Updated antimicrobial dosing recommendations for obese patients.

The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.

Towards Precision Medicine in Clinical Practice: Alinity C vs. UHPLC-MS/MS in Plasma Aripiprazole Determination.

Therapeutic drug monitoring improves the benefit-risk balance of antipsychotic therapy. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is considered the gold-standard method for measuring plasma drug concentrations; however, the Alinity C system has emerged as a promising alternative. This is the first study aimed at comparing UHPLC-MS/MS versus Alinity C in measuring plasma concentrations of aripiprazole and dehydroaripiprazole. A total of 86 plasma samples were analyzed. The active moiety of aripiprazole was measured in 60 samples using both systems and 26 samples were analyzed twice using Alinity C with an intermediate period of 6 months to assess its reproducibility. Spearman's correlation revealed a good association between the two assays (rs = 0.96) and no significance differences were found by McNemar's test when classifying samples between infra-, supra- and therapeutic ranges. Passing-Bablock regression showed a good correlation among methods (rs = 0.93) and a slope of 1.12 indicating a slight tendency of Alinity C to measure higher values than UHPLC-MS/MS. In addition, a good intra-method correlation across the two sequential analyses with Alinity C was obtained (rs = 0.99). Nonetheless, clinical decisions could be different in 15% of the cases depending on the chosen method. No differences were found in active moiety determination by Alinity C depending on the concentration of aripiprazole and dehydroaripiprazole of the samples.

NEmecum: herramienta digital de ayuda a la prescripción y dispensación de fórmulas de nutrición enteral y preparados infantiles / NEmecum: digital tool for assisting in the prescription and dispensing of enteral nutrition formulas and infant preparations

Introducción: existe una amplia variedad de fórmulas o preparados de nutrición enteral y fórmulas o preparados infantiles. La consulta de información relacionada debe hacerse en las herramientas propias de cada laboratorio, lo que dificulta la visión crítica y la comparativa entre las mismas. Objetivo: describir el desarrollo de NEmecum como la primera web que permite realizar una búsqueda dirigida e independiente de fórmulas de nutrición o preparados infantiles, analizar el abanico nutricional actual en España y evaluar los datos de uso de la herramienta. Métodos: se desarrolló la estructura de una base de datos que unifica los parámetros de todas las fórmulas y se analizó el abanico nutricional español. Posteriormente, se seleccionaron los principales algoritmos de búsqueda dirigida y se codificó la herramienta digital. Se llevó a cabo una intensa difusión y se evaluó el impacto obtenido. Se analizaron el perfil de usuarios y centros registrados y los datos de uso de la herramienta y se evaluó su usabilidad mediante el cuestionario System Usability Scale (SUS). Resultados: se obtuvo una web responsive de acceso gratuito (http://nemecum.com) que permite realizar búsquedas dirigidas en base a unos filtros de búsqueda preestablecidos. La herramienta permitió analizar detalladamente el abanico nutricional en España, observándose la gran variedad de fórmulas disponibles de similares características. La campaña de difusión consiguió incrementar su uso de forma exponencial y cuenta actualmente con 1.370 usuarios y 79 centros registrados. La usabilidad fue valorada como excelente. Conclusión: el desarrollo de NEmecum supone una herramienta valiosa en la búsqueda y consulta de datos de fórmulas o preparados de nutrición enteral y fórmulas o preparados infantiles. (AU)

Introduction: there is a wide variety of enteral nutrition and infant formulas preparations. When there is a need to find infomation on a product,only the infomation from industy is available. Comparison amomg products becomes then ardous.Objective: to describe the development of NEmecum as the first website that allows a directed and independent search for enteral nutritionproducts and infant formulas, currently available in Spain, and to evaluate the initial use of NEmecum.Methods: the structure of a database that unifies the parameters of all formulas was developed, and the nutritional composition of all formulaswas analyzed. Subsequently, the main search algorithms were selected and the digital tool was codified. Intensive dissemination was performedand the impact was evaluated. The profile of users and registered centers and the use of the tool were analyzed, and its usability was evaluatedusing the System Usability Scale (SUS) questionnaire.Results: a free-access responsive website (http://nemecum.com) that allows searches based on pre-established search filters was obtained. Thistool allows for a detailed analysis available formulas in Spain by observing a wide variety of formulas with similar characteristics. The disseminationcampaign managed to increase its use exponentially, currently reaching 1,370 users and 79 registered centers. Usability was rated as excellent.Conclusion: the development of the NEmecum represents a valuable tool in the search and consultation of the characteristics of enteral nutritionformulas and infant preparations. (AU)

NEmecum: digital tool for assisting in the prescription and dispensing of enteral nutrition formulas and infant preparations / NEmecum: herramienta digital de ayuda a la prescripción y dispensación de fórmulas de nutrición enteral y preparados infantiles.

Introduction: Introduction: there is a wide variety of enteral nutrition and infant formulas preparations. When there is a need to find infomation on a product, only the infomation from industy is available. Comparison amomg products becomes then ardous. Objective: to describe the development of NEmecum as the first website that allows a directed and independent search for enteral nutrition products and infant formulas, currently available in Spain, and to evaluate the initial use of NEmecum. Methods: the structure of a database that unifies the parameters of all formulas was developed, and the nutritional composition of all formulas was analyzed. Subsequently, the main search algorithms were selected and the digital tool was codified. Intensive dissemination was performed and the impact was evaluated. The profile of users and registered centers and the use of the tool were analyzed, and its usability was evaluated using the System Usability Scale (SUS) questionnaire. Results: a free-access responsive website (http://nemecum.com) that allows searches based on pre-established search filters was obtained. This tool allows for a detailed analysis avalaible formulas in Spain by observing a wide variety of formulas with similar characteristics. The dissemination campaign managed to increase its use exponentially, currently reaching 1,370 users and 79 registered centers. Usability was rated as excellent. Conclusion: the development of the NEmecum represents a valuable tool in the search and consultation of the characteristics of enteral nutrition formulas and infant preparations.

Introducción: Introducción: existe una amplia variedad de fórmulas o preparados de nutrición enteral y fórmulas o preparados infantiles. La consulta de información relacionada debe hacerse en las herramientas propias de cada laboratorio, lo que dificulta la visión crítica y la comparativa entre las mismas. Objetivo: describir el desarrollo de NEmecum como la primera web que permite realizar una búsqueda dirigida e independiente de fórmulas de nutrición o preparados infantiles, analizar el abanico nutricional actual en España y evaluar los datos de uso de la herramienta. Métodos: se desarrolló la estructura de una base de datos que unifica los parámetros de todas las fórmulas y se analizó el abanico nutricional español. Posteriormente, se seleccionaron los principales algoritmos de búsqueda dirigida y se codificó la herramienta digital. Se llevó a cabo una intensa difusión y se evaluó el impacto obtenido. Se analizaron el perfil de usuarios y centros registrados y los datos de uso de la herramienta y se evaluó su usabilidad mediante el cuestionario System Usability Scale (SUS). Resultados: se obtuvo una web responsive de acceso gratuito (http://nemecum.com) que permite realizar búsquedas dirigidas en base a unos filtros de búsqueda preestablecidos. La herramienta permitió analizar detalladamente el abanico nutricional en España, observándose la gran variedad de fórmulas disponibles de similares características. La campaña de difusión consiguió incrementar su uso de forma exponencial y cuenta actualmente con 1.370 usuarios y 79 centros registrados. La usabilidad fue valorada como excelente. Conclusión: el desarrollo de NEmecum supone una herramienta valiosa en la búsqueda y consulta de datos de fórmulas o preparados de nutrición enteral y fórmulas o preparados infantiles.

Ampicillin Stability in a Portable Elastomeric Infusion Pump: A Step Forward in Outpatient Parenteral Antimicrobial Therapy.

Outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion pumps is postulated as a very promising solution to treat complicated infections, such as endocarditis or osteomyelitis, that require patients to stay in hospital during extended periods of time, thus reducing their quality of life and increasing the risk of complications. However, stability studies of drugs in elastomeric devices are scarce, which limits their use in OPAT. Therefore, we evaluated the stability of ampicillin in sodium chloride 0.9% at two different concentrations, 50 and 15 mg/mL, in an elastomeric infusion pump when stored in the refrigerator and subsequently in real-life conditions at two different temperatures, 25 and 32 °C, with and without the use of a cooling device. The 15 mg/mL ampicillin is stable for up to 72 h under refrigeration, allowing subsequent dosing at 25 °C for 24 h with and without a cooling device, but at 32 °C its concentration drops below 90% after 8 h. In contrast, 50 mg/mL ampicillin only remains stable for the first 24 h under refrigeration, and subsequent administration at room temperature is not possible, even with the use of a cooling system. Our data support that 15 mg/mL AMP is suitable for use in OPAT if the volume and rate of infusion are tailored to the dosage needs of antimicrobial treatments.

Design and biopharmaceutical preclinical characterisation of a new thermosensitive hydrogel for the removal of gastric polyps.

BACKGROUND AND AIMS: Submucosal injection agents are widely used solutions in gastric polyp resection techniques. Currently, many different solutions are used in clinical practice, but most are not authorised for this use or are not biopharmaceutical characterised. The objective of this multidisciplinary work is to test the efficacy of a novel thermosensitive hydrogel designed specifically for this indication. METHODS: A mixture design of various components (Pluronic®, hyaluronic acid and sodium alginate) was carried out to select the combination with optimal properties for this use. Three final thermosensitive hydrogels were selected on which biopharmaceutical characterisation was performed and stability and biocompatibility were analysed. Efficacy in maintaining elevation was tested ex vivo on pig mucosa and in vivo in pigs RESULTS: The mixture design allowed selection of the ideal combinations of agents for the characteristics sought. The thermosensitive hydrogels studied showed high values of hardness and viscosity at 37 °C, maintaining good syringeability. One of them demonstrated superiority in maintaining polyp elevation in the ex vivo assay and non-inferiority in the in vivo assay. CONCLUSION: The thermosensitive hydrogel specifically designed for this use is promising both for its biopharmaceutical characteristics and for its demonstrated efficacy. This study lays the foundation for evaluating the hydrogel in humans.

Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection.

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosis.

Clinical research in hospital pharmacy during the fight against COVID-19.

The health crisis resulting from the rapid spread of SARS-CoV-2 worlwide, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise,  important measures have been adopted in healthcare and research centers  aimed at halting the pandemic as soon as possible. The objective of this study is  to gather the main aspects of the clinical research studies undertaken by the  Departments of Hospital Pharmacy (DHP) of Spain during the COVID-19 crisis. The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of DHP had been led at least one CT.  The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination  with Institutional Review Boards, has adopted a fast-track review procedure to  accelerate authorizations for CTs related to the treatment or prevention of  COVID-19. There have also been numerous public and private calls for financing  research projects aimed at contributing to the fight against this virus. Despite  the pandemic, actions have been taken to continue ongoing CTs and studies  while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that  incorporate changes to CT protocols that will have to be applied until the  pandemic is over. In this health emergency, the scientific community has found  itself in a race against time to generate evidence. It is at this moment that  hospital pharmacists emerge as key players in clinical research and are  contributing to a rational, effective and safe healthcare decision-making.

La presente crisis sanitaria derivada de la rápida expansión del virus SARS-CoV- 2 a nivel mundial, así como la falta de evidencia de los tratamientos empleados  actualmente, ha provocado la aparición de un gran número de ensayos clínicos y estudios observacionales. Del mismo modo, ha ocasionado la puesta en marcha  de importantes medidas en el entorno sanitario e investigador con el fin de  conseguir detener la evolución de la pandemia lo antes posible. El objetivo del  actual trabajo es recopilar aspectos fundamentales relacionados con la  investigación clínica desarrollada por los servicios de farmacia hospitalaria  durante la crisis provocada por la COVID-19. La iniciativa de la Sociedad  Española de Farmacia Hospitalaria de actuar como promotor de ensayos clínicos  ha posibilitado que el 13% de estos servicios de farmacia hospitalaria haya  podido liderar uno. En este sentido, la Agencia Española de Medicamentos y  Productos Sanitarios, junto con los Comités de Ética de Investigación, ha  acelerado los procedimientos de autorización de nuevos ensayos clínicos  destinados a tratar o prevenir la COVID-19. Asimismo, han sido numerosas las  convocatorias públicas y privadas destinadas a la financiación de proyectos de  diversa índole con el fin de contribuir a la lucha contra este virus. A pesar de la  irrupción de la pandemia, también han surgido acciones destinadas a mantener  las actividades de los ensayos clínicos y estudios puestos previamente en  marcha, garantizando la seguridad y bienestar del paciente. Concretamente, la  Agencia Española de Medicamentos y Productos Sanitarios y la Agencia Europea  de Medicamentos han publicado guías que incluyen cambios en los protocolos de los ensayos clínicos que deben mantenerse mientras dure la pandemia. La  emergencia sanitaria actual ha obligado a la comunidad científica a la generación de evidencia a contrarreloj. Por ello, en este momento en el que se requiere del  mayor rigor posible, el farmacéutico de hospital debe alzarse como una figura  clave en la investigación en salud, contribuyendo a que las decisiones sanitarias  sean racionales, eficientes y seguras.

La investigación clínica de la farmacia hospitalaria en la lucha contra la COVID-19 / Clinical research in hospital pharmacy during the fight against COVID-19

La presente crisis sanitaria derivada de la rápida expansión del virus SARS-CoV-2 a nivel mundial, así como la falta de evidencia de los tratamientos empleados actualmente, ha provocado la aparición de un gran número de ensayos clínicos y estudios observacionales. Del mismo modo, ha ocasionado la puesta en marcha de importantes medidas en el entorno sanitario e investigador con el fin de conseguir detener la evolución de la pandemia lo antes posible. El objetivo del actual trabajo es recopilar aspectos fundamentales relacionados con la investigación clínica desarrollada por los servicios de farmacia hospitalaria durante la crisis provocada por la COVID-19. La iniciativa de la Sociedad Española de Farmacia Hospitalaria de actuar como promotor de ensayos clínicos ha posibilitado que el 13% de estos servicios de farmacia hospitalaria haya podido liderar uno. En este sentido, la Agencia Española de Medicamentos y Productos Sanitarios, junto con los Comités de Ética de Investigación, ha acelerado los procedimientos de autorización de nuevos ensayos clínicos destinados a tratar o prevenir la COVID-19. Asimismo, han sido numerosas las convocatorias públicas y priva-das destinadas a la financiación de proyectos de diversa índole con el fin de contribuir a la lucha contra este virus. A pesar de la irrupción de la pandemia, también han surgido acciones destinadas a mantener las actividades de los ensayos clínicos y estudios puestos previamente en marcha, garantizando la seguridad y bienestar del paciente. Concretamente, la Agencia Española de Medicamentos y Productos Sanitarios y la Agencia Europea de Medicamentos han publicado guías que incluyen cambios en los protocolos de los ensayos clínicos que deben mantenerse mientras dure la pandemia. La emergencia sanitaria actual ha obligado a la comunidad científica a la generación de evidencia a contrarreloj. Por ello, en este momento en el que se requiere del mayor rigor posible, el farmacéutico de hospital debe alzarse como una figura clave en la investigación en salud, contribuyendo a que las decisiones sanitarias sean racionales, eficientes y seguras

The health crisis resulting from the rapid spread of SARS-CoV-2 worlwide, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise, important measures have been adopted in healthcare and research centers aimed at halting the pandemic as soon as possible. The objective of this study is to gather the main aspects of the clinical research studies undertaken by the Departments of Hospital Pharmacy (DHP) of Spain during the COVID-19 crisis. The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of DHP had been led at least one CT. The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination with Institutional Review Boards, has adopted a fast-track review procedure to accelerate authorizations for CTs related to the treatment or prevention of COVID-19. There have also been numerous public and private calls for financing research projects aimed at contributing to the fight against this virus. Despite the pandemic, actions have been taken to continue ongoing CTs and studies while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that incorporate changes to CT protocols that will have to be applied until the pandemic is over. In this health emergency, the scientific community has found itself in a race against time to generate evidence. It is at this moment that hospital pharmacists emerge as key players in clinical research and are contributing to a rational, effective and safe healthcare decision-making