The clinical efficacy of artemether/lumefantrine (Coartem®)

Current World Health Organization (WHO) guidelines for the treatment of uncomplicated falciparum malaria recommend the use of artemisinin-based combination therapy (ACT). Artemether/lumefantrine is an ACT prequalified by the WHO for efficacy, safety and quality, approved by Swissmedic in December 2008 and recently approved by the USA FDA. Coartem® is a fixed-dose combination of artemether and lumefantrine. Its two components have different modes of action that provide synergistic anti-malarial activity. It is indicated for the treatment of infants, children and adults with acute, uncomplicated infection due to Plasmodium falciparum or mixed infections including P. falciparum. A formulation with improved palatability has been developed especially for children (Coartem® Dispersible), which rapidly disperses in a small amount of water for ease of administration

Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases

The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

Breast cancer mortality trends in England and the assessment of the effectiveness of mammography screening: population-based study.

OBJECTIVE: To investigate whether mortality statistics show an effect of mammographic screening on population-based breast cancer mortality in England. DESIGN: Joinpoint regression analyses, and other analyses, of population-based mortality data. SETTING: Analysis of mortality rates in the Oxford region, UK (1979-2009) because, unlike the rest of England, all causes of death mentioned on each death certificate for its residents (not just the underlying cause) are available prior to commencement of the English National Breast Screening Programme (NHSBSP). In addition, analysis of English national breast cancer mortality rates (1971-2009). PARTICIPANTS: Women who died from breast cancer in the Oxford region (1979--2009) and England (1971--2009) MAIN OUTCOME MEASURES: Age-specific mortality rates, and age-standardized mortality rates. Joinpoint regression analysis was used to estimate years ('joinpoints') in which trends changed, and annual percentage change between joinpoints, with confidence intervals. RESULTS: In the Oxford region, trends for breast cancer mortality based on underlying cause and on mentions were very similar. For all ages combined, mortality rates peaked for both underlying cause and mentions in 1985 and then started to decline, prior to the introduction of the NHSBSP in 1988. Between 1979 and 2009, for mortality measured as underlying cause, rates declined by -2.1% (95% CI -2.7 to -1.4) per year for women aged 40-49 years (unscreened), and by the same percentage per year (-2.1% [-2.4 to -1.7]) for women aged 50-64 years (screened). In England, the first estimated changes in trend occurred prior to the introduction of screening, or before screening was likely to have had an effect (between 1982 and 1989). Thereafter, the downward trend was greatest in women aged under 40 years: -2.0% per year (-2.8 to -1.2) in 1988-2001 and -5.0% per year (-6.7 to -3.3) in 2001-2009. There was no evidence that declines in mortality rates were consistently greater in women in age groups and cohorts that had been screened at all, or screened several times, than in other (unscreened) women, in the same time periods. Conclusions Mortality statistics do not show an effect of mammographic screening on population-based breast cancer mortality in England

Factors associated with consultation rates in general practice in England, 2013-14

Background Workload in general practice has risen during the last decade, but the factors associated with this increase are unclear. Aim To examine factors associated with consultation rates in general practice. Design and setting A cross-sectional study. A sample of 304,937 patients registered at 316 English practices between 2013 and 2014 was drawn from the Clinical Practice Research Datalink. Method We linked age, sex, ethnicity, smoking status, and deprivation measures with practice level data on staffing, rurality, training practice status, and Quality and Outcomes Framework performance. We conducted multilevel analyses of patient consultation rates. Results Consultations were grouped into three types: General practitioner or nurse (All), general practitioner (GP), and nurse. Non-smokers consulted less than current smokers (All: RR=0.88, 95% CI: 0.87 to 0.89; GP: 0.88 [0.87 to 0.89]; nurse: 0.91 [0.90 to 0.92]. Consultation rates were higher for those in the most deprived quintile compared to the least deprived quintile (All: 1.18 [1.16 to 1.19]; GP: 1.17 [1.15 to 1.19]; nurse: 1.13 [1.11 to 1.15]. For all three consultation types, consultation rates increased with age, female sex, and varied by ethnicity. Rates in practices with between &gt;8 and &lt;=19 full time equivalent (FTE) GPs were higher compared to those with &lt;=2 FTE GPs (All: 1.26 [1.06 to 1.49]; GP: 1.36 [1.19 to 1.56]). Conclusions Our analyses show consistent trends in factors related to consultation rates in general practice across three types of consultation. These data can be used inform the development of more sophisticated staffing models, and resource allocation formulae.</p

The falling rates of hospital admission, case fatality, and population-based mortality for subarachnoid hemorrhage in England, 1999–2010

OBJECTIVE: In this study, the authors examined trends in population-based hospital admission rates, patient-level case fatality rates (CFRs), and population-based mortality rates for nontraumatic (spontaneous) subarachnoid hemorrhage (SAH) in England. METHODS: Population-based admission and mortality data (59,599 people admitted to a hospital with SAH, 1999–2010; 37,836 people whose death certificates mentioned SAH, 1995–2010) were analyzed. RESULTS: Hospital admission rates for SAH per million population declined by 18.3%, from 100.4 (95% CI 97.6−103.1) in 1999 to 82.0 (95% CI 79.7−84.4) in 2010. CFRs at less than 30 days per 100 patients decreased by 18.2%, from 29.7 (95% CI 28.5−31.0) in 1999 to 24.3 (95% CI 23.2−25.5) in 2010. Population-based mortality rates per million population, where SAH was recorded as underlying cause of death on the death certificate, declined by 39.8%, from 41.2 (95% CI 39.5−43.0) in 1999 to 24.8 (95% CI 23.6−26.1) in 2010. CONCLUSIONS: Population-based hospital admission rates, patient-level CFRs, and population-based mortality rates all declined between 1999 and 2010. Part of the decline in mortality rates for SAH is likely to be attributable to a decline in incidence. It is also, in part, attributable to increased survival after SAH. The available data do not allow us to compare the effects of different treatment methods for SAH on case fatality and mortality. During the period of study, mortality rates declined by almost 40%, and it is likely that there are a number of factors contributing to this substantial improvement in outcomes for SAH patients in England