Is investment in Indigenous land and sea management going to the right places to provide multiple co-benefits?

Indigenous land and sea management (ILSM) has been the focus of large government investment in Australia and globally. Beyond environmental benefits, such investments can deliver a suite of social, cultural and economic co-benefits, aligning with the objectives of Indigenous communities and of governments for culturally appropriate socio-economic development. Nevertheless, there have been very few studies done on the spatial distribution of this investment and the extent to which its associated co-benefits address socio-economic disadvantage, which is unevenly distributed across Australia. This study draws on Australian ILSM programmes to examine the spatial and temporal distribution of investment for ILSM between 2002–2012 and considers implications for the distribution of associated co-benefits. Mapping and analysis of 2600 conservation projects revealed that at least $462M of investment in ILSM projects had occurred at 750 discrete sites throughout Australia. More than half of this investment in ILSM has been concentrated in northern Australia, in disadvantaged remote and very remote areas where a high percentage of the population is Indigenous, and Indigenous land ownership extensive. Our research has shown that ILSM investment has successfully been spatially distributed to areas with high needs for multiple social, economic, environmental and health and well-being co-benefit outcomes

The Use of Theories, Models, and Frameworks to Inform the Uptake of Evidence-based Practices in Veterinary Medicine–A Scoping Review

Evidence based practices (EBPs) provide strategies to improve the health, welfare and productivity of animal species. However, ensuring implementation and uptake into routine practice of these EBPs is often challenging. In human health research, one approach used to improve uptake of EBPs is the use of theories, models and/or frameworks (TMFs), however the extent of the use of this approach in veterinary medicine is unknown. The aim of this scoping review was to identify existing veterinary uses of TMFs to inform the uptake of EBPs, and to understand the focus of these applications. Searches were conducted in CAB Abstracts, MEDLINE, Embase and Scopus, alongside grey literature, and ProQuest Dissertations & Theses. The search strategy consisted of a list of known existing TMFs that have been used to improve uptake of EBPs in human health, alongside more generic terminology for implementation and terminology relevant to veterinary medicine. Peer reviewed journal articles and grey literature detailing the use of a TMF to inform uptake of EBP(s) in a veterinary context were included. The search identified 68 studies that met the eligibility criteria. Included studies represented a diverse spread of countries, areas of veterinary concern and EBP. A range of 28 different TMFs were used, although the Theory of Planned Behaviour (TPB) predominated, featuring in 46% of included studies (n = 31). The majority of studies (n = 65, 96%) utilised a TMF with the aim to understand and/or explain what influences implementation outcomes. Only 8 studies (12%) reported the use of a TMF alongside/in conjunction with the actual implementation of an intervention. It is clear there has been some use to date of TMFs to inform uptake of EBPs in veterinary medicine, however it has been sporadic. There has been a heavy reliance on usage of the TPB and other similar classic theories. This has typically been to inform the understanding of factors, such as barriers and facilitators, that may influence the outcome of an implementation effort without then applying this knowledge to the actual implementation of an intervention. Furthermore, there has been a lack of acknowledgement of wider contextual factors and consideration of sustainability of interventions. There is clear potential to increase and expand the usage of TMFs to improve uptake of EBPs in veterinary medicine, including utilising a wider range of TMFs and developing interdisciplinary collaborations with human implementation experts

A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance.

K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Universal health care no guarantee of equity: Comparison of socioeconomic inequalities in the receipt of coronary procedures in patients with acute myocardial infarction and angina

<p>Abstract</p> <p>Background</p> <p>In Australia there is a socioeconomic gradient in morbidity and mortality favouring socioeconomically advantaged people, much of which is accounted for by ischaemic heart disease. This study examines if Australia's universal health care system, with its mixed public/private funding and delivery model, may actually perpetuate this inequity. We do this by quantifying and comparing socioeconomic inequalities in the receipt of coronary procedures in patients with acute myocardial infarction (AMI) and patients with angina.</p> <p>Methods</p> <p>Using linked hospital and mortality data, we followed patients admitted to Western Australian hospitals with a first admission for AMI (n = 5539) or angina (n = 7401) in 2001-2003. An outcome event was the receipt, within a year, of a coronary procedure—angiography, angioplasty and/or coronary artery bypass surgery (CABG). Socioeconomic status was assigned to each individual using an area-based measure, the SEIFA Index of Disadvantage. Multivariable proportional hazards regression was used to model the association between socioeconomic status and procedure rates, allowing for censoring and adjustment of multiple covariates. Mediating models examined the effect of private health insurance.</p> <p>Results</p> <p>In the AMI patient cohort, socioeconomic gradients were not evident except that disadvantaged women were more likely than advantaged women to undergo CABG. In contrast, in the angina patient group there were clear socioeconomic gradients for all procedures, favouring more advantaged patients. Compared with patients in the most disadvantaged quintile of socioeconomic status, patients in the least disadvantaged quintile were 11% (1-21%) more likely to receive angiography, 52% (29-80%) more likely to undergo angioplasty and 30% (3-55%) more likely to undergo CABG. Private health insurance explained some of the socioeconomic variation in rates.</p> <p>Conclusions</p> <p>Australia's universal health care system does not guarantee equity in the receipt of high technology health care for patients with ischaemic heart disease. While such a system might ensure equity for patients with AMI, where guidelines for treatment are relatively well established, this is not the case for angina patients, where health care may be less urgent and more discretionary.</p

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Abstracts from the NIHR INVOLVE Conference 2017

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Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio