Psychosocial Characteristics and Obstetric Health of Women Attending a Specialist Substance Use Antenatal Clinic in a Large Metropolitan Hospital

Objective. This paper reports the findings comparing the obstetrical health, antenatal care, and psychosocial characteristics of pregnant women with a known history of substance dependence (n = 41) and a comparison group of pregnant women attending a general antenatal clinic (n = 47). Method. Face-to-face interviews were used to assess obstetrical health, antenatal care, physical and mental functioning, substance use, and exposure to violence. Results. The substance-dependent group had more difficulty accessing antenatal care and reported more obstetrical health complications during pregnancy. Women in the substance-dependent group were more likely to report not wanting to become pregnant and were less likely to report using birth control at the time of conception. Conclusions. The profile of pregnant women (in specialised antenatal care for substance dependence) is one of severe disadvantage and poor health. The challenge is to develop and resource innovative and effective multisectoral systems to educate women and provide effective care for both women and infants

Neurometabolite Levels in Alcohol Use Disorder Patients During Baclofen Treatment and Prediction of Relapse to Heavy Drinking

Background and Aims: Baclofen, a GABAB agonist, is used as a treatment for alcohol dependence. We aimed to examine brain metabolites following administration of baclofen or placebo in alcohol dependent individuals enrolled in a randomized placebo-controlled trial.Methods: Participants included 31 alcohol dependent individuals (recent drinking: N = 16; and abstinent: N = 15) who had received daily baclofen (BAC 30–75 mg = 20) or placebo (PL = 11) for at least 2 weeks (average 17 days). Using in vivo proton magnetic resonance spectroscopy (1H-MRS), spectra from the right parietal lobe were analyzed to obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate (NAA) 120 min following administration of PL or BAC.Results: When weighting alcohol dependent participants according to recent alcohol consumption (within 24 h), there were significant differences between BAC and PL on parietal concentrations of GSH (p < 0.01) and NAA (p < 0.05). Multiple linear regression revealed a significant predictive effect of GSH on heavy drinking days at 12 weeks follow-up (Model: F = 14.28, R2 = 0.85; GSH: B = −1.22, p = 0.01) and also percentage days abstinent at 12 weeks follow-up (Model: F = 6.50, R2 = 0.72; GSH: B = 0.99, p = 0.06).Conclusion: Our data provide preliminary evidence that the effect of baclofen may be mediated by increased parietal concentrations of the antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr levels were also predictive of improved drinking outcomes in the trial and suggests a role for neural oxidative stress in alcohol use disorder

The hepatic transcriptome in human liver disease

The transcriptome is the mRNA transcript pool in a cell, organ or tissue with the liver transcriptome being amongst the most complex of any organ. Functional genomics methodologies are now being widely utilized to study transcriptomes including the hepatic transcriptome. This review outlines commonly used methods of transcriptome analysis, especially gene array analysis, focusing on publications utilizing these methods to understand human liver disease. Additionally, we have outlined the relationship between transcript and protein expressions as well as summarizing what is known about the variability of the transcriptome in non-diseased liver tissue. The approaches covered include gene array analysis, serial analysis of gene expression, subtractive hybridization and differential display. The discussion focuses on primate whole organ studies and in-vitro cell culture systems utilized. It is now clear that there are a vast number research opportunities for transcriptome analysis of human liver disease as we attempt to better understand both non-diseased and disease hepatic mRNA expression. We conclude that hepatic transcriptome analysis has already made significant contributions to the understanding of human liver pathobiology

More than three times as many Indigenous Australian clients at risk from drinking could be supported if clinicians used AUDIT-C instead of unstructured assessments

Background Aboriginal and Torres Strait Islander (‘Indigenous’) Australians experience a greater burden of disease from alcohol consumption than non-Indigenous peoples. Brief interventions can help people reduce their consumption, but people drinking at risky levels must first be detected. Valid screening tools (e.g., AUDIT-C) can help clinicians identify at-risk individuals, but clinicians also make unstructured assessments. We aimed to determine how frequently clinicians make unstructured risk assessments and use AUDIT-C with Indigenous Australian clients. We also aimed to determine the accuracy of unstructured drinking risk assessments relative to AUDIT-C screening. Finally, we aimed to explore whether client demographics influence unstructured drinking risk assessments. Methods We performed cross-sectional analysis of a large clinical dataset provided by 22 Aboriginal Community Controlled Health Services in Australia. We examined instances where clients were screened with unstructured assessments and with AUDIT-C within the same two-monthly period. This aggregated data included 9884 observations. We compared the accuracy of unstructured risk assessments against AUDIT-C using multi-level sensitivity and specificity analysis. We used multi-level logistic regression to identify demographic factors that predict risk status in unstructured assessments while controlling for AUDIT-C score. Results The primary variables were AUDIT-C score and unstructured drinking risk assessment; demographic covariates were client age and gender, and service remoteness. Clinicians made unstructured drinking risk assessments more frequently than they used AUDIT-C (17.11% and 10.85% of clinical sessions respectively). Where both measures were recorded within the same two-month period, AUDIT-C classified more clients as at risk from alcohol consumption than unstructured assessments. When using unstructured assessments, clinicians only identified approximately one third of clients drinking at risky levels based on their AUDIT-C score (sensitivity = 33.59% [95% CI 22.03, 47.52], specificity = 99.35% [95% CI 98.74, 99.67]). Controlling for AUDIT-C results and demographics (gender and service remoteness), clinicians using unstructured drinking risk assessments were more likely to classify older clients as being at risk from alcohol consumption than younger clients. Conclusions Evidence-based screening tools like AUDIT-C can help clinicians ensure that Indigenous Australian clients (and their families and communities) who are at risk from alcohol consumption are better detected and supported

Baclofen Response in Alcohol Dependent Patients Concurrently Receiving Antidepressants: Secondary Analysis From the BacALD Study

Background and Aims: There is little information with regards to the efficacy of baclofen among alcohol patients concurrently receiving antidepressants (AD). The present study aimed to conduct a secondary analysis of the moderating role of antidepressants in the BacALD trial which evaluated the efficacy of baclofen to reduce alcohol consumption in alcohol dependent patients.Methods: Alcohol dependent patients (N = 104) were treated for 12 weeks with 30 mg/day of baclofen (21 = AD and 15 = no AD), 75 mg baclofen (19 = AD and 16 = no AD) or placebo (17 = AD and 16 = no AD). Patients were included in the trial if they were concurrently receiving anti-depressants upon enrolment but were excluded if they commenced antidepressants 2 months prior to enrolment. Patients were also excluded in the case of concurrent psychotropic medications, active major mental disorder such as bipolar disorder, psychosis, or history of suicide attempt. Predefined primary outcomes included time to lapse (any drinking), relapse (>5 drinks per day in men and >4 in women). Other outcomes included drinks per drinking day, number of heavy drinking days, and percentage days abstinent and frequency of adverse events.Results: For the number of days to first lapse, there was a trend of significance for the interaction baclofen × AD (Log Rank: χ2 = 2.98, P = 0.08, OR: 0.41, 95%CI: 0.15–1.12). For the number of days to relapse, there was a trend of significance for the interaction of baclofen × AD (Log Rank: χ2 = 3.72, P = 0.05, OR: 3.40, 95%CI: 1.01–11.46). Placing significant baseline variables into the models as covariates (tobacco, ALD) weakened these interactions (P's > 0.15). There were no significant effects of ADs on the frequency of adverse events reported (P's > 0.19).Conclusion: Concurrent receipt of ADs commenced more than 2 months prior to baclofen treatment did not negatively impact on drinking outcomes. Future research examining the interaction between commencing ADs during baclofen treatment on alcohol dependent patients is required.Trial Registration: ClinicalTrials.gov, NCT01711125, https://clinicaltrials.gov/ct2/show/NCT0171112

Support for Aboriginal health services in reducing harms from alcohol : 2-year service provision outcomes in a cluster randomized trial

Background and aims There is a higher prevalence of unhealthy alcohol use among Indigenous populations, but there have been few studies of the effectiveness of screening and treatment in primary health care. Over 24 months, we tested whether a model of service-wide support could increase screening and any alcohol treatment. Design Cluster-randomized trial with 24-month implementation (12 months active, 12 months maintenance). Setting Australian Aboriginal Community Controlled primary care services. Participants Twenty-two services (83 032 clients) that use Communicare practice software and see at least 1000 clients annually, randomized to the treatment arm or control arm. Intervention and comparator Multi-faceted early support model versus a comparator of waiting-list control (11 services). Measurements A record (presence = 1, absence = 0) of: (i) Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) screening (primary outcome), (ii) any-treatment and (iii) brief intervention. We received routinely collected practice data bimonthly over 3 years (1-year baseline, 1-year implementation, 1-year maintenance). Multi-level logistic modelling was used to compare the odds of each outcome before and after implementation. Findings The odds of being screened within any 2-month reference period increased in both arms post-implementation, but the increase was nearly eight times greater in early-support services [odds ratio (OR) = 7.95, 95% confidence interval (CI) = 4.04–15.63, P < 0.001]. The change in odds of any treatment in early support was nearly double that of waiting-list controls (OR = 1.89, 95% CI = 1.19–2.98, P = 0.01) but was largely driven by decrease in controls. There was no clear evidence of difference between groups in the change in the odds of provision of brief intervention (OR = 1.95, 95% CI = 0.53–7.17, P = 0.32). Conclusions An early support model designed to aid routine implementation of alcohol screening and treatment in Aboriginal health services resulted in improvement of Alcohol Use Disorders Identification Test—Consumption screening rates over 24 months of implementation, but the effect on treatment was less clear

KCRS: A Blockchain-Based Key Compromise Resilient Signature System

Digital signatures are widely used to assure authenticity and integrity of messages (including blockchain transactions). This assurance is based on assumption that the private signing key is kept secret, which may be exposed or compromised without being detected in the real world. Many schemes have been proposed to mitigate this problem, but most schemes are not compatible with widely used digital signature standards and do not help detect private key exposures. In this paper, we propose a Key Compromise Resilient Signature (KCRS) system, which leverages blockchain to detect key compromises and mitigate the consequences. Our solution keeps a log of valid certificates and digital signatures that have been issued on the blockchain, which can deter the abuse of compromised private keys. Since the blockchain is an open system, KCRS also provides a privacy protection mechanism to prevent the public from learning the relationship between signatures. We present a theoretical framework for the security of the system and a provably-secure construction. We also implement a prototype of KCRS and conduct experiments to demonstrate its practicability