Bmc Med
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Each year, at least 280,000 children are born with sickle cell disease (SCD) in resource-limited settings. For cost, logistic and political reasons, the availability of SCD testing is limited in such settings and consequently 50-90 % of affected children die undiagnosed before their fifth birthday. ⋯ If repeatable both in newborn babies and under real-life conditions, and if marketed at an affordable price, Sickle SCAN™ could revolutionize the survival prospects for children born with SCD in resource-limited areas. Please see related article: http://dx.doi.org/10.1186/s12916-015-0473-6.
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Neoadjuvant breast cancer trials are important for speeding up the introduction of new treatments for patients with early breast cancer and for the highly productive translational research which they facilitate. Meta-analysis of trial data shows clear correlation between pathological response at surgery after neoadjuvant chemotherapy and longer-term outcomes at an individual patient level. However, this does not appear to be present on individual trial level analysis, when correlating improved outcome for the investigational arm for the primary endpoint (pathological response) with longer-term outcomes. ⋯ The correlation between pathological response and longer-term outcomes in trials is dependent on many factors. These include definitions of pathological response, both complete and partial; assessment methods for pathological response at surgery; subtype and prognosis of breast cancer at diagnosis; number of patients recruited; adjuvant treatments; the mechanism of action of the investigational drug; the length of follow-up at the time of reporting; the definitions used in longer-term outcomes analysis; clonal heterogeneity; and new adaptive trial designs with additional neo/adjuvant treatments. Future developments of neoadjuvant breast cancer trials are discussed. With so many factors influencing the correlation of longer-term outcomes for trial-level data, we conclude that the main focus of neoadjuvant trials should remain the primary endpoint of pathological response. Neoadjuvant breast cancer trials are very important investigational studies that will continue to increase our understanding of the disease and offer the potential of more rapid introduction of new treatments for women with high-risk early breast cancer. In the future, we are likely to see both novel trial designs adopted in the neoadjuvant context and modifications of neo/adjuvant treatments for pathological non-responders within clinical trials. Both of these have the intention of improving longer-term outcomes for patients who do not have a good pathological response to first-line neoadjuvant treatment. If successful, these developments are likely to reduce further any positive correlation between pathological response and longer-term outcomes.
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Historical Article
Research impact in the community-based health sciences: an analysis of 162 case studies from the 2014 UK Research Excellence Framework.
The 2014 UK Research Excellence Framework (REF2014) generated a unique database of impact case studies, each describing a body of research and impact beyond academia. We sought to explore the nature and mechanism of impact in a sample of these. ⋯ REF2014 both inspired and documented significant efforts by UK researchers to achieve impact. But in contrast with the published evidence on research impact (which depicts much as occurring indirectly through non-linear mechanisms), this sub-panel seems to have captured mainly direct and relatively short-term impacts one step removed from patient outcomes. Limited impacts on morbidity and mortality, and researchers' relatively low emphasis on the processes and interactions through which indirect impacts may occur, are concerns. These findings have implications for multi-stakeholder research collaborations such as UK National Institute for Health Research Collaborations for Leadership in Applied Health Research and Care, which are built on non-linear models of impact.
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Non-communicable diseases (NCDs) place enormous burdens on individuals and health systems. While there has been significant global progress to guide the development of national NCD monitoring programs, many countries still struggle to adequately establish critical information systems to prioritise NCD control approaches. ⋯ In this paper, we use the recent experience of the Pacific as a case study to highlight four key lessons about prioritising strategies for health information system development for monitoring NCDs: first, NCD interventions must be chosen strategically, taking into account local disease burden and capacities; second, NCD monitoring efforts must align with those interventions so as to be capable of evaluating progress; third, in order to ensure efficiency and sustainability, NCD monitoring strategies must be integrated into existing health information systems; finally, countries should monitor the implementation of key policies to control food and tobacco industries. Prioritising NCD interventions to suit local needs is critical and should be accompanied by careful consideration of the most appropriate and feasible monitoring strategies to track and evaluate progress.
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Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. ⋯ Current artemether-lumefantrine dosing recommendations achieve day 7 lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas with emerging parasite resistance. In these groups, adherence and treatment response should be monitored closely. Higher, more frequent, or prolonged dosage regimens should now be evaluated in very young children, particularly if malnourished, and in patients with hyperparasitemia.