Azithromycin Augments Bacterial Uptake and Anti-Inflammatory Macrophage Polarization in Cystic Fibrosis.

BACKGROUND: Azithromycin (AZM) is widely being used for treating patients with cystic fibrosis (pwCF) following clinical trials demonstrating improved lung function and fewer incidents of pulmonary exacerba-tions. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. METHODS: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs), were differentiated into monocyte-derived macrophages (MDMs) and subsequently infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. RESULTS: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected; however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM d'd not restore endocytosis in CF, another essential feature of M2 macrophages. CONCLUSIONS: This study highlights the cellular functions and molecular targets of AZM which may involve an improved uptake of both Gram-positive and Gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Antimicrobial stewardship: Prescribing across the primary care health professions.

We examined the patterns of antibiotic prescribing by medical and non-medical prescribers (dentists, nurse practitioners, and midwives) in Australia. We explored trends in the dispensed use of antibiotics (scripts and defined daily dose [DDD] per 1000 population/day) by Australian prescribers over the 12-year period, 2005-2016. We obtained data on dispensed prescriptions of antibiotics from registered health professionals subsidized on the Pharmaceutical Benefits Scheme (PBS). There were 216.2 million medical and 7.1 million non-medical dispensed prescriptions for antibiotics over 12 years. The top four antibiotics for medical prescribers were doxycycline; amoxicillin, amoxicillin plus clavulanic acid, and cefalexin, constituting 80% of top 10 use in 2005 and 2016; the top three for non-medical were amoxicillin, amoxicillin plus clavulanic acid and metronidazole (84% of top 10 use in 2016). The proportional increase in antibiotic use was higher for non-medical than medical prescribers. While medical prescribers preferentially prescribed broad-spectrum and non-medical prescribers moderate-spectrum antibiotics, there was a large increase in the use of broad-spectrum antibiotics over time by all prescribers. One in four medical prescriptions were repeats. Overprescribing of broad-spectrum antibiotics conflicts with national antimicrobial stewardship initiatives and guidelines. The proportional higher increase in antibiotic use by non-medical prescribers is a concern. To reduce inappropriate use of antibiotics and antimicrobial resistance, educational strategies targeted at all medical and non-medical prescribers are needed to align prescribing with current best practice within the scope of practice of respective prescribers.

Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium.

Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air pollution, the environmentally persistent free radical (EPFR) DCB230, was used to mimic pollution exposure four hours prior to infection. Some wells were pretreated with antioxidant, astaxanthin, for 24 hours prior to EPFR-DCB230 exposure and/or SARS-CoV-2 infection. Outcomes included viral replication, epithelial integrity, surface receptor expression (ACE2, TMPRSS2), cytokine mRNA expression (TNF-α, IFN-ß), intracellular signaling pathways, and oxidative defense enzymes. SARS-CoV-2 infection induced a mild phenotype in NECs, with some cell death, upregulation of the antiviral cytokine IFN-ß, but had little effect on intracellular pathways or oxidative defense enzymes. Prior exposure to EPFR-DCB230 increased SARS-CoV-2 replication, upregulated TMPRSS2 expression, increased secretion of the proinflammatory cytokine TNF-α, inhibited expression of the mucus producing MUC5AC gene, upregulated expression of p21 (apoptosis pathway), PINK1 (mitophagy pathway), and reduced levels of antioxidant enzymes. Pretreatment with astaxanthin reduced SARS-CoV-2 replication, downregulated ACE2 expression, and prevented most, but not all EPFR-DCB230 effects. Our data suggest that oxidant damage to the respiratory epithelium may underly the link between poor air quality and increased COVID-19. The apparent protection by antioxidants warrants further research.

Factors in childhood associated with lung function decline to adolescence in cystic fibrosis.

BACKGROUND: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life. METHODS: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017. RESULTS: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0-5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4-13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV1/FVC p = 0.001, FEF25-75p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1p = 0.05, FEF25-75p = 0.02). No examined factor predicted a decline in the FVC Z-score. CONCLUSIONS: Action in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.

Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3.

INTRODUCTION: Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown. AIM: To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment. METHODS: A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test. RESULTS: Twenty-eight patients (15 male, aged 0.08-18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was -0.58 (95% CI -0.75 to -0.41), and post initiation was -0.25 (95% CI -0.46 to -0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea-Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1-10.1) at initiation to 2.7 events/hour (IQR 0.7-5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen. CONCLUSION: The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

Resveratrol and Astaxanthin Protect Primary Human Nasal Epithelial Cells Cultured at an Air-liquid Interface from an Acute Oxidant Exposure.

Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to the airway epithelium from OS. Resveratrol and astaxanthin are nutritional compounds that have shown diverse benefits including protection against OS and inflammation in various situations. The aim of this study was to examine the utility of pre-treatment with resveratrol and astaxanthin to prevent the negative effects of oxidant exposure and restore redox homeostasis in a well-differentiated epithelium grown from primary human nasal epithelial cells (NECs) at the air-liquid interface. Fully differentiated NECs were pretreated with the antioxidants for 24 hours and the cultured epithelia was subsequently exposed to hydrogen peroxide (H2O2) for 1 hour to induce an acute OS. Responses measured included mitochondrial reactive oxygen species (mtROS) generation, redox status (GSH/GSSG ratio), cellular ATP, and signaling pathways (SIRT1, FOXO3, p21, PINK1, PARKIN, NRF2). Following H2O2 exposure, mtROS production increased by 4-fold compared with control (p<0.01) and pre-treatment with resveratrol or astaxanthin reduced this by 50% (p<0.05). H2O2 exposure reduced GSH/GSSG ratio and this decline was prevented by antioxidants pre-treatment. H2O2 exposure caused 2.5-fold increase in p21 mRNA expression compared with control (p<0.05), while a slight decrease in p21 mRNA expression was observed when cells were pre-treated with resveratrol or astaxanthin. Our results demonstrate that antioxidants, resveratrol, and astaxanthin were able to protect cells from an acute OS. These agents show promise that encourages further research.

Redox Homeostasis in Well-differentiated Primary Human Nasal Epithelial Cells.

Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions but can be disturbed by environmental exposures. The mechanism(s) underlying the induction and impact of OS on airway epithelium and how these influences on respiratory disease is poorly understood. The aim of this study was to develop a stress response model in primary human nasal epithelial cells (NECs) grown at the air-liquid interface (ALI) into a well-differentiated epithelium and to use this model to investigate the mechanisms underlying OS. Hydrogen peroxide (H2O2) was used to induce acute OS and the responses were measured with trans epithelial electrical resistance (TEER), membrane permeability, cell death (LDH release), mitochondrial reactive oxygen species (mtROS) generation, redox status (GSH/GSSG ratio), cellular ATP, and signaling pathways (SIRT1, FOXO3, p53, p21, PINK1, PARKIN, NRF2). Following 25 mM (sensitive) or 50mM (resistant) H2O2 exposure, cell integrity decreased (p<0.05), GSH/GSSG ratio reduced (p<0.05), and ATP production declined by 83% (p<0.05) in the sensitive and 55% (p<0.05) in the resistant group; mtROS production increased 3.4-fold (p<0.001). Significant inter-individual differences between healthy humans with regards to susceptibility to OS, and differential activation of various pathways (FOXO3, PARKIN) were observed. These intra-individual differences in susceptibility to OS may be attributed to resistant individuals having more mitochondria or greater mitochondrial function.

Anti-inflammatory effects of lenabasum, a cannabinoid receptor type 2 agonist, on macrophages from cystic fibrosis.

BACKGROUND: Lenabasum is an oral synthetic cannabinoid receptor type 2 agonist previously shown to reduce the production of key airway pro-inflammatory cytokines known to play a role in cystic fibrosis (CF). In a double-blinded, randomized, placebo-control phase 2 study, lenabasum lowered the rate of pulmonary exacerbation among patients with CF. The present study was undertaken to investigate anti-inflammatory mechanisms of lenabasum exhibits in CF macrophages. METHODS: We used monocyte-derived macrophages (MDMs) from healthy donors (n = 15), MDMs with CFTR inhibited with C-172 (n = 5) and MDMs from patients with CF (n = 4). Monocytes were differentiated to macrophages and polarized into classically activated (M1) macrophages by LPS or alternatively activated (M2) macrophages by IL-13 in presence or absence of lenabasum. RESULTS: Lenabasum had no effect on differentiation, polarization and function of macrophages from healthy individuals. However, in CF macrophages lenabasum downregulated macrophage polarization into the pro-inflammatory M1 phenotype and secretion of the pro-inflammatory cytokines IL-8 and TNF-α in a dose-dependent manner. An improvement in phagocytic activity was also observed following lenabasum treatment. Although lenabasum did not restore the impaired polarization of anti-inflammatory M2 macrophage, it reduced the levels of IL-13 and enhanced the endocytic function of CF MDMs. The effects of lenabasum on MDMs with CFTR inhibited by C-172 were not as obvious. CONCLUSION: In CF macrophages lenabasum modulates macrophage polarization and function in vitro in a way that would reduce inflammation in vivo. Further studies are warranted to determine the link between activating the CBR2 receptor and CFTR.

Clinical outcomes of an integrated primary-secondary model of care for individuals with complex type 2 diabetes: a non-inferiority randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the study was to determine if a Beacon model of integrated care utilising general practitioners (GPs) with special interests could achieve similar clinical outcomes to a hospital-based specialist diabetes outpatient clinic. METHODS: This pragmatic non-inferiority multisite randomised controlled trial assigned individuals with complex type 2 diabetes to care delivered by a Beacon clinic or to usual care delivered by a hospital outpatient department, in a 3:1 ratio. Owing to the nature of the study, researchers were only blinded during the allocation process. Eligible participants were aged 18 or over, had been referred by their usual GP to the hospital central referral hub with type 2 diabetes and had been triaged to be seen within 30 or 90 days. The intervention consisted of diabetes management in primary care by GPs with a special interest who had been upskilled in complex diabetes under the supervision of an endocrinologist. The primary outcome was HbA1c at 12 months post-recruitment. The non-inferiority margin was 4.4 mmol/mol (0.4%). Both per-protocol and intention-to-treat analyses are reported. RESULTS: Between 27 November 2012 and 14 July 2015, 352 individuals were recruited and 305 comprised the intention-to-treat sample (71 in usual care group and 234 in the Beacon model group). The Beacon model was non-inferior to usual care for both the per-protocol (difference -0.38 mmol/mol [95% CI -4.72, 3.96]; -0.03% [95% CI -0.43, 0.36]) and the intention-to-treat (difference -1.28 mmol/mol [95% CI -5.96, 3.40]; -0.12% [95% CI -0.55, 0.31]) analyses. Non-inferiority was sustained in a sensitivity analysis at 12 months. There were no statistically or clinically significant differences in the secondary outcomes of BP, lipids or quality of life as measured by the 12 item short-form health survey (SF-12v2) and the diabetes-related quality of life (DQoL-Brief) survey. Safety indicators did not differ between groups. Participant satisfaction on the eight-item client satisfaction questionnaire (CSQ-8) was good in both groups, but scores were significantly higher in the Beacon model group than the usual care group (mean [SD] 28.4 [4.9] vs 25.6 [4.9], respectively, p < 0.001). CONCLUSIONS/INTERPRETATION: In individuals with type 2 diabetes, a model of integrated care delivered in the community by GPs with a special interest can safely achieve clinical outcomes that are not inferior to those achieved with gold-standard hospital-based specialist outpatient clinics. Individuals receiving care in the community had greater satisfaction. Further studies will determine the cost of delivering this model of care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000380897 FUNDING: The study was funded by the Australian National Health and Medical Research Council (GNT1001157).

A comparison of EQ-5D-3L population norms in Queensland, Australia, estimated using utility value sets from Australia, the UK and USA.

PURPOSE: To provide population norms for the EQ-5D-3L by age and gender based on a representative adult sample in Queensland, Australia; to assess differences in health-related quality of life by applying the Australian, UK and USA value sets to these data; and to assess differences in utility scores for key preventive health indicators. METHODS: A cross-sectional computer-assisted telephone interview survey (March-June 2011) with 5,555 adults. Respondents rated their impairment (none, moderate, severe problems) across five domains (mobility, self-care, usual activities, pain and discomfort, anxiety or depression) using the validated EQ-5D-3L health-related quality of life instrument. Utility score indexes were derived using the Australian, UK and USA value sets. RESULTS: Forty per cent of adults reported pain and discomfort while 3% indicated problems with self-care. Approximately one in six had limitations with mobility, usual activities or anxiety or depression. The three value sets performed similarly in discriminating differences based on most characteristics, and clinically meaningful differences were seen for age, body weight, physical activity and daily smoking. There were no differences in utility scores for gender. CONCLUSIONS: This is the first study to report general population findings for the Australian EQ-5D-3L value set. Overall, the Australian value set performed comparably with other value sets commonly used in the Australian population; however, differences were observed. Results will enable further refinement to health and economic studies in an Australian-specific context.

Hospital admissions, emergency department utilisation and patient activation for self-management among people with diabetes.

AIMS: To assess the relationship between patient activation for self-management and admissions to hospital or attendances at emergency departments among people with diabetes, after controlling for other known associations. METHODS: Patients were randomly selected from Australia's National Diabetes Services Scheme and invited to participate in the Living with Diabetes Study, which is a longitudinal survey providing a comprehensive examination of health care utilisation, well-being and disease progression. Data was collected for 3951 participants. RESULTS: Outcome events were defined as 1 or more hospitalization and 1 or more visits to an emergency department in the preceding 12 months. Logistic regression analyses showed six variables remained significantly associated with both outcomes: age, income, disease duration and severity, current depression and PAM stage. Patients at PAM stage 1 were 1.4 times more likely to be hospitalised (p=0.023) and 1.3 times more likely to have visited emergency (p=0.049) compared to those at stage 4. CONCLUSIONS: Low levels of activation are associated with higher utilisation of hospital resources even after controlling for relevant factors such as disease severity and co-morbid depression. Most will be gained by moving patients from PAM stage 1 to a higher level of activation.

Patterns and determinants of influenza and pneumococcal immunisation among adults with chronic disease living in Queensland, Australia.

Using findings from a random, computer assisted telephone survey of households, this paper examines influenza and pneumococcal immunisation coverage and predictors of immunisation in 2203 adults with asthma, diabetes or a cardiovascular condition living in Queensland, Australia. 47% and 31% of high-risk persons were immunised against influenza and pneumococcus respectively. Immunisation coverage varied across chronic conditions and increased with age, being significantly higher for those aged 65 years and older and consequently eligible for free vaccination. Poor self reported health status was an independent predictor of pneumococcal vaccination status for people with asthma, diabetes or a cardiovascular condition; however it was only an independent predictor of influenza immunisation status for people with diabetes. Extending free vaccination to all people at risk may increase immunisation rates for younger people with a chronic condition.

The role of patient activation in frequent attendance at primary care: a population-based study of people with chronic disease.

OBJECTIVE: This study explores a range of relevant socio-demographic, physical and psychological factors in a unique examination of the risk factors for frequent attendance at primary care. The impact of patient activation for self-management on health service utilisation is of particular interest. METHODS: A population-based sample of people with chronic disease from Queensland, Australia, was interviewed using computer assisted telephone surveying. Data were collected from a random sample of 1470 people with either diabetes or a cardiovascular condition. RESULTS: As participants became more activated they were less likely to frequently attend their main health care provider for assistance with their chronic condition. For both conditions the association was graduated and for participants with a cardiovascular condition this association remained statistically significant even after controlling for other potentially influential factors such as disease severity, length of time since diagnosis, and psychological distress. CONCLUSION: Characteristics of the individual, including patient activation and psychological functioning, as well as disease factors contribute to primary care consulting patterns among people with chronic illness. PRACTICAL IMPLICATIONS: Efforts to improve patient activation for self-management should remain a central element of chronic care.

Communicating with the coroner: how religion, culture, and family concerns may influence autopsy decision making.

Based on coronial data gathered in the state of Queensland in 2004, this article reviews how a change in legislation may have impacted autopsy decision making by coroners. More specifically, the authors evaluated whether the requirement that coronial autopsy orders specify the level of invasiveness of an autopsy to be performed by a pathologist was affected by the further requirement that coroners take into consideration a known religion, culture, and/or raised family concern before making such an order. Preliminary data reveal that the cultural status of the deceased did not affect coronial autopsy decision making. However, a known religion with a proscription against autopsy and a raised family concern appeared to be taken into account by coroners when making autopsy decisions and tended to decrease the invasiveness of the autopsy ordered from a full internal examination to either a partial internal examination or an external-only examination of the body. The impact of these findings is briefly discussed.

Gender differences in social network size and satisfaction in adults in their 70s.

Strong social support is associated with lower mortality and morbidity and better self-rated health in later life. The aim of this study was to compare social network size and satisfaction in men (N = 2589) and women (n = 3152), aged 72-78 years. Women reported significantly larger networks (Difference 1.36, 95% CI 0.89, 1.83) than men. However, being separated, divorced or single had a significantly greater impact on men's social networks (Difference 0.92, 95% CI 0.17, 1.68). Poor mental health and sensory impairments were associated with smaller networks and lower satisfaction with support for both men and women.

Increasing the information available to coroners: the effect on autopsy decision-making.

This paper details research completed in 2007 which investigated autopsy decision-making in a death investigation. The data was gathered during the first year of operation in Queensland, Australia, of a new Coroners Act which changed the process of death investigation in three ways which are important to this paper. First, it required a greater amount of information to be gathered at the scene by police: this included a thorough investigation of the circumstances of the death, including statements from witnesses, friends and family, as well as evidence gathering at the scene. Second, it required coroners, for the first time, to determine the level of invasiveness required in the autopsy to complete the death investigation. Third, it enabled any genuine family concerns to be communicated to the coroner. The outcome of such information was threefold: (i) a greater amount of information offered to the coroner led to a decrease in the number of full internal autopsies ordered, but an increase in the number of partial internal autopsies ordered; (ii) this shift in autopsy decision-making by coroners saw certain factors given greater importance than others in decisions to order full internal, or external only, autopsies; (iii) a raised family concern had a significant impact on autopsy decision-making and tended to decrease the invasiveness of the autopsy ordered by the coroner.

Symptoms reported by women in midlife: menopausal transition or aging?

OBJECTIVE: The aim of this study was to determine which symptoms commonly reported by women at midlife are associated with the menopausal transition, after adjusting for aging, life events, sociodemographics, and lifestyle factors. METHODS: Middle-aged women participating in the Australian Longitudinal Study on Women's Health between 1996 (survey 1, ages 45-50 y) and 2007 (survey 5) were included in the analyses if natural menopause status could be determined at any survey (n = 8,649 of 13,716 participants). Natural menopause status was determined from reported menstruation patterns. A survival function describing age at menopause was computed. Logistic regression models for repeated measures were used to estimate the association between menopausal stage and symptom prevalence. RESULTS: There were 6,814 (79%) women who reached natural menopause before 2007. The median age at menopause was 52 years. Compared with the premenopausal phase, menopause was associated with hot flushes (odds ratio, 8.6 [95% CI, 7.5-9.9]), night sweats (odds ratio, 5.5 [95% CI, 4.8-6.3]), and, to a lesser extent, stiff or painful joints (odds ratio, 1.6 [95% CI, 1.4-1.8]), difficulty sleeping (odds ratio, 1.4 [95% CI, 1.2-1.6]), and poor/fair self-rated health (odds ratio, 1.6 [95% CI, 1.3-1.9]), after controlling for confounders. Prevalence of some symptoms was still raised more than 7 years after menopause. Headaches/migraines were negatively associated with aging, and urinary incontinence was positively associated with aging. CONCLUSIONS: Treatment such as hormone therapy should be targeted to vasomotor symptoms, which are most strongly associated with menopause rather than to less specific symptoms related to aging per se.

The coronial system in Queensland: the effects of new legislation on decision-making.

The purpose of this article is to detail research completed in 2007 which investigated the way in which coroners made decisions in a death investigation, with a particular focus on their autopsy decision-making. The data were gathered during the first year of operation of a new Coroners Act in Queensland, Australia, which required a greater amount of information to be gathered at the scene by police, and this included a thorough investigation of the circumstances of the death, including statements from witnesses, friends and family, as well as evidence-gathering at the scene. This article addresses the outcomes of that increased information on coronial decision-making in three ways: first, whether or not the greater amount of information offered to coroners enabled them to be less reliant on full internal autopsies to establish cause of death; secondly whether certain factors were more influential in decision-making; and thirdly, whether the information gathered at the scene negates the need for full internal autopsies in many situations, irrespective of the decision-making by coroners.