Faculty Bibliography

INTRODUCTION: Electronic cigarette (EC) use is growing dramatically with use highest among young adults and current smokers. One of the most common reasons for using ECs is interest in quitting or reducing cigarettes per day (CPD); however there are few randomized controlled trials (RCT) on the effect of ECs on smoking abstinence and reduction. METHODS: We conducted a two-arm; double-blind RCT. Subjects were randomized to receive 3-weeks of either disposable 4.5% nicotine EC (intervention) or placebo EC. The primary outcome was self-reported reduction of >/=50% in the number of CPDs smoked at week 3 (end of treatment) compared to baseline. Study subjects (n=99) were young adult (21-35), current smokers (smoked >/=10 CPDs) living in NYC. RESULTS: Compared with baseline, a significant reduction in CPDs was observed at both study time periods (1 and 3 weeks) for intervention (p<.001) and placebo (p<.001) groups. Between-group analyses showed significantly fewer CPDs in the intervention group compared to the placebo group at week 3 (p=.03), but not at any other follow-up periods. The logistic regression analysis showed that using a greater number of ECs, treatment condition and higher baseline readiness to quit were significantly associated with achieving >/=50% reduction in CPDs at the end of treatment. CONCLUSION: A diverse young adult sample of current everyday smokers, who were not ready to quit, was able to reduce smoking with the help of ECs. Further study is needed to establish the role of both placebo and nicotine containing ECs in increasing both reduction and subsequent cessation.

BACKGROUND AND AIMS: To address barriers to implementing the "Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)" in medical settings, we adapted the traditional interviewer-administered (IA) ASSIST to an audio-guided computer assisted self-interview (ACASI) format. This study sought to validate the ACASI ASSIST by estimating the concordance, correlation, and agreement of scores generated using the ACASI versus the reference standard IA ASSIST. Secondary aims were to assess feasibility and compare ASSIST self-report to drug testing results. DESIGN: Participants completed the ACASI and IA ASSIST in a randomly assigned order, followed by drug testing. SETTING: Urban safety-net primary care clinic in New York City, USA. PARTICIPANTS: A total of 393 adult patients. MEASUREMENTS: Scores generated by the ACASI and IA ASSIST; drug testing results from saliva and hair samples. FINDINGS: Concordance between the ACASI and IA ASSIST in identifying moderate-high risk use was 92-99% for each substance class. Correlation was excellent for global scores (ICC = 0.94, CI 0.92-0.95) and for substance-specific scores for tobacco (ICC = 0.93, CI 0.91-0.94), alcohol (ICC = 0.91, CI 0.89-0.93) and illicit drugs (ICC = 0.85, CI 0.85-0.90), and good for prescription drugs (ICC = 0.68, CI 0.61-0.73). Ninety-four percent of differences in global scores fell within anticipated limits of agreement. Among participants with a positive saliva test, 74% self-reported use on the ACASI ASSIST. The ACASI ASSIST required a median time of 3.7 minutes (range 0.7-15.4), and 21 (5.3%) participants requested assistance. CONCLUSIONS: The computer self-administered Alcohol, Smoking and Substance Involvement Screening Test appears to be a valid alternative to the interviewer-administered approach for identifying substance use in primary care patients.

BACKGROUND: Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction. METHODS: Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European). RESULTS: A total of 11 SNPs in eight genes showed nominally significant associations (P<0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3 rs7165224; DBI rs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2A rs1650420 were previously reported in associations with drug addiction or related phenotypes. CONCLUSIONS: The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction.

BACKGROUND: On October 2012, Hurricane Sandy struck New York City, resulting in unprecedented damages, including the temporary closure of Bellevue Hospital Center and its primary care office-based buprenorphine program. OBJECTIVES: At 6 months, we assessed factors associated with higher rates of substance use in buprenorphine program participants that completed a baseline survey one month post-Sandy (i.e. shorter length of time in treatment, exposure to storm losses, a pre-storm history of positive opiate urine drug screens, and post-disaster psychiatric symptoms). METHODOLOGY: Risk factors of interest extracted from the electronic medical records included pre-disaster diagnosis of Axis I and/or II disorders and length of treatment up to the disaster. Factors collected from the baseline survey conducted approximately one month post-Sandy included self-reported buprenorphine supply disruption, health insurance status, disaster exposure, and post-Sandy screenings for PTSD and depression. Outcome variables reviewed 6 months post-Sandy included missed appointments, urine drug results for opioids, cocaine, and benzodiazepines. RESULTS: 129 (98%) patients remained in treatment at 6 months, and had no sustained increases in opioid-, cocaine-, and benzodiazepine-positive urine drug tests in any sub-groups with elevated substance use in the baseline survey. Contrary to our initial hypothesis, diagnosis of Axis I and/or II disorders pre-Sandy were associated with significantly less opioid-positive urine drug findings in the 6 months following Sandy compared to the rest of the clinic population. CONCLUSION: These findings demonstrate the adaptability of a safety net buprenorphine program to ensure positive treatment outcomes despite disaster-related factors.

OBJECTIVE: The goal of the study was to evaluate whether enhanced normative feedback recovery curves are needed for treatment of substance use problems. METHOD: Patient predictors of outcome were examined using data from four substance abuse treatment clinics. RESULTS: Baseline severity of symptoms/functioning, employment, and craving were found to be associated with rate of change in symptoms/functioning. Several other variables were associated with rate of change in alcohol use, although in the opposite direction than found in efficacy trials. CONCLUSIONS: The results point to the complexity of designing feedback systems using normative recovery curves for those with substance use problems and highlight the important differences between real-world treatment of those with substance use problems compared to data from efficacy trials.

AIM: Drug addiction is characterized, in part, by deregulation of synaptic plasticity in circuits involved in reward, stress, cue learning, and memory. This study was designed to assess whether 185 variants in 32 genes central to synaptic plasticity and signal transduction contribute to vulnerability to develop heroin and/or cocaine addiction. METHODS: Analyses were conducted in a sample of 1860 subjects divided according to ancestry (African and European) and drug of abuse (heroin or cocaine). RESULTS: Eighteen SNPs in 11 genes (CDK5R1, EPHA4, EPHA6, FOSL2, MAPK3, MBP, MPDZ, NFKB1, NTRK2, NTSR1, and PRKCE) showed significant associations (P < 0.01), but the signals did not survive correction for multiple testing. SNP rs230530 in the NFKB1 gene, encoding the transcription regulator NF-kappa-B, was the only SNP indicated in both ancestry groups and both addictions. This SNP was previously identified in association with alcohol addiction. SNP rs3915568 in NTSR1, which encodes neurotensin receptor, and SNP rs1389752 in MPDZ, which encodes the multiple PDZ domain protein, were previously associated with heroin addiction or alcohol addiction, respectively. CONCLUSIONS: The study supports the involvement of genetic variation in signal transduction pathways in heroin and cocaine addiction and provides preliminary evidence suggesting several new risk or protective loci that may be relevant for diagnosis and treatment success.

BACKGROUND: Drug addiction is influenced by genetic factors. AIM: To determine if genetic variants in the serotonergic and adrenergic pathways are associated with heroin and/or cocaine addiction. SUBJECTS & METHODS: The study examined 140 polymorphisms in 19 genes in 1855 subjects with predominantly European or African ancestries. RESULTS: A total of 38 polymorphisms (13 genes) showed nominal associations, including novel associations in S100A10 (p11) and SLC18A2 (VMAT2). The association of HTR3B SNP rs11606194 with heroin addiction in the European ancestry subgroup remained significant after correction for multiple testing (p corrected = 0.04). CONCLUSION: The study strengthens our previous findings of association of polymorphisms in HTR3A, HTR3B and ADRA1A. The study suggests partial overlap in genetic susceptibility between populations of different ancestry and between heroin and cocaine addiction.

Background: ED-based SBIRT for alcohol and drug use has the potential to affect public health greatly. Time and resource constraints limit implementation. Objectives: We aimed to determine whether particular chief complaints could be used to identify patients likely to screen positive for unhealthy alcohol or drug use, thus reducing the proportion of patients needing to be screened and increasing the efficiency of SBIRT. Methods: Cross-sectional study using baseline data from NIDA CTN0047: SMART-ED, a multicenter, randomized 3-arm SBIRT trial which screened 14,972 ED patients. Free-text chief complaints were coded using a tested algorithm, then reviewed and further collapsed by multiple team members to ensure agreement. The 454 excluded patients had missing data, complaints related to alcohol or drug use, or complaints stated by <15 subjects. Positive screens were defined as AUDIT-C > 4 for men and >3 for women (alcohol) and DAST >3 (drugs) - to detect the spectrum of unhealthy alcohol or drug use (from at-risk to dependence). We rank-ordered the chief complaints by their (Figure presented) sensitivity and positive predictive value using two strategies: 1) to minimize the number of chief complaints and 2) to assess the fewest number of ED patients. Our goal was to identify 75% of ED patients having positive assessments using these strategies. Results: The screening assessments were positive in 5,805/14,561 (39.9%) for alcohol and 2,454/14,494 (16.9%) for drugs. We collapsed the free-text chief complaints into 50 usable categories. To identify 75% of all ED patients having positive assessments using the first strategy would require including 19 chief complaints for alcohol screening and 20 chief complaints for drug screening. Adapting the second strategy, we would need to screen at least 71% and 68% of all ED patients for alcohol and drugs respectively to identify 75% of those having positive assessments. (See Table 47 and Figure 47.) Conclusion: In this multi-ED study, unhealthy alcohol and drug use was exceptionally prevalent. Using chief complaints did not significantly improve the efficiency of SBIRT for AOD

BACKGROUND: Very brief single-item screening questions (SISQs) for alcohol and other drug use can facilitate screening in health care settings, but are not widely used. Self-administered versions of the SISQs could ease barriers to their implementation. OBJECTIVE: We sought to validate SISQs for self-administration in primary care patients. DESIGN: Participants completed SISQs for alcohol and drugs (illicit and prescription misuse) on touchscreen tablet computers. Self-reported reference standard measures of unhealthy use, and more specifically of risky consumption, problem use, and substance use disorders, were then administered by an interviewer, and saliva drug tests were collected. PARTICIPANTS: Adult patients aged 21-65 years were consecutively enrolled from two urban safety-net primary care clinics. MAIN MEASURES: The SISQs were compared against reference standards to determine sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for alcohol and drug use. KEY RESULTS: Among the 459 participants, 22 % reported unhealthy alcohol use and 25 % reported drug use in the past year. The SISQ-alcohol had sensitivity of 73.3 % (95 % CI 65.3-80.3) and specificity of 84.7 % (95 % CI 80.2-88.5), AUC = 0.79 (95 % CI 0.75-0.83), for detecting unhealthy alcohol use, and sensitivity of 86.7 % (95 % CI 75.4-94.1) and specificity of 74.2 % (95 % CI 69.6-78.4), AUC = 0.80 (95 % CI 0.76-0.85), for alcohol use disorder. The SISQ-drug had sensitivity of 71.3 % (95 % CI 62.4-79.1) and specificity of 94.3 % (95 % CI 91.3-96.6), AUC = 0.83 (95 % CI 0.79-0.87), for detecting unhealthy drug use, and sensitivity of 85.1 (95 % CI 75.0-92.3) and specificity of 88.6 % (95 % CI 85.0-91.6), AUC = 0.87 (95 % CI 0.83-0.91), for drug use disorder. CONCLUSIONS: The self-administered SISQs are a valid approach to detecting unhealthy alcohol and other drug use in primary care patients. Although self-administered SISQs may be less accurate than the previously validated interviewer-administered versions, they are potentially easier to implement and more likely to retain their fidelity in real-world practice settings.

Drugs of abuse activate the mesolimbic dopaminergic pathway. Genetic variations in the dopaminergic system may contribute to drug addiction. Several processes are shared between cocaine and heroin addictions but some neurobiological mechanisms may be specific. This study examined the association of 98 single nucleotide polymorphisms in 13 dopamine-related genes with heroin addiction (OD) and/or cocaine addiction (CD) in a sample of 801 African Americans (315 subjects with OD +/- CD, 279 subjects with CD, and 207 controls). Single-marker analyses provided nominally significant evidence for associations of 24 SNPs) in DRD1, ANKK1/DRD2, DRD3, DRD5, DBH, DDC, COMT and CSNK1E. A DRD2 7-SNPs haplotype that includes SNPs rs1075650 and rs2283265, which were shown to alter D2S/D2L splicing, was indicated in both addictions. The Met allele of the functional COMT Val158Met was associated with protection from OD. None of the signals remained significant after correction for multiple testing. The study results are in accordance with the results of previous studies, including our report of association of DRD1 SNP rs5326 with OD. The findings suggest the presence of an overlap in genetic susceptibility for OD and CD, as well as shared and distinct susceptibility for OD in subjects of African and European descent.