Transitions Through Stages of Alcohol Use, Use Disorder and Remission: Findings from Te Rau Hinengaro, The New Zealand Mental Health Survey.

AIMS: To understand transitions from alcohol use to disorder, we examine timing of transitions between stages of alcohol use and associations between transitions and socio-demographic factors. SHORT SUMMARY: Using nationally representative data, we found that the majority of alcohol use disorders develop by age 25. Increased alcohol use within a participant's cohort was associated with subsequent transition across all stages of alcohol use and disorder. Fifty percent of dependence cases had not remitted after 9 years. METHODS: A nationally representative sample with a 73% response rate included 12,992 participants aged 16 and older. The Composite International Diagnostic Interview (CIDI 3.0) was used to assess age at initial alcohol consumption, commencement of regular consumption, symptoms of alcohol abuse and dependence, and year-long remission. Alcohol consumption in an age- and gender-matched cohort, education, gender and age at commencement of use were investigated as covariates. RESULTS: Among all respondents, 94.6% used alcohol, 85.1% used alcohol regularly, 11.4 and 4.6% had developed alcohol abuse and dependence disorders, respectively. Of those with an abuse or dependence disorder, 79.9 and 67.2% had remitted, respectively. Increased alcohol use within a participant's cohort was associated with subsequent transition across all stages. The majority of disorders had developed by age 25. Considerable time was spent with disorder; 50% of dependence cases had not remitted after 9 years. Men were at greater risk of disorder and less likely to remit. CONCLUSIONS: Interventions should target young people and cohort-specific consumption with resources also allocated to long-term treatment provision for alcohol dependency.

Alcohol abuse in developed and developing countries in the World Mental Health Surveys: Socially defined consequences or psychiatric disorder?

BACKGROUND: Previous single country research has raised concerns that: (1) the DSM-IV diagnosis of alcohol abuse (AA) is met primarily through the hazardous use criterion related to drinking and driving and (2) that the hazardous use and social consequences AA criteria primarily reflect varying socioeconomic and cultural factors rather than psychiatric disorder. METHODS: Using representative cross-national data from the 21 countries in the World Mental Health surveys, adults meeting DSM-IV lifetime criteria for AA but not dependence from 10 developed (n=46,071) and 11 developing (n=49,761) countries were assessed as meeting AA with the hazardous use or the social consequences criteria. RESULTS: Between 29.3% (developed) and 16.2% (developing) of respondents with AA met only the hazardous use criterion. AA cases with and without hazardous use were similar in age-of-onset, course, predictors, and psychopathological consequences in both developed and developing countries. DISCUSSION AND CONCLUSIONS: Despite some associations of the AA criteria with socioeconomic factors, the hazardous use and social consequences criteria were significantly associated with psychiatric predictors and sequelae. The findings indicate that these criteria reflect psychiatric disorder and are appropriate for inclusion as DSM-5 Alcohol Use Disorder criteria. SCIENTIFIC SIGNIFICANCE: These findings support a psychiatric rather than a sociocultural view of the hazardous use and social consequences symptoms and provide evidence that they are appropriate diagnostic criteria cross-nationally with utility in a wide range of socioeconomic environments. This suggests consideration for their adoption by ICD-11. Further research is needed on the implications of these results for prevention and treatment.

Drop out from out-patient mental healthcare in the World Health Organization's World Mental Health Survey initiative.

BACKGROUND: Previous community surveys of the drop out from mental health treatment have been carried out only in the USA and Canada. AIMS: To explore mental health treatment drop out in the World Health Organization World Mental Health Surveys. METHOD: Representative face-to-face household surveys were conducted among adults in 24 countries. People who reported mental health treatment in the 12 months before interview (n = 8482) were asked about drop out, defined as stopping treatment before the provider wanted. RESULTS: Overall, drop out was 31.7%: 26.3% in high-income countries, 45.1% in upper-middle-income countries, and 37.6% in low/lower-middle-income countries. Drop out from psychiatrists was 21.3% overall and similar across country income groups (high 20.3%, upper-middle 23.6%, low/lower-middle 23.8%) but the pattern of drop out across other sectors differed by country income group. Drop out was more likely early in treatment, particularly after the second visit. CONCLUSIONS: Drop out needs to be reduced to ensure effective treatment.

Patients' expectations of screening and preventive treatments.

PURPOSE: An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS: Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS: The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION: Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to overestimate benefits may affect patients' decisions to use such interventions, and practitioners should be aware of this tendency when discussing these interventions with patients.

Chlamydia trachomatis testing sensitivity in midstream compared with first-void urine specimens.

PURPOSE: Traditionally first-void urine specimens are used to test for Chlamydia trachomatis. In contrast, midstream urine specimens are traditionally recommended for microscopy and culture of presumptive bacterial urinary tract infections. The ability to test for both C trachomatis and urinary tract infection on a single midstream urine specimen would greatly aid clinical practice, as an urinary tract infection is an extremely common complaint in primary care. This study set out to determine how well positive C trachomatis results obtained on first-void specimens would correlate with positive findings in matched midstream specimens. METHODS: One hundred women with a first-void urine specimen positive for C trachomatis also provided midstream specimens for comparison. All specimens had C trachomatis testing performed using a DNA detection method. RESULTS: Of the 100 eligible participants with a first-void specimen positive for C trachomatis, 96 (96%) also had a positive midstream specimen (95% exact confidence limits, 90.1%, 98.9%). CONCLUSIONS: These results suggest that by using newer nucleic acid amplification techniques (NAATs), timing of specimen collection is not so important in testing for C trachomatis as previously thought. The sensitivity of NAAT testing on midstream urine specimens in women is sufficiently equivalent to testing on first-void specimens to consider in clinical practice and research settings where first-void specimens have formerly been collected.

Distal ureteral calculi: US follow-up.

PURPOSE: To assess accuracy of ultrasonographic (US) follow-up of distal ureteral calculi by using computed tomography (CT) and conventional radiography (kidneys, ureters, and bladder) as reference standards. MATERIALS AND METHODS: The study was approved by the Regional Ethics Committee, and written informed consent was obtained. One hundred fifty-eight patients with CT-diagnosed symptomatic ureteral calculi, for whom follow-up imaging was ordered, were enrolled from February 2006 to December 2008. Six were excluded, having not met study entry criteria, with 121 men (mean age, 49 years; range, 20-91 years) and 31 women (mean age, 44 years; range, 34-77 years) completing the protocol with adequate reference standard imaging. Targeted transabdominal US occurred coincidently with follow-up CT (n = 92) or radiography (n = 60), with US evaluation prospectively compared considering sensitivity and specificity. Statistical analysis was performed with a χ(2) test, t test, or paired t test, as appropriate. RESULTS: Results of nine US examinations were nondiagnostic because of inadequate ureteral visualization, and among these, two cases showed residual distal calculi. Of the remaining 143 patients, 33 had residual distal calculi, all visualized with US. There was a single false-positive study, giving sensitivity, including nondiagnostic US examinations, of 94.3% (95% confidence interval [CI]: 80.8%, 99.3%) and specificity of 99.1% (95% CI: 95.3%, 100%). All calculi appeared hyperechoic with posterior acoustic shadowing. Additional diagnostic features included presence of a hypoechoic rim and Doppler twinkle artifact. Mean stone length was 7.2 mm ± 2.6 (standard deviation) (range, 4-18 mm). Mean ureteral length visualized was 36.4 mm (range, 12-77 mm), with calculi positioned at a mean of 13.1 mm ± 11.2 (range, 0-40 mm) from the ureterovesical junction (UVJ). Nondiagnostic results were more likely with bladder volume of 110 mL or less (eight [16%] of 50 vs one [1%] of 102, P = .0009). CONCLUSION: Ureteral calculi within 35 mm of the UVJ can be accurately followed-up by using transabdominal US, which substantially reduces patient radiation burden.

Multiple aspects of sexual orientation: prevalence and sociodemographic correlates in a New Zealand national survey.

Sexual orientation consists of multiple components. This study investigated both sexual identity and same-sex sexual behavior. Data came from the New Zealand Mental Health Survey, a nationally representative community sample of New Zealanders aged 16 years or older, interviewed face-to-face (N = 12,992, 48% male). The response rate was 73.3%. Self-reported sexual identity was 98.0% heterosexual, 0.6% bisexual, 0.8% homosexual, 0.3% "Something else," and 0.1% "Not sure." Same-sex sexual behavior with a partner was more common: 3.2% reported same-sex sexual experience only and 1.9% reported both experience and a relationship. For analysis of childhood and lifecourse, five sexuality groups were investigated: homosexual, bisexual, and heterosexual divided into those with no same-sex sexual experience, experience only, and experience and relationship. The non-exclusively heterosexual groups were more likely to have experienced adverse events in childhood. Educational achievement and current equivalized household income did not differ systematically across the sexuality groups. Only 9.4% of the exclusively heterosexual lived alone, compared with 16.7% of bisexuals and 19.0% of homosexuals. Heterosexuals were more likely than bisexuals or homosexuals to have ever married or had biological children, with differences more marked for males than for females. Heterosexuals with no same-sex sexual experience were more likely to be currently married than the other two heterosexual groups. Restricting comparisons to heterosexual, bisexual, and homosexual identification ignores the diversity within heterosexuals. Differences between the bisexual and homosexual groups were small compared with the differences between these groups and the exclusively heterosexual group, except for sex (80.8% of bisexuals were female).

Cross-national comparisons of sex differences in opportunities to use alcohol or drugs, and the transitions to use.

Sex differences in opportunities to use alcohol or drugs, and transition to use, were investigated in 15 surveys, in 2001-2004 (Europe 6; Americas 3; Africa 2, Asia 3; Oceania 1). The paper focuses on 18-29 year olds (N = 9,873). The World Mental Health Survey Initiative oversaw the surveys; each country obtained its own funding. A complex picture emerged with different results for alcohol and for drugs and for opportunity to use and the transition to use. Sex differences in opportunity to use alcohol were small except in Lebanon and Nigeria, whereas for drugs, the largest differences were in Mexico and Colombia.

Early cannabis use and estimated risk of later onset of depression spells: Epidemiologic evidence from the population-based World Health Organization World Mental Health Survey Initiative.

Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age > or =17 years) risk of a depression spell, using data on 85,088 subjects from 17 countries participating in the population-based World Health Organization World Mental Health Survey Initiative (2001-2005). In all surveys, multistage household probability samples were evaluated with a fully structured diagnostic interview for assessment of psychiatric conditions. The association between early-onset cannabis use and later risk of a depression spell was studied using conditional logistic regression with local area matching of cases and controls, controlling for sex, age, tobacco use, and other mental health problems. The overall association was modest (controlled for sex and age, risk ratio = 1.5, 95% confidence interval: 1.4, 1.7), was statistically robust in 5 countries, and showed no sex difference. The association did not change appreciably with statistical adjustment for mental health problems, except for childhood conduct problems, which reduced the association to nonsignificance. This study did not allow differentiation of levels of cannabis use; this issue deserves consideration in future research.

A profile of prognostic and molecular factors in European and Maori breast cancer patients.

BACKGROUND: New Zealand Maori have a poorer outcome from breast cancer than non-Maori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Maori and European breast cancer patients from Christchurch, New Zealand. METHODS AND RESULTS: Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Maori, 310 European) were evaluated. Fewer tumours were high grade in Maori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival.In addition, tumour and serum samples from a sub-cohort of 14 Maori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. CONCLUSIONS: In this Christchurch cohort of breast cancer patients, Maori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences.

Rapid-cycling bipolar disorder: cross-national community study.

BACKGROUND: The epidemiology of rapid-cycling bipolar disorder in the community is largely unknown. AIMS: To investigate the epidemiological characteristics of rapid-cycling and non-rapid-cycling bipolar disorder in a large cross-national community sample. METHOD: The Composite International Diagnostic Interview (CIDI version 3.0) was used to examine the prevalence, severity, comorbidity, impairment, suicidality, sociodemographics, childhood adversity and treatment of rapid-cycling and non-rapid-cycling bipolar disorder in ten countries (n = 54 257). RESULTS: The 12-month prevalence of rapid-cycling bipolar disorder was 0.3%. Roughly a third and two-fifths of participants with lifetime and 12-month bipolar disorder respectively met criteria for rapid cycling. Compared with the non-rapid-cycling, rapid-cycling bipolar disorder was associated with younger age at onset, higher persistence, more severe depressive symptoms, greater impairment from depressive symptoms, more out-of-role days from mania/hypomania, more anxiety disorders and an increased likelihood of using health services. Associations regarding childhood, family and other sociodemographic correlates were less clear cut. CONCLUSIONS: The community epidemiological profile of rapid-cycling bipolar disorder confirms most but not all current clinically based knowledge about the illness.

First and subsequent nonmelanoma skin cancers: incidence and predictors in a population of New Zealand renal transplant recipients.

BACKGROUND: Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancers (NMSCs). The aims of this study were to determine the incidence and subsequent history of NMSCs in RTRs, together with risk factors. METHODS: All patients transplanted between July 1972 and March 2007, and followed up at Christchurch Hospital, New Zealand, were studied. Immunosuppression regimens were mostly prednisone, azathioprine, cyclosporine and prednisone, mycophenolate mofetil, cyclosporine since 1998. RESULTS: Of 384 RTRs, 96 developed at least one NMSC. The median time to first NMSC was 18.3 years (95% CI 14.2, 22.9) from transplant, as estimated by survival analysis. Individual predictors of first NMSC in RTRs were older age at first transplant (P < 0.0001), male sex (P = 0.006) and initial immunosuppression regimen (P = 0.001); only age (P < 0.0001) and male gender (P = 0.003) were significant predictors in a joint model. The mean rate of subsequent NMSCs was 1.67 per year (95% CI = 1.32, 2.11). Older age at first renal transplant (P = 0.009) or at discovery of the first NMSC (P = 0.01) was associated with a higher annual rate of new NMSC following the discovery of the first NMSC. The median survival time to a second NMSC was 2.2 years (CI 1.4, 3.0). Fourteen patients died of metastatic squamous cell carcinoma (15% case fatality). CONCLUSIONS: NMSCs are a major health issue for RTRs, especially in older males. Once RTRs have developed their first NMSC, ongoing surveillance and prompt treatment are essential.

Smoking estimates from around the world: data from the first 17 participating countries in the World Mental Health Survey Consortium.

OBJECTIVE: To contribute new multinational findings on basic descriptive features of smoking and cessation, based upon standardised community surveys of adults residing in seven low-income and middle-income countries and 10 higher-income countries from all regions of the world. METHODS: Data were collected using standardised interviews and community probability sample survey methods conducted as part of the WHO World Mental Health Surveys Initiative. Demographic and socioeconomic correlates of smoking are studied using cross-tabulation and logistic regression approaches. Within-country sample weights were applied with variance estimation appropriate for complex sample survey designs. RESULTS: Estimated prevalence of smoking experience (history of ever smoking) and current smoking varied across the countries under study. In all but four countries, one out of every four adults currently smoked. In higher-income countries, estimated proportions of former smokers (those who had quit) were roughly double the corresponding estimates for most low-income and middle-income countries. Characteristics of smokers varied within individual countries, and in relation to the World Bank's low-medium-high gradient of economic development. In stark contrast to a sturdy male-female difference in the uptake of smoking seen in each country, there is no consistent sex-associated pattern in the odds of remaining a smoker (versus quitting). CONCLUSION: The World Mental Health Surveys estimates complement existing global tobacco monitoring efforts. The observed global diversity of associations with smoking and smoking cessation underscore reasons for implementation of the Framework Convention on Tobacco Control provisions and prompt local adaptation of prevention and control interventions.

The Kessler Psychological Distress Scale in Te Rau Hinengaro: the New Zealand Mental Health Survey.

OBJECTIVE: The aim of the present study was to compare two versions of the Kessler 10-item scale (K10), as measures of population mental health status in New Zealand. METHOD: A nationwide household survey of residents aged > or = 16 years was carried out between 2003 and 2004. The World Mental Health Composite International Diagnostic Interview (CIDI 3.0) was used to obtain DSM-IV diagnoses. Serious mental illness (SMI) was defined as for the World Mental Health Surveys Initiative and the USA National Comorbidity Survey Replication. Participants were randomly assigned to receive the 'past month' K10 or the 'worst month in the past 12 months' K10. There were 12 992 completed interviews; 7435 included the K10. The overall response rate was 73.3%. Receiver operator characteristic (ROC) curves were used to examine the ability of both K10 versions to discriminate between CIDI 3.0 cases and non-cases, and to predict SMI. RESULTS: Scores on both versions of the K10 were higher for female subjects, younger people, people with fewer educational qualifications, people with lower household income and people resident in more socioeconomically deprived areas. Both versions of the K10 were effective in discriminating between CIDI 3.0 cases and non-cases for anxiety disorder, mood disorders and any study disorder. The worst month in the past 12 months K10 is a more effective predictor than the past 1 month K10 of SMI (area under the curve: 0.89 vs 0.80). CONCLUSIONS: Either version of the K10 could be used in repeated health surveys to monitor the mental health status of the New Zealand population and to derive proxy prevalence estimates for SMI. The worst month in the past 12 months K10 may be the preferred version in such surveys, because it is a better predictor of SMI than the past month K10 and also has a more logical relationship to 12 month disorder and 12 month service use.

Sonographic appearances of the endometrium after termination of pregnancy in asymptomatic versus symptomatic women.

OBJECTIVE: The purpose of this study was to describe normal sonographic appearances of the endometrium in asymptomatic women after elective termination of pregnancy (TOP) and to determine whether sonographic findings are discriminatory in symptomatic women after TOP. METHODS: Sonographic parameters were compared in prospectively recruited women after elective TOP. The first 38 were asymptomatic. In a later group, 105 had symptoms suggestive of retained products of conception (RPOC). Endometrial thickness, cavity irregularity, echogenicity of cavity contents, color Doppler flow, and resistive indices (RIs) were assessed. In the symptomatic group, sonographic findings were correlated with symptoms and histologic results. RESULTS: There was a marked overlap in sonographic appearances between the groups. The endometrial cavity is commonly irregular and thickened and may show prominent color Doppler flow in women with an uneventful course as well as in women with histologically proven RPOC. Differences between asymptomatic and symptomatic women were only seen for: endometrial thickness (10.8 mm [range, 1-29 mm] versus 15.3 mm [range, 1.8-34 mm]; P = .0005), and cavity irregularity was greater in symptomatic women (P = .001). Color Doppler flow mean RIs were similar. Symptoms were similar in women proceeding to curettage versus no curettage; no significant relationship was found between individual symptoms and sonographic parameters. Chorionic villi were seen in 47 of 56 women (84%) with positive histologic results. CONCLUSIONS: Sonographic appearances and symptoms correlate poorly with each other and with histologic results. Sonography has limited benefits in triaging women with suspected RPOC after TOP in the first trimester. Our findings support a more conservative approach to suspected RPOC after TOP.

Association of chromosome band 8q22 copy number gain with high grade invasive breast carcinomas by assessment of core needle biopsies.

Genetic analysis of breast tumor core needle biopsies may provide early diagnostic information that is useful to direct subsequent clinical management. We report metaphase comparative genomic hybridization (CGH) analysis of 42 core needle biopsies prospectively sampled from invasive ductal breast carcinomas of 41 patients, and show that recurrent chromosomal copy number changes are associated with histologically defined tumor features. As far as is known, this is the first time CGH profiles from diagnostic breast tumor core needle biopsies have been reported in association with pathological data in such detail. A comparison of Grade 1 (n = 7), Grade 2 (n = 16), and Grade 3 tumors (n = 19) revealed a chromosomal copy number gain involving 8q22 that was associated with higher grade (1/7 vs. 16/19, respectively) and therefore altered cell differentiation status. CGH results were validated using tumor touch imprints prepared from a subgroup from the same sample set (n = 18) by fluorescence in situ hybridization (FISH) and two probes selected from regions of interest within 8p21 and 8q22. Overall concordance between CGH and FISH for 8p21 and 8q22 imbalances was 9/18 (50%) and 12/18 (67%), respectively. When FISH and CGH data were combined, and tumors classified according to better defined resected tumor histology available for 34cases, 19/19 Grade 3 tumors showed 8q22 gain compared with 0/6 Grade 1 tumors and 4/9 Grade 2 tumors. Further comprehensive studies are required to verify the biological significance of this association and its potential to facilitate early clinicopathological assessment of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys.

BACKGROUND: Alcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organization's (WHO's) World Mental Health (WMH) Survey Initiative. METHODS AND FINDINGS: Household surveys with a combined sample size of 85,052 were carried out in the Americas (Colombia, Mexico, United States), Europe (Belgium, France, Germany, Italy, Netherlands, Spain, Ukraine), Middle East and Africa (Israel, Lebanon, Nigeria, South Africa), Asia (Japan, People's Republic of China), and Oceania (New Zealand). The WHO Composite International Diagnostic Interview (CIDI) was used to assess the prevalence and correlates of a wide variety of mental and substance disorders. This paper focuses on lifetime use and age of initiation of tobacco, alcohol, cannabis, and cocaine. Alcohol had been used by most in the Americas, Europe, Japan, and New Zealand, with smaller proportions in the Middle East, Africa, and China. Cannabis use in the US and New Zealand (both 42%) was far higher than in any other country. The US was also an outlier in cocaine use (16%). Males were more likely than females to have used drugs; and a sex-cohort interaction was observed, whereby not only were younger cohorts more likely to use all drugs, but the male-female gap was closing in more recent cohorts. The period of risk for drug initiation also appears to be lengthening longer into adulthood among more recent cohorts. Associations with sociodemographic variables were consistent across countries, as were the curves of incidence of lifetime use. CONCLUSIONS: Globally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more recent cohorts, who also have higher levels of illegal drug use and extensions in the period of risk for initiation.