Faculty Bibliography

Objectives. In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural, pharmacy-based intervention was implemented to determine whether expanding pharmacy practice to include provision of HIV risk reduction and social/medical services information during the syringe sale would (a) improve pharmacy staff attitudes toward IDUs (b) increase IDU syringe customers, and (c) increase prescription customer base in New York City neighborhoods with high burden of HIV and illegal drug activity. Methods. Pharmacies (n = 88) were randomized into intervention (recruited IDU syringe customers into the study and delivered intervention activities), primary control (recruited IDU syringe customers only) and secondary control (did not recruit IDUs or deliver intervention activities) arms. Results. Pharmacy staff in the intervention versus secondary control pharmacies showed significant decreases in the belief that selling syringes to IDUs causes community loitering. Conclusions. Structural interventions may be optimal approaches for changing normative attitudes about highly stigmatized populations.

AIMS: We evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence. METHODS: This 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome. RESULTS: The 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of >/=42 mug/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths. CONCLUSIONS: The vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence.

Stress is a significant risk factor in the development of drug addictions and in addiction relapse susceptibility. This hypothesis-driven study was designed to determine if specific SNPs in genes related to stress response are associated with heroin and/or cocaine addiction in African Americans. The analysis included 27 genes (124 SNPs) and was performed independently for each addiction. The sample consisted of former heroin addicts in methadone maintenance treatment (n = 314), cocaine addicts (n = 281), and controls (n = 208). Fourteen SNPs showed nominally significant association with heroin addiction (p < 0.05), including the African-specific, missense SNP rs5376 (Asn334Ser) in the galanin receptor type 1 gene (GALR1) and the functional FKBP5 intronic SNP rs1360780. Thirteen SNPs showed association with cocaine addiction, including the synonymous SNPs rs237902, in the oxytocin receptor gene (OXTR), and rs5374 in GALR1. No signal remained significant after correction for multiple testing. Four additional SNPs (GALR1 rs2717162, AVP rs2282018, CRHBP rs1875999, and NR3C2 rs1040288) were associated with both addictions and may indicate common liability. The study provides preliminary evidence for novel association of variants in several stress-related genes with heroin and/or cocaine addictions and may enhance the understanding of the interaction between stress and addictions.

The time required to conduct drug and alcohol screening has been a major barrier to its implementation in mainstream healthcare settings. Because patient self-administered tools are potentially more efficient, we translated the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) into an audio guided computer assisted self interview (ACASI) format. This study reports on the test-retest reliability of the ACASI ASSIST in an adult primary care population. Adult primary care patients completed the ACASI ASSIST, in English or Spanish, twice within a 1-4week period. Among the 101 participants, there were no significant differences between test administrations in detecting moderate to high risk use for tobacco, alcohol, or any other drug class. Substance risk scores from the two administrations had excellent concordance (90-98%) and high correlation (ICC 0.90-0.97) for tobacco, alcohol, and drugs. The ACASI ASSIST has good test-retest reliability, and warrants additional study to evaluate its validity for detecting unhealthy substance use.

BACKGROUND: Stress is a critical risk factor affecting both the development of and the relapse to drug addictions. Drug addictions are caused by genetic, environmental and drug-induced factors. The objective of this hypothesis-driven association study was to determine if genetic variants in stress-related genes are associated with heroin addiction. METHODS: 112 selected genetic variants in 26 stress-related genes were genotyped in 852 case subjects and 238 controls of predominantly European ancestry. The case subjects are former heroin addicts with a history of at least one year of daily multiple uses of heroin, treated at a methadone maintenance treatment program (MMTP). The two most promising SNPs were subsequently tested in an African-American sample comprising of 314 cases and 208 control individuals. RESULTS: Nineteen single nucleotide polymorphisms (SNPs) in 9 genes (AVP, AVPR1A, CRHR1, CRHR2, FKBP5, GAL, GLRA1, NPY1R and NR3C2) showed nominally significant association with heroin addiction. The associations of two FKBP5 SNPs that are part of one haplotype block, rs1360780 (intron 2) and rs3800373 (the 3' untranslated region), remained significant after correction for multiple testing (Pcorrected=0.03; OR=2.35, Pcorrected=0.0018; OR=2.85, respectively). The two SNPs also showed nominally significant association (P<0.05) with heroin addiction in an independent African-American cohort. FKBP5 is a co-chaperone that regulates glucocorticoid sensitivity. These FKBP5 SNPs were previously associated with diverse affective disorders and showed functional differences in gene expression and stress response. This study also supports our and others' previous reports of association of the GAL SNP rs694066 and the AVPR1A SNPs rs11174811, rs1587097 and rs10784339 with heroin and general drug addiction, respectively. CONCLUSIONS: This study suggests that variations in the FKBP5 gene contribute to the development of opiate addiction by modulating the stress response. These findings may enhance the understanding of the interaction between stress and heroin addiction.

BACKGROUND: Female injection drug users (IDUs) may report differences in injection behaviours that put them at greater risk for hepatitis C virus (HCV). Few studies have examined these in association with HCV incidence. METHODS: Longitudinal data from a cohort of 417 HCV-uninfected IDU aged 30 or younger were analysed. Cox proportional hazards was used to model female sex as a predictor of new HCV infection. General estimating equation (GEE) analysis was used to model female sex as a predictor of HCV-associated risk behaviour prospectively. RESULTS: Women were significantly more likely than men to become infected with HCV during study follow-up (HR 1.4, p<0.05), and were also more likely than men to report high-risk injecting behaviours, especially in the context of sexual and injecting relationships. Sex differences in injecting behaviours appeared to explain the relationship between sex and HCV infection. CONCLUSIONS: Young women's riskier injection practices lead to their higher rates of HCV infection. Further study on the impact of intimate partnership on women's risk behaviour is warranted.

BACKGROUND: The prevalence of alcohol, tobacco, and other drug (ATOD) use among emergency department (ED) patients is high and many of these patients have unrecognized and unmet substance use treatment needs. Identification of patients in the ED with problem substance use is not routine at this time. METHODS: We examined screening data, including standardized measures of ATOD use (HSI, AUDIT-C, DAST-10), from 14,866 ED patients in six hospitals across the United States. We expected younger age, male gender, higher triage acuity, and other substance use severity (ATOD) to be associated both with use versus abstinence and with severity of each substance use type. We used negative binomial hurdle models to examine the association between covariates and (1) substance use versus abstinence (logistic submodel) and with (2) severity among those who used substances (count submodel). RESULTS: Rates of use and problem use in our sample were similar to or higher than other ED samples. Younger patients and males were more likely to use ATOD, but the association of age and gender with severity varied across substances. Triage level was a poor predictor of substance use severity. Alcohol, tobacco, and drug use were significantly associated with using other substances and severity of other substance use. CONCLUSION: Better understanding of the demographic correlates of ATOD use and severity and the patterns of comorbidity among classes of substance can inform the design of optimal screening and brief intervention procedures addressing ATOD use among ED patients. Tobacco may be an especially useful predictor.

There are few clinical trials of 12-step treatments for individuals with serious mental illness and alcohol or drug dependence. This randomized trial assessed the effects of adding a 12-session 12-step facilitation therapy (TSF), adapted from that used in Project MATCH, to treatment as usual in an outpatient dual diagnosis program. Participants were 121 individuals dually diagnosed with alcohol dependence and a serious mental disorder, followed during 12 weeks of treatment and 36 weeks post-treatment. Participants receiving TSF had greater participation in 12-step programs, but did not demonstrate greater improvement in alcohol and drug use. However, considered dimensionally, greater participation in TSF was associated with greater improvement in substance use, and greater 12-step participation predicted decreases in frequency and intensity of drinking. Findings suggest that future work with TSF in this population should focus on maximizing exposure to TSF, and maximizing the effect of TSF on 12-step participation.

In October 2012, Bellevue Hospital Center (Bellevue) in New York City was temporarily closed as a result of Hurricane Sandy, the largest hurricane in US history. Bellevue's primary care office-based buprenorphine program was temporarily closed and later relocated to an affiliate public hospital. Previous research indicates that the relationships between disaster exposure, substance use patterns, psychiatric symptoms, and mental health services utilization is complex, with often conflicting findings regarding post-event outcomes (on the individual and community level) and antecedent risk factors. In general, increased use of tobacco, alcohol, and illicit drugs is associated with both greater disaster exposure and the development or exacerbation of other psychiatric symptoms and need for treatment. To date, there is limited published information regarding post-disaster outcomes among patients enrolled in office-based buprenorphine treatment, as the treatment modality has only been relatively approved recently. Patients enrolled in the buprenorphine program at the time of the storm were surveyed for self-reported buprenorphine adherence and illicit substance and alcohol use, as well as disaster-related personal consequences and psychiatric sequelae post-storm. Baseline demographic characteristics and insurance status were available from the medical record. Analysis was descriptive (counts and proportions) and qualitative, coding open-ended responses for emergent themes. There were 132 patients enrolled in the program at the time of the storm; of those, 91 were contacted and 89 completed the survey. Almost half of respondents reported disruption of their buprenorphine supply. Unexpectedly, patients with psychiatric comorbidity were no more likely to report increased use/relapse as a result. Rather, major risk factors associated with increased use or relapse post-storm were: (1) shorter length of time in treatment, (2) exposure to storm losses such as buprenorphine supply disruption, (3) a pre-storm history of red flag behaviors (in particular, repeat opioid-positive urines), and (4) new-onset post-storm psychiatric symptoms. Our findings highlight the relative resilience of buprenorphine as an office-based treatment modality for patients encountering a disaster with associated unanticipated service disruption. In responding to future disasters, triaging patient contact and priority based on a history of red-flag behaviors, rather than a history of psychiatric comorbidity, will likely optimize resource allocation, especially among recently enrolled patients. Additionally, patients endorsing new-onset psychiatric manifestations following disasters may be an especially high-risk group for poor outcomes, warranting further study.

High-risk social ties portend differences in opportunity for HIV exposures and may contribute to racial/ethnic disparities in HIV transmission. Discrimination may affect the formation of high-risk social ties and has not been explored as a possible explanation for these persistent disparities. Using data from injection and non-injection drug users, we examined the association between the number of high-risk sex and drug ties with discrimination due to race, drug use, and incarceration stratified by race/ethnicity. Negative binomial regression models were used. While blacks had significantly fewer injecting ties than Latinos and whites, blacks who reported racial discrimination compared to blacks who did not, had more sex and injecting ties. Latinos who reported drug use discrimination compared to Latinos who did not also had more sex ties. Latinos and whites who reported drug use discrimination had more injecting ties than Latinos and whites who did not. Discrimination is associated with high-risk social ties among all racial/ethnic groups. But, these data highlight different forms of discrimination within racial/ethnic group are associated with risky social ties. More research is needed to confirm these findings and further explore the association between various forms of discrimination and social ties that may help explain racial/ethnic disparities in HIV.