A novel lipophilic amiloride derivative efficiently kills chemoresistant breast cancer cells.

Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells.

Effectiveness and safety of pembrolizumab as first-line treatment for non-small cell lung cancer in real clinical practice.

INTRODUCTION: Pembrolizumab is currently the drug for the first-line treatment of stage-IV non-small cell lung cancer. The objective of this study is to measure the effectiveness of pembrolizumab as a first-line treatment and to analyze its safety in real clinical practice. METHODS: This was a retrospective study that included patients with metastatic non-small cell lung cancer who had received pembrolizumab as a first-line treatment between 1 June 2018 and 31 January 2021. Variables related to the patients, treatment, and drug's efficacy and safety were collected. RESULTS: A total of 50 patients were analyzed. The median real-world progression-free survival and real-world overall survival of those who received pembrolizumab in monotherapy were 10.5 months (95% CI: 2.3-18.6) and 18.9 months (95% CI: 16.9-20.8), respectively. The median real-world progression-free survival and real-world overall survival of those who received the drug with chemotherapy was 7.9 months (95% CI: 4.1-11.7) and 13.3 months (95% CI: 0.0-27), respectively. Mostly digestive (48.3%) and endocrine (41.4%) immune-related adverse events were detected among the patients who received pembrolizumab in monotherapy, whereas mostly digestive immune-related adverse events (85.7%) and hematological toxicities (71.5%) were observed in those treated with pembrolizumab plus chemotherapy. CONCLUSION: Pembrolizumab has proven its effectiveness in terms of increasing real-world progression-free survival and real-world overall survival in real clinical practice. The main adverse events were digestive toxicities with pembrolizumab in monotherapy and with chemotherapy.

Physicochemical Stability of Hospital Parenteral Nutrition Solutions: Effect of Changes in Composition and Storage Protocol.

(1) Background: Parenteral nutrition (PN) is a technique used for the administration of nutrients to patients for whom traditional routes cannot be used. It is performed using solutions with extremely complex compositions, which can give rise to a large number of interactions. These interactions can impact their stability and put the patient's life at risk. The aim of this study is to determine how changes in composition and storage protocol affect the stability of NP solutions. (2) Methods: Twenty-three samples were prepared according to routine clinical practice, with modifications to the concentration of some components. The samples were stored at room temperature (RT) and refrigerated (4 °C). Measurements of the droplet diameter, pH, density and viscosity were performed for both storage protocols on days 1, 3, 10 and 14. (3) Results: The samples with the lowest concentration of lipids (PN13-17) and proteins (PN18-22) showed a larger droplet diameter than the rest of the samples throughout the experiments. The USP limits were exceeded for some of the measurements of these sample groups. The pH density and viscosity remained relatively constant under the conditions studied. (4) Conclusions: The PN samples were considered stable and safe for administration under real-world conditions, but the samples with the lowest concentrations of lipids and proteins showed a tendency towards emulsion instability.

Electron Microscopy for the Stability Assessment of Parenteral Nutrition Admixtures: Focus on Precipitation.

(1) Background: parenteral nutrition (PN) is indispensable for patients unable to receive oral or enteral feeding. However, the complexity of PN solutions presents challenges regarding stability and compatibility. Precipitation reactions may occur. The most frequent is the formation of calcium phosphate (Ca-P). The different factors influencing these reactions must be considered to ensure patient safety. (2) Methods: eight paediatric PN solutions were prepared, following standard protocols. Samples were stored at room temperature and in a refrigerator. Electron microscopy, coupled with energy dispersive X-ray spectroscopy (EDS), was employed. Precipitates were analysed for composition and morphology. (3) Results: precipitates were observed in all samples, even at day 0. Crystalline structures, predominantly composed of calcium or magnesium, sometimes associated with chlorine or phosphorus, were detected. Additionally, amorphous precipitates, contained heterogeneous compositions, including unexpected elements, were identified. (4) Conclusions: various precipitates, primarily calcium- or magnesium-based, can form in PN solutions, although it is not expected that they can form under the real conditions of use. Calcium oxalate precipitation has been characterised, but the use of organic calcium and phosphate salts appears to mitigate calcium phosphate precipitation. Electron microscopy provides interesting results on NP precipitation, but sample preparation may present technical limitations that affect the interpretation of the results.

Predicted concentrations of antineoplastic drugs in the aquatic environment: The case of Ría de Vigo (NW, Spain).

The European Medicines Agency (EMA) mandates Environmental Risk Assessments (ERAs) since 2006 to determine potential risks of new marketed medicines. Drugs with a Predicted Environmental Concentration (PEC) in inland surface waters exceeding 0.01 µg L-1 require further environmental risk assessment. PEC may be refined based on prevalence data and/or based on the treatment regimen. In this study, based on EMA regulations, refined PEC of 108 antineoplastic drugs in coastal waters were determined based on the consumption in a coastal health area during 2021, identifying six drugs with potential environmental risk in surface waters (hydroxyurea, capecitabine, abiraterone, ibrutinib, imatinib and 5-fluorouracil) and two in marine ecosystem (hydroxyurea and capecitabine). Comparison of these refined PECs with data from marketing laboratories revealed significant disparities, suggesting the need for regular updates, especially with changes in drug indications or financing. Notably, the identified drugs are not yet on the main reference lists of emerging contaminants.

Evaluation of the Stability of Newborn Hospital Parenteral Nutrition Solutions.

(1) Background: parenteral nutrition (PN) solutions are an extremely complex mixture. It is composed of a multitude of chemical elements that can give rise to a large number of interactions that condition its stability and safety. The aim of this study was to evaluate the stability of PN solutions for preterm infants. (2) Methods: eight samples were prepared according to the protocol for prescribing PN in preterm infants. Samples PN1-PN7 had the normal progression of macronutrients and standard amounts of micronutrients for a 1 kg preterm infant. The PN8 sample had a high concentration of electrolytes, with the idea of forcing stability limits. Samples were stored both at room temperature and under refrigeration. Measurements of globule size, pH, density, and viscosity were performed in both storage protocols on different days after processing. (3) Results: the changes in the composition of the samples did not affect the evolution of the stability at the different measurement times and temperatures. Viscosity was affected by the compositional changes made in the PN samples, but no alterations due to time or temperature were observed. Density and pH remained stable, without significant changes due to time, storage temperature, or different composition. (4) Conclusion: all samples remained stable during the study period and did not undergo significant alterations due to compositional changes or different experimental conditions.

Colostrum Quality in Different Goat Breeds Reared in Northern Italy.

This study aimed to characterize the colostrum quality in three different local goat breeds of Northern Italy (i.e., Frisa Valtellinese, Orobica, and Lariana) and a cosmopolitan one (i.e., Camosciata delle Alpi) (n = 30 per breed), reared under traditional semi-extensive and intensive systems, respectively. Lariana showed the highest percentage of fat (10.18 ± 3.14%) and total solids (30.73 ± 4.89%) but the lowest percentage of lactose (1.87 ± 0.82%; p < 0.05); Orobica had the lowest percentage of fat (7.13 ± 2.48%), total solids (24.11 ± 5.48%), and protein (10.77 ± 4.53%) but the highest percentage of lactose (3.16 ± 0.73%; p < 0.05). This suggests that breeds which have a more pronounced meat aptitude (i.e., Frisa and Lariana) have a higher concentration of components than breeds with more dairy aptitude (i.e., Orobica and Camosciata). Uni- and multivariate analyses showed that IgG is the parameter that best differentiates local breeds from cosmopolitan ones (p < 0.01). Colostrum from Frisa goats showed the highest IgG concentration (100.90 ± 8.11 mg/mL), while the lowest concentration was in the Camosciata breed (74.75 ± 20.16 mg/mL). Finally, the highest lactoferrin concentration was in Frisa (1781.3 ± 892.6 µg/mL) and the lowest in Camosciata and Lariana (763.1 ± 357.9 and 1148.0 ± 858.6 µg/mL, respectively; p < 0.05). Differences between Camosciata and local breeds could be due to the different farming systems, in addition to the genetic characteristics. The higher quality of colostrum produced by some local goats could be an adaptive characteristic that helps the growth and survival of the kids.

Goat mammary gland metabolism: An integrated Omics analysis to unravel seasonal weight loss tolerance.

Seasonal weight loss (SWL), is a major limitation to animal production. In the Canary Islands, there are two dairy goat breeds with different levels of tolerance to SWL: Majorera (tolerant) and Palmera (susceptible). Our team has studied the response of these breeds to SWL using different Omics tools. The objective of this study was to integrate such results in a data driven approach and using dedicated tools, namely the DIABLO method. The outputs of our analysis mainly separate unrestricted from restricted goats. Metabolites behave as "hub" molecules, grouping interactions with several genes and proteins. Unrestricted goats upregulated protein synthesis, along with arginine catabolism and adipogenesis pathways, which are related with higher anabolic rates and a larger proportion of secretory tissue, in agreement with their higher milk production. Contrarily, restricted goats seemingly increased the synthesis of acetyl-CoA through serine and acetate conversion into pyruvate. This may have occurred to increase fatty acid synthesis and/or to use them as an energy source in detriment to glucose, which was more available in the diet of unrestricted goats. Lastly, restricted Palmera upregulated the expression of PEBP4 and GPD1 genes compared to all other groups, which might support their use as putative biomarkers for SWL susceptibility. SIGNIFICANCE: Seasonal weight loss (SWL) is a major issue influencing animal production in the tropics and Mediterranean. By studying its impact on the mammary gland of tolerant and susceptible dairy goat breeds, using Omics, we aim at surveying the tissue for possible biomarkers that reflect these traits. In this study, data integration of three Omics (transcriptomics, proteomics and metabolomics) was performed using bioinformatic tools, to relate putative biomarkers and evaluate all three levels of information; in a novel approach. This information can enhance selection programs, lowering the impact of SWL on food production systems.

Exposure to anandamide on young rats causes deficits in learning, temporal perception and induces changes in NMDA receptor expression.

Human use of marijuana at an early age has been reported to lead to cognitive impairment. However, researchers have not yet clearly determined whether this impairment is due to marijuana-induced alterations in the developing nervous system and whether this deficit persists into adulthood after marijuana use has ceased. We administered anandamide to developing rats to assess the effect of cannabinoids on development. We subsequently evaluated learning and performance on a temporal bisection task in adulthood and assessed the expression of genes encoding principal subunits of NMDA receptors (Grin1, Grin2A, and Grin2B) in the hippocampus and prefrontal cortex. Rats in two age groups, namely, 21-day-old and 150-day-old rats, received intraperitoneal injections of anandamide or the vehicle for 14 days. Both groups performed a temporal bisection test, which included listening to tones of different durations and classifying them as short or long. The expression of the Grin1, Grin2A and Grin2B mRNAs was evaluated using quantitative PCR in both age groups after extracting mRNA from the hippocampus and prefrontal cortex. We observed a learning impairment in the temporal bisection task (p < 0.05) and changes in the response latency (p < 0.05) in rats that received anandamide. Furthermore, these rats exhibited decreased expression of Grin2b (p = 0.001) compared to those that received the vehicle. In human subjects, the use of cannabinoids during development induces a long-term deficit, but this deficit is not observed in subjects who use cannabinoids in adulthood. Rats treated with anandamide earlier in development took longer to learn the task, suggesting that anandamide exerts a harmful effect on cognition in developing rats. Administration of anandamide during early stages of development induced deficits in learning and other cognitive processes that depend on an adequate estimation of time. The cognitive demands of the environment must be considered when evaluating the cognitive effects of cannabinoids on developing or mature brains. High cognitive demands might induce differential expression of NMDA receptors that improves cognitive capacity, overcoming altered glutamatergic function.

Cellular transformation promotes the incorporation of docosahexaenoic acid into the endolysosome-specific lipid bis(monoacylglycerol)phosphate in breast cancer.

Bis(monoacylglycero)phosphates (BMPs), a class of lipids highly enriched within endolysosomal organelles, are key components of the lysosomal intraluminal vesicles responsible for activating sphingolipid catabolic enzymes. While BMPs are understudied relative to other phospholipids, recent reports associate BMP dysregulation with a variety of pathological states including neurodegenerative diseases and lysosomal storage disorders. Since the dramatic lysosomal remodeling characteristic of cellular transformation could impact BMP abundance and function, we employed untargeted lipidomics approaches to identify and quantify BMP species in several in vitro and in vivo models of breast cancer and comparative non-transformed cells and tissues. We observed lower BMP levels within transformed cells relative to normal cells, and consistent enrichment of docosahexaenoic acid (22:6) fatty acyl chain-containing BMP species in both human- and mouse-derived mammary tumorigenesis models. Our functional analysis points to a working model whereby 22:6 BMPs serve as reactive oxygen species scavengers in tumor cells, protecting lysosomes from oxidant-induced lysosomal membrane permeabilization. Our findings suggest that breast tumor cells might divert polyunsaturated fatty acids into BMP lipids as part of an adaptive response to protect their lysosomes from elevated reactive oxygen species levels, and raise the possibility that BMP-mediated lysosomal protection is a tumor-specific vulnerability that may be exploited therapeutically.

Regorafenib and trifluridine/tipiracil in real clinical practice.

Background: Colorectal cancer is the ninth leading cause of death in Spain. The latest therapeutic developments in the advanced stages of this disease are the oral drugs trifluridine/tipiracil and regorafenib. Objective: Results of clinical trials (CTs) are not in real conditions and therefore, we want to study the effectiveness and the safety profile in the usual clinical practice and compare it with the bibliography. Materials and Methods: A retrospective and unicentric study was carried out in a health area of 500,000 inhabitants. Patients who started treatment with regorafenib and/or trifluridine/tipiracil were included from the date of marketing until June 2019. Patient-related variables, pathology, effectiveness, and treatment toxicity were collected. The statistical analysis was carried out with the PSPP program. Results: Fifty-four patients were analyzed. Men accounted for 59.3% of patients. Regorafenib was the treatment for 22.2% of patients and 77.8% received trifluridine/tipiracil. The reason for the drug's suspension was the disease progression in 85.2% of patients. No patient had a full response and 3.2% achieved partial response. The median progression-free survival time in treatments with regorafenib was 2.5 months (95% confidence interval [CI]: 0.0-5.4) and the overall survival time was 3.1 months (95% CI: 0.0-6.7), while in treatments with trifluridine/tipiracil, these data were, respectively, 2.8 (95% CI: 2.5-3.2) and 5.7 months (95% CI: 3.8-7.6). Side effects occurred in 91.7% of patients treated with regorafenib and in 100% of treated with trifluridine/tipiracil. Hematological adverse reactions were, on average, 0.4 ± 0.5/patient with regorafenib and 1.5 ± 0.9 with trifluridine/tipiracil. General (77.8%) and gastrointestinal disorders (50%) were common with both drugs. Conclusions: The effectiveness results of standard clinical practice are lower than those described in CTs and in the literature. The toxicity profile does reproduce what is described in the bibliography.

Telemedicine informatics application for nutritional support surveillance of instutionalized persons in nursing homes from a hospital pharmacy service.

INTRODUCTION: Institutionalized patients who require nutrition support regularly visit the Unit of Nutrition Support of the Hospital Pharmacy  Service. During these visits, prior to establishing a nutrition regime and  followup scheme, an initial nutritional status assessment is performed.  Telemedicine and Telepharmacy have expanded in recent years for remote  monitoring of institutionalized persons. OBJECTIVE: To evaluate the implementation of a Telemedicine informatics application for nutritional support surveillance of instutionalized  persons in nursing homes from a hospital pharmacy service. Method: A multidisciplinary team led by the Hospital Pharmacy Service was  created. Data of institutionalized persons in nursing homes needing artificial  nutritional support was extracted from the SILICON prescription system and  the internal ecords of the hospital pharmacy service. Nursing homes were  selected on the basis of their previous experience using the Telemedicine  informatics application TELEA. The following nutritional  support variables were  assessed: score on Mini-Nutritional Assessment questionnaire; a 24-h  food record; pressure ulcer control; and laboratory parameters. The existing  information flow between nursing homes and hospital specialists was analyzed.  The functionalities available on TELEA were considered. RESULTS: In 2021, over 300 institutionalized persons from 28 nursing homes  were incluided for nutritional support surveillance program of the hospital  pharmacy service. The project was implemented in two nursing homes serving  38 patients, although only 13 were involved in the nutrition surveillance  program of the Nutrition Support Unit. Nutritional status assessment and  nutritional support surveillance reports were adapted to the Telemedicine  informatics application. Paper reports were replaced  with electronic data or  online questionnaires available on the informatics application. An information  flow protocol was established. An instantaneous messaging and alert system  was activated, which allowed continuous communication. Some Telepharmacy  requests were categorized as preferential when the clinical status of the patient  so required. All the information generated during the nutritional status  assessment and nutritional support surveillance process was integrated into  the electronic medical history of each patient. CONCLUSIONS: TELEA-based nutritional support surveillance facilitates the  continuum of care by enabling direct communication between nursing homes  and secondary care for institutionalized persons. This model makes it possible  to record nutrition-related data on the electronic medical history of patients  through a Telepharmacy process. This model also eliminates paper  prescriptions and medical reports, and unnecessary travels. A nutritional status  profile should also be made available to facilitate nutrition surveillance in institutionalized persons with chronic diseases. That  would be the first step for a new integrated healthcare informatics application  for frail/polymorbid elderly patients.

Introducción: Los pacientes institucionalizados que requieren soporte  nutricional artificial acuden de forma periódica a las consultas de la Unidad de  Soporte Nutricional del Servicio de Farmacia. En ellas se realiza una  valoración nutricional inicial, a partir de la cual se establece la pauta nutricional  y el plan de seguimiento. La Telemedicina y la Telefarmacia se han  expandido en los últimos años para la monitorización remota de personas  institucionalizadas. OBJETIVO: Evaluar la implementación de una aplicación informática de Telemedicina para la vigilancia del soporte nutricional de personas  nstitucionalizadas en residencias de ancianos desde un servicio de farmacia hospitalaria.Método: Se formó un equipo multidisciplinar liderado por el Servicio de Farmacia. Los datos de pacientes institucionalizados que requieren soporte nutricional artificial se obtuvieron del programa SILICON y de los  registros internos del Servicio de Farmacia. Se eligieron las primeras  residencias candidatas según la experiencia previa en el manejo de la  aplicación informática de asistencia domiciliaria. Se analizaron llas variables de  soporte nutricional necesarias para el seguimiento nutricional: Mini  Nutritional Assessment, recordatorio de ingestas de las últimas 24 horas,  control de úlceras por presión y parámetros analíticos. Se analizó el flujo de  información existente entre las residencias sociosanitarias y la atención  hospitalaria y se valoraron las opciones disponibles a través de la plataforma  tecnológica de asistencia domiciliaria. RESULTADOS: El Servicio de Farmacia realizó seguimiento nutricional a más de  300 pacientes institucionalizados en 28 residencias sociosanitarias en el año  2021. El proyecto se implantó en dos residencias sociosanitarias que cuentan  con 38 pacientes institucionalizados, aunque solo 13 pacientes estaban en  seguimiento por la Unidad de Soporte Nutricional. Todos los registros  generados en la valoración y seguimiento nutricional se adecuaron a la  aplicación informática de asistencia domiciliaria, se cambiaron los registros en  papel por información incluida en la plataforma o cuestionarios online  facilitados a través de la misma. Además, se protocolizó el flujo de información  generada y se activó un sistema de mensajería con alertas que  permite una comunicación continua. En caso de que la situación clínica  del  paciente lo requiera se puede programar una teleconsulta preferente.Toda la  información generada en el proceso de valoración y seguimientonutricional de  cada paciente se integró en la historia clínica electrónica. CONCLUSIONES: El seguimiento nutricional a través de la aplicación informática de asistencia domiciliaria facilita la continuidad asistencial por el establecimiento de una comunicación directa entre las residencias  sociosanitarias y la atención hospitalaria, permitiendo la integración de la  información nutricional de los pacientes en la historia clínica electrónica  mediante un proceso de Telefarmacia. Se han eliminado las prescripciones en  papel, informes clínicos impresos y los desplazamientos innecesarios. El  desarrollo de este perfil podría ser extensible al seguimiento nutricional de  pacientes con patologías crónicas, y ser el precedente de un nuevo programa  de cuidado integral del paciente anciano frágil o pluripatológico.

Aplicación informática de Telemedicina parala vigilancia del soporte nutricional de personas institucionalizadas en residencias de ancianos desde un servicio de farmacia hospitalaria / Telemedicine informatics application for nutritional support surveillance of instutionalized persons in nursing homes from a hospital pharmacy service

Introducción: Los pacientes institucionalizados que requieren soporte nutricional artificial acuden de forma periódica a las consultas de la Unidad deSoporte Nutricional del Servicio de Farmacia. En ellas se realiza una valoración nutricional inicial, a partir de la cual se establece la pauta nutricional y elplan de seguimiento. La Telemedicina y la Telefarmacia se han expandido enlos últimos años para la monitorización remota de personas institucionalizadas.Objetivo: Evaluar la implementación de una aplicación informática deTelemedicina para la vigilancia del soporte nutricional de personas institucionalizadas en residencias de ancianos desde un servicio de farmaciahospitalaria.Método: Se formó un equipo multidisciplinar liderado por el Servicio deFarmacia. Los datos de pacientes institucionalizados que requieren soportenutricional artificial se obtuvieron del programa SILICON y de los registrosinternos del Servicio de Farmacia. Se eligieron las primeras residenciascandidatas según la experiencia previa en el manejo de la aplicación informática de asistencia domiciliaria. Se analizaron llas variables de soportenutricional necesarias para el seguimiento nutricional: Mini NutritionalAssessment, recordatorio de ingestas de las últimas 24 horas, control deúlceras por presión y parámetros analíticos. Se analizó el flujo de información existente entre las residencias sociosanitarias y la atención hospitalariay se valoraron las opciones disponibles a través de la plataforma tecnológica de asistencia domiciliaria.Resultados: El Servicio de Farmacia realizó seguimiento nutricional amás de 300 pacientes institucionalizados en 28 residencias sociosanitariasen el año 2021. (AU)

Introduction: Institutionalized patients who require nutrition supportregularly visit the Unit of Nutrition Support of the Hospital Pharmacy Service. During these visits, prior to establishing a nutrition regime and followup scheme, an initial nutritional status assessment is performed. Telemedicine and Telepharmacy have expanded in recent years for remotemonitoring of institutionalized persons.Objective: To evaluate the implementation of a Telemedicine informaticsapplication for nutritional support surveillance of instutionalized persons innursing homes from a hospital pharmacy service.Method: A multidisciplinary team led by the Hospital Pharmacy Servicewas created. Data of institutionalized persons in nursing homes needingartificial nutritional support was extracted from the SILICON prescriptionsystem and the internal ecords of the hospital pharmacy service. Nursing homes were selected on the basis of their previous experience usingthe Telemedicine informatics application TELEA. The following nutritional support variables were assessed: score on Mini-Nutritional Assessmentquestionnaire; a 24-h food record; pressure ulcer control; and laboratoryparameters. The existing information flow between nursing homes andhospital specialists was analyzed. The functionalities available on TELEAwere considered.Results: In 2021, over 300 institutionalized persons from 28 nursinghomes were incluided for nutritional support surveillance program of thehospital pharmacy service. The project was implemented in two nursinghomes serving 38 patients, although only 13 were involved in the nutrition surveillance program of the Nutrition Support Unit. Nutritional statusassessment and nutritional support surveillance reports were adapted tothe Telemedicine informatics application. (AU)

Extensive Sheep and Goat Production: The Role of Novel Technologies towards Sustainability and Animal Welfare.

Sheep and goat extensive production systems are very important in the context of global food security and the use of rangelands that have no alternative agricultural use. In such systems, there are enormous challenges to address. These include, for instance, classical production issues, such as nutrition or reproduction, as well as carbon-efficient systems within the climate-change context. An adequate response to these issues is determinant to economic and environmental sustainability. The answers to such problems need to combine efficiently not only the classical production aspects, but also the increasingly important health, welfare, and environmental aspects in an integrated fashion. The purpose of the study was to review the application of technological developments, in addition to remote-sensing in tandem with other state-of-the-art techniques that could be used within the framework of extensive production systems of sheep and goats and their impact on nutrition, production, and ultimately, the welfare of these species. In addition to precision livestock farming (PLF), these include other relevant technologies, namely omics and other areas of relevance in small-ruminant extensive production: heat stress, colostrum intake, passive immunity, newborn survival, biomarkers of metabolic disease diagnosis, and parasite resistance breeding. This work shows the substantial, dynamic nature of the scientific community to contribute to solutions that make extensive production systems of sheep and goats more sustainable, efficient, and aligned with current concerns with the environment and welfare.

Physical and Dietary Intervention with Opuntia ficus-indica (Nopal) in Women with Obesity Improves Health Condition through Gut Microbiota Adjustment.

Obesity is a multifactorial disease resulting in excessive accumulation of fat. Worldwide, obesity is an important public health problem, affecting a large proportion of the world population. The tender cactus Opuntia ficus-indica, commonly known in Mexico as "nopal", is widely distributed in this country, Latin America, South Africa, and the Mediterranean area. Nopal cladodes are commonly marketed in different forms as fresh, frozen, or pre-cooked, and used as fresh green vegetable. The aim of this study was to evaluate the capability of nopal to improve the health condition of participants affected by obesity, in a physical and dietary intervention, through gut microbiota modification. These results were contrasted with the effect of nopal in the gut microbiota of normal weight participants. We describe the association among biochemical, anthropometric markers, and the gut microbiota diversity found in fecal samples of the obese and normal weight groups. The results presented in this work suggest that caloric restriction, addition of nopal to the diet and physical activity, promote changes in the gut microbiota in obese women, improving the host metabolism, as suggested by the correlation between some bacterial species with biochemical and anthropometrical parameters.

Switching between reference adalimumab and biosimilars in chronic immune-mediated inflammatory diseases: A systematic literature review.

AIMS: Adalimumab is a biological therapy used to treat different chronic inflammatory diseases. At present, there is an increasing number of adalimumab biosimilars. To assume the acceptability of interchangeability between reference adalimumab and biosimilars, there should be evidence about efficacy and safety of this switching. Regulation of this practice falls under the authority of individual European Union Member States. The aim of this study is to systematically review the evidence on the efficacy, safety and immunogenicity of switching between reference adalimumab and biosimilars in different chronic immune-mediated inflammatory diseases. METHODS: Studies presenting data about switching between reference adalimumab and biosimilars were identified by sensitive search strategies in Medline and EMBASE from 1 January 2004 to 30 June 2021. RESULTS: A total of 471 references were obtained and 21 finally included in the analysis (total number of patients switching: 2802). Eight different adalimumab biosimilars were tested after receiving reference adalimumab. Eight articles included rheumatoid arthritis (RA), one miscellaneous rheumatic disease, six psoriasis (PSO) and six inflammatory bowel disease (IBD) patients. Overall, the efficacy results in the switching groups were comparable to those obtained in the arms of continuous biosimilar and continuous reference adalimumab. There were no significant differences in treatment emergent adverse events, anti-drug or neutralising antibodies among the three groups. CONCLUSIONS: Switching between reference adalimumab and biosimilars has no impact on efficacy, safety and immunogenicity in patients with RA, PSO and IBD. This finding was consistent for the different adalimumab biosimilars analysed. These conclusions could probably be extended to other rheumatic diseases such as psoriatic arthritis and ankylosing spondylitis.

Metodología Lean: diseño y evaluación de un modelo estandarizado de almacenaje de medicación / LEAN methodology: design and assessment of a standardized medication storage model

OBJETIVO: El objetivo del estudio es evaluar los resultados de la aplica-ción de la metodología Lean en el diseño de un modelo estandarizado de almacenaje de medicación en las unidades de hospitalización. MÉTODO: Estudio descriptivo y retrospectivo desarrollado entre septiembre de 2017 y enero de 2019 en un hospital de tercer nivel. Se creó un equipo multidisciplinar liderado por el Servicio de Farmacia. Se empleó la metodología Lean para establecer los elementos y criterios de organización e identificación que conformaron el modelo estandarizado de almacenaje de medicación. Se revisaron y cuantificaron los stocks de cada unidad de hospitalización, se consensuó la medicación con la supervisora de cada unidad y se estimó el impacto económico de la implantación del modelo estandarizado. Se diseñó y envió una encuesta para evaluar la satisfacción de enfermería con el nuevo modelo. RESULTADOS: El modelo estandarizado de almacenaje se aplicó en 20 unidades de enfermería y supuso una reducción global del 56,72% en el número de presentaciones de principios activos disponibles (5.688 versus2.462). Se disminuyó el número de presentaciones de principios activos de medicamentos de alto riesgo en un 40,73% (631 versus 374). La eliminación de este despilfarro supuso un ahorro económico de 25.357,98 (Euro). Se recibieron 58 respuestas a la encuesta de satisfacción del personal de enfermería (20,70% del total de encuestas enviadas), de las que un 22,40% correspondieron al turno fijo y 77,60% al turno rotativo. La media de la satisfacción global (valorada entre 1 y 10) fue de 5,79 ± 3,61. CONCLUSIONES: La aplicación de la metodología Lean es útil para la gestión de stocks de medicación de las unidades de hospitalización. La implantación del modelo estandarizado de almacenaje conlleva un ahorro económico y una reducción del número de presentaciones de principios activos y de medicamentos de alto riesgo. El personal de enfermería está conforme con la implantación del modelo, lo que nos plantea seguir en esta línea de mejora

OBJECTIVE: The objective of this study was to assess the results of applying Lean Methodology in the design of a standardized medication storage model in hospitalization departments. METHOD: Descriptive and retrospective study conducted between September 2017 and January 2019 in a tertiary level hospital. The Pharmacy Service led the creation of a multidisciplinary team. Lean Methodology was used to establish the components and organization and identification criteria that made up the standardized medication storage model. The stocks of each hospitalization department were reviewed and quantified, the final amount of stock needed was agreed with the supervisor of each department, and the economic impact of the implementation of the standardized medication model was assessed. A questionnaire was designed and sent to nursing staff to determine their level of satisfaction with the new model. RESULTS: The standardized medication storage model was scaled up to 20 nursing departments, leading to an overall reduction of 56.72% in the number of pharmaceutical dosage forms available (5,688 vs 2,462). The number of high-risk drugs was reduced by 40.73% (631 vs 374). This elimination of wastage achieved a saving of (Euro)25,357.98. A total of 58 nurses returned the questionnaires (20.70% of the total): 22.40% worked a fixed shift and 77.60% worked a rotating shift. The mean score on overall satisfaction was 5.79 ± 3.61 (scores ranged from 1 to 10). CONCLUSIONS: The application of Lean Methodology is very useful for the management of medication stocks in hospitalization departments. The implementation of a standardized medication storage model leads to economic savings and a marked reduction in the number of active ingredients and high-risk medications. The nursing staff were satisfied with the implementation of the model, suggesting that we should continue to pursue this effective line of action

Direct costs in patients with chronic inflammatory arthropathies on biological therapy: a real-world data study.

OBJECTIVES: The aim of the study was to assess the direct costs for the Spanish Health System of patients with chronic inflammatory arthropathies treated with biological therapies in daily clinical practice and to establish possible factors associated with lower costs. METHODS: A descriptive, observational and retrospective study was conducted. Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who started a biological therapy between 1 January 2009 and 31 December 2016 were included. Variables related to socioeconomic status, disease and biological therapy were included. The annual cost of biological treatment and other direct medical costs were calculated for each disease. The analysis of costs was based on the National Health Service perspective. The time horizon comprised the 8-year long study period. RESULTS: A total of 422 biological therapy lines were analysed. The annual biological therapy cost per patient was €12,494±3,865 for rheumatoid arthritis, €11,248±2,763 for ankylosing spondylitis and €12,263±35,155 for psoriatic arthritis (p=0.008). The cost of biological therapies entailed about 80% of the total cost of these diseases. Hospital admission was a factor which contributed to an increasing cost in all these conditions. A longer duration of the biological therapy was associated with lower cost in all the diseases. CONCLUSIONS: The cost of ankylosing spondylitis is lower than that of rheumatoid arthritis and psoriatic arthritis. The biological therapy is the factor with the highest impact on the overall cost of these diseases. Preventing hospital admissions and a higher persistence to the biological therapy can contribute to lower costs for the system.

Medication persistence on biological therapies prescribed for the treatment of chronic inflammatory arthropathies: a real-world data study.

OBJECTIVES: Medication persistence, defined as the duration of time from its initiation to its discontinuation, is a surrogate for treatment effectiveness. The aim of the study was to evaluate persistence and causes of biological therapy (BT) suspension in patients with chronic inflammatory arthropathies: rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Single institution, descriptive, retrospective cohort study. Adult patients with chronic inflammatory arthropathies on BT between January 2009 and December 2016 were included. Persistence to BT was compared considering the type of pathology and treatment. The Kaplan-Meier test was used to analyse medication persistanence and factors associated with it. An analysis of reasons for therapy discontinuation was performed. RESULTS: Three hundred and sixty-two patients were included in the study, which comprised 478 BT lines. For all patients, the 12-month persistence rate was 71.3% (341 out of 478). At the end of the study, 45.2% of the patients continued on their initial BT. Median treatment persistence was 1489 days (CI 95% 1195 to 1783). Longer BT persistence was associated with naïve BT patients: 1945 days (95% CI 1523 to 2367; P<0.001) and ankylosing spondylitis diagnosis: 2402 days (95% CI 1604 to 3200; P=0.014). The most frequent causes of treatment discontinuation were therapeutic failure (47.6%) and adverse drug events (28.2%). CONCLUSIONS: We found good long-term persistence in patients with chronic inflammatory arthropathies treated with BT. Patients with rheumatoid arthritis had significantly shorter persistence compared with those with ankylosing spondylitis and psoriatic arthritis. Naïve BT was associated with longer persistence. Therapeutic failure was the main cause of BT withdrawal.