Cost-Effectiveness of Pembrolizumab Regimens for the First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma in Argentina.

INTRODUCTION: The phase III KEYNOTE-048 trial showed that the programmed death receptor 1 (PD-1) inhibitor pembrolizumab, in the combined positive score (CPS) ≥ 1 population and combined with platinum + 5-fluorouracil in the total population, improves survival over cetuximab + platinum + 5-fluorouracil in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We evaluated the cost-effectiveness of pembrolizumab as monotherapy in the CPS ≥ 1 population or combined with platinum + 5-fluorouracil in the total population versus cetuximab + platinum + 5-fluorouracil from the social security perspective in Argentina. METHODS: A partitioned survival model projected costs and outcomes over 20 years with 3% annual discounting. Health state occupancy was modeled using KEYNOTE-048 Kaplan-Meier curves until the final analysis data cutoff, followed by parametric extrapolations guided by statistical criteria. Costs for initial and subsequent treatments, disease and adverse events management, and terminal care were included (AR $74.00 = 1 USD). Time-on-treatment and EuroQol five-dimension scores were taken from KEYNOTE-048. Utilities were derived using an Argentina-specific algorithm. RESULTS: With pembrolizumab monotherapy, patients accrued 1.1040 additional life-years and 0.8768 additional quality-adjusted life-years (QALYs), for incremental cost-effectiveness ratios (ICERs) of AR $135,801/life-year and AR $170,985/QALY gained over cetuximab + platinum + 5-fluorouracil. Additional life-years and QALYs gained with pembrolizumab combination therapy versus cetuximab + platinum + 5-fluorouracil were 1.3296 and 1.0536, respectively (ICERs of AR $680,143/life-year and AR $858,306/QALY). Considering a threshold of AR $1,676,122/QALY gained, pembrolizumab monotherapy and combination therapy had an 88.0% and a 77.1% probability of being cost-effective, respectively. CONCLUSION: Pembrolizumab either as monotherapy or in combination with chemotherapy offers substantial survival gains for patients with R/M HNSCC at small additional costs, making it a cost-effective treatment versus cetuximab + platinum + 5-FU in Argentina.

Cost-Effectiveness of Pembrolizumab for the Adjuvant Treatment of Melanoma Patients with Lymph Node Involvement Who Have Undergone Complete Resection in Argentina.

INTRODUCTION: The KEYNOTE-054 trial demonstrated that adjuvant pembrolizumab improves recurrence-free survival in completely resected stage III melanoma versus watchful waiting (hazard ratio [HR] = 0.57; 98.4% confidence interval [CI], 0.43-0.74). We evaluated the cost-effectiveness of pembrolizumab in Argentina, where watchful waiting is still widely used among these patients despite the high risk of recurrence with surgery alone. METHODS: A four-health state model was used (recurrence-free, locoregional recurrence [LR], distant metastases [DM], death). Lifetime medical costs to payers (72.08 Argentine pesos [AR$] = 1.00 U.S. dollar [USD]) and outcomes (3% annual discount) were assessed, together with incremental cost-effectiveness ratios (ICERs). First and LR→DM recurrences were modeled using KEYNOTE-054 and real-world data, respectively. No benefits of adjuvant treatment were assumed post-progression. Pre-DM and post-DM mortality was based on KEYNOTE-054 and on a network meta-analysis of advanced treatments expected in each arm, respectively. Utilities were derived from KEYNOTE-054 Euro-QoL data using an Argentinian algorithm, and from the literature. Public ex-factory drug prices were used. RESULTS: Patients in the pembrolizumab and the watchful waiting arms accrued 8.78 and 5.83 quality-adjusted life-years (QALYs), 9.91 and 6.98 life-years, and costs of AR$12,698,595 (176,174 USD) and AR$11,967,717 (166,034 USD), respectively. The proportion of life-years accrued that were recurrence-free was 80.8% and 56.9% in the pembrolizumab and the watchful waiting arms, respectively. Pembrolizumab patients gained 2.94 life-years and 2.96 QALYs versus watchful waiting; the ICER per QALY was AR$247,094 (3428 USD). Recurrence rates and advanced melanoma treatments were the key drivers of the ICER. At a threshold of AR$1,445,325 (29,935 USD) per QALY, pembrolizumab had an 83.5% probability of being cost-effective versus watchful waiting. CONCLUSIONS: Adjuvant pembrolizumab after complete resection of melanoma with node involvement is highly cost-effective relative to watchful waiting in Argentina, across disease stage subgroups and BRAF mutational status. This strongly supports its coverage and reimbursement across the entire health system.

Inestabilidad posterior de hombro. Resultados de la reconstrucción artroscópica en pacientes sin defectos óseos significativos / Posterior shoulder instability. Arthroscopic reconstruction in patients without significant bone defects

Presentamos los resultados de una serie de casos de pacientes con inestabilidad posterior de hombro, sin defectos óseos ni retroversión glenoidea significativos, tratados con técnica artroscópica de reparación cápsulolabral con anclajes. Entre 2010 y 2019, dieciocho pacientes con inestabilidad posterior de hombro fueron tratados con una reparación cápsulolabral artroscópica con anclajes, en el mismo centro quirúrgico y por el mismo cirujano. Fueron dieciséis hombres y dos mujeres con una edad promedio de 30.5 años (en un rango de diecinueve a cuarenta y cuatro años). Con un seguimiento promedio de 64.4 meses (en un rango entre trece y ciento dieciséis meses) los pacientes fueron evaluados clínicamente con el test de Kim, Jerk y test de aprehensión. También utilizamos los scores de WOSI, ASES, Rowe, radiografía, tomografía computada y resonancia magnética, para las evaluaciones pre y postoperatorias. Tipo de estudio: Serie de casos. Nivel de evidencia: IV

Objective: We present the results of a case series of patients with posterior shoulder instability without significant bone defects or excessive glenoid retroversion treated with arthroscopic capsule-labral repair with suture anchors.Methods: Between 2010 and 2019, 18 patients with posterior shoulder instability underwent an arthroscopic capsule-labral repair with suture anchors. All the cases were operated on at the same surgical center by the same surgeon. The patients were 16 men and two women with an average age of 30.5 years (range 19 to 44 years). With a mean follow up of 64.4 months (range 13-116 months), the patients were clinically evaluated by the Kim, Jerk, and Apprehension tests. Furthermore, the WOSI, ASES, and ROWE scores, X Rays, CT Scans, and MRIs were also used for pre and postoperative assessment. Results: We did not find any case of recurrence of instability. At the final follow up, the Kim's, Jerk, and Apprehension tests were negative in all the patients. The posterior drawer test decreased translation at an average of 2 pluses. The mean WOSI Score risen from 35.2 to 86.5, the ASES from 33.3 to 85.3, and the Rowe from 20.3 to 91.1. Two patients showed moderate to severe degenerative changes at the final X-Rays. The postoperative MRIs of 12 patients demonstrated an anatomic reduction and adequate healing of the posterior labrum.Conclusions: The arthroscopic repair of the labrum with anchors is a reliable, reproducible, and effective technique that warrants satisfactory results in selected posterior shoulder instability cases without significant glenoid bone loss or excessive retroversion. Type of study: Case series. Level of evidence: IV

Rapid experimental evolution of reproductive isolation from a single natural population.

Ecological speciation occurs when local adaptation generates reproductive isolation as a by-product of natural selection. Although ecological speciation is a fundamental source of diversification, the mechanistic link between natural selection and reproductive isolation remains poorly understood, especially in natural populations. Here, we show that experimental evolution of parasite body size over 4 y (approximately 60 generations) leads to reproductive isolation in natural populations of feather lice on birds. When lice are transferred to pigeons of different sizes, they rapidly evolve differences in body size that are correlated with host size. These differences in size trigger mechanical mating isolation between lice that are locally adapted to the different sized hosts. Size differences among lice also influence the outcome of competition between males for access to females. Thus, body size directly mediates reproductive isolation through its influence on both intersexual compatibility and intrasexual competition. Our results confirm that divergent natural selection acting on a single phenotypic trait can cause reproductive isolation to emerge from a single natural population in real time.

Host defense triggers rapid adaptive radiation in experimentally evolving parasites.

Adaptive radiation occurs when the members of a single lineage evolve different adaptive forms in response to selection imposed by competitors or predators. Iconic examples include Darwin's finches, Caribbean anoles, and Hawaiian silverswords, all of which live on islands. Although adaptive radiation is thought to be an important generator of biodiversity, most studies concern groups that have already diversified. Here, we take the opposite approach. We experimentally triggered diversification in the descendants of a single population of host-specific parasites confined to different host "islands." We show rapid adaptive divergence of experimentally evolving feather lice in response to preening, which is a bird's main defense against ectoparasites. We demonstrate that host defense exerts strong phenotypic selection for crypsis in lice transferred to different colored rock pigeons (Columba livia). During four years of experimental evolution (∼60 generations), the lice evolved heritable differences in color. Strikingly, the observed color differences spanned the range of phenotypes found among congeneric lice adapted to other species of birds. To our knowledge, this is the first real-time demonstration that microevolution is fast enough to simulate millions of years of macroevolutionary change. Our results further indicate that host-mediated selection triggers rapid divergence in the adaptive radiation of parasites, which are among the most diverse organisms on Earth.

Avances en impuestos del tabaco: el caso de Argentina

[RESUMEN]. En mayo de 2016, el Poder Ejecutivo de Argentina sancionó el decreto 626, que aumentó los impuestos internos de los cigarrillos de 60% a 75%, lo que implicó un aumento de 50% en su precio medio de venta al público. Esta medida fue impulsada desde la Fundación Interamericana del Corazón (FIC) Argentina a través de una estrategia que incluyó el desarrollo de investigaciones locales para determinar la viabilidad y el impacto de la medida, la elaboración de una propuesta política, el trabajo en red con otras organizaciones de la sociedad civil nacionales e internacionales, acciones de incidencia colaborativa con referentes del Poder Ejecutivo Nacional y la implementación de una estrategia de comunicación. La particularidad de cada uno de los contextos económicos, sociales, políticos e institucionales de los países de la Región de las Américas requiere que las propuestas políticas se adecúen a la realidad local. La experiencia de trabajo desarrollada por FIC Argentina sirve como guía para otras organizaciones que en la Región buscan impulsar aumentos de los impuestos al tabaco u otras políticas destinadas a proteger la salud pública, adaptando las recomendaciones internacionales y la evidencia local al contexto de cada país. En este artículo se comparte una serie de lecciones aprendidas que pueden servir en otros países.

[ABSTRACT]. In May 2016, the executive branch of the Government of Argentina ratified Decree 626, which raised domestic taxes on cigarettes from 60% to 75%, amounting to a 50% increase in their average retail price. This measure was promoted by Argentina’s InterAmerican Heart Foundation (FIC Argentina) through a strategy that included conducting local research to assess the measure’s viability and impact; drafting a policy proposal; working in coordination with other national and international civil society organizations; pursuing collaborative incidence activities with key members of the national executive branch; and implementing a communications strategy. The uniqueness of each economic, social, political, and institutional context in the countries of the Region of the Americas makes it necessary to adapt policy to local conditions. The work experience of FIC Argentina serves as a roadmap for other organizations in the Region that seek to promote an increase in taxes on tobacco products or other policies designed to protect public health by adapting international recommendations and local evidence to each country’s specific context. This article presents a series of lessons learned that may prove useful in other countries.

[RESUMO]. Em maio de 2016, as autoridades do poder executivo da Argentina sancionaram o Decreto 626 que determinou um aumento da tributação interna dos cigarros de 60% a 75%, implicando em um aumento de 50% no preço médio de venda ao consumidor. Esta medida foi apoiada pela Fundação Interamericana do Coração (FIC) Argentina que adotou uma estratégia que abrangeu a realização de pesquisas locais para determinar a viabilidade e o impacto de tal medida, a elaboração de uma proposta política, o trabalho em rede com outras organizações nacionais e internacionais da sociedade civil, ações colaborativas com representantes do poder executivo nacional e a implementação de uma campanha de comunicação. As particularidades dos contextos econômicos, sociais, políticos e institucionais de cada país da Região das Américas exigem que as propostas políticas se adéquem à realidade local. A experiência de trabalho realizado pela FIC Argentina serve de modelo a outras organizações que defendem o aumento da tributação dos cigarros e outras políticas de proteção da saúde pública, com a adaptação das recomendações internacionais ao contexto de cada país e o uso das evidências locais. Este artigo expõe uma série de ensinamentos que podem servir a outros países da Região.

[New strides in tobacco taxation: the case of ArgentinaAvanços na tributação dos cigarros: o caso da Argentina]. / Avances en impuestos del tabaco: el caso de Argentina.

In May 2016, the executive branch of the Government of Argentina ratified Decree 626, which raised domestic taxes on cigarettes from 60% to 75%, amounting to a 50% increase in their average retail price. This measure was promoted by Argentina's InterAmerican Heart Foundation (FIC Argentina) through a strategy that included conducting local research to assess the measure's viability and impact; drafting a policy proposal; working in coordination with other national and international civil society organizations; pursuing collaborative incidence activities with key members of the national executive branch; and implementing a communications strategy. The uniqueness of each economic, social, political, and institutional context in the countries of the Region of the Americas makes it necessary to adapt policy to local conditions. The work experience of FIC Argentina serves as a roadmap for other organizations in the Region that seek to promote an increase in taxes on tobacco products or other policies designed to protect public health by adapting international recommendations and local evidence to each country's specific context. This article presents a series of lessons learned that may prove useful in other countries.

Em maio de 2016, as autoridades do poder executivo da Argentina sancionaram o Decreto 626 que determinou um aumento da tributação interna dos cigarros de 60% a 75%, implicando em um aumento de 50% no preço médio de venda ao consumidor. Esta medida foi apoiada pela Fundação Interamericana do Coração (FIC) Argentina que adotou uma estratégia que abrangeu a realização de pesquisas locais para determinar a viabilidade e o impacto de tal medida, a elaboração de uma proposta política, o trabalho em rede com outras organizações nacionais e internacionais da sociedade civil, ações colaborativas com representantes do poder executivo nacional e a implementação de uma campanha de comunicação. As particularidades dos contextos econômicos, sociais, políticos e institucionais de cada país da Região das Américas exigem que as propostas políticas se adéquem à realidade local. A experiência de trabalho realizado pela FIC Argentina serve de modelo a outras organizações que defendem o aumento da tributação dos cigarros e outras políticas de proteção da saúde pública, com a adaptação das recomendações internacionais ao contexto de cada país e o uso das evidências locais. Este artigo expõe uma série de ensinamentos que podem servir a outros países da Região.

Evaluaciones económicas en un sistema de salud fragmentado: oportunidades y desafíos metodológicos para Argentina / Economic Evaluations in a Fragmented Health System: Opportunities and Methodological Challenges for Argentina

INTRODUCCIÓN: La particularidad del sistema de salud argentino, que se encuentra fragmentado en tres subsistemas y con más de 900 financiadores, lleva a reflexionar sobre cuál es la posibilidad de desarrollar evaluaciones económicas (EE) en forma global y que sirvan de modo eficiente al proceso de toma de decisiones. OBJETIVOS: Identificar y discutir los desafíos metodológicos que implican el diseño de EE en un sistema de salud caracterizado por la fragmentación, la no integración en la prestación de servicios y la presencia de múltiples financiadores. Analizar los aspectos claves de la formulación de las EE y su aplicabilidad en nuestro contexto, así como también la generalización y transferibilidad de sus resultados hacia el sistema de salud en su conjunto. MÉTODOS: Se realizó una búsqueda sistemática de la literatura en las principales fuentes bibliográficas. Se relevaron indicadores a nivel provincial y sectorial. Asimismo, se citan ejemplos de estudios de EE que demuestran las diferencias intersectoriales en los principales elementos metodológicos que componen una EE. CONCLUSIONES: Las características de nuestro sistema de salud fragmentado implican diferencias en términos de estructuras de costos, perspectiva de análisis y umbrales de disponibilidad a pagar según la entidad involucrada. Ello tiene repercusiones metodológicas en la elaboración y en los resultados de las EE y, por tanto, condiciona la aplicabilidad o generalización de los resultados a nivel nacional.

Avances en impuestos del tabaco: el caso de Argentina / New strides in tobacco taxation: the case of Argentina / Avanços na tributação dos cigarros: o caso da Argentina

RESUMEN En mayo de 2016, el Poder Ejecutivo de Argentina sancionó el decreto 626, que aumentó los impuestos internos de los cigarrillos de 60% a 75%, lo que implicó un aumento de 50% en su precio medio de venta al público. Esta medida fue impulsada desde la Fundación Interamericana del Corazón (FIC) Argentina a través de una estrategia que incluyó el desarrollo de investigaciones locales para determinar la viabilidad y el impacto de la medida, la elaboración de una propuesta política, el trabajo en red con otras organizaciones de la sociedad civil nacionales e internacionales, acciones de incidencia colaborativa con referentes del Poder Ejecutivo Nacional y la implementación de una estrategia de comunicación. La particularidad de cada uno de los contextos económicos, sociales, políticos e institucionales de los países de la Región de las Américas requiere que las propuestas políticas se adecúen a la realidad local. La experiencia de trabajo desarrollada por FIC Argentina sirve como guía para otras organizaciones que en la Región buscan impulsar aumentos de los impuestos al tabaco u otras políticas destinadas a proteger la salud pública, adaptando las recomendaciones internacionales y la evidencia local al contexto de cada país. En este artículo se comparte una serie de lecciones aprendidas que pueden servir en otros países.

ABSTRACT In May 2016, the executive branch of the Government of Argentina ratified Decree 626, which raised domestic taxes on cigarettes from 60% to 75%, amounting to a 50% increase in their average retail price. This measure was promoted by Argentina's InterAmerican Heart Foundation (FIC Argentina) through a strategy that included conducting local research to assess the measure's viability and impact; drafting a policy proposal; working in coordination with other national and international civil society organizations; pursuing collaborative incidence activities with key members of the national executive branch; and implementing a communications strategy. The uniqueness of each economic, social, political, and institutional context in the countries of the Region of the Americas makes it necessary to adapt policy to local conditions. The work experience of FIC Argentina serves as a roadmap for other organizations in the Region that seek to promote an increase in taxes on tobacco products or other policies designed to protect public health by adapting international recommendations and local evidence to each country's specific context. This article presents a series of lessons learned that may prove useful in other countries.

RESUMO Em maio de 2016, as autoridades do poder executivo da Argentina sancionaram o Decreto 626 que determinou um aumento da tributação interna dos cigarros de 60% a 75%, implicando em um aumento de 50% no preço médio de venda ao consumidor. Esta medida foi apoiada pela Fundação Interamericana do Coração (FIC) Argentina que adotou uma estratégia que abrangeu a realização de pesquisas locais para determinar a viabilidade e o impacto de tal medida, a elaboração de uma proposta política, o trabalho em rede com outras organizações nacionais e internacionais da sociedade civil, ações colaborativas com representantes do poder executivo nacional e a implementação de uma campanha de comunicação. As particularidades dos contextos econômicos, sociais, políticos e institucionais de cada país da Região das Américas exigem que as propostas políticas se adéquem à realidade local. A experiência de trabalho realizado pela FIC Argentina serve de modelo a outras organizações que defendem o aumento da tributação dos cigarros e outras políticas de proteção da saúde pública, com a adaptação das recomendações internacionais ao contexto de cada país e o uso das evidências locais. Este artigo expõe uma série de ensinamentos que podem servir a outros países da Região.

Impacto clínico y económico en pacientes incidentes en diálisis según condición de ingreso / Clinical and economic impact on incident dialysis patients according to admission condition

INTRODUCCIÓN La enfermedad renal crónica es una patología de alta prevalencia a nivel mundial, con creciente número de pacientes con nuevo diagnóstico y acceso a instancias críticas con insuficiencia funcional en estadíos terminales. Se trata de una entidad con doble efecto; es tributaria de patologías crónicas prevalentes con gran carga de morbimortalidad cardiovascular y uso de recursos sanitarios (como diabetes o hipertensión arterial) y al mismo tiempo multiplica el impacto del riesgo (tanto clínico como económico) atribuible a las mismas. El primer año en tratamiento con diálisis de estos pacientes es donde se registran la mayor cantidad de eventos clínicos y muertes, con gran consumo de recursos sanitarios. OBJETIVO Establecer el efecto de las condiciones clínicas de pacientes incidentes a diálisis en la cantidad y severidad de eventos así como el gasto sanitario incurrido durante el primer año posterior al ingreso a tratamiento. MÉTODOS Se seleccionó una muestra retrospectiva de 20.256 pacientes incidentes en diálisis provenientes de 8 financiadores representativos de los subsectores del sistema de salud argentino, entre enero 2010 y diciembre 2015, y se los siguió durante un año posterior a la fecha de ingreso o bien su baja antes de dicho plazo por muerte, trasplante o recuperación funcional. Se consideraron variables epidemiológicas, clínicas y de cobertura relevantes para evaluar la morbimortalidad. Se aplicaron secuencialmente análisis univariantes y multivariantes para evaluar el impacto de dichos parámetros en la mortalidad (modelo de riesgos proporcionales de Cox) y aparición de eventos, consumo de prestaciones y gasto asociado (regresión logística). RESULTADOS Se encontró una alta tasa de mortalidad precoz, con un 66% de los óbitos ocurridos en el primer semestre de seguimiento; las variables asociadas con este desenlace fueron (en orden de significancia) la edad >65 años, presencia de catéter transitorio al ingreso, diagnóstico de diabetes, albuminemia <4 g/dl, diagnóstico de insuficiencia cardíaca y angina persistente. Con respecto a los eventos de internación fueron 5 veces más frecuentes en períodos cercanos al ingreso a diálisis, con duplicación en la duración de las instancias, hasta 3 veces mayor consumo de prácticas asociadas y costos 8 veces superiores (1er vs 2do semestre), encontrándose diferencias específicas entre financiadores y modelos de contratación. El gasto mensual ponderado de un paciente incidente en diálisis (tratamiento dialítico + complicaciones) resultó entre 15 a 35 veces más elevado que el valor per cápita de cobertura convencional, y este gasto llegó a ser hasta 45 veces en el período precoz (1er semestre) por aumento de complicaciones. DISCUSIÓN La población incidente en diálisis estudiada presenta alta morbimortalidad, asociada con condiciones de riesgo conocidas y de alto impacto. La carga de consumo de servicios y costos es mayor en los períodos cercanos al momento de ingreso, evidenciando una potencial falta de seguimiento previo o selección adecuada de pacientes para acceder al tratamiento

Revisión del artículo original publicado por Arce, Lacroze, Butler y Barclay "Reconstrucción artroscópica del LCA. técnica y resultados" en la revista Artroscopia Vol.1 Nº1 en 1994 / Review of the original article published by Arce, Lacroze, Butler and Barclay "Arthroscopic reconstruction of the LCA technique and results" in the arthroscopy journal Vol.1 Nº1 in 1994

Este clásico comenta el articulo original "Reconstrucción Artroscópica del LCA. Técnica Quirúrgica y Resultados" publicado por Arce, Lacroze, Butler y Barclay hace 25 años en el Vol. 1 N° 1 de la Revista Artroscopía. El trabajo clásico estuvo basado en la reconstrucción con técnica artroscópica del ligamento cruzado anterior utilizando injerto del tendón rotuliano. Esta fue uno de las primeras publicaciones en idioma español sobre esta entonces novedosa técnica quirúrgica.

This classic discusses the original article "Arthroscopic ACL Reconstruction. Surgical Technique and Results" by Arce, Lacroze, Butler and Barclay published 25 years ago at the Journal Revista Artroscopía Vol.1 # 1. This classic paper was based on the arthroscopic technique for ACL reconstruction with patellar tendon graft. This article was one of the first publications in spanish language about what, at the time, was a novel surgical technique.