Large-Scale Dynamics of Self-propelled Particles Moving Through Obstacles: Model Derivation and Pattern Formation.

We model and study the patterns created through the interaction of collectively moving self-propelled particles (SPPs) and elastically tethered obstacles. Simulations of an individual-based model reveal at least three distinct large-scale patterns: travelling bands, trails and moving clusters. This motivates the derivation of a macroscopic partial differential equations model for the interactions between the self-propelled particles and the obstacles, for which we assume large tether stiffness. The result is a coupled system of nonlinear, non-local partial differential equations. Linear stability analysis shows that patterning is expected if the interactions are strong enough and allows for the predictions of pattern size from model parameters. The macroscopic equations reveal that the obstacle interactions induce short-ranged SPP aggregation, irrespective of whether obstacles and SPPs are attractive or repulsive.

Análisis costo-efectividad de lenalidomida en combinación con dexametasona frente a bortezomib combinado con dexametasona en el tratamiento en segunda línea del mieloma múltiple en Chile / Cost-effectiveness of lenalidomide in combination with dexamethasone compared to bortezomib in combination with dexamethasone for the second-line treatment of multiple myeloma in Chile

CONTEXTO: El mieloma múltiple es una neoplasia de las células plasmáticas de la medula ósea. Las terapias disponibles no son curativas y la mayoría de los pacientes se vuelve refractario al tratamiento. Agentes como lenalidomida y bortezomib han demostrado su eficacia en el tratamien-to en segunda línea de estos pacientes. OBJETIVO: Evaluar el costo-efectividad de la combinación lenalidomida/dexametasona frente a bortezomib/dexametasona en pacientes con mieloma múltiple, no candidatos a trasplante, previamente tratados con bortezomib, desde la perspectiva del sistema nacional de salud chileno. METODOLOGÍA: Se empleó un modelo de Markov que simula la evolución de una cohorte de pacientes a través de cuatro estados de salud (preprogresión en tratamiento, preprogresión sin tratamiento, progresión o muerte) en un horizonte temporal de 25 años. Los datos de eficacia, uso de recursos y frecuencia de efectos adversos fueron extraídos de los ensayos sobre mieloma múltiple MM-009 y MM-010 y de un estudio retrospectivo de retratamiento con bortezomib. Todos los parámetros fueron validados por expertos. Se aplicó una tasa de descuento en costos y beneficios de 3%. La robustez de los resultados fue evaluada mediante un análisis de sensibilidad univariante y probabilístico. RESULTADOS: El tratamiento con lenalidomida/dexametasona proporciona 1,41 años de vida y 0,83 años de vida ajustados por calidad incrementales respecto a bortezomib/dexametasona, con un costo incremental de 11 864 597,86 pesos chilenos (19 589,86 dólares). La ratio de cos-to-efectividad y costo-utilidad incremental se cifró en 8 410 266,92 pesos chilenos (13 886,35 dólares) por año de vida ganado y 14 271 896,16 pesos chilenos (23 564,59 dólares) por año de vida ajustado por calidad respectivamente. CONCLUSIÓN: La lenalidomida/dexametasona representa una alternativa potencialmente costo-efectiva, desde la perspectiva del sistema nacional de salud chileno, para el tratamiento en segunda línea de pacientes con mieloma múltiple no candidatos a trasplante.

BACKGROUND: Multiple myeloma is a hematologic malignancy affecting bone marrow derived plasma cells. Current therapies are not able to eradicate the disease and most patients become refractory to the treatment. Lenalidomide and bortezomib have proved effective in the second-line treatment of these patients. OBJECTIVE: To evaluate the cost-effectiveness of lenalidomide in combination with dexamethasone compared to bortezomib in combination with dexamethasone in patients with multiple myeloma previously treated with bortezomib, from the perspective of the Chilean National Health Service. METHODOLOGY: A four-state Markov model (preprogression on treatment; preprogression off treatment, progression and death) was used to simulate the evolution of a cohort of multiple myeloma patients over a 25-year time horizon. Efficacy data, resource use and frequency of adverse events were extracted from MM009/010 studies and a retrospective analysis of retreatment with bortezomib. All inputs were validated by experts. A 3% annual discount rate was used for costs and health outcomes. The robustness of the results was evaluated through univariate and probabilistic sensitivity analyses. RESULTS: Lenalidomide in combination with dexamethasone treatment provided 1.41 incremental life years and 0.83 incremental quality-adjusted life years in comparison with bortezomib in combination with dexamethasone, with an incremental cost of 11 864 597.86 CLP (19 589.86 US$). The incremental cost-effectiveness and cost-utility ratio were estimated at 8 410 266.92 CLP (13 886,35 US$) / incremental life year and 14 271 896.16 CLP (23 564,59 US$)/incremental quality-adjusted life years, respectively. CONCLUSIONS: Lenalidomide in combination with dexamethasone represents a potentially cost-effective alternative for the second-line treatment of patients with multiple myeloma who are not eligible for transplantation, from the perspective of the Chilean National Health Service.

Impacto económico de las exacerbaciones agudas en EPOC / No disponible

Objetivo: Sintetizar la información disponible acerca de estudios económicos relacionados con las exacerbaciones agudas asociadas a la EPOC publicados en España durante los últimos 5 años. Material y Métodos: Revisión ordenada de la literatura (MedLine/Pubmed, Cochrane Library, ISI WOK y Google Scholar) sobre estudios económicos referentes a la EPOC y las exacerbaciones agudas (EA-EPOC) en los últimos 5 años (2011-2015). Se incluyeron artículos originales y revisiones de costes directos, uso de recursos o evaluaciones económicas desde la perspectiva del SNS español. Los costes fueron actualizados a €, 2016. Resultados: Se identificaron 8 artículos de costes y uso de recursos, además de evaluaciones económicas de la EPOC y exacerbaciones realizados en España. La presencia de EA-EPOC se asoció a unos peores resultados clínicos, mayor uso de recursos, así como a un mayor coste medio anual por paciente (3.200,4 €vs. 1.403,1 €). El coste directo anual por exacerbación osciló entre 347,7 € y 482,8 €, de los cuales, más del 70% estaban asociados a las hospitalizaciones. Asimismo, existe una tendencia al aumento en el coste directo en pacientes de EPOC en España en los últimos años (2006-2010), por aumento de costes por paciente ingresado (p<0,001). Conclusiones: En nuestro país, el manejo de las EA-EPOC, y más específicamente, de las hospitalizaciones asociadas, constituye la mayor parte de los costes directos y uso de recursos atribuibles a la EPOC. La introducción de estrategias preventivas podría reducir de manera considerable los costes directos y el uso de recursos asociadas a las EA-EPOC en España

Objective: To review and synthesize the available information on economic evaluations related to acute exacerbations of COPD published in Spain during the last 5 years. Material and Method: A comprehensive review of the literature (MedLine/Pubmed, Cochrane Library, ISI WOK y Google Scholar) on economic evaluations related to COPD and acute exacerbations in Spain between 2011 and 2015 was performed. Original articles and reviews of the literature on direct cost, resource use and economic evaluations from the Spanish NHS perspective were included. Costs were update to Spanish €, 2016. Results: A total of 8 studies regarding direct cost, use of resources and economic evaluations of COPD published in Spain during the last 5 years were identified. The presence of exacerbations in COPD patients was associated with worse clinic outcomes together with an increase in use of resources and mean cost per COPD patient and year (3,200.4 € vs. 1,403.1 €) compared with patients without exacerbations. The average direct cost of an exacerbation ranged from 347.7 € and 482.8 €. The highest proportion of this cost (70%) was attributable to hospitalizations. In addition, there is a trend towards an increase in the mean cost per COPD patient in Spain during the last years (2006-2010), as the mean cost per hospitalized patient has risen during this period (p<0.001). Conclusion: In Spain, exacerbations-associated hospitalizations account for the largest portion of COPD expenses. The introduction of preventive strategies may reduce considerably healthcare costs and resource use related to COPD exacerbations

Peripheral-blood mononuclear cell responses to recombinant hepatitis C virus antigens in patients with chronic hepatitis C.

Peripheral blood mononuclear cell proliferative responses in vitro to recombinant yeast or Escherichia coli hepatitis C virus fusion proteins were evaluated in 20 patients with chronic hepatitis C who were reactive for antibody to hepatitis C virus (on enzyme immunoassay, version 2.0, and a four-antigen recombinant immunoblot assay). Twenty age-matched, healthy individuals negative for antibody to hepatitis C virus were used as a control group. Peripheral-blood mononuclear cells from all chronic hepatitis C patients with antibodies to hepatitis C virus antigens c22 and c100-3 proliferated in vitro in response to the corresponding recombinant hepatitis C virus fusion protein. Peripheral-blood mononuclear cells from 75% of patients infected with hepatitis C virus proliferated in response to cytidine monophosphate-keto-3-deoxyoctulosonic acid-core recombinant antigen but there was no proliferative response to cytidine monophosphate-keto-3-deoxyoctulosonic acid-EF (derived from the NS5 region). All hepatitis C virus-infected patients had 33c antibody, but peripheral-blood mononuclear cells from only 9 of 14 (64%) proliferated in vitro in response to 33c. Ninety-five percent of all hepatitis C virus-infected patients had peripheral-blood mononuclear cells that proliferated in response to at least one recombinant hepatitis C virus fusion protein. The numbers and percentages of CD3 T cells, CD19 B cells and natural killer cells from patients with chronic hepatitis C virus infection did not differ from those in the healthy control group. However, the number of non-major histocompatibility complex-restricted cytotoxic T cells (CD3-positive, CD56-positive, CD16-positive) was increased in patients with chronic hepatitis C virus infection (p < 0.05).