A road safety strategy for Norfolk Island, an Australian external territory

Norfolk Island is an Australian external territory in Oceania. The significant road safety reforms in Australia from the 1970s onward bypassed the island, and most road safety ‘silver bullets’ adopted in other Australian jurisdictions were not introduced. While legislative amendments in 2010 introduced mandatory seat belt wearing for vehicle occupants on Norfolk Island, other critical issues face the community including drink driving by residents and visitors, occupant protection for vehicle passengers, and the provision of a more protective road environment. The release of the first Norfolk Island road safety strategy 2014-2016 proposed, inter alia: • a lower BAC of 0.05 and the introduction of compulsory driver alcohol and drug testing by police; • targeted enforcement of occupant protection for vehicle passengers, particularly for passengers riding on vehicle tray backs; • education interventions to challenge values held by some members of the community that support unsafe road use; • ensuring that driver information, training and testing is adequate for all drivers; • identification and rectification of hazardous roadside infrastructure, particularly barrier protection at “high drop locations” within the road network; and • developing a specification for vehicle standards for vehicles imported into Norfolk Island. Norfolk Island is engaging in a process of integration with the Australian community, and wider issues relating to funding and resources have impacted on the implementation of the road safety strategy. The response to the strategy will be discussed, particularly in terms of current attempts to address drink driving and the provision of a safer road environment.

Prostate cancer organoids: A potential new tool for testing drug sensitivity

Recent technical advances have enabled for the first time, reliable in vitro culture of prostate cancer samples as prostate cancer organoids. This breakthrough provides the significant possibility of high throughput drug screening covering the spectrum of prostate cancer phenotypes seen clinically. These advances will enable precision medicine to become a reality, allowing patient samples to be screened for effective therapeutics ex vivo, with tailoring of treatments specific to that individual. This will hopefully lead to enhanced clinical outcomes, avoid morbidity due to ineffective therapies and improve the quality of life in men with advanced prostate cancer.

Testing the effectiveness of a Practice Development intervention on changing the culture of evidence based practice in an acute care environment

In this age of evidence-based practice, nurses are increasingly expected to use research evidence in a systematic and judicious way when making decisions about patient care practices. Clinicians recognise the role of research when it provides valid, realistic answers in practical situations. Nonetheless, research is still perceived by some nurses as external to practice and implementing research findings into practice is often difficult. Since its conceptual platform in the 1960s, the emergence and growth of Nursing Development Units, and later, Practice Development Units has been described in the literature as strategic, organisational vehicles for changing the way nurses think about nursing by promoting and supporting a culture of inquiry and research-based practice. Thus, some scholars argue that practice development is situated in the gap between research and practice. Since the 1990s, the discourse has shifted from the structure and outcomes of developing practice to the process of developing practice, using a Practice Development methodology; underpinned by critical social science theory, as a vehicle for changing the culture and context of care. The nursing and practice development literature is dominated by descriptive reports of local practice development activity, typically focusing on reflection on processes or outcomes of processes, and describing perceived benefits. However, despite the volume of published literature, there is little published empirical research in the Australian or international context on the effectiveness of Practice Development as a methodology for changing the culture and context of care - leaving a gap in the literature. The aim of this study was to develop, implement and evaluate the effectiveness of a Practice Development model for clinical practice review and change on changing the culture and context of care for nurses working in an acute care setting. A longitudinal, pre-test/post-test, non-equivalent control group design was used to answer the following research questions: 1. Is there a relationship between nurses' perceptions of the culture and context of care and nurses' perceptions of research and evidence-based practice? 2. Is there a relationship between engagement in a facilitated process of Practice Development and change in nurses' perceptions of the culture and context of care? 3. Is there a relationship between engagement in a facilitated process of Practice Development and change in nurses' perceptions of research and evidence-based practice? Through a critical analysis of the literature and synthesis of the findings of past evaluations of Nursing and Practice Development structures and processes, this research has identified key attributes consistent throughout the chronological and theoretical development of Nursing and Practice Development that exemplify a culture and context of care that is conducive to creating a culture of inquiry and evidence-based practice. The study findings were then used in the development, validation and testing of an instrument to measure change in the culture and context of care. Furthermore, this research has also provided empirical evidence of the relationship of the key attributes to each other and to barriers to research and evidence-based practice. The research also provides empirical evidence regarding the effectiveness of a Practice Development methodology in changing the culture and context of care. This research is noteworthy in its contribution to advancing the discipline of nursing by providing evidence of the degree to which attributes of the culture and context of care, namely autonomy and control, workplace empowerment and constructive team dynamics, can be connected to engagement with research and evidence-based practice.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Testing a belief-based intervention encouraging sun safety among adolescents in a high risk area

Objective. To provide a preliminary test of a Theory of Planned Behavior (TPB) belief-based intervention to increase adolescents’ sun protective behaviors in a high risk area, Queensland, Australia. Methods. In the period of October-November, 2007 and May-June, 2008, 80 adolescents (14.53 ± 0.69 years) were recruited from two secondary schools (one government and one private) in Queensland after obtaining student, parental, and school informed consent. Adolescents were allocated to either a control or intervention condition based on the class they attended. The intervention comprised three, one hour in-school sessions facilitated by Cancer Council Queensland employees with sessions covering the belief basis of the TPB (i.e., behavioral, normative, and control [barrier and motivator] sun-safe beliefs). Participants completed questionnaires assessing sun-safety beliefs, intentions, and behavior pre- and post-intervention. Repeated Measures Multivariate Analysis of Variance was used to test the effect of the intervention across time on these constructs. Results. Students completing the intervention reported stronger sun-safe normative and motivator beliefs and intentions and the performance of more sun-safe behaviors across time than those in the control condition. Conclusion. Strengthening beliefs about the approval of others and motivators for sun protection may encourage sun-safe cognitions and actions among adolescents.

Assessment of function and clinical utility of alcohol and other drug web sites : an observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

I know, but I don’t care : how awareness of Queensland’s drug driving testing methods impact upon perceptions of deterrence and offending behaviours

An increasing body of research is highlighting the involvement of illicit drugs in many road fatalities. Deterrence theory has been a core conceptual framework underpinning traffic enforcement as well as interventions designed to reduce road fatalities. Essentially the effectiveness of deterrence-based approaches is predicated on perceptions of certainty, severity, and swiftness of apprehension. However, much less is known about how the awareness of legal sanctions can impact upon the effectiveness of deterrence mechanisms and whether promoting such detection methods can increase the deterrent effect. Nevertheless, the implicit assumption is that individuals aware of the legal sanctions will be more deterred. This study seeks to explore how awareness of the testing method impacts upon the effectiveness of deterrence-based interventions and intentions to drug drive again in the future. In total, 161 participants who reported drug driving in the previous six months took part in the current study. The results show that awareness of testing had a small effect upon increasing perceptions of the certainty of apprehension and severity of punishment. However, awareness was not a significant predictor of intentions to drug drive again in the future. Importantly, higher levels of drug use were a significant predictor of intentions to drug drive in the future. Whilst awareness does have a small effect on deterrence variables, the influence of levels of drug use seems to reduce any deterrent effect.

Rethinking the literacy capabilities of pre-service primary teachers in testing times

As a group of committed literacy teacher educators from five universities across three Australian states, the authors bring professional critique to the problematic issue of what counts in current and possible future measures of pre-service teachers’ literacy capacity. In times when normalising models of literacy assessment ignore innovative developments in technologies, we provide an example of what is happening at the ‘chalk-face’ of literacy teacher education. This paper describes a study that demonstrates how responsible alignment of teacher accreditation requirements with a scholarly impetus to incorporate digital literacies to prepare pre-service teachers will help address changing educational needs and practices (AITSL 2012; Gillen & Barton 2010; Hattie 2003; Johnson, Smith, Willis, Levine & Haywood 2011; Klein 2006; Masny & Cole 2012; OECD 2011).

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide : Phase I clinical trial of three dosing schedules in patients with solid malignancies

Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25 mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration. © 2006 Elsevier Ltd. All rights reserved.

Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

Background The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry. Objectives To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009. Selection criteria All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). Data collection and analysis Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one. Main results Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day). Authors' conclusions Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.

Crushed tablets : does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.