CP 6691 Research Methods Guide to critical summary of quantitative literature reviews 1- Provide a complete APA reference to the article you will be reporting about in class (authors, year of publication, title, journal, volume, etc.) 2- Start by stating whether the article is a primary (original) or a secondary source. Was the article peer-reviewed? Is it from a reputable source? 3- Literature reviews survey many academic sources to provide a current overview of a particular topic. Describe what is the topic (problem) of the literature review you chose and why is this topic relevant for counselors and the counseling profession– mention populations (P) and variables that have a bearing on the topic of the review. 4- Provide a brief overview of the relationships, contradictions, inconsistencies and gaps in the literature identified by the authors. 5- What suggestions or next steps are mentioned? 1 REVIEW doi:10.1111/j.1360-0443.2010.02932.x Health outcomes associated with methamphetamine use among young people: a systematic review add_2932 991..1002 Brandon D. L. Marshall1,2 & Daniel Werb1,2 British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, Vancouver, BC, Canada,1 School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada2 ABSTRACT Objectives Methamphetamine (MA) use among young people is of significant social, economic and public health concern to affected communities and policy makers. While responses have focused upon various perceived severe harms of MA use, effective public health interventions require a strong scientific evidence base. Methods We conducted a systematic review to identify scientific studies investigating health outcomes associated with MA use among young people aged 10–24 years. The International Classification of Diseases (ICD-10) was used to categorize outcomes and determine the level of evidence for each series of harms. Results We identified 47 eligible studies for review. Consistent associations were observed between MA use and several mental health outcomes, including depression, suicidal ideation and psychosis. Suicide and overdose appear to be significant sources of morbidity and mortality among young MA users. Evidence for a strong association between MA use and increased risk of human immunodeficiency virus (HIV) and other sexually transmitted infections is equivocal. Finally, we identified only weak evidence of an association between MA use and dental diseases among young people. Conclusions Available evidence indicates a consistent relationship between MA use and mental health outcomes (e.g. depression, psychosis) and an increased risk of mortality due to suicide and overdose. We found insufficient evidence of an association between MA use and other previously cited harms, including infectious diseases and dental outcomes. As such, future research of higher methodological quality is required to further investigate possible associations. Current interventions should focus attention upon MA-related health outcomes for which sound scientific evidence is available. Keywords Adolescent, drug use, methamphetamine, systematic review, youth. Correspondence to: Brandon D. L. Marshall, Michael Smith Foundation for Health Research Senior Graduate Trainee, Urban Health Research Initiative, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada. E-mail: bmarshall@cfenet.ubc.ca Submitted 18 September 2009; initial review completed 27 October 2009; final version accepted 21 December 2009 INTRODUCTION The use of amphetamine-type substances (ATS) and methamphetamine (MA) in particular is recognized increasingly as a major global health problem [1]. The 2009 World Drug Report suggests that the global prevalence of MA use is second only to cannabis, with estimates suggesting that up to 51 million individuals (1.2% of the global population aged 15–64 years) have used MA at least once in the past 12 months [2]. Although, globally, MA consumption has remained relatively constant since 2002, regions such as South America and the Middle East have experienced significant increases, particularly among young people [3]. In the United States, data from the 2007 National Survey on Drug Use and Health (NSDUH) indicate that 0.1% of 12–17-year-olds and 0.4% of 18–25-year-olds reported using MA in the past month, representing more than 150 000 young users in the United States [4]. In many countries, responses to MA consumption among youth have focused primarily upon supply reduction through precursor chemical regulation, drug seizures and the dismantling of clandestine MA laboratories [5]. Although these methods appear to be successful in some instances at reducing MA-related hospital and treatment admissions [6,7], recent analyses have demonstrated that their overall impact appears to be temporary [8]. Given the limited effectiveness of these interventions several drug policy organizations, including the United Nations Office on Drugs and Crime, have called for a more © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 992 Brandon D. L. Marshall & Daniel Werb balanced approach aimed at reducing both the supply and demand of MA [3,9]. Prevention and treatment programmes that work to decrease the number of new users, limit harm among novice users and reduce morbidity among chronic users are the central tenets of MA demand reduction strategies for adolescents and youth [5]. However, if effective public health responses to MA use are to be implemented, a clear and comprehensive understanding of the specific harms associated with MA use among youth is necessary. Although several reviews examining the harms associated with MA use have been published [10–12], few are systematic and none have focused upon the use of MA and associated harm among young people. Because many MA-related health outcomes may present only after long-term chronic use [13], the health implications for novice and young users may be significantly different and thus require further investigation. MA use may affect individuals differently depending upon their physical and psychological developmental stage, therefore more evidence is also required to inform the development and implementation of treatment models for MA dependence among young people [14]. Finally, a systematic review of MA-related health harms among youth is of particular relevance to clinical settings, where physicians may wish to screen young patients for morbidities associated with the use of MA and counsel current users to reduce future harms. Therefore, we conducted a systematic review to evaluate the scientific evidence base regarding health outcomes associated with MA use among individuals aged 10–24 years. Given the high level of public concern regarding the harms of MA use [15], we sought to adhere to the most rigorous methodological standards for conducting systematic reviews to provide a solid evidence base for future MA-related research and knowledge translation activities. METHODS We followed the guidelines developed and recommended by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) group [16]. Search strategy We conducted a comprehensive review of 30 electronic databases to identify potentially relevant studies, dissertations and conference proceedings, including: MEDLINE®; Ovid MEDLINE® In-Process and Other NonIndexed Citations; EBM Reviews, including the Cochrane Database of Systematic Reviews; EMBASE; International Pharmaceutical Abstracts; Journals@Ovid; CINAHL; PsychINFO; Science Citation Index Expanded and Social Sciences Citation Index (via Web of Science®); CAB Direct; ERIC; Sociological Abstracts; SocINDEX; Academic Search Complete; LGBT Life; ProQuest Dissertations and Theses; Conference Papers Index; Native Health Research Database; BioMed Central; and the NLM Gateway Meeting Abstracts database. Search terms included methamphetamine and common variants, youth, adolescent, juvenile and young people. Where possible, methodological filters were used to exclude case reports and case series. Hand-searching of relevant conference proceedings, reference lists of published reviews and included studies was also conducted. We restricted our search to English-language publications but did not restrict with respect to year of publication. All searches were conducted between 2 January 2009 and 31 January 2009. The detailed search strategy may be found in the online version of this paper (see Supporting Information details at the end of this paper). Inclusion criteria Studies were eligible for inclusion if they were published in a peer-reviewed journal, dissertation database or academic conference proceedings. Grey literature, case reports and case series were excluded. Consistent with the World Health Organization (WHO) definition of young people (i.e. adolescents and youth) [17], studies were excluded if the mean or median age of the sample was greater than 24 or less than 10 years of age. Where necessary, we contacted study authors for additional data. Reviews and editorials were excluded. In cases where conference abstracts and peer-reviewed publications presented identical data, we opted to include the most recent publication. To be eligible for inclusion, studies must have examined a specific and well-defined group of MA users. Studies assessing use of broad classes of drugs (e.g. stimulants) were excluded. However, to be consistent with previous reviews [10,18], we chose to include studies that examined the effects of amphetamine or methamphetamine. In order to maximize clinical relevance of our findings, health outcomes were categorized according to the WHO International Classification of Diseases (ICD)-10 [19]. Studies that did not report an outcome with an analogous ICD-10 code (e.g. drug dealing, syringe sharing) were excluded. We also excluded disorders designated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as being diagnosed in infancy, childhood or adolescence (e.g. attention deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) [20]. Given that these disorders usually present first during childhood or early adolescence, it is probable that they are antecedents as opposed to consequences of MA use. Fetal or infant outcomes related to the prenatal use of MA during pregnancy were © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 Health outcomes and methamphetamine use also excluded, although complications during pregnancy or childbirth were eligible for inclusion. The primary author (B.M.) screened the titles and abstracts of each record. Studies that did not meet our eligibility criteria were excluded, while full-text articles were retrieved for all studies for which eligibility was unclear. Full-text versions of the remaining articles were then screened independently by both authors (B.M. and D.W.). Based upon the inclusion criteria, studies were categorized as ‘potentially relevant’ or ‘irrelevant’ by each author. Classifications were then compared for each record and any discrepancies were discussed until a consensus was reached. Data extraction and analysis A standardized form was created to manage data extraction for each eligible record. Information regarding the size, scope, sample, methods and results of each study were entered by one author (B.M.) and checked independently for accuracy and completeness by the other (D.W.). Quality assessment Eligible studies were assessed for methodological quality using a modified version of the Downs & Black checklist for the reporting of health care studies [21]. This checklist has been shown to be a valid and reliable tool for the assessment of the methodological quality of observational studies [21]. Higher scores out of a total score of 18 represent higher overall methodological quality. Each study was scored by the primary author (B.M.) and verified independently by the co-author (D.W.). Detailed information regarding the checklist items and scoring criteria are available online (see Supporting Information details at the end of this paper). RESULTS Literature search Database and hand-searching yielded a total of 2097 potentially eligible studies published between 1970 and 2009. An initial screening led to the exclusion of 1866 records; a further 182 were removed following an assessment of the full-text articles. Initial agreement between the authors was substantial (k = 0.70); consensus-based reasons for exclusion are provided in Fig. 1. We were unable to determine the age distribution of the samples presented in two studies despite attempting to contact study authors for further information; thus, 47 publications that met our inclusion criteria were included in the final qualitative synthesis. Summaries of each study and their main findings are presented in Table 1. 993 Methodological quality assessment The modified Downs & Black scores ranged from 6 to 17, with a median score of 13 [interquartile range (IQR): 10–16]. We observed a statistically significant trend of improving methodological quality over time (r2 = 0.26, P < 0.001). An analysis of the checklist subdomains revealed that ‘external validity’ received the poorest score across all studies, with only 13 (28%) containing samples representative of the entire population from which they were recruited (i.e. comprising the entire population, an unselected sample of consecutive patients or a random sample). Summary of included studies Of the 47 studies included in the review, the majority were conducted in Canada and the United States (n = 26, 55%), with the remaining studies conducted in Thailand (n = 9, 19%), Australia (n = 3, 6%), Taiwan (n = 3, 6%), Japan (n = 2, 4%) and one study (2%) conducted in South Africa, China, Argentina and the United Kingdom, respectively. The median sample size was 478 (IQR: 172–1795). Most studies employed cross-sectional designs (n = 34, 72%), while few used case–control designs (n = 6, 13%), prospective cohorts (n = 5, 11%) or retrospective reviews (n = 2, 4%). The majority relied upon self-reported MA use (n = 36, 77%), with recall periods varying between life-time use and use in the past week. Five (11%) studies used a combination of selfreport and urine tests to define MA use [22–26], four (9%) studies relied on a diagnosis of MA dependence [27–30] and two (4%) studies relied on MA positive toxicology tests from coroner’s reports [31,32]. Potential confounding factors were assessed inconsistently across studies, and only 18 (38%) studies presented an adjusted or stratified analysis. The studies included in this review examined a variety of health outcomes, although more than half (n = 27, 57%) assessed diseases and conditions classified as mental and behavioural disorders. Outcomes involving infectious diseases [e.g. human immunodeficiency virus (HIV), sexually transmitted infections (STIs)] were also common (n = 13, 28%). Eight (17%) studies examined outcomes classified as ‘external causes of morbidity and mortality’, an ICD-10 category that includes experiencing violence, suicide and self-harm. Two (4%) studies examined health outcomes related to injuries and poisonings (i.e. overdose) and two (4%) assessed the association between MA use and dental diseases. Diseases during pregnancy and childbirth were identified in one study. One paper examining emergency room use and one describing overall mortality were also included. © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 Brandon D. L. Marshall & Daniel Werb 2,085 unique records identified through database searching 12 additional records identified through other sources (i.e., hand searching and citation lists) 2,097 records eligible for inclusion Included Eligibility Screening Identification 994 2,097 records screened 1,866 records excluded based on screening of title and abstract 231 full-text articles assessed for eligibility 182 full-text articles excluded: • 52 – outcome not eligible • 46 – no quantitative data • 41 – age criterion not met • 27 – MA not an exposure • 8 – duplicated data • 7 – case series • 1 – article not in English 49 studies eligible for qualitative synthesis 2 studies articles excluded since age information could not be obtained from authors 47 studies included in qualitative synthesis Figure 1 Flowchart of screening and selection process Mental and behavioural disorders Studies examining mental and behavioural disorders spanned the entire time-period (i.e. 1970–2009) and were of variable methodological quality. Analyses of data from the nationally representative Youth Risk Behavior Survey (YRBS) in the United States have suggested that suicidal ideation and eating disorders are more common among youth who have ever used MA [33–35]. The NSDUH has also been used to examine mental heath outcomes associated with MA use among youth in the United States. Using responses from the K6 Scale (a validated tool used to screen individuals for severe mental illness [36]), HermanStahl et al. demonstrated that elevated scores were more common among youth who reported recently using MA; however, this association did not persist in a multivariate model [37]. MA users in this large nationally representative sample were also more likely to have been the recipient of mental health treatment, and were at increased risk for having a past year DSM-IV diagnosis for alcohol or drug use disorders [38,39]. Symptoms of MA-induced psychosis among young MA users were well described within eligible studies. One of the earliest studies included in our review demonstrated that young MA injectors reported higher rates of paranoia compared to those who consumed MA orally [26]. Another early study observed an increased risk of hallucinations and paranoia among daily MA users compared to those who used MA less frequently [40]. Hallucinations have been found to be one of the most common health problems reported by MA users [41–43]. Frequent use of MA has also been associated with elevated scores on the hypochondriasis and schizophrenia subscales of the Minnesota Multiphasic Personality Inventory [27,44]. The link between MA use and depression has been examined in a number of different settings. For example, treatment samples in Taiwan and the United States have shown that individuals seeking treatment for MA dependence are more likely to be diagnosed with major depressive disorder upon entry, and that this is particularly acute among those who initiated MA use at 15 years or younger [22,45,46]. In Chiang Rai, Thailand, depressive symptoms were shown to be elevated among students who tested positive for MA in urinalysis, although this association failed to remain significant in multivariate © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Cross-sectional (At Risk Youth Study) Cross-sectional (At Risk Youth Study) Cross-sectional venue-based sample Cross-sectional school-based sample Nationally representative sample (YRBS) Nationally representative sample (YRBS) Cross-sectional Cross-sectional Nationally representative household survey (NSDUH) Cross-sectional school-based sample Wood 2008, Canada [57] Werb 2008, Canada [61] Walls 2008, USA [59] Plüddemann 2008, South Africa [51] Pisetsky 2008, USA [33] Luncheon 2008, USA [34] Celentano 2008, Thailand [52] Celentano 2008 [47] Wu 2007, USA [39] Poulin 2007, Canada [78] Nationally representative survey (NSDUH) Cross-sectional (At Risk Youth Study) Martin 2009, Canada [77] Herman-Stahl 2007, USA [37] Prospective cohort Sutcliffe 2009, Thailand [53] Nationally representative sample (YRBS) Prospective cohort Sutcliffe 2009, Thailand [48] Noffsinger 2007, USA [35] Study design Study Table 1 Summary of included studies (n = 47). 23 645 individuals aged 18–25 Nevada high school students 12 990 high school students in Atlantic provinces. 24 409 individuals aged 16–23 1189 sexually active MA users; age: 18–25 658 sexually active MA users; age: 18–25 6826 female high school students in United States 13 917 high school students in United States 4605 grade 8 students in Cape Town 142 LGBT youth; age: 14–21 478 street youth recruited through street outreach; median age: 22 478 street youth recruited through street outreach; median age: 22 478 street youth recruited through street outreach; median age: 22 519 sexually active MA users recruited through street outreach; age: 18–25 863 sexually active MA users recruited through street outreach; age: 18–25 Participant characteristics 17 10 16 17 15 15 16 14 13 15 16 16 15 12 16 Score Self-reported MA use in the past 12 months Self-reported life-time history of MA use Self-reported non-medical MA use in the past 12 months Self-reported life-time history of MA use Self-reported frequency of MA use past 3 months Self-reported frequency of MA use past 3 months Self-reported life-time history of MA use Self-reported life-time history of MA use Self-reported MA use Self-reported life-time history of MA use Self-reported MA use in the past 6 months Self-reported life-time history of MA use Self-reported MA use in the past 6 months Self-reported frequency of MA use in the past 3 months Self-reported MA use Exposure measurement High K6 Scale score: screening tool for severe mental illness Suicide attempt, suicidal ideation Depressive symptoms (CES-D scale) High K6 scale scores more common among MA users [OR = 2.8 (2.1–3.7)] but not significant in multivariate model MA users more likely to report suicide attempts and suicidal ideation (both P < 0.001) MA users more likely to report elevated depression symptoms All outcomes more common among MA users. Frequent MA use only associated with depression among males [AOR = 1.3 (1.0–1.6)] Depression symptoms (CES-D cut-off ⱖ22) Mental health treatment, DSM-IV diagnosis of alcohol or drug use disorders Frequent MA not associated with prevalent STI for women or men MA use was associated independently with suicidal ideation [AOR = 2.2 (1.4–3.3)] Eating disorders more common among MA-using females (OR = 3.3) and males (OR = 12.9) STIs more common among MA users MA use associated with suicidal ideation (AOR = 2.98, P < 0.05) but not with suicide attempts Overdose associated with MA injection [AOR = 2.33 (1.25–4.32)] and non-injection [AOR = 2.00 (1.06–3.77)] MA use not associated with HCV but was associated with mental illness [OR = 1.79 (1.18–2.73)] and ER use [AOR = 1.66 (1.04–2.66)] MA use not associated with experiencing assault [AOR = 1.20 (0.70–2.07)] Frequency of MA use not associated with STI incidence for women [RR = 1.63 (0.62–4.29)] or men [RR = 1.55 (0.74–3.26)] Depression less likely among early [AOR = 0.44 (0.26–0.74)] and late [AOR = 0.66 (0.43–1.00)] cessation group Main findings Prevalence of laboratory-confirmed STI Suicidal ideation Ever had an eating disorder (self-reported) Ever had an STI (told by health care worker) Suicide attempt, suicidal ideation Self-reported non-fatal overdose in the past 6 months Laboratory-confirmed HCV, selfreported mental illness and ER use Self-reported victim of assault in the past 6 months Incidence of laboratory-confirmed STI Depression symptoms at last visit (CES-D cut-off ⱖ22) Outcome(s) Health outcomes and methamphetamine use 995 Addiction, 105, 991–1002 © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Case–control treatment sample Cross-sectional treatment sample Nationally representative survey (NSDUH) Cross-sectional Case–control study Cross-sectional Cross-sectional Cross-sectional treatment sample Cross-sectional treatment sample Case–control study Cross-sectional (UFO Study) Cross-sectional treatment sample Yen 2006, Taiwan [22] Yen 2006, Taiwan [46] Wu 2006, USA [38] Sommers 2006, USA [41] Miura 2006, Japan [79] Martin 2006, Canada [42] Baskin-Sommers 2006, USA [60] Yen 2005, Taiwan [23] Rawson 2005, USA [43] Palmer 2005, USA [27] Ochoa 2005, USA [62] McGregor 2005, Thailand [28] Retrospective review Prospective cohort (VAHCS) Degenhardt 2007, Australia [50] Callor 2005, USA [31] Prospective cohort (VAHCS) Degenhardt 2007, Australia [49] Cross-sectional treatment sample Cross-sectional Garofalo 2007, USA [72] McGrath 2005, China [64] Study design Study Table 1 Cont. 9 10 164 suicide cases in Utah; age: 2) Depression and anxiety (CIS-R and GHQ > 2) HIV prevalence, psychological distress (GSI) Outcome(s) High prevalence of MA among suicide completers (9%) MA users more likely to report teeth grinding (P < 0.001) and jaw pain (P < 0.001) Greater withdrawal severity associated with year of MA use (P < 0.001) Injecting MA and heroin associated with overdose [AOR = 1.7 (1.2–2.7)] MA users scored higher on schizophrenia (P = 0.017) and hypochondriasis (P = 0.027) scales Depression (P = 0.015) and hallucinations (P = 0.009) more common among MA group Frequency of MA use not associated with suicidal ideation Self-harm not associated with MA use MA users more likely to report hallucinations (P = 0.024) and test positive for HCV (P = 0.014) MA users more likely to report treatment [AOR = 8.7 (4.0–19)] More frequent MA use associated with a greater number of self-reported psychological problems MA use associated with alcohol dependence [AOR = 32 (15–69)] and abuse [AOR = 17 (9–35)] Early-onset females more likely to have depressive disorder (P = 0.002). MA use associated with depressive symptoms, adjustment disorder, any disorder, and >1 comorbid disorders (versus 0) Early depression and anxiety not predictive of future MA use in adulthood [AOR–1.1 (0.7 = 1.8)] Current MA use associated with CIS-R and early MA associated with GHQ > 2 in adulthood MA use not independently associated with HIV positivity or psychological distress Main findings 996 Brandon D. L. Marshall & Daniel Werb Addiction, 105, 991–1002 © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Cross-sectional treatment sample Cross-sectional (PHRAYA) Cross-sectional (UFO Study) Cross-sectional (PHRAYA) Cross-sectional treatment sample Prospective cohort Cross-sectional treatment sample Cross-sectional Hospital-based case–control study Case–control study Retrospective review of deaths Cross-sectional treatment sample Cross-sectional Retrospective review Beyrer 2004, Thailand [54] Paz-Bailey 2003, Thailand [55] Shafer 2002, USA [56] Sattah 2002, Thailand [24] Vongsheree 2001, Thailand [25] Hawke 2000, Canada and USA [45] Uchida 1995, Japan [29] Hall 1994, Australia [40] Little 1988, USA [30] Di Cugno 1981, Argentina [63] Kalant 1975, Canada [32] Gardner 1972, UK [26] Cox 1972, Canada [44] Davis 1970, USA [58] 75 patients with hepatitis; mean age: 21 75 drug users 104 patients with non-opioid drug abuse; mean age: 23 26 deaths involving MA in Ontario; median age: 24 198 youth in a treatment programme 104 pregnant women in hospital; mean age: 23 231 drug users; median age: 24 94 incarcerated youth; mean age: 18 937 youth in treatment programmes; age: 15–18 1725 youth attending detoxification clinic; mean age: 22 Youth attending vocational schools; mean age: 18 304 young IDU; median age: 22 Youth attending vocational schools; mean age: 18 535 youth at a treatment centre; age: 4) Mean DMF index significantly higher for MA users (P < 0.01) and MA/marijuana users (P < 0.001) compared to controls No association between MA use and pregnancy complications Daily MA users more likely to report hallucinations and paranoia Suicide attempters more likely diagnosed with MA-induced psychotic disorder (P < 0.05) MA users more likely to have: depression (P = 0.008), dysthymia (P = 0.001) and PTSD (P = 0.006) MA use not associated with HIV infection Depression score higher for MA users (P < 0.001) but not significant in model MA associated with HIV infection [OR = 2.5 (0.9–7.3)] MA use associated with CT among women [OR = 2.6 (1.1–6.1)] but not significant in model Participants admitted for MA less likely to report STD symptoms [AOR = 0.5 (0.3–0.8)] MA use during sex not associated with HIV [AOR = 0.8 (0.5–1.5)] AOR: adjusted odds ratio; ARR: adjusted rate ratio; CES-D: Centre for Epidemiologic Studies depression scale; CT: Chlamydia trachomatis; CIS-R: Clinical Interview Schedule; DMF index: Decayed, Missing, Filled index; ER: emergency room; GHQ: General Health Questionnaire; GSI: Global Symptom Inventory; HCV: hepatitis C; HIV: human immunodeficiency virus; IDU: injection drug user; LGBT: lesbian, gay, bisexual or transgender; MA: methamphetamine; MMPI: Minnesota Multiphasic Personality Inventory; MSM: men who have sex with men; NSDUH: National Survey on Drug Use and Health; PHRAYA: prevalence of HIV, STD, Drug Use and Risk Behaviors in Adolescents and Young Adults; PTSD: post-traumatic stress disorder; STD: sexually transmitted disease; STI: sexually transmitted infection; UFO Study: ‘You-Find-Out’ Study; VAHCS: Victoria Adolescent Health Cohort Study; YMS: Young Men’s Survey; YRBS: youth risk behaviour survey. Cross-sectional (YMS) Harawa 2004, USA [80] Health outcomes and methamphetamine use 997 Addiction, 105, 991–1002 998 Brandon D. L. Marshall & Daniel Werb analyses [24]. In Chiang Mai, Celentano et al. observed that frequent MA use (defined as ⱖ4 days per week) was associated with depressive symptoms, although only among males [47]. However, a recent prospective cohort study of young Thai MA users found that depressive symptoms decreased significantly among those who stopped using MA over the 12-month study period [48]. In Australia, analyses of a prospective cohort of high school students found evidence to suggest that MA initiation during adolescence was associated with adulthood depression, whereas early depression was not predictive of future MA use [49,50]. Infectious diseases All studies examining infectious disease outcomes were conducted in North America or Thailand, except for one South African study demonstrating that recent and lifetime users of MA were more likely to have been told by a health care worker that they had an STI [51]. In Thailand, STI outcomes (i.e. self-reported symptoms and laboratory-confirmed diagnoses) and their relationship with MA use have been well described. The majority of studies have reported non-significant findings. For example, in a large prospective cohort study of sexually active MA users in Chiang Mai province, frequent MA use was not associated with either prevalence [52] or incidence [53] of laboratory-confirmed STIs. A separate Thai study examining self-reported STI symptoms among a treatment sample of drug users observed that symptoms were less common among those seeking treatment for MA abuse, compared to those with opioid dependence [54]. One school-based study has shown a significantly increased risk of Chlamydia trachomatis infection among MA-using women, although this association did not persist in a multivariate model [55]. Four studies examined the association between MA use and HIV prevalence. Two were conducted among young MSM populations in the United States and both reported null results. In an analysis of data from the multi-site Young Men’s Survey, MA use during sex was not associated with HIV infection, and in a smaller community-based study in Chicago, recent MA use failed to reach significance in a multivariate model. Evidence to suggest an increased risk of infectious diseases (i.e. HIV and hepatitis C virus) among young MA injectors is also equivocal [42,56–58]. External causes of morbidity and mortality Several studies have assessed the relationship between MA use and intentional self-harm and suicide. For example, in a cross-sectional analysis of Nevada students who completed the 2005 YRBS, participants who reported ever using MA were also more likely to report attempting suicide [35]. In a Japanese treatment sample, suicide attempts were more common among those diagnosed with MA-induced psychosis [29]. A populationbased 5-year review of suicide cases in Utah observed a high prevalence of MA (9%) in toxicological samples [31]. In contrast, two community-based studies failed to show an association between MA use and intentional self-harm [59,60]. Injuries and poisonings Two studies examined non-fatal overdose among young drug users [61,62]. These studies report significantly elevated risks of overdose among non-injection MA users [61], as well as among those who inject MA either on its own or in combination with other illicit drugs such as heroin [61,62]. Diseases of the oral cavity, salivary glands and jaws Evidence to suggest a strong association between MA use and dental diseases among young people is scant. One case control study conducted in Argentina observed a greater number of decayed, missing or extracted teeth among MA users compared to controls [63]. One other cross-sectional study of detained Chinese youth reported that teeth grinding and jaw pain were more common among a group of primarily amphetamine users [64]. However, both studies scored 9 on the modified Downs & Black checklist and contained significant misclassification, confounding and generalizability problems. Diseases during pregnancy, childbirth and the perperium One hospital-based case control study of pregnant women observed that women who reported MA use were no more likely to experience complications during pregnancy compared to non-MA-using controls [30]. Other outcomes In one recent study conducted in Canada, street youth who ever used MA were more likely to report using the emergency room in the past 6 months [57]. The only study eligible for inclusion in our review that addressed mortality was a retrospective review of 26 deaths involving MA in Ontario, Canada between 1972 and 1973. The authors estimated the mortality rate among MA users to be four times that of the general population [32]. DISCUSSION In the present systematic review we identified consistent, scientifically sound evidence of an association between MA use among youth and a number of health outcomes, © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 Health outcomes and methamphetamine use including depression, psychosis, behavioural problems and concurrent drug and alcohol use disorders. Furthermore, the results of our review suggest that suicide and overdose probably contribute to increased morbidity and mortality among young MA users. However, we failed to observe a strong evidence base for several previously cited MA-related harms, including an increased risk of HIV/ STI infection and onset of dental diseases such as tooth decay among MA users. Many studies did not meet the methodological standards proposed by Downs & Black for the reporting of health care studies [21]. Due largely to the high proportion of cross-sectional studies based on convenience or treatment samples, fewer than a third of eligible studies met the criteria for external validity. Future research of higher methodological quality is therefore required before conclusions can be reached regarding many of the harms frequently perceived to be associated with MA use among youth. Few studies have reported data relevant to the development of effective prevention and treatment interventions targeted towards MA using young people [14]. One randomized controlled trial to examine the effectiveness of a preventive intervention for MA use has been conducted [65]. Other interventions, including the Montana Meth Project (MMP), have approached MA consumption among youth as a ‘consumer product marketing problem’, relying upon saturation-level advertising to graphically depict perceived negative health and social consequences of MA use through social marketing [66]. Empirical evidence to support the campaign is, however, weak; in fact, the graphic depiction of MA users as unhygienic and dangerous appears to have coincided with increases in the acceptability of MA use among target populations [67]. Given the disputed effectiveness of social marketing campaigns rooted in the perception and exaggeration of MA-related harms [67], evidence-based interventions that rely upon scientifically rigorous evidence are recommended. The paucity of sound evidence regarding the association between MA use and dental diseases warrants special consideration. Given that extensive media and public health attention has focused upon the oral health effects of MA use (i.e. ‘meth mouth’) [68,69], it is surprising that we identified only two studies examining dental outcomes among youth. While it is possible that extensive tooth decay and MA-induced caries may only present after several years of chronic MA use (and thus may result in the exclusion of studies from this review on account of the older median age of study samples), some authors have noted the lack of valid evidence supporting a specific risk of dental diseases associated exclusively with MA use [70]. Several mechanisms have been proposed (e.g. MA-induced xerostomia, increased consumption of soft drinks, reduced hygienic behaviours [71]), 999 although it is noteworthy that all causal pathways remain hypothetical [70]. Further epidemiological research in this area is therefore required. In many eligible studies [22,24,52,55,72], the strength of bivariate associations between MA use and health outcomes diminished greatly after controlling for potential confounders, and the observed confounded relationships indicate that MA use may often act as a marker of other causal factors. Given these findings, future studies should assess potential confounders carefully and adjust for them using stratified or multivariate analyses. Furthermore, cross-sectional designs (such as those employed by a majority of the included studies) fail to disentangle the temporal relationship between MA use and hypothesized harms. It is likely that several conditions examined in this review are, in fact, risk factors or antecedents for MA use as opposed to outcomes. Prospective cohort studies that follow individuals’ MA use trajectories and health outcomes over time are therefore crucial to the creation of better-informed evidence-based policies and interventions for MA prevention and treatment. For example, although many cross-sectional studies have identified a link between MA use and depression, only with the publication of more recent studies using prospective cohort designs [48–50] have experts begun to delineate the temporal relationship between MA use and depression. Evidence from these studies suggests that MA use (particularly in early adolescence) precedes the onset of depressive symptoms in adulthood. This information is critical for intervention, and research able to identify temporal relationships between MA use and health outcomes should be prioritized. The lack of a consistent association between MA use and some health outcomes (e.g. STI symptoms) may be due to measurement bias in the ascertainment of exposures or outcomes. The vast majority of studies utilized self-reported measures of drug use and other risk behaviours (e.g. condom use); however, these measures have been shown to have reasonable validity in a number of settings [73–75]. Furthermore, self-reported MA use has been shown to have substantial agreement with urinalysis among youth seeking treatment for substance abuse [76]. None the less, it is possible that observed null associations do not represent evidence of no effect, but are instead indicative of systematic or random misclassification diluting true relationships between MA use and harms. Our review is limited by the fact that we excluded some potential sources of data such as grey literature and case series. However, we argue that drug policy and public health responses are best informed by high-quality peerreviewed evidence, and thus we opted to restrict our search to peer-reviewed sources. As in all systematic reviews, it is possible that we missed some eligible studies © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 1000 Brandon D. L. Marshall & Daniel Werb in our search strategy. We sought to mitigate this bias by duplicating our search and by contacting authors to obtain necessary information. We also recognize that the selection and qualitative synthesis of eligible studies is ultimately a subjective process. However, having two reviewers conduct the screening procedure independently, using a standardized form to extract the data, and assessing methodological quality using a validated checklist, helped to ensure a level of objectivity in our search strategy. We conclude that despite widespread government and public alarm concerning MA use among young people, there remains limited rigorous scientific evidence for many of the perceived harms related to MA use. Despite the limitations of the available evidence, however, it is clear that MA use is associated with certain acute health outcomes. Until further research of sufficient methodological quality is conducted, current preventive and treatment interventions should concentrate on harms for which strong and consistent associations with MA use have been established. Declarations of interest None. Acknowledgements We would particularly like to thank Dr Thomas Kerr, Dr Jean Shoveller, Dr Jane Buxton, Dr Thomas Patterson, Kathryn Hornby, Deborah Graham and Tricia Collingham for their research and administrative assistance. 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Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. © 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction Addiction, 105, 991–1002 This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
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