Katherine M. Conigrave

Genetical genomic determinants of alcohol consumption in rats and humans

BackgroundWe have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations.ResultsIn the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption.ConclusionOur results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well-defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption.

The accessibility, acceptability, health impact and cost implications of primary healthcare outlets that target injecting drug users: A narrative synthesis of literature

BACKGROUND Injecting drug users (IDUs) are at increased risk of health problems ranging from injecting-related injuries to blood borne viral infections. Access to primary healthcare (PHC) is often limited for this marginalised group. Many seek care at emergency departments and some require hospital admission due to late presentation. The costs to both the individual and the health system are such that policymakers in some settings have implemented IDU-targeted PHC centres, with a number of models employed. However, there is insufficient evidence on the effectiveness of these centres to inform health service planning. A systematic review examining such interventions is not possible due to the heterogeneous nature of study designs. Nevertheless, an integrative literature review of IDU-targeted PHC may provide useful insights into the range of operational models and strategies to enhance the accessibility and acceptability of these services to the target population. METHODS Available literature describing the impact of IDU-targeted PHC on health outcomes, cost implications and operational challenges is reviewed. A narrative synthesis was undertaken of material sourced from relevant journal publications, grey literature and policy documents. RESULTS Several models have proven accessible and acceptable forms of PHC to IDUs, improving the overall healthcare utilisation and health status of this population with consequent savings to the health system due to a reduction in visits to emergency departments and tertiary hospitals. CONCLUSIONS Although such findings are promising, there remains a dearth of rigorous evaluations of these targeted PHC, with the public health impact of such outlets yet to be systematically documented.

The reliability of sensitive information provided by injecting drug users in a clinical setting: Clinician-administered versus audio computer-assisted self-interviewing (ACASI)

Abstract Research with injecting drug users (IDUs) suggests greater willingness to report sensitive and stigmatised behaviour via audio computer-assisted self-interviewing (ACASI) methods than during face-to-face interviews (FFIs); however, previous studies were limited in verifying this within the same individuals at the same time point. This study examines the relative willingness of IDUs to report sensitive information via ACASI and during a face-to-face clinical assessment administered in health services for IDUs. During recruitment for a randomised controlled trial undertaken at two IDU-targeted health services, assessments were undertaken as per clinical protocols, followed by referral of eligible clients to the trial, in which baseline self-report data were collected via ACASI. Five questions about sensitive injecting and sexual risk behaviours were administered to participants during both clinical interviews and baseline research data collection. “Percentage agreement” determined the magnitude of concordance/discordance in responses across interview methods, while tests appropriate to data format assessed the statistical significance of this variation. Results for all five variables suggest that, relative to ACASI, FFI elicited responses that may be perceived as more socially desirable. Discordance was statistically significant for four of the five variables examined. Participants who reported a history of sex work were more likely to provide discordant responses to at least one socially sensitive item. In health services for IDUs, information collection via ACASI may elicit more reliable and valid responses than FFI. Adoption of a universal precautionary approach to complement individually tailored assessment of and advice regarding health risk behaviours for IDUs may address this issue.

Attitudes and beliefs of emergency department staff regarding alcohol-related presentations

OBJECTIVE This study examined emergency department (ED) staff attitudes and beliefs about alcohol-related ED presentations in order to recommend improved detection and brief intervention strategies. METHODS The survey was conducted at two inner-Sydney hospital EDs in 2006 to explore ED clinical staffs attitudes, current practice and barriers for managing alcohol-related ED presentations. The sample included N=78 ED staff (54% nurses, 46% doctors), representing a 30% response rate. RESULTS Management of alcohol-related problems was not routine among ED staff, with only 5% usually formally screening for alcohol problems, only 16% usually conducting brief interventions, and only 27% usually providing a referral to specialist treatment services. Over 85% of ED staff indicated that lack of patient motivation made providing alcohol interventions very difficult. Significant predictors of good self-reported practice among ED staff for patients with alcohol problems included: being a doctor, being confident and having a sense of responsibility towards managing patients with alcohol-related problems. CONCLUSIONS This study reported that many staff lack the confidence or sense of clinical responsibility to fully and appropriately manage ED patients with alcohol-related problems. ED staff appear to require additional training, resources and support to enhance their management of patients with alcohol-related problems.

Using breath carbon monoxide to validate self-reported tobacco smoking in remote Australian Indigenous communities

BackgroundThis paper examines the specificity and sensitivity of a breath carbon monoxide (BCO) test and optimum BCO cutoff level for validating self-reported tobacco smoking in Indigenous Australians in Arnhem Land, Northern Territory (NT).MethodsIn a sample of 400 people (≥16 years) interviewed about tobacco use in three communities, both self-reported smoking and BCO data were recorded for 309 study participants. Of these, 249 reported smoking tobacco within the preceding 24 hours, and 60 reported they had never smoked or had not smoked tobacco for ≥6 months. The sample was opportunistically recruited using quotas to reflect age and gender balances in the communities where the combined Indigenous populations comprised 1,104 males and 1,215 females (≥16 years). Local Indigenous research workers assisted researchers in interviewing participants and facilitating BCO tests using a portable hand-held analyzer.ResultsA BCO cutoff of ≥7 parts per million (ppm) provided good agreement between self-report and BCO (96.0% sensitivity, 93.3% specificity). An alternative cutoff of ≥5 ppm increased sensitivity from 96.0% to 99.6% with no change in specificity (93.3%). With data for two self-reported nonsmokers who also reported that they smoked cannabis removed from the analysis, specificity increased to 96.6%.ConclusionIn these disadvantaged Indigenous populations, where data describing smoking are few, testing for BCO provides a practical, noninvasive, and immediate method to validate self-reported smoking. In further studies of tobacco smoking in these populations, cannabis use should be considered where self-reported nonsmokers show high BCO.

Alcohol Consumption Patterns and HbA1c, C-Peptide and Insulin Concentrations in Men

Objective: Observational studies support inverse associations between moderate alcohol consumption and fasting insulin concentrations, but the importance of drinking pattern on the effect of alcohol on insulin sensitivity has not been fully explored. We examined the relations of alcohol consumption patterns—including average daily consumption, frequency of consumption and drinking with meals—to fasting insulin, fasting c-peptide and hemoglobin A1c (HbA1c). Methods: A cross-sectional study of 462 disease-free men selected from the Health Professionals’ Follow-up Study to provide information on a range of drinking patterns. Study participants were 48 to 82 years of age who provided a blood sample and detailed information on diet, life-style and alcohol consumption patterns in 1994. Among the study participants, 267 men provided a fasting blood sample and contributed to the analyses of insulin and c-peptide. Results: Biologic markers were not strongly related to average alcohol consumption. Compared to abstainers, differences in insulin concentrations—all statistically non-significant—were 0.06, 1.25, 1.02, and 0.12 μU/mL for consumers of <1, 1–1.9, 2–2.9, 3+ drinks per day, respectively. The frequency of alcohol consumption was inversely related to fasting c-peptide and insulin concentrations after controlling for average alcohol consumption and other potential confounding variables. Compared to men who reported consuming alcohol one to three days per week, c-peptide concentrations were 0.08 ng/mL and 0.29 ng/mL lower (p-trend = 0.04) in men who reported consuming alcohol on four to five days per week and six to seven days per week, respectively. Men who consumed alcohol on most days also had lower fasting insulin levels than more irregular drinkers (p-trend = 0.05). Conclusions: Our results suggest that frequent alcohol consumption is inversely related to fasting c-peptide and insulin concentrations.

Why are alcohol-related emergency department presentations under-detected? An exploratory study using nursing triage text

INTRODUCTION AND AIMS This study examined two methods of detecting alcohol-related emergency department (ED) presentations, provisional medical diagnosis and nursing triage text, and compared patient and service delivery characteristics to determine which patients are being missed from formal diagnosis in order to explore why alcohol-related ED presentations are under-detected. DESIGN AND METHODS Data were reviewed for all ED presentations from 2004 to 2006 (n = 118,881) for a major teaching hospital in Sydney, Australia. Each record included two nursing triage free-text fields, which were searched for over 60 alcohol-related terms and coded for a range of issues. Adjusted odds ratios were used to compare diagnostically coded alcohol-related presentations to those detected using triage text. RESULTS Approximately 4.5% of ED presentations were identified as alcohol-related, with 24% of these identified through diagnostic codes and the remainder identified by triage text. Diagnostic coding was more likely if the patient arrived by ambulance [odds ratio (OR) = 2.35] or showed signs of aggression (OR = 1.86). Failure to code alcohol-related issues was more than three times (OR = 3.23) more likely for patients with injuries. DISCUSSION AND CONCLUSIONS Alcohol-related presentations place a high demand on ED staff and less than one-quarter have an alcohol-related diagnosis recorded by their treating doctor. In order for routine ED data to be more effective for detecting alcohol-related ED presentations, it is recommended that additional resources such as an alcohol health worker be employed in Australian hospitals. These workers can educate and support ED staff to identify more clearly and record the clinical signs of alcohol and directly provide brief interventions.

Twenty-year trends in benzodiazepine dispensing in the Australian population

Considerable concern has been expressed about overprescribing of benzodiazepines and related harms. Past analyses have relied on World Health Organization‐defined daily doses (DDD) which are sometimes out of keeping with clinical usage. This study examines 20‐year (1992–2011) trends of benzodiazepine dispensing in Australia using both DDD and Ashton equivalent dose.

Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment

Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study.

Improving services for prevention and treatment of substance misuse for Aboriginal communities in a Sydney Area Health Service

INTRODUCTION AND AIMS Substance misuse among Aboriginal Australians is both a symptom of disadvantage and suffering but also a cause of health and social problems. Few data are available on how mainstream drug and alcohol services meet the needs of Aboriginal Australians. We assessed acceptability and accessibility of mainstream services for Aboriginal Australians with alcohol or drug use disorders in an urban Area Health Service (AHS). We identified priorities for improvement and an implementation plan. METHODS We collected feedback via consultation with client groups, with the Aboriginal community and community organisations, with staff of the AHS and of the local Aboriginal Medical Service (AMS) and through direct observation. We examined attendance data. RESULTS Aboriginal people were well represented in this mainstream service, partly because of existing collaboration with the AMS. Good points in the service were reported to be priority appointments for new Aboriginal clients, professional and caring service and collaboration with the AMS. Suggested improvements included increased cultural sensitivity of communication, more appropriate physical surrounds and printed materials, having Aboriginal staff available, peer support groups and integration of health care for individual, family and community. The action plan included increased recruitment and career opportunities for Aboriginal staff, strengthened partnerships with the Aboriginal community, including ongoing collaboration with the AMS in improving and monitoring mainstream service quality. DISCUSSION AND CONCLUSIONS Given the adverse impact of substance use disorders, there is a pressing need for services to work with Aboriginal communities to optimise the quality of mainstream treatment services.