Effects of dopamine receptor D4 variation on alcohol and tobacco use and on novelty seeking: Multivariate linkage and association analysis

The dopamine D4 receptor gene contains a polymorphic sequence consisting of a variable number of 48-base-pair (bp) repeats, and there have been a number of reports that this polymorphism is associated with variation in novelty seeking or in substance abuse and addictive behaviors. In this study we have assessed the linkage and association of DRD4 genotype with novelty seeking, alcohol use, and smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited from the Australian Twin Registry (ATR). We found no evidence of linkage or association of the DRD4 locus with any of the phenotypes. We made use of repeated measures for some phenotypes to increase power by multivariate genetic analysis, but allelic effects were still non-significant. Specifically, it has been suggested that the DRD4 7-repeat allele is associated with increased novelty seeking in males but we found no evidence for this, despite considerable power to do so. We conclude that DRD4 variation does not have an effect on use of alcohol and the problems that arise from it, on smoking, or on novelty seeking behavior. (C) 2003 Wiley-Liss, Inc.

Effects of reduction in heroin supply on injecting drug use: analysis of data from needle and syringe programmes

n early 2001 there was a dramatic decline in the availability of heroin in New South Wales (NSW), Australia, where previously heroin had been readily available at a low price and high purity.1 The decline was confirmed by Australia's strategic early warning system, which revealed a reduction in heroin supply across Australia and a considerable increase in price,2 particularly from January to April 2001. This "heroin shortage" provided a natural experiment in which to examine the effect of substantial changes in price and availability on injecting drug use and its associated harms in Australia's largest heroin market,2 a setting in which harm reduction strategies were widely used. Publicly funded needle and syringe programmes were introduced to Australia in 1987, and methadone maintenance programmes, which were established in the 1970s, were significantly expanded in 1985 and again in 1999.

Comorbidity: Cannabis and complexity

Cannabis is one of the most commonly used illicit drugs, and its effects have traditionally been seen as less harmful than outcomes associated with the highly prevalent use of alcohol and other illicit substances (e.g., cocaine and amphetamines), and injecting drugs. Consequently, less attention has been focused on developing and evaluating interventions in this area. However, current research supports the idea that cannabis does pose a number of acute and chronic health risks to the individual and to society. The authors review findings concerning the physiological and neurological effects of cannabis, prevalence of use, and studies concerning its possible role as a "gateway" drug. Diagnostic criteria for cannabis dependence and abuse are discussed, with a focus on whether a cannabis withdrawal syndrome exists and if so how it can be diagnosed. There is strong support for a link between cannabis and the development and exacerbation of psychosis and other mental health conditions (e.g., anxiety, depression). Further research is needed to determine the underlying neurochemical processes and their possible contribution to etiology, as well as the social factors that contribute to the increasing use of cannabis by young people. In addition there is a need for systematic evaluation using randomized controlled trials to determine effective prevention and treatment strategies. A number of public health programs that address cannabis use are reviewed along with available evidence for their effectiveness.

Early and mid Holocene tool-use and processing of taro (Colocasia esculenta), yam (Dioscorea sp.) and other plants at Kuk Swamp in the highlands of Papua New Guinea

Recent multidisciplinary investigations document an independent emergence of agriculture at Kuk Swamp in the highlands of Papua New Guinea. In this paper we report preliminary usewear analysis and details of prehistoric use of stone tools for processing starchy food and other plants at Kuk Swamp. Morphological diagnostics for starch granules are reported for two potentially significant economic species, taro (Colocasia esculenta) and yam (Dioscorea sp.), following comparisons between prehistoric and botanical reference specimens. Usewear and residue analyses of starch granules indicate that both these species were processed on the wetland margin during the early and mid Holocene. We argue that processing of taro and yam commences by at least 10,200 calibrated years before present (cal BP), although the taro and yam starch granules do not permit us to distinguish between wild or cultivated forms. From at least 6950 to 6440 cal BP the processing of taro, yam and other plants indicates that they are likely to have been integrated into cultivation practices on the wetland edge.

"Crack down on the celebrity junkies": does media coverage of celebrity drug use pose a risk to young people?

This study analysed news media content to examine the role played by celebrity drug use in young people's perceptions of drug use. We know that young people have access to discourses of drug use through music and other media which may emphasise short term gains (of pleasure or sexual success) over longer term health and social problems. This study goes beyond a simple modelling approach by using Media Framing Analysis (MFA) to take an in-depth look at the messages themselves and how they are 'framed'. New stories about Amy Winehouse's drug use were used and we conducted focus groups with young people asking them questions about drugs, celebrity and the media. Frames identified include: 'troubled genius', 'losing patience' and 'glamorization or gritty realism'. Initially, the press championed Winehouse's musical talent but soon began to tire of her recklessness; the participants tended to be unimpressed with Winehouse's drug use, characterising her as a promising artist who had 'gone off the rails'. Young people were far more critical of Winehouse than might be expected, demonstrating that concerns about the influence of celebrity drug use and its impact on future health risk behaviour among young people may have been over-simplified and exaggerated. This study illustrates the need to understand young people and their frames of reference within popular culture when designing drug awareness information relevant to them. Furthermore, it indicates that critical media skills analysis may contribute to health risk education programmes related to drug use.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

An investigation of the relationship between antemortem and postmortem drug concentrations in blood

In the field of postmortem toxicology, principles from pharmacology and toxicology are combined in order to determine if exogenous substances contributed to ones death. In order to make this determination postmortem and (whenever available) antemortem blood samples may be analyzed. This project focused on evaluating the relationship between postmortem and antemortem blood drug levels, in order to better define an interpretive framework for postmortem toxicology. To do this, it was imperative to evaluate the differences in antemortem and postmortem drug concentrations, determine the role microbial activity and evaluate drug stability. Microbial studies determined that the bacteria Escherichia coli and Pseudomonas aeruginosa could use the carbon structures of drugs as a source of food. This would suggest prior to sample collection, microbial activity could potentially affect drug levels. This process however would stop before toxicologic evaluation, as at autopsy blood samples are stored in tubes containing the antimicrobial agent sodium fluoride. Analysis of preserved blood determined that under the current storage conditions sodium fluoride effectively inhibited microbial growth. Nonetheless, in many instances inconsistent drug concentrations were identified. When comparing antemortem to postmortem results, diphenhydramine, morphine, codeine and methadone, all showed significantly increased postmortem drug levels. In many instances, increased postmortem concentrations correlated with extended postmortem intervals. Other drugs, such as alprazolam, were likely to have concentration discrepancies when short antemortem to death intervals were coupled with extended postmortem intervals. While still others, such as midazolam followed the expected pattern of metabolism and elimination, which often resulted in decreased postmortem concentrations. The importance of drug stability was displayed when reviewing the clonazepam/ 7-aminoclonazepam data, as the parent drug commonly converted to its metabolite even when stored in the presence of a preservative. In instances of decreasing postmortem drug concentrations the effect of refrigerated storage could not be ruled out. A stability experiment, which contained codeine, produced data that indicated concentrations could continue to decline under the current storage conditions. The cumulative data gathered for this experiment was used to identify concentration trends, which subsequently aided in the development of interpretive considerations for the specific analytes examined in the study.

Social capital, HIV risk behavior and substance use among recent Latino immigrants in South Florida

Social capital, or social cohesion or group connectedness, can influence both HIV risk behavior and substance use. Because recent immigrants undergo a change in environment, one of the consequences can be a change in social capital. There may be an association among changes in social capital, and HIV risk behavior and substance use post immigration. The dissertation focused on the interface of these three variables among recent Latino immigrants (RLIs) in South Florida. The first manuscript is a systematic review of social capital and HIV risk behavior, and served as a partial background for the second and third manuscripts. Twelve papers with a measure of social capital as an independent variable and HIV risk as the dependent variable were included in the analysis. Eleven studies measured social capital at the individual level, and one study measured social capital at the group level. HIV risk was influenced by social capital, but the type of influence was dependent on the type of social capital and on the study population. Cognitive social capital, or levels of collective action, was protective against HIV in both men and women. The role of structural social capital, or levels of civic engagement/group participation, on HIV risk was dependent on the type of structural social capital and varied by gender. Microfinance programs and functional group participation were protective for women, while dysfunctional group participation and peer-level support may have increased HIV risk among men. The second manuscript was an original study assessing changes in social capital and HIV risk behavior pre to post immigration among RLIs in South Florida (n=527). HIV risk behavior was assessed through the frequency of vaginal-penile condom use, and the number of sexual partners. It was a longitudinal study using secondary data analysis to assess changes in social capital and HIV risk behavior pre immigration to two years post immigration, and to determine if there was a relationship between the two variables. There was an 8% decrease in total social capital (p < .05). Reporting of 'Never use' of condoms in the past 90 days increased in all subcategories (p < .05). Single men had a decrease in number of sexual partners (p < .05). Lower social capital measured on the dimension of 'friend and other' was marginally associated with fewer sexual partners. The third manuscript was another original study looking at the association between social capital and substance use among RLIs in South Florida (n=527). Substance use with measured by frequency of hazardous alcoholic drinking, and illicit drug use. It was a longitudinal study of social capital and substance-use from pre to two years post immigration. Post-immigration, social capital, hazardous drinking and illicit drug use decreased (p<.001). After adjusting for time, compared to males, females were less likely to engage in hazardous drinking (OR=.31, p<.001), and less likely to engage in illicit drug use (OR=.67, p=.01). Documentation status was a moderator between social capital and illicit drug use. 'Business' and 'Agency' social capital were associated with changes in illicit drug use for documented immigrants. After adjusting for gender and marital status, on average, documented immigrants with a one-unit increase in 'business' social capital were 1.2 times more likely to engage in illicit drug use (p<.01), and documented immigrants with one-unit increase in 'agency' social capital were 38% less likely to engage in illicit drug use (p<.01). 'Friend and other' social capital was associated with a decrease in illicit drug use among undocumented immigrants. After adjusting for gender and marital status, on average, undocumented immigrants with a one-unit increase in 'friend and other' social capital were 45% less likely to engage in hazardous drinking and 44% less likely to use illicit drugs (p<.01, p<.05). Studying these three domains is relevant because HIV continues to be a public health issue, particularly in Miami-Dade County, which is ranked among other U.S. regions with high rates of HIV/AIDS prevalence. Substance use is associated with HIV risk behavior; in most studies, increased substance use is associated with increased chances of HIV risk behavior. Immigration, which is the hypothesized catalyst for the change in social capital, has an impact on the dynamic of a society. Greater immigration can be burdensome on the host country's societal resources; however immigrants are also potentially a source of additional skilled labor for the workforce. Therefore, successful adaption of immigrants can have a positive influence on receiving communities. With Florida being a major receiver of immigrants to the U.S, this dissertation attempts to address an important public health issue for South Florida and the U.S. at large.

Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer

Peer reviewed

Examining the Crack Epidemic and Subsequent Drug Policy through Identifying Trends in Outpatient Substance Abuse Treatment for Crack Use/Abuse: 1995-2005

Disparities in the crack/cocaine discourse have changed drastically since its inception over 30 years ago. Since the late 1980s, research examining this particular abuse has become more complex as both nationally and globally crack use/abuse has been examined within various contexts. Crack use has often been framed as an African American problem in part resulting from the high volume of African Americans seeking treatment for illnesses associated with their crack-cocaine use, and more African Americans dying from crack-cocaine overdose. This logical fallacy persists despite evidence showing African Americans have lower substance use/abuse compared to Caucasians. Given the impact of the crack epidemic as well as its related drug policies on African American communities and their families, further examination of crack use/abuse is necessary. This study will discuss the crack epidemic historically and examine crack use among clients of a large sample of outpatient substance abuse treatment units over a decade period between 1995 and 2005.

CURB-65 and Other Markers of Illness Severity in Community-Acquired Pneumonia Among HIV-Positive Patients

As the relative burden of community-acquired bacterial pneumonia among HIV-positive patients increases, adequate prediction of case severity on presentation is crucial. We sought to determine what characteristics measurable on presentation are predictive of worse outcomes. We studied all admissions for community-acquired bacterial pneumonia over one year at a tertiary centre. Patient demographics, comorbidities, HIV-specific markers and CURB-65 scores on Emergency Department presentation were reviewed. Outcomes of interest included mortality, bacteraemia, intensive care unit admission and orotracheal intubation. A total of 396 patients were included: 49 HIV-positive and 347 HIV-negative. Mean CURB-65 score was 1.3 for HIV-positive and 2.2 for HIV-negative patients (p < 0.0001), its predictive value for mortality being maintained in both groups (p = 0.03 and p < 0.001, respectively). Adjusting for CURB-65 scores, HIV infection by itself was only associated with bacteraemia (adjusted odds ratio [AOR] 7.1, 95% CI [2.6-19.5]). Patients with < 200 CD4 cells/µL presented similar CURB-65 adjusted mortality (aOR 1.7, 95% CI [0.2-15.2]), but higher risk of intensive care unit admission (aOR 5.7, 95% CI [1.5-22.0]) and orotracheal intubation (aOR 9.1, 95% CI [2.2-37.1]), compared to HIV-negative patients. These two associations were not observed in the > 200 CD4 cells/µL subgroup (aOR 2.2, 95% CI [0.7-7.6] and aOR 0.8, 95% CI [0.1-6.5], respectively). Antiretroviral therapy and viral load suppression were not associated with different outcomes (p > 0.05). High CURB-65 scores and CD4 counts < 200 cells/µL were both associated with worse outcomes. Severity assessment scales and CD4 counts may both be helpful in predicting severity in HIV-positive patients presenting with community-acquired bacterial pneumonia.