Use of generic and condition-specific measures of health-related quality of life in NICE decision-making: systematic review, statistical modelling and survey.

© Queen’s Printer and Controller of HMSO 2014Background: The National Institute for Health and Care Excellence recommends the use of generic preference-based measures (GPBMs) of health for its Health Technology Assessments (HTAs). However, these data may not be available or appropriate for all health conditions. Objectives: To determine whether GPBMs are appropriate for some key conditions and to explore alternative methods of utility estimation when data from GPBMs are unavailable or inappropriate. Design: The project was conducted in three stages: (1) A systematic review of the psychometric properties of three commonly used GPBMs [EQ-5D, SF-6D and Health Utilities Index Mark 3 (HUI3)] in four broadly defined conditions: visual impairment, hearing impairment, cancer and skin conditions. (2) Potential modelling approaches to ‘map’ EQ-5D values from condition-specific and clinical measures of health [European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy – General Scale (FACT-G)] are compared for predictive ability and goodness of fit using two separate data sets. (3) Three potential extensions to the EQ-5D are developed as ‘bolt-on’ items relating to hearing, tiredness and vision. They are valued using the time trade-off method. A second valuation study is conducted to fully value the EQ-5D with and without the vision bolt-on item in an additional sample of 300 people. Main outcome measures: Comparisons of EQ-5D, SF-6D and HUI3 in four conditions with various generic and condition-specific measures. Mapping functions were estimated between EORTC QLQ-C30 and FACT-G with EQ-5D. Three bolt-ons to the EQ-5D were developed: EQ + hearing/vision/tiredness. A full valuation study was conducted for the EQ + vision. Results: (1) EQ-5D was valid and responsive for skin conditions and most cancers; in vision, its performance varied according to aetiology; and performance was poor for hearing impairments. The HUI3 performed well for hearing and vision disorders. It also performed well in cancers although evidence was limited and there was no evidence in skin conditions. There were limited data for SF-6D in all four conditions and limited evidence on reliability of all instruments. (2) Mapping algorithms were estimated to predict EQ-5D values from alternative cancer-specific measures of health. Response mapping using all the domain scores was the best performing model for the EORTC QLQ-C30. In an exploratory analysis, a limited dependent variable mixture model performed better than an equivalent linear model. In the full analysis for the FACT-G, linear regression using ordinary least squares gave the best predictions followed by the tobit model. (3) The exploratory valuation study found that bolt-on items for vision, hearing and tiredness had a significant impact on values of the health states, but the direction and magnitude of differences depended on the severity of the health state. The vision bolt-on item had a statistically significant impact on EQ-5D health state values and a full valuation model was estimated. Conclusions: EQ-5D performs well in studies of cancer and skin conditions. Mapping techniques provide a solution to predict EQ-5D values where EQ-5D has not been administered. For conditions where EQ-5D was found to be inappropriate, including some vision disorders and for hearing, bolt-ons provide a promising solution. More primary research into the psychometric properties of the generic preference-based measures is required, particularly in cancer and for the assessment of reliability. Further research is needed for the development and valuation of bolt-ons to EQ-5D.UK Medical Research Council (MRC) as part of the MRC-NIHR methodology research programme (reference G0901486

In vitro Adoption and Propagation of High Pathogenic Avian Influenza (HPAI) Virus Subtype H5N1 in non-avian Host System

The paradigmatic, fatal and devastating ailment called avian influenza or bird flu is a highly contagious viral disease caused by type A influenza virus, It primarily affects the respiratory, digestive and/or nervous system of chickens, turkeys, guinea fowls and other avian species and less commonly pigs and other species of mammals including human. In India, The first pandemic outbreak of Avian Influenza was reported during 2006. In this study, we selected an isolate of high pathogenic avian influenza (A/Ck/Jalgaon/India/12419/2006) H5N1 virus and propagated in chicken embryo fibroblast. Later this virus was adopted and propagated in Madin-Darby canine kidney cells (MDCK) and Vero cells. Infected non-avian cells with an avian virus shown cytopathic effects like rounding, cytoplasmic elongation, syncytia formation and later stages fluffing from the attached surface. The harvested virus suspension shown increased haemagglutination titre (HA) than viral suspension from chicken embryo fibroblast culture and the presence of virus was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). The obtained result reveals that virus had capacity to adopt for the invitro culture and propagate in non avian host cells with higher titre. This infers the chance of virus to cross the host barrier and probable chance of infection in human being

Ectopic expression of HNF4α in Het1A cells induces an invasive phenotype

\ua9 2023 The AuthorsBarrett\u27s oesophagus (BO) is a pathological condition in which the squamous epithelium of the distal oesophagus is replaced by an intestinal-like columnar epithelium originating from the gastric cardia. Several somatic mutations contribute to the intestinal-like metaplasia. Once these have occurred in a single cell, it will be unable to expand further unless the altered cell can colonise the surrounding squamous epithelium of the oesophagus. The mechanisms by which this happens are still unknown. Here we have established an in vitro system for examining the competitive behaviour of two epithelia. We find that when an oesophageal epithelium model (Het1A cells) is confronted by an intestinal epithelium model (Caco-2 cells), the intestinal cells expand into the oesophageal domain. In this case the boundary involves overgrowth by the Caco-2 cells and the formation of isolated colonies. Two key transcription factors, normally involved in intestinal development, HNF4α and CDX2, are both expressed in BO. We examined the competitive ability of Het1A cells stably expressing HNF4α or CDX2 and placed in confrontation with unmodified Het1A cells. The key result is that stable expression of HNF4α, but not CDX2, increased the ability of the cells to migrate and push into the unmodified Het1A domain. In this situation the boundary between the cell types is a sharp one, as is normally seen in BO. The experiments were conducted using a variety of extracellular substrates, which all tended to increase the cell migration compared to uncoated plastic. These data provide evidence that HNF4α expression could have a potential role in the competitive spread of BO into the oesophagus as HNF4α increases the ability of cells to invade into the adjacent stratified squamous epithelium, thus enabling a single mutant cell eventually to generate a macroscopic patch of metaplasia

Pragmatic intervention for increasing self-directed exercise behaviour and improving important health outcomes in people with multiple sclerosis : a randomised controlled trial

Background: Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed forpeople with multiple sclerosis (PwMS). Objective: The objective of this study was to assess the effects of a practically implemented exercise programme onself-directed exercise behaviour and important health outcomes in PwMS to nine months of follow-up. Methods: We conducted a parallel-arm, randomised controlled trial: 120 PwMS (Expanded Disability Status Scale (EDSS) 1.0-6.5) randomised to a three-month exercise intervention plus usual care, or usual care only. Two supervised plus one homeexercisesession (weeks 1-6) were followed by one supervised and two home-exercise sessions (weeks 7-12). Cognitivebehaviouraltechniques promoted long-term exercise behaviour change. Outcomes were blindly assessed at baseline and atthree and nine months after randomisation. The primary outcome was self-reported exercise behaviour (Godin Leisure TimeExercise Questionnaire (GLTEQ)). Secondary outcomes included fatigue and health-related quality of life (HRQoL). Results: The intervention increased self-reported exercise (9.6 points; 95% CI: 2.0 to 17.3 points; p = 0.01) andimproved fatigue (p<0.0001) and many HRQoL domains (p≤0.03) at three months. The improvements in emotionalwell-being (p = 0.01), social function (p = 0.004) and overall quality of life (p = 0.001) were sustained for nine months. Conclusion: This pragmatic approach to implementing exercise increases self-reported exercise behaviour, improves fatigue and leads to a sustained enhancement of HRQoL domains in PwMS

Gender, war and militarism: making and questioning the links

The gender dynamics of militarism have traditionally been seen as straightforward, given the cultural mythologies of warfare and the disciplining of ‘masculinity’ that occurs in the training and use of men's capacity for violence in the armed services. However, women's relation to both war and peace has been varied and complex. It is women who have often been most prominent in working for peace, although there are no necessary links between women and opposition to militarism. In addition, more women than ever are serving in many of today's armies, with feminists rather uncertain on how to relate to this phenomenon. In this article, I explore some of the complexities of applying gender analyses to militarism and peace work in sites of conflict today, looking most closely at the Israeli feminist group, New Profile, and their insistence upon the costs of the militarized nature of Israeli society. They expose the very permeable boundaries between the military and civil society, as violence seeps into the fears and practices of everyday life in Israel. I place their work in the context of broader feminist analysis offered by researchers such as Cynthia Enloe and Cynthia Cockburn, who have for decades been writing about the ‘masculinist’ postures and practices of warfare, as well as the situation of women caught up in them. Finally, I suggest that rethinking the gendered nature of warfare must also encompass the costs of war to men, whose fundamental vulnerability to psychological abuse and physical injury is often downplayed, whether in mainstream accounts of warfare or in more specific gender analysis. Feminists need to pay careful attention to masculinity and its fragmentations in addressing the topic of gender, war and militarism

"It All Ended in an Unsporting Way": Serbian Football and the Disintegration of Yugoslavia, 1989-2006

Part of a wider examination into football during the collapse of Eastern European Communism between 1989 and 1991, this article studies the interplay between Serbian football and politics during the period of Yugoslavia's demise. Research utilizing interviews with individuals directly involved in the Serbian game, in conjunction with contemporary Yugoslav media sources, indicates that football played an important proactive role in the revival of Serbian nationalism. At the same time the Yugoslav conflict, twinned with a complex transition to a market economy, had disastrous consequences for football throughout the territories of the former Yugoslavia. In the years following the hostilities the Serbian game has suffered decline, major financial hardship and continuing terrace violence, resulting in widespread nostalgia for the pre-conflict era

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

The complications of ‘hiring a hubby’: gender relations and the commoditisation of home maintenance in New Zealand

This paper examines the commoditization of traditionally male domestic tasks through interviews with handymen who own franchises in the company ‘Hire a Hubby’ in New Zealand and homeowners who have paid for home repair tasks to be done. Discussions of the commoditization of traditionally female tasks in the home have revealed the emotional conflicts of paying others to care as well as the exploitative and degrading conditions that often arise when work takes place behind closed doors. By examining the working conditions and relationships involved when traditionally male tasks are paid for, this paper raises important questions about the valuing of reproductive labour and the production of gendered identities. The paper argues that while working conditions and rates of pay for ‘hubbies’ are better than those for people undertaking commoditized forms of traditionally female domestic labour, the negotiation of this work is still complex and implicated in gendered relations and identities. Working on the home was described by interviewees as an expression of care for family and a performance of the ‘right’ way to be a ‘Kiwi bloke’ and a father. Paying others to do this labour can imply a failure in a duty of care and in the performance of masculinity