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Model-based pharmacoeconomic analysis of anti-VEGF strategies for neovascular age-related macular degeneration: a value-based comparison of real-world administration approaches

Objectives

To evaluate the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) using a value-based model that considers drug durability, dosing regimens and real-world administration strategies, including safe vial fractionation.

Design and setting

Model-based pharmacoeconomic analysis using data from randomised clinical trials and network meta-analyses. Analysis conducted from the payer perspective using cost data from the Spanish National Health System.

Methods

A model-based analysis compared five anti-VEGF agents—innovator and biosimilar ranibizumab, aflibercept 2 mg, brolucizumab and faricimab—across three dosing regimens: fixed, Pro Re Nata and Treat-and-Extend (TAE). Administration formats included single-use vials, prefilled syringes and vial fractionation (VF), with or without dead-space-free (DSF) syringes to minimise waste. The primary outcome was cost per optimal responder, defined as a patient gaining ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, with and without adverse events. Cost-effectiveness was evaluated using Number Needed to Treat (NNT), Net Efficacy Adjusted for Risk-NNT (adjusted for safety) and incremental cost-effectiveness ratios. Secondary outcomes included the number of treated patients and optimal responders achievable within a fixed 1 000 000 budget.

Results

The most cost-effective strategy was aflibercept 2 mg under a TAE regimen using DSF VF, with a total cost of 6214 per patient and a cost per optimal responder of 27 155. Under a fixed budget of 1 000 000, this approach allowed treatment of 160 patients, yielding 36 optimal responders. Faricimab with DSF VF ranked second, with a total cost of 5847 and a cost per optimal responder of 28 652, treating 171 patients and achieving 34 responders. In contrast, single-use vials without VF led to substantially higher total costs (eg, 11 305 for aflibercept TAE) and lower treatment capacity (eg, 88 patients treated).

Conclusions

This model demonstrates that combining durable agents, extended dosing intervals and optimised delivery strategies (eg, prefilled syringes and DSF VF) can substantially improve the cost-effectiveness and sustainability of anti-VEGF therapy in public health systems.

Impact of proactively inviting people with advanced cancer to talk about the end of life: a randomised clinical trial protocol

Por: Julia-Torras · J. · Garcia-Salanova · A. · Monforte-Royo · C. · Jimeno Ariztia · M. · Balaguer · A. · Crespo · I.
Introduction

There is evidence that talking about the end of life with patients facing a life-threatening disease is not upsetting, and in fact, it may even be beneficial. However, both patients and health professionals can find it difficult to engage in these conversations. The aim of this clinical trial is to explore whether proactively inviting people with advanced cancer to share their thoughts about death and dying is distressing for them, comparing the impact with usual clinical practice (ie, a reactive approach to these issues).

Methods and analysis

A stepped-wedge cluster randomised controlled trial involving six palliative care units in Spain will be conducted. Each unit will recruit participants for both the experimental and control groups. Units will be randomised to determine the order in which they will begin implementing the intervention: GO-TaD (Give the Opportunity to Talk about Death thoughts). The trial will involve six sequences and seven periods (steps), with four patients per period (patients in each period will be different). The primary outcome will be emotional distress, assessed with the Detecting Emotional Distress scale. The following secondary variables will also be analysed: hopelessness, using the Beck Hopelessness Scale; quality of the patient–professional relationship, with the Patient–Doctor Relationship Questionnaire (PDRQ-9); and quality of life, with the Palliative Outcome Scale . The trial will follow the CONSORT extension for stepped-wedge cluster randomised designs. The primary analysis will include all eligible patients, applying mixed-effects regression models for binary results and mixed linear models for continuous data. Results will be reported as risk differences and ORs, with 95% confidence intervals. Analyses by sub-groups of interest (eg, age, gender, type of palliative care unit) will also be conducted. All analyses will be performed using R.

Ethics and dissemination

Ethical approval has been obtained from the researchers' university and all participating centres. Results will be disseminated through peer-reviewed open access publications, academic conferences and presentations to clinical audiences.

Trial registration number

NCT06420609.

Recommendations for the use of biomarkers for the management of adults with sepsis: a scoping review and critical appraisal

Por: Mateos-Haro · M. · Garcia-Santa-Vinuela · A. · Molano-Franco · D. · Sola · I. · Gordo-Vidal · F. · Martin-Delgado · M. C. · Lopez-Alcalde · J. · Zamora · J.
Objective

A synthesis and appraisal of the recommendations for biomarkers in practice guidelines concerning sepsis is required to consolidate evidence-based practice. We generated an evidence gap map (EGM) on the use of biomarkers for managing adults with sepsis.

Design

Scoping review.

Data sources

MEDLINE, Guidelines International Network, Pan American Health Organization, Trip Database and UpToDate were searched from 2016 to March 2025.

Eligibility criteria

Guidance documents (GD) that searched at least one literature source and provided clinical recommendations for the use of biomarkers for the management (diagnosis and prognosis, including treatment response) of adults with sepsis.

Data extraction and synthesis

Two reviewers independently applied the eligibility criteria and extracted data. We used the AGREE-II (Appraisal of Guidelines for Research and Evaluation) tool to assess the GD quality. GDs that scored ≥50% on the AGREE-II 'Rigour of development' domain were considered robust. We also applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate if the recommendations were strong or conditional.

Results

We found 10 GDs, with only half (4/8) having a robust methodology. There were 31 recommendations concerning biomarkers. Among these, 24 (77.4%) recommendations were about single biomarkers, with lactate (23; 74.2%) and procalcitonin (8; 25.8%) most frequently recommended. Biomarker testing focused on prognosis in 28 (90.3%) recommendations. Overall, 16 (51.6%) recommendations were graded strong and 13 (42.0%) were conditional, which we displayed in an EGM.

Conclusions

The methodology of GDs concerning adult sepsis was poor. Our review calls for more prudent use of biomarkers in specific prognostic scenarios and in combination with standard clinical assessments. Enhancing the methodological quality of future GDs is essential to generate more valid and robust recommendations for optimising patient care.

Experiences of Females With Late Diagnosis of Autism: Descriptive Qualitative Study

imageBackground Females with autism often receive late diagnoses—especially those with average or above-average intellectual abilities—highlighting the need to explore the unique experiences of this population for better health care support. Objective To explore the experiences and perceptions of females who received a late diagnosis on the autism spectrum in terms of coping and managing their diagnosis. Methods A descriptive qualitative study was conducted from December 2022 to March 2023 using semistructured interviews with 14 late-diagnosed autistic female subjects. Purposive and snowball sampling were employed, and thematic analysis of the interview data was performed using ATLAS.ti v.9 software. Findings were reported following standards for reporting qualitative research guidelines. Results Two main themes emerged: (a) getting a diagnosis: fitting into the norm, and (b) navigating the distinct significance for autistic females. The findings indicated that masking strategies contribute to delayed diagnoses, and social and health care stigma surrounding autism in females was evident. Areas for improving access to resources and support programs were identified. Discussion The results show that masking and camouflaging are predominant strategies among autistic females, contributing to delayed diagnoses and exposing them to additional risks. Enhancing resources and training for health care professionals is necessary to address the specific needs of this population.

Microbiota composition of <i>Culex perexiguus</i> mosquitoes during the West Nile virus outbreak in southern Spain

by Marta Garrigós, Mario Garrido, María José Ruiz-López, María José García-López, Jesús Veiga, Sergio Magallanes, Ramón Soriguer, Isabel Moreno-Indias, Jordi Figuerola, Josué Martínez-de la Puente

West Nile virus (WNV) is a flavivirus naturally circulating between mosquito vectors and birds, occasionally infecting horses and humans and causing epidemiologically relevant outbreaks. In Spain, the first big WNV outbreak was recorded in 2020, resulting in 77 people infected and 8 fatalities, most of them in southern Spain. Culex perexiguus was identified as the primary vector of WNV maintaining its enzootic circulation of the virus. Growing evidence highlights the role of mosquito microbiota as a key component determining the vectorial capacity of mosquitoes, largely contributing to disease epidemiology. Here, we develop, to our knowledge, the first identification of the microbiota composition of this mosquito vector under natural conditions and test for the potential relationship between mosquito microbiota composition and WNV infection. To do so, we collected mosquitoes in a natural area of southern Spain during the 2020 WNV outbreak and identified the microbiota composition of mosquitoes using a 16S rRNA gene metabarcoding approach. The microbiota of Cx. perexiguus was dominated by the phylum Proteobacteria. The most abundant families were Burkholderiaceae and Erwiniaceae, including the genera Burkholderia, Erwinia, and Pantoea. The genus Wolbachia, which use to dominate the microbiota of Cx. pipiens and negatively interact with WNV according to the literature, had a low prevalence and relative abundance in Cx. perexiguus and its abundance did not differ between WNV-positive and WNV-negative mosquito pools. The microbiota diversity and composition of Cx. perexiguus were not significantly related to the WNV infection status. These results provide the first identification of the mosquito microbiota in an endemic area of WNV circulation in Spain.

Continuidad de vínculos con el ser querido fallecido y los cuidados de Enfermería de Salud Mental según el Modelo Tidal

El objetivo principal es analizar de qué manera el Modelo Tidal favorece la reconstrucción de significados en el duelo como continuidad de vínculos. El duelo es un proceso complejo que tiene componentes naturales y construidos, en ocasiones, las personas dolientes validan la continuidad de vínculos con la persona fallecida por medio de la organización de las autonarrativas. El manejo de este fenómeno es interdisciplinario donde destaca la Enfermería de Salud Mental orientada por el Modelo Tidal el cual se apoya en la historia personal para la reconstrucción de los significados tras la muerte de un ser querido favoreciendo la adaptación a través del cuidado. Conclusión principal: El abordaje de la continuidad de vínculos desde el Modelo Tidal favorece la adaptación al duelo centrado en la persona y su historia al afianzar la reconstrucción de significados que mejoren la calidad de vida por medio del cuidado enfocado en las necesidades actuales.

Prevalencia del catéter venoso periférico en un hospital terciario: elección en función del tratamiento

Objetivo: Determinar la prevalencia del catéter venoso periférico y conocer si su elección es adecuada en función del tratamiento. Metodología: Estudio observacional transversal realizado en la Unidad de Medicina Interna de un hospital de tercer nivel. Análisis descriptivo e inferencial mediante explotación de datos de forma pseudoanonimizada y retrospectiva. Resultados: El 96,6% de pacientes fueron portadores de catéteres venosos periféricos con una media de días de catéter de 3, 62. Los motivos de retirada más frecuentes fueron la extravasación (51,4%), el fin de tratamiento (16,2%) y la flebitis (12,8%). El tratamiento endovenoso fue superior a 6 días en un 40,4% de los pacientes y considerado vesicante y/o irritante en un 56,4%. Conclusiones: Existe un sobre uso del catéter venoso periférico, resultando primordial el diseño e implementación de estrategias con enfoque multidisciplinar que favorezcan una adecuada elección y manejo de los accesos vasculares.

Leche materna versus sacarosa ante punción venosa y heel prick

Introducción: Las intervenciones que realizamos a los RN ingresados en nuestra unidad pueden causar dolor y estrés, traduciéndose en signos conductuales y fisiológicos. Método: Se realizó un ensayo clínico controlado aleatorizado en la UCI de neonatos durante un año, el objetivo fue conocer si existen diferencias significativas en cuanto al uso de leche materna vs sacarosa 25% como método analgésico no farmacológico en la realización de procedimientos dolorosos (punción venosa y punción del talón). Se usó para evaluar el dolor la escala de Susan Given Bells (antes y tras 2minutos de nuestra intervención). Material: Se incluyeron los recién nacidos entre 25-40 se-manas de gestación y que no cumpliesen criterios de exclusión. Resultados: Se usó para el análisis estadístico la t-student y el test de chi cuadrado, observando como principal resultado que en la extracción venosa (N=59) es más efectivo el uso de leche materna, sufriendo menor aumento del dolor tras la misma(p<0,029). También se observa relación significativa entre la edad gestacional corregida y el dolor tras la extracción venosa, obteniendo que los recién nacidos > 32 semanas tienen mayor aumento de dolor posterior (p<0,011). En la de punción de talón (N=76), no se hallaron diferencias entre la sacarosa y leche materna, tampoco al analizar otras variables (sexo, edad gestacional, crecimiento intrauterino retardado, llanto o canguro) Conclusiones: Se propone el uso de leche materna como método anal-gésico para el control del dolor en punción de talón y extracción venosa. Ya que demuestra su eficacia y carece de efectos secundarios.

La matrona del pueblo en el siglo XX en España. El relato biográfico de Dña. Estrella de Dios Zarza

Objetivo principal: Conocer las experiencias laborales y la vida de una matrona del siglo pasado. Metodología: Cualitativa. Análisis de contenido. Resultados principales: Dificultad para conciliar vida personal y laboral. Soledad. Malas condiciones laborales. Conclusión principal: La profesión de matrona se desempeñaba en condiciones dificiles y con pocos medios.

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