Therapeutic drug monitoring (TDM) of atazanavir in pregnancy

Purpose of the study: Pregnant women experience physiological changes during pregnancy resulting in clinically significant alterations in antiretroviral pharmacokinetics (PK). Therefore, achieving and maintaining optimal plasma concentrations of antiretroviral drugs is essential for maternal health and minimising the risk of mother-to-child transmission of HIV. The aim of this study is to describe atazanavir/ritonavir (ATV/r) PK during pregnancy. Methods: Pregnant HIV-positive women received ATV/r as part of their routine pre-natal care. Demographic and clinical data were collected, and ATV plasma concentrations [ATV] were determined in the first (T1), second (T2) and third (T3) trimester using HPLC-MS/MS (LLQ=0.05 µg/mL). Postpartum (PP) sampling was performed where applicable. Antepartum (AP) and PP PK parameters were compared using a one-way ANOVA. Summary of results: From January 2007, 44 women (37 black African) were enrolled in the study. All received ATV/r at a standard dose of 1 tablet once daily (300/100 mg od). 24 women were receiving ART prior to pregnancy, and 20 women initiated ATV/r during pregnancy. Median (range) gestation at treatment initiation in these patients was 23.5 weeks (7–35). At the time nearest to delivery 31 patients had an undetectable plasma viral load (pVL), 6 patients had detectable pVL and 2 were unavailable. [ATV] were determined in 11/44 (T1); 25/44 (T2); 35/44 (T3) and 28/44 (PP) patients. Time of TDM sampling, gestation time and [ATV] (geometric mean; 95% CI) are given in the Table. 6 patients were either below or approaching the ATV MEC (0.15 µg/mL) during pregnancy; of these, 4/6 achieved undetectable pVL at the time of delivery (1=pVL of 291 copies/mL; 1 unavailable). [ATV] were significantly lower at T2/T3 relative to T1/PP. Equally, in a paired analysis of 28 patients (T2/T3 vs. PP), [ATV] were significantly reduced at T2/T3 (P=0.003). Conclusions: This study represents one of the larger cohorts of women undergoing TDM for ATV in pregnancy. Lower [ATV] were seen in T2 and T3 when compared to T1. However, such findings were not associated with viral breakthrough or HIV transmissions. Nonetheless, careful monitoring of women in pregnancy is required, and if there is concern for inadequate levels, dose adjustment of ATV upward from 300 mg to 400 mg may be an option

Meaningful engagement: computer-based interactive media art in public space.

Interactive technologies, including electronic devices are increasingly being utilized as a medium for artistic expression and have been placed in freely accessible public environments with mixed results. When audiences encounter computer-based interactive media arts in a public space they are drawn by various interactivities, to play and experiment with them. However, whether the audience is able to gain a meaningful experience through those physical interactivities has remained an issue of both theoretical and practical debate. This paper will focus on these aspects, most specifically through the study of interactive art in freely accessible public space. The author proposes four new conceptual/analytical tools for examining the subject. It is anticipated that this paper will provide possible alternative strategies for both artists and art researchers in this field with a purpose to enhance intellectual engagement with their audiences, so as to succeed in leading interactors to obtain meaningful experience and rewards

Lessons from the evaluation of the UK's NHS R&D Implementation Methods Programme

Background: Concern about the effective use of research was a major factor behind the creation of the NHS R&D Programme in 1991. In 1994, an advisory group was established to identify research priorities in research implementation. The Implementation Methods Programme (IMP) flowed from this, and its commissioning group funded 36 projects. In 2000 responsibility for the programme passed to the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D, which asked the Health Economics Research Group (HERG), Brunel University, to conduct an evaluation in 2002. By then most projects had been completed. This evaluation was intended to cover: the quality of outputs, lessons to be learnt about the communication strategy and the commissioning process, and the benefits from the projects. Methods: We adopted a wide range of quantitative and qualitative methods. They included: documentary analysis, interviews with key actors, questionnaires to the funded lead researchers, questionnaires to potential users, and desk analysis. Results: Quantitative assessment of outputs and dissemination revealed that the IMP funded useful research projects, some of which had considerable impact against the various categories in the HERG payback model, such as publications, further research, research training, impact on health policy, and clinical practice. Qualitative findings from interviews with advisory and commissioning group members indicated that when the IMP was established, implementation research was a relatively unexplored field. This was reflected in the understanding brought to their roles by members of the advisory and commissioning groups, in the way priorities for research were chosen and developed, and in how the research projects were commissioned. The ideological and methodological debates associated with these decisions have continued among those working in this field. The need for an effective communication strategy for the programme as a whole was particularly important. However, such a strategy was never developed, making it difficult to establish the general influence of the IMP as a programme. Conclusion: Our findings about the impact of the work funded, and the difficulties faced by those developing the IMP, have implications for the development of strategic programmes of research in general, as well as for the development of more effective research in this field

Evaluation of the Succession Planning Development Pathway for Consultant Nurses, Midwives and Allied Health Professionals.

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Comparison of governance approaches for the control of antimicrobial resistance: Analysis of three European countries

Policy makers and governments are calling for coordination to address the crisis emerging from the ineffectiveness of current antibiotics and stagnated pipe-line of new ones – antimicrobial resistance (AMR). Wider contextual drivers and mechanisms are contributing to shifts in governance strategies in health care, but are national health system approaches aligned with strategies required to tackle antimicrobial resistance? This article provides an analysis of governance approaches within healthcare systems including: priority setting, performance monitoring and accountability for AMR prevention in three European countries: England, France and Germany. Advantages and unresolved issues from these different experiences are reported, concluding that mechanisms are needed to support partnerships between healthcare professionals and patients with democratized decision-making and accountability via collaboration. But along with this multi-stakeholder approach to governance, a balance between regulation and persuasion is needed

The Foundation Supernova Survey: Measuring Cosmological Parameters with Supernovae from a Single Telescope

Measurements of the dark energy equation-of-state parameter, $w$, have been limited by uncertainty in the selection effects and photometric calibration of $z<0.1$ Type Ia supernovae (SNe Ia). The Foundation Supernova Survey is designed to lower these uncertainties by creating a new sample of $z<0.1$ SNe Ia observed on the Pan-STARRS system. Here, we combine the Foundation sample with SNe from the Pan-STARRS Medium Deep Survey and measure cosmological parameters with 1,338 SNe from a single telescope and a single, well-calibrated photometric system. For the first time, both the low-$z$ and high-$z$ data are predominantly discovered by surveys that do not target pre-selected galaxies, reducing selection bias uncertainties. The $z>0.1$ data include 875 SNe without spectroscopic classifications and we show that we can robustly marginalize over CC SN contamination. We measure Foundation Hubble residuals to be fainter than the pre-existing low-$z$ Hubble residuals by $0.046 \pm 0.027$ mag (stat+sys). By combining the SN Ia data with cosmic microwave background constraints, we find $w=-0.938 \pm 0.053$, consistent with $\Lambda$CDM. With 463 spectroscopically classified SNe Ia alone, we measure $w=-0.933\pm0.061$. Using the more homogeneous and better-characterized Foundation sample gives a 55% reduction in the systematic uncertainty attributed to SN Ia sample selection biases. Although use of just a single photometric system at low and high redshift increases the impact of photometric calibration uncertainties in this analysis, previous low-$z$ samples may have correlated calibration uncertainties that were neglected in past studies. The full Foundation sample will observe up to 800 SNe to anchor the LSST and WFIRST Hubble diagrams.Comment: 30 pages, 17 figures, accepted by Ap

Factors influencing quality of life following lower limb amputation for peripheral arterial occlusive disease: a systematic review of the literature

Background: The majority of lower limb amputations are undertaken in people with peripheral arterial occlusive disease,\ud and approximately 50% have diabetes. Quality of life is an important outcome in lower limb amputations; little is known\ud about what influences it, and therefore how to improve it.\ud Objectives: The aim of this systematic review was to identify the factors that influence quality of life after lower limb\ud amputation for peripheral arterial occlusive disease.\ud Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science and Cochrane databases were searched to identify\ud articles that quantitatively measured quality of life in those with a lower limb amputation for peripheral arterial occlusive\ud disease. Articles were quality assessed by two assessors, evidence tables summarised each article and a narrative\ud synthesis was performed.\ud Study design: Systematic review.\ud Results: Twelve articles were included. Study designs and outcome measures used varied. Quality assessment scores\ud ranged from 36% to 92%. The ability to walk successfully with a prosthesis had the greatest positive impact on quality\ud of life. A trans-femoral amputation was negatively associated with quality of life due to increased difficulty in walking\ud with a prosthesis. Other factors such as older age, being male, longer time since amputation, level of social support and\ud presence of diabetes also negatively affected quality of life.\ud Conclusion: Being able to walk with a prosthesis is of primary importance to improve quality of life for people with lower\ud limb amputation due to peripheral arterial occlusive disease. To further understand and improve the quality of life of this\ud population, there is a need for more prospective longitudinal studies, with a standardised outcome measure

Membership categorization, culture and norms in action

In this article, we examine the extent to which membership categorization analysis (MCA) can inform an understanding of reasoning within the public domain where morality, policy and cultural politics are visible (Smith and Tatalovich, 2003). Through the examination of three examples, we demonstrate how specific types of category device(s) are a ubiquitous feature of accountable practice in the public domain where morality matters and public policy intersect. Furthermore, we argue that MCA provides a method for analysing the mundane mechanics associated with everyday cultural politics and democratic accountability assembled and presented within news media and broadcast settings