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

Effect of pulsed methylprednisolone on pain, in patients with HTLV-1-associated myelopathy

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load. Treatment was well tolerated in all but one patient. Significant improvements in pain were: observed immediately, unrelated to duration of disease and maintained for three months. Improvement in gait was only seen on Day 3 of treatment. Baseline cytokine concentrations did not correlate to baseline pain or gait impairment but a decrease in tumour necrosis factor-alpha (TNF-α) concentration after pulsed methylprednisolone was associated with improvements in both. Until compared with placebo, treatment with pulsed methylprednisolone should be offered to patients with HAM/TSP for the treatment of pain present despite regular analgesia

Voxel-based magnetic resonance image postprocessing in epilepsy

OBJECTIVE: Although the general utility of voxel-based processing of structural magnetic resonance imaging (MRI) data for detecting occult lesions in focal epilepsy is established, many differences exist among studies, and it is unclear which processing method is preferable. The aim of this study was to compare the ability of commonly used methods to detect epileptogenic lesions in magnetic resonance MRI-positive and MRI-negative patients, and to estimate their diagnostic yield. METHODS: We identified 144 presurgical focal epilepsy patients, 15 of whom had a histopathologically proven and MRI-visible focal cortical dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure origin, 27 of whom had resections. We applied four types of voxel-based morphometry (VBM), three based on T1 images (gray matter volume, gray matter concentration, junction map [JM]) and one based on normalized fluid-attenuated inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy controls. RESULTS: The four maps had different sensitivity and specificity profiles. All maps showed detection rates for focal cortical dysplasia patients (MRI positive and negative) of >30% at a strict threshold of p 60% with a liberal threshold of p < 0.0001 (uncorrected), except for gray matter volume (14% and 27% detection rate). All maps except nFSI showed poor specificity, with high rates of false-positive findings in controls. In the MRI-negative patients, absolute detection rates were lower. A concordant nFSI finding had a significant positive odds ratio of 7.33 for a favorable postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and nFSI was rare, yet showed good specificity throughout the thresholds. SIGNIFICANCE: All VBM variants had specific diagnostic properties that need to be considered for an adequate interpretation of the results. Overall, structural postprocessing can be a useful tool in presurgical diagnostics, but the low specificity of some maps has to be taken into consideration

Seroprevalence of HTLV-1 and HTLV-2 amongst mothers and children in Malawi within the context of a systematic review and meta-analysis of HTLV seroprevalence in Africa

OBJECTIVES: Human T‐lymphotropic virus (HTLV)‐1 causes T‐cell leukaemia and myelopathy. Together with HTLV‐2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother‐to‐child transmission. To provide context, we conducted a systematic review and meta‐analysis of HTLV seroprevalence in African women and children. METHODS: Stored samples from a previous childhood cancer and BBV study were analysed. ELISA was used for HTLV screening followed by immunoblot for confirmation and typing. Standard methods were used for the systematic review. RESULTS: HTLV seroprevalence was 2.6% (11/418) in mothers and 2.2% (12/534) in children. Three mothers carried HTLV‐1 alone, seven had HTLV‐2 and one was dually infected. Three children carried HTLV‐1 alone, seven had HTLV‐2 and two were dually infected. Only two corresponding mothers of the 12 HTLV‐positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV‐1 varied from 0 to 17% and of HTLV‐2 from 0 to 4%. CONCLUSIONS: In contrast to findings from other studies in Africa, the seroprevalence of HTLV‐2 was higher than that of HTLV‐1 in Malawi and one of the highest for the African region. The lack of mother–child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa

Running a hospital patient safety campaign: a qualitative study

Purpose – Research on patient safety campaigns has mostly concentrated on large-scale multi-organisation efforts, yet locally led improvement is increasingly promoted. The purpose of this paper is to characterise the design and implementation of an internal patient safety campaign at a large acute National Health Service hospital trust with a view to understanding how to optimise such campaigns. Design/methodology/approach – The authors conducted a qualitative study of a campaign that sought to achieve 12 patient safety goals. The authors interviewed 19 managers and 45 frontline staff, supplemented by 56 hours of non-participant observation. Data analysis was based on the constant comparative method. Findings – The campaign was motivated by senior managers’ commitment to patient safety improvement, a series of serious untoward incidents, and a history of campaign-style initiatives at the trust. While the campaign succeeded in generating enthusiasm and focus among managers and some frontline staff, it encountered three challenges. First, though many staff at the sharp end were aware of the campaign, their knowledge, and acceptance of its content, rationale, and relevance for distinct clinical areas were variable. Second, the mechanisms of change, albeit effective in creating focus, may have been too limited. Third, many saw the tempo of the campaign as too rapid. Overall, the campaign enjoyed some success in raising the profile of patient safety. However, its ability to promote change was mixed, and progress was difficult to evidence because of lack of reliable measurement. Originality/value – The study shows that single-organisation campaigns may help in raising the profile of patient safety. The authors offer important lessons for the successful running of such campaigns.The Department of Health Policy Research programme as part of a wider programme of research on behavioural and cultural change to support quality and safety in the NHS. Write up of this paper was supported by a Wellcome Trust Senior Investigator award (MDW) WT097899

Innovation sustainability in challenging health-care contexts : embedding clinically led change in routine practice

The need for organizational innovation as a means of improving health-care quality and containing costs is widely recognized, but while a growing body of research has improved knowledge of implementation, very little has considered the challenges involved in sustaining change – especially organizational change led ‘bottom-up’ by frontline clinicians. This study addresses this lacuna, taking a longitudinal, qualitative case-study approach to understanding the paths to sustainability of four organizational innovations. It highlights the importance of the interaction between organizational context, nature of the innovation and strategies deployed in achieving sustainability. It discusses how positional influence of service leads, complexity of innovation, networks of support, embedding in existing systems, and proactive responses to changing circumstances can interact to sustain change. In the absence of cast-iron evidence of effectiveness, wider notions of value may be successfully invoked to sustain innovation. Sustainability requires continuing effort through time, rather than representing a final state to be achieved. Our study offers new insights into the process of sustainability of organizational change, and elucidates the complement of strategies needed to make bottom-up change last in challenging contexts replete with competing priorities

Mitigating agency risk between investors and ventures’ managers

The general management literature has long focused on the agency risks involved in the relationship between general managers and shareholders. Shareholders can deploy contractual and non-contractual mechanisms to reduce these inefficiencies. This study examines - based on a broad international sample of investment contracts - how the use of contractual and non-contractual mechanisms is related to the degree of risks associated with the venture’s development stage as well as how these practices differ across countries. Hypotheses are tested using a proprietary dataset of 265 hand-collected investment contracts associated with ventures in the U.S., Israel and nine European countries. Findings suggest that the use of mitigating contractual and non-contractual mechanisms is related to the degree of agency risks, and that these practices vary across countries. This study draws implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with managers and entrepreneurs

Jet vetoing and Herwig++

We investigate the simulation of events with gaps between jets with a veto on additional radiation in the gap in Herwig++. We discover that the currently-used random treatment of radiation in the parton shower is generating some unphysical behaviour for wide-angle gluon emission in QCD 2 to 2 scatterings. We explore this behaviour quantitatively by making the same assumptions as the parton shower in the analytical calculation. We then modify the parton shower algorithm in order to correct the simulation of QCD radiation.Comment: 18 pages, 11 figure

Prompt photon and associated heavy quark production at hadron colliders with kt-factorization

In the framework of the kt-factorization approach, the production of prompt photons in association with a heavy (charm or beauty) quarks at high energies is studied. The consideration is based on the O(\alpha \alpha_s^2) off-shell amplitudes of gluon-gluon fusion and quark-(anti)quark interaction subprocesses. The unintegrated parton densities in a proton are determined using the Kimber-Martin-Ryskin prescription. The analysis covers the total and differential cross sections and extends to specific angular correlations between the produced prompt photons and muons originating from the semileptonic decays of associated heavy quarks. Theoretical uncertainties of our evaluations are studied and comparison with the results of standard NLO pQCD calculations is performed. Our numerical predictions are compared with the recent experimental data taken by the D0 and CDF collaborations at the Tevatron. Finally, we extend our results to LHC energies.Comment: 14 pages, 10 figure