The utility of empirical mupirocin for eradication of methicillin-resistant Staphylococcus aureus colonisation in Far North Queensland, Australia

Methicillin-resistant Staphylococcus aureus (MRSA) infections are common in Far North Queensland (FNQ) and their incidence is increasing. Decolonisation regimens that include topical mupirocin are recommended in Australian guidelines to reduce recurrent infection. Mupirocin resistance was identified in 3,932/15,851 (24.8%) methicillin-sensitive Staphylococcus aureus (MSSA) isolates and in 533/5,134 (10.4%) MRSA isolates from FNQ between 1997 and 2016. Factors associated with mupirocin resistance in multivariate analysis were an MSSA isolate, age < 40 years, rural residence and female gender. These data support the use of mupirocin in MRSA decolonisation in FNQ, although addressing the underlying social determinants of health that drive the incidence of S. aureus infections remain a priority for local healthcare provision

Suicides in Aboriginal and non-Aboriginal people following hospital admission for suicidal ideation and self-harm: A retrospective cohort data linkage study from the Northern Territory

Purpose: This study aimed to explore risk factors for suicide in Aboriginal and non-Aboriginal people following hospital admission for suicidal ideation and self-harm in the Northern Territory, Australia to help clarify opportunities for improved care and intervention for these population groups. Methods: Individuals with at least one hospital admission involving suicidal ideation and/or self-harm between 1 July 2001 and 31 December 2013 were retrospectively recruited and followed up using linked mortality records to 31 December 2014. Survival analyses stratified by Indigenous status identified socio-demographic and clinical characteristics from index hospital admissions associated with suicide. Results: Just over half of the 4391 cohort members identified as Aboriginal (n = 2304; 52.4%). By 2014, 281 deaths were observed comprising 68 suicides, representing a 2.6% and 2.0% probability of suicide for Aboriginal and non-Aboriginal people, respectively. After adjusting for other characteristics, a higher risk of suicide was associated with male sex (Aboriginal adjusted hazard ratio: 4.14; 95% confidence interval: [1.76, 9.75]; non-Aboriginal adjusted hazard ratio: 5.96; 95% confidence interval: [1.98, 17.88]) and repeat hospital admissions involving self-harm (Aboriginal adjusted hazard ratio: 1.37; 95% confidence interval: [1.21, 1.55]; non-Aboriginal adjusted hazard ratio: 1.29; 95% confidence interval: [1.10, 1.51]). Severe mental disorders were associated with a four times higher risk of suicide (adjusted hazard ratio: 4.23; 95% confidence interval: [1.93, 9.27]) in Aboriginal people only. Conclusion: The findings highlight non-clinical risk factors for suicide that suggest the need for comprehensive psychosocial assessment tailored to Aboriginal and non-Aboriginal people hospitalised with suicidal ideation or self-harm. Implementing appropriate management and aftercare within a broader public health framework is needed to support recovery and reduce long-term suicide risk in the community, especially for Aboriginal people and males

Evaluation of an Australian indigenous housing programme: community level impact on crowding, infrastructure function and hygiene

Background and Aim: Housing programmes in indigenous Australian communities have focused largely on achieving good standards of infrastructure function. The impact of this approach was assessed on three potentially important housing-related influences on child health at the community level: (1) crowding, (2) the functional state of the house infrastructure and (3) the hygienic condition of the houses.\ud \ud Methods: A before-and-after study, including house infrastructure surveys and structured interviews with the main householder, was conducted in all homes of young children in 10 remote Australian indigenous communities.\ud \ud Results: Compared with baseline, follow-up surveys showed (1) a small non-significant decrease in the mean number of people per bedroom in the house on the night before the survey (3.4, 95% CI 3.1 to 3.6 at baseline vs 3.2, 95% CI 2.9 to 3.4 at follow-up; natural logarithm transformed t test, t=1.3, p=0.102); (2) a marginally significant overall improvement in infrastructure function scores (Kruskal–Wallis test, χ2=3.9, p=0.047); and (3) no clear overall improvement in hygiene (Kruskal–Wallis test, χ2=0.3, p=0.605).\ud \ud Conclusion: Housing programmes of this scale that focus on the provision of infrastructure alone appear unlikely to lead to more hygienic general living environments, at least in this study context. A broader ecological approach to housing programmes delivered in these communities is needed if potential health benefits are to be maximised. This ecological approach would require a balanced programme of improving access to health hardware, hygiene promotion and creating a broader enabling environment in communities.\u

Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival

Extent: 14 p.The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K), promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML) cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting such pathways in cancer.Daniel Thomas, Jason A. Powell, Benjamin D. Green, Emma F. Barry, Yuefang Ma, Joanna Woodcock, Stephen Fitter, Andrew C.W. Zannettino, Stuart M. Pitson, Timothy P. Hughes, Angel F. Lopez, Peter R. Shepherd, Andrew H. Wei, Paul G. Ekert and Mark A. Guthridg

Hearing and justice: the link between hearing impairment in early childhood and youth offending in Aboriginal children living in remote communities of the Northern Territory, Australia

Background: High prevalence of chronic middle ear disease has persisted in Australian Aboriginal children, and the related hearing impairment (HI) has been implicated in a range of social outcomes. This study investigated the association between HI in early childhood and youth offending. Method: This was a retrospective cohort study of 1533 Aboriginal children (born between 1996 and 2001) living in remote Northern Territory communities. The study used linked individual-level information from health, education, child protection and youth justice services. The outcome variable was a youth being “found guilty of an offence”. The key explanatory variable, hearing impairment, was based on audiometric assessment. Other variables were: child maltreatment notifications, Year 7 school enrolment by mother, Year 7 school attendance and community ‘fixed- effects’. The Cox proportional hazards model was used to estimate the association between HI and youth offending; and the Royston R2 measure to estimate the separate contributions of risk factors to youth offending. Results: The proportion of hearing loss was high in children with records of offence (boys: 55.6%, girls: 36.7%) and those without (boys: 46.1%; girls: 49.0%). In univariate analysis, a higher risk of offending was found among boys with moderate or worse HI (HR: 1.77 [95% CI: 1.05–2.98]) and mild HI (HR: 1.54 [95% CI:1.06–2.23]). This association was attenuated in multivariable analysis (moderate HI, HR: 1.43 [95% CI:0.78–2.62]; mild HI, HR: 1.37 [95% CI: 0.83– 2.26]). No evidence for an association was found in girls. HI contributed 3.2% and 6.5% of variation in offending among boys and girls respectively. Factors contributing greater variance included: community ‘fixed-effects’ (boys: 14.6%, girls: 36.5%), child maltreatment notification (boys: 14.2%, girls: 23.9%) and year 7 school attendance (boys: 7.9%; girls 12.1%). Enrolment by mother explained substantial variation for girls (25.4%) but not boys (0.2%). Conclusion: There was evidence, in univariate analysis, for an association between HI and youth offending for boys however this association was not evident after controlling for other factors. Our findings highlight a range of risk factors that underpin the pathway to youth-offending, demonstrating the urgent need for interagency collaboration to meet the complex needs of vulnerable children in the Northern Territory.Vincent Yaofeng He, Jiunn-Yih Su, Steven Guthridge, Catia Malvaso, Damien Howard, Tamika Williams and Amanda Leac

Effects of IRF5 Lupus Risk Haplotype on Pathways Predicted to Influence B Cell Functions

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by the IRF5 risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with the IRF5 risk haplotype have a heightened interferon signature, even in an unstimulated state (P = 0.011), while patients with the IRF5 protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE

Immune profiling in Puerto Rican injection drug users with and without HIV-1 infection

Antiretroviral therapy has been effective in suppressing HIV viral load and enabling people living with HIV to experience longer, more conventional lives. However, as people living with HIV are living longer, they are developing aging-related diseases prematurely and are more susceptible to comorbidities that have been linked to chronic inflammation. Coincident with HIV infection and aging, drug abuse has also been independently associated with gut dysbiosis, microbial translocation, and inflammation. Here, we hypothesized that injection drug use would exacerbate HIV-induced immune activation and inflammation, thereby intensifying immune dysfunction. We recruited 50 individuals not using injection drugs (36/50 HIV+) and 47 people who inject drugs (PWID, 12/47 HIV+). All but 3 of the HIV+ subjects were on antiretroviral therapy. Plasma immune profiles were characterized by immunoproteomics, and cellular immunophenotypes were assessed using mass cytometry. The immune profiles of HIV+/PWID−, HIV−/PWID+, and HIV+/PWID+ were each significantly different from controls; however, few differences between these groups were detected, and only 3 inflammatory mediators and 2 immune cell populations demonstrated a combinatorial effect of injection drug use and HIV infection. In conclusion, a comprehensive analysis of inflammatory mediators and cell immunophenotypes revealed remarkably similar patterns of immune dysfunction in HIV-infected individuals and in people who inject drugs with and without HIV-1 infection

Remote health workforce turnover and retention: What are the policy and practice priorities?

BACKGROUND:Residents of remote communities in Australia and other geographically large countries have comparatively poorer access to high-quality primary health care. To inform ongoing policy development and practice in relation to remote area health service delivery, particularly in remote Indigenous communities, this review synthesizes the key findings of (1) a comprehensive study of workforce turnover and retention in remote Northern Territory (NT) of Australia and (2) a narrative review of relevant international literature on remote and rural health workforce retention strategies. This synthesis provides a valuable summary of the current state of international knowledge about improving remote health workforce retention. MAIN TEXT:Annual turnover rates of NT remote area nurses (148%) and Aboriginal health practitioners (80%) are very high and 12-month stability rates low (48% and 76%, respectively). In remote NT, use of agency nurses has increased substantially. Primary care costs are high and proportional to staff turnover and remoteness. Effectiveness of care decreases with higher turnover and use of short-term staff, such that higher staff turnover is always less cost-effective. If staff turnover in remote clinics were halved, the potential savings would be approximately A$32 million per annum. Staff turnover and retention were affected by management style and effectiveness, and employment of Indigenous staff. Review of the international literature reveals three broad themes: Targeted enrolment into training and appropriate education designed to produce a competent, accessible, acceptable and 'fit-for-purpose' workforce; addressing broader health system issues that ensure a safe and supportive work environment; and providing ongoing individual and family support. Key educational initiatives include prioritising remote origin and Indigenous students for university entry; maximising training in remote areas; contextualising curricula; providing financial, pedagogical and pastoral support; and ensuring clear, supported career pathways and continuing professional development. Health system initiatives include ensuring adequate funding; providing adequate infrastructure including fit-for-purpose clinics, housing, transport and information technology; offering flexible employment arrangements whilst ensuring a good 'fit' between individual staff and the community (especially with regard to cultural skills); optimising co-ordination and management of services that empower staff and create positive practice environments; and prioritising community participation and employment of locals. Individual and family supports include offering tailored financial incentives, psychological support and 'time out'. CONCLUSION:Optimal remote health workforce stability and preventing excessive 'avoidable' turnover mandates alignment of government and health authority policies with both health service requirements and individual health professional and community needs. Supportive underpinning policies include: Strong intersectoral collaboration between the health and education sectors to ensure a fit-for-purpose workforce;A funding policy which mandates the development and implementation of an equitable, needs-based formula for funding remote health services;Policies that facilitate transition to community control, prioritise Indigenous training and employment, and mandate a culturally safe work context; andAn employment policy which provides flexibility of employment conditions in order to be able to offer individually customised retention packages There is considerable extant evidence from around the world about effective retention strategies that contribute to slowing excessive remote health workforce turnover, resulting in significant cost savings and improved continuity of care. The immediate problem comprises an 'implementation gap' in translating empirical research evidence into actions designed to resolve existing problems. If we wish to ameliorate the very high turnover of staff in remote areas, in order to provide an equitable service to populations with arguably the highest health needs, we need political and executive commitment to get the policy settings right and ensure the coordinated implementation of multiple strategies, including better linking existing strategies and 'filling the gaps' where necessary.John Wakerman, John Humphreys, Deborah Russell, Steven Guthridge, Lisa Bourke, Terry Dunbar, Yuejen Zhao, Mark Ramjan, Lorna Murakami-Gold and Michael P. Jone