Gliptins - do they increase cardiovascular risk or benefit?

INTRODUCTION: In 2008, the US FDA required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase-4 inhibitors ('gliptins'). AREAS COVERED: The cardiovascular safety trials of saxagliptin and alogliptin have recently been published and are the subject of this evaluation. EXPERT OPINION: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53 trial and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care were both multicentre, randomised, double-blind, placebo-controlled, Phase IV clinical trials. These trials showed that saxagliptin and alogliptin did not increase the primary end point, which was a composite of cardiovascular outcomes that did not include hospitalisations for heart failure. However, saxagliptin significantly increased hospitalisation for heart failure, which was a component of the secondary end point. The effect of alogliptin on hospitalisations for heart failure has not been reported. Neither agent improved cardiovascular outcomes. As there is no published evidence of improved outcomes with gliptins, it is unclear to us why these agents are so widely available for use. We suggest that the use of gliptins be restricted to Phase IV clinical trials until such time as cardiovascular safety and benefits/superiority are clearly established

Dapagliflozin – do we need it registered for type 2 diabetes?

INTRODUCTION: Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) promote the excretion of glucose to reduce glycated hemoglobin (HbA1c) levels. Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved. AREAS COVERED: We evaluated a recent Phase III clinical trial with dapagliflozin. EXPERT OPINION: Dapagliflozin was studied as add-on therapy to sitagliptin with or without metformin, and was shown to lower HbA1c levels and body weight. The incidence of hypoglycaemia was low with dapagliflozin, but it did increase the incidence of urogenital infections. As no clear benefits have been identified for dapagliflozin over canagliflozin, which was the first gliflozin registered by the FDA, we do not fully understand why it was necessary to register dapagliflozin. Given that there are no completed cardiovascular/clinical outcome studies with dapagliflozin, and therefore no evidence of beneficial effect, it also seems premature to be using it extensively or considering it as an alternative to the clinically proven metformin.

Updates in inducible transgene expression using viral vectors : from transient to stable expression

The prospect of economically producing useful biologics in plants has greatly increased with the advent of viral vectors. The ability of viral vectors to amplify transgene expression has seen them develop into robust transient platforms for the high-level, rapid production of recombinant proteins. To adapt these systems to stably transformed plants, new ways of deconstructing the virus machinery and linking its expression and replication to chemically controlled promoters have been developed. The more advanced of these stable, inducible hyper-expression vectors provide both activated and amplified heterologous transgene expression. Such systems could be deployed in broad acre crops and provide a pathway to fully exploit the advantages of plants as a platform for the manufacture of a wide spectrum of products.

"Nursing is no place for men" ― A thematic analysis of male nursing students experiences of undergraduate nursing education

Background: Surprisingly, opinion about whether men are suitable within the profession continues to be a divided issue. Men enter the profession for a multitude of reasons, yet barriers whether emotional, verbal or sexual are still present. Aim: The aim of this study was to examine the experience of men “training” to be registered nurses within a regional New Zealand context. Design: A Narrative Analysis approach was used. Participants: Five New Zealand men currently undertaking their bachelor of nursing degree at a regional tertiary institute were interviewed as to their experiences of what it meant to be a man in “training”. Method: A thematic analysis was undertaken and guided by an understanding of the way personal narratives informs the human sciences especially within the context of nursing praxis. Four key themes were identified. Results: Four key themes were identified: A career with flexibility and promise; perceived gender inequality in providing care; developing professional boundaries with female colleagues and being unique has its advantages. Conclusion: The men in this study were attracted to the profession by career stability and advancement; the opportunities for travel also figured highly. At times they felt excluded and marginalised because of their minority status within their group and the feminine nature of the curriculum. The men attempted to dispel the myth around male nurse sexual stereotypes. Some of the students behaved in a manner to exert their heterosexualness. The students in this study sensed their vulnerability in choosing nursing as a career. However, all the participants saw nursing as viable and portable career in terms of advancement and travel.

Audit pricing and product differentiation in small private firms : evidence from Thailand

Purpose – There is limited evidence on how differences in economic environments affect the demand for and supply of auditing. Research on audit pricing has mainly focused on large client markets in developed economies; in contrast, the purpose of this paper is to focus on the small client segment in the emerging economy of Thailand which offers a choice between auditors of two different qualities. Design/methodology/approach – This paper is based on a random stratified sample of small clients in Thailand qualifying for audit exemption. The final sample consists of 1,950 firm-year observations for 2002-2006. Findings – The authors find evidence of product differentiation in the small client market, suggesting that small firms view certified public accountants as superior and pay a premium for their services. The authors also find that audit fees have a positive significant association with leverage, metropolitan location and client size. Audit risk and audit opinion are not, however, significantly associated with audit fees. Furthermore, the authors find no evidence that clients whose financial year ends in the auditors’ busy period pay significantly higher audit fees, and auditors engage in low-balling on initial engagements to attract audit clients. Research limitations/implications – The research shows the importance of exploring actual decisions regarding audit practice and audit pricing in different institutional and organizational settings. Originality/value – The paper extends the literature from developed economies and large/listed market setting to the emerging economy and small client market setting. As far as the authors are aware, this is the first paper to examine audit pricing in the small client market in an emerging economy.

Defining a ‘democratic elite’ : key media in the battle for social responsibility

This paper offers a definition of elite media arguing their content focus will sufficiently meet social responsibility needs of democracy. Its assumptions come from the Finkelstein and Leveson Inquiries and regulatory British Royal Charter (2013). These provide guidelines on how media outlets meet ‘social responsibility’ standards, e.g. press has a ‘responsibility to be fair and accurate’ (Finkelstein); ethical press will feel a responsibility to ‘hold power to account’ (Leveson); news media ‘will be held strictly accountable’ (RC). The paper invokes the British principle of media opting-in to observe standards, and so serve the democracy. It will give examples from existing media, and consider social responsibility of media more generally. Obvious cases of ‘quality’ media: public broadcasters, e.g. BBC, Al-Jazeera, and ‘quality’ press, e.g. NYT, Süddeutscher Zeitung, but also community broadcasters, specialised magazines, news agencies, distinctive web logs, and others. Where providing commentary, these abjure gratuitous opinion -- meeting a standard of reasoned, informational and fair. Funding is almost a definer, many such services supported by the state, private trusts, public institutions or volunteering by staff. Literature supporting discussion on elite media will include their identity as primarily committed to a public good, e.g. the ‘Public Value Test’, Moe and Donders (2011); with reference also to recent literature on developing public service media. Within its limits the paper will treat social media as participants among all media, including elite, and as a parallel dimension of mass communication founded on inter-activity. Elite media will fulfil the need for social responsibility, firstly by providing one space, a ‘plenary’ for debate. Second is the notion of building public recognition of elite media as trustworthy. Third is the fact that elite media together are a large sector with resources to sustain social cohesion and debate; notwithstanding pressure on funds, and impacts of digital transformation undermining employment in media more than in most industries.