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Background There is a high burden of skin and soft tissue infections (SSTI) – including cellulitis – among Aboriginal and Torres Strait Islander peoples living in remote communities. In tropical environments, such as the Torres Strait, cellulitis accounts for 37% of potentially preventable hospitalisations. This study aimed to evaluate the safety, effectiveness and community acceptance of outpatient antibiotic treatment for the management of skin infections in the Torres Strait. Methods This was a 12-month prospective, observational study commencing in January 2019 involving 295 adults with a skin infection across the Torres Strait. Results Most (276/295 (94%)) participants were treated successfully in the community. Of 295 enrolled patients, 151 of 295 (51%) had cellulitis, 59 of 295 (20%) had a skin abscess and 85 of 295 (28%) had a wound infection. Of the 77 of 278 (27%) infections accompanied by systemic features, 63 of 77 (82%) were managed in the community. Staphylococcus aureus was the most frequent isolate, at 165 of 261 (63%); 56 of 165 (33%) were methicillin resistant. In the 276 community-managed cases, oral trimethoprim/sulfamethoxazole was initially used in 159 (57%), oral flucloxacillin in 75 (27%) and intravenous cefazolin plus oral probenecid in 32 (13%). The clinical course was complicated in eight of 232 (3%) patients who had complete follow-up data: seven patients required hospitalisation after initial treatment in the community and one had an antibiotic side-effect. All 232 patients with complete follow-up data were content with the care they received. Conclusions Outpatient management of skin infection in the Torres Strait is effective, safe and appreciated by patients.

This practitioner-oriented article represents a strand of research by the author into the practice of developing financially quantified value propositions for customers, which is the focus of this article. There is an appendix that spells out other meanings of the word ‘value’. The data used were gathered over a 5-year period from attendance and keynote addresses on the topic of value. In total, twelve conferences and 1,200 marketing practitioners were asked about their value propositions (defined in this article) via audience response systems in order to guarantee honest answers. The results indicate that fewer than 3% have financially quantified value propositions. This compares with a verbal estimate from McKinsey of 5%. The main conclusion, while only indicative, is that it is a very low percentage of UK companies. A review of the literature on value propositions failed to reveal any kind of quantitative process for developing financially quantified value propositions, so the author developed such a process and tested it on 20 organizations, global and local in order to refine it. This article sets out the results of this work and is summarized here as a six-step process. It is important to point out that the author of this article is deeply involved in the growing community of academics and practitioners who are striving to convince organizations that it is not only about creating value for customers, but also about creating value for employees, for all stakeholders and, of course for the Planet. All of this, however, is contingent upon creating value for customers, the major issue spelled out in this article.

The reduced prevalence of insulin resistance and type 2 diabetes (T2D) in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomized controlled trial of hookworm infection in 40 people at risk of T2D involved treatment with either 20 or 40Necator americanusthird-stage larvae (L3) or Placebo. Primary outcome was safety, with homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), and body mass being the key metabolic outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced transient gastrointestinal symptoms. FBG and HOMA-IR were significantly lowered in both hookworm-treated groups at 1-year, and body mass was significantly lowered after L3-20 treatment at 2-years. Overall, hookworm infection was well tolerated in people at risk of T2D, and were associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.

With legislation around the world placing more emphasis on corporate governance and control procedures and with the increasing potential penalties on individual directors, the need for an objective and well-structured review and approval process is becoming greater and spells out the consequences for stakeholder value if this goal is not achieved. This paper makes the case for the supremacy of shareholder value added as the principal goal of corporate strategy. It also spells out a methodology for assessing risk and adjusting corporate strategy accordingly. This methodology is probabilistic rather than mathematical, hence the William Bruce Cameron quotation above.

PurposeThe objective of this short research-informed, practitioner-orientated paper is to provide a viewpoint on interactive marketing pre and post COVID-19.Design/methodology/approachThis is a conceptual article designed to articulate a viewpoint that despite COVID-19 the strategic considerations that marketers need to make remain unchanged.FindingsAs a result of the pandemic, there is much more obvious use of interactivity in other, aligned functions such as sales and customer services. The effectiveness of interactive marketing will only be increased by having focus on the fundamental roles of the marketing discipline, strategy and segmentation, and understanding customers at the individual level. We also need reminding briefly that the rules of competition had changed well before the COVID-19 pandemic. The traditional make and sell model has been substantially replaced by new technology-enabled organisations without the restrictions of high fixed costs and cloying bureaucracy. Customers can now search for and evaluate products and services independent of suppliers and now have as much information about suppliers as suppliers have of customers. This is the backcloth against which marketers face the challenges at the beginning of 2021. We conclude that there is a great future ahead. There is no reason why the best of interactive marketing will not be capable of building relationships that are great for customers, great for the people who create them, great for all stakeholders and great for the environment.Originality/valueThis is a practitioner viewpoint outlining the view that COVID-19 has not had as great of an impact on interactive marketing practice as technological change has and that interactive marketing will continue to develop after COVID-19 has receded.

BACKGROUND No consensus germline testing guidelines currently exist for glioma patients. Hence such testing is not routinely performed. The prevalence and type of germline pathogenic variants in these brain tumors remains unknown. DESIGN/ METHODS A retrospective review of patients treated at Baylor College of Medicine with paired tumor/normal sequencing using the Tempus xT tumor/normal matched approach from August 2018- April 2022 was performed. Corresponding clinical data was collected for these patients. RESULTS We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wildtype, 3/42 (7.1%) of Astrocytoma, IDH mutant and 1/26 (3.8%) of Oligodendroglioma, IDH mutant and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH and CHEK2 were seen more commonly (3/15 or 20% each). BRCA1 variants were seen in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Second hit somatic variants were seen in 3/15 patients (20%). A second somatic hit was seen in NF1, MUTYH and MSH2 in one patient (7%) each. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. Median overall survival was 1.6 years for glioblastoma, IDH wildtype patients with a pathogenic germline variant compared to 1.79 years for glioblastoma, IDH wildtype patients without it (p = 0.67). CONCLUSIONS Although not routinely performed in glioma patients, pathogenic germline variants occurred in ~10% of our patients. Only 40% of these patients were referred to genetics. These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further research to confirm the occurrence and types of pathogenic germline variants in patients with IDH wildtype compared to IDH mutant tumors is necessary.

Screen-printed textiles from remote Australian Aboriginal communities are a widely acclaimed and celebrated form of cultural expression. They bring substantial benefits to artists and their communi...

Acute poststreptococcal glomerulonephritis (APSGN) is an immune complex-induced glomerulonephritis that develops as a sequela of streptococcal infections. This article provides guidelines for the surveillance of APSGN due to group A Streptococcus (Strep A). The primary objectives of APSGN surveillance are to monitor trends in age- and sex-specific incidence, describe the demographic and clinical characteristics of patients with APSGN, document accompanying risk factors, then monitor trends in frequency of complications, illness duration, hospitalization rates, and mortality. This document provides surveillance case definitions for APSGN, including clinical and subclinical APSGN based on clinical and laboratory evidence. It also details case classifications that can be used to differentiate between confirmed and probable cases, and it discusses the current investigations used to provide evidence of antecedent Strep A infection. The type of surveillance recommended depends on the burden of APSGN in the community and the objectives of surveillance. Strategies for minimal surveillance and enhanced surveillance of APSGN are provided. Furthermore, a discussion covers the surveillance population and additional APSGN-specific surveillance considerations such as contact testing, active follow up of cases and contacts, frequency of reporting, surveillance visits, period of surveillance, and community engagement. Finally, the document presents core data elements to be collected on case report forms, along with guidance for documenting the course and severity of APSGN.

BackgroundBetween 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival.MethodsA retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis.FindingsThe cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18–42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4–12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death.InterpretationSurvival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes.

Background In July 2018, participants at a Waiben (Thursday Island) conference declared that it was time for a locally driven research agenda for the Torres Strait and Queensland Northern Peninsula Area. For decades, they felt exploited by outside researchers. They identified a lack of respect and consultation, with few benefits for their people. Methods In response, the Australian Institute of Tropical Health and Medicine (Waiben Campus‐Ngulaigau Mudh) invited a consultative group of elders and senior health providers to develop a research program based on local cultural and health needs. The aim was to promote research skills through a learn-by-doing approach. Four workshops were conducted over 2019. Key financial and in-kind support was provided by the Australian Institute of Tropical Health and Medicine, Hot North, and Queensland Health’s Torres and Cape Hospital and Health Service. Results The first workshop attracted 24 people; none had previous research experience. The workshop format evolved over 2019, mainly guided by the participants. Overall, feedback was positive, and participant research proposals remain in various stages of development. Conclusions Although suspended during the COVID-19 pandemic, this is a long-term investment in community-driven research that seeks to translate health benefits to the people. This model may apply to other communities, especially in rural and remote Australia. Warning This article contains the names and/or images of deceased Aboriginal and Torres Strait Islander peoples.

Although surgery has been shown to provide a survival benefit in patients with glioblastoma multiforme (GBM), tumor location and geometry may restrict maximal resection. Additionally, the margin of resection cavity contains infiltrating tumor cells that result in recurrence and therapy resistance. Laser interstitial thermal therapy (LITT) is a treatment modality that uses thermal energy to destroy tumor cells. LITT is useful for tumors that are not appropriate for conventional surgical resection. Our laboratory has developed a LITT model to study LITT in a genetically engineered mouse model of GBM. The combination of heat activated nanoparticles and LITT represents an opportunity to target the infiltrating tumor margin, extending the treatment penumbra. We hypothesized that heat-activated liposomes containing doxorubicin (ThermoDox, Celsion) would demonstrate infiltration into the brain parenchyma after treatment with LITT. We treated tumor-bearing mice with LITT or sham (laser fiber implanted but not activated) after either ThermoDox (5mg/kg) or PBS infusion, 30 minutes before performing LITT or sham treatment. We euthanized these mice 1 hour after LITT or sham treatment, harvested brains, and performed immunofluorescence to identify doxorubicin in parenchymal cells. Doxorubicin was identified in 100% of mice treated with LITT following ThermoDox administration which is in contrast with groups treated with LITT and PBS, sham and ThermoDox, and sham and PBS. Here, we show that heat-activated nanoparticles are disrupted through hyperthermia followed by the release of doxorubicin only in the presence of hyperthermia, which paves way for the clinical use of ThermoDox as adjunct chemotherapy following LITT in treatment-resistant GBM treatment.

Appendicitis is a leading cause of surgical hospital admission. To date, there have been no published epidemiological studies describing appendicitis in tropical and remote Australia and none specifically documenting appendicitis in Indigenous Australians. This descriptive study used available state data to investigate appendicitis across Far North Queensland (FNQ).Queensland Health hospital admission data for FNQ was analysed to explore appendicitis epidemiology and outcomes in FNQ, 2012-2018. Population data for the same time period provided rates.Over the study period, 3458 hospital presentations for appendicitis were available for analysis. Mean incidence was 178 per 100 000/yr. Median age was 27 years with 50.1% female patients. The annual rate of appendicitis was higher in the Indigenous population. Most patients had a laparoscopic procedure with a low rate of conversion to open surgery (2.6%). More than 80% of patients were discharged from hospital in less than 3 days. Intensive care (ICU) admission rate was low overall (1.1%) although higher for Indigenous people (2.4%). Following discharge, the hospital re-admission rate was 3.8% and all-cause mortality was 0.03%.The incidence of appendicitis in FNQ is higher than that reported in the rest of Australia in both Indigenous and non-Indigenous populations. Despite logistical challenges of health care, clinical outcomes are in line with best practice across the country. Clinicians in FNQ should maintain a high index of suspicion for diagnosing appendicitis in rural and remote settings.

PURPOSE The aim of this systematic review was to identify models of community disability, rehabilitation and lifestyle service delivery in non-metropolitan areas of Australia, and to describe these models through an Integrated People-Centred Health Services (IPCHS) lens. MATERIALS AND METHODS We identified peer-reviewed studies published between 2000 and June 2021 that met the following criteria: described or evaluated a community service delivery model, intervention or program in regional, rural or remote Australia; provided for people with a disability or a potentially disabling health condition. A scoring rubric was developed covering the five IPCHS strategies. RESULTS Nineteen studies were included in the review. We identified a range of service delivery models providing support to people with a range of disabilities or conditions. We report evidence of the use of the IPCHS strategies in ways relevant to the local context. DISCUSSION Several strengths emerged, with many services tailored to individual need, and significant community engagement. Innovative rural service delivery approaches were also identified. Key areas requiring action included improved coordination or integration within and across professions and sectors. There was limited evidence of co-production of solutions or participatory governance. While people-centred approaches show promise to improve community-based services, large-scale fundamental change is required.IMPLICATIONS FOR REHABILITATIONCommunity-based disability and rehabilitation services in rural and remote Australia performed well at delivering tailored care and engaging in community consultation.These services must urgently implement strategies to enhance community ownership of solutions and participatory governance.Services must place a greater focus on explicit strategies to integrate and coordinate across services and professions, and to create an enabling environment, to deliver people-centred care.The World Health Organisation Integrated People-Centred Health Services framework provides an important roadmap to improving service delivery in rural and remote Australian communities.

Skin infections such as impetigo and scabies are common in Aboriginal Australian and Torres Strait Islander children living in rural and remote settings. Effective health promotion is a key element when addressing health literacy aimed at reducing the burden of skin disease. Community-driven health promotion provides a potentially effective and sustainable model for improved health outcomes.A one-day community-driven skin health promotional event was conducted on Waiben [Thursday Island] with the aim of improving local Torres Strait Islander children's appreciation of the importance of skin health through art, music and creation of a video. Participants completed written pre- and post-questionnaires to determine their response.Fifty-two children participated in the event; median (range) age was 11 (9-12) years and all identified as Torres Strait Islander. Overall, 34 of 50 children (68%) felt that participating in this workshop improved their skin health knowledge.Skin health promotion can be successful achieved through a locally conceived, locally driven and locally owned approach. SO WHAT?: This skin health promotional event could be a model for other health promotion activities in the Torres Strait.

Issue addressed: Building the health promotion evaluation capacity of a workforce requires more than a focus on individual skills and confidence. We must also consider the organisational systems and supports that enable staff to embed learnings into practice. This paper describes the processes used to build health promotion evaluation capacity of staff in an Aboriginal Community Controlled Health Service (ACCHS). Methods: To build health promotion evaluation capacity three approaches were used: (i) workshops and mentoring; (ii) strengthening systems to support program reporting; and (iii) recruitment of staff with skills and experience. Pre- and post-questionnaires determined levels of individual skills and confidence, updated systems were assessed for adequacy to support new health promotion practices and surveys captured the usefulness of workshops and mentoring. Results: There was increased participant skills and confidence. Participants completed program impact evaluation reports and results were successfully presented at national conferences. The health promotion team was then able to update in-house systems to support new health promotion practices. Ongoing collaboration with experienced in-house researchers provided basic research training and professional mentoring. Conclusions: Building health promotion evaluation capacity of staff in an ACCHS can be achieved by providing individual skill development, strengthening organisational systems and utilising professional support. So what?: Health promotion practitioners have an ongoing professional obligation to improve the quality of routine practice and embrace new initiatives. This report outlines a process of building evaluation capacity that promotes quality reporting of program impacts and outcomes, reflects on ways to enhance program strengths, and communicates these findings internally and to outside professional bodies. This is particularly significant for ACCHSs responsible for addressing the high burden of preventable disease in Aboriginal and Torres Strait Islander populations.

Background Abdominal obesity and presence of the metabolic syndrome (MetS) significantly increase the risk of developing diseases such as Type 2 diabetes mellitus (T2DM) with escalating emergence of MetS and T2DM constituting a significant public health crisis worldwide. Lower prevalence of inflammatory and metabolic diseases such as T2DM in countries with higher incidences of helminth infections suggested a potential role for these parasites in the prevention and management of certain diseases. Recent studies confirmed the potential protective nature of helminth infection against MetS and T2DM via immunomodulation or, potentially, alteration of the intestinal microbiota. This Phase 1b safety and tolerability trial aims to assess the effect of inoculation with helminths on physical and metabolic parameters, immune responses, and the microbiome in otherwise healthy women and men. Methods Participants eligible for inclusion are adults aged 18–50 with central obesity and a minimum of one additional feature of MetS recruited from the local community with a recruitment target of 54. In a randomised, double-blind, placebo-controlled design, three groups will receive either 20 or 40 stage three larvae of the human hookworm Necator americanus or a placebo. Eligible participants will provide blood and faecal samples at their baseline and 6-monthly assessment visits for a total of 24 months with an optional extension to 36 months. During each scheduled visit, participants will also undergo a full physical examination and complete diet (PREDIMED), physical activity, and patient health (PHQ-9) questionnaires. Outcome measurements include tolerability and safety of infection with Necator americanus, changes in metabolic and immunological parameters, and changes in the composition of the faecal microbiome. Discussion Rising cost of healthcare associated with obesity-induced metabolic diseases urgently calls for new approaches in disease prevention. Findings from this trial will provide valuable information regarding the potential mechanisms by which hookworms, potentially via alterations in the microbiota, may positively influence metabolic health. Trial registration The protocol was registered on ANZCTR.org.au on 05 June 2017 with identifier ACTRN12617000818336. Alternatively, a Google search using the above trial registration number will yield a direct link to the trial protocol within the ANZCTR website.

Introduction: Cardiovascular disease (CVD) is the commonest cause of death across the globe; incidence and prevalence rates are increasing. Together, CVD and diabetes mellitus are responsible for a quarter of the health gap observed between Aboriginal Australians and Torres Strait Islanders, and non-Indigenous Australians. Numerous programs have been proposed and implemented to Close the Gap; ideally, these should be evidence-based Objective: The aim of this review is to evaluate primary prevention measures and programs that aim to reduce CVD risk in minority Indigenous populations around the world. Methods: A search of PubMed, the Cochrane Library and the Elsevier Scopus Database was initially conducted using the terms “cardiovascular disease”, “population groups”, “primary prevention”, "health services, indigenous”, "indigenous health", "risk assessment" and “risk management”. Results were then assessed per inclusion/exclusion criteria. A second reviewer independently evaluated the publications and review process to ensure agreement. Results: The initial search produced 37 publications; 19 met the inclusion criteria and were incorporated into a comparative table. Most were descriptive, mixed-methods, audit or intervention studies. Heterogeneity of study design prevented statistical analysis. Conclusion: Addressing CVD risk in minority Indigenous populations is a multifactorial challenge; there is substantial room for improvement in routine risk assessment and management. Holistic approaches need to embrace local cultural perceptions of health and wellbeing. Validated risk reduction tools, individualised management plans, polypills and computer based decision support tools are promising to improve outcomes for those at risk. Refereed/Peer-reviewed

Continuity of care matters; however, expansion and specialisation of the health system tends to fragment care. Continuity of care is accompanied by a range of patient benefits, including reduced all-cause mortality; lower rates of hospital presentation and preventable admission; and improved patient satisfaction. Potential concerns have been raised about some aspects of continuity of care, but these are outweighed by the perceived benefits. There are many barriers to achieving continuity, especially in rural and remote settings. Some practical solutions have been proposed that include adapting clinic procedures, utilising a small team approach, improving staff retention and ongoing advocacy.

Aims There is increasing evidence on the role of helminth infections in modifying autoimmune and allergic diseases. These infections may have similar effect in other inflammatory processes, such as insulin resistance. This review aims to examine the literature on the effect of helminthic infections on metabolic outcomes in humans. Methods Using the PRISMA protocol, we searched the literature using PubMed, MEDLINE, and a manual review of reference lists. Human studies published in English after 1995 were included. Four papers were included in this review. Data was extracted and a meta-analysis was conducted using a random-effects model. Heterogeneity was assessed using Tau2 and I2 tests. Results The included studies found that infection was associated with lower glucose levels, less insulin resistance, and/or a lower prevalence of metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM). Meta-analysis showed that participants with a previous or current helminth infection were 50% less likely to have an endpoint of metabolic dysfunction in comparison to uninfected participants (OR 0.50; 95% CI 0.38–0.66). Conclusion This review has shown that helminth infections can be associated with improved metabolic outcomes. Understanding of the mechanisms underlying this relationship could facilitate the development of novel strategies to prevent or delay T2DM.

There is now evidence linking antibiotic burden in infancy and subsequent risk factors for cardiometabolic disease. In this study we assessed the metabolic health of a community-based cohort of Aboriginal Australians aged 15–25 years and retrospectively examined their early childhood antibiotic burden to identify a possible link between the two. Metabolic health data were extracted from electronic files of 433 participants in prior Young Persons Checks between 2013 and 2016. More than one-third were overweight or obese. Males had more metabolic syndrome than females (20.6% vs 10%; P=0.03). Metabolic syndrome was twice as common in the 20- to 25-year age group than in the 15- to 19-year age group (19.8% vs 9.7%; P

Background A healthy start predicts better health in later life. Many remote-living Aboriginal and Torres Strait Islander Australian families lack access to consistent, culturally-safe health services. This paper presents a study of implementation of the Baby One Program (BOP). The BOP was designed as a family-centred, Indigenous Healthworker-led, home-visiting model of care focused on promoting family health to give children the best start to life. It was developed by Aboriginal community-controlled Apunipima Cape York Health Council and delivered in Queensland Cape York remote communities. We aimed to determine how the BOP was implemented, enablers, strategies used and formative implementation outcomes. Methods The qualitative approach utilised theoretical and purposive sampling to explore people’s experiences of a program implementation process. Data were generated from semi-structured interviews with four family members enrolled in the BOP and 24 Apunipima staff members. In addition, twenty community members, including two program users, participated in a men’s community focus group. The findings are presented according to themes arising from the data. Results The BOP was rolled out in nine remote Cape York communities between July 2014 and December 2015 and there was high uptake. Indigenous Healthworkers were supported by midwives and maternal and child health nurses to deliver health education to 161 eligible families. The key to effective implementation of family-centred care appeared to be the relationships formed between health practitioners, especially Indigenous Healthworkers, and families. The data revealed the following themes: challenging environments for new families and valuing cultural ways, resourcing program delivery, working towards a team approach, negotiating the cultural interface, engaging families, exchanging knowledge through ‘yarning’, strengthening the workforce, and seeing health changes in families. Healthworker education and training, and knowledge exchange between Healthworkers, midwives and nurses was critical to program effectiveness. The program continues to grow despite substantial logistic, financial and practical challenges. Conclusions This study describes an evolving process and explores how health providers connect with families and how the program responds to family and cultural issues. Program development is ongoing; strengthened by more community-level involvement, embedded strategies for ongoing self-evaluation and continuous quality improvements that are responsive to family needs. Electronic supplementary material The online version of this article (10.1186/s12884-018-1711-7) contains supplementary material, which is available to authorized users.

The interactions between tumors cells and their microenvironment are increasingly recognized as contributors to tumor growth and therapeutic resistance in glioblastoma (GBM). Mesenchymal Stem Cells (MSCs) have been implicated as components of the microenvironment of several cancers, but their contribution to GBM remains obscure. Recently we reported that GBMs contain cells resembling human mesenchymal stem cells, called Glioma-associated-MSCs (GA-hMSCs), based on our ability to isolate these cells from patient tumors (Figueroa, et al. Can Res 2017. 77, 5808–5819). In order to characterize the function of these cells in vivo, we used a PDGFRb promoter driven mouse model to track and modulate the behavior of endogenous MSCs (PDGFRb + cells). To generate tumors that mimic gliomas, we injected the RCAS-PDGF avian retrovirus into PDGFRb EGFP/nTVA mice. These mice express EGFP in PDGFRb expressing cells and RCAS receptor TVA under the control of the Nestin promoter and develop tumors. Immunostaining these tumors for GFP and CD31 determined that MSC like cells reside around blood vessels and are likely the major contributor of microvascular proliferation often seen in human gliomas. Additionally, we sought to see if there was communication between MSCs localized around blood vessels and the tumor. To this end, mice with Cre recombinase expression under the PDGFRb promoter were implanted with a GL-261 tumor harboring a dsRed/eGFP Cre recombinase/LoxP site. In these mice, tumor color change from red to green indicates transfer of Cre mRNA or protein from PDGFRb+ cells (MSCs) to tumor cells (GL-261dsRed/eGFP). We observed red to green transition in tumors, indicating that there is transfer of mRNA or protein, and further suggesting that there is direct communication between the tumor microenvironment and the tumor. Taken together, our findings emphasize the crucial role of MSCs in the tumor microenvironment.

Objective: To describe the process of gaining consensus across regional organisations in formulating measures to improve coordination of care for people from remote Far North Queensland communities coming to town (Cairns) to access health care. Design: This is a descriptive study that includes survey data from workshop participants. Setting: Coming to town for health care poses great challenges, especially for Indigenous Australians from remote communities. Numerous organisations are involved, communications are fragmented and there is no central coordinating body. The system frequently fails to deliver necessary services. This generates preventable cost burdens through missed flights, missed appointments, missed treatment opportunities and extra administration. Workshop organisers invited key service providers from across Far North Queensland. Main outcome measures: Using real-case scenarios, the task was to identify and prioritise the central issues and explore ways to address them. Participants jointly crafted the final recommendations and also posted suggestions on a 'wish-list' board. A participant assessment survey was conducted at the end of the workshop, followed by an online survey 6 weeks later. Results:There were 32 participants. The concluding survey indicated the workshop was well received and people valued the collaboration. There were six primary recommendations plus numerous wish-list suggestions. The best-supported recommendation was establishment of a coming to town Hub with a local coordinating team and community-based representatives. Conclusion: Implementation of the workshop recommendations and support of all key service providers should be culturally acceptable and resource-efficient with better health outcomes for travellers, their families and communities.

Gurriny Yealamucka Health Service Aboriginal Corporation (GYHSAC) is an Indigenous community-controlled health organisation providing comprehensive primary care to the people of Yarrabah in far north Queensland, Australia. GYHSAC conducts an annual Young Person's Health Check (YPC) for people aged 15-25 years based on the Medical Benefits Schedule Item 715. However, the YPC is constantly evolving to meet the needs of the community, and in 2016, in response to concerns about psychological risk among Indigenous youth, GYHSAC teamed up with James Cook University to trial an adapted PHQ-9 depression screening tool (aPHQ-9) as part of the YPC. This study describes the 2016 YPC event, reports the prevalence of depressive symptoms, examines local issues related to the use of the screening tool and proposes recommendations for future health screening. Experienced health professionals conducted the aPHQ-9 assessment in a private area of the clinic. One-in-five young people were found to have moderate-severe symptoms or self-harm ideation in the previous 2 weeks they were referred to the mental health service. The aPHQ-9 screening process was found to be straightforward and well accepted by staff and youth. Importantly, it provided valuable 'space' to facilitate communication on sensitive issues and was a conduit for speedy referral and follow up by trained staff. Based on our experience, we recommend dedicated depression screening in future routine community health checks for young people and adults Refereed/Peer-reviewed

The poor outcome of patients with glioblastoma (GBM) is at least partly due to the inability to deliver therapeutic agents to the tumor. We have shown that exosomes, naturally occurring nano-size extracellular vesicles, are capable of delivering antiglioma microRNAs (MiRs) to brain tumors (Lang, FM et al. Neuro Oncol, 2018;20(3):380–390). However, our studies suggested that there is significant opportunity to increase packaging efficiency and delivery specificity of exosomes. To this end, we engineered exosomes to express specific viral proteins (called eExos) in order to enhance packaging and delivery capabilities of antiglioma genes. These eExos are created by transfecting HEK 293 cells with plasmids containing viral proteins and a plasmid of the therapeutic gene. After 72 hrs, differential ultracentrifugation was used to isolate the exosomes. To test the efficacy of these novel eExos, we transfected them with a plasmid containing Cre recombinase (as the therapeutic gene), and treated U87 cells harboring a dsRed/eGFP Cre recombinase/LoxP site (U87dsR/GFP). In in vitro studies, treatment of U87dsR/GFP with a single dose of eExos resulted in 82% conversion rate of cells from red to green, compared to control exosomes (< 18% green cells). In in vivo studies, a single intratumoral injection of eExos into mice harboring 7-day old intracranial U87dsR/GFP gliomas, resulted in significant increases in green cells compared to control exosomes when tumors were harvested at day 10. Mechanistic studies employing florescent microscopy demonstrate that in contrast to natural exosomes, eExos deliver their cargo to the nucleus rather than to lysosomes, avoiding degradation of the delivered agent and facilitating expression of the plasmid. We conclude that eExos, engineered to contain specific viral proteins, are capable of packaging and delivering antiglioma genes more effectively than natural exosomes and may overcome the current inability to deliver biological therapeutic agents to brain tumors.