OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.

Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents. Deletion of OCaR1 led to extensive Ca2+ release from NAADP-responsive granules under basal conditions as well as upon stimulation of GPCR receptors. Moreover, OCaR1 deletion exacerbated the disease phenotype in murine models of severe and chronic pancreatitis. Our findings showed OCaR1 as a gatekeeper of Ca2+ release that endows NAADP-sensitive secretory granules with an autoregulatory mechanism preventing uncontrolled exocytosis and pancreatic tissue damage.

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 of long-acting aripiprazole through population pharmacokinetic modelling.

Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole. A total of 93 patients were included, 21 for model development and 71 for external model evaluation. A one-compartment model with linear absorption and elimination adequately described both aripiprazole and dehydro-aripiprazole concentrations. The weight of the patients has been shown to be the factor that most influences the absorption. However, the metabolizing phenotype for CYP2D6 and the concomitant treatment with strong inhibitors of this cytochrome have been shown to be the covariates that most influence total drug exposure. This is the first popPK model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.

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.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. METHODS: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. RESULTS: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. CONCLUSIONS: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Enhancing Therapeutic Drug Monitoring in Inflammatory Bowel Disease: A Comparative Analysis of Rapid Point-of-Care Infliximab, Adalimumab and Anti-Drug Antibodies' Determination against ELISA.

The introduction of point-of-care (POC) assays into clinical practice in patients with inflammatory disease enables on-demand therapeutic decision making. The aim of this study was to compare the POC test Quantum blue (Bühlmann Laboratories) for infliximab (IFX), adalimumab (ADL), and its anti-drug antibodies with the traditional ELISA assay (Promonitor). A total of 200 serum samples were analyzed. Samples were classified into the following three different groups; sub-therapeutic range (IFX < 3 µg/mL and ADL < 5 µg/mL); therapeutic range (IFX: 3-7 µg/mL and ADL: 5-12 µg/mL) and supra-therapeutic range (IFX levels > 7 µg/mL and ADL levels > 12 µg/mL). Significant higher values were measured using the POC test (p < 0.001) for IFX results but no differences in ADL trough levels were observed (p = 0.3101). Spearman's correlation indicated a good correlation between the two assays (rs = 0.88 for ADL and rs = 0.93 for IFX), and McNemar's test revealed significant differences (p = 0.016) when classifying IFX samples between therapeutic and supra-therapeutic ranges but no significant differences were found among the other ranges for either IFX or ADL. These results show that we should be cautious when using these rapid measurement methods, and new targets should probably be defined for IFX when using this new analytical method.

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.

Efficacy and Safety of Inhaled Ethanol in Early-Stage SARS-CoV-2 Infection in Older Adults: A Phase II Randomized Clinical Trial.

BACKGROUND: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection. METHODS: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations. RESULTS: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations. CONCLUSIONS: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.

PI(3,5)P2 and NAADP: Team players or lone warriors? - New insights into TPC activation modes.

NAADP (nicotinic acid adenine dinucleotide phosphate) is a second messenger, releasing Ca2+ from acidic calcium stores such as endosomes and lysosomes. PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) is a phospho-inositide, residing on endolysosomal membranes and likewise releasing Ca2+ from endosomes and lysosomes. Both compounds have been shown to activate endolysosomal two-pore channels (TPCs) in mammalian cells. However, their effects on ion permeability as demonstrated specifically for TPC2 differ. While PI(3,5)P2 elicits predominantly Na+-selective currents, NAADP increases the Ca2+ permeability of the channel. What happens when both compounds are applied simultaneously was unclear until recently.

TELEA-Farmacia: Pharmaceutical care by Telepharmacy to oncology patients from a hospital pharmacy service.

OBJECTIVE: To describe the implementation of a pilot Telepharmacy project (TELEA-Farmacia) in adult patients with cancer, analyze the results obtained, and identify opportunities for improvement, from a hospital  pharmacy service. METHOD: Between October and December 2021, oncology patients, collecting  their oral antineoplastic drugs at the Unit of Oncology Pharmacy of the hospital pharmacy service were stratified using the MAPEX model. Oncology patients  candidates for inclusion in the TELEA-Farmacia project included "medium-high  priority" hospital pharmacy patients, along with oncology patients who,  according to pharmacist's opinion, could benefit from Telepharmacy. On a  weekly basis, oncology patients recorded on the TELEA platform their biological  measurements and completed the questionnaires on medication  adherence and pain. Questionnaires on quality of life were completed on a  monthly basis. To score health indicators, oncology patients accessed TELEA  through the SERGAS-MOBIL app or a web browser. Follow-up of health  indicators was performed by the Unit of Oncology Pharmacy of the hospital  pharmacy service. RESULTS: The study sample included 29 oncology patients (48% were male)  with a mean age of 59 years (44-75). According to the stratification model,  31% were low-priority patients, 62% had medium-priority, and 7%  had high  priority. The digital gap in patients with advanced ages was the main obstacle  to inclusion. Reports were monitored daily, and a total of 364 responses were  received. In the presence of alarming reports and/or out-of-range values,  active monitoring and/or telephonic follow-up were initiated. Pharmaceutical  care was adapted to the health problem detected according to individual  patient needs. CONCLUSIONS: The Telemedicine pilot project TELEA-Farmacia made it possible  to test TELEA in patients with cancer in a real-life context. TELEA facilitated  continuous follow-up, early detection of drug-related problems, and the  identification of new needs and improvement points. To such purpose, clinical  oncology pharmacists combined face-to-face consults with patient stratification  and remote follow-up. This study demonstrated that new  stratification models are necessary in hospital pharmacy services to identify  patients with technology skills who can benefit from using Telemedicine tools  as TELEA.

OBJETIVO: Describir la implantación de un proyecto piloto de Telefarmacia (TELEA-Farmacia) en el paciente oncológico adulto y analizar los resultados recabados, así como identificar las oportunidades de mejora, desde un servicio de farmacia hospitalario.Método: Entre octubre y diciembre de 2021, los pacientes oncológicos a  tratamiento con antineoplásicos orales citados en la consulta de farmacia oncológica del servicio de farmacia de hospital fueron estratificados a  través del modelo MAPEX. Se consideraron susceptibles de inclusión en TELEA- Farmacia a quienes requerían atención farmacéutica con "prioridad media-alta" y a aquellos que, según criterio farmacéutico, pudieran beneficiarse de la herramienta. A través del aplicativo TELEA se programaron semanalmente biomedidas y cuestionarios de adherencia y evaluación del  dolor, y mensualmente un cuestionario de calidad de vida. Accediendo a TELEA  mediante la aplicación móvil SERGAS-MÓBIL o un navegador web, los  pacientes oncológicos respondieron a los indicadores de salud programados, de cuyo seguimiento fue responsable la Unidad de Farmacia Oncológica del  servicio de farmacia de hospital. RESULTADOS: Se incluyeron 29 pacientes oncológicos (48% hombres), con una  media de 59 años (44-75). Un 31% fueron de prioridad baja, 62% media y 7%  alta según el modelo de estratificación, siendo la brecha digital existente  en edades avanzadas el principal impedimento para la inclusión. Se realizó un  seguimiento diario de las notificaciones, recibiéndose un total de 364  respuestas. A partir de las consideradas alarmantes y de los valores fuera de  rango, se procedió al seguimiento activo y/o contacto telefónico,  proporcionando atención farmacéutica adaptada al problema de salud  detectado en función de las necesidades. CONCLUSIONES: El proyecto piloto de Telemedicina TELEA-Farmacia permitió testar la herramienta en pacientes oncológicos en vida real, facilitando el seguimiento continuado, la detección temprana de problemas  relacionados con medicamentos y la identificación de nuevas necesidades y  puntos de mejora para su implantación definitiva en la actividad asistencial.  Para ello, fue necesario compaginar la actividad presencial en consulta con el tiempo requerido para la estratificación y seguimiento telemático. Además, ha evidenciado la necesidad de disponer de nuevos modelos de  estratificación en un servicio de farmacia de hospital para la atención  farmacéutica que contemplen el manejo de las tecnologías por parte de los  pacientes, para identificar así a quienes más se puedan beneficiar de la  herramienta de Telemedicina TELEA.

TELEA-Farmacia: Atención farmacéutica mediante Telefarmacia a pacientes oncológicos desde un servicio de farmacia hospitalaria / TELEA-Farmacia: Pharmaceutical care by Telepharmacy to oncology patients from a hospital pharmacy service

Objetivo: Describir la implantación de un proyecto piloto de Telefarmacia (TELEA-Farmacia) en el paciente oncológico adulto y analizar losresultados recabados, así como identificar las oportunidades de mejora,desde un servicio de farmacia hospitalario.Método: Entre octubre y diciembre de 2021, los pacientes oncológicosa tratamiento con antineoplásicos orales citados en la consulta de farmaciaoncológica del servicio de farmacia de hospital fueron estratificados a travésdel modelo MAPEX. Se consideraron susceptibles de inclusión en TELEA-Farmacia a quienes requerían atención farmacéutica con “prioridad media-alta”y a aquellos que, según criterio farmacéutico, pudieran beneficiarse de laherramienta. A través del aplicativo TELEA se programaron semanalmentebiomedidas y cuestionarios de adherencia y evaluación del dolor, y mensualmente un cuestionario de calidad de vida. Accediendo a TELEA mediantela aplicación móvil SERGAS-MÓBIL o un navegador web, los pacientesoncológicos respondieron a los indicadores de salud programados, de cuyoseguimiento fue responsable la Unidad de Farmacia Oncológica del serviciode farmacia de hospital.Resultados: Se incluyeron 29 pacientes oncológicos (48% hombres),con una media de 59 años (44-75). Un 31% fueron de prioridad baja,62% media y 7% alta según el modelo de estratificación, siendo la brecha. digital existente en edades avanzadas el principal impedimento para lainclusión. Se realizó un seguimiento diario de las notificaciones, recibiéndose un total de 364 respuestas. A partir de las consideradas alarmantesy de los valores fuera de rango, se procedió al seguimiento activo y/ocontacto telefónico, proporcionando atención farmacéutica adaptada alproblema de salud detectado en función de las necesidades. (AU)

Objective: To describe the implementation of a pilot Telepharmacy project (TELEA-Farmacia) in adult patients with cancer, analyze the resultsobtained, and identify opportunities for improvement, from a hospital pharmacy service.Method: Between October and December 2021, oncology patients,collecting their oral antineoplastic drugs at the Unit of Oncology Pharmacy of the hospital pharmacy service were stratified using the MAPEXmodel. Oncology patients candidates for inclusion in the TELEA-Farmaciaproject included “medium-high priority” hospital pharmacy patients, alongwith oncology patients who, according to pharmacist’s opinion, couldbenefit from Telepharmacy. On a weekly basis, oncology patients recorded on the TELEA platform their biological measurements and completedthe questionnaires on medication adherence and pain. Questionnaires onquality of life were completed on a monthly basis. To score health indicators, oncology patients accessed TELEA through the SERGAS-MOBIL appor a web browser. Follow-up of health indicators was performed by theUnit of Oncology Pharmacy of the hospital pharmacy service.Results: The study sample included 29 oncology patients (48% weremale) with a mean age of 59 years (44-75). According to the stratificationmodel, 31% were low-priority patients, 62% had medium-priority, and 7%. had high priority. The digital gap in patients with advanced ages was themain obstacle to inclusion. Reports were monitored daily, and a total of364 responses were received. In the presence of alarming reports and/orout-of-range values, active monitoring and/or telephonic follow-up wereinitiated. Pharmaceutical care was adapted to the health problem detected according to individual patient needs. (AU)

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at -20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at -20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

Medication adherence to obeticholic acid: a real-world experience using medication event monitoring systems.

OBJECTIVE: We designed a clinical study to analyze patterns of adherence to  obeticholic acid, factors influencing the adherence and potential correlation with  treatment efficacy by using MEMS® cap in practice daily. Method: A multicenter prospective observational study of patients with primary  biliary cholangitis. Adherence will be measured by MEMS® cap, pill count, and  patient-reported outcomes during 3 months. The quality of life will be self- reported using the Chronic Liver Disease Questionnaire test, European Quality of  Life 5-Dimension Questionnaire test and Itch Severity Scale. CONCLUSIONS: We expect to clarify if there is correlation between adherence with  treatment efficacy and to identify causes for poor compliance and introduce  measures to reduce its prevalence.

OBJETIVO: Diseñamos un estudio clínico para analizar los patrones de adherencia al ácido obeticólico, los factores que influyen en la adherencia y  la posible correlación con la eficacia del tratamiento mediante el uso de  MEMS® cap en la práctica clínica diaria.Método: Estudio observacional prospectivo multicéntrico de pacientes con  colangitis biliar primaria. La adherencia se medirá mediante MEMS® cap, el  recuento de comprimidos y se registrarán los resultados comunicados por el  paciente durante 3 meses. La calidad de vida será autoinformada utilizando el  Cuestionario de Enfermedad Hepática Crónica, el Cuestionario Europeo de  Calidad de Vida en cinco dimensiones y la Escala de Intensidad del Picor. CONCLUSIONES: Esperamos identificar si existe una relación entre la adherencia  con la efectividad del tratamiento e identificar las causas de la  falta de adherencia para poder introducir medidas para reducir su prevalencia.

Adherencia terapéutica de ácido obeticólico: experiencia real utilizando sistemas demonitorización de medicación electrónicos / Medication adherence to obeticholic acid: a real-world experience using medication event monitoring systems

Objetivo: Diseñamos un estudio clínico para analizar los patrones deadherencia al ácido obeticólico, los factores que influyen en la adherencia y la posible correlación con la eficacia del tratamiento mediante eluso de MEMS® cap en la práctica clínica diaria.Método: Estudio observacional prospectivo multicéntrico de pacientescon colangitis biliar primaria. La adherencia se medirá mediante MEMS®cap, el recuento de comprimidos y se registrarán los resultados comunicados por el paciente durante 3 meses. La calidad de vida será autoinformada utilizando el Cuestionario de Enfermedad Hepática Crónica,el Cuestionario Europeo de Calidad de Vida en cinco dimensiones y laEscala de Intensidad del Picor.Conclusiones: Esperamos identificar si existe una relación entre laadherencia con la efectividad del tratamiento e identificar las causasde la falta de adherencia para poder introducir medidas para reducir suprevalencia. (AU)

Objective: We designed a clinical study to analyze patterns of adherence to obeticholic acid, factors influencing the adherence and potentialcorrelation with treatment efficacy by using MEMS® cap in practice daily.Method: A multicenter prospective observational study of patients withprimary biliary cholangitis. Adherence will be measured by MEMS® cap,pill count, and patient-reported outcomes during 3 months. The qualityof life will be self-reported using the Chronic Liver Disease Questionnairetest, European Quality of Life 5-Dimension Questionnaire test and ItchSeverity Scale.Conclusions: We expect to clarify if there is correlation between adherence with treatment efficacy and to identify causes for poor complianceand introduce measures to reduce its prevalence. (AU)

A Review of Population Pharmacokinetic Analyses of Linezolid.

In recent years, many studies on population pharmacokinetics of linezolid have been conducted. This comprehensive review aimed to summarize population pharmacokinetic models of linezolid, by focusing on dosage optimization to maximize the probability of attaining a certain pharmacokinetic-pharmacodynamic parameter in special populations. We searched the PubMed and EMBASE databases for population pharmacokinetic analyses of linezolid using a parametric non-linear mixed-effect approach, including both observational and prospective trials. Of the 32 studies, 26 were performed in adults, four in children, and one in both adults and children. High between-subject variability was determined in the majority of the models, which was in line with the variability of linezolid concentrations previously detected in observational studies. Some studies found that patients with renal impairment, hepatic failure, advanced age, or low body weight had higher exposure and adverse reactions rates. In contrast, lower concentrations and therapeutic failure were associated with obese patients, young patients, and patients who had undergone renal replacement techniques. In critically ill patients, the inter-individual and intra-individual variability was even greater, suggesting that this population is at an even higher risk of underexposure and overexposure. Therapeutic drug monitoring may be warranted in a large proportion of patients given that the Monte Carlo simulations demonstrated that the one-size-fits-all labeled dosing of 600 mg every 12 h could lead to toxicity or therapeutic failure for high values of the minimum inhibitory concentration of the target pathogen. Further research on covariates, including renal function, hepatic function, and drug-drug interactions related to P-glycoprotein could help to explain variability and improve linezolid dosing regimens.

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics.

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit-risk balance and, consequently, patients' quality of life.