Faculty Bibliography
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Hepatitis B virus and hepatitis C virus services offered by substance abuse treatment programs in the United States
Although substance abuse treatment programs are important contact points for providing health services for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, availability of services in these programs has not been well characterized. This study evaluated the spectrum of HBV and HCV services offered by substance abuse treatment programs within the National Drug Abuse Treatment Clinical Trials Network. Our survey of substance abuse treatment program administrators covered availability of testing for HBV and HCV; hepatitis A virus (HAV) and HBV immunization; and HCV medical and nonmedical services. There were also questions covering clarity of guidelines for HBV and HCV testing and HAV and HBV immunization. Differences between methadone and nonmethadone programs were examined. Despite the importance of substance abuse in sustaining the hepatitis epidemics, few programs offer comprehensive HBV and HCV testing or HCV health care services. Interventions to improve access to hepatitis services for substance-abusing patients are needed.
PMCID:3272317
PMID: 22035702
ISSN: 0740-5472
CID: 166497
Helping Alliance, Retention, and Treatment Outcomes: A Secondary Analysis From the NIDA Clinical Trials Network Women and Trauma Study
We examined the association between the therapeutic alliance and treatment outcomes among 223 women with posttraumatic stress disorder (PTSD) and substance use disorders who participated in a multisite clinical trial of group treatments for trauma and addictions in the United States throughout 2004 and 2005. General linear models indicated that women who received Seeking Safety, a cognitive-behavioral treatment, had significantly higher alliance ratings than those in Women's Health Education, a control group. Alliance was related to significant decreases in PTSD symptoms and higher attendance in both interventions. Alliance was not related to substance use outcomes. Implications and limitations of the findings are discussed.
PMCID:3639137
PMID: 22475068
ISSN: 1082-6084
CID: 166697
Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia
BACKGROUND: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. METHOD: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30mg) or placebo for 12weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. RESULTS: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p=.45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p=.048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. CONCLUSION: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia
PMID: 22169248
ISSN: 1573-2509
CID: 150124
Comprehensive genomic characterization of squamous cell lung cancers
ISI:000309167100041
ISSN: 0028-0836
CID: 5270602
A high-resolution map of human evolutionary constraint using 29 mammals
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
PMID: 21993624
ISSN: 1476-4687
CID: 3543122
Crystal Structures of Human Anti-V2 mAbs 697-30D and 8.9D and What We Can Learn From Their Antigen-Binding Sites [Meeting Abstract]
ISI:000295790500312
ISSN: 0889-2229
CID: 2961972
Smoking Cessation Treatment among Patients in Community-Based Substance Abuse Rehabilitation Programs: Exploring Predictors of Outcome as Clues Toward Treatment Improvement
Background: Predictors of smoking cessation (SC) treatment outcome were explored in a multisite clinical trial of SC treatment at community-based, outpatient, substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network. Objectives: To explore baseline demographic and clinical predictors of abstinence during treatment. Methods: Cigarette smokers from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned to SC treatment as an adjunct to substance abuse treatment as usual or to substance abuse treatment as usual. SC treatment consisted of group counseling (weeks 1-8) plus transdermal nicotine patch treatment (21 mg/day, weeks 1-6; 14 mg/day, weeks 7-8). Demographic and clinical predictors of smoking abstinence were evaluated among those patients assigned to the active SC condition (N = 153) using logistic regression. Results: Abstinence during treatment was positively associated with younger age, Hispanic or Caucasian (as opposed to African American) ethnicity/race, employment or student status, fewer cigarettes per day at baseline, lower severity of the primary substance problem at baseline, and higher methadone doses (among the subsample in methadone treatment). Conclusions and Scientific Significance: During future efforts to improve SC treatments among drug- and alcohol-dependent patients, consideration should be given to adequate treatment to reduce the severity of the primary drug or alcohol problem, tailoring treatments for patients with greater severity of smoking and of the primary substance problem, and culturally sensitive interventions. Analysis of predictors of outcome may be a useful tool for treatment development
PMCID:4101995
PMID: 21854292
ISSN: 1097-9891
CID: 136946
Barriers to providing health services for HIV/AIDS, hepatitis C virus infection and sexually transmitted infections in substance abuse treatment programs in the United States
We sought to identify barriers to offering services for HIV/AIDS, hepatitis C virus, and sexually transmitted infections in substance abuse treatment programs. We surveyed treatment program administrators and clinicians within the National Drug Abuse Treatment Clinical Trials Network to evaluate the availability of medical and non-medical services for patients with or at risk for acquiring these infections. A substantial proportion of programs do not offer services (particularly medical services) for these infections. The most commonly cited barriers were funding, health insurance benefits, patient acceptance, and staff training. The findings highlight a missed opportunity to positively impact these infectious disease epidemics
PMCID:3102428
PMID: 21491291
ISSN: 1545-0848
CID: 134683
A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia
BACKGROUND: In a previous pilot study, MK-0777--a gamma-aminobutyric acid (GABA)(A) alpha2/alpha3 partial agonist--was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schizophrenia. METHODS: Sixty people with DSM-IV schizophrenia entered a 4-week, multi-center, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized to: MK-0777 3 mg b.i.d. (n = 18); MK-0777 8 mg b.i.d. (n = 21); or placebo (n = 21). Participants were clinically stable. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, AX-Continuous Performance Test, and N-Back were used to assess cognition. The University of California San Diego (UCSD) Performance Based Skills Assessment-2 and the Schizophrenia Cognition Rating Scale assessed functional capacity and served as functional outcome coprimary measures. RESULTS: There were no significant group differences on the primary outcome measure, the MATRICS Consensus Cognitive Battery composite score. Secondary analyses suggested that participants randomized to placebo performed significantly better on visual memory and reasoning/problem-solving tests than participants assigned to either MK-0777 dose. There were no significant group differences on the AX-Continuous Performance Test or N-Back d prime scores or UCSD Performance-Based Skills Assessment-2 and Schizophrenia Cognition Rating Scale total scores. In general, MK-0777 was well-tolerated with minimal side effects. CONCLUSIONS: The study results suggest that MK-0777 has little benefit for cognitive impairments in people with schizophrenia. The GABA(A) receptor remains a promising target, but a more potent partial agonist with greater intrinsic activity at the GABA(A) alpha2 site might be needed for cognitive enhancement in schizophrenia
PMCID:3058394
PMID: 21145041
ISSN: 1873-2402
CID: 134301
Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2
It is fundamentally important that signaling gradients provide positional information to govern morphogenesis of multicellular organisms. Morphogen gradients can generate different cell types in specific spatial order at distinct threshold concentrations. However, it is largely unknown whether and how signaling gradients also control cell polarities by acting as global cues. Here, we show that Wnt signaling gradient provides directional information to a field of cells. Vangl2, a core component in planar cell polarity, forms Wnt-induced receptor complex with Ror2 to sense Wnt dosages. Wnts dose-dependently induce Vangl2 phosphorylation of serine/threonine residues and Vangl2 activities depend on its levels of phosphorylation. In the limb bud, Wnt5a signaling gradient controls limb elongation by establishing PCP in chondrocytes along the proximal-distal axis through regulating Vangl2 phosphorylation. Our studies have provided new insight to Robinow syndrome, Brachydactyly Type B1, and spinal bifida which are caused by mutations in human ROR2, WNT5A, or VANGL.
PMCID:3062198
PMID: 21316585
ISSN: 1878-1551
CID: 2137602
