Bringing genetics into primary care: findings from a national evaluation of pilots in England

Objectives: Developments in genetic knowledge and clinical applications are seen as rendering traditional modes of organizing genetics provision increasingly inappropriate. In common with a number of developed world countries the UK has sought to increase the role of primary care in delivering such services. However, efforts to reconfigure service delivery face multiple challenges associated with divergent policy objectives, organizational boundaries and professional cultures. This paper presents findings from an evaluation of an English initiative to integrate genetics into 'mainstream' clinical provision in the National Health Service. Methods: Qualitative research in 11 case-study sites focusing on attempts by pilots funded by the initiative to embed knowledge and provision within primary care illustrating barriers faced and the ways in which these were surmounted. Results: Lack of intrinsic interest in clinical genetics among primary care staff was compounded by national targets that focused their attention elsewhere and by service structures that rendered genetics a peripheral concern demanding minimal engagement. Established divisions between the commissioning of mainstream and specialist services, along with the pressures of shorter-term targets, impeded ongoing funding. Conclusions: More wide-ranging policy and organizational support is required if the aim of entrenching genetics knowledge and practice across the Health Service is to be realized

The medium-term sustainability of organisational innovations in the national health service

Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

A rare feature of advanced COPD

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Variation, variability, and the origin of the avian endocranium:Insights from the anatomy of alioramus altai (theropoda: Tyrannosauroidea)

The internal braincase anatomy of the holotype of Alioramus altai, a relatively small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied using high-resolution computed tomography. A number of derived characters strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new species (e.g., endocranial position of the gasserian ganglion, internal ramification of the facial nerve). Also present are features intermediate between the basal theropod and avialan conditions that optimize as the ancestral condition for Coelurosauria--a diverse group of derived theropods that includes modern birds. The expression of several primitive theropod features as derived character states within Tyrannosauroidea establishes previously unrecognized evolutionary complexity and morphological plasticity at the base of Coelurosauria. It also demonstrates the critical role heterochrony may have played in driving patterns of endocranial variability within the group and potentially reveals stages in the evolution of neuroanatomical development that could not be inferred based solely on developmental observations of the major archosaurian crown clades. We discuss the integration of paleontology with variability studies, especially as applied to the nature of morphological transformations along the phylogenetically long branches that tend to separate the crown clades of major vertebrate groups

The Scottish Academic Foundation Year Programme: what, why and how?

The Foundation Programme is well established in the UK and serves as the generic training scheme into which newly qualified doctors enter after gaining a medical degree. Although individual programmes have many differences, the range of competencies needing to be fulfilled to progress is uniform across Scotland and the rest of the UK. Some final year medical undergraduates may apply for the Academic Foundation Programme; this is designed to facilitate exposure to academic medicine over and above the clinical experience offered to Foundation Year doctors. This paper describes characteristics of the Academic Foundation Programme in general, with a particular focus on Scotland, which is one Foundation School

A unifying mathematical framework for experimental TCR-pMHC kinetic constants

Receptor binding and triggering are central in Immunology as T cells activated through their T cell receptors (TCR) by protein antigens orchestrate immune responses. In order to understand receptor-ligand interactions, many groups working with different experimental techniques and assays have generated a vast body of knowledge during the last decades. However, in recent years a type of assays, referred to as two-dimensional or membrane-to-membrane, has questioned our current understanding of the role of different kinetic constants (for instance, on- versus off-rate constants) on TCR-ligand interaction and subsequent T cell activation. Here we present a general mathematical framework that provides a unifying umbrella to relate fundamental and effective (or experimentally determined) kinetic constants, as well as describe and compare state-of-the-art experimental methods. Our framework is able to predict the correlations between functional output, such as 1/EC50, and effective kinetic constants for a range of different experimental assays (in two and three dimensions). Furthermore, our approach can be applied beyond Immunology, and serve as a “translation method” for the biochemical characterization of receptor-ligand interactions

On-going collaborative priority-setting for research activity: a method of capacity building to reduce the research-practice translational gap

Background: International policy suggests that collaborative priority setting (CPS) between researchers and end users of research should shape the research agenda, and can increase capacity to address the research-practice translational gap. There is limited research evidence to guide how this should be done to meet the needs of dynamic healthcare systems. One-off priority setting events and time-lag between decision and action prove problematic. This study illustrates the use of CPS in a UK research collaboration called Collaboration and Leadership in Applied Health Research and Care (CLAHRC). Methods: Data were collected from a north of England CLAHRC through semi-structured interviews with 28 interviewees and a workshop of key stakeholders (n = 21) including academics, NHS clinicians, and managers. Documentary analysis of internal reports and CLAHRC annual reports for the first two and half years was also undertaken. These data were thematically coded. Results: Methods of CPS linked to the developmental phase of the CLAHRC. Early methods included pre-existing historical partnerships with on-going dialogue. Later, new platforms for on-going discussions were formed. Consensus techniques with staged project development were also used. All methods demonstrated actual or potential change in practice and services. Impact was enabled through the flexibility of research and implementation work streams; ‘matched’ funding arrangements to support alignment of priorities in partner organisations; the size of the collaboration offering a resource to meet project needs; and the length of the programme providing stability and long term relationships. Difficulties included tensions between being responsive to priorities and the possibility of ‘drift’ within project work, between academics and practice, and between service providers and commissioners in the health services. Providing protected ‘matched’ time proved difficult for some NHS managers, which put increasing work pressure on them. CPS is more time consuming than traditional approaches to project development. Conclusions: CPS can produce needs-led projects that are bedded in services using a variety of methods. Contributing factors for effective CPS include flexibility in use and type of available resources, flexible work plans, and responsive leadership. The CLAHRC model provides a translational infrastructure that enables CPS that can impact on healthcare systems

Salmeterol plus fluticasone propionate versus fluticasone propionate plus montelukast: a randomised controlled trial investigating the effects on airway inflammation in asthma

<p>Abstract</p> <p>Background</p> <p>Few studies have compared treatment strategies in patients with asthma poorly controlled on low dose inhaled corticosteroids, and little is known about the effects of different treatments on airway inflammation. In this double-blind, placebo-controlled, parallel group study, we compared the effects of salmeterol plus fluticasone propionate (FP) (Seretide™; SFC) and FP plus montelukast (FP/M) on sputum inflammatory markers, airway responsiveness, lung function, and symptoms in adult asthmatics.</p> <p>Methods</p> <p>Sixty-six subjects were randomised to SFC or FP/M for 12 weeks. The primary outcome was changes in neutrophil, eosinophil, macrophage, lymphocyte, and epithelial cell levels in induced sputum. Additional outcomes included the change in other sputum markers of airway inflammation, airway responsiveness, symptom control, and lung function.</p> <p>Results</p> <p>Both treatments had no significant effect on induced sputum inflammatory cells, although there was a trend for a reduction in sputum eosinophils. Both treatments significantly improved airway responsiveness, whereas SFC generally led to greater improvements in symptom control and lung function than FP/M. FP/M led to significantly greater reductions in sputum cysteinyl leukotrienes than SFC (treatment ratio 1.80; 95% CI 1.09, 2.94).</p> <p>Conclusion</p> <p>Both treatments led to similar control of eosinophilic airway inflammation, although PEF and symptom control were better with SFC.</p> <p>Study number</p> <p>SAM40030 (SOLTA)</p