Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report [Dapson-induzierte Agranulozytose]

A 34-year-old female patient with a three year history of generalized granuloma annulare was treated systemically with dapsone (DADPS). Six weeks after the onset of treatment, the patient developed an extensive tonsillitis of the base of the tongue with fever and malaise. Routine laboratory work showed a leukocytopenia with agranulocytosis. Further investigation revealed a marked decrease of the enzyme activity of N-acetyltransferase 2, which plays an important role in dapsone metabolism. Treatment included the cessation of dapsone, antibiotic coverage, and G-CSF leading to the rapid improvement of symptoms and normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a rare event and is interpreted as an idiosyncratic reaction. Depending on genetic polymorphisms of various enzymes, dapsone can be metabolized to immunologically or toxicologically relevant intermediates. Because of the risk of severe hematologic reactions, dapsone should only be employed for solid indications and with appropriate monitoring. [Article in German]

Including or excluding conflicts of interest among expert peer reviewers had little impact on funding success, a case study from Australia

Competition for research funding is intense and the opinions of an expert peer reviewer can mean the difference between success and failure in securing funding. The allocation of expert peer reviewers is therefore vitally important and funding agencies strive to avoid using reviewers who have real or perceived conflicts of interest. This article examines the impact of including or excluding peer reviewers based on their conflicts of interest, and the final ranking of funding proposals. Two 7-person review panels assessed a sample of National Health and Medical Research Council (NHMRC) of Australia proposals in Basic Science or Public Health. Using a pre-post comparison, the proposals were first scored after the exclusion of reviewers with a high or medium conflict, and re-scored after the return of reviewers with medium conflicts. The main outcome measures are the agreements in ranks and funding success before and after excluding the medium conflicts. Including medium conflicts of interest had little impact on the ranks or funding success. The Bland–Altman 95% limits of agreement were ± 3.3 ranks and ± 3.4 ranks in the two panels which both assessed 36 proposals. Overall there were three proposals (4%) that had a reversed funding outcome after including medium conflicts. Relaxing the conflict of interest rules would increase the number of expert reviewers included in the panel discussions which could increase the quality of peer review and make it easier to find reviewers.

Expanded review criteria : the case of nonpharmacological interventions in dementia

This paper challenges the assumptions underlying many reviews and offers alternative criteria for examining evidence for nonpharmacological interventions. We evaluated 27 reviews examining interventions for persons with dementia as they relate to the issues of selection based on randomized controlled trial (RCT) design. Reviews were described by type of intervention, level of cognitive function, and criteria for inclusion. Of the 27 reviews, 46% required RCTs for inclusion and most had stringent inclusion criteria. This resulted in poor utilization of the literature and low ecological validity. Eliminating most of the available data poses a critical problem to clinical and research development. Studies meeting strict methodological criteria may not generalize to the greater population or may exclude sub-populations and interventions. Limitations of double-blind RCTs and potential design solutions are set forth based on appropriate populations, problems, interventions, and settings characteristics.

Risk management and high reliability : a case study of Australian airport management

This thesis investigated risk management and organisational reliability in airports from the perspective of complex sociotechnical systems (CSSs). Two research studies were undertaken, the first focusing on the processes by which disruptive events occur, are detected and responded to; the second exploring the presence of organisational reliability traits within airports. A key result of the studies was the development of new approach: the Critical Incident Disturbance Process model that detailed a means to understand and analyse how disruptions in complex CSSs might be influenced by vulnerability reduction and enhanced risk management. Further, this thesis identified and defined the concept of 'compartmentalised reliability' in complex sociotechnical systems, extending existing knowledge of high reliability theory.

Investigating the link between transit oriented development and sustainable travel behavior in Brisbane : a case-control study

The purpose of this research is to empirically test the prevailing view that transit oriented development enhances the use of more sustainable modes of transport using Brisbane, Australia as a case. Transit oriented development has been adopted as a new policy tool to reduce car-based travel worldwide. Despite being a billion dollar investment, the impacts of transit oriented development on promoting sustainable travel behavior is not conclusive. The research uses a case-control approach to empirically investigate this relationship based on travel behavior data collected from 88 individuals living in two contrasting neighborhoods in Brisbane: Kelvin Grove Urban Village – a transit oriented development, and Annerley – a traditional suburb (non-transit oriented development). A comparative investigation of travel behavior was subsequently conducted using distance travelled by modes and purposes between the neighborhoods. Results show that the availability of opportunity and services located within the transit oriented development reduces the car use by 5% and increases the use of active transport by 4%. The findings in this research support the implementation of TOD policies in Brisbane.

Tales of science and defiance : the case for co-learning and collaboration in bridging the science/emotion divide in water recycling debates

Although science is generally assumed to be well integrated into rational decision-making models, it can be used to destabilise consultative processes, particularly when emotions are involved. Water policies are often seen as debates over technical and engineering issues, but can be highly controversial. Recycled water proposals, in particular, can create highly emotive conflicts. Through a case study regarding the rejection of recycled water proposals in the south-east Queensland, Australia, we explore the influence of science and emotions in contemporary water planning. We highlight the dangers inherent in promoting technical water planning issues at the expense of appropriate consideration of citizen concerns. Combining the science–policy interface and stakeholder engagement literatures, we advocate for collaborative decision-making processes that accommodate emotions and value judgements. A more collaborative stakeholder engagement model, founded on the principles of co-learning, has the potential to broaden the decision-making base and to promote better and more inclusive decision-making.

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia

Background As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. Methods Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. Results It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0–42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17 860 per infection averted (median, $13 651–24 287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. Conclusions The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.