Health technology assessment: an Australian perspective.

Like many other countries, Australia has placed increasing emphasis on the assessment of medical technologies over the past decade. This emphasis is shaped in part by financial constraints, and in part by the organization of the health care system and its dominance by publicly-funded hospitals. Two committees, the Superspecialty Services Subcommittee of the Australian Health Ministers' Advisory Council, and the National Health Technology Advisory Panel have been particularly influential in developing guidelines for technology assessment. These guidelines emphasize not only the accumulation of primary data during the implementation of a new technology, but also a follow-up process for on-going evaluation of the contributions of a particular technology to clinical care. Presently the two committees are being merged into one agency named the Australian Health Technology Advisory Committee. This agency will be given enhanced authority to guide the diffusion and utilization of new technologies into the delivery process for health care.     

Chlorofluorocarbon to hydrofluoroalkane formulations: an industry perspective

The medications prescribed to treat asthma are provided in a range of delivery systems, designed to give patients a choice in how they take their inhaled medication. These include the mainstay of asthma therapy, the metered dose inhaler (MDI), and the breath-operated inhalers. One of the major challenges that all the leading companies in the respiratory area have faced in recent years is the environmental effects of chlorofluorocarbons. The pharmaceutical industry recognized the need to reformulate MDI products containing chlorofluorocarbons, and a number of companies began to develop alternatives in the late 1980s. To help facilitate this change in products, an industry consortium was formed (International Pharmaceutical Aerosol Consortium), and this has managed many of the overarching issues. After an extensive search was conducted, the most suitable alternatives were the hydrofluoroalkanes, which do not contain chlorine, are ozone friendly, and have lower global-warming potentials than the chlorofluorocarbons that they are replacing. To date it is estimated that the industry has invested over $1.0 billion ($US) on global research and development efforts. The first countries to launch the nonchlorofluorocarbon MDIs have been in Europe, and now salbutamol and 2 inhaled steroids are widely available across Europe in their nonchlorofluorocarbon form. Clinical testing has been extensive, and patient acceptance of the new products has proved to be high. Maintaining the smooth progress of the global transition is important, and continued dialogue between all key stakeholders should ensure success in this area.     

The future of artificial lungs: an industry perspective

 The artificial lung was first developed in 1939 and transformed from a research project to a commercial product in the 1970s. The commercial product is called an oxygenator. Driven by a market desire and market growth in conjunction with the growth of cardiac surgery, many companies developed competitive oxygenators. After a couple of decades of competitive development, oxygenator technology has improved drastically. As the oxygenator market has matured, it has become less profitable and now shows a low growth rate. Because of this, industry has reduced the development effort for future oxygenators. However, thanks to these developments, we now have a significant technology base to apply to the artificial lung. Now it is time to go to the next step toward a true artificial lung. To achieve this, the most important thing to understand is the market needs. Received: July 30, 2002 Correspondence to:A. Nogawa     

Low-level vancomycin resistance in Staphylococcus aureus—an Australian perspective

Low-level vancomycin resistance in Staphylococcus aureus has emerged as a clinical problem over the past 8 years. The clinical relevance of this resistance has been questioned, and laboratory detection remains difficult and time consuming. There is, however, increasing evidence linking low-level vancomycin resistance with glycopeptide treatment failure in serious Staphylococcus aureus infections. Diagnostic laboratories and clinicians need to be aware of this resistance phenotype, to have procedures in place to detect the resistance, and to have strategies for managing patients with infections caused by resistant strains.     

International medical graduates: the Australian perspective.

Australia, like many other developed countries, has faced medical workforce shortages. This situation has been attributed to the increasing demands from an aging population and a decline in the hours worked by medical practitioners. These shortages, which are usually in the areas of greatest medical need in Australia, have led to an increasing dependence on international medical graduates (IMGs). The Australian government is slowly moving towards self sufficiency by expanding education and training opportunities for Australian doctors. In the interim, Australia relies heavily on IMGs to supplement the medical workforce. Australia's population is concentrated in the coastal regions, and IMGs are often required to service the more sparsely populated rural and remote areas, which find it difficult to attract and retain local medical graduates.Health funding in Australia is provided jointly by the federal (central) government and six state and two territory governments. Funding from the federal government provides for university based medical education and general practice postgraduate training. State and territory governments fund postgraduate specialist training and provide funding for a public hospital system.Although a national accreditation process for IMGs exists, many IMGs are recruited directly to Australian hospitals and community practices without adequate assessment of their qualifications or language and clinical skills. The current two-tiered system, in which service demands can override quality and standards, can no longer be tolerated. There is an urgent need for a uniformly applied national standard for all IMGs entering Australia and for a strategy to implement it.     

Reproductive decision making before and after predictive testing for Huntington's disease: an Australian perspective

A retrospective study examined both pre- and post-result reproductive decision making for 281 people at risk for Huntington's disease aged 18-45 years who had undergone predictive testing in one centre in Australia between 1990 and 2002. Forty-eight per cent of subjects had one or more pre-result pregnancies, and of these, three had prenatal linkage testing. One high-risk (50%) pregnancy was terminated. Four couples chose an alternative reproductive option. Following testing, data were available for 231 subjects, and no significant difference was found between mutation carriers and non-carriers in the occurrence of post-result pregnancies. This contrasts with the finding of a recent European study, although the outcome of the present study may have been influenced by loss of follow-up data for 50 subjects. Five carriers (17%) had a total of six prenatal tests. Four showed a carrier result and these pregnancies were terminated. Two carriers utilized an alternative reproductive option (donor insemination and pre-implantation genetic diagnosis). The results of this study confirm previous findings of a low uptake of prenatal testing and alternative reproductive options by people at risk for Huntington's disease undergoing predictive testing.     

Morphostasis: an evolving perspective

In an earlier article, I proposed a pathway by which morphostasis (tissue homeostasis) may have evolved. It began in single-celled organisms and culminated in the mammalian immune system. This evolutionary path is now traced from its source — the intracellular surveillance within an isolated cell of its own internal health. Morphostasis sequentially incorporates heat shock proteins, apoptosis, cell adhesion molecules, complement components, gap junctions, phagocytes, natural killer cells, cytotoxic T-cells, helper cells and antibodies. I propose that the sequence leading to the insertion of gap junctions is an ancestor of the complement attack sequence. Although contentious, this deduction is intriguing, since numerous, minimal clues support the proposition. The broad hypothesis emphasizes a theme that may prove to be a useful framework on which to hang a better understanding of immunology and embryology. It highlights points where a concentrated research effort may rapidly advance our understanding of both.     

Biomedical application of an electronic nose

The analysis of volatiles secreted outside the human body to get information on the health status of the individuals has been proposed several times in the past. This kind of analysis is complex both from the point of view of sample collection and data interpretation when, for instance, gas chromatography is utilized. In the recent years the advent of chemical sensors and chemical sensors systems (the so-called electronic noses) opened the way to the possibility of fast and simple analysis of odors in many fields, and, recently, among them, in medicine. In this paper some examples of these applications are illustrated. The results, although preliminary, encourage in pursuing these researches that can give rise to a better comprehension of the role of smell and odor in humans and, possibly in the near future, in novel diagnostic tools.     

Microbiota-targeted therapies: an ecological perspective

The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long-term community residents: "a fecal transplant in a capsule." The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic.     

Epidemiological, clinical and laboratory aids for the diagnosis of neonatal herpes -- an Australian perspective

Neonatal herpes is rare in Australia, possibly because of the older average age at pregnancy compared with other developed countries, low herpes simplex virus (HSV)-2 seroprevalence in the general community, low risk of HSV-2 acquisition during pregnancy and relatively high HSV-1 seroprevalence in adults. Guidelines on herpes management in pregnancy have been produced by the Australian Society for Infectious Diseases and endorsed by the Australian College of Obstetricians and Gynaecologists. However, diagnosing and managing neonatal infection remains difficult. Until an effective strategy to prevent neonatal herpes is developed, our efforts should focus on improving early diagnosis of HSV disease in the neonate and developing more effective strategies to reduce early reactivation and long-term morbidity.     

T-cell development: an extrathymic perspective

Summary:  The lymph nodes (LNs) harbor a cryptic T-lymphopoietic pathway that is dramatically amplified by oncostatin M (OM). OM-transgenic mice generate massive amounts of T lymphocytes in the absence of Lin^–c-Kit^hiIL-7Rα^– lymphoid progenitors and of reticular epithelial cells. Extrathymic T cells that develop along the OM-dependent LN pathway originate from Lin^–c-Kit^loIL-7Rα⁺ lymphoid progenitors and are different from classic T cells in terms of turnover kinetics and function. Positive selection does not obey the same rules in the thymus and the LNs, where positive selection of developing T cells is supported primarily by epithelial and hematopoietic cells, respectively. Extrathymic T cells undergo enhanced homeostatic proliferation and thereby acquire some properties of memory T cells. Following antigen encounter, extrathymic T-cells initiate proliferation and cytokine secretion more readily than classic T cells, but their accumulation is limited by an exquisite susceptibility to apoptosis. Studies on in vitro and in vivo extrathymic T-cell development have yielded novel insights into the essence of a primary T-lymphoid organ. Furthermore, comparison of the thymic and OM-dependent extrathymic pathways shows how the division of labor between primary and secondary lymphoid organs influences the repertoire and homeostasis of T lymphocytes.