhardt5,6, Mark Stoové1,2, Thomas Kerr7,8,Matthew Hickman9, Campbell Aitken1 and Paul Dietze1,2AbstractBackground: Cohort studies provide an excellent opportunity to monitor changes in behaviour and diseasetransmission over time. In Australia, cohort studies of people who inject drugs (PWID) have generally focused onolder, in-treatment injectors, with only limited outcome measure data collected. In this study we specifically soughtto recruit a sample of younger, largely out-of-treatment PWID, in order to study the trajectories of their drug useover time.Methods: Respondent driven sampling, traditional snowball sampling and street outreach methods were used torecruit heroin and amphetamine injectors from one outer-urban and two inner-urban regions of Melbourne,Australia. Information was collected on participants’ demographic and social characteristics, drug use characteristics,drug market access patterns, health and social functioning, and health service utilisation. Participants are followed-up on an annual basis.Results: 688 PWID were recruited into the study. At baseline, the median age of participants was 27.6 years (IQR:24.4 years – 29.6 years) and two-thirds (67%) were male. Participants reported injecting for a median of 10.2 years(range: 1.5 months – 21.2 years), with 11% having injected for three years or less. Limited education,unemployment and previous incarceration were common. The majority of participants (82%) reported recent heroininjection, and one third reported being enrolled in Opioid Substitution Therapy (OST) at recruitment. At 12 monthsfollow-up 458 participants (71% of eligible participants) were retained in the study. There were few differences indemographic and drug-use characteristics of those lost to follow-up compared with those retained in the study,with attrition significantly associated with recruitment at an inner-urban location, male gender, and providingincomplete contact information at baseline.Conclusions: Our efforts to recruit a sample of largely out-of-treatment PWID were limited by drug marketcharacteristics at the time, where fluctuating heroin availability has led to large numbers of PWID accessing low-threshold OST. Nevertheless, this study of Australian injectors will provide valuable data on the natural history ofdrug use, along with risk and protective factors for adverse health outcomes associated with injecting drug use.Comprehensive follow-up procedures have led to good participant retention and limited attrition bias.Keywords: Injecting drug use, Cohort, Longitudinal studies, Australia* Correspondence: danielle@burnet.edu.au1Centre for Population Health, Burnet Institute, 85 Commercial Rd,Melbourne, VIC 3004, Australia2Department of Epidemiology and Preventive Medicine, Monash University,99 Commercial Rd, Melbourne, VIC 3004, AustraliaFull list of author information is available at the end of the article© 2013 Horyniak et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.Horyniak et al. Harm Reduction Journal 2013, 10:11http://www.harmreductionjournal.com/content/10/1/11BackgroundPeople who inject drugs (PWID) are exposed to blood-borne virus (BBV) infections [1,2], injecting-related in-juries [3,4] and risk of overdose [5-7], and experiencegreater levels of both physical and mental impairmentcompared with the general population [8-14]. Meta-analysis of cohort studies has shown that PWID have agreatly increased risk of premature death, attributable toboth AIDS and non AIDS-related causes [15], with mor-tality among opiate injectors estimated to be approxi-mately 19 times higher than the general population [16].Additionally, injecting drug use is associated with arange of social and economic harms [17-21].Our ability to respond to the significant morbidity andmortality associated with injecting drug use is limited byour lack of understanding of the complex ways in whichdrug-related harms are produced, and the ways in whichinterventional efforts can be optimised. Most Australianand much international research among this populationhas been cross-sectional, which captures only a singletime point and cannot explore how patterns of risk be-haviour, and subsequent health outcomes may changeduring a person’s injecting career.Cohort studies provide a unique opportunity to meas-ure changes in behavior and disease transmission overtime. They can, however, be difficult studies to conduct;they require sufficient funding to facilitate follow-upover time [22], and are subject to cohort effects, as wellas selection bias if they experience high levels of attri-tion, particularly if loss to follow-up is associated withimportant participant characteristics [23,24]. Addition-ally, controlling for confounding when assessing rela-tionships between behaviour and disease transmissioncan prove challenging [25,26].Cohort studies involving PWID have proven especiallydifficult; although studies have achieved follow-up ratesof 68-80%, attrition is often associated with factors suchas homelessness, incarceration and early death [27-33].While a number of successful PWID cohorts are ongoingin the USA and Canada, in Australia such studies havebeen relatively rare. In Australia, longitudinal studiesamong PWID have been conducted among in-treatmentsamples [34], which comprise mainly long-term injectorswho are either injecting infrequently or not at all, and thusmay not provide accurate information about the preva-lence and incidence of risk behaviour and disease. Whencommunity-based cohorts have been conducted, they havebeen limited by short duration of follow-up [35,36]. Out-comes measured in these studies have primarily focusedon either hepatitis C incidence or drug treatment out-comes, with limited data collected on health outcomesmore broadly [34-37]. Further, most studies involvingPWID in Australia are generally focused on an older sam-ple of PWID who initiated and became entrenched ininjecting drug use in the mid-late 1990s, a period that wascharacterised by the ready availability of heroin [38] -markedly different to the drug market characteristics oftoday. It is not clear whether patterns of drug use and re-lated risk behaviour among this older cohort is reflectiveof newer, younger injectors. For these reasons, we needlong-term studies of Australian PWID that include thosepeople who have commenced injecting more recently andcontinue to regularly inject drugs in contemporary drugmarket conditions.The Melbourne Injecting Drug User Cohort Study(MIX) was designed to explore the natural history ofinjecting drug use, as well as to identify risk and protect-ive factors for adverse health outcomes and healthservice utilisation among PWID. We aimed to recruit alarge sample of young, out-of-treatment PWID, withequal numbers preferring heroin or methamphetamineas their drug of choice. In this paper we report onmethods used to recruit and retain MIX participants, de-scribe the cohort’s baseline characteristics, and explorefactors associated with attrition at 12 months follow-up.MethodsSettingThe study was conducted in Melbourne, the second lar-gest city in Australia (population ~4 million (2009)) andcapital city of the state of Victoria [39]. Baseline recruit-ment was conducted between November 2008 and March2010, across one outer-urban and two inner-urban(Inner-West and Central) areas of Melbourne where illicitdrug markets had been identified through previous studiesand/or where primary needle and syringe exchangeprograms (NSPs) were located (Figure 1).Eligibility criteriaIndividuals were eligible for the study if they: (1) reportedbeing aged between 18 and 30 years old; (2) had injectedeither heroin or methamphetamine at least six times overthe previous six months; (3) were currently residing inMelbourne; (4) were willing to provide detailed contact in-formation including their full name, residential addressand telephone number; and (5) were able and willing toprovide a valid Medicare card number, to be used, alongwith other personal details, for data linkage (Medicare isAustralia’s universal health-care system which provides ac-cess to free or subsidised medical and allied health ser-vices; the Medicare number is unique for each individuallisted on the system).A sixth criterion, ‘not currently being prescribed Opi-oid Substitution Therapy (OST)’ was withdrawn threemonths into the study due to the high number of other-wise eligible participants who were being excluded (only31 participants were enrolled into the study during thistime). This decision was made in light of the drug marketHoryniak et al. Harm Reduction Journal 2013, 10:11 Page 2 of 14http://www.harmreductionjournal.com/content/10/1/11situation in Melbourne at the time, where fluctuating her-oin availability and purity led to ever-increasing numbersof PWID accessing low-threshold OST and cycling in andout of treatment regularly [38,40,41].Amendments were also made to the selection criterionregarding age, as it came to light that the PWID popula-tion in Melbourne is ageing, while uptake of injection isdecreasing [42], making it difficult to recruit youngerPWID. As such PWID who were slightly older than thetarget age range, but were not on OST, were also in-cluded in the study. The financial and time constraintsof the longitudinal study design were also a factor inthese decisions.Pilot interviewsThirty-two pilot interviews were conducted betweenMarch and August 2008 to identify any ambiguities orother problems within the questionnaire. Pilot partici-pants were PWID who were previously known to re-searchers, and who met the study eligibility criteria. Pilotinterviews are not reported separately to baseline data inthis report.Recruitment strategiesParticipants were recruited using Respondent DrivenSampling (RDS), street outreach and snowball sampling,in order to maximise the number and diversity of partic-ipants recruited over a limited time period [43].Respondent driven samplingRDS is a modified chain-referral sampling techniqueused for the recruitment of hard-to-reach populations[44]. A small number of ‘seed’ participants are selectedfrom the chosen population, and monetary incentivesare used to facilitate recruitment of additional partici-pants through seeds’ social networks. Weighted analysisbased on social network sizes is conducted to adjust forthe bias that is generally associated with chain-referralmethods [44,45].Up to five PWID from each recruitment site who wereknown to study researchers through participation in pre-vious studies or through agency referral, and met thestudy eligibility criteria, acted as the seeds. Followinginterview, each seed received a set of uniquely numberedrecruitment coupons and was invited to recruit a max-imum of three peers into the study. The coupons di-rected interested parties to contact researchers via afree-call telephone number, in order to be screened forstudy eligibility. Once eligibility was confirmed, an ap-pointment time was made to conduct the interview.Additional seeds were added as required to boost re-cruitment (on an ad hoc basis).Street outreach and snowball samplingA team of researchers regularly attended each of the re-cruitment locations. Eligible participants were recruitedthrough word of mouth and flyers posted in relevant com-munity agencies. PWID who met the eligibility criteriaFigure 1 Geographic location of recruitment sites, and distribution of participants by postcode of residence at baseline.Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 3 of 14http://www.harmreductionjournal.com/content/10/1/11and were known to researchers through participation inprevious studies were also actively recruited. These partic-ipants were then given the opportunity to invite their con-tacts to also participate in the study. Participants recruitedthrough street outreach and snowball sampling also re-ceived RDS coupons to distribute to their peers. All partic-ipants who returned an RDS coupon are considered ashaving been recruited through the RDS arm of the study.Questionnaire design and administrationInterviewer-administered questionnaires were conductedusing hand-held personal digital assistants (PDAs). In-formation was entered into a database constructed usingQuestionnaire Design System Versions 2.4-2.6 (NOVAResearch Company, Maryland, USA).To protect participant confidentiality, contact detailsand survey data were entered into two separate data-bases. Detailed contact information was recorded to en-hance the likelihood of successful follow-up, includingthe participant’s full name, date of birth, alias or streetname, residential address, land and mobile telephonenumbers, and contact details for a nominated friend orrelative who was likely to know the participant’s where-abouts during the study. Medicare number and RDScoupon details were also recorded in this database. Aunique identifier was assigned to each participant usingan algorithm based on the participant’s first name, sur-name and year of birth.The study questionnaire covered four domains: demo-graphic and social characteristics; drug use characteris-tics and drug market access; health and socialfunctioning; and health service utilisation. Standardisedand validated questionnaire items were used where ap-propriate. Details of selected variables collected areoutlined in Table 1.Eligibility screening and interviews were conductedon-site either in a public space (e.g. park, outdoor cafe)or in a mobile study van, with interviews taking 39 mi-nutes on average to complete (SD: 18 minutes). Partici-pants were reimbursed AU$30 (US$19.83 in November2008) for their time and out-of-pocket expenses in ac-cordance with accepted practice [46], and an additionalAU$10 for each coupon returned which resulted in aneligible interview.Follow-up proceduresIdeally, participants will be followed up annually for aminimum of four years (incorporating completion ofa structured interview, as well as the collection of ablood sample for BBV testing). Given the anticipateddifficulty in retaining participants we employed a var-iety of strategies to maintain contact with participantsbetween interviews.In addition to the extensive contact information col-lected at baseline, participants received a follow-up cardnoting the approximate date of their next interview andlisting a free-call telephone number to contact re-searchers and update their details as required. Field-based researchers maintained contact with participantsthey encountered in the field, and updated contact de-tails when possible.Two to four weeks prior to their scheduled follow-update researchers attempted to contact participants, ini-tially via telephone (using both voice calling and textmessaging). If telephone contact was unsuccessful re-searchers posted a letter to the participant’s home ad-dress or attempted contact through their nominatedfriend or relative. Field-based researchers actively soughtout participants who were due for follow-up, and sys-tematically recorded information received through theirnetworks about a participant’s whereabouts (e.g. if theyhad been incarcerated). Telephone interviews wereconducted with participants who were no longer resid-ing in Melbourne if valid contact details were available.In order to maximise the number of participants com-pleting each follow-up interview, interviews could beconducted up to two months prior to the scheduledfollow-up date if opportunistic contact was made. Therewas no end-point at which participants became ineligibleto complete an interview, however, to avoid overlap inreferent time periods, at least six months must haveelapsed between interviews.The follow-up interview was conducted using thesame procedures as the baseline interview, with minorchanges to the questionnaire to reduce repetition and in-corporate prospectively occurring events. Participantswere again reimbursed AU$30 per interview. Receipt offurther study funding facilitated the collection of venousblood samples, to be tested for HIV, hepatitis B and hepa-titis C infection. Participants who agree to provide a bloodsample at each follow-up interview receive an additionalAU$10 for the extra time and inconvenience involved.Staff trainingStudy staff received extensive training in field-based datacollection, including the use of PDAs, administration ofthe questionnaire and adherence to standard operatingprocedures for field-based researchers, as well as com-pleting accredited training courses in phlebotomy andBBV pre-and-post-test counselling.Ethics approvalThe study was approved by the Victorian Department ofHuman Services (now Department of Health) and MonashUniversity Human Research Ethics Committees. Writteninformed consent, including consent to access Medicareinformation, was obtained from all participants.Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 4 of 14http://www.harmreductionjournal.com/content/10/1/11Analysis and reportingWe conducted analyses to explore variations in partici-pant socio-demographic characteristics, patterns of druguse and health status by recruitment site using the chi-square test for categorical variables, Wilcoxon rank-sumtest for non-parametric continuous variables and theKruskal-Wallis test for non-parametric continuous vari-ables across more than two groups. Multivariable logisticregression was conducted to identify independent corre-lates of attrition at 12-months follow-up. Analyses wereconducted using Stata Version 11.1 (Statacorp LP, Texas,USA), with a significance level of p<0.05. Missing dataare not reported.This manuscript has been prepared in accordance withthe Strengthening the Reporting of Observational Stud-ies in Epidemiology (STROBE) Statement [47].ResultsBaseline characteristicsSix hundred and ninety-four PWID were recruited intothe study, but due to a technical error, baseline data forsix participants were lost, resulting in a final sample of688 participants. The median age of participants was27.6 years (IQR: 24.4 years – 29.6 years). Participantswere predominantly male (67%) and had been injectingdrugs for a median of 10.2 years (range: 1.5 months –21.2 years), with 11% of participants reporting injectingfor three years or less (n=76). The majority of partici-pants had not completed high school (80%), were un-employed (86%) and were dependent on governmentbenefits as their main source of income (86%). Onehundred and thirty-one participants (19%) reported be-ing homeless or living in unstable accommodation suchas boarding houses at the time of interview. The vastTable 1 Summary of variables collected at baselineinterviewArea ofinterestVariables collected DetailsDemographicand socialcharacteristicsGender 1Questions from thecriminality section of theOpiate Treatment Index (OTI)were used to measureprevalence of property crime,violent crime, drug dealingand fraud in the past monthDate of birthEducation statusEmployment historyIncomeCurrent livingcircumstancesCountry of birthLanguage spoken athomeIndigenous statusCriminal activity(including OTI1)Incarceration historyDug usecharacteristicsAge at injectinginitiation2The Alcohol Use DisordersIdentification Test (AUDIT)was developed by the WorldHealth Organisation as a briefassessment tool to identifyhazardous and harmfulpatterns of alcoholconsumption, focussingprimarily on symptomsoccurring in the recent pastPattern of drug use atinjecting initiationAlcohol use (AUDIT2)Drug use historyCurrent drug useDrug market accessand purchasecharacteristicsDrug treatmenthistorySocial networksHealth andsocialfunctioningHeight 3The Short-Form 8 (SF-8)assesses physical and mentalhealth over the past monthbased on questions coveringeight domains: physicalfunctioning, role limitationsdue to physical health, bodilypain, general healthperceptions, vitality, socialfunctioning, role limitationsdue to emotional problems,and mental health.WeightChronic healthconditionsPhysical and mentalhealth (SF-83)Quality of life (PWI4) 4The Personal WellbeingIndex (PWI) uses an 11-pointLikert scale to measurequality of life according toeight domains: standard ofliving, health, achieving inlife, relationships, safety,community-connectedness,future security, andspirituality/religion.BBV testing historyand current statusRisk of BBV infection(BBV-TRAQ-SV5)Drug overdose history5The Blood Borne VirusTransmission Risk AssessmentQuestionnaire Short Version(BBV-TRAQ-SV) measuresparticipation in high-riskTable 1 Summary of variables collected at baselineinterview (Continued)practices for the transmissionof blood-borne viruses. Itconsists of 15 items relatingto needle and syringecontamination, otherinjecting equipment sharing,and second personcontamination.Health serviceutilisationType of servicesattended(e.g. hospital, GP,PWID PHC clinic)Frequency of serviceattendanceReasons forattendance (drug-related, other)Costs incurred forattendanceHoryniak et al. Harm Reduction Journal 2013, 10:11 Page 5 of 14http://www.harmreductionjournal.com/content/10/1/11majority of participants reported injecting heroin duringthe month prior to recruitment (82%, n=563). Of theremaining participants, 27% reported only recent am-phetamine injection (n=34), 48% reported injectingneither heroin nor amphetamine but other drugs, pre-dominantly pharmaceutical opiates (n=60) and 25% hadabstained from drug injection in the past month (n=31).One third of participants (35%) were prescribed OST atthe time of interview, with those out-of-treatment sig-nificantly younger (median age: 27.3 years vs. 28.2 years;p=0.025), than those in treatment.One third of participants were recruited through RDS(36%, n=246), with RDS-recruited participants generallysimilar to those recruited through street outreach andsnowball sampling. Fifty-three per cent of participants(n=361) were recruited from Melbourne’s Inner West,26% from Central Melbourne (n=177), and 22% fromthe Outer-urban site (n=150). Participants generally re-sided in close proximity to recruitment sites (Figure 1). Sig-nificant differences were detected in socio-demographicand drug use characteristics of participants across recruit-ment sites (Table 2). Participants from the Inner-West andCentral sites were less likely to be born in Australia com-pared with those from the outer-urban site (76% and 77%,respectively vs. 93%), reflecting the significant South-EastAsian and Horn of Africa migrant communities in theseareas. Patterns of substance use varied across sites, with40% of participants from each of the inner-urban sitesreporting abstaining from alcohol consumption in the pastmonth, compared with 23% of participants from the outer-urban site. Participants from the outer-urban site com-menced injecting at a median age of 16 years (IQR: 14–18),slightly younger than other participants (median: 17, IQR:15–20 in Inner-West, and 17, IQR: 15–19 in Central), andwere significantly less likely to report heroin as their firstdrug injected (52% vs. 72% and 60% in Inner-West andCentral respectively). At baseline, a smaller proportion ofouter-urban participants reported recent heroin injectioncompared with those from other areas (50% vs. 94%(Inner-West) and 86% (Central)), with 11% injecting am-phetamines only, and 32% injecting other drugs only.Frequency of recent heroin injection was lowest in theouter-urban site, where a greater proportion of participantsreported being on OST at baseline (48% vs. 34% in Inner-West and 28% in Central). Patterns of recent attendance atPWID-specific primary health care (PHC) services, generalpractice (GP) clinics and hospital outpatient clinics werealso significantly different across recruitment sites.Retention at twelve months follow-upAt twelve months follow-up, 30 participants (4%) wereknown to be incarcerated, to have died or to no longerbe residing in Australia, and an additional 10 partici-pants (1%) voluntarily withdrew from the study. Of theparticipants who were eligible for follow-up, 458 (71%)were retained in the study (Figure 2), and completedfollow-up interviews a median of 357 days post-baseline(IQR: 317–435 days).The baseline characteristics of participants who com-pleted a 12-month follow-up interview were comparedwith those who did not. Independent correlates ofattrition were: recruitment from Inner West or CentralMelbourne, male gender, and failing to provide a telephonenumber or residential address at baseline (Table 3).DiscussionThe MIX cohort constitutes the largest Australiancommunity-based PWID cohort to-date, and differs fromother Australian PWID cohorts in several important ways.Firstly, our cohort is recruited from the community,and includes a large sample of out-of-treatment PWID;just over one third of our participants were prescribedOST at recruitment, compared with 51%-63% of street-based PWID and NSP-attendees interviewed in recentVictorian drug trend monitoring studies [48-50]. Assuch, it does not possess the selection effects associatedwith recruitment from a particular place, such as treat-ment facilities. Although PWID who regularly attendprimary care centres or pharmacies to obtain pharmaco-therapy treatment may be easier to retain in longitudinalstudies, PWID in-treatment tend to be different to thoseout-of-treatment, commonly being older and furtherprogressed in their injecting careers [34,40]. At the timeof recruitment, the heroin market in Melbourne hadbeen relatively depressed for some time [38,51], and re-search suggests that this reduction in heroin supply wasassociated with both reduced heroin injection amongcurrent injectors and reduced initiation into injecting[42,52]. This decreased the pool of newer, out-of-treat-ment PWID, preventing us from recruiting as large asample of these users as hoped. Despite this, our cohortwill still provide vital information about transitions intoand out of drug treatment and the factors which motiv-ate these decisions. Further, the inclusion of individualsboth in and out of treatment will allow for assessmentsof a range of barriers to treatment as well as evaluationsof the impact of treatment.Participants in our cohort were recruited from threelocations across Melbourne, where illicit drug marketsand/or NSPs are located, with significant differences insocio-demographic and drug use patterns detected acrosssites. The Inner-West and Central areas are historicallyworking-class and industrial; today, they include largepublic housing estates, and are home to significant Asianmigrant populations, and more recently, refugee popula-tions from the Horn of Africa [53-55]. Following a transi-tion from predominantly private dealing, street-basedheroin markets emerged in these areas in the mid-1990sHoryniak et al. Harm Reduction Journal 2013, 10:11 Page 6 of 14http://www.harmreductionjournal.com/content/10/1/11Table 2 Socio-demographic, drug use and health characteristics at baseline, by recruitment locationVariable Recruitment locationχ2Inner-West Central Outer-urbanN=361 N=177 N=150 p-valuen (%) n (%) n (%)Recruitment method0.615RDS 130 (36) 67 (38) 49 (33)Other 231 (64) 110 (62) 101 (67)Demographic and social characteristicsSex0.920Female 119 (33) 58 (33) 52 (35)Male 242 (67) 119 (67) 98 (65)AgeMedian (IQR) 27.4 (24.4-29.3) 28.0 (24.4-29.8) 27.8 (23.9-29.6) 0.579Aboriginal/Torres Strait Islander status0.534Yes 22 (6) 12 (7) 6 (4)No 339 (94) 165 (93) 144 (96)Country of birth<0.001Australia 275 (76) 136 (77) 139 (93)Other 84 (24) 40 (23) 11 (7)Main income source (last month)0.140Wage or salary 28 (8) 15 (9) 15 (10)Government pension or benefits 308 (85) 150 (85) 131 (89)Other1 25 (7) 11 (6) 2 (1)Employment status0.547Not employed 311 (86) 154 (87) 125 (83)Employed 50 (14) 22 (13) 25 (17)Education0.055Did not complete year 10 118 (33) 49 (28) 64 (43)Completed year 10–11 169 (47) 85 (48) 63 (42)Completed high school or higher 74 (21) 43 (24) 23 (15)Current accommodation type<0.001Owner-occupied 97 (27) 27 (15) 30 (20)Private rental 103 (29) 41 (24) 48 (32)Public housing 104 (29) 54 (30) 49 (33)No stable accommodation 55 (15) 55 (31) 21 (14)Incarceration history0.150Never been in prison 145 (40) 76 (43) 55 (37)Incarcerated once 123 (34) 46 (26) 42 (28)Incarcerated two or more times 92 (26) 54 (31) 51 (35)Recent arrest (last 12 months)0.299Yes 201 (56) 86 (49) 82 (56)No 159 (44) 89 (51) 64 (44)Drug use characteristicsAge at first injection<0.001Median (IQR) 17 (15–20) 17 (15–19) 16 (14–18)Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 7 of 14http://www.harmreductionjournal.com/content/10/1/11Table 2 Socio-demographic, drug use and health characteristics at baseline, by recruitment location (Continued)Duration of injecting career (years)0.004Median (range) 9.7 (<1-20.5) 10.2 (<1-21.2) 11.3 (1.1-21.2)First drug injected 261 (72) 106 (60) 78 (52)<0.001Heroin 91 (25) 63 (36) 59 (39)Amphetamines 4 (1) 5 (3) 1 (1)Other stimulant 3 (1) 2 (1) 10 (7)Other opiate 2 (1) 1 (1) 2 (1)OtherDrugs injected last month<0.001Heroin only 172 (48) 85 (48) 22 (15)Heroin and other drugs 165 (46) 67 (38) 52 (35)Amphetamines only 9 (3) 8 (5) 17 (11)Other drugs only2 4 (1) 8 (5) 48 (32)Did not inject in last week 11 (3) 9 (5) 11 (7)Frequency of heroin injection (last week)0.022Median (range) 5 (1–60) 4 (1–50) 3 (1–28)Frequency of methamphetamine injection(last week) 0.047Median (range) 2 (1–25) 2 (1–42) 2 (1–28)Ever been on OST 0.072Yes 260 (72) 115 (65) 114 (77)No 99 (28) 61 (35) 35 (23)Currently on OST 0.001Yes 121 (34) 50 (28) 71 (48)No 238 (66) 126 (72) 78 (52)Frequency of alcohol use (last month)0.001Never 146 (40) 69 (39) 34 (23)Once per week or less 119 (33) 48 (27) 51 (34)Two to three times per week 31 (9) 20 (11) 26 (18)Four or more times per week 65 (18) 39 (22) 38 (26)Heroin overdose (lifetime)0.654Yes 141 (39) 68 (39) 64 (43)No 219 (61) 107 (61) 84 (57)Heroin overdose (last six months)0.799Yes 36 (26) 18 (27) 14 (22)No 104 (74) 50 (74) 50 (78)Health characteristicsBBV status (self-reported)3 n=324 n=162 n=143HCV positive 164 (51) 80 (49) 64 (45) 0.863Number of health services used (last month) n=352 n=172 n=148Median (range) 1 (0–7) 1 (0–9) 1 (0–5) 0.013Health services used (last month)4Hospital Emergency Department 47 (13) 22 (12) 24 (16) 0.593Hospital Inpatients 14 (4) 10 (6) 11 (7) 0.260Hospital Outpatients 10 (3) 15 (9) 8 (5) 0.012Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 8 of 14http://www.harmreductionjournal.com/content/10/1/11and continue to remain active despite ongoing policing[38,53,56]. In contrast, the outer-urban recruitment siteis home to a predominantly Anglo-Australian commu-nity, with manufacturing and construction the main in-dustries [57,58]; MIX study participants from this sitedisplayed a preference for amphetamine and pharma-ceutical opiate injection, presumably reflecting limitedaccess to heroin due to geographic distance from activeheroin markets. Differences in patterns of alcohol con-sumption were also recorded across research sites andmay reflect a number of factors including neighbour-hood liquor outlet density [59] and differing cultural at-titudes towards alcohol consumption. The role of thegeographical environment in drug use and associatedrisks and harms warrants further investigation, and willbe examined in future.Rather than focusing specifically on BBV incidence ordrug treatment outcomes – the main focus of previouscohorts of Australian PWID [34-37] - our study collectsdata on a broad range of other health outcomes, includ-ing patterns of drug injection and injecting cessation,physical and mental health, and engagement with healthservices. Of particular interest is the fact that although58% of participants reported attending a GP clinic in thepast month, just 17% reported recent attendance at oneof the five state-funded free PWID-specific PHC clinics,despite these clinics generally being located reasonablyclose to participants’ residences. Further analysis is re-quired to explore the characteristics of clients attendingthese services and their presenting complaints, and tounderstand the ways in which patterns of health serviceutilisation are associated with factors such as recruit-ment site, service availability and patterns of drug use.The use of prospective data will also enable examinationof longer-term drug use and other health outcomesamong PWID attending these services.Table 2 Socio-demographic, drug use and health characteristics at baseline, by recruitment location (Continued)General Practice 200 (56) 95 (54) 105 (71) 0.003PWID Primary Health Care Centre 55 (15) 41 (23) 22 (15) 0.047Ambulance 25 (7) 15 (9) 14 (9) 0.620Psychologist/psychiatrist 45 (13) 30 (17) 22 (15) 0.362Other5 45 (13) 33 (19) 22 (15) 0.1651 Includes criminal activity, sex work, being supported by spouse or family member, no current income.2 Includes cocaine, ecstasy, pharmaceutical stimulants, benzodiazepines, Unisom and participants who reported >1 drug injected most often.3 Among those who reported ever being tested for HCV.4 Among participants who completed question (n=675 - 684); Not mutually exclusive.5 Includes specialist physician, dentist, allied health service.Figure 2 Participant flow diagram.Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 9 of 14http://www.harmreductionjournal.com/content/10/1/11Table 3 Correlates of attrition at 12-monthsVariable Followed-up Not followed-up Univariate MultivariableN=458 N=230 OR (95% CI) OR (95% CI)n (%) n (%)Recruitment methodRDS 164 (36) 82 (36) 1Other 294 (64) 148 (64) 1.00 (0.72-1.40)Recruitment locationInner West 230 (50) 131 (57) 2.02 (1.30-3.14)** 2.10 (1.33-3.32)**Central 111 (24) 66 (29) 2.11 (1.29-3.45)** 1.80 (1.25-2.60)**Outer-Urban 117 (26) 33 (14) 1 1SexMale 285 (62) 174 (76) 1 1Female 173 (38) 56 (24) 0.53 (0.37-0.76)** 0.56 (0.38-0.80)**AgeMedian (IQR) 27.8 (24.1-29.7) 27.3 (24.6-29.4) 0.98 (0.94-1.03)Aboriginal/Torres Strait Islander statusYes 25 (6) 15 (7) 1No 433 (95) 215 (94) 1.21 (0.62-2.34)Country of birthAustralia 373 (82) 177 (78) 1Other 84 (18) 51 (22) 0.78 (0.53-1.16)Main income source (last month)Wage or salary 36 (8) 22 (10) 1Government pension or benefits 392 (86) 197 (86) 0.82 (0.47-1.44)Other1 28 (6) 10 (4) 0.58 (0.24-1.43)Employment statusNot employed 391 (86) 199 (87) 1Employed 66 (14) 31 (13) 0.92 (0.58-1.46)EducationDid not complete year 10 139 (31) 91 (40) 1Completed year 10–11 223 (49) 94 (41) 0.64 (0.45-0.92)*Completed high school or higher 94 (21) 45 (20) 0.73 (0.47-1.14)Current accommodation typeOwner-occupied 104 (23) 50 (22) 1Private rental 115 (25) 77 (34) 1.39 (0.89-2.17)Public housing 146 (32) 61 (27) 0.87 (0.55-1.36)No stable accommodation 90 (20) 41 (18) 0.95 (0.57-1.56)Incarceration historyNever been in prison 194 (43) 82 (36) 1Incarcerated once 136 (30) 75 (33) 1.30 (0.89-1.91)Incarcerated two or more times 126 (28) 71 (31) 1.33 (0.90-1.97)Recent arrest (last 12 months)Yes 236 (52) 133 (59) 1No 218 (48) 94 (41) 0.77 (0.55-1.06)Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 10 of 14http://www.harmreductionjournal.com/content/10/1/11While we used a combination of RDS, traditionalsnowballing and street outreach to ensure that a diversesample of PWID were included in the study, there werefew significant differences across recruitment arms.While not the focus of this paper, further analysis, in-cluding the calculation of RDS-weighted populationprevalence estimates, will facilitate better understandingof the usefulness of this recruitment strategy.Despite having worked in these field sites for a numberof years [60,61], and conducting formative research priorto study commencement (field-based observations andpilot interviews), the Melbourne drug market is dynamic,and unanticipated changes in both people accessing themarket, and availability of different drug types did occur[62,63]. In response, a number of changes to the eligibilitycriteria of the study, as well as study procedures wereimplemented.Firstly, we relaxed our age restriction on eligibility,which resulted in the inclusion of 95 participants aged30–31, and 38 participants aged over 31 in the study. Assuch our sample is slightly older than initially hoped,with a median age of 27.6 years, making them slightlyyounger than participants in the Victorian cohort recruitedby Crofts et al. in the early 1990s [37], but older thancohorts recruited in Sydney and Melbourne in the mid-2000s [35,36]. It has been noted that PWID in this juris-diction are an ageing population; repeat cross-sectionalsurveys have indicated that the median age of NSP at-tendees in Victoria has increased significantly from 26years in 1997 to 35 years in 2010 [50]. Similar increasesin mean ages have been observed among PWID surveyparticipants in Victoria’s illicit drug trends monitoringsystem over the past ten years [48,64]. This is likely tobe due to the population of ageing PWID who initiatedinjecting in the 1980s and 1990s and continue to injecttoday, combined with decreasing numbers of youngpeople initiating injection [42]. The median year ofinjecting initiation among our sample, however, was1999 (IQR: 1996–2003), with a median delay of one yearto regular injecting drug use. Thus, while a proportionof participants initiated injecting during the latter yearsof the heroin ‘glut’ [38], there are few participants in ourstudy for whom drug use was already entrenched duringthis period, with the majority commencing regularinjecting in the setting of limited heroin availability.Our study initially aimed to recruit both primary her-oin and methamphetamine injectors, as most previousAustralia cohorts have been comprised mostly of heroinTable 3 Correlates of attrition at 12-months (Continued)Age at first injectionMedian (range) 17 (11–32) 17 (8–29) 0.99 (0.94-1.03)Duration of injecting career (years)Median (range) 10.0 (<1-20.8) 10.3 (<1-21.2) 1.00 (0.96-1.03)Ever been on OSTYes 335 (73) 154 (68) 1No 121 (27) 74 (32) 1.33 (0.94-1.88)Currently on OSTYes 175 (38) 67 (29) 1No 281 (62) 161 (71) 1.50 (1.06-2.11)*Drugs injected last monthHeroin only 187 (41) 92 (40) 1Heroin and other drugs 183 (40) 101 (44) 1.11 (0.53-2.34)Amphetamines only 22 (5) 12 (5) 1.47 (0.69-3.13)Other drugs only 48 (11) 12 (5) 0.51 (0.26-1.00)Did not inject last month 18 (4) 13 (6) 1.12 (0.79-1.59)Telephone number providedat baselineYes 440 (96) 195 (85) 1 1No 18 (4) 35 (15) 4.39 (2.42-7.94)** 2.90 (1.53-5.48)**Home address provided at baselineYes 454 (99) 212 (92) 1 1No 4 (1) 18 (8) 9.64 (3.22-28.82)** 6.58 (2.05-21.08)*** p<0.05, **p<0.01; Hosmer-Lemeshow test: p=0.96.Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 11 of 14http://www.harmreductionjournal.com/content/10/1/11injectors [36,37,65] and, despite reported recent in-creases in crystal methamphetamine use, relatively littlewas known about patterns of methamphetamine injec-tion. By the time study recruitment commenced how-ever, recent reports of crystal methamphetamine use hadagain decreased [66], meaning that only a small numberof primary methamphetamine injectors met the studyeligibility criteria. Nonetheless, prospective data collec-tion will enable ongoing monitoring of trends in meth-amphetamine use, and provide opportunities to explorepotential changes in drug use and health outcomes asparticipants transition between different patterns of pri-mary heroin and methamphetamine use.While other Australian PWID cohorts have been lim-ited by short durations of follow-up, the MIX cohort willbe followed up annually for a minimum of four years(with funding for further follow-up to be sought). At 12-months’ follow-up, the retention rate was 71%, compar-able to similar international studies, which had follow-uprates from 68%-83% reported over durations ranging fromthree months to four years [27-30,32]. Similar to otherlongitudinal studies of vulnerable populations, we foundthat the collection of detailed contact information at base-line, comprehensive follow-up procedures and an ongoingfield presence that allowed researchers to build familiarityand trust with participants, were all integral in trackingrespondents [67,68]; participants who did not providecomplete contact details at baseline were more likely to belost to follow-up. Importantly, while attrition was associ-ated with male gender, those lost to follow-up were other-wise similar to participants retained in the study, thuslimiting the impact of attrition bias on our findings. Thelong duration of follow-up, combined with future datalinkage through administrative data (e.g. the Medicaresystem) beyond the period of face-to-face follow-up willproduce rich and versatile data enabling a better under-standing of the natural history of injecting drug use andpatterns of morbidity and mortality (overall, as well asamong particular subgroups of PWID). These data willbe integral to the evaluation of health and social inter-ventions among this group.LimitationsDue to ethical considerations, we were not permitted torecruit participants younger than 18 years of age, how-ever due to a miscommunication a small number ofparticipants aged 16 and 17 were inadvertently recruitedinto the study; ethics approval has been obtained to usedata from these participants. It remains unclear whetherthis population of adolescent PWID are being targetedeffectively by research or health interventions.Given the complexities involved with street-based re-cruitment across multiple field sites, involving a large re-search team, it was not possible to monitor how manyPWID were invited but declined to participate in thestudy. Unwillingness to consent to the provision of Medi-care information may have been associated with decliningto participate in the study.As with much PWID research, our data may be lim-ited by selection bias, and as behavioural data were self-reported, also by recall and social acceptability bias.Future data linkage and BBV testing will enable us to as-sess the accuracy of some self-reported variables.ConclusionsAlthough PWID can be difficult to retain in longitudinalstudies, well-planned follow-up procedures and an on-going field presence can lead to high levels of retentionand minimal attrition bias. Data from the MIX cohortwill allow for the exploration of the natural history ofinjecting drug use, and the identification of both riskand protective factors for adverse health outcomes asso-ciated with injecting drug use in Australia.AbbreviationsBBV: Blood borne virus; GP: General practice; MIX: Melbourne injecting druguser cohort Study; NSP: Needle and syringe exchange program; OST: Opioidsubstitution therapy; PDA: Personal digital assistant; PHC: Primary health care;PWID: People who inject drugs; RDS: Respondent driven sampling;STROBE: Strengthening the reporting of observational studies inEpidemiology.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsDH was involved in project coordination, baseline recruitment and datacollection, conducted the data analysis and led the writing of themanuscript. PH was involved in the study design, baseline recruitment andparticipant follow-up. RJ was responsible for data management and assistedwith analysis. PD is the chief investigator on the MIX study, and a chiefinvestigator within the Drug Policy Modelling Project. All other authors wereinvolved in the initial study design and development, and have contributedto and approved the final manuscript.Acknowledgements and fundingThe authors wish to thank the study participants, and the staff of thecommunity-based organisations who assisted with recruitment. Thank you tomembers of the MIX study team who assisted with participant recruitment,follow-up and interviewing: Jessica Andrews, Stuart Armstrong, ShelleyCogger, Danielle Collins, Duyen Duong, Robyn Dwyer, Adonis Espinosa,Lucinda Franklin, Daniel O’Keefe, Amy Kirwan, Tara Newen, Oanh Nguyen,Cerissa Papanastasiou, DeArne Quelch, Rebecca Reale and Jessica Wade.The MIX Study is conducted as part of the Drug Policy Modelling Program(www.dpmp.unsw.edu.au); the study is funded by The Colonial FoundationTrust and the National Health and Medical Research Council (NHMRC Grant#545891). DH receives support from the Australian Government through anAustralian Postgraduate Award and through the Burnet Institute Centre forResearch Excellence into Injecting Drug Use (CREIDU). PD is supported by anARC Future Fellowship, PH by an NHMRC Postdoctoral Fellowship and LD byan NHMRC Senior Research Fellowship. MS receives support through CREIDU.TK is supported by the Michael Smith Foundation for Health Research andthe Canadian Institutes for Health Research. The authors gratefully acknowledgethe contribution to this work of the Victorian Operational Infrastructure SupportProgram. The funding bodies played no role in the study design, data analysis orpreparation of the manuscript for publication.Horyniak et al. Harm Reduction Journal 2013, 10:11 Page 12 of 14http://www.harmreductionjournal.com/content/10/1/11Author details1Centre for Population Health, Burnet Institute, 85 Commercial Rd,Melbourne, VIC 3004, Australia. 2Department of Epidemiology and PreventiveMedicine, Monash University, 99 Commercial Rd, Melbourne, VIC 3004,Australia. 3Kirby Institute, University of New South Wales, Corner Boundaryand West Streets, Darlinghurst, NSW 3020, Australia. 4National Drug ResearchInstitute, Curtin University, 54-62 Gertrude St, Fitzroy, VIC 3065, Australia.5Centre for Health Policy, Programs and Economics, School of PopulationHealth, University of Melbourne, Level 5, 207 Bouverie St, Melbourne, VIC3010, Australia. 6National Drug and Alcohol Research Centre, University ofNew South Wales, 22-32 King St, Randwick, NSW 2031, Australia. 7UrbanHealth Research Initiative, British Columbia Centre for Excellence in HIV/AIDS,Vancouver, BC V6Z 1Y6, Canada. 8Department of Medicine, University ofBritish Columbia, Vancouver, BC V6T 1Z4, Canada. 9School of Social &Community Medicine, University of Bristol, Canynge Hall, Bristol BS8 2PS,United Kingdom.Received: 27 March 2012 Accepted: 14 June 2013Published: 21 June 2013References1. 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Harm Reduction Journal 2013 10:11.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitHoryniak et al. Harm Reduction Journal 2013, 10:11 Page 14 of 14http://www.harmreductionjournal.com/content/10/1/11

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