Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)

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How Dispersion Interactions at the Excited State Can Tune Photochromism of Embedded Chromophores
(American Chemical Society, 2026-01-14) Guido, Ciro A.; Cupellini, Lorenzo; Mennucci, Benedetta; Curutchet Barat, Carles E.
We present QM/MMPol-cLR³, a polarizable embedding quantum mechanics/molecular mechanics (QM/MM) framework that includes explicit, state-specific dispersion terms. This method enables a rigorous treatment of dispersion on top of electrostatic and induction effects in ground- and excited-state calculations. Using QM/MMPol-cLR³, we show that dispersion interactions control excited-state solvatochromism through two distinct mechanisms. In azulene, opposite shifts of the L_a and L_b states arise from state-specific dispersion linked to changes in excited-state polarizability. In bacteriochlorophyll a, dispersion instead stems from the interplay between polarizability changes and transition-dipole-driven response, governing the Q_y and Q_x shifts. Finally, application to the LH2 complex reveals pigment-dependent dispersion shifts between the B800 and B850 rings, impacting the excitation-energy transfer. These results establish dispersion as an essential, nonempirical component for predictive excited-state simulations in complex environments.
Characterization of Ligand Binding in Human Serum Albumin from Atomistic Energy Transfer Simulations
(Wiley-VCH, 2025-12-01) Ergün, Özge; Bertran Mostazo, Andrea; Cubero Jordà, Elena; Galdeano Cantador, Carlos; Curutchet Barat, Carles E.
Förster resonance energy transfer (FRET) is a key biophysical method for probing nanometer‑scale distances in biomolecular systems, but its direct application to protein–ligand complexes suffers from substantial biases due to restricted chromophore orientations and the limited validity of the point‑dipole approximation. This study introduces a protocol for identifying binding sites and characterizing ligand coordination modes in situ by combining fluorescence spectroscopy with efficient atomistic simulations based on the TrESP‑MMPol model. The protocol integrates electrostatic potential‑fitted transition charges with a polarizable classical environment, thereby overcoming the orientation and dielectric-screening assumptions inherent to Förster theory. The protocol has been applied to human serum albumin (HSA) and a library of fluorescent small molecules, including known binders of the HSA, accurately reproducing the binding sites of naproxen, carprofen, and indomethacin, and revealing novel binding scenarios for other molecules. The results show that direct comparison of experimental FRET data with atomistically simulated observables enables discrimination of plausible binding models – including the site and binding mode – and avoids systematic errors in distance estimation. The protocol is particularly attractive to examine targets with a single tryptophan, and can also be extended to other targets of interest in drug discovery via site-labelling with unnatural amino acids.
Extracellular Vesicles from Probiotic and Beneficial Escherichia coli Strains Exert Multifaceted Protective Effects Against Rotavirus Infection in Intestinal Epithelial Cells
(MDPI, 2026-01-18) Cordero, Cecilia; Caballero Roman, Aitor; Martínez-Ruiz, Sergio; Olivo-Martinez, Yenifer; Baldomà Llavinés, Laura; Badía Palacín, Josefa
Rotavirus remains a major cause of severe acute gastroenteritisin infants worldwide. The suboptimal efficacy of current vaccines underscores the needfor alternative microbiome-based interventions, including postbiotics. Extracellularvesicles (EVs) from probiotic and commensal E. coli strains have been shown to mitigatediarrhea and enhance immune responses in a suckling-rat model of rotavirus infection.Here, we investigate the regulatory mechanisms activated by EVs in rotavirus-infectedenterocytes. Methods: Polarized Caco-2 monolayers were used as a model of matureenterocytes. Cells were pre-incubated with EVs from the probiotic E. coli Nissle 1917 (EcN)or the commensal EcoR12 strain before rotavirus infection. Intracellular Ca²⁺concentration, ROS levels, and the expression of immune- and barrier-related genes andproteins were assessed at multiple time points post-infection. Results: EVs from bothstrains exerted broad protective effects against rotavirus-induced cellular dysregulation,with several responses being strain-specific. EVs interfered with viral replication bycounteracting host cellular processes essential for rotavirus propagation. Specifically, EVtreatment significantly reduced rotavirus-induced intracellular Ca²⁺ mobilization, ROSproduction, and COX-2 expression. In addition, both EV types reduced virus-inducedmucin secretion and preserved tight junction organization, thereby limiting viral accessto basolateral coreceptors. Additionally, EVs enhanced innate antiviral defenses viadistinct, strain-dependent pathways: EcN EVs amplified IL-8-mediated responses,whereas EcoR12 EVs preserved the expression of interferon-related signaling genes.Conclusions: EVs from EcN and EcoR12 act through multiple complementarymechanisms to restrict rotavirus replication, spread, and immune evasion. These findingssupport their potential as effective postbiotic candidates for preventing or treatingrotavirus infection.
The (Anti)aromatic Properties of Cyclo[n]Carbons: Myth or Reality?
(Wiley, 2025-12-05) Stasyuk, O. A.; George, G.; Curutchet Barat, Carles E.; Plasser, F.; Stasyuk, A. J.
Recent advances in on-surface chemistry have enabled the synthesis and structural characterization of even-numbered cyclo[n]carbons, traditionally classified as either doubly aromatic (n = 4k + 2) or doubly antiaromatic (n = 4k) based on their in-plane and out-of-plane π-electron circuits. However, recent studies have increasingly questioned this classification, suggesting instead that these molecules are more accurately described as non-aromatic. In this work, we computationally examine the electron affinities and (anti)aromatic character of cyclo[n]carbons with n = 16–30 using energetic, structural, and electronic aromaticity descriptors. Adiabatic electron affinity (AEA) analysis reveals a high degree of uniformity across the series of both nominally aromatic and antiaromatic members. Aromatic stabilization energy (ASE) values, derived from homodesmotic and disproportionation reactions, indicate slight destabilization only for C₁₆ and C₂₀, and low stabilization for the remaining systems. In particular, ASE is less than 2 kcal/mol for cyclo[n]carbons with n ≥ 24. This suggests that neither aromatic nor antiaromatic character significantly contributes to the thermodynamic stability of larger cyclocarbons. EDDB analysis further supports this conclusion, with only about 22%–27% of π-electrons participating in delocalization. While delocalization is slightly greater in cyclo[n]carbons with n = 4k + 2, the difference diminishes with increasing size. Upon two-electron reduction to the dianionic state, all cyclo[n]carbons exhibit bond length equalization and increased delocalization. These results suggest that only small cyclo[n]carbons (n < 24) can be classified as weakly (anti)aromatic, while larger cyclo[n]carbons (n ≥ 24) are more appropriately classified as non-aromatic systems. The aromaticity of all considered cyclocarbons becomes more pronounced in corresponding dianionic forms due to cooperative structural and electronic effects. Thus, this work provides a unified framework for interpreting and predicting the electronic behavior of cyclocarbons.
Mechanical Strain-Controlled Aromaticity in Cyclo[n]Carbons
(Wiley-VCH, 2025-08-13) Stasyuk, O. A.; Curutchet Barat, Carles E.; Stasyuk, A. J.
Cyclocarbons have unique electronic and mechanical properties, but their extreme reactivity makes experimental studies and practical applications highly challenging. In this work, we use molecular modeling to investigate how mechanical strain, including uniaxial tension and radial contraction/expansion, affects the aromaticity of C₁₆ and C₁₈cyclocarbons. Aromaticity was evaluated using magnetic (NICS, GIMIC) and electronic (π-EDDB, AV1245) indices to provide a comprehensive assessment. Our results show that uniaxial tension slightly reduces the (anti)aromaticity of both cyclocarbons, with C₁₆becoming less antiaromatic and C₁₈ less aromatic. Radial expansion leads to almost complete loss of aromaticity, regardless of the initial electronic nature of the cyclocarbon. In turn, radial contraction appears to be an effective approach to enhance electronic delocalization in cyclocarbons, with a particularly notable effect for C₁₈. One of the most significant findings is that an 8% radial contraction transforms moderately aromatic C₁₈into a highly aromatic system with fully equalized bond lengths, offering a potential strategy for designing more stable cyclocarbon systems within mechanically strained architectures.
Impact of vehicle occlusivity on skin delivery and activity of a janus kinase inhibitor: comparison of oil-based formulations
(MDPI, 2025-12-18) Sarango Granda, Paulo; Mohammadi-Meyabadi, Roya; Braza Reyes, Antonio J.; Sosa Díaz, Lilian Elisa; Suñer Carbó, J. (Joaquim); Mallandrich Miret, Mireia; Calpena Campmany, Ana Cristina
Evaluar cómo el tipo de vaselina (líquida o sólida) influye en la estabilidad, liberación, permeación cutánea, retención y eficacia antiinflamatoria de formulaciones lipídicas tópicas con baricitinib (BCT), un inhibidor selectivo de JAK1/JAK2 usado en psoriasis.Metodología:Se desarrollaron formulaciones con Labrafac® Lipophile WL 1349 (MCT) y vaselina líquida (LLV) o sólida (LSV) en concentraciones del 30% y 60%. Se evaluaron:Estabilidad físico-química (60 días).Reología y extensibilidad.Liberación in vitro y permeación ex vivo en piel humana.Retención cutánea.Seguridad (HET-CAM, test de tolerancia en voluntarios sanos).Eficacia in vivo en un modelo murino de psoriasis inducida por imiquimod.Resultados principales:Solo las formulaciones con 30% de vaselina fueron estables durante 60 días.LLV (vaselina líquida) mostró comportamiento newtoniano, mayor extensibilidad, liberación sostenida (≈84% a 50 h) y mayor retención cutánea.LSV (vaselina sólida) mostró comportamiento pseudoplástico, menor extensibilidad y liberación más baja (≈47% a 50 h), pero mayor flujo de permeación ex vivo.Ambas formulaciones mejoraron la hidratación del estrato córneo y redujeron la pérdida transepidérmica de agua, sin causar irritación.En el modelo murino, ambas redujeron eritema, engrosamiento epidérmico, edema y alteraciones histológicas, confirmando la eficacia antiinflamatoria local.Conclusiones:El tipo de vaselina determina de forma decisiva la liberación y actividad del baricitinib.LLV favorece la retención epidérmica y una acción local sostenida, ideal para psoriasis localizada.LSV mejora la permeación transcutánea, aunque puede aumentar el riesgo de exposición sistémica.Estos hallazgos subrayan la importancia de la selección del excipiente en el diseño de formulaciones tópicas seguras y efectivas de inhibidores JAK.
Assessing the value contribution of belumosudil in the treatment of chronic graft-versus-host disease (CGVHD) after the failure of at least two previous lines of systemic therapy through multi-criteria decision analysis
(Wecare-U, 2025-10-15) Bermúdez, Arancha; Escudero Vilaplana, Vicente; Guiu Segura, Josep Maria; Hernández, Ascensión; Herrero Ambrosio, Alicia; Mussetti, Alberto; Poveda Andrés, José Luis; Martín Machín, Celia
Background: Chronic graft-versus-host disease (cGVHD) is a rare and serious complication following allogeneic hematopoietic cell transplantation and a major cause of long-term morbidity and mortality. Approximately half of transplant recipients develop cGVHD, and therapeutic options are particularly limited for patients who fail at least two lines of systemic therapy. In this setting, no treatments are approved in the European Union. Belumosudil, an oral selective ROCK2 inhibitor, is currently under evaluation by the European Medicines Agency (EMA) for this indication. Objective: To evaluate the value contribution of belumosudil for the treatment of cGVHD after failure of two or more systemic therapies, using a Multi-Criteria Decision Analysis (MCDA) approach adapted for orphan drugs in the Spanish healthcare context. Methods: An MCDA was conducted using the EVIDEM framework adapted for orphan drug assessment. A multidisciplinary panel of hematologists, hospital pharmacists, healthcare managers, and a patient representative evaluated 13 quantitative and contextual criteria. Evidence was compiled through a structured literature review and presented in an evidence matrix. Each expert scored the matrix independently and participated in a reflective discussion to contextualize and reassess their evaluations. Results were analysed to determine mean scores, variability, and value contribution. Results: Belumosudil achieved a high overall MCDA score (0.65). The main contributing criteria were disease severity, unmet needs, therapeutic impact, and comparative efficacy. Experts highlighted its favourable clinical profile, symptom control potential, and relevance in a patient population lacking approved alternatives. Contextual criteria also received positive assessments, indicating alignment with health system priorities and feasibility of implementation. Reflective discussion reduced variability and strengthened the consensus on its value. Conclusions: Belumosudil represents a valuable treatment option for patients with advanced cGVHD, a population with significant unmet needs. The use of reflective MCDA enabled a comprehensive and transparent value assessment, integrating clinical, economic, and contextual dimensions. These findings may support value-based decision-making for the adoption of orphan drugs within healthcare systems
Beers, STOPP/START, and PRISCUS: A critical analysis of their evolution and applicability in geriatrics prescribing.
(Universidad de Granada, 2025-03-18) Alemán Fernández, Eliezer; Siverio Mota, Dany; Vicet Muro, Liliana; Delgado-Hernández, René; Machado-Rivero, Manuel Osvaldo
Introduction: Polypharmacy, defined as the concomitant use of five or more medications, is common in older adults. Potentially inappropriate medications (PIMs) are drugs whose risks outweigh their potential benefits in older adults, especially when other effective alternatives are available. The objective of this research is to conduct a comparative analysis of the evolution, cross-cultural adaptations, advantages, and limitations of the Beers, STOPP/START, and PRISCUS criteria to evaluate their applicability in diverse clinical contexts.Method: A critical narrative review of articles retrieved from the PubMed, LILACS, SciELO, and Cochrane databases. The search was limited to the period between 2014 and 2024, with no initial language restrictions applied. Original articles, systematic reviews, clinical practice guidelines, and validation studies were included.Results: Out of the 675 references retrieved, 31 articles were selected after applying the inclusion and exclusion criteria. The Beers criteria accounted for 73.7 % of the total identified publications (n=498/675), and the 11 adaptations of the STOPP/START criteria were noteworthy.Conclusions: The Beers and STOPP/START criteria have transcended their original purpose to become foundational pillars for the development of local tools. Their value lies not only in their direct application but also in their role as reference frameworks for the creation and validation of culturally adapted criteria.
Stepwise Structural Simplification of the Dihydroxyanthraquinone Moiety of a Multitarget Rhein-Based Anti-Alzheimer Lead to Improve Drug Metabolism and Pharmacokinetic Properties
(MDPI, 2024-07-25) Sabaté Lagunas, Raimon; Loza, María Isabel; Brea, José; Muñoz-Torrero López-Ibarra, Diego; Pont Masanet, Caterina; Sampietro, Anna; Pérez Areales, Francisco Javier; Cristiano, Nunzia; Albalat, Agustí; Pérez, Belén; Bartolini, Manuela; De Simone, Angela; Andrisano, Vincenza; Barenys Espadaler, Marta; Teixidó Condomines, Elisabet
Multitarget compounds have emerged as promising drug candidates to cope with complex multifactorial diseases, like Alzheimer’s disease (AD). Most multitarget compounds are designed by linking two pharmacophores through a tether chain (linked hybrids), which results in rather large molecules that are particularly useful to hit targets with large binding cavities, but at the expense of suffering from suboptimal physicochemical/pharmacokinetic properties. Molecular size reduction by removal of superfluous structural elements while retaining the key pharmacophoric motifs may represent a compromise solution to achieve both multitargeting and favorable physicochemical/PK properties. Here, we report the stepwise structural simplification of the dihydroxyanthraquinone moiety of a rhein–huprine hybrid lead by hydroxy group removal—ring contraction—ring opening—ring removal, which has led to new analogs that retain or surpass the potency of the lead on its multiple AD targets while exhibiting more favorable drug metabolism and pharmacokinetic (DMPK) properties and safety profile. In particular, the most simplified acetophenone analog displays dual nanomolar inhibition of human acetylcholinesterase and butyrylcholinesterase (IC₅₀ = 6 nM and 13 nM, respectively), moderately potent inhibition of human BACE-1 (48% inhibition at 15 µM) and Aβ42 and tau aggregation (73% and 68% inhibition, respectively, at 10 µM), favorable in vitro brain permeation, higher aqueous solubility (18 µM) and plasma stability (100/96/86% remaining in human/mouse/rat plasma after 6 h incubation), and lower acute toxicity in a model organism (zebrafish embryos; LC₅₀ >> 100 µM) than the initial lead, thereby confirming the successful lead optimization by structural simplification.
Human-in-the-Loop AI Use in Ongoing Process Verification in the Pharmaceutical Industry
(MDPI, 2025-12-06) Romero Obon, Miquel; Rouaz El Hajoui, Khadija; Sancho-Ochoa, Virginia; Vargas, Ronny; Pérez Lozano, Pilar; Suñé Pou, Marc; García Montoya, Encarna
The pharmaceutical industry’s pursuit of enhanced product quality, regulatory compliance, and operational efficiency has catalyzed the integration of Artificial Intelligence (AI) into Ongoing Process Verification (OPV) frameworks. This comprehensive review examines the synergistic application of Human-in-the-Loop (HITL) AI systems within OPV, contextualized by the evolving regulatory landscape, particularly the newly introduced Annex 22 of the European Union Good Manufacturing Practices (EU-GMP). The review delineates the sector’s strategic shift from traditional validation models toward dynamic, data-driven approaches that leverage AI for real-time monitoring, predictive analytics, and proactive process control. Central to this transformation is the HITL paradigm, which ensures that human expertise remains embedded in critical decision-making loops, thereby safeguarding patient safety, product quality, data integrity, and ethical responsibility. Annex 22 explicitly mandates deterministic behavior, traceability, and explainability for AI models used in GMP-critical applications, excluding adaptive and probabilistic systems from such contexts. The document also reinforces the necessity of multidisciplinary governance, rigorous validation protocols, and risk-based oversight throughout the AI lifecycle. This paper synthesizes current industry practices, regulatory expectations, and technological capabilities, offering a structured framework for compliant AI deployment in OPV. By aligning AI implementation with Annex 22 principles and existing GMP frameworks (e.g., Annex 11 and ICH Q9), the pharmaceutical sector can harness AI’s transformative potential while maintaining robust regulatory compliance. The review concludes with actionable recommendations for integrating HITL AI into OPV strategies, fostering a resilient, transparent, ethical, and future-ready manufacturing ecosystem.
Guiding the starting dose of the once-daily formulation of tacrolimus in " de novo" adult renal transplant patients: a population approach
(Frontiers Media, 2024-09-19) Cruzado, Josep Ma.; Lloberas Blanch, Núria; Fernández Alarcón, Beatriz; Nolberger, Oscar; Vidal Alabró, Anna; Rigo Bonnin, Raúl; Grinyó Boira, Josep M.; Melilli, Edoardo; Montero Pérez, Núria; Manonelles, Anna; Coloma, Ana; Favà Buch, Alexandre; Colom Codina, Helena
Aims: The once-daily extended-release tacrolimus formulation (ER-Tac) has demonstrated similar efficacy and safety to the twice-daily immediate-release formulation (IR-Tac), but few population-based pharmacokinetic models have been developed in de novo kidney transplant patients to optimize doses. Therefore, this study aimed i) at developing a population pharmacokinetic model for ER-Tac in de novo adult kidney transplant patients ii) and identifying genetic factors and time-varying covariates predictive of pharmacokinetic variability to guide tacrolimus dosage during the early post-transplant period. Methods: A total of 1,067 blood tacrolimus concentrations from 138 kidney transplant patients were analyzed. A total of 29 out of 138 patients were intensively sampled for 24 h on the day 5 post-transplantation; meanwhile, for the remaining patients, concentrations were collected on days 5, 10, and 15 after transplantation. Tacrolimus daily doses and genetic and demographic characteristics were retrieved from the medical files. Biochemistry time-varying covariates were obtained on different days over the pharmacokinetic (PK) study. A simultaneous PK analysis of all concentrations was carried out using the non-linear mixed-effects approach with NONMEM 7.5. Results: A two-compartment model with linear elimination and delayed absorption best described the tacrolimus pharmacokinetics. Between-patient variability was associated with oral blood clearance (CL/F) and the central compartment distribution volume (Vc/F). Tacrolimus concentrations standardized to a hematocrit value of 45% significantly improved the model (p < 0.001). This method outperformed the standard covariate modeling of the hematocrit–blood clearance relationship. The effect of the CYP3A5 genotype was statistically (p < 0.001) and clinically significant on CL/F. The CL/F of patients who were CYP3A5*1 carriers was 51% higher than that of CYP3A5*1 non-carriers. Age also influenced CL/F variability (p < 0.001). Specifically, CL/F declined by 0.0562 units per each increased year from the value estimated in patients who were 60 years and younger. Conclusion: The 36% between-patient variability in CL/F was explained by CYP3A5 genotype, age, and hematocrit. Hematocrit standardization to 45% explained the variability of tacrolimus whole-blood concentrations, and this was of utmost importance in order to better interpret whole-blood tacrolimus concentrations during therapeutic drug monitoring. The dose requirements of CYP3A5*/1 carriers in patients aged 60 years or younger would be highest, while CYP3A5*/1 non-carriers older than 60 years would require the lowest doses.
A fast, reproducible and sensitive human-plasma HPLC-fluorescence method to quantify Carvedilol and the error function
(Elsevier B.V., 2025-08-29) Braza Reyes, Antonio J.; Viñas Bastart, Montserrat; Sureda Rosich, Maria; Lastra, Cecilia; Mariño Hernández, Eduardo L.; Modamio Charles, Pilar
El trabajo presenta el desarrollo y validación de un método bioanalítico rápido, sensible y reproducible para la cuantificación de carvedilol en plasma humano mediante cromatografía líquida de alta eficacia (HPLC) con detección por fluorescencia.El método mostró un excelente rendimiento dentro del rango terapéutico (3,91–125 ng/mL), con buena linealidad (CV: 12,05 %), precisión intra- e inter-día (CV: 8,31 % y 10,84 %, respectivamente), exactitud aceptable (RE: 11,51 %) y una recuperación del 89,3 %. Los límites de cuantificación (LLOQ) y de detección (LOD) fueron de 1,95 y 0,98 ng/mL, respectivamente, con un tiempo de retención muy corto (3,15 min) que permite un alto rendimiento analítico.Además, se calculó una función de error analítico (SD = 0,322 + 0,086C), útil para aplicar estrategias de ponderación adecuadas en estudios farmacocinéticos y de monitorización terapéutica. El método obtuvo una puntuación de 0,67 en la métrica AGREE, lo que indica un perfil de sostenibilidad ambiental moderado.En comparación con métodos previos, este procedimiento resulta más económico y eficiente, al prescindir de la espectrometría de masas y reducir significativamente el tiempo de análisis, lo que lo hace idóneo para laboratorios clínicos hospitalarios y para la monitorización de la adherencia terapéutica en pacientes.Aportación personalEste estudio representa un avance relevante porque no solo optimiza la determinación de carvedilol en plasma con un método accesible y rápido, sino que además introduce la función de error como herramienta de mayor rigor analítico, un aspecto poco explorado en la literatura.Desde una perspectiva aplicada, considero que esta metodología puede tener un gran impacto en la farmacia clínica, ya que facilita la individualización de la terapia en pacientes con comorbilidades (insuficiencia hepática, renal o cardíaca) y en población anciana, donde la variabilidad farmacocinética es significativa.Asimismo, la evaluación de la sostenibilidad mediante criterios de química analítica verde es un valor añadido alineado con las tendencias actuales en investigación. Sin embargo, sería deseable avanzar en la sustitución de disolventes tóxicos (éter dietílico y acetonitrilo) para mejorar el perfil ecológico del procedimiento.En resumen, la metodología validada combina robustez científica, aplicabilidad clínica y visión sostenible, lo que la convierte en un referente para futuras investigaciones en monitorización terapéutica y adherencia a tratamientos cardiovasculares.
La producció local de medicaments com a palanca de resiliència sanitària i transició verda
(Col·legi de Farmacèutics de Barcelona, 2025-09-29) Guiu Segura, Josep Maria; Colomé Font, Maria
La pandèmia de COVID-19 va revelar vulnerabilitats en els sistemes de salut globals, com la dependència de les cadenes de subministrament internacionals i les desigualtats en l'accés a medicaments. Aquestes mancances van impulsar la necessitat de produir medicaments localment, especialment en països en desenvolupament, per garantir la seguretat sanitària i reduir la dependència de les importacions. A més, la transició verda en la producció farmacèutica, que promou pràctiques més sostenibles, pot millorar la resiliència del sistema sanitari i reduir costos. La col·laboració internacional és essencial per enfortir la capacitat de producció local i garantir l'accés a medicaments essencials.
Cost-utility analysis of dapagliflozin for the treatment of symptomatic chronic heart failure in Spain
(BioMed Central, 2025-07-24) Escobar, Carlos; Pascual-Figal, Domingo; Guiu Segura, Josep Maria; Capel, Margarita; Pomares Mallol, Elisenda; Caudron, Christian
The objective of this study was to perform a cost-utility analysis of dapagliflozin, as an add-on therapy to standard of care (SoC), compared with SoC, for patients with symptomatic chronic heart failure (HF) in Spain, including patients with reduced and preserved ejection fraction.
Methods: A Markov model was designed to simulate the progression of chronic HF over a lifetime horizon using pooled data from the DAPA-HF and DELIVER trials. Disease progression was captured by transitions between health states, defined by the Kansas City Cardiomyopathy Questionnaire Total Symptom Score. Transient events of hospitalization for HF (HHF), urgent HF visits (UHFV) and cardiovascular (CV) and non-CV death were included. The analysis was conducted from the Spanish National Health System perspective. The results were expressed as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to assess the robustness of the results.
Results: Dapagliflozin + SoC showed an increase in effectiveness (0.31 QALY) and total cost per patient (€1,441) compared to SoC, yielding an incremental cost-utility ratio of €4,611/QALY. Dapagliflozin reduced the incidence of HHF by 136.4 events (752.2 vs. 886.6), UHFV by 38.8 (217.6 vs. 254.4) and CV death by 23.0 (505.8 vs. 528.8) for every 1,000 patients. Dapagliflozin + SoC was cost-effective compared to SoC in 99.9% of iterations at a willingness-to-pay (WTP) threshold of €25,000/QALY.
Conclusions: The analysis shows that dapagliflozin, as add-on therapy to SoC, would be a cost-effective option compared to SoC for the treatment of adult patients with symptomatic chronic HF in Spain at a WTP of €25,000/QALY.
La certificación Board of Pharmacy Specialties (BPS) como estrategia del desarrollo profesional continuo de la farmacia hospitalaria
(Sociedad Española de Farmacia Hospitalaria, 2025-04-25) Guiu Segura, Josep Maria
España se ha consolidado como referente europeo en la certificación de competencias avanzadas de los farmacéuticos hospitalarios, especialmente en oncología, gracias al impulso de iniciativas orientadas a la formación, preparación y recertificación profesional. El Board of Pharmacy Specialties (BPS), entidad internacional de referencia desde 1976, certifica actualmente 15 especialidades. A marzo de 2025, España cuenta con 287 farmacéuticos certificados en nueve áreas, destacando oncología y farmacoterapia. La creciente complejidad clínica y la aparición de nuevas subespecialidades refuerzan la necesidad de integrar la certificación y recertificación en el desarrollo profesional continuo, como garantía de calidad asistencial, seguridad del paciente y excelencia del sistema sanitario.
Value Contribution of Palopegteriparatide in Adult Patients with Chronic Hypoparathyroidism using Multicriteria Decision Analysis (MCDA)
(Springer Verlag, 2025-10-24) Díez, Juan José; Badia, Xavier; Abad, Reyes; Alerany, Carmen; Climente Martí, Mónica; Guiu, Josep Maria; Martín, Isabel; Caballero, María; Muñoz Torres, Manuel
Introduction: The study objective was to determine the value contribution of palopegteriparatide to the treatment of adults with chronic hypoparathyroidism, a rare endocrine disease, through a multi-criteria decision analysis (MCDA).
Methods: The Orphar-SEFH group framework for evaluating orphan drugs was used, along with the weighting performed by 98 national and regional evaluators. A multidisciplinary panel of seven experts individually scored the evidence matrix. The scores were collected and analysed using Microsoft Excel software programmed for MCDA study analysis. The results were discussed in a reflective discussion session.
Results: The expert panel considered chronic hypoparathyroidism to be a moderate-to-severe disease (mean ± SD: 3.3 ± 0.5) due to its multiorgan impact and associated comorbidities, with significant unmet needs (3.6 ± 1.0), particularly related to the lack of the physiological effect due to insufficient levels of parathyroid hormone. The experts found palopegteriparatide as an add-on treatment to conventional therapy (calcium and active vitamin D) to be much more effective than placebo plus conventional therapy, with this criterion receiving the highest score. The safety profile was considered acceptable (1.6 ± 1.1). The participants highlighted the positive impact of palopegteriparatide on patient-reported outcomes (2.9 ± 0.9) compared to placebo because of improvements in quality of life (QoL). Palopegteriparatide was seen as a potentially disease-modifying treatment, which could lead to savings in "other medical costs" (3.1 ± 1.1) and "non-medical/indirect costs" (2.0 ± 0.8), although no evidence was available, especially in the long term. The quality of the evidence was perceived as high (3.6 ± 0.5). The overall value contribution of palopegteriparatide was 0.58 (+ 1 = maximum value) compared to placebo. The study has some limitations, including a relatively small panel size and the exclusion of treatment cost as a criterion due to lack of pricing information at the time of evaluation.
Conclusion: According to MCDA, palopegteriparatide represents a valuable therapeutic option for chronic hypoparathyroidism treatment, particularly due to its demonstrated efficacy, which had an impact on patients' QoL, and the current unmet needs in this therapeutic area.
Explicit criteria for Potentially Inappropriate Medications in Older Adults: A comprehensive systematic review.
(GarVal Editorial, 2025-08-29) Alemán Fernández, Eliezer; Siverio Mota, Dany; Vicet Muro, Liliana; Braza Reyes, Antonio J.; Viñas Bastart, Montserrat; Modamio Charles, Pilar; Delgado-Hernández, René
Context: Potentially inappropriate medications (PIMs) refer to the use of a medication whose risks outweigh the potential benefits in older adults, especially when other effective alternatives are available.
Aims: To identify and analyze explicit criteria developed for detecting PIMs in older adults, highlighting methodological approaches and pharmacological classifications.
Methods: A comprehensive literature search was conducted across seven databases from January 1990 to December 2024, following the PRISMA 2020 guidelines. Criteria developed using expert consensus or evidence-based processes were included.
Results: Out of 3,119 articles, 68 met the inclusion criteria. The Beers and STOPP/START tools were most frequently cited. The Delphi method was the predominant approach for validating the selected tools (73.53%). Commonly flagged medications included tricyclic antidepressants, NSAIDs, and benzodiazepines.
Conclusions: Numerous validated tools exist, although variations in validation methods and drug classification were observed. A global update and harmonization of explicit criteria are necessary for improved geriatric pharmacotherapy.
Keywords: Beers criteria; Delphi method; deprescribing tools; older adults; potentially inappropriate medications; STOPP START criteria.
Rose Bengal-incorporated supramolecular gels as a topical platform for localized antimicrobial photodynamic therapy
(MDPI, 2025-11-26) Anguluri, Kavya; Bagherpour, Saman; Calpena Campmany, Ana Cristina; Halbaut, Lyda; Espargaró Colomé, Alba; Sabaté Lagunas, Raimon; Pérez-García, Lluïsa
Efficient and localized singlet oxygen (SO) generation is essential for improving antimicrobial photodynamic therapy (aPDT). In this study, a bis-imidazolium-based amphiphilic gelator is used, which self-assembles into a supramolecular gel in a water–ethanol medium and incorporates Rose Bengal (RB) as a photosensitizer. The gel network provides a confined environment that promotes SO formation under light irradiation. RB@Gel was characterized with respect to its morphology, degradation behavior, and swelling properties. Biopharmaceutical assessment included in vitro release, ex vivo permeation studies and Hen’s Egg Test–Chorioallantoic Membrane (HET-CAM) assay. Rheological measurements confirmed a viscoelastic profile, indicating structural stability and suitability for localized therapeutic applications. SO production within the gel was quantified using tetrasodium 9,10-anthracenediyl-bis(methylene)dimalonate (NaABMA), showing higher efficiency than that of RB in solution. The RB@Gel exhibited significant aPDT against E. coli in a direct-surface contact assay. Overall, the RB@Gel provides a stable, suitable platform capable of efficient SO generation and potent antibacterial activity, highlighting its promise for localized aPDT applications.
Evaluación Clínica Objetiva Estructurada (ECOE) en el grado de Farmacia de la Universitat de Barcelona
(Congrés Internacional de Docència Universitària i Innovació (CIDUI), 2023-11-27) Lastra, Cecilia; Braza Reyes, Antonio J.; Braun Vives, Joaquin; Mariño Fernández, Cecilia; Rodríguez García, Estela; Ruiz Loscertales, Hèctor; Tobaruela Martínez, Gonzalo; Modamio Charles, Pilar; Mariño Hernández, Eduardo L.
El trabajo presenta la implementación de una Evaluación Clínica Objetiva Estructurada (ECOE) en el Grado de Farmacia de la Universitat de Barcelona, dentro de la asignatura Farmacia Asistencial de quinto curso. Este tipo de prueba, descrita por Harden en 1975, permite evaluar de manera planificada, estructurada y objetiva las competencias clínicas del estudiante, combinando conocimientos teóricos, aplicados y prácticos según los tres primeros niveles de la pirámide de Miller (“saber”, “saber cómo” y “demostrar cómo”).
La iniciativa surge ante la necesidad de incorporar metodologías evaluativas que reflejen de forma más fiel las competencias profesionales del farmacéutico, especialmente aquellas relacionadas con la comunicación, el juicio clínico y la capacidad de resolver problemas en entornos reales. La ECOE se aplicó de manera piloto en diciembre de 2022 con 10 estudiantes voluntarios, distribuidos en un circuito de cuatro estaciones de 10 minutos cada una (duración total: una hora).
Las estaciones fueron: (1) búsqueda de información sobre medicamentos en fuentes bibliográficas; (2) preparación de un caso clínico; (3) simulación de la atención a un paciente en el Aula de Simulación de la Facultad, con escenarios que reproducían una farmacia comunitaria y una zona de atención personalizada; y (4) resolución de actuaciones asistenciales derivadas, como la elaboración de un plan de medicación o la detección de problemas relacionados con medicamentos.
El diseño incluyó hojas de instrucciones detalladas para cada estación y dos encuestas tipo Likert para evaluar la organización de la prueba y la satisfacción del alumnado. Los resultados mostraron una valoración global muy positiva: los estudiantes puntuaron con 4,9/5 la coherencia de las estaciones y su adecuación a situaciones reales, con 4,8/5 la claridad de las instrucciones y con 4,6/5 la organización general. El tiempo disponible (10 minutos por estación) fue el aspecto peor valorado (3,6/5). La estación más sencilla fue la de búsqueda de información y la más compleja, la de actuaciones asistenciales.
La simulación clínica fue el elemento mejor valorado, destacándose por su realismo y su utilidad para aplicar los conocimientos adquiridos. Los participantes señalaron que la ECOE les ayudó a ganar confianza en la comunicación con pacientes y otros profesionales y a percibir la evaluación como una experiencia formativa más que punitiva. En conjunto, consideraron que esta metodología debería implementarse de manera estable en el grado, especialmente para evaluar competencias comunicativas y asistenciales.
Entre los aspectos de mejora, los estudiantes propusieron ampliar el tiempo por estación, realizar sesiones informativas previas y permitir el uso de apuntes propios. Los docentes, por su parte, identificaron la necesidad de optimizar la coordinación logística y la formación de evaluadores y actores simulados.
En conclusión, la ECOE se consolida como una herramienta innovadora y eficaz para evaluar competencias clínicas en Farmacia, favoreciendo una evaluación objetiva, contextualizada y cercana a la práctica profesional. Su implantación progresiva en el plan de estudios contribuiría a fortalecer la formación asistencial y a preparar a los futuros farmacéuticos para un ejercicio profesional más competencial, comunicativo y centrado en el paciente.
Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?
(Fundación Pharmaceutical Care, 2022-01-01) Viñas Bastart, Montserrat; Oms, Míriam; Pedraza-Gutiérrez, Àfrica; Lizano Díez, Irene; Mariño Hernández, Eduardo L.; Modamio Charles, Pilar
Introducción: La utilización de la combinación a dosis fija de tramadol/dexketoprofeno en España y en otros países ha aumentado de forma considerable. La indicación terapéutica autorizada de este medicamento es el tratamiento sintomático a corto plazo del dolor agudo de moderado a intenso en pacientes adultos. El objetivo de este estudio fue describir el patrón de uso de tramadol/dexketoprofeno en el ámbito de la atención primaria de salud.
Método: Se realizó un estudio transversal, descriptivo y multicéntrico. La población de estudio incluyó a todos los pacientes de una Dirección de Atención Primaria (53 equipos de Atención Primaria) que tenían activa la prescripción de tramadol/dexketoprofeno el 28 de marzo de 2018. La población diana fueron aquellos pacientes a los que se les prescribió tramadol/dexketoprofeno durante más de 20 días.
Resultados: Un total de 176 pacientes tenía activa la prescripción de tramadol/dexketoprofeno. Todos los pacientes (100%) tuvieron una duración del tratamiento superior a 5 días y el 72,7% (N=128) superior a 20 días. La duración media del tratamiento fue de 14±160,9 días en pacientes que tenían menos de 20 días de tratamiento y de 224±160,8 días en pacientes que tenían más de 20 días de tratamiento. El 35,1% de los pacientes estaban tratados con más de 2 medicamentos para aliviar el dolor de forma concomitante con tramadol/dexketoprofeno. El médico de atención primaria inició un 65,6% de las prescripciones.
Conclusiones: La combinación a dosis fija de tramadol/dexketoprofeno se utilizó con frecuencia fuera de indicación, de acuerdo con la ficha técnica y la evidencia científica disponible. Este estudio alerta sobre los riesgos potenciales asociados a la utilización de este medicamento en la práctica clínica, como son la falta de efectividad y/o la aparición de efectos adversos.

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