Development and sedative effect of a new formulation of midazolam in chocolate bars

The aim of this work was to assess the stability and sedative effect of midazolam in chocolate bars. The stability of 5 g chocolate bars containing 6 mg midazolam hydrochloride was evaluated at room temperature (25 ± 2 °C), at 4 and 40 °C, by HPLC. Drug plasma levels were measured and the sedative effect was confirmed in six healthy volunteers according to the Ramsay’s scale. Data regarding chocolate bar administration were compared to those from the apple juice solution. Pharmacokinetic data were processed using the WinNonLin 5.2 software. Midazolam in chocolate bars remained stable for 14 days at room temperature and exposed to light; for 90 days at 4 and 40 °C protected from light, and showed a longer shelf life, better flavour and appearance, inducing the same sedative effect as the apple juice preparation. Raspberry flavour masked midazolam unpleasing taste most favourably.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and sedative effect of a new formulation of midazolam in chocolate bars

The aim of this work was to assess the stability and sedative effect of midazolam in chocolate bars. The stability of 5 g chocolate bars containing 6 mg midazolam hydrochloride was evaluated at room temperature (25 ± 2 °C), at 4 and 40 °C, by HPLC. Drug plasma levels were measured and the sedative effect was confirmed in six healthy volunteers according to the Ramsay’s scale. Data regarding chocolate bar administration were compared to those from the apple juice solution. Pharmacokinetic data were processed using the WinNonLin 5.2 software. Midazolam in chocolate bars remained stable for 14 days at room temperature and exposed to light; for 90 days at 4 and 40 °C protected from light, and showed a longer shelf life, better flavour and appearance, inducing the same sedative effect as the apple juice preparation. Raspberry flavour masked midazolam unpleasing taste most favourably.Colegio de Farmacéuticos de la Provincia de Buenos Aire

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

La convivencia en los centros educativos de educación básica en Iberoamérica

La presente aportación recoge la visión de 46 especialistas de quince países iberoamericanos sobre las formas de entender y promover la convivencia escolar en los centros educativos de los distintos países. Sus aportaciones son un conjunto de descripciones, experiencias y valoraciones significativas y en relación al contexto considerado. Las aportaciones no buscan tanto radiografiar la temática a nivel teórico como presentar lo más significativo de cada realidad y las propuestas que, al respecto, se realizan. La orientación es claramente organizativa, si consideramos que una parte común de todas las aportaciones tiene que ver con las políticas de convivencia escolar, programas aplicados, aspectos organizativos a nivel de institución, experiencias significativas y retos para la mejora. Se cubre así y de nuevo un propósito fundamental de la Red AGE, como es el de fomentar el intercambio de experiencias, la promoción del conocimiento sobre administración y gestión educativa y la reflexión sobre la práctica de la gestión. La finalidad última es la de mejorar el funcionamiento de los centros educativos (y, a través de ellos, de los sistemas educativos), procurando sean de calidad y un instrumento para el cambio profesional y social

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial

Background. There is no treatment for septic acute kidney injury (sAKI). The anti-inflammatory activity of prolonged-release pirfenidone (PR-PFD) could be beneficial in this clinical setting. Methods. This study was a double-blind randomized clinical trial in sAKI patients with nephrology consultation at the Civil Hospital of Guadalajara, in addition to the usual treatment of AKI associated with sepsis; patients were randomized to receive either PR-PFD at 1,200 mg/day (group A) or 600 mg/day (group B) or a matched placebo for 7 consecutive days. The primary objective was the decrease in serum creatinine (sCr) and increase in urinary volume (UV); the secondary objectives were changes in serum electrolytes, acid-base status, and mortality. Results. Between August 2016 and August 2017, 88 patients were randomized. The mean age was 54 (17 ± SD) years, and 47% were male. The main site of infection was the lung (39.8%), septic shock was present in 39.1% of the cases, and the mean SOFA score was 8.8 points. 28 patients received PFD 1,200 mg, 30 patients received PFD 600 mg, and 30 patients received placebo. During the study, sCr did not differ among the groups. The reversion rate of sCr, UV, and mortality was not different among the groups (p=0.70, p=0.47, and p=0.38, respectively). Mild adverse events were not different among the groups. Conclusion. PR-PFD did not improve the clinical course of sAKI and seemed to be safe in terms of adverse events. This trial is registered with NCT02530359

A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4-Q75 29.0) and 3.8 μmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients

Validation parameters of the analytical method for to quantify ifosfamide in DBS at 45% HTC.

<p>The intra-day variability with quality controls was performed in three consecutive days, data for days 1 to 3 are depicted as a, b and c, respectively. SD: Standard Deviation. CV: Coefficient Variation. N/R: Not required according to the guidelines. Amount claimed for QC1, QC2 and QC3 were 300, 4000 and 8000 ng/mL, respectively.</p><p>Validation parameters of the analytical method for to quantify ifosfamide in DBS at 45% HTC.</p

Chromatograms for multiple reaction monitoring (MRM) of individual channels.

<p>The figure shows Ifosfamide and cyclophosphamide on 24-h samples. Selectivity to other drugs administered with ifosfamide: vincristine, ondansetron, etoposide, carboplatin and methotrexate.</p