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.

Expanded scope roles in primary health – what makes them work?

Introduction The demand for better integration between primary and secondary healthcare frequently leads to discussion about expanded scope of practice for nursing, paramedic and allied health professionals and the role these clinicians could play in facilitating improved access to timely and appropriate healthcare. From workforce perspective, expanded scope of practice has also been advocated as a mean of fostering workforce retention. Models of expanded scope roles in nursing and paramedicine have been trialled nationally and internationally in both acute and community care settings. Where they have been successful, trials have resulted in reduction in hospital presentation and admission; improved patient access and timeliness; and patient satisfaction. This paper will examine the characteristics of successful expanded scope programs. Method Exploratory case-study analysis of successful integration of expanded health care roles across primary healthcare settings in rural Australia. Results & Conclusions One size does not fill all. Successful models of integrated expanded health care roles in primary health care settings are built on stakeholder’s capacity and preference; community need; and political will. Collaborative, congruent, multi-disciplinary care teams that prioritise patient-centred care within a dynamic primary care setting have merit and are more likely to foster flexibility and sustainability.

The Limited Benefit of Prison in Controlling Crime : On the Threshold of a Political Shift

In 2012 the New Zealand government spent $3.4 billion, or nearly $800 per person, on responses to crime via the justice system. Research shows that much of this spending does little to reduce the changes of re-offending. Relatively little money is spent on victims, the rehabilitation of offenders or to support the families of offenders. This book is based on papers presented at the Costs of Crime forum held by the Institute of Policy Studies in February 2011. It presents lessons from what is happening in Australia, Britain and the United States and focuses on how best to manage crime, respond to victims, and reduce offending in a cost-effective manner in a New Zealand context. It is clear that strategies are needed that are based on better research and a more informed approach to policy development. Such strategies must assist victims constructively while also reducing offending. Using public resources to lock as many people in our prisons as possible cannot be justified by the evidence and is fiscally unsustainable; nor does such an approach make society safer. To reduce the costs of crime we need to reinvest resources in effective strategies to build positive futures for those at risk and the communities needed to sustain them.

The value of political connections : evidence from Korean chaebols

This thesis examines the value of political connections for business groups by constructing a unique dataset that allows us to identify the form and extent of the connections. Results show firms' membership to family-controlled business groups (South Korean chaebol) play a key role in determining the value of political connections. Politically connected chaebol firms experience substantial price increases following the establishment of the connection than other firms, but the reverse is found for other (non-family-controlled) connected business groups.

IT governance stability in a political changing environment : exploring potential impacts in the public sector

Public sector organisations (PSOs) operate in information-intensive environments often within operational contexts where efficiency is a goal. What's more, the rapid adoption of IT is expected to facilitate good governance within public sector organisations but it often clashes with the bureaucratic culture of these organisations. Accordingly, models such as IT Governance (ITG) and government reform -in particular the new public management (NPM)- were introduced in PSOs in an effort to address the inefficiencies of bureaucracy and under performance. This work explores the potential effect of change in political direction and policy on the stability of IT governance in Australian public sector organisations. The aim of this paper is to examine implications of a change of government and the resulting political environment on the effectiveness of the audit function of ITG. The empirical data discussed here indicate that a number of aspects of audit functionality were negatively affected by change in political direction and resultant policy changes. The results indicate a perceived decline in capacity and capability which in turn disrupts the stability of IT governance systems in public sector organisations.

First full-scale trials of pebble matrix filtration

Protecting slow sand filters from high turbidity waters by pre-treatment using Pebble Matrix Filtration (PMF) has been studied in the laboratory at University College London followed by pilot field trials in Papua New Guinea and Serbia. Subsequently, the construction of two full-scale PMF units, one out of concrete (4.8m x4.8m x 3.0m high) and the other using pre-cast Ferro-cement panels (900mm x 1600mm x 20mm thick) with an effective diameter of 4.7m and 3m height, and the combined effective plan area of 40 m2 was completed to protect an existing Slow Sand Filter system at the National Water Supply Drainage Board (NWSDB) in Sri Lanka. Although the plant was completed in April 2008 due to some major repairs to address some leaks and other construction defects in both filters, monitoring was intermittent until November 2008. The results on the plant performance are presented here along with some of the construction problems encountered during the project.

Registration of clinical trials: Challenges for global regulation

In 2004 the International Committee of Medical Journal Editors (ICMJE) issued a statement indicating that from 1 July 2005 registration in a publicly accessible trials registry would be a condition of publication in an ICMJE member journal. The World Health Organisation is coordinating the International Clinical Trials Registry Platform (ICTRP) as a means of providing a standardised framework for registration. This article considers the practical challenges and opportunities that arise from these developments and considers the relevance of trial registration for women and minorities and for developing countries.

National and state-level politics on social media : Twitter, Australian political discussions, and the online commentariat

This paper examines the use of Twitter for long-term discussions around Australian politics, at national and state levels, tracking two hashtags during 2012: #auspol, denoting national political topics, and #wapol, which provides a case study of state politics (representing Western Australia). The long-term data collection provides the opportunity to analyse how the Twitter audience responds to Australian politics: which themes attract the most attention and which accounts act as focal points for these discussions. The paper highlights differences in the coverage of state and national politics. For #auspol, a small number of accounts are responsible for the majority of tweets, with politicians invoked but not directly contributing to the discussion. In contrast, #wapol stimulates a much lower level of tweeting. This example also demonstrates that, in addition to citizen accounts, traditional participants within political debate, such as politicians and journalists, are among the active contributors to state-oriented discussions on Twitter.

Essays in the political economy of voting and reforms

This thesis presents four essays in the political economy of elections and reforms. The first study exploits discontinuities around school entry cut-off dates to show that early childhood conditions can impact the probability to become a top-flight politician. The second study provides empirical estimates of the effect of sequential voting on turnout and bandwagon voting outside the laboratory. The third work describes a novel nonparametric strategy to identify tactical voting patterns directly from balloting results using British election data. Finally, a study is put forward that examines the political feasibility of reforms.

BRAF inhibitors : from the laboratory to clinical trials

BRAF is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Due to the commonality of BRAF mutations, a number of BRAF inhibitors have been developed as tools in the management of patients with cancers dependent on the action of mutant BRAF to drive cellular proliferation. In this review, we examine the current state of clinical trials and laboratory research concerning BRAF inhibitors in development and available for clinical use. We contrast the effectiveness of type-I and type-II BRAF inhibitors, the former typically showing much more restricted inhibitory selectivity and greater patient response rates.

Institutional investors, political connections and analyst following in Malaysia

We examine the association between institutional ownership, political connections, and analyst following in Malaysia from 1999 to 2009. Based on 940 firm-year observations, we document a positive relation between institutional ownership, particularly by Employees Provident Fund (EPF), and analyst following, thus supporting the governance role that institutional investors play in promoting corporate transparency. However, there is no evidence that political connections matter to analyst following. The monitoring role of institutional investors, including EPF, does not appear to be any different between politically connected and non-connected firms.

Clinical trials in pediatrics

“Children are not little adults.” Almost all aspects of children's health including clinical trials and drug development are poor cousins of adult health. Over the years, pediatricians worldwide caution against blind extrapolation of adult data to children as it may result in considerable harm [1,2]. Also, it is increasingly recognized that the roots of many chronic diseases in adulthood stem from childhood and tackling health issues in children lead to improved health in adults [3,4]. Furthermore, investment in early childhood has long-term benefits in adults not only in health but also in other aspects of life such as education and crime reduction [4,5]. Arguably, health at birth is the single most important predictor of health in adulthood as the inequality of an infant at birth has intergenerational effects [5]. The Carolina Abecedarian Project showed that early childhood programs that are of high quality result in substantial societal benefits (e.g., reduction of crime, increased earnings, better education) [4,5]. A recent publication from this project found that this benefit also translated into improved adult health outcomes [4]. In a randomized trial, Campbell and colleagues described that disadvantaged children who were randomized to the intervention group (early education, health screenings and nutrition program) had significantly lower rates of metabolic syndrome, obesity and hypertension, when aged in their mid-30s, compared with the control group [4]...

Exploring the effect of political risks in large infrastructure projects in politically unstable countries using a probabilistic modelling approach

This research aims to explore and identify political risks on a large infrastructure project in an exaggerated environment to ascertain whether sufficient objective information can be gathered by project managers to utilise risk modelling techniques. During the study, the author proposes a new definition of political risk; performs a detailed project study of the Neelum Jhelum Hydroelectric Project in Pakistan; implements a probabilistic model using the principle of decomposition and Bayes probabilistic theorem and answers the question: was it possible for project managers to obtain all the relevant objective data to implement a probabilistic model?

Engaging, persuading, and entertaining citizens : mediatization and the Australian political public sphere

This paper draws upon public sphere theories and the “mediatization of politics” debate to develop a mapping of the Australian political public sphere, with particular reference to television. It discusses the concept of a “political public sphere,” and the contribution of both non-traditional news media genres, such as satirical television and infotainment formats, to an expanded conception of the political public sphere. It considers these questions in the context of two case studies: the Q&A program on the Australian Broadcasting Corporation (ABC), and its uses of social media and interactive formats to engage citizens, and the comedy program Gruen Nation, also on the ABC, which analyzed the use of political advertising to persuade citizens during the 2013 Australian Federal election.

DroplIT, an improved image analysis method for droplet identification in high-throughput crystallization trials

The application of robotics to protein crystallization trials has resulted in the production of millions of images. Manual inspection of these images to find crystals and other interesting outcomes is a major rate-limiting step. As a result there has been intense activity in developing automated algorithms to analyse these images. The very first step for most systems that have been described in the literature is to delineate each droplet. Here, a novel approach that reaches over 97% success rate and subsecond processing times is presented. This will form the seed of a new high-throughput system to scrutinize massive crystallization campaigns automatically. © 2010 International Union of Crystallography Printed in Singapore-all rights reserved.