Entecavir for the treatment of chronic hepatitis B infection

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturer's mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturer's lifetime treatment scenario for HBeAg-negative patients and the ERG's 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.

Nurse-led clinic: Effective and efficient delivery of assessment and review of patients with Hepatitis B and C

Hepatology and gastroenterology services are increasingly utilising the skills and experience of nurse practitioners and nurse specialists to help meet the increasing demand for health care. A new nurse-led assessment clinic has been established in the liver clinic at Geelong Hospital to utilise the expertise of nurses to assess and triage new patients and streamline their pathway through the health care system. The aim of this study is to quantitatively assess the first two years of operation of the nurse assessment clinic at Geelong Hospital, and to assess advantages and disadvantages of the nurse-led clinic. Data was extracted retrospectively from clinical records of new patients at the liver clinic. Quarterly one-month periods were recorded over two-years. Patients were categorised according to the path via which they saw a physician, including missed and rescheduled appointments. The number of appointments, the waiting time from referral to appointments and the number of ‘did-not-attend’ occasions were analysed before and after the institution of the nurse-led assessment clinic. The Mann-Whitney rank sum test of ordinal data was used to generate median wait times. There was shown to be a statistically significant longer waiting time for physician appointment if seen by the nurse first. The difference in waiting time was 10 days. However, there was also a reduction in the number of missed appointments at the subsequent physician clinic. Other advantages have also been identified including effective triage of patients, and organisation of appropriate investigations from the initial nurse assessment.

Hepatitis C virus treatment in the 'real-world': how well do 'real' patients respond?

Background: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. Objectives: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. Methods: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. Results: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). Conclusions: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials.

Tracks to advocacy: journalism studies, animal rights and Australian media law

This article considers the role of animal rights-based journalism and its connection to teaching media law and ethics to undergraduate students in an Australian university arts faculty. An anecdotal discussion of a reflective practice informing the teaching of an undergraduate course in a journalism major relates questions of ethics and law to broader considerations of the role of advocacy in and around journalism, and media practice. It is argued that animal rights-related stories have a role in training media professionals, and also in inspiring journalists to envision their own work as part of the democratic mechanisms of social and legal reform in Australia.

Mind and body: how the health of the body impacts on neuropsychiatry

It has long been established in traditional forms of medicine and in anecdotal knowledge that the health of the body and the mind are inextricably linked. Strong and continually developing evidence now suggests a link between disorders which involve Hypothalamic-Pituitary-Adrenal axis (HPA) dysregulation and the risk of developing psychiatric disease. For instance, adverse or excessive responses to stressful experiences are built into the diagnostic criteria for several psychiatric disorders, including depression and anxiety disorders. Interestingly, peripheral disorders such as metabolic disorders and cardiovascular diseases are also associated with HPA changes. Furthermore, many other systemic disorders associated with a higher incidence of psychiatric disease involve a significant inflammatory component. In fact, inflammatory and endocrine pathways seem to interact in both the periphery and the central nervous system (CNS) to potentiate states of psychiatric dysfunction. This review synthesizes clinical and animal data looking at interactions between peripheral and central factors, developing an understanding at the molecular and cellular level of how processes in the entire body can impact on mental state and psychiatric health.

Feltability of cashmere and other rare animal fibres and the effects of nutrition and blending with wool on cashmere feltability

Felting is a unique attribute of animal fibres used for the production of a range of industrial and apparel textiles. Felting can be an adverse attribute as a consequence of dimensional shrinkage during laundering. As there is little objective information regarding the feltability of rare animal fibres or the factors which may affect felting three investigations were undertaken. A survey (n = 114) of the feltability of cashmere from different origins of production, cashgora, quivet, camel hair, llama, guanaco, bison wool, cow fibre and yak wool quantified the large variation between and within these fibre types. Cashmere from some origins and cashgora produced higher feltball density than the other fibres. Different nutritional management of cashmere goats (n = 35) showed that cashmere grown by poorly fed goats had a lower propensity to felt compared with cashmere grown by better fed goats. A consequence of the progressive blending of cashmere (n = 27) with a low propensity to felt superfine wool (high fibre curvature) increased the propensity of the blend to felt, but when the same cashmere was blended with low curvature superfine wool, there was little or no effect on feltability. The mechanisms which lead to variance in feltability of these fibres were quantified with multiple regression modelling. The mechanisms were similar to those reported for wools, namely variations in the resistance to compression, fibre curvature and mean fibre diameter, with likely effects of fibre crimp form. It is possible to source cashmere and other animal fibres which have different propensities to felt and therefore to produce textiles which are likely to have different textile properties.

The influence of stocking rate and mixed grazing of Angora goats and Merino sheep on animal and pasture production in southern Australia. 4. Gastrointestinal parasitism

Gastrointestinal nematodes limit the growth, production and welfare of goats but there are few reliable sources of information for recommending management practices across flocks. The effects of animal species (Angora goat, Merino sheep, mixed-grazed goats and mixed-grazed sheep at the ratio of 1:1) and stocking rate (SR: 7.5, 10, 12.5 animals/ha) on gastrointestinal parasitism were determined in a replicated experiment on improved annual temperate pastures in southern Australia, from 1981 to 1984. Detailed monitoring of gastrointestinal nematodes was undertaken on animals before, during (five times per year) and at the conclusion of studies using faecal strongyle egg counts (WEC) and total worm counts. Sheep had a greater proportion of nematodes as Teladorsagia spp. and goats a greater incidence of Trichostrongylus spp. Both goats and sheep developed resistance to Nematodirus spp. during the experiment. WEC was similar in goats and sheep at the start of the experimental period but, thereafter, was consistently greater in goats than in sheep. While WEC was highly related to total worm count, the regressions for sheep and goats were different. Increasing the SR increased the WEC of goats and mixed-grazed goats but not of sheep. During the experiment, WEC declined at 7 and 10 animals/ha but increased at 12.5/ha. Mixed grazing with goats provided beneficial effects for sheep at all stocking rates, but the effects for goats were dependent on the stocking rate, being beneficial at 7.5 and 10/ha but harmful at 12.5/ha. The WEC of separately grazed goats were generally higher than the WEC of mixed grazed goats. The WEC of mixed sheep were lower than those of separately grazed sheep. During the experiment, the WEC of mixed grazed sheep declined faster than the WEC of separately grazed sheep but the WEC of separately grazed goats at 12.5/ha and of mixed grazed goats at 10 and 12.5/ha increased. Under the environmental and pastoral conditions examined, Angora wether goats should not be grazed at SR above those recommended for wether sheep. In the present study, the impact of gastrointestinal-nematode infections in goats was reduced at lower SR. Further, mixed grazing of Angora wether goats with wether sheep at or below the recommended SR resulted in reduced gastrointestinal parasitism for both sheep and goats, compared with monospecific grazing conditions. Goats did not represent a gastrointestinal-nematode hazard to sheep. © 2014 CSIRO.

Review on fabrication and applications of ultrafine particles from animal protein fibres

Protein fibre wastes from animal hairs, feathers and insect secreted filaments can be aptly utilized by converting them into ultra-fine particles. Particles from animal protein fibres present large surface-to-weight ratio and significantly enhanced surface reactivity, that have opened up novel applications in both textile and non-textile fields. This review article summarizes the state-of-the-art routes to fabricate ultrafine particles from animal protein fibres, including direct route of mechanical milling of fibres and indirect route from fibre proteins. Ongoing research trends in novel applications of protein fibre particles in various fields, such as biomedical science, environmental protection and composite structures are presented. © 2014 The Korean Fiber Society and Springer Science+Business Media Dordrecht.

The accuracy of Fastloc-GPS locations and implications for animal tracking

Over recent years, a major breakthrough in marine animal tracking has occurred with the advent of Fastloc-GPS that provides highly accurate location data even for animals that only surface briefly such as sea turtles, marine mammals and penguins. We assessed the accuracy of Fastloc-GPS locations using fixed trials of tags in which >45 000 locations were obtained. Procedures for determining the speed of travel and heading were developed by simulating tracks and then adding Fastloc-GPS location errors. The levels of detail achievable for speed and heading estimates were illustrated by using empirical Fastloc-GPS data for a green turtle (Chelonia mydas, Linnaeus, 1758) travelling over 3000 km across the Indian Ocean. The accuracy of Fastloc-GPS locations varied as a function of the number of GPS satellites used in the location calculation. For example, when Fastloc-GPS locations were calculated using 4 GPS satellites, 50% of locations were within 36 m and 95% within 724 m of the true position. These values improved to 18 and 70 m, respectively, when 6 satellites were used. Simulations indicated that for animals travelling around 2·5 km h-1 (e.g. turtles, penguins and seals) and depending on the number of satellites used in the location calculation, robust speed and heading estimates would usually be obtained for locations only 1-6 h apart. Fastloc-GPS accuracy is several orders of magnitude better that conventional Argos tracking or light-based geolocation and consequently will allow new insights into small-scale movement patterns of marine animals.