Bridging the gap between methods research and the needs of policy makers: A review of the research priorities of the National Institute for Health and Clinical Excellence

Objectives: The aim of this study was to establish a list of priority topics for methods research to support decision making at the National Institute for Health and Clinical Excellence (NICE). Methods: Potential priorities for methods research topics were identified through a focused literature review, interviews, an email survey, a workshop and a Web-based feedback exercise. Participants were members of the NICE secretariat and its advisory bodies, representatives from academia, industry, and other organizations working closely with NICE. The Web exercise was open to anyone to complete but publicized among the above groups. Results: A list of potential topics was collated. Priorities for further research differed according to the type of respondent and the extent to which they work directly with NICE. Priorities emerging from the group closest to NICE included: methodology for indirect and mixed treatment comparisons; synthesis of qualitative evidence; research relating to the use of quality-adjusted life-years (QALYs) in decision making; methods and empirical research for establishing the cost-effectiveness threshold; and determining how data on the uncertainty of effectiveness and cost-effectiveness data should be taken into account in the decision-making process. Priorities emerging from the broadest group of respondents (through the Web exercise) included: methods for extrapolating beyond evidence observed in trials, methods for capturing benefits not included in the QALY and methods to assess when technologies should be recommended in the context of further evidence gathering. Conclusions: Consideration needs to be given to the needs of those who use the outputs of research for decision making when determining priorities for future methods research.NIHR Medical Research Council

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

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

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

Health state utility values for diabetic retinopathy: protocol for a systematic review and meta-analysis

Background People with diabetic retinopathy tend to have lower levels of health-related quality of life than individuals with no retinopathy. Strategies for screening and treatment have been shown to be cost-effective. In order to reduce the bias in cost-effectiveness estimates, systematic reviews of health state utility values (HSUVs) are crucial for health technology assessment and the development of decision analytic models. A review and synthesis of HSUVs for the different stages of disease progression in diabetic retinopathy has not previously been conducted. Methods/Design We will conduct a systematic review of the available literature that reports HSUVs for people with diabetic retinopathy, in correspondence with current stage of disease progression and/or visual acuity. We will search Medline, EMBASE, Web of Science, Cost-Effectiveness Analysis Registry, Centre for Reviews and Dissemination Database, and EconLit to identify relevant English-language articles. Data will subsequently be synthesized using linear mixed effects modeling meta-regression. Additionally, reported disease severity classifications will be mapped to a four-level grading scale for diabetic retinopathy. Discussion The systematic review and meta-analysis will provide important evidence for future model-based economic evaluations of technologies for diabetic retinopathy. The meta-regression will enable the estimation of utility values at different disease stages for patients with particular characteristics and will also highlight where the design of the study and HSUV instrument have influenced the reported utility values. We believe this protocol to be the first of its kind to be published

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

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England

Background Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. Methods An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13–24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. Results The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost–effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. Conclusion CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden

The physical-mental health interface during pregnancy planning

Introduction The physical and mental health of women prior to conception can have a significant impact on pregnancy and child outcomes. Given the rising burden of non-communicable diseases, the aim of this analysis was to explore the relationship between mental health, physical health and health behaviour in women planning a pregnancy. Objectives To investigate the association between indices of physical and mental health in a large population of women in the UK planning a pregnancy. Methods Responses to a preconception health digital education tool provided data on the physical and mental health and health behaviour of 131,182 women planning pregnancy. Logistic regression was used to explore associations between mental health and physical health variables. Multiple imputation by chained equations was implemented to handle missing data. Results There was evidence for an association between physical and mental health conditions (OR 2.22; 95% CI 2.14, 2.3). There was also an association between having a mental disorder and physical inactivity (OR 1.14; 95% CI 1.11, 1.18), substance misuse (OR 2.4; 95% CI 2.25, 2.55) and less folic acid use (OR 0.89; 95% CI 0.86,0.92). Conclusions There is a need for greater integration of physical and mental healthcare for women in the preconception period, which could support women, including those who wish to conceive, to optimise their health during this time