Estimates of patient costs related with population morbidity: Can indirect costs affect the results?

A number of health economics works require patient cost estimates as a basic information input. However the accuracy of cost estimates remains in general unspecified. We propose to investigate how the allocation of indirect costs or overheads can affect the estimation of patient costs in order to allow for improvements in the analysis of patient costs estimates. Instead of focusing on the costing method, this paper proposes to highlight changes in variance explained observed when a methodology is chosen. We compare three overhead allocation methods for a specific Spanish population adjusted using the Clinical Risk Groups (CRG), and we obtain different series of full-cost group estimates. As a result, there are significant gains in the proportion of the variance explained, depending upon the methodology used. Furthermore, we find that the global amount of variation explained by risk adjustment models depends mainly on direct costs and is independent of the level of aggregation used in the classification system.Patient costs, Clinical Risk Groups, Variation explained, Overhead allocation

Management of diabetes after hospital discharge

Hemos leído con interés el artículo publicado por Sainz de los Terreros y col que trata la evaluación de un protocolo de seguimiento para diabetes tras el alta hospitalaria1. En el trabajo se detallan los resultados derivados de la optimización –fundamentalmente a través de contacto telefónico– del tratamiento antidiabético. La disminución media global de HbA1c fue significativa (de 8,62 a 7,19%), con un muy bajo porcentaje de efectos adversos en forma de hipoglucemias graves

Transcriptome Analysis of the Brucella abortus BvrR/BvrS Two-Component Regulatory System

International audienceBackgroundThe two-component BvrR/BvrS system is essential for Brucella abortus virulence. It was shown previously that its dysfunction alters the expression of some major outer membrane proteins and the pattern of lipid A acylation. To determine the genes regulated by BvrR/BvrS, we performed a whole-genome microarray analysis using B. abortus RNA obtained from wild type and bvrR mutant cells grown in the same conditions.Methodology/Principal FindingsA total of 127 differentially expressed genes were found: 83 were over expressed and 44 were less expressed in the bvrR mutant. Two operons, the phosphotransferase system and the maltose transport system, were down-regulated. Several genes involved in cell envelope or outer membrane biogenesis were differentially expressed: genes for outer membrane proteins (omp25a, omp25d), lipoproteins, LPS and fatty acid biosynthesis, stress response proteins, chaperones, flagellar genes, and twelve genes encoding ABC transport systems. Ten genes related with carbon metabolism (pckA and fumB among others) were up-regulated in the bvrR mutant, and denitrification genes (nirK, norC and nosZ) were also regulated. Notably, seven transcriptional regulators were affected, including VjbR, ExoR and OmpR that were less expressed in the bvrR mutant. Finally, the expression of eleven genes which have been previously related with Brucella virulence was also altered.Conclusions/SignificanceAll these data corroborate the impact of BvrR/BvrS on cell envelope modulation, confirm that this system controls the carbon and nitrogen metabolism, and suggest a cross-talk among some regulators to adjust the Brucella physiology to the shift expected to occur during the transit from the extracellular to the intracellular niche

The effect of strontium incorporation into sol-gel biomaterials on their protein adsorption and cell interactions

[EN] It is known strontium can both inhibit the osteoclast formation and stimulate the osteoblast maturation, so biomaterials containing this element can favour bone structure stabilisation. The addition of Sr to biomaterials could affect their interactions with proteins and cells. Here, a silica-hybrid sol-gel network doped with different amounts of SrCl2 and applied as coatings on titanium discs was examined. in vitro analysis was performed to determine the potential effect of Sr in the coatings, showing enhanced gene expression of osteogenic markers (alkaline phosphatase and transforming growth factor-beta) in MC3T3-E1 incubated with Sr-doped biomaterials. The examination of inflammatory markers (tumour necrosis factor-alpha and interleukin 10) in RAW 264.7 macrophages revealed an anti-inflammatory potential of these materials. Proteins adsorbed onto the coatings incubated with human serum (3 h at 37 degrees C) were also analysed; mass spectrometry was used to characterise the proteins adhering to materials with different Sr content. Adding Sr to the coatings increased their affinity to APOE and VTNC proteins (associated with anti-inflammatory and osteogenic functions). Moreover, the proteins involved in coagulation processes, such as prothrombin, were more abundant on the coatings containing Sr than on the base sol-gel surfaces. Correlations between gene expression and proteomic results were also examined.This work was supported by MINECO (MAT2017-86043-R); Universitat Jaume I (grant numbers Predoc/2014/25, UJI-B2017-37); Basque Government (grant numbers IT611-13, Predoc/2016/1/0141), and University of the Basque Country (UFI11/56). Authors would like to thank Antonio Coso and Jaime Franco (GMI-Ilerimplant) for their inestimable contribution to this study, and Raquel Oliver, Jose Ortega (UJI), and Iraide Escobes (CIC bioGUNE) for their valuable technical assistance.Romero-Gavilán, F.; Araújo-Gomes, N.; García-Arnáez, I.; Martínez-Ramos, C.; Elortza, F.; Azkargorta, M.; Iloro, I.... (2019). The effect of strontium incorporation into sol-gel biomaterials on their protein adsorption and cell interactions. Colloids and Surfaces B Biointerfaces. 174:9-16. https://doi.org/10.1016/j.colsurfb.2018.10.075S91617

Proteomic analysis of calcium-enriched sol-gel biomaterials

[EN] Calcium is an element widely used in the development of biomaterials for bone tissue engineering as it plays important roles in bone metabolism and blood coagulation. The Ca ions can condition the microenvironment at the tissue-material interface, affecting the protein deposition process and cell responses. The aim of this study was to analyze the changes in the patterns of protein adsorption on the silica hybrid biomaterials supplemented with different amounts of CaCl2, which can function as release vehicles. This characterization was carried out by incubating the Ca-biomaterials with human serum. LC-MS/MS analysis was used to characterize the adsorbed protein layers and compile a list of proteins whose affinity for the surfaces might depend on the CaCl2 content. The attachment of pro- and anti-clotting proteins, such as THRB, ANT3, and PROC, increased significantly on the Ca-materials. Similarly, VTNC and APOE, proteins directly involved on osteogenic processes, attached preferentially to these surfaces. To assess correlations with the proteomic data, these formulations were tested in vitro regarding their osteogenic and inflammatory potential, employing MC3T3-E1 and RAW 264.7 cell lines, respectively. The results confirmed a Ca dose-dependent osteogenic and inflammatory behavior of the materials employed, in accordance with the protein attachment patterns.This work was supported by MINECO [MAT2017-86043-R]; Universitat Jaume I [Grant numbers Predoc/2014/25, UJI-B2017-37]; Basque Government [Grant numbers IT611-13, Predoc/2016/1/0141]; University of the Basque Country [Grant number UFI11/56]. CIC bioGUNE is supported by Basque Department of Industry, Tourism and Trade (Etortek and Elkartek programs), the Innovation Technology Department of the Bizkaia County; The ProteoRed-ISCIII (Grant PRB3 IPT17/0019); CIBERehd Network, and Severo Ochoa Grant (SEV-2016-0644). 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An implementation-focused bio/algorithmic workflow for synthetic biology.

As synthetic biology moves away from trial and error and embraces more formal processes, workflows have emerged that cover the roadmap from conceptualization of a genetic device to its construction and measurement. This latter aspect (i.e. characterization and measurement of synthetic genetic constructs) has received relatively little attention thus far, but it is crucial for their outcome. An end-to-end use case for engineering a simple synthetic device is presented which is supported by information standards and computational methods, and which focuses on such characterization/measurement. This workflow captures the main stages of genetic device design and description and offers standardized tools for both population-based measurement and single-cell analysis. To this end, three separate aspects are addressed. First, the specific vector features. Although device/circuit design has been successfully automated, important structural information is usually overlooked, as is the case of plasmid vectors. The use of the Standard European Vector Architecture (SEVA) is advocated for selecting the optimal carrier of a design and its thorough description, in order to unequivocally correlate digital definitions and molecular devices. A digital version of this plasmid format was developed with the Synthetic Biology Open Language (SBOL) along with a software tool that allows users to embed genetic parts in vector cargoes. This enables annotation of a mathematical model of the device's kinetic reactions formatted with the Systems Biology Markup Language (SBML). From that point onwards the experimental results and their in silico counterparts proceed alongside, with constant feedback to preserve consistency between them. A second aspect involves a framework for the calibration of fluorescence-based measurements. One of the most challenging endeavors in standardization, metrology, is tackled by reinterpreting the experimental output in light of simulation results, allowing us to turn arbitrary fluorescent units into relative measurements. Finally, integration of single-cell methods into a framework for multicellular simulation and measurement is addressed, allowing standardized inspection of the interplay between the carrier chassis and the culture conditions

Model Systems of Precursor Cellular Membranes: Long-Chain Alcohols Stabilize Spontaneously Formed Oleic Acid Vesicles

AbstractOleic acid vesicles have been used as model systems to study the properties of membranes that could be the evolutionary precursors of more complex, stable, and impermeable phospholipid biomembranes. Pure fatty acid vesicles in general show high sensitivity to ionic strength and pH variation, but there is growing evidence that this lack of stability can be counterbalanced through mixtures with other amphiphilic or surfactant compounds. Here, we present a systematic experimental analysis of the oleic acid system and explore the spontaneous formation of vesicles under different conditions, as well as the effects that alcohols and alkanes may have in the process. Our results support the hypothesis that alcohols (in particular 10- to 14-C-atom alcohols) contribute to the stability of oleic acid vesicles under a wider range of experimental conditions. Moreover, studies of mixed oleic-acid-alkane and oleic-acid-alcohol systems using infrared spectroscopy and Langmuir trough measurements indicate that precisely those alcohols that increased vesicle stability also decreased the mobility of oleic acid polar headgroups, as well as the area/molecule of lipid

A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.This work was partially supported by the Fundacion Espanola para la Ciencia y la Tecnologia (UCA PR214), the Asociacion Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019110895RB-I00), and Inversion Territorial Integrada de la Provincia de Cadiz (ITI-0038-2019)

Las comunidades terapéuticas como tratamiento para las drogodependencias: una revisión sistemática del seguimiento a corto plazo

Objetivo. Las comunidades terapéuticas (CT) constituyen uno de los tratamientos más extensos para las drogodependencias; sin embargo, su investigación es escasa. El objetivo fue realizar una revisión sistemática para conocer los elementos metodológicos de los estudios de seguimiento a corto plazo y, a su vez, describir las consecuencias de las CT. Material y método. Se aplicó el "Preferred Reporting Items for Systematic reviews and meta- Analyses" (PRISMA) para la búsqueda en Medline, PsycINFO, PsycARTICLES y PsycCRITIQUES de estudios de seguimiento a corto plazo de CT entre 1980 y 2010. Resultados. El seguimiento consiste en un registro inicial y, al menos, otro al medio año de tratamiento; la muestra mínima contiene 60 usuarios con una mayor prevalencia de hombres solteros;el 50% continúa en seguimiento y/o alcanza la abstinencia. Conclusión. Las CT parecen ser beneficiosas para el ajuste del consumo y otros aspectos psicosociales, aunque la falta de información dificulta garantizar la comparación de estos hallazgos. © 2013 Elsevier España, S.L. y SET. Todos los derechos reservados