Randomised controlled trials and 'unexpected' adverse events associated with newly released drugs : improvements in pharmacovigilance systems are necessary for real-time identification of patient safety risks

Adverse drug events are one of the major causes of morbidity in developed countries, yet the drugs involved in these events have been trialled and approved on the basis of randomised controlled trials (RCTs), regarded as the study design that will produce the best evidence.

Though the focus on adverse drug events has been primarily on processes and outcomes associated with the use of these approved drugs, attention needs to be directed to the way in which the RCT study design is structured. The implementation of controls to achieve internal validity in RCTs may be the very controls that reduce external validity, and contribute to the levels of adverse drug events associated with the release of a new drug to the wider patient population.

An examination of these controls, and the effects they can have on patient safety, underscore the importance of knowing about how the clinical trials of a drug are undertaken, rather than relying only on the recorded outcomes.

As the majority of new drugs are likely to be prescribed to older patients who have one or more comorbidities in addition to that targeted by a new drug, and as the RCTs of those drugs typically under-represent the elderly and exclude patients with multiple comorbidities, timely assessment of drug safety signals is essential.

It is unlikely that regulatory jurisdictions will undertake a reassessment of safety issues for drugs that are already approved. Instead, reliance has been placed on adverse drug event reporting systems. Such systems have a very low reporting rate, and most adverse drug events remain unreported, to the eventual cost to patients and healthcare systems.

This makes it essential for near real-time systems that can pick up safety signals as they occur, so that modifications to the product information (or removal of the drug) can be implemented.

Global and threshold-free transcriptional regulatory networks reconstruction through integrating ChIP-Chip and expression data

Inferring transcriptional regulatory networks from high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed TReNGO (Transcriptional Regulatory Networks reconstruction based on Global Optimization), a global and threshold-free algorithm with simulated annealing for inferring regulatory networks by the integration of ChIP-chip and expression data. Superior to existing methods, TReNGO was expected to find the optimal structure of transcriptional regulatory networks without any arbitrary thresholds or predetermined number of transcriptional modules (TMs). TReNGO was applied to both synthetic data and real yeast data in the rapamycin response. In these applications, we demonstrated an improved functional coherence of TMs and TF (transcription factor)- target predictions by TReNGO when compared to GRAM, COGRIM or to analyzing ChIP-chip data alone. We also demonstrated the ability of TReNGO to discover unexpected biological processes that TFs may be involved in and to also identify interesting novel combinations of TFs.

Stage of perinatal development regulates skeletal muscle mitochondrial biogenesis and myogenic regulatory factor genes with little impact of growth restriction or cross-fostering

Foetal growth restriction impairs skeletal muscle development and adult muscle mitochondrial biogenesis. We hypothesized that key genes involved in muscle development and mitochondrial biogenesis would be altered following uteroplacental insufficiency in rat pups, and improving postnatal nutrition by cross-fostering would ameliorate these deficits. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed on day 18 of gestation. Males and females were investigated at day 20 of gestation (E20), 1 (PN1), 7 (PN7) and 35 (PN35) days postnatally. A separate cohort of Control and Restricted pups were cross-fostered onto a different Control or Restricted mother and examined at PN7. In both sexes, peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), cytochrome c oxidase subunits 3 and 4 (COX III and IV) and myogenic regulatory factor 4 expression increased from late gestation to postnatal life, whereas mitochondrial transcription factor A, myogenic differentiation 1 (MyoD), myogenin and insulin-like growth factor I (IGF-I) decreased. Foetal growth restriction increased MyoD mRNA in females at PN7, whereas in males IGF-I mRNA was higher at E20 and PN1. Cross-fostering Restricted pups onto a Control mother significantly increased COX III mRNA in males and COX IV mRNA in both sexes above controls with little effect on other genes. Developmental age appears to be a major factor regulating skeletal muscle mitochondrial and developmental genes, with growth restriction and cross-fostering having only subtle effects. It therefore appears that reductions in adult mitochondrial biogenesis markers likely develop after weaning.

Regulatory theory insights into the past, present and future of general purpose water accounting standard setting

Purpose – Accounting and water industry experts are developing general-purpose water accounting (GPWA) to report information about water and rights to water. The system has the potential to affect water policies, pricing and management, and investment and other decisions that are affected by GPWA report users' understanding of water risks faced by an entity. It may also affect financial returns to accounting and auditing firms and firms in water industries. In this paper the authors aim to examine the roles of the accounting profession, water industries and other stakeholders in governing GPWA. Recognising that the fate of GPWA depends partly upon regulatory power and economics, they seek to apply regulatory theories that explain financial accounting standards development to speculate about the national and international future of GPWA.

Design/methodology/approach – Official documents, internal Water Accounting Standards Board documents and unstructured interviews underpin the authors' analysis.

Findings – The authors speculate about the benefits that might accrue to various stakeholder groups from capturing the GPWA standard-setting process. They also suggest that internationally, water industries may dominate early GPWA standards development in the public interest and that regulatory capture by accounting or water industry professionals will not necessarily conflict with public interest benefits.

Practical implications – Accounting for water can affect allocations of environmental, economic, social and other resources; also, accounting and water industry professional standing and revenues. In this paper the authors identify factors influencing GPWA standards and standard-setting institutional arrangements, and thereby these resource allocations. The paper generates an awareness of GPWA's emergence and practical implications.

Originality/value – This is an early study to investigate water accounting standard-setting regulatory influences and their impact.

Designing online role plays with a focus on story development to support engagement and critical learning for higher education students

Online role plays, as they are designed for use in higher education in Australia and internationally, are active and authentic learning activities (Wills, Leigh & Ip, 2011). In online role plays, students take a character role in developing a story that serves as a metaphor for real-life experience in order to develop a potentially wide range of subject-related and generic learning outcomes. The characteristics of these stories are rarely considered as factors in the design―and success―of these activities. The unspoken cultural assumptions, norms and rules in the stories that impact on the meanings students make from their experiences are also rarely scrutinised in the online role play literature. This paper presents findings from a case study of an asynchronous text-based online role play involving politics and journalism students from three Australian universities. The findings highlight the centrality of students’ collaborative story-building activity to their engagement and learning, including their development of critical perspectives. The study underlines the importance of certain aspects of the role play's design to support students' story-building activity.

Co-prescription of medication for bipolar disorder and diabetes mellitus : a nationwide population based study with focus on gender differences

Background
Studies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation.
Methods
The Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regression
Results
We found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population.
Conclusions
This study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men.

Forces : teaching ideas with a representational focus

These teaching notes were generated from an Australian Research Council (ARC)
research project titled ‘The Role of Representation in Learning Science’ in which
the topic of Forces was taught to Year 7 students through the adoption of a representation construction approach. A description of several of the activities that were undertaken is given as well as examples of students’ work. Insights into the representation construction apporach that was adopted by the teachers are also provided.

Ideas about matter : teaching ideas with a representational focus

These teaching notes were generated from an Australian Research Council (ARC)
research project titled ‘The Role of Representation in Learning Science’ in which
the topic of Ideas about Matter was taught to Year 7 students through the adoption of a representation construction approach. A description of several of the activities that were undertaken is given as well as examples of students’ work. Insights into the representation construction approach that was adopted by the teachers are also provided.

Simulated jury decision making in online focus groups

Purpose – A significant issue in jury research has been the use of individual jurors to analyse jury decision-making. This paper aimed to examine the applicability of computer-mediated communication to a mock jury deliberation study.

Design/methodology/approach – Groups of three to five Australian residents anonymously attended a secure chat room and participated in a semi-structured discussion about a simulated child sexual assault scenario. Deliberation transcripts were analysed thematically using NVivo. A hermeneutic framework was used to analyse the deliberation transcripts.

Findings – Five interrelated themes were revealed, each reflecting the tools online juries used to communicate, create meaning, and arrive at a verdict. Electronic jury deliberation promoted an understanding of how people make sense of child sexual assault cases in Australia today.

Originality/value – This study advanced the understanding of online decision making in a child sexual assault scenario. It demonstrated that knowledge of how juries deliberate and create meaning could improve our understanding of how verdicts are achieved. Electronic mock juries are a valuable adjunct to traditional jury deliberation studies because they are cost effective, time efficient, and offer wider recruitment opportunities.

Exhibit review : Focus on strangers: photo albums of World War II, Stadtmuseum, Jena, Germany, 2011

Focus on Strangers: Photo Albums of World War II is based on a collaborative research project conducted by two German universities (Carl von Ossietzky Universität Oldenburg and Friedrich Schiller Universität Jena) and was conceptualized in cooperation with four German city museums in Oldenburg, Munich, Frankfurt, and Jena. While the exhibition continues a tradition of museological projects examining Germany’s war history, such as the Wehrmachtsaustellung, which provoked fi erce public debate, Focus on Strangers moves beyond most conventional approaches in a signifi cant way. Th e exhibition pays tribute to the recent development in which private traces of memory have become part of the public perception of history, in this case the history of World War II.