Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-naive adults with CHC.

Identifiability and definiteness in Chinese

This article explores how the pragmatic notion of identfiability is encoded in Chinese. It presents a detailed analysis of the distinctive linguistic devices, including lexical, morphological, and position in sentence, which are employed in Chinese to indicate the interpretation of referents in respect of identifiability. Of the major determiners in Chinese, demonstratives are developing uses of a definite article, and yi 'one' + classier has developed uses of an indefinite article, although morphologically and in some cases also functionally they have not yet been fully grammaticalized. What makes Chinese further different from languages like English is the interpretation in this regard of what are called indeterminate lexical encodings, which include bare NPs and cardinality expressions. They by themselves are neutral in respect of the interpretation of identifiability. For indeterminate expressions, there is a strong but seldom absolute correlation between the interpretation of identiability or nonidentfiability and their occurrence in different positions in a sentence. Unlike the cases with several other languages without articles like Czech, Hindi, and Indonesian, the features of definiteness and indefiniteness cannot be obligatorily and uniquely specified for nominal expressions in Chinese. The findings in this article lead to the conclusion that definiteness as a grammatical category defined in the narrow sense has not been fully developed in Chinese.

Developing and evaluating authentic integration between research and coursework in professional doctorate programs

Integration has always been a prominent issue debated in the burgeoning literature on professional doctorate programs. This focus on integration, however, has largely involved the integration between theoretical and practical understandings of various professions. Exploring the integration between research and coursework components of professional doctorate programs has received less attention. This article explores the character of the integration between coursework and research in several professional doctorate programs at a number of Australian research-intensive universities and universities of technology. Using a content analysis methodology, this research charted the various models for sequencing research and coursework and established whether integration was an explicit or implicit goal of the espoused curriculum. It also sought to explore whether there were differences in the levels of integration in professional doctorate programs across different types of universities or patterns of variation across disciplines.

The roles of depression and anxiety in the understanding and treatment of Obstructive Sleep Apnea Syndrome

Obstructive Sleep Apnea Syndrome (OSAS) is a debilitating condition stemming from disruption to the respiratory system during sleep. At present, the nature of the relationship between OSAS and mood, specifically depression and anxiety, is still unclear. The purpose of this paper is to shed some light on this relationship. PsycINFO was used to locate relevant papers on this topic. This literature search formed the basis of our investigation. Results showed that the anxiety and depression methodology is weak. It is now clear that there is an urgent need to better understand the roles of anxiety and depression in OSAS. For example, the research literature suggests that depression and anxiety covary with OSAS. However, because of methodological issues, such as difficulties involved in diagnosis and the use of inappropriate instruments, this conclusion remains tenuous. Future directions are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

Institutional governance systems and variations in national competitive advantage: An integrative framework

Creating competitive industries has become one of the key tasks of governments. Different adaptation outcomes in industries across nations cannot be accounted for fully simply by an emphasis on firm-level capabilities, market-driven policies, or state-level policies. We propose an integrative framework that draws on both the strategic management and political economy literature to explain variations in national industrial competitiveness.. We discuss differences with respect to institutional characteristics and capabilities, competitive outcomes, conditions of best fit, and who bears the cost of industry adaptation.

Charlatan philosopher and wise enchantress: Seduction and authority in eighteenth-century French discourses on happiness

In late 1757 Rousseau wrote a series of moral letters on happiness to Mme Sophie d'Houdetot. He distinguished himself and his teaching from the empty babble and hypocrisy prevalent in 'the century of philosophy and reason'. Philosophers were charlatans peddling happiness. This paper shows how Rousseau's critique of philosophy reworks the standard image of charlatans in the public square. It highlights a questioning and a gendering of reason implicit in the issue of credentials for teaching happiness. Against the dubious authority of the philosopher, Rousseau casts Sophie as the wise enchantress whose gentle influence inspires her tutor. He places moral authority outside the public square in a private, feminine domain. Rousseau's ideal woman cannot be a tainted charlatan like him. Yet the very opposition puts her in her place. (Author abstract)

Product performance and specification in new product development

This paper deals with product performance and specification in new product development. There are many different definitions of performance and specification in the literature. These are reviewed and a new classification scheme for product performance is proposed. The link between performance and specification is discussed in detail using a new model for the new product development process. The new model involves two stages, with each containing three main phases, and is useful for making decisions with regards to product performance and specification.

Standardising bull breeding soundness evaluations and reporting in Australia

There is substantial variation in bull breeding soundness evaluation procedures and reports in Australia; the situation is compounded by difficulties in interpretation and the validity of many reports. In an effort to overcome this, the scientific literature was reviewed [Fordyce G. In: Fordyce G, editor. Bull fertility: selection and management in Australia. Eight Mile Plains, Australia: Australian Cattle Vets; 2002] and the needs of stakeholders were considered in preparing a manual, Evaluating and Reporting Bull Fertility [Entwistle KW, Fordyce G. Evaluating and reporting bull fertility. Eight Mile Plains, Australia: Australian Cattle Vets; 2003.] that outlined standards for assessing and reporting bull breeding soundness. A new recording and reporting system, called Bull Reporter, is based on standards from this manual and groups bull fertility traits into five summary categories: Scrotum, Physical, Crush-side Semen, Sperm Morphology, and Serving. The client will generally select which categories they wish to have included in the evaluation to suit their specific purposes. While there is adequate room for comments, the veterinarian is not required to make an overall judgment of whether the bull has normal capacity to sire calves under natural mating management, but ensures the standards for each selected category are met. Professional, standardised, easy-to-read reports are produced either electronically [Entwistle KW, Fordyce G. Evaluating and reporting bull fertility. Eight Mile Plains, Australia: Australian Cattle Vets; 2003.] or manually. A bull owner or their agent signs the certificate to affirm that bulls have not undergone procedures to rectify faults which may have otherwise caused them to fail the standards. An accreditation system for assessing sperm morphology was established because of its demonstrated relationship with pregnancy rates and because of the difficulties in achieving consistent and accurate assessments among laboratories. It is considered that Bull Reporter is applicable to beef and dairy bulls across all levels of management, genotypes and environments throughout Australia, with substantial potential for application elsewhere in the world. Crown Copyright (c) 2006 Published by Elsevier Inc. All rights reserved.