Nutrición parenteral e identificación de subpoblaciones con necesidades nutricionales similares

[email protected] disponibilidad de formulaciones parenterales normalizadas en relación a los aportes de nutrientes, plantea la problemática de su idoneidad en relación a las necesidades nutritivas de los pacientes. El objetivo de este trabajo es identificar subpoblaciones de pacientes con necesidades calórico-proteicas similares y valorar su adecuación a formulaciones normalizadas. Con este fin, se evaluaron, de forma prospectiva las necesidades calórico- proteicas de 100 pacientes adultos metabólicamente estables en tratamiento con nutrición parenteral total. Los aportes calóricos se estudiaron por Harris-Benedict (con corrección de Long) y los aportes proteicos se calcularon en función del grado de estrés. Las necesidades calórico-proteicas se analizaron mediante un análisis de cluster mediante el algoritmo de partición alrededor de los mediodes. Se consideró que cuando la formulación de nutrición parenteral contenía aportes equivalentes a ± 20% de las necesidades medias de cada subpoblación era adecuada para satisfacer los requerimientos calórico- proteicos de los pacientes. El porcentaje de pacientes, en función del número de subpoblaciones identificadas, que recibirían aportes adecuados a sus requerimientos se tomó como variable de estudio comparativo. En el caso de dos subpoblaciones, para la subpoblación 1 (N = 35), las necesidades de glucosa, lípidos y aminoácidos son: 275 (IC 95%: 265-285) g, 83 (IC 95%: 78- 88) g y 89 (IC 95%: 86-92) y para la subpoblación 2 (N = 65), 195 (IC 95%: 187-203) g, 58 (IC 95%: 56-61) g y 74 (IC 95%: 72-77) g, respectivamente. En el caso de tres subpoblaciones, estas mismas necesidades de nutrientes son para la subpoblación 1 (N = 19): 295 (IC 95%: 283- 306) g, 91 (IC 95%: 84-97) g y 91 (IC 95%: 86-95); para la subpoblación 2 (N = 45), 234 (IC 95%: 227-240) g, 67 (IC 95%: 64-70) g, y 84 (IC 95%: 82-86) g; y para la subpoblación 3 (N = 36): 172 (IC 95%: 165-179) g, 55 (IC 95%: 52-57) g y 68 (IC 95%: 64-71) g, respectivamente. La utilización de una, dos o tres formulaciones, que contengan aportes equivalentes a ± 20% de las necesidades medias de cada subpoblación, satisfacen los requerimientos de glucosa, lípidos y proteínas en el 45% (IC 95%: 36% a 55%), 74% (IC 95%: 65% a 83) y 82% (IC 95%: 74% a 89%) de los pacientes, respectivamente. En suma, el desarrollo de tres formulaciones normalizadas de nutrición parenteral permite satisfacer las necesidades nutricionales de al menos el 74% de los pacientes adultos metabólicamente estables subsidiarios de nutrición parenteral total.The aim of this study is to identify patients subpopulations with similar caloric and proteic needs (CPN) and developing and assessing the utility of standarized formulations of total parenteral nutrition (TPN) with equivalents supplies to the average patients needs of each identified subpopulation. CPN of one hundred metabolically stables adults patients in treatment with TPN were evaluated consecutively. Caloric supplies were calculated with the Harris-Benedict equation, with the Long corrections and proteics supplies were evaluated according to stress level. The identification of patients subpopulation according to the CPN was made through the cluster analysis with partitioning around mediods algorithm. We considered the formulation with equivalent supplies to the average needs of each subpopulation was adequated to the patients caloric-proteic requirements when their difference was lower than 20%. The percentage of patients who received adequated supplies were compared between the subpopulations identified. In case of two subpopulations, glucose, lipids and amino acid needs are: 275 (CI 95%: 265-285) g, 83 (CI 95%: 78-88) g and 89 (CI 95%: 86-92) g in subpopulation 1 (N = 35), and 195 (CI 95%: 187-203) g, 58 (CI 95%: 56-61) g and 74 (CI 95%: 72-77) g in subpopulation 2 (N = 65), respectively. In case of three subpopulations, in subpopulation 1 (N = 19), glucose, lipids and amino acid needs are: 295 (CI 95%: 283-306) g, 91 (CI 95%: 84-97) g and 91 (CI 95%: 86-95); 234 (CI 95%: 227-240) g, 67 (CI 95%: 64-70) g and 84 (CI 95%: 82-86) g to the subpopulation 2 (N = 45) and 172 (CI 95%: 165- 179) g, 55 (CI 95%: 52-57) g, and 68 (CI 95%: 64-71) g to the subpopulation 3 (N = 36) respectively. In general, caloric and proteic supplies are equal to the patients needs, but there was a tendendy to overfeeding in patients with lower CPN. The utilization of one, two or three formulations with equivalent supplies to the average needs of each subpopulation was adequated to the patients in the 45% (CI 95%: 36%-55%), 75% (CI 95%: 65%- 83%) and 82% (CI 95%: 74%-89%), respectively. Therefore, the development of three normalized formulations of total parenteral nutrition allows to satisfy the patients nutritional needs at least the 74% of the patients

Interacción de los antineoplásicos orales con los alimentos: revisión sistemática

[email protected]ón: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA). Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los alimentos con medicamentos antineoplásicos orales y establecer recomendaciones para su administración. Métodos: Se realizó una búsqueda bibliográfica en Medline y The Cochrane Library para el periodo comprendido entre enero de 1966 a marzo de 2008, enfocada a identificar las publicaciones sobre interacciones fármaco alimento con antineoplásicos orales. El análisis bibliográfico consta de dos fases. En la primera fase se excluyeron los artículos que por título y contenido del resumen no se correspondían con el objetivo planteado; en la segunda fase se eliminaron las referencias duplicadas en ambas bases de datos. Los criterios de inclusión para seleccionar los artículos fueron: diseño (revisiones sistemáticas, metaanálisis, ensayos clínicos randomizados Fase I y II), población (pacientes adultos; >19 años de edad), intervención evaluada (administración de antineoplásicos orales bajo condiciones de ayuno o con alimentos) y medida del resultado de la iFA (cálculo del IC90% de la razón entre la media geométrica de valores del área bajo la curva de concentraciones plasmáticas (ABC) o la concentración plasmática máxima (Cmax) con y sin alimentos). Se excluyeron las publicaciones que como medida de resultado no hacían referencia al dictamen de bioequivalencia establecido por la Food and Drugs Administration (FDA). La valoración crítica de los artículos seleccionados se realizó según las recomendaciones que de acuerdo con la FDA deben cumplir estos estudios. Resultados: En la búsqueda inicial se obtuvieron 850 referencias (98,5% Medline + y 1,4% Cochrane). En la primera fase se excluyeron el 87,7% (746) de los artículos, correspondiendo el 100% a la búsqueda en Medline. En la segunda fase, quedaron 40 artículos (5,2% de los iniciales) para su lectura crítica a texto completo, a los que se añadieron cuatro más no indexados en Medline. De la lectura crítica de los 44 artículos finales, se excluyeron 25 artículos (20 artículos originales, 4 comunicaciones cortas y 1 metanálisis) por no incluir como medida de resultado el dictamen de bioequivalencia. Los 19 (2,2%) artículos restantes proporcionaron información sobre 19 fármacos antineoplásicos orales, en 210 pacientes y 146 voluntarios sanos. De estos 19 fármacos, el 63% no presentan iFA o interacciones fármaco-alimento, pudiéndose administrar indistintamente con/sin alimentos; el 21% se deben administrar con alimentos y sólo el 16% presentan interacción fármaco alimento, por lo que se deben administrar sin alimentos. Discusión: Actualmente, la importancia clínica de las interacciones fármaco alimento con antineoplásicos orales se identifica más directamente con la seguridad del paciente que con la efectividad del tratamiento. Ante el desarrollo de estos agentes orales, su irrupción en la terapia oncológica desplazando a la terapia parenteral, con costes mensuales de miles de euros, hay necesidad de realizar estudios farmacocinéticos y farmacodinámicos bien diseñados. Su objetivo debe de ser comparar su biodisponibilidad en presencia o ausencia de alimentos con la respuesta clínica. Mientras tanto, establecer recomendaciones para su administración en relación con los alimentos, es inconsistente para algunos de estos fármacos y su resultado incierto por la falta de estudios fundamentados en el dictamen de bioequivalencia establecido por la FDA.Introduction: studies on bioavailability are part of the clinical development of drugs for oral use in order to identify potential drug-food interactions. For oral antitumor drugs, their clinical importance is currently recognized although regrettably the information available presents variability concerning the scientific evidence. Objectives: To review the available scientific evidence about oral anti-tumor medications and establish the recommendations for their administration with foods. Methods: We carried out a bibliographic search in Medline and The Cochrane Library for the period January of 1966 to March of 2008, focused on identifying those publications about drug-food interactions with oral antitumor medications. The bibliographical analysis was made in two steps. During the first phase, we excluded those articles in which the title or their content did not correspond with the objective settled; during the second phase, we deleted all the references duplicated in both databases. The inclusion criteria to select the articles were: design (systematic reviews, meta-analysis, Phase I and Phase II randomized clinical trials), population (adult patients; >19 years of age), intervention evaluated (administration of oral anti-tumor drugs under fasting conditions or with food) and measurement of the iFA results (calculation of the 90% CI of the odds ratio between the geometric mean of the values under the curve of the plasma concentrations (ABC) or the maximal plasma concentration (Cmax) with and without foods). We excluded those publications that did not make reference to the bioequivalence dictamen established by the Food and Drugs Administration (FDA) in their outcomes measurement. A critical appraisal of the selected articles was done according to the recommendations that the FDA established to be met by these studies. Results: At the initial search we obtained 850 references (98.5% Medline + and 1.4% Cochrane). During the first phase, we excluded 87.7% (746) of the articles, 100% of them corresponding to the search in Medline. During the second phase, 40 studies remained (5.2% of the initial ones) for full-text critical appraisal, to which four studies were added not indexed in Medline. From the critical appraisal of the 44 final articles, 25 were excluded (20 original articles, 4 short communications, and 1 meta-analysis) because they did not include as an outcome measure the bioequivalence dictamen. The 19 (2.2%) remaining articles provided information on 19 oral anti-tumor drugs in 210 patients and 146 healthy volunteers. Of these 19 drugs, 63% did not present drugfood interactions, with the possibility of administering them either with or without food; 21% have to be administered with foods and only 16% present drug-food interactions, so they have to be administered without foods. Discussion: Currently, the clinical importance of drugfood interactions with oral anti-tumor drugs is identified more directly with the patient's safety than with the efficacy of the therapy. Given the development of these oral agents, their incorporation into the oncologic strategy displacing parenteral therapy, with monthly costs of thousands of Euros, it is necessary to perform well-designed studies on pharmacokinetics and pharmacodynamics. Their goal has to be comparing their bioavailability in the presence or absence of foods with the clinical response. In the meanwhile, to establish recommendations for their administration in relation to foods is inconsistent for some of these drugs and their results is uncertain given the lack of studies based on the FDAbioequivalence dictamen

Sesión Necrológica en Homenaje al Excmo. Señor Don Juan Manuel Reol Tejada

The Dr. Juan Manuel Reol Tejada was born on August 26, 1933 in Burgos. Took possession as Academician on November 14, 1991. Died on September 9, 2008. The Necrological Session was celebrated on March 5, 2009, with the intervention of the Academicians D. César Nombela, N. Víctor Jiménez Torres, Antonio L. Doadrio Villarejo and María Teresa Miras Portugal. It was presided by the Academic María Teresa Miras Portugal, Chairwoman of the Royal National Academy of Pharmacy.El Excmo. Sr. D. Juan Manuel Reol Tejada nació el 26 de agosto de 1933 en Burgos. Tomó posesión como Académico de Número el día 14 de noviembre de 1991. Falleció el 9 de septiembre de 2008. La Sesión Necrológica se celebró el día 5 de marzo de 2009. En dicha sesión participaron el Excmo. Sr. D. César Nombela, Académico de Número, D. N. Víctor Jímenez Torres, Académico de Número, el Excmo. Sr. D. Antonio Doadrio, Académico de Número y la Excma. Sra. Dña. María Teresa Miras Portugal, Presidenta de la Real Academia Nacional de Farmacia

A MIMO-OFDM testbed, channel measurements, and system considerations for outdoor-indoor WiMAX

The design, implementation, and test of a real-time flexible 2×2 (Multiple Input Multiple Output-Orthogonal Frequency Division Multiplexing) MIMO-OFDM IEEE 802.16 prototype are presented. For the design, a channel measurement campaign on the 3.5GHz band has been carried out, focusing on outdoor-indoor scenarios. The analysis of measured channels showed that higher capacity can be achieved in case of obstructed scenarios and that (Channel Distribution Information at the Transmitter) CDIT capacity is close to (Channel State Information at the Transmitter) CSIT with much lower complexity and requirements in terms of channel estimation and feedback. The baseband prototype used an (Field Programmable Gate Array) FPGA where enhanced signal processing algorithms are implemented in order to improve system performance. We have shown that for MIMO-OFDM systems, extra signal processing such as enhanced joint channel and frequency offset estimation is needed to obtain a good performance and approach in practice the theoretical capacity improvements

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Multi-institutional experience of genetic diagnosis in Ecuador: national registry of chromosome alterations and polymorphisms

Antecedentes: la detección de anomalías cromosómicas es fundamental en diversas áreas médicas; para diagnosticar defectos de nacimiento, trastornos genéticos e infertilidad, entre otros fenotipos complejos, en personas de una amplia gama de edades. De ahí que el presente estudio quiera contribuir al conocimiento del tipo y frecuencia de alteraciones cromosómicas y polimorfismos en Ecuador. Métodos: Se fusionaron y analizaron registros citogenéticos de diferentes provincias ecuatorianas para construir un registro nacional de acceso abierto de alteraciones cromosómicas y polimorfismos. Resultados: De 28.806 cariotipos analizados, 6.008 (20,9%) presentaron alteraciones. El síndrome de Down fue la alteración autosómica más frecuente (88,28%), seguido del síndrome de Turner (60,50%), una aneuploidía gonosómica. Un alto porcentaje recurrente de mosaicismo del síndrome de Down (7,45%) informado aquí, así como por los registros preliminares ecuatorianos anteriores, podría estar asociado con la ubicación geográfica y la composición ancestral mixta. Las translocaciones (2,46%) y polimorfismos (7,84%) no fueron tan numerosos como las autosomopatías (64,33%) y las gonosomopatías (25,37%). Como complemento a las pruebas citogenéticas convencionales, las herramientas moleculares han permitido identificar regiones de alteraciones submicroscópicas o genes candidatos que posiblemente puedan estar implicados en los síntomas y fenotipos de los pacientes. Conclusión: El Registro Nacional Ecuatoriano de Alteraciones y Polimorfismos Cromosómicos proporciona una línea de base para comprender mejor las anomalías cromosómicas en el Ecuador y por ende su manejo clínico y conocimiento.Background: Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador. Methods: Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open-access national registry of chromosome alterations and polymorphisms. Results: Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes. Conclusion: The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing