Exploring In Vitro/In Vivo Correlation: Lessons Learned from Analyzing Phase I Results of the US EPA's ToxCast Project

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DESAFÍOS DE LA REGIÓN METROPOLITANA DE LA CONFLUENCIA FRENTE A LA EXPLOTACIÓN DE VACA MUERTA

En el presente trabajo nos proponemos dirigir la mirada hacia la denominada Región Metropolitana de la Confluencia (RMC), asentada sobre el valle irrigado y conformada por un grupo de municipios de Río Negro y Neuquén que se han planteado abordar de manera conjunta las problemáticas que trajo aparejadas el acelerado crecimiento demográfico derivado en gran medida del “fenómeno Vaca Muerta”.Nuestro marco analítico es la Prospectiva, estrechamente vinculada con la planificación del desarrollo en tanto propicia la construcción de una visión de futuro dinámica y a largo plazo y genera la posibilidad de identificar las acciones necesarias para convertir esa visión en políticas públicas, a través de programas o proyectos.La RMC, en un proceso de trabajo colectivo y dentro del financiamiento del Programa Desarrollo de Áreas Metropolitanas del Interior (DAMI), acordó la necesidad de contar con estudios y propuestas en torno a cinco lineamientos: el ambiental, el logísticoproductivo, el de movilidad y transporte, el de conectividad vial y ferroviaria y el institucional. Si bien este abordaje responde a problemáticas coyunturales, con una mirada situada en el corto y el mediano plazo, es el ejercicio de ciudadanía compartida y la oportunidad de comprenderse como región lo que puede significar un salto cualitativo.El desafío consiste en plantear conjuntamente un horizonte, un escenario deseado, en el que se puedan identificar con nitidez las dimensiones estratégicas del desarrollo

Ideas fuerza para el desarrollo y consolidación de la Región Metropolitana Confluencia

La explotación de la formación no convencional Vaca Muerta, localizada en la norpatagonia argentina, registra diariamente nuevos récords, luego de retomar las operaciones suspendidas en el marco de la pandemia por coronavirus. El impacto en el territorio de esta actividad intensiva es significativo, tanto desde el punto de vista ambiental como socioeconómico. En el presente trabajo analizaremos las derivaciones del denominado «fenómeno Vaca Muerta» y los efectos de la pospandemia en el territorio de la Región Metropolitana Confluencia, integrada por el sistema de ciudades más importante de la norpatagonia argentina. Con visión prospectiva, se identifican las ideas fuerza o aquellas iniciativas que permiten avanzar en la construcción de un escenario deseado, estableciendo lineamientos de acción en el corto, mediano y largo plazo. El trabajo apunta, además, a generar ideas y propuestas de integración y consolidación de la Región Metropolitana Confluencia, a partir de las investigaciones anteriores

Entrevista a Ramón Martínez Guarino (Agosto 2023)

Ramón Martínez Guarino es arquitecto, uruguayo de nacimiento y neuquino por elección. Trabaja en planificación desde hace décadas y cuenta con un extenso recorrido en la materia. Entre sus antecedentes se destaca el diseño de numerosos proyectos de desarrollo en diversas provincias de Argentina y también en Uruguay. Fue profesor en la Maestría de Ordenamiento Territorial y Desarrollo Urbano de la Universidad de la República de Montevideo y dictó cursos de Posgrado en Universidades de México y de nuestro país. Publicó libros sobre planificación y asimismo de cuentos y relatos.En 1997, como titular del COPADE, el emblemático organismo creado para planificar el desarrollo de la Provincia del Neuquén, lideró el grupo que redactó el plan estratégico “Neuquén 2020”, programa que proyectó una provincia con perfil agroforestal, productora de alimentos para el mundo con tres coordenadas complementarias: turismo, energía y minería”.A continuación, transcribimos la entrevista que mantuvimos con el objeto de compartir sus ideas y experiencias

[Budget impact analysis for peginterferon beta-1a in relapsing remitting multiple sclerosis in Italy]

 BACKGROUND: Peginterferon beta-1a, injected every two weeks, is the first approved pegylated interferon beta-1a for the treatment of relapsing remitting multiple sclerosis (RRMS). The objective of this analysis was to estimate the economic impact due to the introduction of peginterferon beta-1a in Italy.METHODS: This analysis was conducted with a three-year time horizon with the support of a simple decision-analytic model adopting the perspective of the Italian National Healthcare Service (NHS). Healthcare costs sustained by the Italian NHS to manage the RRMS population (drug treatment, monitoring, relapse management, adverse events management) were calculated over 3 years and compared in two scenarios: the base scenario where interferons-beta and glatiramer acetate (GA) are used to treat RRMS patients, and an alternative scenario where peginterferon beta-1a can also be used to treat RRMS patients. The target population was approximately 35,500, 37,500 and 39,500 patients at year 1, 2 and 3 respectively, based on the published literature and market data. The efficacy of treatments was simulated as a reduction of relapse rates and was derived from a Network Meta-analysis. Unit costs were based on current prices and tariffs, and the published literature. A one-way sensitivity analysis was developed.RESULTS: According to current price and described assumptions, it was estimated that the introduction of peginterferon beta-1a would result in a decrease of total costs when compared with the base scenario. The cost in the base scenario was estimated to be  € 321.5, € 339.7 and € 357.8 million in years 1, 2, and 3, respectively. In the alternative scenario, the same costs resulted in about € 321.1, € 338.6 and € 356.2 million, respectively. The cumulative budget impact over three years period was approximately a cost saving of € 3.1 million (about 0.3% saving).CONCLUSION: The adoption of peginterferon beta-1a for the treatment of RRMS would be viewed as economically sustainable by the Italian NHS.[Article in Italian

[Cost-effectiveness analysis of peginterferon beta-1a in Italian relapsing remitting multiple sclerosis management]

BACKGROUND: Peginterferon beta-1a is indicated in adult patients for the treatment of relapsing remitting multiple sclerosis (RRMS). The efficacy and safety of peginterferon beta-1a was demonstrated in the placebo-controlled ADVANCE trial.OBJECTIVE: The objective of this study was to assess the cost-effectiveness of peginterferon beta-1a as compared with injectable first-line treatments for RRMS in Italy.METHODS: The cost-effectiveness analysis was developed through a Markov model with lifetime simulation in the perspective of the Italian National Healthcare Service (NHS). It was added an alternative scenario to take into account the Italian societal perspective. Outcomes were measured in terms of life years (LYs), quality adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratio (ICER). The natural progression of the disease was informed by the published literature and previously published modelling exercises. The efficacy of treatments was simulated as reduction of disability progression (EDSS) and relapse rate. Efficacy data were derived from a published network meta-analysis. Unit costs were based on current prices and tariffs, and the published literature. A 3.5% discount rate was applied to costs and outcomes. One-way and probabilistic sensitivity analyses were developed and cost-effectiveness acceptability curves generated.RESULTS: Peginterferon beta-1a was more effective than the comparators in terms of survival (19.94 vs.19.68-19.81 discounted LYs, respectively), and QALYs (9.07 vs. 8.06 and 8.55 discounted QALY, respectively). In the perspective of the Italian NHS, the ICER was € 11,111/QALY vs. interferon beta-1a 30 µg, € 12,604/QALY vs. interferon beta-1a 22 µg, € 10,580/QALY and € 16,702/QALY vs. interferon beta-1b 250 µg and € 22,023/QALY vs. glatiramer acetate 20 mg. Peginterferon beta-1a dominated interferon beta-1a 44 µg. In the societal perspective, peginterferon beta-1a was dominant due to being more effective and with a lower social cost compared to first-line injectable treatments (interferon beta -1a, interferon beta-1b, glatiramer acetate) for RRMS. The outcomes of the sensitivity analyses confirmed the trend of the base case results.CONCLUSIONS: Peginterferon beta-1a shows a favourable pharmaco-economic profile for the treatment of RRMS. Even if an official threshold for the cost-effectiveness does not exist in Italy, the ICER values obtained were far below the commonly accepted thresholds (30,000-50,000 €/per QALY gained).[Article in Italian

[Pegylation and interferons in multiple sclerosis]

Pegylation is a procedure used for drug development since the 1970s and consists of the conjugation of a polyethylene glycol molecule (PEG) to a drug. PEG has shown to be safe and effective in improving the pharmacokinetic and pharmacodynamic profile of drugs. Recently, a 20 kDa linear chain of PEG was conjugated to interferon beta-1a with the aim to offer a new treatment option to relapsing-remitting multiple sclerosis (RRMS) patients. Due to a prolonged bioavailability, this new drug can be administered less frequently (every two weeks) than the other interferons beta available, thus allowing to hypothesize a better adherence to the treatment, which, in turn, should result in better clinical and economic outcomes. A phase III clinical trial has proven its effectiveness compared to placebo in RRMS patients, as well as a safety profile comparable to that found in other interferon beta preparations. The immunogenicity of this new molecule is < 1%, thus minimizing the suppression or reduction of interferon beta biological activity that could come from the development of Neutralizing Antibodies (NAbs).[Article in Italian

Evaluation of the applicability of existing (Q)SAR models for predicting the genotoxicity of pesticides and similarity analysis related with genotoxicity of pesticides for facilitating of grouping and read across

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Hair analysis for detection of triptans occasionally used or overused by migraine patients-a pilot study

Purpose The aim of this study is to evaluate the detection rate of almotriptan, eletriptan, frovatriptan, sumatriptan, rizatriptan, and zolmitriptan in the hair of migraineurs taking these drugs; the degree of agreement between type of self-reported triptan and triptan found in hair; if the concentrations in hair were related to the reported cumulative doses of triptans; and whether hair analysis was able to distinguish occasional use from the overuse of these drugs. Methods Out of 300 headache patients consecutively enrolled, we included 147 migraine patients who reported to have taken at least one dose of one triptan in the previous 3 months; 51 % of the patients overused triptans. A detailed pharmacological history and a sample of hair were collected for each patient. Hair samples were analyzed by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) by a method that we developed. Results All the triptans could be detected in the hair of the patients. The agreement between type of self-reported triptan and type of triptan found in hair was from fair to good for frovatriptan and zolmitriptan and excellent for almotriptan, eletriptan, sumatriptan, and rizatriptan (P &lt; 0.01, Cohen’s kappa). The correlation between the reported quantities of triptan and hair concentrations was statistically significant for almotriptan, eletriptan, rizatriptan, and sumatriptan (P &lt; 0.01, Spearman’ s rank correlation coefficient). The accuracy of hair analysis in distinguishing occasionally users from overusers was high for almotriptan (ROC AUC = 0.9092), eletriptan (ROC AUC = 0.8721), rizatriptan (ROC AUC = 0.9724), and sumatriptan (ROC AUC = 0.9583). Conclusions Hair analysis can be a valuable system to discriminate occasional use from triptan overuse