Cost-Effectiveness of Lorlatinib for the Treatment of Adult Patients with Anaplastic Lymphoma Kinase Positive Advanced Non-Small Cell Lung Cancer in Spain.

Purpose: The objective of the present study was to evaluate the efficiency of lorlatinib compared to alectinib and brigatinib for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated, in Spain. Methods: A partitioned survival model comprised progression free, non-intracranial progression, intracranial progression, and death health states was constructed to estimate the total costs, life-years gained (LYG) and quality-adjusted life years (QALYs) accumulated in a lifetime horizon. Overall survival (OS) and progression-free survival (PFS) for lorlatinib were obtained from the CROWN study. For alectinib and brigatinib, a network meta-analysis of randomized controlled trials was conducted to estimate OS and PFS hazard ratios versus crizotinib. Utilities were estimated based on EQ-5D-5L data derived from the CROWN (lorlatinib), ALEX (alectinib) and ALTA-1L (brigatinib) studies. According to the Spanish National Health Service perspective the total costs (expressed in euros using a 2021 cost year) included drug acquisition and the administration's subsequent treatment, ALK+ advanced NSCLC management and adverse-event management, and palliative care. Unitary costs were obtained from local cost databases and literature. Costs, LYGs and QALYs were discounted at 3% annually. Deterministic and probabilistic sensitivity analyses were used to test the model's robustness. Results: Lorlatinib provided higher health outcomes (+0.70 LYG/patient, +1.42 QALYs/patient) and lower costs (-€9239/patient) than alectinib. Lorlatinib yielded higher LYG (+1.74) and QALYs (+2.30) versus brigatinib but higher costs/patient (+€36,627), resulting in an incremental-cost-effectiveness-ratio of €15,912/QALY gained. Conclusion: The results of this study suggest that lorlatinib may be a dominant treatment option versus alectinib. Considering a willingness-to-pay threshold of €25,000/QALY, lorlatinib may be an efficient option compared to brigatinib.

Electrochemical Exfoliation of Graphene Oxide: Unveiling Structural Properties and Electrochemical Performance.

An electrochemical exfoliation method for the production of graphene oxide and its characterization by electrochemical techniques are presented here. Graphite rods are used as working electrode in a three-electrode electrochemical cell, and electro-exfoliation is achieved by applying anodic polarization in a sulfuric acid solution. The electrochemical process involved two steps characterized by an intercalation at lower potential and an exfoliation at higher potential. The electrochemical behavior of the produced GO is studied through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). X ray Photoelectronic Spectroscopy (XPS), Raman spectroscopy, Transmission Electron Microscopy (TEM), and Atomic Force Microscopy (AFM) are employed to characterize the structural and chemical properties of the exfoliated GO. The results demonstrate that the electrochemical exfoliation method yields GO materials with varying degrees of oxidation, defect density, and crystallite size, depending on the applied potential and acid concentration. The graphene oxide samples exhibited distinct electrochemical properties, including charge transfer resistance, interfacial capacitance, and relaxation times for the charge transfer, as revealed by CV and EIS measurements with a specifically selected redox probe. The comprehensive characterization performed provides valuable insights into the structure-property relationships of the GO materials synthesized through electrochemical exfoliation of graphite.

Morphology of Penicillium rubens Biofilms Formed in Space.

Fungi biofilms have been found growing on spacecraft surfaces such as windows, piping, cables, etc. The contamination of these surfaces with fungi, although undesirable, is highly difficult to avoid. While several biofilm forming species, including Penicillium rubens, have been identified in spacecraft, the effect of microgravity on fungal biofilm formation is unknown. This study sent seven material surfaces (Stainless Steel 316, Aluminum Alloy, Titanium Alloy, Carbon Fiber, Quartz, Silicone, and Nanograss) inoculated with spores of P. rubens to the International Space Station and allowed biofilms to form for 10, 15, and 20 days to understand the effects of microgravity on biofilm morphology and growth. In general, microgravity did not induce changes in the shape of biofilms, nor did it affect growth in terms of biomass, thickness, and surface area coverage. However, microgravity increased or decreased biofilm formation in some cases, and this was incubation-time- and material-dependent. Nanograss was the material with significantly less biofilm formation, both in microgravity and on Earth, and it could potentially be interfering with hyphal adhesion and/or spore germination. Additionally, a decrease in biofilm formation at 20 days, potentially due to nutrient depletion, was seen in some space and Earth samples and was material-dependent.

Cost-Effectiveness Analysis of Axicabtagene Ciloleucel vs. Tisagenlecleucel for the Management of Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Spain.

The study aimed to assess the cost-effectiveness of axicabtagene ciloleucel (axi-cel) vs. tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 lines of systemic therapy in Spain. A lifetime partitioned survival mixture cure model, which comprises pre-progression, post-progression, and death health states, was used to estimate the accumulated costs and outcomes in terms of life years gained (LYG) and quality-adjusted life years (QALY). A matching-adjusted indirect comparison was used to reweight patient-level data from ZUMA-1, the pivotal clinical trial for axi-cel, to aggregate-level data from the pivotal tisa-cel trial, JULIET. The analysis was performed from the National Health System perspective, thus only direct costs were included. Sensitivity analyses (SA) were performed. Axi-cel yielded 2.74 incremental LYG and 2.31 additional QALY gained per patient compared to tisa-cel. Total incremental lifetime costs for axi-cel versus tisa-cel were €30,135/patient. The incremental cost-effectiveness ratio of axi-cel versus tisa-cel resulted in €10,999/LYG and the incremental cost-utility ratio in €13,049/QALY gained. SA proved robustness of the results. Considering the frequently assumed willingness-to-pay thresholds in Spain (€22,000/QALY and €60,000/QALY), axi-cel is a cost-effective treatment vs. tisa-cel for adult patients with R/R DLBCL in Spain.

Targeted screening for human immunodeficiency virus infection in Spanish emergency departments: an analysis of epidemiologic and economic impact. / Cribado dirigido del virus de la inmunodeficiencia humana en los servicios de urgencias en España: análisis de las consecuencias epidemiológicas y económicas.

OBJECTIVES: To evaluate the potential epidemiologic and economic impact of applying an HIV screening protocol in hospital emergency departments (ED) and compare it to current clinical practice in Spain. MATERIAL AND METHODS: We estimated the cumulative incidence of human immunodeficiency virus (HIV) infections and associated costs in Spain for a 20-year time horizon based on a model comprised of various health states with different risks for HIV transmission. The impact of current clinical practices in Spain, in which there is no established protocol for HIV screening, was compared to the potential impact of applying a targeted screening protocol in persons who come to the ED with certain conditions suggestive of HIV infection (diagnosis of a sexually transmitted infection, mononucleosis, herpes zoster infection, community-acquired pneumonia; practice of chemsex, and need for postexposure prophylaxis). RESULTS: Screening all persons with a condition suggestive of HIV infection in hospital EDs would require an investment of €20 million over 20 years, but it would prevent 13 615 new infections (reducing the incidence by 20.6%, down from 66 265 to 52 650 cases) in comparison with the current diagnostic approaches. Such a reduction in the incidence of HIV infection would potentially save €4411 million over 20 years, giving a return of €224 per euro invested. CONCLUSION: A protocol for targeted screening of persons in circumstances suggestive of risk for HIV infection in Spain would increase diagnoses, avert new infections, and generate savings in comparison with screening practices currently in effect.

OBJETIVO: El objetivo del análisis fue evaluar el impacto epidemiológico y económico de protocolizar el cribado dirigido del virus de la inmunodeficiencia humana (VIH) en los servicios de urgencias hospitalarios (SUH) comparado con la actual práctica clínica en España. METODO: Mediante un modelo formado por varios estados de salud con diferentes riesgos de transmisión se estimó la incidencia acumulada de infecciones por VIH y los costes asociados, en 20 años, en España. El análisis comparó la protocolización del cribado dirigido a personas que presentan alguna condición indicadora (CI) de infección por VIH (diagnóstico de enfermedad de transmisión sexual, síndrome mononucleósido, herpes zóster, neumonía adquirida en la comunidad, práctica del chemsex y profilaxis postexposición) que acuden a los SUH frente a la actual práctica clínica en España en la que el cribado del VIH no está protocolizado. RESULTADOS: El cribado dirigido a personas con alguna CI de VIH en los servicios de urgencias requeriría una inversión de 20 millones de euros en 20 años, pero evitaría 13.615 nuevas infecciones (de 66.265 a 52.650 casos; ­20,6%) comparado con la actual estrategia de diagnóstico. La reducción de la incidencia de VIH supondría unos ahorros potenciales de 4.411 millones de euros en 2 décadas, con un retorno económico de 224 € por euro invertido. CONCLUSIONES: Protocolizar el cribado dirigido a personas con alguna CI de VIH en los SUH en España podría incrementar el diagnóstico, evitar nuevas infecciones de VIH y generar ahorros versus el cribado no protocolizado realizado en la práctica clínica actual.

Epidemiologic and Economic Analysis of Rapid Antiretroviral Therapy Initiation with Bictegravir/Emtricitabine/Tenofovir Alafenamide in Spain.

OBJECTIVE: This study aimed to assess the potential epidemiological and economic impact of rapid initiation of human immunodeficiency virus (HIV) treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) on HIV transmission compared with the current initiation observed in clinical practice in Spain. METHODS: A transmission model was adapted to estimate the cumulative HIV infection incidence and potential cost savings based on the number of HIV infections prevented among men who have sex with men, heterosexual males and females, and people who inject drugs (PWID) over a 20-year time horizon. The analysis compared rapid antiretroviral therapy (ART) initiation with B/F/TAF (9 days from diagnosis until treatment initiation) versus current ART initiation practice (with an average of 35 days from diagnosis to treatment). People living with HIV were distributed according to their treatment status. Risk for transmission was assigned to undiagnosed, diagnosed in care and not receiving ART, and receiving ART but virally unsuppressed, which was estimated by sexual contact, needles and syringes shared among PWID, state of HIV infection, and ART use. RESULTS: In the base-case analysis, rapid ART initiation with B/F/TAF is expected to prevent 992 new HIV infections over the next 20 years compared with current ART initiation practices. Considering the lifetime costs of treating HIV infection, the reduction in HIV incidence could result in potential cost savings of €323 million. CONCLUSIONS: These results suggest that rapid ART initiation with B/F/TAF in newly diagnosed patients with HIV is a high-value strategy for the Spanish National Health System and society, reducing HIV incidence and thereby reducing future related direct and indirect costs of care.

Cribado dirigido del virus de la inmunodeficiencia humana en los servicios de urgencias en España: análisis de las consecuencias epidemiológicas y económicas / Targeted screening for human immunodeficiency virus infection in Spanish emergency departments: an analysis of epidemiologic and economic impact

Objetivo. El objetivo del análisis fue evaluar el impacto epidemiológico y económico de protocolizar el cribado dirigi- do del virus de la inmunodeficiencia humana (VIH) en los servicios de urgencias hospitalarios (SUH) comparado con la actual práctica clínica en España. Método. Mediante un modelo formado por varios estados de salud con diferentes riesgos de transmisión se estimó la incidencia acumulada de infecciones por VIH y los costes asociados, en 20 años, en España. El análisis comparó la protocolización del cribado dirigido a personas que presentan alguna condición indicadora (CI) de infección por VIH (diagnóstico de enfermedad de transmisión sexual, síndrome mononucleósido, herpes zóster, neumonía adquirida en la comunidad, práctica del chemsex y profilaxis postexposición) que acuden a los SUH frente a la actual práctica clínica en España en la que el cribado del VIH no está protocolizado. Resultados. El cribado dirigido a personas con alguna CI de VIH en los servicios de urgencias requeriría una inversión de 20 millones de euros en 20 años, pero evitaría 13.615 nuevas infecciones (de 66.265 a 52.650 casos; –20,6%) comparado con la actual estrategia de diagnóstico. La reducción de la incidencia de VIH supondría unos ahorros potenciales de 4.411 millones de euros en 2 décadas, con un retorno económico de 224 € por euro invertido. Conclusiones. Protocolizar el cribado dirigido a personas con alguna CI de VIH en los SUH en España podría incrementar el diagnóstico, evitar nuevas infecciones de VIH y generar ahorros versus el cribado no protocolizado realizado en la práctica clínica actual.

Objective. To evaluate the potential epidemiologic and economic impact of applying an HIV screening protocol in hospital emergency departments (ED) and compare it to current clinical practice in Spain. Methods. We estimated the cumulative incidence of human immunodeficiency virus (HIV) infections and associated costs in Spain for a 20-year time horizon based on a model comprised of various health states with different risks for HIV transmission. The impact of current clinical practices in Spain, in which there is no established protocol for HIV screening, was compared to the potential impact of applying a targeted screening protocol in persons who come to the ED with certain conditions suggestive of HIV infection (diagnosis of a sexually transmitted infection, mononucleosis, herpes zoster infection, community-acquired pneumonia; practice of chemsex, and need for postexposure prophylaxis). Results. Screening all persons with a condition suggestive of HIV infection in hospital EDs would require an investment of €20 million over 20 years, but it would prevent 13615 new infections (reducing the incidence by 20.6%, down from 66265 to 52650 cases) in comparison with the current diagnostic approaches. Such a reduction in the incidence of HIV infection would potentially save €4411 million over 20 years, giving a return of €224 per euro invested. Conclusion. A protocol for targeted screening of persons in circumstances suggestive of risk for HIV infection in Spain would increase diagnoses, avert new infections, and generate savings in comparison with screening practices currently in effect.

Cost-minimization analysis of immunoglobulin treatment of primary immunodeficiency diseases in Spain.

Primary immunodeficiency diseases (PID), which are comprised of over 400 genetic disorders, occur when a component of the immune system is diminished or dysfunctional. Patients with PID who require immunoglobulin (IG) replacement therapy receive intravenous IG (IVIG) or subcutaneous IG (SCIG), each of which provides equivalent efficacy. We developed a cost-minimization model to evaluate costs of IVIG versus SCIG from the Spanish National Healthcare System perspective. The base case modeled the annual cost per patient of IVIG and SCIG for the mean doses (per current expert clinical practice) over 1 year in terms of direct (drug and administration) and indirect (lost productivity for adults and parents/guardians of pediatric patients) costs. It was assumed that all IVIG infusions were administered in a day hospital, and 95% of SCIG infusions were administered at home. Drug costs were calculated from ex-factory prices obtained from local databases minus the mandatory deduction. Costs were valued on 2018 euros. The annual modeled costs were €4,266 lower for patients with PID who received SCIG (total €14,466) compared with those who received IVIG (total €18,732). The two largest contributors were differences in annual IG costs as a function of dosage (- €1,927) and hospital administration costs (- €2,688). However, SCIG incurred training costs for home administration (€695). Sensitivity analyses for two dose-rounding scenarios were consistent with the base case. Our model suggests that SCIG may be a cost-saving alternative to IVIG for patients with PID in Spain.

Effects of valinomycin doping on the electrical and structural properties of planar lipid bilayers supported on polyelectrolyte multilayers.

Supported Lipid Bilayers (SLBs) on Polyelectrolyte Multilayers (PEMs) have large potential as models for developing sensor devices. SLBs can be designed with receptors and channels, which benefit from the biological environment of the lipid layers, to create a sensing interface for ions and biomarkers. PEMs assembled by the Layer-by-Layer (LBL) technique and used as supports for a lipid bilayer enable an easy integration of the bilayer on almost any surface and device. For electrochemical sensors, LBL assembly enables nanoscale tunable separation of the lipid bilayer from the electrode surface, avoiding undesired effects of the electrode surface on the lipid bilayers. We study the fabrication of valinomycin-doped SLBs on PEMs as a model system for biophysical studies and for selective ion sensing. SLBs are fabricated from dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylserine (DOPS) 50:50 vesicles doped with valinomycin, as a K+-selective carrier. SLBs were deposited on electrodes coated with poly(allyl amine hydrochloride) (PAH) and poly(styrene sodium sulfonate) (PSS) multilayers. Lipid bilayer formation was monitored by using Quartz Crystal Microbalance with Dissipation (QCMD) technique and Atomic Force Microscopy (AFM). Electrochemical impedance spectroscopy (EIS) and potentiometric measurements were performed to assess K+ selectivity over other ions and the potential of valinomycin-doped SLBs for K+-sensing.

Second-line treatment with lesinurad and allopurinol versus febuxostat for management of hyperuricemia: a cost-effectiveness analysis for Spanish patients.

INTRODUCTION/OBJECTIVES: Lesinurad, in combination with allopurinol, has been approved for treatment of patients with gout which do not reach therapeutic serum urate target with xanthine oxidase inhibitors monotherapy. The study aimed to assess the incremental cost-effectiveness ratio of adding lesinurad to allopurinol as second-line therapy, compared to febuxostat for patients with gout in Spain. METHOD: A Markov model representing disease evolution was used to estimate the lifetime accumulated cost and benefits in terms of quality-adjusted-life-year (QALY). Patients could either continue with second-line treatment with lesinurad (200 mg/daily) plus allopurinol (400 mg/daily) or febuxostat (80 mg/daily) switch to allopurinol monotherapy (271 mg/daily) in case of intolerance or discontinue treatment. The treatment's efficacy captured in the transition probabilities between health states were derived from CLEAR and EXCEL trials. Quality of life related to gout severity and flare frequency was considered by means of utilities. The total cost estimation (€, 2019) included drug acquisition cost, disease monitoring, and flare management cost. Unitary local costs derived from databases and literature. A 3% annual discount rate was applied for cost and outcomes. RESULTS: Lesinurad plus allopurinol provided higher QALYs (14.79) than febuxostat (14.69). Total accrued cost/patient was lower with lesinurad and allopurinol (€50,631.51) versus febuxostat (€56,698.64). Lesinurad plus allopurinol resulted more effective and less costly (dominant option) versus febuxostat. CONCLUSIONS: Lesinurad plus allopurinol therapy compared with febuxostat seems an effective option for the management of hyperuricemia in patients who did not reach serum urate target to previous allopurinol monotherapy, associated to cost-savings for the Spanish Health System.Key Points• Lesinurad, in combination with allopurinol, has been recently authorized as second-line treatment of hyperuricemia in gout patients.• Lesinurad plus allopurinol provided higher effectiveness in terms of quality-adjusted-life-years (14.79) than febuxostat (14.69).• Lesinurad plus allopurinol resulted less costly (total cost/per patient) compared with febuxostat.• Lesinurad plus allopurinol resulted a dominant option compared with febuxostat.

Gramicidin ion channels in a lipid bilayer supported on polyelectrolyte multilayer films: an electrochemical impedance study.

Supported membranes on polymer cushions are of fundamental interest as models for cell membranes. The use of polyelectrolyte multilayers (PEMs) assembled by the layer by layer (LbL) technique as supports for a bilayer allows for easy integration of the lipid bilayer on surfaces and devices and for nanoscale tunable spacing of the lipid bilayer. Controlling ionic permeability in lipid bilayers supported on PEMs triggers potential applications in sensing and as models for transport phenomena in cell membranes. Lipid bilayers displaying gramicidin channels are fabricated on top of polyallylamine hydrochloride (PAH) and polystyrene sulfonate (PSS) multilayer films, by the assembly of vesicles of phosphatidylcholine and phosphatidylserine, 50 : 50 M/M, carrying gramicidin (GA). Quartz crystal microbalance with dissipation shows that the vesicles with GA fuse into a bilayer. Atomic force microscopy reveals that the presence of GA alters the bilayer topography resulting in depressions in the bilayer of around 70 nm in diameter. Electrochemical impedance spectroscopy (EIS) studies show that supported bilayers carrying GA have smaller resistances than the bilayers without GA. Lipid layers carrying GA display a higher conductance for K+ than for Na+ and are blocked in the presence of Ca2+.

High Resistivity Lipid Bilayers Assembled on Polyelectrolyte Multilayer Cushions: An Impedance Study.

Supported membranes on top of polymer cushions are interesting models of biomembranes as cell membranes are supported on a polymer network of proteins and sugars. In this work lipid vesicles formed by a mixture of 30% 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 70% 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS) are assembled on top of a polyelectrolyte multilayer (PEM) cushion of poly(allylamine hydrochloride) (PAH) and poly(styrene sodium sulfonate) (PSS). The assembly results in the formation of a bilayer on top of the PEM as proven by means of the quartz crystal microbalance with dissipation technique (QCM-D) and by cryo-transmission electron microscopy (cryo-TEM). The electrical properties of the bilayer are studied by electrochemical impedance spectroscopy (EIS). The bilayer supported on the PEMs shows a high resistance, on the order of 10(7) Ω cm(2), which is indicative of a continuous, dense bilayer. Such resistance is comparable with the resistance of black lipid membranes. This is the first time that such values are obtained for lipid bilayers supported on PEMs. The assembly of polyelectrolytes on top of a lipid bilayer decreases the resistance of the bilayer up to 2 orders of magnitude. The assembly of the polyelectrolytes on the lipids induces defects or pores in the bilayer which in turn prompts a decrease in the measured resistance.

Electrochemical preparation and characterization of polypyrrole/stainless steel electrodes decorated with gold nanoparticles.

The electrosynthesis and characterization of polypyrrole(PPy)/stainless steel electrodes decorated with gold nanoparticles and the performance of the composite electrode for sensing applications is described. PPy films were grown in potassium perchlorate and sodium salicylate solutions under comparable electropolymerization conditions. Polymer films prepared in the presence of perchlorate ions exhibited worm-like structures, whereas columnar structures were obtained in salicylate-containing solutions. Voltammetric response of PPy films prepared in salicylate solutions was more reversible. PPy films were decorated with gold nanoparticles obtained by a double step potentiostatic electrodeposition routine that allowed fine control of deposit characteristics. Analysis of deposits was performed by means of SEM and confocal Raman spectroscopy. The electrocatalytic activity of the Au/PPy electrodes was assessed for the electro-oxidation of hydrazine and hydroxylamine. Results showed a successful optimization of the route of synthesis that rendered nanocomposite electrode materials with promising applications in electrochemical sensing.

Electrochemical determination of the glass transition temperature of thin polyelectrolyte brushes at solid-liquid interfaces by impedance spectroscopy.

Devising strategies to assess the glass transition temperature (Tg) of polyelectrolyte assemblies at solid-electrolyte interfaces is very important to understand and rationalize the temperature-dependent behavior of polyelectrolyte films in a wide range of settings. Despite the evolving perception of the importance of measuring Tg under aqueous conditions in thin film configurations, its straightforward measurement poses a challenging situation that still remains elusive in polymer and materials science. Here, we describe a new method based on electrochemical impedance spectroscopy (EIS) to estimate the glass transition temperature of planar polyelectrolyte brushes at solid-liquid interfaces. To measure Tg, the charge transfer resistance (Rct) of a redox probe diffusing through the polyelectrolyte brush was measured, and the temperature corresponding to the discontinuous change in Rct was identified as Tg. Furthermore, we demonstrate that impedance measurements not only facilitate the estimation of Tg but also enable a reliable evaluation of the transport properties of the polymeric interface, i.e., determination of diffusion coefficients, close to the thermal transition. We consider that this approach bridges the gap between electrochemistry and the traditional tools used in polymer science and offers new opportunities to characterize the thermal behavior of complex polymeric interfaces and macromolecular assemblies.