Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and comorbid substance misuse: randomised controlled trial

Objectives To evaluate the effectiveness of integrated motivational interviewing and cognitive behaviour therapy in addition to standard care for patients with psychosis and a co-morbid substance use problem. Design Two-centre, open, rater-blind randomised controlled trial Setting UK Secondary Care Participants 327 patients with clinical diagnoses of schizophrenia, schizophreniform or schizoaffective disorder and DSM-IV diagnoses of drug and/or alcohol dependence or abuse Interventions Participants were randomly allocated to integrated motivational interviewing and cognitive behaviour therapy or standard care. Therapy has two phases. Phase one – “motivation building” – concerns engaging the patient, then exploring and resolving ambivalence for change in substance use. Phase two –“Action” – supports and facilitates change using cognitive behavioural approaches. Up to 26 therapy sessions were delivered over one year. Main outcomes The primary outcome was death from any cause or admission to hospital in the 12 months after therapy. Secondary outcomes were frequency and amount of substance use (Timeline Followback), readiness to change, perceived negative consequences of use, psychotic symptom ratings, number and duration of relapses, global assessment of functioning and deliberate self harm, at 12 and 24 months, with additional Timeline Followback assessments at 6 and 18 months. Analysis was by intention-to-treat with robust treatment effect estimates. Results 327 participants were randomised. 326 (99.7%) were assessed on the primary outcome, 246 (75.2%) on main secondary outcomes at 24 months. Regarding the primary outcome, there was no beneficial treatment effect on hospital admissions/ death during follow-up, with 20.2% (33/163) of controls and 23.3% (38/163) of the therapy group deceased or admitted (adjusted odds-ratio 1.16; P= 0.579; 95% confidence interval 0.68 to 1.99). For secondary outcomes there was no treatment effect on frequency of substance use or perceived negative consequences, but a statistically significant effect of therapy on amount used per substance-using day (adjusted odds-ratios: (a) for main substance 1.50; P=0.016; 1.08 to 2.09, (b) all substances 1.48; P=0.017; 1.07 to 2.05). There was a statistically significant treatment effect on readiness to change use at 12 months (adjusted odds-ratio 2.05; P=0.004; 1.26 to 3.31), not maintained at 24 months. There were no treatment effects on assessed clinical outcomes. Conclusions Integrated motivational interviewing and cognitive behaviour therapy for people with psychosis and substance misuse does not improve outcome in terms of hospitalisation, symptom outcomes or functioning. It does result in a reduction in amount of substance use which is maintained over the year’s follow up. Trial registration Current Controlled Trials: ISRCTN14404480

Obsessive-compulsive disorder: Prevalence, comorbidity, impact, and help-seeking in the British National Psychiatric Morbidity Survey of 2000

Objective: There is little information about obsessive-compulsive disorder in large representative community samples. The authors aimed to establish obsessive-compulsive disorder prevalence and its clinical typology among adults in private households in Great Britain and to obtain generalizable estimates of impairment and help-seeking.Method: Data from the British National Psychiatric Morbidity Survey of 2000, comprising 8,580 individuals, were analyzed using appropriate measurements. The study compared individuals with obsessive-compulsive disorder, individuals with other neurotic disorders, and a nonneurotic comparison group. ICD-10 diagnoses were derived from the Clinical Interview Schedule-Revised.Results: the authors identified 114 individuals (74 women, 40 men) with obsessive-compulsive disorder, with a weighted 1-month prevalence of 1.1%. Most individuals (55%) in the obsessive-compulsive group had obsessions only. Comorbidity occurred in 62% of these individuals, which was significantly greater than the group with other neuroses (10%). Co-occurring neuroses were depressive episode (37%), generalized anxiety disorder (31%), agoraphobia or panic disorder (22%), social phobia (17%), and specific phobia (15%). Alcohol dependence was present in 20% of participants, mainly men, and drug dependence was present in 13%. Obsessive-compulsive disorder, compared with other neurotic disorders, was associated with more marked social and occupational impairment. One-quarter of obsessive-compulsive disorder participants had previously attempted suicide. Individuals with pure and comorbid obsessive-compulsive disorder did not differ according to most indices of impairment, including suicidal behavior, but pure individuals were significantly less likely to have sought help (14% versus 56%).Conclusions: A rare yet severe mental disorder, obsessive-compulsive disorder is an atypical neurosis, of which the public health significance has been underestimated. Unmet need among individuals with pure obsessive-compulsive disorder is a cause for concern, requiring further investigation of barriers to care and interventions to encourage help-seeking.

Chronic alcohol intake upregulates hepatic expression of carotenoid cleavage enzymes and PPAR in rats

Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15′-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9′10′-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation of CMO2 has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPARγ, PPARα, and TRβ as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPARγ, PPARα, and TRβ and upregulated protein levels of CMO2, PPARγ, and PPARα. There was a positive correlation of PPARγ with CMO1(r = 0.89; P<0.0001) and both PPARγ and PPARα with CMO2 (r = 0.72, P< 0.001 and r = 0.62, P< 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPARγ expression and lower vitamin A status in the liver. © 2010 American Society for Nutrition.

Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Validity of alcohol screening instruments in general population gender studies: an analytical review

The present study is an analytical review of the methodology used in studies of efficacy of screening instruments to detect harmful use/ alcohol dependence according to the gender in population surveys. Systematic review of bibliography was done, using data from Web of Science, Pubmed and PsycInfo. Population studies were included without date range, in English, Spanish or Portuguese languages, with sample of adults, evaluating psychometric characteristics of any alcohol screening instrument, whereas studies in special population or under treatment as well as prevalence of alcohol consumption were excluded. Thirteen studies were selected to be included in the present review. According to the studies, the instruments that presented a better performance among men were AUDIT and its derivatives (6 studies) and CAGE (2 studies), whereas among women, AUDIT and its derivatives (7 studies), followed by CAGE (3 studies). The increase of consumption and problems related to alcohol use and its implications for public health indicate the need and urgency for adequacy of screening instruments to differences of gender in general population. The population surveys in the area are scarce. Furthermore, the found studies present heterogeneous methodology which makes accurate comparisons difficult.

DNA-Interactive Properties of Crotamine, a Cell-Penetrating Polypeptide and a Potential Drug Carrier

Crotamine, a 42-residue polypeptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, has been shown to be a cell-penetrating protein that targets chromosomes, carries plasmid DNA into cells, and shows specificity for actively proliferating cells. Given this potential role as a nucleic acid-delivery vector, we have studied in detail the binding of crotamine to single- and double-stranded DNAs of different lengths and base compositions over a range of ionic conditions. Agarose gel electrophoresis and ultraviolet spectrophotometry analysis indicate that complexes of crotamine with long-chain DNAs readily aggregate and precipitate at low ionic strength. This aggregation, which may be important for cellular uptake of DNA, becomes less likely with shorter chain length. 25-mer oligonucleotides do not show any evidence of such aggregation, permitting the determination of affinities and size via fluorescence quenching experiments. The polypeptide binds non-cooperatively to DNA, covering about 5 nucleotide residues when it binds to single (ss) or (ds) double stranded molecules. The affinities of the protein for ss-vs. ds-DNA are comparable, and inversely proportional to salt levels. Analysis of the dependence of affinity on [NaCl] indicates that there are a maximum of,3 ionic interactions between the protein and DNA, with some of the binding affinity attributable to non-ionic interactions. Inspection of the three-dimensional structure of the protein suggests that residues 31 to 35, Arg-Trp-Arg-Trp-Lys, could serve as a potential DNA-binding site. A hexapeptide containing this sequence displayed a lower DNA binding affinity and salt dependence as compared to the full-length protein, likely indicative of a more suitable 3D structure and the presence of accessory binding sites in the native crotamine. Taken together, the data presented here describing crotamine-DNA interactions may lend support to the design of more effective nucleic acid drug delivery vehicles which take advantage of crotamine as a carrier with specificity for actively proliferating cells. Citation: Chen P-C, Hayashi MAF, Oliveira EB, Karpel RL (2012) DNA-Interactive Properties of Crotamine, a Cell-Penetrating Polypeptide and a Potential Drug Carrier. PLoS ONE 7(11): e48913. doi:10.1371/journal.pone.0048913

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (and were not genotype 3, indicated no strong evidence of excess mortality. We found little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

Self-reported alcohol consumption and its association with adherence and outcome of antiretroviral therapy in the Swiss HIV Cohort Study

BACKGROUND: Alcohol consumption leading to morbidity and mortality affects HIV-infected individuals. Here, we aimed to study self-reported alcohol consumption and to determine its association with adherence to antiretroviral therapy (ART) and HIV surrogate markers. METHODS: Cross-sectional data on daily alcohol consumption from August 2005 to August 2007 were analysed and categorized according to the World Health Organization definition (light, moderate or severe health risk). Multivariate logistic regression models and Pearson's chi(2) statistics were used to test the influence of alcohol use on endpoints. RESULTS: Of 6,323 individuals, 52.3% consumed alcohol less than once a week in the past 6 months. Alcohol intake was deemed light in 39.9%, moderate in 5.0% and severe in 2.8%. Higher alcohol consumption was significantly associated with older age, less education, injection drug use, being in a drug maintenance programme, psychiatric treatment, hepatitis C virus coinfection and with a longer time since diagnosis of HIV. Lower alcohol consumption was found in males, non-Caucasians, individuals currently on ART and those with more ART experience. In patients on ART (n=4,519), missed doses and alcohol consumption were positively correlated (P<0.001). Severe alcohol consumers, who were pretreated with ART, were more often off treatment despite having CD4+ T-cell count <200 cells/microl; however, severe alcohol consumption per se did not delay starting ART. In treated individuals, alcohol consumption was not associated with worse HIV surrogate markers. CONCLUSIONS: Higher alcohol consumption in HIV-infected individuals was associated with several psychosocial and demographic factors, non-adherence to ART and, in pretreated individuals, being off treatment despite low CD4+ T-cell counts.

Association of alcohol craving and proximal outcomes of a residential treatment program for patients with alcohol use disorders

Background: Alcohol craving is an essential construct in research and treatment of alcohol use disorders (AUD). Craving is mostly investigated in association with concurrent variables or distal treatment outcomes at follow-up. Objectives: The aim of this study is to examine craving at admission and its relevance for essential proximal outcomes at discharge from AUD treatment such as positive alcohol expectancy, abstinent-related self-efficacy, and substance-related coping, as well as patients’ demographic and AUD characteristics. Methods: In total, 36 patients were recruited within an inpatient treatment AUD program. Results: An association between craving and positive alcohol expectancies at discharge was found in the regression model even when the respective expectancies, age, gender, and severity of alcohol dependence at admission were controlled for (F(2,29)1⁄432.71, p50.001). Craving explained 2.3% of the variance of change in positive alcohol expectancy. Conclusion: The results suggest a low predictive value of craving for positive alcohol expectancy. In addition, we found significant associations between the craving and the severity of AUD and alcohol consumption before admission. Future studies should include proximal outcomes related to treatment efficacy as well as distal outcomes.

Resistance to Temptation: The Interaction of External and Internal Control on Alcohol Use During Residential Treatment for Alcohol Use Disorder

Background: There is evidence that drinking during residential treatment is related to various factors, such as patients’ general control beliefs and self-efficacy, as well as to external control of alcohol use by program’s staff and situations where there is temptation to drink. As alcohol use during treatment has been shown to be associated with the resumption of alcohol use after discharge from residential treatment, we aimed to investigate how these variables are related to alcohol use during abstinenceoriented residential treatment programs for alcohol use disorders (AUD). Methods: In total, 509 patients who entered 1 of 2 residential abstinence-oriented treatment programs for AUD were included in the study. After detoxification, patients completed a standardized diagnostic procedure including interviews and questionnaires. Drinking was assessed by patients’ selfreport of at least 1 standard drink or by positive breathalyzer testing. The 2 residential programs were categorized as high or low control according to the average number of tests per patient. Results: Regression analysis revealed a significant interaction effect between internal and external control suggesting that patients with high internal locus of control and high frequency of control by staff demonstrated the least alcohol use during treatment (16.7%) while patients with low internal locus of control in programs with low external control were more likely to use alcohol during Treatment (45.9%). No effects were found for self-efficacy and temptation. Conclusions: As alcohol use during treatment is most likely associated with poor treatment outcomes, external control may improve treatment outcomes and particularly support patients with low internal locus of control, who show the highest risk for alcohol use during treatment. High external control may complement high internal control to improve alcohol use prevention while in treatment. Key Words: Alcohol Dependence, Alcohol Use, Locus of Control, Alcohol Testing.

Childhood sexual victimization: Risk factor for drug use and sexual risk behaviors

The purpose of this dissertation was to survey men in the Harris County Jail (HCJ) to establish a more valid estimate of childhood sexual abuse (CSA) prevalence in a jailed-based population; to assess whether inmates with a history of CSA were at greater risk for use of drugs and alcohol and engaging in high-risk sexual behaviors than those without histories of childhood sexual abuse. ^ The first study determined the prevalence of childhood sexual abuse among incarcerated males in a county jail. In this study, sixty-three percent of the subjects reported having been sexually abused. Sixty-one percent reported abuse pre-puberty and 10% reported abuse post puberty. In pre-puberty abuse the initiation of first abuse occurred at a mean age of 5.6 years (SD 5.096, range: 2–13 years). ^ The second study explored the association between inmates with histories of CSA as a risk factor for sexual risk behaviors. A history of sexual abuse did not appear to be associated with an elevated risk of sexual risk behaviors. ^ The third study explored a history of drug use and a history of CSA among the inmates. A chi-square test showed that the inmates who reported a history of CSA, was significantly greater for the following drugs: Marijuana (02), Crack (03), Heroin/Morphine (.03), Amphetamines/Speed (01), Downers/Barbiturates (.001), Methamphetamine/Crystal Meth (.001), Valium .02), LSD/Acid (.001), and Inhalants (.001), p < .05). Significance was not found in alcohol, tobacco, cocaine, Quaaludes and methadone. ^ The research from this study provides empirical data supporting previous research. The current data shows that incarcerated inmates have a high prevalence of childhood sexual abuse and drug use. Sexual victimization as a child does not appear to be associated with an elevated risk of unsafe sexual behaviors. However, men who used drugs were twice as likely to have engaged in unprotected sex with casual and regular partners, and rarely used condoms with paid sex. Although our study methods do not permit a causal explanation for this association, we believe it is of concern. Finally, data in this study shows that sexually abused children are likely candidates for adult criminal behavior. ^

Behavioral cognitions and factors related to hepatitis B vaccine acceptance and compliance in a cohort of drug users in Houston, Texas

Purpose. Drug users are a large group of those at highest risk for contracting Hepatitis B (HBV). This study sought to identify predictors of HBV vaccine acceptance and compliance in a cohort of current drug users in Houston, Texas. Perceived severity of HBV, perceived risk of HBV, perceived peer support of HBV vaccine, and perceived benefits of HBV vaccine were also examined assess their relationship to HBV compliance. ^ Methods. A randomized intervention study was conducted in a cohort of current drug users in Houston, Texas. Participants were recruited by community outreach workers from two urban neighborhoods in Houston known for high drug use. Participants were randomized to a standard vaccine schedule group or an accelerated vaccine schedule group. Participants were also randomized to either a standard behavioral intervention group or an enhanced behavioral intervention group designed to increase HBV vaccine acceptance and compliance. Baseline visits included an interview for demographic factors, drug and sexual behaviors, and HBV beliefs; and participants received the first dose of the HBV vaccine and one of the behavioral interventions. ^ Results. Of 1,643 screening participants, 77% accepted the HBV vaccine. Participants ages ≥50 were twice as likely to accept the vaccine. African Americans and less frequent drug users were also significantly more likely to accept the vaccine. Of the 1,259 participants who enrolled in the study, 75% were compliant to the HBV vaccine. Predictors of compliance were found to be race, housing status, and alcohol use. Speedball users were found to be 74% less likely to be compliant the HBV vaccine. None of the behavioral constructs assessed were found to significantly predict HBV compliance. However, additional analyses found that there were significant changes in mean scores of the behavioral concepts when measured at six month follow-up. ^ Conclusion. Results from this study indicate that when offered a free vaccine in the drug user community, a large percentage will be compliant to the vaccine series. The behavioral cognitions commonly used in HBV compliance research need to be extended to accurately fit this cohort. Also, vaccine intervention focus needs to be on reaching the homeless segment of the drug users and the speedball users. ^

HIV prevalence and contextual risk-factors among injection drug users in Harris County, Texas

Injection drug use is the third most frequent risk factor for new HIV infections in the United States. A dual mode of exposure: unsafe drug using practices and risky sexual behaviors underlies injection drug users' (IDUs) risk for HIV infection. This research study aims to characterize patterns of drug use and sexual behaviors and to examine the social contexts associated with risk behaviors among a sample of injection drug users. ^ This cross-sectional study includes 523 eligible injection drug users from Houston, Texas, recruited into the 2009 National HIV Behavioral Surveillance project. Three separate set of analyses were carried out. First, using latent class analysis (LCA) and maximum likelihood we identified classes of behavior describing levels of HIV risk, from nine drug and sexual behaviors. Second, eight separate multivariable regression models were built to examine the odds of reporting a given risk behavior. We constructed the most parsimonious multivariable model using a manual backward stepwise process. Third, we examined whether HIV serostatus knowledge (self-reported positive, negative, or unknown serostatus) is associated with drug use and sexual HIV risk behaviors. ^ Participants were mostly male, older, and non-Hispanic Black. Forty-two percent of our sample had behaviors putting them at high risk, 25% at moderate risk, and 33% at low risk for HIV infection. Individuals in the High-risk group had the highest probability of risky behaviors, categorized as almost always sharing needles (0.93), seldom using condoms (0.10), reporting recent exchange sex partners (0.90), and practicing anal sex (0.34). We observed that unsafe injecting practices were associated with high risk sexual behaviors. IDUs who shared needles had higher odds of having anal sex (OR=2.89, 95%CI: 1.69-4.92) and unprotected sex (OR=2.66, 95%CI: 1.38-5.10) at last sex. Additionally, homelessness was associated with needle sharing (OR=2.24, 95% CI: 1.34-3.76) and cocaine use was associated with multiple sex partners (OR=1.82, 95% CI: 1.07-3.11). Furthermore, twenty-one percent of the sample was unaware of their HIV serostatus. The three groups were not different from each other in terms of drug-use behaviors: always using a new sterile needle, or in sharing needles or drug preparation equipment. However, IDUs unaware of their HIV serostatus were 33% more likely to report having more than three sexual partners in the past 12 months; 45% more likely to report to have unprotected sex and 85% more likely to use drug and or alcohol during or before at last sex compared to HIV-positive IDUs. ^ This analysis underscores the merit of LCA approach to empirically categorize injection drug users into distinct classes and identify their risk pattern using multiple indicators and our results show considerable overlap of high risk sexual and drug use behaviors among the high-risk class members. The observed clustering pattern of drug and sexual risk behavior among this population confirms that injection drug users do not represent a homogeneous population in terms of HIV risk. These findings will help develop tailored prevention programs.^

Sentencing and dispositions of youth DUI and other alcohol offenses: a guide for judges and prosecutors.

Mode of access: Internet.

Evaluation of the Alcohol Use and Traffic Safety Curriculum (K-12). Section II - volume 7a. Final report.

National Highway Traffic Safety Administration, Office of Driver and Pedestrian Programs, Washington, D.C.