Integration of modeling and simulation into hospital-based decision support systems guiding pediatric pharmacotherapy

<p>Abstract</p> <p>Background</p> <p>Decision analysis in hospital-based settings is becoming more common place. The application of modeling and simulation approaches has likewise become more prevalent in order to support decision analytics. With respect to clinical decision making at the level of the patient, modeling and simulation approaches have been used to study and forecast treatment options, examine and rate caregiver performance and assign resources (staffing, beds, patient throughput). There us a great need to facilitate pharmacotherapeutic decision making in pediatrics given the often limited data available to guide dosing and manage patient response. We have employed nonlinear mixed effect models and Bayesian forecasting algorithms coupled with data summary and visualization tools to create drug-specific decision support systems that utilize individualized patient data from our electronic medical records systems.</p> <p>Methods</p> <p>Pharmacokinetic and pharmacodynamic nonlinear mixed-effect models of specific drugs are generated based on historical data in relevant pediatric populations or from adults when no pediatric data is available. These models are re-executed with individual patient data allowing for patient-specific guidance via a Bayesian forecasting approach. The models are called and executed in an interactive manner through our web-based dashboard environment which interfaces to the hospital's electronic medical records system.</p> <p>Results</p> <p>The methotrexate dashboard utilizes a two-compartment, population-based, PK mixed-effect model to project patient response to specific dosing events. Projected plasma concentrations are viewable against protocol-specific nomograms to provide dosing guidance for potential rescue therapy with leucovorin. These data are also viewable against common biomarkers used to assess patient safety (e.g., vital signs and plasma creatinine levels). As additional data become available via therapeutic drug monitoring, the model is re-executed and projections are revised.</p> <p>Conclusion</p> <p>The management of pediatric pharmacotherapy can be greatly enhanced via the immediate feedback provided by decision analytics which incorporate the current, best-available knowledge pertaining to dose-exposure and exposure-response relationships, especially for narrow therapeutic agents that are difficult to manage.</p

Molecular evolution of a gene cluster of serine proteases expressed in the Anopheles gambiae female reproductive tract

<p>Abstract</p> <p>Background</p> <p>Genes involved in post-mating processes of multiple mating organisms are known to evolve rapidly due to coevolution driven by sexual conflict among male-female interacting proteins. In the malaria mosquito <it>Anopheles gambiae </it>- a monandrous species in which sexual conflict is expected to be absent or minimal - recent data strongly suggest that proteolytic enzymes specifically expressed in the female lower reproductive tissues are involved in the processing of male products transferred to females during mating. In order to better understand the role of selective forces underlying the evolution of proteins involved in post-mating responses, we analysed a cluster of genes encoding for three serine proteases that are down-regulated after mating, two of which specifically expressed in the atrium and one in the spermatheca of <it>A. gambiae </it>females.</p> <p>Results</p> <p>The analysis of polymorphisms and divergence of these female-expressed proteases in closely related species of the <it>A. gambiae </it>complex revealed a high level of replacement polymorphisms consistent with relaxed evolutionary constraints of duplicated genes, allowing to rapidly fix novel replacements to perform new or more specific functions. Adaptive evolution was detected in several codons of the 3 genes and hints of episodic selection were also found. In addition, the structural modelling of these proteases highlighted some important differences in their substrate specificity, and provided evidence that a number of sites evolving under selective pressures lie relatively close to the catalytic triad and/or on the edge of the specificity pocket, known to be involved in substrate recognition or binding. The observed patterns suggest that these proteases may interact with factors transferred by males during mating (e.g. substrates, inhibitors or pathogens) and that they may have differently evolved in independent <it>A. gambiae </it>lineages.</p> <p>Conclusions</p> <p>Our results - also examined in light of constraints in the application of selection-inference methods to the closely related species of the <it>A. gambiae </it>complex - reveal an unexpectedly intricate evolutionary scenario. Further experimental analyses are needed to investigate the biological functions of these genes in order to better interpret their molecular evolution and to assess whether they represent possible targets for limiting the fertility of <it>Anopheles </it>mosquitoes in malaria vector control strategies.</p

Risks and success conditions for the French sanitary service of health students

International audienceAbstract Background French sanitary service of health students was a pledge of the French Presidency. It is mainly presented as a massive information campaign on good practices in health made by “thousands of health students going into the enterprises and schools”. We tried to skip this orientation and to go to actions in favor of people’s empowerment and ability in health choices. Objectives Our program was designed to change students’ ideas on prevention, by focusing on reflexivity, motivational approaches, education and ethic in health promotion, of peer-to-peer effects and concrete use of educational tools for teen-agers groups. We developed students’ autonomy and ability to negotiate their project with the prevention structures. Training was 11 workshops (2 hours each), of 15 to 20 students (mixing medical, pharmaceutical, dental and midwives), and e-learning. Then they had 5 months to negotiate with their place of intervention (secondary schools and apprenticeship centers) and create their own new project. Intervention lasted for one week, full time, in various teen-agers settings, so that to reduce social and territorial inequities in health. Results After a first test (28 students in 6 settings), 250 students acted in 72 teen-agers’ facilities. Problem occurs in 1 case (lack of negotiation and preparation before the intervention) and satisfaction of both students and facilities are high. At the same times, we had to face constraints due to double bind policies of the state authorities (i.e. as asking for more training time and reducing training financing, asking to send students in deprived or isolated areas and reimbursing scarcely the costs). Conclusions An educational program on training and students’ autonomy works if we take care on five points: learning of educational process in health, control of peer-to-peer effects, reduction of health inequities, and reinforcement of local health promotion policies. This also needs state policies that are ready to play the game. Key messages Training of health students to develop their autonomy and ability in health education works. Inconsistency in State policies is the major problem

Perception du malade chronique chez les professionnels de santé : une évolution marquée par les indicateurs d’évaluation de programmes d’éducation thérapeutique du patient entre 2011 et 2017 au CHU de Clermont-Ferrand, France

International audienc

Analysis of Perceived Competitive Forces Influencing Tree Tomato Value Chains in Rwanda

The globalization of economies has added many new challenges to global agriculture. Agriculture not only needs to compete in foreign markets but also in domestic markets. The production and export of tree tomatoes remain extremely weak in Rwanda despite horticulture sector-specific economic policies in favour of the production and export of horticultural crops by the government of Rwanda. The goal of this study was to analyse the competitive performance of Rwanda's tree tomato value chain to shape the tree tomato industry in Rwanda for the benefit of smallholder farmers and the Rwandan Economy. One hundred twenty (120) respondents were surveyed for this study using a semi-structured questionnaire and focus group discussions. Participants were stratified into groups as traders (80), institutional consumers (12), and household consumers (28) all from Bugesera, Nyabihu, Rubavu districts and Kigali markets (Nyabugogo, Nyarugenge and Kimironko). Key enablers (International Centre for Research in Agroforestry, Rwanda Agricultural Board, National Agricultural Export Board, and Ministry of Commerce and Financial institutions) provided useful information related to the tree tomato value chain in Rwanda. The findings of this study show that factors that hamper the tree tomato value chain competitiveness in Rwanda are related to bargaining power. Overall 63% of respondents who were tree tomato suppliers and 58.43% of respondents who were tree tomato buyers agreed that the bargaining power of suppliers and buyers hamper the competitiveness of the value chain. The study found that 70% of traders and 57% of consumers and institutional consumers preferred the tree tomato. Therefore, tree tomato is highly linked to consumers, traders, and institutions than banana which is the 38th fruit highly scored. The severity of the threat to the tree tomato industry is new entrants into the tree tomato industry, the intensity of rivalry in existing key competitors, and the severity of the threat of substitutes. The strategies proposed to improve on the competitiveness of the tree tomato industry comprise of improving collaboration of tree tomato chain actors. This study found that 75.69% of the sampled key actors agree that the highest criteria to be considered are the product quality, and 64.74% of the sampled key actors settled on product quality as the least criteria