Findings of the first ANZICS conference on the role of intensive care in Rapid Response Teams.

Rapid Response Teams (RRTs) are specialised teams introduced into hospitals to improve the outcomes of deteriorating ward patients. Although Rapid Response Systems (RRSs) were developed by the intensive care unit (ICU) community, there is variability in their delivery, and consultant involvement, supervision and leadership appears to be relatively infrequent. In July 2014, the Australian and New Zealand Intensive Care Society (ANZICS) convened the first conference on the role of intensive care medicine in RRTs in Australia and New Zealand. The conference explored RRSs in the broader role of patient safety, resourcing and staffing of RRTs, effect on ICU workload, different RRT models, the outcomes of RRT patients and original research projects in the area of RRSs. Issues around education and training of both ICU registrars and nurses were examined, and the role of team training explored. Measures to assess the effectiveness of the RRS and RRT at the level of health system and hospital, team performance and team effectiveness were discussed, and the need to develop a bi-national ANZICS RRT patient database was presented. Strategies to prevent patient deterioration in the 'pre-RRT' period were discussed, including education of ward nurses and doctors, as well as an overarching governance structure. The role of the ICU in deteriorating ward patients was debated and an integrated model of acute care presented. This article summarises the findings of the conference and presents recommendations on the role of intensive care medicine in RRTs in Australia and New Zealand.

The HWMD maturity model: a foundational framework to measure effectiveness of institutional research e-infrastructures

There is a nationally recognised need for a framework and tools to measure progress in implementing e-infrastructures for research from an institutional, organisational unit and service perspective. This paper describes the development of a prototype maturity model and self-assessment tool in response to that need. The authors present a background to the environment of technology enabling services for research and the challenges of fluidity of boundaries around traditional services and roles as institutions respond to the needs of the research community. The conceptual basis of the model is presented along with the model and its various elements that explain how the model is in its current form. The information provided in this paper, combined with field site test feedback, will promote discussion and debate amongst the community and opportunities will present to gather input to optimise the model. The next steps would be to further elaborate and test the constructs and indicators of the model in field test sites and to further develop the self -assessment tool.

Development of a conceptual model of cancer caregiver health literacy.

Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy.

Protocol-directed sedation versus non-protocol-directed sedation to reduce duration of mechanical ventilation in mechanically ventilated intensive care patients (review)

Background : The sedation needs of critically ill patients have been recognized as a core component of critical care and meeting these is vital to assist recovery and ensure humane treatment. There is growing evidence to suggest that sedation requirements are not always optimally managed. Sub-optimal sedation incorporates both under- and over-sedation and has been linked to both short-term (e.g. length of stay) and long-term (e.g. psychological recovery) outcomes. Various strategies have been proposed to improve sedation management and address aspects of assessment as well as delivery of sedation.

Objectives : To assess the effects of protocol-directed sedation management on the duration of mechanical ventilation and other relevant patient outcomes in mechanically ventilated intensive care unit (ICU) patients. We looked at various outcomes and examined the role of bias in order to examine the level of evidence for this intervention.

Search methods : We searched the Cochrane Central Register of Controlled trials (CENTRAL) (2013; Issue 11), MEDLINE (OvidSP) (1990 to November 2013), EMBASE (OvidSP) (1990 to November 2013), CINAHL (BIREME host) (1990 to November 2013), Database of Abstracts of Reviews of Effects (DARE) (1990 to November 2013), LILACS (1990 to November 2013), Current Controlled Trials and US National Institutes of Health Clinical Research Studies (1990 to November 2013), and reference lists of articles. We re-ran the search in October 2014. We will deal with any studies of interest when we update the review.

Selection criteria : We included randomized controlled trials (RCTs) conducted in adult ICUs comparing management with and without protocol-directed sedation.

Data collection and analysis : Two authors screened the titles and abstracts and then the full-text reports identified from our electronic search. We assessed seven domains of potential risk of bias for the included studies. We examined the clinical, methodological and statistical heterogeneity and used the random-effects model for meta-analysis where we considered it appropriate. We calculated the mean difference (MD) for duration of mechanical ventilation and risk ratio (RR) for mortality across studies, with 95% confidence intervals (CI).

Main results : We identified two eligible studies with 633 participants. Both included studies compared the use of protocol-directed sedation, specifically protocols delivered by nurses, with usual care. We rated the risk of selection bias due to random sequence generation low for one study and unclear for one study. The risk of selection bias related to allocation concealment was low for both studies. We also assessed detection and attrition bias as low for both studies while we considered performance bias high due to the inability to blind participants and clinicians in both studies. Risk due to other sources of bias, such as potential for contamination between groups and reporting bias, was considered unclear. There was no clear evidence of differences in duration of mechanical ventilation (MD -5.74 hours, 95% CI -62.01 to 50.53, low quality evidence), ICU length of stay (MD -0.62 days, 95% CI -2.97 to 1.73) and hospital length of stay (MD -3.78 days, 95% CI -8.54 to 0.97) between people being managed with protocol-directed sedation versus usual care. Similarly, there was no clear evidence of difference in hospital mortality between the two groups (RR 0.96, 95% CI 0.71 to 1.31, low quality evidence). ICU mortality was only reported in one study preventing pooling of data. There was no clear evidence of difference in the incidence of tracheostomy (RR 0.77, 95% CI 0.31 to 1.89). The studies reported few adverse event outcomes; one study reported self extubation while the other study reported re-intubation; given this difference in outcomes, pooling of data was not possible. There was significant heterogeneity between studies for duration of mechanical ventilation (I2 = 86%, P value = 0.008), ICU length of stay (I2 = 82%, P value = 0.02) and incidence of tracheostomy (I2 = 76%, P value = 0.04), with one study finding a reduction in duration of mechanical ventilation and incidence of tracheostomy and the other study finding no difference.

Authors' conclusions : There is currently insufficient evidence to evaluate the effectiveness of protocol-directed sedation. Results from the two RCTs were conflicting, resulting in the quality of the body of evidence as a whole being assessed as low. Further studies, taking into account contextual and clinician characteristics in different ICU environments, are necessary to inform future practice. Methodological strategies to reduce the risk of bias need to be considered in future studies.

Model to predict inpatient mortality from information gathered at presentation to an emergency department: The Triage Information Mortality Model (TIMM)

OBJECTIVES: To derive and validate a mortality prediction model from information available at ED triage. METHODS: Multivariable logistic regression of variables from administrative datasets to predict inpatient mortality of patients admitted through an ED. Accuracy of the model was assessed using the receiver operating characteristic area under the curve (ROC-AUC) and calibration using the Hosmer-Lemeshow goodness of fit test. The model was derived, internally validated and externally validated. Derivation and internal validation were in a tertiary referral hospital and external validation was in an urban community hospital. RESULTS: The ROC-AUC for the derivation set was 0.859 (95% CI 0.856-0.865), for the internal validation set was 0.848 (95% CI 0.840-0.856) and for the external validation set was 0.837 (95% CI 0.823-0.851). Calibration assessed by the Hosmer-Lemeshow goodness of fit test was good. CONCLUSIONS: The model successfully predicts inpatient mortality from information available at the point of triage in the ED.

The asymptotic distribution of the CADF unit root test in the presence of heterogeneous AR(p) errors

The CADF test of Pesaran (J Appl Econ 22:265–312, 2007) are among the most popular univariate tests for cross-section correlated panels around. Yet, the existing asymptotic analysis of this test statistic is limited to a model in which the errors are assumed to follow a simple AR(1) structure with homogenous autoregressive coefficients. One reason for this is that the model involves an intricate identification issue, as both the serial and cross-section correlation structures of the errors are unobserved. The purpose of the current paper is to tackle this issue and in so doing extend the existing analysis to the case of AR((Formula presented.)) errors with possibly heterogeneous coefficients.

Pooled panel unit root tests and the effect of past initialization

This paper analyzes the role of initialization when testing for a unit root in panel data, an issue that has received surprisingly little attention in the literature. In fact, most studies assume that the initial value is either zero or bounded. As a response to this, the current paper considers a model in which the initialization is in the past, which is shown to have several distinctive features that makes it attractive, even in comparison to the common time series practice of making the initial value a draw from its unconditional distribution under the stationary alternative. The results have implications not only for theory, but also for applied work. In particular, and in contrast to the time series case, in panels the effect of the initialization need not be negative but can actually lead to improved test performance.

Panel cointegration and the monetary exchange rate model

This paper re-examines the validity of the monetary exchange rate model during the post-Bretton Woods era for 18 OECD countries. Our analysis simultaneously considers the presence of both cross-sectional dependence and multiple structural breaks, which have not received much attention in previous studies of the monetary model. The empirical results indicate that the monetary model emerges only when the presence of structural breaks and cross-country dependence has been taken into account. Evidence is also provided suggesting that the breaks in the monetary model can be derived from the underlying purchasing power parity relation. © 2008 Elsevier B.V. All rights reserved.

Competitive inhibition of survivin using a cell-permeable recombinant protein induces cancer-specific apoptosis in colon cancer model

Endogenous survivin expression has been related with cancer survival, drug resistance, and metastasis. Therapies targeting survivin have been shown to significantly inhibit tumor growth and recurrence. We found out that a cell-permeable dominant negative survivin (SurR9-C84A, referred to as SR9) competitively inhibited endogenous survivin and blocked the cell cycle at the G1/S phase. Nanoencapsulation in mucoadhesive chitosan nanoparticles (CHNP) substantially increased the bioavailability and serum stability of SR9. The mechanism of nanoparticle uptake was studied extensively in vitro and in ex vivo models. Our results confirmed that CHNP-SR9 protected primary cells from autophagy and successfully induced tumor-specific apoptosis via both extrinsic and intrinsic apoptotic pathways. CHNP-SR9 significantly reduced the tumor spheroid size (three-dimensional model) by nearly 7-fold. Effects of SR9 and CHNP-SR9 were studied on 35 key molecules involved in the apoptotic pathway. Highly significant (4.26-fold, P≤0.005) reduction in tumor volume was observed using an in vivo mouse xenograft colon cancer model. It was also observed that net apoptotic (6.25-fold, P≤0.005) and necrotic indexes (3.5-fold, P≤0.05) were comparatively higher in CHNP-SR9 when compared to void CHNP and CHNP-SR9 internalized more in cancer stem cells (4.5-fold, P≤0.005). We concluded that nanoformulation of SR9 did not reduce its therapeutic potential; however, nanoformulation provided SR9 with enhanced stability and better bioavailability. Our study presents a highly tumor-specific protein-based cancer therapy that has several advantages over the normally used chemotherapeutics.

The local power of the CADF and CIPS panel unit root tests

Very little is known about the local power of second generation panel unit root tests that are robust to cross-section dependence. This article derives the local asymptotic power functions of the cross-section argumented Dickey–Fuller Cross-section Augmented Dickey-Fuller (CADF) and CIPS tests of Pesaran (2007), which are among the most popular tests around.

Exploring spatiotemporal trends in commercial fishing effort of an abalone fishing zone: a GIS-based hotspot model

Assessing patterns of fisheries activity at a scale related to resource exploitation has received particular attention in recent times. However, acquiring data about the distribution and spatiotemporal allocation of catch and fishing effort in small scale benthic fisheries remains challenging. Here, we used GIS-based spatio-statistical models to investigate the footprint of commercial diving events on blacklip abalone (Haliotis rubra) stocks along the south-west coast of Victoria, Australia from 2008 to 2011. Using abalone catch data matched with GPS location we found catch per unit of fishing effort (CPUE) was not uniformly spatially and temporally distributed across the study area. Spatial autocorrelation and hotspot analysis revealed significant spatiotemporal clusters of CPUE (with distance thresholds of 100's of meters) among years, indicating the presence of CPUE hotspots focused on specific reefs. Cumulative hotspot maps indicated that certain reef complexes were consistently targeted across years but with varying intensity, however often a relatively small proportion of the full reef extent was targeted. Integrating CPUE with remotely-sensed light detection and ranging (LiDAR) derived bathymetry data using generalized additive mixed model corroborated that fishing pressure primarily coincided with shallow, rugose and complex components of reef structures. This study demonstrates that a geospatial approach is efficient in detecting patterns and trends in commercial fishing effort and its association with seafloor characteristics.

Innovative delivery mechanisms: Australian aid partnership with churches in Papua New Guinea

The Australian Aid programme is currently valued at AUD5 billion. The majority of this aid flows to the Asia Pacific region with Papua New Guinea and Indonesia being the largest recipients. In addition to traditional delivery mechanisms-bilateral and multilateral-the Australian Government has piloted a small partnership activity with Churches in Papua New Guinea. This paper will consider this model and the benefit it brings. Possible extension of this partnership model to non-Christian religious faiths in other countries, such as Islamic nationwide organisations in Indonesia, is also discussed.

EpCAM aptamer-mediated survivin silencing sensitized cancer stem cells to doxorubicin in a breast cancer model

Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology. Here we report that survivin, a key protein implicated in drug resistance, is overexpressed in cancer stem cell pool of doxorubicin-resistant breast cancer cells. Moreover, by utilising an active targeting system consisting of an RNA aptamer targeted against the epithelial cell adhesion molecule and a Dicer substrate survivin siRNA, we could deliver a high dose of the siRNA to cancer stem cells in xenograft tumours. Importantly, silencing of survivin with this aptamer-siRNA chimera in cancer stem cell population led to the reversal of chemoresistance, such that combined treatment with low dose of doxorubicin inhibited stemness, eliminated cancer stem cells via apoptosis, suppressed tumour growth, and prolonged survival in mice bearing chemoresistant tumours. This strategy for in vivo cancer stem cell targeting has wide application for future effective silencing of anti-death genes and in fact any dysregulated genes involved in chemoresistance and tumour relapse.

A GARCH model for testing market efficiency

In this paper we propose a generalised autoregressive conditional heteroskedasticity (GARCH) model-based test for a unit root. The model allows for two endogenous structural breaks. We test for unit roots in 156 US stocks listed on the NYSE over the period 1980 to 2007. We find that the unit root null hypothesis is rejected in 40% of the stocks, and only in four out of the nine sectors the null is rejected for over 50% of stocks. We conclude with an economic significance analysis, showing that mostly stocks with mean reverting prices tend to outperform stocks with non-stationary prices.

Social presence – connecting pre-service teachers as learners using a blended learning model

The national reform agenda for early childhood education and care across Australia has led to an increased demand for qualified early childhood teachers. In response, universities have developed innovative approaches in delivering early childhood teacher educa tion courses designed to support existing diploma qualified educators to gain their teaching qualifications. One such course at a major Australian University incorporated a flexible multi-modal option of study which included community -based, on line e-learning and face -to- face intensive tutorials. This paper reports on a study examining the outcomes for students undertaking their studies using this course delivery mode. The study sought to examine the students’ perceptions of the efficacy of the teaching and learning approach in meeting their learning needs, and the factors that were most influential in informing these perceptions. The findings indicated that it was the inclusion of contact and a social presence in the online learning environment which was most influential.