ABSTRACT
The conformation of poly(methyl methacrylate) (PMMA)-based single-chain nanoparticles (SCNPs) and their corresponding linear precursors in the presence of deuterated linear PMMA in deuterated dimethylformamide (DMF) solutions has been studied by small-angle neutron scattering (SANS). The SANS profiles were analyzed in terms of a three-component random phase approximation (RPA) model. The RPA approach described well the scattering profiles in dilute and crowded solutions. Considering all the contributions of the RPA leads to an accurate estimation of the single chain form factor parameters and the Flory-Huggins interaction parameter between PMMA and DMF. The value of the latter in the dilute regime indicates that the precursors and the SCNPs are in good solvent conditions, while in crowding conditions, the polymer becomes less soluble.
ABSTRACT
(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.
ABSTRACT
OBJECTIVE: Patients included in MAINRITSAN2 trial received either an individually tailored or a fixed-schedule therapy with rituximab as maintenance treatment of antineutrophil cytoplasm antibody associated vasculitides. The aim of this study was to compare the real-world costs of both arms. METHOD: We performed a cost-minimization analysis over an 18-month time period, estimating direct costs -drug acquisition, preparation, administration and monitoring costs- from the health system perspective. We conducted a number of additional sensitivity analyses with different assumptions for unit costs, with further scenarios including the interquartile range of the tailored-infusion group results, different number of monitoring visits for fixed-schedule regimen and different number of reported severe adverse events. A cost- effectiveness analysis was conducted as a sensitivity analysis using the absolute difference in the relapse rate and its confidence interval. RESULTS: The individually tailored maintenance therapy with rituximab was shown to be a cost-saving treatment compared to the fixed-schedule therapy (6,049 euros vs. 7,850 euros). Savings resulted primarily from lower drug acquisition costs (2,861 vs. 4,768 euros) and lower preparation and administration costs (892 vs. 1,486 euros), due to the lower number of infusions per patient in the tailored-infusion regimen. The tailoredinfusion regimen presented higher monitoring costs (2,296 vs. 1,596 euros). This result was replicated in all assumptions considered in the sensitivity analysis of cost-minimization approach. CONCLUSIONS: From the perspective of the health system, the tailoredtherapy regimen seems to be the preferable option in terms of direct costs. Further studies assessing all the effects and costs associated to vasculitides maintenance treatment with rituximab are needed to support clinical management and healthcare planning.
Objetivo: Los pacientes incluidos en el ensayo MAINRITSAN2 recibieron una pauta individualizada o un esquema fijo de rituximab como tratamiento de mantenimiento para la vasculitis asociada con anticuerpos contra el citoplasma de los neutrófilos. El objetivo de este estudio es comparar los costes reales de ambos esquemas de tratamiento.Método: Se llevó a cabo un análisis de minimización de costes sobre un periodo de 18 meses, estimando los costes directos adquisición del fármaco, preparación, administración y costes de monitorización desde la perspectiva del sistema de salud. Se realizaron varios análisis de sensibilidad con diferentes supuestos para los costes unitarios, añadiendo escenarios que incluían el rango intercuartílico de los resultados en el grupo de la pauta individualizada, diferente número de visitas de control para el grupo que seguía el esquema fijo y distinto número de eventos adversos registrados. Se realizó un análisis de coste-efectividad como parte del análisis de sensibilidad usando la diferencia absoluta en la tasa de recaída y su intervalo de confianza.Resultados: El esquema de tratamiento con la pauta individualizada demostró una reducción del coste en comparación con el esquema de dosis fijas (6.049 versus 7.850 euros). El ahorro se debió principalmente a un menor coste en la adquisición del fármaco (2.861 versus 4.768 euros) dexchlorphey a menos costes de preparación y administración (892 versus 1.486 euros), debido al menor número de infusiones por paciente en el brazo del esquema individualizado. Este esquema individualizado presentó mayores costes de monitorización (2.296 versus 1.596 euros). Este resultado se repitió en todos los supuestos considerados en el análisis de sensibilidad desde el enfoque de minimización de costes.Conclusiones: Desde la perspectiva del sistema de salud, la pauta individualizada parece ser la opción preferible en términos de costes directos. No obstante, son necesarios más estudios que evalúen todos los efectos y costes asociados al tratamiento de mantenimiento con rituximab de la vasculitis por anticuerpo anticitoplasma de neutrófilo para respaldar el manejo clínico y la asistencia sanitaria.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/economics , Cost Control/methods , Precision Medicine/economics , Rituximab/therapeutic use , Antigens, CD19 , Cost-Benefit Analysis , Drug Costs , Female , Health Care Costs , Humans , Infusions, Intravenous , Lymphocyte Count , Male , Medication Therapy Management/economics , Rituximab/administration & dosageABSTRACT
OBJETIVO: Los pacientes incluidos en el ensayo MAINRITSAN2 recibieronuna pauta individualizada o un esquema fijo de rituximab como tratamiento de mantenimiento para la vasculitis asociada con anticuerpos contra el citoplasma de los neutrófilos. El objetivo de este estudio es comparar los costes reales de ambos esquemas de tratamiento. MÉTODO: Se llevó a cabo un análisis de minimización de costes sobre un periodo de 18 meses, estimando los costes directos -adquisición del fármaco, preparación, administración y costes de monitorización- desde la perspectiva del sistema de salud. Se realizaron varios análisis de sensibilidad con diferentes supuestos para los costes unitarios, añadiendo escenarios que incluían el rango intercuartílico de los resultados en el grupo de la pauta individualizada, diferente número de visitas de control para el grupo que seguía el esquema fijo y distinto número de eventos adversos registrados. Se realizó un análisis de coste-efectividad como parte del análisis de sensibilidad usan-do la diferencia absoluta en la tasa de recaída y su intervalo de confianza. RESULTADOS: El esquema de tratamiento con la pauta individualizada demostró una reducción del coste en comparación con el esquema de dosis fijas (6.049 versus 7.850 euros). El ahorro se debió principalmente a un menor coste en la adquisición del fármaco (2.861 versus 4.768 euros) y a menos costes de preparación y administración (892 versus 1.486 euros), debido al menor número de infusiones por paciente en el brazo del esquema individualizado. Este esquema individualizado presentó mayo-res costes de monitorización (2.296 versus 1.596 euros). Este resultado se repitió en todos los supuestos considerados en el análisis de sensibilidad desde el enfoque de minimización de costes. CONCLUSIONES: Desde la perspectiva del sistema de salud, la pauta individualizada parece ser la opción preferible en términos de costes directos. No obstante, son necesarios más estudios que evalúen todos los efectos y costes asociados al tratamiento de mantenimiento con rituximab de la vasculitis por anticuerpo anticitoplasma de neutrófilo para respaldar el manejo clínico y la asistencia sanitaria
OBJECTIVE: Patients included in MAINRITSAN2 trial received either an individually tailored or a fixed-schedule therapy with rituximab as maintenance treatment of antineutrophil cytoplasm antibody associated vasculi-tides. The aim of this study was to compare the real-world costs of both arms. METHOD: We performed a cost-minimization analysis over an 18-month time period, estimating direct costs-drug acquisition, preparation, administration and monitoring costs- from the health system perspective. We conducted a number of additional sensitivity analyses with different assumptions for unit costs, with further scenarios including the interquartile range of the tailored-infusion group results, different number of monitoring visits for fixed-schedule regimen and different number of reported severe adverse events. A cost-effectiveness analysis was conducted as a sensitivity analysis using the absolute difference in the relapse rate and its confidence interval. RESULTS: The individually tailored maintenance therapy with rituximab was shown to be a cost-saving treatment compared to the fixed-schedule therapy (6,049 euros vs. 7,850 euros). Savings resulted primarily from ower drug acquisition costs (2,861 vs. 4,768 euros) and lower prepara-tion and administration costs (892 vs. 1,486 euros), due to the lower number of infusions per patient in the tailored-infusion regimen. The tailored-infusion regimen presented higher monitoring costs (2,296 vs. 1,596 euros). This result was replicated in all assumptions considered in the sensitivity analysis of cost-minimization approach. CONCLUSIONS: From the perspective of the health system, the tailored-therapy regimen seems to be the preferable option in terms of direct costs. Further studies assessing all the effects and costs associated to vasculitides maintenance treatment with rituximab are needed to support clinical ma-nagement and healthcare planning
Subject(s)
Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/economics , Rituximab/administration & dosage , Rituximab/economics , Cost Efficiency Analysis , Drug Costs , Clinical ProtocolsABSTRACT
The kinin B1 receptor (B1R) plays a role in inflammatory and metabolic processes. B1R deletion (B1 -/-) protects mice from diet-induced obesity and improves insulin and leptin sensitivity. In contrast, genetic reconstitution of B1R exclusively in adipose tissue reverses the lean phenotype of B1 -/- mice. To study the cell-nonautonomous nature of these effects, we transplanted epididymal white adipose tissue (eWAT) from wild-type donors (B1 +/+) into B1 -/- mice (B1 +/+âB1 -/-) and compared them with autologous controls (B1 +/+âB1 +/+ or B1 -/-âB1 -/-). We then fed these mice a high-fat diet for 16 weeks and investigated their metabolic phenotypes. B1 +/+âB1 -/- mice became obese but not glucose intolerant or insulin resistant, unlike B1 -/-âB1 -/- mice. Moreover, the endogenous adipose tissue of B1 +/+âB1 -/- mice exhibited higher expression of adipocyte markers (e.g., Fabp4 and Adipoq) and changes in the immune cell pool. These mice also developed fatty liver. Wild-type eWAT transplanted into B1 -/- mice normalized circulating insulin, leptin, and epidermal growth factor levels. In conclusion, we demonstrated that B1R in adipose tissue controls the response to diet-induced obesity by promoting adipose tissue expansion and hepatic lipid accumulation in cell-nonautonomous manners.
Subject(s)
Adipose Tissue, White/metabolism , Receptor, Bradykinin B1/metabolism , Adipose Tissue, White/transplantation , Animals , Body Composition/genetics , Body Composition/physiology , Diet, High-Fat/adverse effects , Flow Cytometry , Glucose/metabolism , Insulin Resistance/genetics , Insulin Resistance/physiology , Liver/metabolism , Male , Mice , Receptor, Bradykinin B1/genetics , Weight Gain/genetics , Weight Gain/physiologyABSTRACT
Single-chain polymer nanoparticles (SCNPs) obtained through chain collapse by intramolecular cross-linking are attracting increasing interest as components of all-polymer nanocomposites, among other applications. We present a dielectric relaxation study on the dynamics of mixtures of poly(vinyl methyl ether) (PVME) and polystyrene (PS)-based SCNPs with various compositions. Analogous dielectric measurements on a miscible blend of PVME with the linear precursor chains of the SCNPs are taken as reference for this study. Both systems present completely different behaviors: While the blend with the linear precursor presents dynamics very similar to that reported for PVME/PS miscible blends, in the PVME/SCNP mixtures there are an appreciable amount of PVME segments that are barely affected by the presence of SCNPs, which nearly vanishes only for mixtures with high SCNP content. Interestingly, in the frame of a simple two-phase system, our findings point towards the existence of a SCNP-rich phase with a constant PVME fraction, regardless of the overall concentration of the mixture. Moreover, the dynamics of the PVME segments in this SCNP-rich phase display an extreme dynamic heterogeneity, a signature of constraint effects.
ABSTRACT
Ionic liquids (ILs) have shown advantages in organic synthesis and catalysis, energy storage and conversion, and a variety of pharmaceutical applications. Understanding the miscibility behavior of IL/monomer, IL/polymer, and IL/polymer nanoparticle mixtures is critical for the use of ILs as green solvents in polymerization processes as well as to rationalize recent observations concerning the superior solubility of some proteins in ILs when compared to standard solvents. In this work, the most relevant results obtained in terms of extended three-component Flory-Huggins theory concerning the extra solvent power (ESP) of ILs when compared to traditional nonionic solvents for monomeric solutes (Case I), linear polymers (Case II), dry (i.e., without IL inside) globular single-chain polymer nanoparticles (SCNPs) (Case III), and wet (i.e., with IL inside) globular SCNPs (Case IV) are presented. Moreover, useful ESP maps are drawn for the first time for IL mixtures corresponding to Cases I, II, III, and IV at a constant temperature and pressure. Finally, a potential pathway to improve the miscibility of nonionic polymers in ILs is proposed.
Subject(s)
Ionic Liquids/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Solvents/chemistry , WettabilityABSTRACT
In this study the superior stability against degradation induced by ultrasound irradiation of water-soluble single-chain polymer nanoparticles when compared to their parent precursor polymers is reported, and a loop scission mechanism in support of such behavior is suggested.
Subject(s)
Nanoparticles/chemistry , Water/chemistry , Polymers/chemistry , SonicationABSTRACT
Controlling the spatial distribution of catalytic sites in metallo-folded single-chain nanoparticles (SCNPs) is a first step toward the rational design of improved catalytic soft nano-objects. Here an unexplored pathway is reported for tuning the internal structure of metallo-folded SCNPs. Unlike the conventional SCNP synthesis in good solvent (protocol I), the proposed new route (protocol II) is based on the use of amphiphilic random copolymers and transfer, after SCNP formation, from selective to good (nonselective) solvent conditions. The size and morphology of the SCNPs obtained by the two protocols, and the corresponding spatial distribution of the catalytic sites, have been determined by combining results from size exclusion chromatography with triple detection, small-angle X-ray scattering and molecular dynamics (MD) simulations. Remarkably, the use of these protocols allows the tuning of the internal structure of the metallo-folded SCNPs, as supported by MD simulations results. While the conventional protocol I yields a homogeneous distribution of the catalytic sites in the SCNP, these are arranged into clusters in the case of protocol II.
Subject(s)
Metal Nanoparticles/chemistry , Organometallic Compounds/chemistry , Polymers/chemistry , Molecular Dynamics Simulation , Molecular Structure , Organometallic Compounds/chemical synthesis , Particle Size , Polymers/chemical synthesis , Solvents/chemistryABSTRACT
The recent ability to manipulate and visualize single atoms at atomic level has given rise to modern bottom-up nanotechnology. Similar exquisite degree of control at the individual polymeric chain level for producing functional soft nanoentities is expected to become a reality in the next few years through the full development of so-called "single chain technology". Ultra-small unimolecular soft nano-objects endowed with useful, autonomous and smart functions are the expected, long-term valuable output of single chain technology. This review covers the recent advances in single chain technology for the construction of soft nano-objects via chain compaction, with an emphasis in dynamic, letter-shaped and compositionally unsymmetrical single rings, complex multi-ring systems, single chain nanoparticles, tadpoles, dumbbells and hairpins, as well as the potential end-use applications of individual soft nano-objects endowed with useful functions in catalysis, sensing, drug delivery and other uses.
