DNA content abnormality frequently develops in the right/proximal colon in patients with primary sclerosing cholangitis and inflammatory bowel disease and is highly predictive of subsequent detection of dysplasia.

AIMS: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD, termed PSC-IBD) have a higher risk of harbouring nonconventional and/or invisible dysplasias, especially in the right/proximal colon, than those with IBD alone. We postulated that DNA content abnormality may be frequently detected in the right/proximal colon in PSC-IBD patients, even in the absence of dysplasia, and that this may predispose to progression to nonconventional and/or invisible dysplasias that are often associated with increased rates of aneuploidy and advanced neoplasia. METHODS AND RESULTS: DNA flow cytometry was performed on 96 morphologically benign colon biopsies taken throughout the colon from 25 PSC-IBD patients during the surveillance colonoscopy that preceded the next procedure that detected dysplasia. Thirty (31%) of the 96 benign colon biopsies in this dysplasia group demonstrated abnormal DNA content, with a propensity for the right/proximal colon (70%) (P < 0.001). In contrast, only one (1%) of 87 benign colon biopsies from 20 IBD patients without neoplasia (control group) demonstrated DNA content abnormality, and it was from the left colon. For analysis per patient, 48% (12 of 25) of the patients in the dysplasia group had abnormal DNA content compared with 5% (1 of 20) of the control group (P = 0.002). Of the 12 PSC-IBD patients with DNA content abnormality, invisible dysplasia was detected in 10 (83%) patients on follow-up, nine (75%) of whom had nonconventional dysplasia. CONCLUSION: PSC-IBD patients have an increased risk of developing abnormal DNA content in the right/proximal colon, predating the detection of dysplasia.

Persistent or recurrent Barrett's neoplasia after an endoscopic therapy session is associated with DNA content abnormality and can be detected by DNA flow cytometric analysis of paraffin-embedded tissue.

Endoscopic therapy is currently the standard of care for the treatment of high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) in patients with Barrett's esophagus (BE). Visible lesions are treated with endoscopic mucosal resection (EMR), which is often coupled with radiofrequency ablation (RFA). However, endoscopic therapy may require multiple sessions (one session every 2-3 months) and does not always assure complete eradication of neoplasia. Furthermore, despite complete eradication, recurrences are not uncommon. This study assesses which potential risk factors can predict a poor response after endoscopic sessions. Forty-five BE patients who underwent at least one endoscopic session (EMR alone or ablation with or without preceding EMR) for the treatment of HGD/IMC, low-grade dysplasia (LGD), or indefinite for dysplasia (IND) were analyzed. DNA flow cytometry was performed on 82 formalin-fixed paraffin-embedded samples from the 45 patients, including 78 HGD/IMC, 2 LGD, and 2 IND. Eight non-dysplastic BE samples were used as controls. Three to four 60-micron thick sections were cut from each tissue block, and the area of HGD/IMC, LGD, or IND was manually dissected. Potential associations between clinicopathologic risk factors and persistent/recurrent HGD/IMC following each endoscopic session were examined using univariate and multivariate Cox models with frailty terms. Sixty (73%) of the 82 specimens showed abnormal DNA content (aneuploidy or elevated 4N fraction). These were all specimens with HGD/IMC (representing 77% of that group). Of these 60 HGD/IMC samples with abnormal DNA content, 42 (70%) were associated with subsequent development of persistent/recurrent HGD/IMC (n = 41) or esophageal adenocarcinoma (EAC; n = 1) within a mean follow-up time of 16 months (range: 1 month to 9.4 years). In contrast, only 6 (27%, all HGD/IMC) of the 22 remaining samples (all with normal DNA content) were associated with persistent/recurrent HGD/IMC. For outcome analysis per patient, 11 (24%) of the 45 patients developed persistent/recurrent HGD/IMC or EAC, despite multiple endoscopic sessions (mean: 3.6, range: 1-11). In a univariate Cox model, the presence of abnormal DNA content (hazard ratio [HR] = 3.8, p = 0.007), long BE segment ≥ 3 cm (HR = 3.4, p = 0.002), endoscopic nodularity (HR = 2.5, p = 0.042), and treatment with EMR alone (HR = 2.9, p = 0.006) were significantly associated with an increased risk for persistent/recurrent HGD/IMC or EAC. However, only abnormal DNA content (HR = 6.0, p = 0.003) and treatment with EMR alone (HR = 2.7, p = 0.047) remained as significant risk factors in a multivariate analysis. Age ≥ 60 years, gender, ethnicity, body mass index (BMI) ≥ 30 kg/m2, presence of hiatal hernia, and positive EMR lateral margin for neoplasia were not significant risk factors for persistent/recurrent HGD/IMC or EAC (p > 0.05). Three-month, 6-month, 1-year, 3-year, and 6-year adjusted probabilities of persistent/recurrent HGD/IMC or EAC in the setting of abnormal DNA content were 31%, 56%, 67%, 79%, and 83%, respectively. The corresponding probabilities in the setting of normal DNA content were 10%, 21%, 28%, 38%, and 43%, respectively. In conclusion, in BE patients with baseline HGD/IMC, both DNA content abnormality and treatment with EMR alone were significantly associated with persistent/recurrent HGD/IMC or EAC following each endoscopic session. DNA content abnormality as detected by DNA flow cytometry identifies HGD/IMC patients at highest risk for persistent/recurrent HGD/IMC or EAC, and it also serves as a diagnostic marker of HGD/IMC with an estimated sensitivity of 77%. The diagnosis of HGD/IMC in the setting of abnormal DNA content may warrant alternative treatment strategies as well as long-term follow-up with shorter surveillance intervals.

Generational sex work and HIV risk among Indigenous women in a street-based urban Canadian setting.

In Canada, Indigenous women are over-represented among new HIV infections and street-based sex workers. Scholars suggest that Aboriginal women's HIV risk stems from intergenerational effects of colonisation and racial policies. This research examined generational sex work involvement among Aboriginal and non-Aboriginal women and the effect on risk for HIV acquisition. The sample included 225 women in street-based sex work and enrolled in a community-based prospective cohort, in partnership with local sex work and Aboriginal community partners. Bivariate and multivariate logistic regression modeled an independent relationship between Aboriginal ancestry and generational sex work and the impact of generational sex work on HIV infection among Aboriginal sex workers. Aboriginal women (48%) were more likely to be HIV-positive, with 34% living with HIV compared to 24% non-Aboriginal women. In multivariate logistic regression model, Aboriginal women remained three times more likely to experience generational sex work (AOR:2.97; 95%CI:1.5,5.8). Generational sex work was significantly associated with HIV (AOR = 3.01, 95%CI: 1.67-4.58) in a confounder model restricted to Aboriginal women. High prevalence of generational sex work among Aboriginal women and three-fold increased risk for HIV infection are concerning. Policy reforms and community-based, culturally safe and trauma informed HIV-prevention initiatives are required for Indigenous sex workers.

Increased Active Inflammation in the Colon is Not a Reliable Predictor of an Elevated Risk of Dysplasia in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

Although the increased risk of colorectal neoplasia in patients with both primary sclerosing cholangitis (PSC) and ulcerative colitis (UC; termed PSC-UC) is well documented, the mechanism through which concomitant PSC increases the risk of colorectal neoplasia remains unclear. Given that the risk of colorectal neoplasia in UC is positively correlated with increased histologic inflammation, this study sought to investigate whether increased histologic inflammation could be used to stratify the risk of dysplasia development in patients with PSC-UC. Twenty patients with PSC-UC and dysplasia were compared with 30 control patients with PSC-UC who had no history of neoplasia. For each patient, all surveillance biopsies were scored using a 4-point scoring system: (1) no epithelial neutrophils = 0, (2) cryptitis only = 1, (3) cryptitis plus crypt abscess in <50% of crypts = 2, and (4) crypt abscess in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration = 3. A score was designated for each biopsy, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores derived from all colonoscopies for each patient were used to determine the patient's overall mean, maximum, and inflammation burden scores. In both the dysplasia and control groups, the 3 summative inflammation scores were calculated independently for the entire colon, right colon, and left colon. The dysplasia group consisted of 14 (70%) men and 6 (30%) women, with a mean age of 27 years at UC diagnosis and a long history of pancolitis (mean duration: 17 y). A total of 49 dysplastic lesions were detected in the dysplasia group, and 8 (40%) of the 20 patients had multifocal dysplasia. The majority of dysplastic lesions belonged to nonconventional subtypes (n = 28; 57%) and were located in the right colon (n = 37; 76%). Irrespective of the colon segment, there was no significant difference in the 3 summative inflammation scores between the dysplasia and control groups (P > 0.05). However, in each group, the 3 summative inflammation scores were significantly higher in the right colon than in the left colon (P< 0.05). In conclusion, patients with PSC-UC exhibit increased histologic inflammation in the right colon compared with the left colon, regardless of the presence of dysplasia. Although this may provide an explanation for the predominance of right-sided colorectal neoplasia in patients with PSC-UC, increased histologic inflammation does not reliably predict an elevated risk of dysplasia in patients with PSC-UC. These findings reinforce the current recommendation for annual endoscopic surveillance for all patients with PSC-UC, irrespective of the extent and severity of inflammation.

Injection drug use and HIV antiretroviral therapy discontinuation in a Canadian setting.

We investigated whether drug-related behaviors predicted antiretroviral therapy (ART) discontinuation among a cohort of injection drug users (IDU) in a Canadian setting. Cox regression analyses were used to investigate the impact of drug use patterns on rates of ART discontinuation among a sample of HIV-positive IDU in Vancouver, Canada between May 1996 and April 2008. In total, 408 HIV-positive IDU initiated ART during the study period, among whom 257 (63.0%) discontinued ART at least once. Rates of ART discontinuation were not significantly elevated among those who reported ongoing injection of heroin, cocaine, or other illicit drugs in comparison to those who reported not injecting drugs. However, public drug use was significantly predictive of ART discontinuation. Our findings may contribute to a reconsideration of the role of active drug use in determining retention in ART programs among IDU.

Sex-for-Crack exchanges: associations with risky sexual and drug use niches in an urban Canadian city.

BACKGROUND: While crack cocaine has been associated with elevated sexual risks and transmission of HIV/STIs, particularly in the context of street-based sex work, few empirical studies have examined correlates of direct sex-for-crack exchanges. This study longitudinally examined the correlates of sex-for-crack exchanges and associated effects on sexual risk outcomes among street-based female sex workers (SW) who use drugs in Vancouver, Canada. METHODS: Data were drawn from a prospective cohort of street-based SWs (2006-2008), restricted to those who smoke crack cocaine. Multivariable generalized estimating equations (GEE) were employed to examine the correlates of exchanging sex for crack. A confounding model using GEE quasi-Poisson regression modeled the independent effect of exchanging sex for crack on number of clients/week. RESULTS: Of 206 SWs, 101 (49%) reported sex-for-crack exchanges over 18 months of follow-up. In multivariable GEE analyses, sharing a crack pipe with a client (aOR = 1.98; 95%CI: 1.27-3.08) and smoking crack in a group of strangers (e.g., in an alley or crackhouse) (aOR = 1.70; 95% CI: 1.13-2.58) were independently correlated with sex-for-crack exchanges. In our confounding model, exchanging sex for crack (aIRR = 1.34; 95% CI: 1.07-1.69) remained significantly associated with servicing a greater number (>10) of clients/week. CONCLUSIONS: These findings reveal elevated sexual- and drug- risk patterns among those who exchange sex for crack. The physical and social environment featured prominently in our results as a driver of sex-for-crack exchanges, highlighting the need for gender-sensitive multilevel approaches to harm reduction, STI and HIV prevention that address SWs' environment, individual level factors, and the interplay between them.

Physician experience and rates of plasma HIV-1 RNA suppression among illicit drug users: an observational study.

BACKGROUND: Despite the availability of antiretroviral therapy (ART), suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART. METHODS: Using data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA < 500 copies/mL among antiretroviral-naïve subjects initiating ART. Physician experience was defined as a continuous variable measured per 100 HIV-infected patients previously enrolled in the province-wide HIV treatment registry by that physician at the time a patient was enrolled. RESULTS: Between May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85%) achieved a plasma HIV RNA < 500 copies/mL during the study period. In a multivariate analysis, greater physician experience was independently associated with higher rates of plasma HIV RNA suppression (adjusted hazard ratio [AHR] = 1.17, 95% confidence interval [CI]: 1.03-1.34) after adjustment for adherence to ART. Other factors associated with viral suppression included engagement in methadone maintenance therapy (AHR = 1.61, 95% CI: 1.23-2.09), ≥ 95% adherence to ART (AHR = 2.42, 95% CI: 1.80-3.26), baseline CD4 count (AHR = 0.89, 95% CI: 0.83-0.96) and baseline plasma HIV-1 RNA (AHR = 0.65, 95% CI: 0.53-0.81). CONCLUSIONS: In this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.

Emergency department utilization among a cohort of HIV-positive injecting drug users in a Canadian setting.

BACKGROUND: Human immunodeficiency virus (HIV)-positive injection drug users (IDUs) are known to be at risk for multiple medical problems that may necessitate emergency department (ED) use; however, the relative contribution of HIV disease vs. injection-related complications has not been well described. OBJECTIVES: We examined factors associated with ED use among a prospective cohort of HIV-positive IDUs in a Canadian setting. METHODS: We enrolled HIV-positive IDUs into a community-recruited prospective cohort study. We modeled factors associated with the time to first ED visit using Cox regression to determine factors independently associated with ED use. In sub-analyses, we examined ED diagnoses and subsequent hospital admission rates. RESULTS: Between December 5, 2005 and April 30, 2008, 428 HIV-positive IDUs were enrolled, among whom the cumulative incidence of ED use was 63.7% (95% confidence interval [CI] 59.1-68.3%) at 12 months after enrollment. Factors independently associated with time to first ED visit included: unstable housing (hazard ratio [HR] 1.5; 95% CI 1.1-2.0) and reporting being unable to obtain needed health care services (HR 2.2; 95% CI 1.2-4.1), whereas CD4 count and viral load were non-significant. Skin and soft tissue infections accounted for the greatest proportion of ED visits (17%). Of the 2461 visits to the ED, 419 (17%) were admitted to the hospital. CONCLUSIONS: High rates of ED use were observed among HIV-positive IDUs, a behavior that was predicted by unstable housing and limited access to primary care. Factors other than HIV infection seem to be driving ED use among this population in the post-highly active antiretroviral therapy era.

Increased Risk of Non-conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patients with primary sclerosing cholangitis and inflammatory bowel disease [termed PSC-IBD] have a higher risk of developing colorectal neoplasia than those with IBD alone. The mechanism by which concomitant PSC increases the risk of colorectal neoplasia remains unknown. Seven distinct non-conventional dysplastic subtypes have been recently described in IBD, including crypt cell dysplasia, hypermucinous dysplasia, goblet cell-deficient dysplasia, dysplasia with increased Paneth cell differentiation [DPD], sessile serrated lesion [SSL]-like dysplasia, traditional serrated adenoma [TSA]-like dysplasia, and serrated dysplasia, not otherwise specified [NOS]. Despite the lack of high-grade morphological features, crypt cell, hypermucinous, and goblet cell-deficient dysplasias often show molecular features characteristic of advanced neoplasia [i.e. aneuploidy and KRAS mutations] and are more frequently associated with advanced neoplasia than conventional dysplasia on follow-up. We aimed to characterise clinicopathological features of dysplasia found in PSC-IBD patients. METHODS: A cohort of 173 PSC-IBD patients were analysed. All dysplastic lesions were subtyped as either conventional or non-conventional dysplasia. The clinicopathological features of PSC-IBD patients with neoplasia were also compared with those of non-PSC IBD patients with neoplasia. RESULTS: There were 109 [63%] men and 64 [37%] women, with a mean age of 26 years at IBD diagnosis and a long history of IBD [mean duration: 14 years]. Ulcerative colitis was the most common IBD subtype [80%], and the majority of patients [92%] had a history of pancolitis. A total of 153 dysplastic lesions were detected in 54 [31%] patients, 35 [65%] of whom had multifocal dysplasia. One additional patient presented with colorectal cancer [CRC] without a history of dysplasia. Dysplasia was often non-conventional [n = 93; 61%], endoscopically/grossly invisible [n = 101; 66%], and right/proximal-sided [n = 90; 59%]. All seven non-conventional subtypes were identified, including 46 [30%] crypt cell dysplasia, 23 [15%] hypermucinous dysplasia, 12 [8%] goblet cell-deficient dysplasia, seven [5%] DPD, three [2%] TSA-like dysplasia, one [1%] SSL-like dysplasia, and one [1%] serrated dysplasia NOS. Follow-up information was available for 86 lesions, of which 32 [37%] were associated with subsequent detection of advanced neoplasia [high-grade dysplasia or CRC] within a mean follow-up time of 55 months. PSC-IBD patients with neoplasia were more likely to have pancolitis [98%, p = 0.039] and a longer IBD duration [mean: 17 years, p = 0.021] than those without neoplasia [89% and 12 years, respectively]. When compared with a cohort of non-PSC IBD patients with neoplasia, the PSC-IBD group with neoplasia was more often associated with non-conventional [61%, p <0.001], invisible [66%, p <0.001], and right/proximal-sided [59%, p = 0.045] dysplasias [vs 25%, 21%, and 47%, respectively, for the non-PSC IBD group]. The rate of advanced neoplasia was nearly 2-fold higher in the PSC-IBD group [37%] compared with the non-PSC IBD group [22%] [p = 0.035]. CONCLUSIONS: Nearly a third of PSC-IBD patients developed dysplasia, which is often associated with non-conventional dysplastic features, invisible endoscopic/gross appearance, right/proximal-sided colon, multifocality, and advanced neoplasia on follow-up. These findings underscore the importance of recognising these non-conventional subtypes by practising pathologists and the need for careful and frequent endoscopic surveillance, with random biopsies, in PSC-IBD patients.

Adherence and plasma HIV RNA response to antiretroviral therapy among HIV-seropositive injection drug users in a Canadian setting.

HIV-positive individuals who use injection drugs (IDU) may have lower rates of adherence to highly active antiretroviral therapy (ART). However, previous studies of factors associated with adherence to ART among IDU have been limited primarily to samples drawn from clinical settings and in areas with financial barriers to healthcare.We evaluated patterns of ART adherence and rates of plasma HIV RNA response among a Canadian cohort of community-recruited IDU. Using data from a community-recruited cohort of antiretroviral-naive HIV-infected IDU, we investigated ART adherence patterns based on prescription refill compliance and factors associated with time to plasma HIV-1 RNA suppression (<500 copies/mL) using Cox proportional hazards regression in a setting with universal health care, including free ART. Between 1996 and 2008, 267 antiretroviral-naive HIV-infected IDU initiated ART and had a median of 51 months (inter-quartile range: 17-95 months) of follow-up. Overall, 81 (30.3%) were ≥95% adherent during the first year of HAART and 187 (70.0%) achieved HIV RNA suppression at least once over the study period, for an incidence-density of 34.5 (95% confidence interval [CI]: 29.8-39.9) per 100 person-years. The Kaplan-Meier cumulative plasma HIV RNA suppression rates at 12 months after the initiation of ART were 80.8% (95% CI: 71.2-88.7) for adherent and 28.9% (95% CI: 22.8-36.1) for non-adherent participants. While several socio-demographic characteristics and drug-using behaviours were identified as barriers to successful treatment in unadjusted analyses, the factor most strongly associated with time to HIV RNA suppression in multivariate analysis was adherence to ART of at least 95% (adjusted hazard ratio [AHR] = 6.0, 95% CI: 4.2-8.6, p<0.001). These results demonstrate low rates of adherence to ART among a community-recruited cohort of IDU and reinforce the importance of adherence as the key determinant of successful virological response to antiretroviral therapy.

Female gender predicts lower access and adherence to antiretroviral therapy in a setting of free healthcare.

BACKGROUND: Barriers to HIV treatment among injection drug users (IDU) are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors--and gender differences in particular--that may pose barriers to antiretroviral therapy (ART), especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system. METHODS: We evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance. RESULTS: Between May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5-91.6), among whom 341 (63%) were male and 204 (37%) were female. Within the six-month period prior to the baseline interview, 133 (39%) men and 62 (30%) women were on ART (p=0.042). After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR]=0.70; 95% Confidence Interval: 0.53-0.93). CONCLUSIONS: Despite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.

Homelessness and adherence to antiretroviral therapy among a cohort of HIV-infected injection drug users.

Homelessness is prevalent among HIV-infected injection drug users (IDU) and may adversely affect access and adherence to antiretroviral therapy (ART). There are limited descriptions of the effect of homelessness on adherence to ART in long-term cohorts of HIV-infected IDU. We used data from a community-recruited prospective cohort of HIV-infected IDU, including comprehensive ART dispensation records, in a setting where HIV care is free. We examined the relationship between the homelessness measured longitudinally, and the odds of ≥95% adherence to ART using generalized estimating equations logistic regression modeling adjusting for sociodemographics, drug use, and clinical variables. Between May 1996 and September 2008, 545 HIV-infected IDU were recruited and eligible for the present study. The median follow-up duration was 23.8 months (IQR 8.5-91.6 months) contributing 2,197 person-years of follow-up. At baseline, homeless participants were slightly younger (35.8 vs. 37.9 years, p = 0.01) and more likely to inject heroin at least daily (37.1% vs. 24.6%. p = 0.004) than participants who had housing. The multivariate model revealed that homelessness (adjusted odds ratio [AOR] 0.66; 95% CI: 0.53-0.84) and frequent heroin use (AOR 0.40; 95% CI: 0.30-0.53) were significantly and negatively associated with ART adherence, whereas methadone maintenance was positively associated (AOR 2.33; 95% CI: 1.86-2.92). Sub-optimal ART adherence was associated with homelessness and daily injection heroin use among HIV-infected IDU. Given the survival benefit of ART, it is critical to develop and evaluate innovative strategies such as supportive housing and methadone maintenance to address these risk factors to improve adherence.

A dose-dependent relationship between exposure to a street-based drug scene and health-related harms among people who use injection drugs.

While the community impacts of drug-related street disorder have been well described, lesser attention has been given to the potential health and social implications of drug scene exposure on street-involved people who use illicit drugs. Therefore, we sought to assess the impacts of exposure to a street-based drug scene among injection drug users (IDU) in a Canadian setting. Data were derived from a prospective cohort study known as the Vancouver Injection Drug Users Study. Four categories of drug scene exposure were defined based on the numbers of hours spent on the street each day. Three generalized estimating equation (GEE) logistic regression models were constructed to identify factors associated with varying levels of drug scene exposure (2-6, 6-15, over 15 hours) during the period of December 2005 to March 2009. Among our sample of 1,486 IDU, at baseline, a total of 314 (21%) fit the criteria for high drug scene exposure (>15 hours per day). In multivariate GEE analysis, factors significantly and independently associated with high exposure included: unstable housing (adjusted odds ratio [AOR] = 9.50; 95% confidence interval [CI], 6.36-14.20); daily crack use (AOR = 2.70; 95% CI, 2.07-3.52); encounters with police (AOR = 2.11; 95% CI, 1.62-2.75); and being a victim of violence (AOR = 1.49; 95 % CI, 1.14-1.95). Regular employment (AOR = 0.50; 95% CI, 0.38-0.65), and engagement with addiction treatment (AOR = 0.58; 95% CI, 0.45-0.75) were negatively associated with high exposure. Our findings indicate that drug scene exposure is associated with markers of vulnerability and higher intensity addiction. Intensity of drug scene exposure was associated with indicators of vulnerability to harm in a dose-dependent fashion. These findings highlight opportunities for policy interventions to address exposure to street disorder in the areas of employment, housing, and addiction treatment.

High lifetime pregnancy and low contraceptive usage among sex workers who use drugs- an unmet reproductive health need.

BACKGROUND: The objective of this study was to describe levels of pregnancy and contraceptive usage among a cohort of street-based female sex workers (FSWs) in Vancouver. METHODS: The study sample was obtained from a community-based prospective cohort study (2006-2008) of 211 women in street-based sex work who use drugs, 176 of whom had reported at least one prior pregnancy. Descriptive statistics were used to estimate lifetime pregnancy prevalence, pregnancy outcomes (miscarriage, abortion, adoption, child apprehension, child custody), and contraceptive usage. In secondary analyses, associations between contraceptive usage, individual and interpersonal risk factors and high number of lifetime pregnancies (defined as greater than the sample mean of 4) were examined. RESULTS: Among our sample, 84% reported a prior pregnancy, with a mean of 4 lifetime pregnancies (median = 3; IQR: 2-5). The median age of women reporting 5+ pregnancies was 38 years old [interquartile range (IQR): 25.0-39.0] compared to 34 years [IQR: 25.0-39.0] among women reporting 4 or fewer prior pregnancies. 45% were Caucasian and 47% were of Aboriginal ancestry. We observed high rates of previous abortion (median = 1;IQR:1-3), apprehension (median = 2; IQR:1-4) and adoption (median = 1; IQR:1-2) among FSWs who reported prior pregnancy. The use of hormonal and insertive contraceptives was limited. In bivariate analysis, tubal ligation (OR = 2.49; [95%CI = 1.14-5.45]), and permanent contraceptives (e.g., tubal ligation and hysterectomy) (OR = 2.76; [95%CI = 1.36-5.59]) were both significantly associated with having five or more pregnancies. CONCLUSION: These findings demonstrate high levels of unwanted pregnancy in the context of low utilization of effective contraceptives and suggest a need to improve the accessibility and utilization of reproductive health services, including family planning, which are appropriately targeted and tailored for FSWs in Vancouver.

Compulsory drug detention center experiences among a community-based sample of injection drug users in Bangkok, Thailand.

BACKGROUND: Despite Thailand's official reclassification of drug users as "patients" deserving care and not "criminals," the Thai government has continued to rely heavily on punitive responses to drug use such as "boot camp"-style compulsory "treatment" centers. There is very little research on experiences with compulsory treatment centers among people who use drugs. The work reported here is a first step toward filling that gap. METHODS: We examined experiences of compulsory drug treatment among 252 Thai people who inject drugs (IDU) participating in the Mitsampan Community Research Project in Bangkok. Multivariate logistic regression was used to identify factors independently associated with a history of compulsory treatment experience. RESULTS: In total, 80 (31.7%) participants reported a history of compulsory treatment. In multivariate analyses, compulsory drug detention experience was positively associated with current spending on drugs per day (adjusted odds ratio [AOR] = 1.86; 95%CI: 1.07 - 3.22) and reporting drug planting by police (AOR = 1.81; 95%CI: 1.04 - 3.15). Among those with compulsory treatment experience, 77 (96.3%) reported injecting in the past week, and no difference in intensity of drug use was observed between those with and without a history of compulsory detention. CONCLUSION: These findings raise concerns about the current approach to compulsory drug detention in Thailand. Exposure to compulsory drug detention was associated with police abuse and high rates of relapse into drug use, although additional research is needed to determine the precise impact of exposure to this form of detention on future drug use. More broadly, compulsory "treatment" based on a penal approach is not consistent with scientific evidence on addressing drug addiction and should be phased out in favor of evidence-based interventions.

A comparison of drug use and risk behavior profiles among younger and older street youth.

Among 559 street youth recruited between 2005 and 2007 in Vancouver, Canada, young drug users (<21 years of age) were compared with older drug users (≥21 years) with regard to recent drug use and sexual practices using multiple logistic regression. Older youth were more likely to be male and of Aboriginal ancestry, to have more significant depressive symptoms, to have recently engaged in crack smoking, and to have had a recent history of injection drug use. Young drug users, by contrast, were more likely to have engaged in recent binge alcohol use. Efforts to reduce drug use-related harm among street youth may be improved by considering the highly prevalent use of "harder" drugs and risk for depression among older youth.

Gastric Intestinal Metaplasia in Mucosa Adjacent to Gastric Cancers Is Rarely Associated With the Aneuploidy That Is Characteristic of Gastric Dysplasia or Cancer.

Most gastric cancers (GCs) are thought to develop via gastric intestinal metaplasia (GIM)-dysplasia-carcinoma pathway. Patients with extensive and/or incomplete GIM have been reported to have a higher risk of GC. GIM can also display dysplasia-like cytoarchitectural atypia limited to the bases of gastric pits without surface involvement. However, only a small proportion of GIM patients will develop gastric neoplasia, and it remains questionable if GIM is a direct precursor. A cohort of 82 GC patients with GIM who underwent gastrectomy were analyzed. DNA flow cytometry was performed on 109 GIM samples (including 88 predominantly complete GIM and 21 predominantly incomplete GIM subclassified based on morphology) obtained from adjacent mucosa of the 82 GCs. Only 2 (2%) of the 109 GIM samples demonstrated aneuploidy, both from 2 minority patients (Asian and Hispanic) with limited and complete GIM and no cytoarchitectural atypia. The remaining 107 GIM samples showed mild to focally moderate basal gland (metaplastic) atypia limited to the bases of gastric pits, but they all demonstrated normal DNA content regardless of anatomic location, histologic GIM subtype, or varying degrees of basal gland atypia. In conclusion, the vast majority of the GIM samples (98%) lack the aneuploidy that is characteristic of gastric dysplasia or cancer. This indicates that aneuploidy usually occurs after the development of gastric dysplasia rather than at the stage of GIM. The finding also suggests that the presence of GIM alone may not be sufficient to suggest an increased risk for GC and that the inclusion of other high-risk features (ie, extensive GIM, dysplasia, racial minorities, and/or family history of GC in a first-degree relative) and/or aneuploidy ought to play a role in the selection of GIM patients who may warrant endoscopic surveillance. Finally, GIM with mild to focally moderate basal gland atypia is likely to represent metaplastic atypia in most cases.

Syringe sharing and HIV incidence among injection drug users and increased access to sterile syringes.

OBJECTIVES: We assessed the effects of syringe exchange program (SEP) policy on rates of HIV risk behavior and HIV incidence among injection drug users. METHODS: Using a multivariate generalized estimating equation and Cox regression methods, we examined syringe borrowing, syringe lending, and HIV incidence among a prospective cohort of 1228 injection drug users in Vancouver, British Columbia. RESULTS: We observed substantial declines in rates of syringe borrowing (from 20.1% in 1998 to 9.2% in 2003) and syringe lending (from 19.1% in 1998 to 6.8% in 2003) following SEP policy change. These declines coincided with a statistically significant increase in the proportion of participants accessing sterile syringes from nontraditional SEP sources (P < .001). In multivariate analyses, the period following the change in SEP policy was independently associated with a greater than 40% reduction in syringe borrowing (adjusted odds ratio [AOR] = 0.57; 95% confidence interval [CI] = 0.49, 0.65) and lending (AOR = 0.52; 95% CI = 0.45, 0.60), as well as declining HIV incidence (adjusted hazard ratio = 0.13; 95% CI = 0.06, 0.31). CONCLUSIONS: Widespread syringe distribution appears to be a more effective SEP policy than do more restrictive SEP policies that limit syringe access. Efforts should be made to ensure that SEP policies and program design serve to maximize rather than hinder syringe access.

Survival sex work involvement among street-involved youth who use drugs in a Canadian setting.

BACKGROUND: Drug users engaged in survival sex work are at heightened risk for drug- and sexual-related harms. We examined factors associated with survival sex work among street-involved youth in Vancouver, Canada. METHODS: From September 2005 to November 2007, baseline data were collected for the At-Risk Youth Study (ARYS), a prospective cohort of street-recruited youth aged 14-26 who use illicit drugs. Using multiple logistic regression, we compared youth who reported exchanging sex for money, drugs etc. with those who did not. RESULTS: The sample included 560 youth: median age 22; 179 (32%) female; 63 (11%) reporting recent survival sex work. Factors associated with survival sex work in multivariate analyses included non-injection crack use [adjusted odds ratio (AOR) = 3.45, 95% confidence interval (CI): 1.75-6.78], female gender (AOR = 3.02, 95% CI: 1.66-5.46), Aboriginal ethnicity (AOR = 2.35, 95% CI: 1.28-4.29) and crystal methamphetamine use (AOR = 2.02, 95% CI: 1.13-3.62). In subanalyses, the co-use of crack cocaine and methamphetamine was shown to be driving the association between methamphetamine and survival sex work. CONCLUSIONS: This study demonstrates a positive interactive effect of dual stimulant use in elevating the odds of survival sex work among street youth who use drugs. Novel approaches to reduce the harms associated with survival sex work among street youth who use stimulants are needed.

Inability to access addiction treatment and risk of HIV infection among injection drug users recruited from a supervised injection facility.

BACKGROUND: Treatment for drug addiction is effective in reducing the harms of injection drug use, including infection with HIV and/or hepatitis C. We sought to examine the prevalence and correlates of being unable to access addiction treatment in a representative sample of injection drug users randomly recruited from a supervised injection facility. METHODS: Using generalized estimating equations, we determined the prevalence and factors associated with being unable to access addiction treatment. RESULTS: Between 1 July 2004 and 30 June 2006, 889 individuals completed at least one interview and were included in this analysis. At each interview, approximately 20% of respondents reported trying but being unable to access any type of drug or alcohol treatment in the previous 6 months. Being unable to access treatment was independently associated with recent incarceration, daily use of heroin and borrowing used syringes. In a secondary question, the majority of individuals reported waiting lists were the reason for being unable to access treatment. CONCLUSION: Given the independent association between inability to access addiction treatment and elevated HIV risk behavior, these results suggest expanding addiction treatment may contribute significantly to HIV prevention efforts in this population.