The "lessons" of the Australian "heroin shortage"

Heroin use causes considerable harm to individual users including dependence, fatal and nonfatal overdose, mental health problems, and blood borne virus transmission. It also adversely affects the community through drug dealing, property crime and reduced public amenity. During the mid to late 1990s in Australia the prevalence of heroin use increased as reflected in steeply rising overdose deaths. In January 2001, there were reports of an unpredicted and unprecedented reduction in heroin supply with an abrupt onset in all Australian jurisdictions. The shortage was most marked in New South Wales, the State with the largest heroin market, which saw increases in price, dramatic decreases in purity at the street level, and reductions in the ease with which injecting drug users reported being able to obtain the drug. The abrupt onset of the shortage and a subsequent dramatic reduction in overdose deaths prompted national debate about the causes of the shortage and later international debate about the policy significance of what has come to be called the "Australian heroin shortage". In this paper we summarise insights from four years' research into the causes, consequences and policy implications of the "heroin shortage"

A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease

© 2020, The Author(s). Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases

Parental supply of alcohol and alcohol consumption in adolescence: prospective cohort study

Background: Parents are a major supplier of alcohol to adolescents, yet there is limited research examining the impact of this on adolescent alcohol use. This study investigates associations between parental supply of alcohol, supply from other sources, and adolescent drinking, adjusting for child, parent, family and peer variables. Method: A cohort of 1927 adolescents was surveyed annually from 2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4 standard drinks on any occasion); parental supply of alcohol; supply from other sources; child, parent, family and peer covariates. Results: After adjustment, adolescents supplied alcohol by parents had higher odds of drinking whole beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33–2.45] than those not supplied by parents. However, parental supply was not associated with bingeing, and those supplied alcohol by parents typically consumed fewer drinks per occasion (incidence rate ratio 0.86, 95% CI 0.77–0.96) than adolescents supplied only from other sources. Adolescents obtaining alcohol from non-parental sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86–3.45) and bingeing (OR 3.51, 95% CI 2.53–4.87). Conclusions: Parental supply of alcohol to adolescents was associated with increased risk of drinking, but not bingeing. These parentally-supplied children also consumed fewer drinks on a typical drinking occasion. Adolescents supplied alcohol from non-parental sources had greater odds of drinking and bingeing. Further follow-up is necessary to determine whether these patterns continue, and to examine alcohol-related harm trajectories. Parents should be advised that supply of alcohol may increase children's drinking

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs:a systematic review and meta-analysis

BACKGROUND AND AIM: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID. METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95. CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade

The impact of changes to heroin supply on blood-borne virus notifications and injecting related harms in New South Wales, Australia

BACKGROUND: In early 2001 Australia experienced a sudden and unexpected disruption to heroin availability, know as the 'heroin shortage'. This 'shortage has been linked to a decrease in needle and syringe output and therefore possibly a reduction in injecting drug use. We aimed to examine changes, if any, in blood-borne viral infections and presentations for injecting related problems related to injecting drug use following the reduction heroin availability in Australia, in the context of widespread harm reduction measures. METHODS: Time series analysis of State level databases on HIV, hepatitis B, hepatitis C notifications and hospital and emergency department data. Examination of changes in HIV, hepatitis B, hepatitis C notifications and hospital and emergency department admissions for injection-related problems following the onset of the heroin shortage; non-parametric curve-fitting of number of hepatitis C notifications among those aged 15–19 years. RESULTS: There were no changes observed in hospital visits for injection-related problems. There was no change related to the onset heroin shortage in the number of hepatitis C notifications among persons aged 15–19 years, but HCV notifications have subsequently decreased in this group. No change occurred in HIV and hepatitis B notifications. CONCLUSION: A marked reduction in heroin supply resulted in no increase in injection-related harm at the community level. However, a delayed decrease in HCV notifications among young people may be related. These changes occurred in a setting with widespread, publicly funded harm reduction initiatives

Impact of unstable housing on all-cause mortality among persons who inject drugs

BACKGROUND: Illicit drug injecting is a well-established risk factor for morbidity and mortality. However, a limited number of prospective studies have examined the independent effect of unstable housing on mortality among persons who inject drugs (PWIDs). In this study we sought to identify if a relationship exists between unstable housing and all-cause mortality among PWIDs living in Vancouver, Canada. METHODS: PWIDs participating in two prospective cohort studies in Vancouver, Canada were followed between May 1996 and December 2012. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariate Cox proportional hazards regression to determine factors associated with all-cause mortality and to investigate the independent relationship between unstable housing and time to all-cause mortality. RESULTS: During the study period, 2453 individuals were followed for a median of 69 months (Inter-quartile range [IQR]: 34 – 113). In total, there were 515 (21.0%) deaths for an incidence density of 3.1 (95% Confidence Interval [CI]: 2.8 – 3.4) deaths per 100 person years. In multivariate analyses, after adjusting for potential confounders including HIV infection and drug use patterns, unstable housing remained independently associated with all-cause mortality (adjusted hazard ratio [AHR] = 1.30, 95% CI: 1.08 – 1.56). CONCLUSIONS: These findings demonstrate that unstable housing is an important risk factor for mortality independent of known risk factors including HIV infection and patterns of drug use. This study highlights the urgent need to provide supportive housing interventions to address elevated levels of preventable mortality among this population

Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice

Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging

Symptoms predicting remission after divalproex augmentation with olanzapine in partially nonresponsive patients experiencing mixed bipolar I episode: a post-hoc analysis of a randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Rating scale items in a 6-week clinical trial of olanzapine versus placebo augmentation in patients with mixed bipolar disorder partially nonresponsive to ≥14 days of divalproex monotherapy were analyzed to characterize symptom patterns that could predict remission. At baseline, the two treatment groups were similar.</p> <p>Findings</p> <p>Factor analysis with Varimax rotation was performed <it>post hoc </it>on baseline items of the 21-Item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS). Backwards-elimination logistic regression ascertained factors predictive of protocol-defined endpoint remission (HDRS-21 score ≤ 8 and YMRS score ≤ 12) with subsequent determination of optimally predictive factor score cutoffs.</p> <p>Factors for Psychomotor activity (YMRS items for elevated mood, increased motor activity, and increased speech and HDRS-21 agitation item) and Guilt/Suicidality (HDRS-21 items for guilt and suicidality) significantly predicted endpoint remission in the divalproex+olanzapine group. No factor predicted remission in the divalproex+placebo group. Patients in the divalproex+olanzapine group with high pre-augmentation psychomotor activity (scores ≥10) were more likely to remit compared to those with lower psychomotor activity (odds ratio [OR] = 3.09, 95% confidence interval [CI] = 1.22-7.79), and patients with marginally high Guilt/Suicidality (scores ≥2) were less likely to remit than those with lower scores (OR = 0.37, 95% CI = 0.13-1.03). Remission rates for divalproex+placebo vs. divalproex+olanzapine patients with high psychomotor activity scores were 22% vs. 45% (p = 0.08) and 33% vs. 48% (p = 0.29) for patients with low Guilt/Suicidality scores.</p> <p>Conclusions</p> <p>Patients who were partially nonresponsive to divalproex treatment with remaining high vs. low psychomotor activity levels or minimal vs. greater guilt/suicidality symptoms were more likely to remit with olanzapine augmentation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov; <url>http://clinicaltrials.gov/ct2/show/NCT00402324?term=NCT00402324&rank=1</url>, Identifier: NCT00402324</p

Simultaneous measurement of the ratio B(t->Wb)/B(t->Wq) and the top quark pair production cross section with the D0 detector at sqrt(s)=1.96 TeV

We present the first simultaneous measurement of the ratio of branching fractions, R=B(t->Wb)/B(t->Wq), with q being a d, s, or b quark, and the top quark pair production cross section sigma_ttbar in the lepton plus jets channel using 0.9 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV collected with the D0 detector. We extract R and sigma_ttbar by analyzing samples of events with 0, 1 and >= 2 identified b jets. We measure R = 0.97 +0.09-0.08 (stat+syst) and sigma_ttbar = 8.18 +0.90-0.84 (stat+syst)} +/-0.50 (lumi) pb, in agreement with the standard model prediction.Comment: submitted to Phys.Rev.Letter