A novel DRD2 single-nucleotide polymorphism associated with schizophrenia predicts age of onset : HapMap tag-single-nucleotide polymorphism analysis

Background: Dopamine D2 receptor (DRD2) is thought to be critical in regulating the dopaminergic pathway in the brain which is known to be important in the aetiology of schizophrenia. It is therefore not surprising that most antipsychotic medication acts on the Dopamine D2 receptor. DRD2 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and DRD2 polymorphisms have been associated with reduced brain expression. We have previously identified a genetic variant in DRD2, rs6277 to be strongly implicated in schizophrenia susceptibility. Methods: To identity new associations in the DRD2 gene with disease status and clinical severity, we genotyped seven single nucleotide polymorphisms (SNPs) in DRD2 using a multiplex mass spectrometry method. SNPs were chosen using a haplotype block-based gene-tagging approach so the entire DRD2 gene was represented. Results: One polymorphism rs2734839 was found to be significantly associated with schizophrenia as well as late onset age. Individuals carrying the genetic variation were more than twice as likely to have schizophrenia compared to controls. Conclusions: Our results suggest that DRD2 genetic variation is a good indicator for schizophrenia risk and may also be used as a predictor age of onset.

Protective factors associated with young passenger intervening in risky driving situations

While the negative influence of passengers on driving is usually studied, young passengers may protect against young drivers’ crash involvement by speaking out and trying to stop unsafe driving behavior. This study sought to examine psychosocial constructs of young passengers who are likely to intervene in their friends’ risky driving. Method: University students aged 17 to 25 years who were single (n = 123) or in a romantic relationship (n = 130) completed an online survey measuring protective factors. Results: The combination of individual, friend and (for participants in a relationship) romantic partner protective factors predicted self-reported passenger intervening intentions. Impact on Industry: Since peer passengers often increase young drivers’ crash risk, research on passenger intervening has significant implications for road safety strategies. The findings provide support for the operationalization of protective factors in strategies that target passenger intervening behavior.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

Subacute effects of ecstasy on mood : an exploration of associated risk factors

Ecstasy use may result in lowered mood, anxiety or aggression in the days following use. Yet, few studies have investigated what factors increase the risk of experiencing such symptoms. Ecstasy users (at least once in the last 12 months) who subsequently took ecstasy (n=35) over the next week, were compared on measures of mood, sleep, stress and drug use, with those who abstained (n=21) that week. Measures were administered the week prior to ecstasy use and 1 and 3 days following use, or the equivalent day for abstainers. Mood symptoms were assessed using the Kessler-10 self-report psychological distress scale, a subjective mood rating (1-10), and the depression, anxiety and hostility items of the clinician-rated Brief Psychiatric Rating Scale. Timeline followback methods were used to collect information on drug use and life stress in the past month. Self-reported sleep quality was also assessed. Ecstasy use was not associated with subacute depressive, anxiety or aggressive symptoms. Rather, lowered mood and increased psychological distress were associated with self-reported hours and quality of sleep obtained during the 3-day follow up. These findings highlight the importance of considering sleep disruption in understanding the short-term mood effects of ecstasy use.

Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry

Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking

Key priorities for Australian infection control : summary of findings from the launch of the Centre for Research Excellence in Reducing Healthcare Associated Infections

The launch of the Centre of Research Excellence in Reducing Healthcare Associated Infection (CRE-RHAI) took place in Sydney on Friday 12 October 2012. The mission of the CRE-RHAI is to generate new knowledge about strategies to reduce healthcare associated infections and to provide data on the cost-effectiveness of infection control programs. As well as launching the CRE-RHAI, an important part of this event was a stakeholder Consultation Workshop, which brought together several experts in the Australian infection control community. The aims of this workshop were to establish the research and clinical priorities in Australian infection control, assess the importance of various multi-resistant organisms, and to gather information about decision making in infection control. We present here a summary and discussion of the responses we received.

Ureaplasma speioces are associated with chorioamnionitiis in late preterm placentas

Background: Preterm birth is a major cause of neonatal morbidity and mortality, with 75% of preterm births occurring late preterm. Previous studies have investigated the microbial diversity within placentas delivered early preterm but there has been no investigation of the prevalence of bacteria, particularly Ureaplasma spp. in late preterm placentas. Method: Women giving birth late preterm (320 – 366 weeks of gestation) in Cincinnati were recruited for this study. Samples of chorioamnion were collected aseptically at the time of delivery, shipped to QUT and tested for Ureaplasma spp. and other bacteria by culture and/or PCR assays. The presence of bacteria was correlated with adverse pregnancy outcomes, including histological chorioamnionitis (tissue sections read by US pathologists). Results: To date, Ureaplasma spp. have been detected in 15/270 (5.5%) of placentas by culture and 19/270 (7%) by PCR. Ureaplasma presence correlated with histological chorioamnionitis (12/19%; 63%). However, the presence of other bacteria was not associated with chorioamnionitis (5%). Chorioamnionitis was unevenly distributed in ethnic groups, with a higher incidence in African-Americans’ (6/7; 86%), compared to Caucasians’ (6/12; 50%) who were colonised with ureaplasmas. Conclusion: This study is the first to report the prevalence of ureaplasmas in women (7%) who deliver late preterm. Ureaplasma spp. were associated with a higher incidence of chorioamnionitis (63% compared to 15% for non-infected women). This data strongly suggests that ureaplasmas are a cause of late preterm deliveries and African-American women are at greater risk of chorioamnionitis.

The public health challenges of mental health problems and associated difficulties

Mental health is a major global health issue. Neuropsychiatric conditions are the most significant cause of disability worldwide, and account for 14% of the global burden of disease. Depression in particular places a huge burden on society, with the Global Burden of Disease 2000 study listing it as the fourth leading cause of disease burden worldwide and the largest non-fatal disease burden. In Australia, mental disorders are startlingly common and related to significant disability. The 2007 National Survey of Mental Health and Wellbeing revealed that the lifetime prevalence of any mental disorder was 45%, and within the last 12 months 20% of Australians met criteria for a mental disorder. Many of the articles in this issue explore mental health issues in young people. Indeed, mental health issues account for a large proportion of the disease burden in young people. Across the globe, mental health disorders caused the greatest number of years lost to disability(YLDs) amongst young people aged 10 to 24 years (45% of total YLDs). Depression caused the highest number of disability-adjusted life-years (DALYs) across this age group, accounting for 8. 2% of DALYs alone.6 It is clear that mental health is a critical area of focus for researchers, practitioners, and policy makers.

Children with autistic spectrum disorder have an associated risk of depression

Over recent years there has been an increase in the literature examining youth with Autism Spectrum Disorders (ASD). The growth in this area of research has highlighted a significant gap in our understanding of suitable interventions for people with ASD and the treatment of co-occurring psychiatric disorders.1-3 Children with ASD are at increased risk of experiencing depressive symptoms and developing depression; however with very few proven interventions available for preventing and treating depression in children with ASD, there is a need for further research in this area.

A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

Implementation Guide for Surveillance of Central Line Associated Bloodstream Infection -- [Consultation Edition]

The implementation guide for the surveillance of CLABSI in intensive care units (ICU) was produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care(ACSQHC), and endorsed by the ACSQHC HAI Advisory Committee. State surveillance units, the ACSQHC and the Australian and New Zealand Intensive Care Society (ANZICS) have representatives on the Technical Working Group, and have provided input into this document.

Malnutrition and poor food intake are associated with prolonged hospital stay, frequent readmissions, and greater in-hospital mortality: Results from the Nutrition Care Day Survey 2010

Background & aims The Australasian Nutrition Care Day Survey (ANCDS) ascertained if malnutrition and poor food intake are independent risk factors for health-related outcomes in Australian and New Zealand hospital patients. Methods Phase 1 recorded nutritional status (Subjective Global Assessment) and 24-h food intake (0, 25, 50, 75, 100% intake). Outcomes data (Phase 2) were collected 90-days post-Phase 1 and included length of hospital stay (LOS), readmissions and in-hospital mortality. Results Of 3122 participants (47% females, 65 ± 18 years) from 56 hospitals, 32% were malnourished and 23% consumed ≤ 25% of the offered food. Malnourished patients had greater median LOS (15 days vs. 10 days, p < 0.0001) and readmissions rates (36% vs. 30%, p = 0.001). Median LOS for patients consuming ≤ 25% of the food was higher than those consuming ≤ 50% (13 vs. 11 days, p < 0.0001). The odds of 90-day in-hospital mortality were twice greater for malnourished patients (CI: 1.09–3.34, p = 0.023) and those consuming ≤ 25% of the offered food (CI: 1.13–3.51, p = 0.017), respectively. Conclusion The ANCDS establishes that malnutrition and poor food intake are independently associated with in-hospital mortality in the Australian and New Zealand acute care setting.

Resting metabolic rate is associated with hunger, self-determined meal size, and daily energy intake and may represent a marker for appetite

Background: There are strong logical reasons why energy expended in metabolism should influence the energy acquired in food-intake behavior. However, the relation has never been established, and it is not known why certain people experience hunger in the presence of large amounts of body energy. Objective: We investigated the effect of the resting metabolic rate (RMR) on objective measures of whole-day food intake and hunger. Design: We carried out a 12-wk intervention that involved 41 overweight and obese men and women [mean ± SD age: 43.1 ± 7.5 y; BMI (in kg/m2): 30.7 ± 3.9] who were tested under conditions of physical activity (sedentary or active) and dietary energy density (17 or 10 kJ/g). RMR, daily energy intake, meal size, and hunger were assessed within the same day and across each condition. Results: We obtained evidence that RMR is correlated with meal size and daily energy intake in overweight and obese individuals. Participants with high RMRs showed increased levels of hunger across the day (P < 0.0001) and greater food intake (P < 0.00001) than did individuals with lower RMRs. These effects were independent of sex and food energy density. The change in RMR was also related to energy intake (P < 0.0001). Conclusions: We propose that RMR (largely determined by fat-free mass) may be a marker of energy intake and could represent a physiologic signal for hunger. These results may have implications for additional research possibilities in appetite, energy homeostasis, and obesity. This trial was registered under international standard identification for controlled trials as ISRCTN47291569.