Characterisation of Polycaprolatone-Based Scaffold Plus Recombinant Human Morphogenetic Protein - 2 (RHBMP-2) in an Ovine Thoracic Spine Model

This thesis represents a step forward in the development of a pre-clinical model investigating a suitable substitute for host bone for use in human spinal fusion. By way of an animal model, it examines the biological performance of a novel bone graft substitute comprised of a combination of a custom-designed biodegradable material and biologics.

Does it matter whether friends, parents, or peers drink walk? Identifying which normative influences predict young pedestrian's decisions to walk while intoxicated

Drink walking, that is walking in a public place while intoxicated, is associated with increased risk of injury and fatality. Young people and males are especially prone to engaging in this behaviour, yet little is known about the factors associated with individual’s decisions to drink walk. The present research explores the role of different normative influences (friendship group norm, parent group norm, university peer group norm) and perceived risk, within an extended theory of planned behaviour (TPB) framework, in predicting young people’s self-reported drink walking intentions. One hundred and eighteen young people (aged 17-25 years) completed a survey including sociodemographic measures and extended TPB measures related to drink walking. Overall the extended TPB explained 72.8% of the variance in young people’s intentions to drink walk in the next six months with attitude, perceived behavioural control, friendship group norm, and gender (male) emerging as significant predictors. Males, as compared with females, had higher intentions to drink walk and lower perceptions of risk regarding drink walking. Together, these findings provide a clearer indication of the salient normative influences and gender differences in young pedestrian’s decisions to walk while intoxicated. Such findings can be used to inform future interventions designed to reduce injuries and fatalities associated with drink walking.

Young novice drivers and the risky behaviours of parents and friends during the Provisional (intermediate) licence phase : a brief report

Purpose While there is research indicating that many factors influence the young novice driver's increased risk of road crash injury during the earliest stages of their independent driving, there is a need to further understand the relationship between the perceived risky driving behaviour of parents and friends and the risky behaviour of drivers with a Provisional (intermediate) licence. Method As part of a larger research project, 378 drivers aged 17–25 years (M = 18.22, SD = 1.59, 113 males) with a Provisional licence completed an online survey exploring the perceived riskiness of their parents’ and friends’ driving, and the extent to which they pattern (i.e. base) their driving behaviour on the driving of their parents and friends. Results Young drivers who reported patterning their driving on their friends, and who reported they perceived their friends to be risky drivers, reported more risky driving. The risky driving behaviour of young male drivers was associated with the perceived riskiness of their fathers’ driving, whilst for female drivers the perceived riskiness of their mothers’ driving approached significance. Conclusions The development and application of countermeasures targeting the risky behaviour of same-sex parents appears warranted by the robust research findings. In addition, countermeasures need to encourage young people in general to be non-risky drivers; targeting the negative influence of risky peer groups specifically. Social norms interventions may minimise the influence of potentially-overestimated riskiness.

Parents’ perception about children’s academic stress and child care related issues

The present study intends to understand the parents' perception about children's academic stress and child care related issues. A group of 139 parents, 68 fathers and 71 mothers, participated in the study voluntarily and they were selected following convenience sampling technique. In order to achieve the objective of the study, a specially designed semi-structured questionnaire was used. Findings disclosed that about one-third of the fathers (29.4%) and one-tenth of the mothers (9.9%) frankly admitted that they could not provide quality care and guidance to their children and in this regard significant difference was observed between fathers and mothers (p<.05). More than four-fifth of the parents stated that they should be friendly with their children so that children feel comfortable to share their personal issues with them. More than one-fifth fathers (27.9%) and one-fourth mothers (16.9%) applied corporal punishment as they believed it is necessary to discipline them and/or for better academic performance.

Safety and efficacy of the combination of trastuzumab with docetaxel for HER2-positive women with advanced breast cancer : a review of the existing clinical trials and results of the expanded access programme in the UK

Trastuzumab is a humanised monoclonal antibody against the extracellular domain of HER2 (human epidermal growth factor receptor-2) that is overexpressed in about 25% of human breast cancers. It has shown clinical benefit in HER2-positive breast cancer cases when used alone or in combination with chemotherapy. Trastuzumab increases the response rate to chemotherapy and prolongs survival when used in combination with taxanes. In this article, we review the clinical trials where trastuzumab has been administered together with docetaxel, and we present the results of the trastuzumab expanded access programme (EAP) in the UK. Combination of trastuzumab with docetaxel results in similar response rates and time-to-progression with the trastuzumab/paclitaxel combinations. The toxicity of the combination and the risk of heart failure are low. The clinical data for the docetaxel/trastuzumab combination indicate a favourable profile from both the efficacy and the safety point of view and confirm the feasibility and safety of trastuzumab administration both as monotherapy and in combination with docetaxel. © 2004 Blackwell Publishing Ltd.

Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX) : an open-label randomised phase III trial

Background: Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. Methods: In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (≥18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m 2 intravenous infusion on day 1, and vinorelbine 25 mg/m 2 intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m 2 intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m 2 over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11·3 months vs 10·1 months; hazard ratio for death 0·871 [95% CI 0·762-0·996]; p=0·044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3). Interpretation: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. Funding: Merck KGaA. © 2009 Elsevier Ltd. All rights reserved.

EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier Ltd.

Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer

Background: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. Patients and methods: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m2, day 1) and vinorelbine (25 mg/m2 on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m, followed by 250 mg/m2 weekly thereafter). Results: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. Conclusion: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone. © 2007 European Society for Medical Oncology.

Experience, recursive awareness and understanding in autism spectrum disorders : insights of parents and teachers in Singapore

Provision of an individually responsive education requires a comprehensive understanding of the inner worlds of learners, such as their feelings and thoughts. However, this is difficult to achieve when learners, such as those with Autism Spectrum Disorders (ASD) and cognitive difficulties, have problems with communication. To address this issue, the current exploratory descriptive study sought the views of 133 Singaporean parents and teachers of school-age learners with ASD and cognitive difficulties regarding the inner experience of their children and students. The findings highlight the variety of abilities and difficulties found in how these learners experience their own mental states and understand those of others. These abilities and difficulties are characterized according to type of mental state and analysed in line with three qualia, those of experience, recursive awareness and understanding. The findings indicate that learners show a greater awareness of their own mental states compared to their ability to understand these same mental states in others. Educational implications are discussed.

Fever management in children : Vietnamese parents' and paediatric nurses' knowledge, beliefs and practices

This thesis comprised two studies: an exploratory study and a cross-sectional survey, guided by the Theory of Planned Behaviour. It explored parents' and paediatric nurses' knowledge, beliefs and practices about fever management in Vietnam. The research highlights the determinants of parents' and nurses' intentions to manage childhood fever which can be targeted for future interventions to integrate latest evidence-based practices.

Physical activity promotion as a school priority : what do parents think?

The demands and responsibilities placed on schools in contemporary education systems are vast. However, with growing obesity levels and physical inactivity, the prevention of chronic disease has focused on youth populations, with schools playing the focal educative asset in this strategy. Parents play a decisive role in their child’s educational setting, and as fee and tax payers, are ultimately a consumer. Parents (82 males and 208 females) of secondary school children were recruited from three private (n=151) and two government schools (n=150) in Brisbane, Australia. The mean (standard deviation) age was 44.57 (6.21) years. Participants responded to a series of questions about physical activity at their child’s school, in addition to completing the International Physical Activity Questionnaire. Data were analysed using descriptive statistics, frequency distributions and logistic regressions. Parents were deemed sufficiently physically active if they participated in at least 150 minutes of moderate-to-vigorous physical activity per week. Overall, 83 (59.7%) parents from private and 60 (50.8%) parents from government schools were deemed sufficiently physically active. Concerning whether physical activity promotion should be a priority at their child’s school, 111 (73.5%) parents from private schools either agreed or strongly agreed, as opposed to 97 (64.7%) parents from government schools. Logistic regressions indicated that the concept of physical activity promotion being prioritised at schools was dependent on whether the child attended a private school (OR =1.34, z = 2.30, p = 0.02), and whether the participant was sufficiently active (OR =.71, z = -2.48, p = 0.01). Physical activity promotion within schools may provide substantial future benefits on a population scale. The demands on schools may need to be addressed to meet the needs of students and the desires of their parents.

The construction of parents as learners about pre-school children’s development

The concept of the lifelong learner—the idea that people should be active learners throughout the lifespan—has since the 1990s gained importance in public policy. Governments in relatively wealthy countries have made the argument that the economic future of nations is tied to the ongoing participation of citizens in learning opportunities that will assist them to participate fully in society and increase their chances of employment in changing workforce conditions. More recently, policy attention has focused on the other end of the lifespan, the first years of life. With the early years now recognised as crucial for later educational success, policy attention has also focused on the importance of parenting in the early years. In the UK and Australia, for example, the effects of state interventions to facilitate ‘good parenting’ and pre-school children’s ‘readiness’ for formal schooling have been felt in a range of settings including community health services, the home and the pre-school (Gillies, 2005; Nichols & Jurvansuu, 2008; Millei & Lee, 2007; Vincent, Ball & Braun, 2010). In Australia, government policy has explicitly proposed a model of parenting as a learning process, and has urged people to cultivate their identities as learners in order to carry out their responsibilities as parents. In part the policy objectives have been to support parents to ensure that all children get a healthy and successful start to life...

The impact on clinical practice of a postgraduate clinical pharmacy programme, incorporating competency-based performance evaluation

Background A goal of the postgraduate clinical pharmacy programme (PGCPP) at the University of Queensland is to enhance clinical practice. Aims To evaluate student perceptions of the impact of the PGCPP on practice and the inclusion of a competency-based performance evaluation as a formative component of the curriculum. Method In 2010, students completed a questionnaire to evaluate the impact of the PGCPP. In 2011, formative competency-based performance evaluations were conducted as a component of the course and the questionnaire was repeated. Responses, competency ratings and evaluation feedback were collated. Data were analysed using descriptive statistics. Results 51/57 (89%) of students completed the questionnaire in 2010 and 2011. Over 90% of students agreed or strongly agreed that the PGCPP enhanced practice, knowledge, confidence and contribution to patient care. Responses were similarly positive after the inclusion of the performance evaluation. Conclusion This study demonstrated that the PGCPP is achieving the goal of enhancing the practice of pharmacists.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Purpose The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). Patients and Methods In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). Results A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Conclusion Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.