Hospital Universitario Puerto Real

Aims There is limited information regarding the clinical impact of the concurrent use of thiazides and loop diuretics (LD) after an episode of acute heart failure (AHF) hospitalization. We aimed to evaluate the impact of thiazide prescription at discharge on top of LD on the short-term risk of AHF readmission. Methods We included 3384 consecutive patients discharged from January 2008 to September 2021 after an admission for AHF in a single teaching center. The association between thiazides on discharge across the intensity of LD treatment and 30-day AHF readmission was explored by Cox regression analysis. A validation cohort of 622 patients was also examined. Results The mean age of the patients was 73.8 ± 11.2 years, 1672 (47.5%) were women, and 1733 (51.2%) patients showed left ventricular ejection fraction > 50%. The median (IQR) NT-proBNP was 3409 (1829–6963) pg/mL. At discharge, 754 (22.3%) patients received high LD doses (> 80 mg/day) and 187 (5.5%) thiazides. At 30 days, we registered 76 (2.2%) deaths and 449 (13.3%) AHF readmissions. Thiazides at discharge were not associated with the risk of 30-day AHF readmission (HR = 0.92). However, this association was differentially influenced by the intensity of LD doses (p-value for interaction = 0.030), with a lower AHF-readmission risk in those with LD dose > 80 mg/day (p = 0.038), and a neutral association in those receiving low LD dose (≤ 80 mg/day) (p = 0.541). Conclusions In patients discharged after an episode of AHF, thiazide prescription was associated with a lower risk of 30-day AHF readmission when they were prescribed in patients receiving high LD doses.

Background and Importance Unresectable or metastatic cholangiocarcinoma (CCUoM) is a type of biliary tract cancer with poor prognosis. Results from the pivotal trial ‘TOPAZ-1’ suggest that adding durvalumab (anti-PD-L1) to standard therapy (platinum-gemcitabine (PtGem)) may improve survival outcomes. Aim and Objectives Evaluate the effectiveness and safety of durvalumab with PtGem (PtGemDur) as first-line therapy for CCUoM, with a comparison to a historical cohort, PtGem, and with results from TOPAZ-1. Material and Methods A retrospective descriptive study of patients with CCUoM. Two cohorts were included: patients treated with PtGem from 06/2018–06/2021 and those treated with PtGemDur (current cohort) from 06/2021–06/2024. Data collected from Oncofarm software and medical records were: sex, age, ECOG and tumour location. Effectiveness was evaluated in terms of overall survival (OS) and progression-free survival (PFS) according to the Kaplan-Meier method, using SPSS statistical software. Safety was determined from the type of adverse events (AEs) and discontinuations. Results A total of 34 patients were included, 25 received PtGem and 9 PtGemDur. Data collected in the historical cohort were: median age 66 (41–81) years, 64% men, ECOG1: 76%, rest ECOG0 and 76% intrahepatic. In the current cohort: median age 70 (49–80) years, 92% men, ECOG0: 55.6%, rest ECOG1 and 55.6% intrahepatic. In TOPAZ-1, median age 64 (20–84) years, 49.6% men, ECOG0: 50.7% and 55.7% intrahepatic. Median OS was 13 (9.9–18.4) months with PtGem and with PtGemDur was not reached. Median PFS was 9 (7.6–23.2) months with PtGem and 9 (8.8–10.2) months for PtGemDur. In TOPAZ-1 OS was 12.8 (11.1–14) months and PFS 7.2 (6.7–7.4) months. Regarding toxicity, 92% had AEs of any grade with PtGem, 100% with PtGemDur and 99.4% in TOPAZ-1. The most frequent AEs were haematologic, 31% in historical cohort vs 15.4% in current cohort and digestive, 13.8% vs 23.1%. Discontinuations were 68% vs 44%. There were no immune-mediated effects. In TOPAZ-1 48.2% were haematologic, 40.2% digestive and 12.7% immune-mediated. Discontinuations occurred in 13%. Conclusion and Relevance In our study, the current cohort sample is small, so results obtained need to mature to confirm the benefits in OS. The PFS results are similar to and slightly superior to those of TOPAZ-1. In terms of safety, AEs were similar in both cohorts and with respect to the TOPAZ-1. No immune-mediated effects were observed in our populations. Conflict of Interest No conflict of interest

Background and Importance First-line treatment for metastatic non-small-cell lung cancer (NSCLC) includes combinations based on immunotherapy and chemotherapy. Strategies involving nivolumab + ipilimumab (NIVO + IPI) and pembrolizumab (PEMBRO) can be considered alternatives with similar clinical benefit. However, they differ in management and toxicity, and have not been directly or indirectly compared. Aim and Objectives To evaluate the efficacy of PEMBRO and NIVO + IPI in patients with metastatic squamous NSCLC and PD-L1 < 1%, based on subgroup analyses of pivotal clinical trials (CTs), and to assess the economic impact in our centre. Material and Methods Data from the KEYNOTE-407 (PEMBRO) and CHECKMATE-9LA (NIVO + IPI) clinical trials were analysed to identify differences in overall survival (OS) among subgroups of patients with squamous NSCLC and PD-L1 < 1%. Interaction and indirect treatment comparison (ITC) adjusted analyses using Bucher’s method, were performed to determine whether the differences between treatments were statistically significant and clinically relevant. Additionally, the budgetary impact of both therapies was evaluated in our centre. Results No statistically significant interaction was observed among the three patient subgroups based on PD-L1 for PEMBRO (p = 0.37), nor for NIVO + IPI between squamous and non-squamous histologies (p = 0.19). Therefore, conducting an ICT exclusively with the PD-L1 < 1% subgroup would not be methodologically appropriate. An ICT between NIVO + IPI and PEMBRO in squamous NSCLC, regardless of PD-L1 expression, showed no significant differences in OS (HR 0.90; 95% CI 0.65–1.26; p = 0.54). Similarly, although methodologically incorrect, an ICT for the PD-L1 < 1% subgroup showed no significant differences (HR 0.80; 95% CI 0.53–1.20; p = 0.27). PEMBRO was more cost-effective, offering a 67% savings per patient compared to NIVO + IPI, according to current hospital pricing, translating to an annual savings of €62,407 in hospital expenses. Conclusion and Relevance Subgroup analyses do not demonstrate a superior clinical benefit of NIVO + IPI over PEMBRO in patients with squamous NSCLC and PD-L1 < 1%. The apparent differences lack methodological validity and are attributable to chance. PEMBRO is the more cost-efficient option in our centre. Conflict of Interest No conflict of interest

Background and Importance Atopic dermatitis (AD) is a chronic inflammatory dermatological condition that often requires systemic treatments when topical therapies are insufficient. Previously, the only available systemic treatments were immunosuppressants. However, recently, monoclonal antibodies and oral small molecule therapies have been approved, offering more targeted and effective treatment options with fewer side effects Aim and Objectives To analyse whether the different therapeutic options could be considered as equivalent therapeutic alternatives (ETA) in AD. Material and Methods A systematic search was conducted in PubMed, including randomised, double-blind, phase 2–3 controlled trials that assessed systemic therapies combined with topical corticosteroids (TCS). Efficacy was measured as a 75% reduction in the Eczema Area and Severity Index (EASI75) at week 16. The analysis was performed using R and RStudio software (v4.04) to estimate Bayesian statistics, with placebo as the reference. ETA¹ guidelines were applied to determine therapeutic positioning, using a delta value of 12% as the maximum acceptable non-inferiority margin, based on Blauvelt et al., 2021.² Results Six studies were included. All therapies showed favourable reductions in EASI75 compared to placebo, with statistically significant differences. As upadacitinib 30 mg demonstrated the most favourable outcomes (0.51 (0.44;0.58)), a subsequent analysis was performed to compare its efficacy against the other therapeutic alternatives. As shown in figure 1, abrocitinib 200 mg (−0.07 (−0.19; 0.05)) and dupilumab 300 mg weekly (−0.10 (−0.20; 0.00)) showed the most similar efficacy result; in fact, statistically difference was not shown. • Download figure • Open in new tab • Download powerpoint Abstract 6ER-035 Figure 1 Conclusion and Relevance This study identifies upadacitinib, abrocitinib and weekly-dupilumab as highly effective options. However, according to the Pharmacovigilance Risk Assessment Committee (PRAC) recommendations about JAK inhibitors (JAKi) safety and the unapproved weekly-dupilumab dose, only biweekly dupilumab, lebrikizumab and tralokinumab are considered viable ETAs. References and/or Acknowledgements • Alegre Del Rey EJ, Fénix Caballero S, Castaño Lara R, Sierra García F. Assessment and positioning of drugs as equivalent therapeutic alternatives. Med Clin (Barc). 2014; 143 (2):85–90. doi:10.1016/j.medcli.2013.11.033 • Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De Bruin-Weller M, Barbarot S, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate to severe atopic dermatitis: a randomised clinical trial. JAMA Dermatol. 1 September 2021; 157 (9):1047–55. Conflict of Interest No conflict of interest

Background and Importance The European Medicines Agency (EMA) has recently granted approval for the use of capivasertib in the treatment of locally advanced or metastatic oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with PIK3CA/AKT1/PTEN alterations that has progressed during or after endocrine therapy. Aim and Objectives To evaluate whether capivasertib and the main current standard treatments are equivalent therapeutic alternatives (ETA) by performing an indirect treatment comparison (ITC). Material and Methods In May 2024, a literature search was conducted in PubMed using the following criteria: treatment of HR+ HER2- breast cancer with capivasertib, alpelisib, or or cyclin-dependent kinase 4/6 inhibitors in combination with fulvestrant, in patients with PIK3CA alterations and progression on endocrine therapy. The comparison variable was progression-free survival (PFS). The Bucher method was used for the ITC. In order to establish therapeutic the optimal therapeutic positioning, the ETA guideline ¹ was applied. In accordance with the ESMO-MCBS criteria, the non-inferiority delta value (∆) was established as 0.65, and its inverse 1.54. The Shakespeare method was used to determine the probability of the result exceeding the equivalence ∆. Results The comparison included a phase III study on capivasertib, one on palbociclib, and one on abemaciclib. Alpelisib and ribociclib were not included in the analysis as they failed to meet the established criteria for comparison. The results of the clinical trials and the indirect comparison are presented below:View this table: • View inline • View popup Abstract 4CPS-180 Table 1 The probability of a result falling outside the specified range for palbociclib was 35.7% above, 3.7% below, and 21.0% above for abemaciclib. Conclusion and Relevance In accordance with the ETA guideline, capivasertib cannot be considered ETAs in comparison to palbociclib and abemaciclib. There is no evidence indicating a superior efficacy of capivasertib in combination with fulvestrant compared to palbociclib and abemaciclib in combination with fulvestrant. Given the toxicity profile of capivasertib, the recommended initial treatment option for of CDK4/6 inhibitors remains unchanged. References and/or Acknowledgements • Alegre Del Rey EJ, et al. Med Clin (Barc) 2014 −07–22; 143 (2):85–90. Conflict of Interest No conflict of interest

Background and Importance At present, a considerable number of drugs are available for the treatment of refractory psoriatic arthritis (PsA). However, the lack of direct comparative studies of the available alternatives results in considerable uncertainty regarding their respective therapeutic positions. Aim and Objectives To develop a network meta-analysis (NMA) to provide a comparison of the efficacy of treatments in PsA. Material and Methods A systematic review was conducted on 1 March 2024 in PubMed and Embase. Inclusion criteria: phase II/III randomised controlled trials (RCTs) that included biological disease-modifying antirheumatic drugs (bDMARDs) (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, brodalumab, remtolumab, bimekizumab, guselkumab, risankizumab, and tildrakizumab) and targeted synthetic (tsDMARD) (tofacitinib, upadacitinib, and deucravacitinib) as treatments for patients with PsA, reporting outcomes for the American College of Rheumatology 50% improvement criteria (ACR50). Exclusion criteria: patients under 18 years-old. Efficacy outcome: ACR50 at week 12 or the forthcoming time point. The NMA combined direct and indirect evidence in order to calculate pooled odds ratios (ORs) using Bayesian methodology. The GEMTC and BUGSNET packages for R-Statistics and the MetaInsight application were utilised for this analysis. Results A total of 53 RCTs with 22,365 patients and 51 different intervention arms were included. An NMA using Bayesian random effects models was performed for the ACR50 outcome against placebo. Ixekizumab 80mg every 2 weeks (IXE80 Q2W) demonstrated the most favourable outcome in comparison to the comparator and was therefore used as the reference treatment. The NMA comparing all treatments to IXE80 Q2W demonstrated no treatment superiority, and the majority of comparisons did not reveal statistically significant differences. Nevertheless, IXE80 exhibited statistically significant superiority (p<0.05) in comparison to the following treatments: abatacept, apremilast 20 mg and 30 mg, etanercept 50 mg, guselkumab, risankizumab, secukinumab 75 mg, tildrakizumab 20 mg and 100 mg, tofacitinib 5 mg, and ustekinumab 45 mg Q12W. A sensitivity analysis employing frequentist methods corroborated the consistency of these results. Conclusion and Relevance Ixekizumab 80 mg Q2W has been demonstrated to be an efficacious standard treatment, with no other treatment demonstrating superior efficacy. Furthermore, the safety criteria must be considered into account when determining the optimal therapeutic positioning of drugs in this clinical context. Conflict of Interest No conflict of interest

Background and Importance Fosaprepitant is a prodrug of aprepitant, a neurokinin-1(NK1) receptor antagonist widely used in antiemetic protocols, often in combination with other agents, to prevent nausea and vomiting in highly emetogenic regimens. Polysorbate 80, an excipient in the formulation, has been associated with infusion site reactions (ISRs). Therefore, optimising the administration protocol for fosaprepitant is essential to minimise adverse events and enhance patient safety. Aim and Objectives This study aims to evaluate the incidence of ISRs associated with fosaprepitant use in highly emetogenic regimens and assess the effectiveness of preventive measures implemented in clinical practice. Material and Methods A retrospective analysis was conducted at a university hospital where fosaprepitant was integrated into the antiemetic protocol starting in December 2023. Fosaprepitant was prepared in 100 mL of 0.9% sodium chloride, mixed with 12 mg of dexamethasone and 8 mg of ondansetron, and administered over 20 minutes, adhering to physicochemical guidelines established by Moya-Gil et al (J Anal Bioanal Tech 2016). Following a noted increase in ISRs in January 2024, pharmacists and nurses reviewed the preparation and administration processes. Data were collected from December 2023 to September 2024, through the Farmis-Oncofarm system. Corrective measures implemented in February 2024 included dilution in 250 mL of saline, extending the infusion time to at least 30 minutes, continuous monitoring of infusion rates, and comprehensive training for healthcare staff and patients. Statistical analysis was performed using SPSS 20. Results Among the 1537 fosaprepitant infusions, the overall incidence of infusion site reactions (ISRs) was 1.30% (20/1537), affecting 4.16% of patients (15/361). Of the total reported complications related to the infusion site, 76.92% were attributed to fosaprepitant (20/26) including phlebitis and extravasation. After the intervention, ISRs decreased significantly from 13 cases pre-intervention (301 infusions) to seven post-intervention (1236 infusions), resulting in a statistically significant reduction (RR 0.13; 95% CI 0.05–0.33; p<0.05). The study’s limitations include its retrospective design, potential variability in clinical practice, and possible underreporting of adverse reactions, which may affect the validity of the findings. Conclusion and Relevance The implementation of preventive measures significantly reduced fosaprepitant-related ISRs. These findings highlight the importance of a multidisciplinary approach and continuous monitoring to optimise antiemetic protocols and enhance patient safety during cancer treatment. Conflict of Interest No conflict of interest

A consensus study of experts was conducted to establish a definition of the concept of super-responders (SR) in atopic dermatitis (AD). The study employed a Delphi methodology based on 2 rounds to define the concept of SR in AD, exploring the opinions of expert dermatologists in AD from across Spain regarding a series of statements developed after a systematic review. Consensus was predefined as an agreement of ≥ 80% among all respondents. In the first round, 4 statements reached consensus. In the second round, 2 additional statements reached consensus. To illustrate these definitions, a set of practical cases was provided, and the level of agreement among experts was evaluated. According to the agreed statements, time is important when defining the achievable response as SR. The concept of SR should associate a rapid response (before week 16), include both symptom variables, such as the Eczema Area and Severity Index and Investigators Global Assessment (IGA) and patient-reported outcomes, including pruritus or the Patient-Oriented Eczema Measure. This concept should be associated with complete or nearly complete clearance of lesions (IGA 0–1), and with sustained responses over time (at week 52). Mild flares (IGA ≤ 2) may occur without varying according to the patient’s age.

In 2023, the General Directorate of Pharmacy of the Ministry of Health commissioned the Advisory Committee on the Financing of Pharmaceuticals for the National Health System (CAPF, Comité Asesor para la Financiación de la Prestación Farmacéutica del Sistema Nacional de Salud) to produce a guideline for the evaluation of the efficiency of medicines. The aim of this methodological note is to present their main points. The guideline includes 17 dimensions that an economic evaluation of medicines must encompass, the design of a reference case, and a checklist for evaluating the methodological quality and reporting. This guideline should serve as a foundational document for reforming the health technologies evaluation processes of the Ministry of Health. The guideline can also assist researchers, public health professionals, health technology companies and decision makers in assessing the validity of findings and conclusions from health economic evaluations.

Resumen La presentación de un cáncer de colón en una hernia inguinal es un hallazgo infrecuente. Su diagnóstico representa un reto en la práctica clínica, siendo en su mayoría un hallazgo intraoperatorio. En cuanto al tratamiento quirúrgico no existe hoy en día consenso sobre la mejor vía de abordaje o el uso rutinario de malla.

Motivation Pollinators play a crucial role in maintaining Earth's terrestrial biodiversity. However, rapid human‐induced environmental changes are compromising the long‐term persistence of plant‐pollinator interactions. Unfortunately, we lack robust, generalisable data capturing how plant‐pollinator communities are structured across space and time. Here, we present the EuPPollNet (European Plant‐Pollinator Networks) database, a fully open European‐level database containing harmonised taxonomic data on plant‐pollinator interactions referenced in both space and time, along with other ecological variables of interest. In addition, we evaluate the taxonomic and sampling coverage of EuPPollNet, and summarise key structural properties in plant‐pollinator networks. We believe EuPPollNet will stimulate research to address data gaps in plant‐pollinator interactions and guide future efforts in conservation planning. Main Types of Variables Included EuPPollNet contains 1,162,109 interactions between plants and pollinators from 1864 distinct networks, which belong to 52 different studies distributed across 23 European countries. Information about sampling methodology, habitat type, biogeographic region and additional taxonomic rank information (i.e. order, family, genus and species) is also provided. Spatial Location and Grain The database contains 1214 different sampling locations from 13 different natural and anthropogenic habitats that fall in 7 different biogeographic regions. All records are geo‐referenced and presented in the World Geodetic System 1984 (WGS84). Time Period and Grain Species interaction data was collected between 2004 and 2021. Major Taxa and Level of Measurement The database contains interaction data at the species level for 94% of the records, including a total of 1411 plant and 2223 pollinator species. The database includes data on 6% of the European species of flowering plants, 34% of bees, 26% of butterflies and 33% of syrphid species at the European level. Software Format The database was built with R and is stored in ‘.rds’ and ‘.csv’ formats. Its construction is fully reproducible and can be accessed at: https://doi.org/10.5281/zenodo.14747448 .

Background West Nile Virus (WNV) exemplifies the complexities of managing vector-borne diseases, expanding globally due to human activities and ecological changes. Originating from Africa and transmitted by Culex mosquitoes, WNV is now reported across multiple continents. The aim of this study was to identify the environmental, ecological, and individual factors influencing WNV transmission. Methods An umbrella review was conducted. Comprehensive searches were performed in PubMed, Scopus, Web of Science, Embase, and LILACS. Inclusion criteria were reviews involving WNV transmission agents (reservoirs, vectors, hosts) and associative analyses between environmental, ecological, or individual factors and WNV transmission. Data extraction and quality appraisal were performed using templates and the AMSTAR 2 tool. Results From 404 retrieved studies, 23 systematic reviews and meta-analyses were included. Almost 70 % were low or critically low quality. The co-occurrence network highlighted emerging research on climate change and environmental factors. Temperature, precipitation, and land use significantly influence WNV transmission. Warmer temperatures enhance mosquito populations and viral replication, while extreme weather events like droughts increase mosquito-human contact. Climate change significantly contributes to WNV dynamics by altering temperature and precipitation patterns, enhancing vector proliferation, and extending transmission seasons. Ecological factors such as higher avian diversity, vegetation indexes, and distribution of mosquito species can impact WNV transmission significantly. Education and income levels influence preventive behaviors and infection risk, with lower socioeconomic status linked to higher WNV risk. Certain occupational groups are also at elevated risk of WNV infection. Conclusion Environmental factors like temperature and precipitation critically affect WNV transmission by influencing mosquito behavior and avian reservoir dynamics. Socio-economic status and education levels significantly impact individual preventive behaviors and infection risk. Multifactorial influences on infection risk make necessary integrated surveillance systems and public health strategies. Longitudinal studies with One Health approaches are necessary to better understand WNV dynamics and reduce WNV transmission.

Aim Macaronesian cloud forests are insular ecosystems subjected to local environmental variability, but the responses of their tree species to climate variations have never been studied. Our aim was to assess how the variation in environmental conditions associated with the geographical location of several islands in three Macaronesian archipelagos affects the growth patterns and drought‐resistance of the dominant cloud forests trees. Location Azores, Madeira and Canary archipelagos. Portugal and Spain. Taxon Lauraceae, Aquifoliaceae, Clethraceae, Oleaceae, Rosaceae and Cupressaceae. Methods We assessed variations in the radial growth response of 10 cloud forest tree species from 18 populations on 5 islands along a geographical gradient in Macaronesia. We quantified the influence of local climatic variables and North Atlantic Oscillation (NAO) and East Atlantic Pattern (EA) circulation patterns on tree growth and how drought events affected to the resistance, recovery and resilience indices estimated for these species. Results Trees from the same island showed similar growth patterns, particularly in islands with marked hydric stress. In Madeira and the Canary Islands, radial growth was mainly determined by water availability, winter NAO negatively affected growth and droughts caused abrupt narrow growth‐ring width. In the Azores, the effect of the EA was positive, as it increased temperature and relative humidity and promoted growth. Trees from wetter environments demonstrated higher growth resistance to drought, while trees from drier sites showed faster growth recovery after drought events. Main Conclusions Homogeneous growth patterns among species from the same island suggested that the radial growth of trees in cloud forests is mostly determined by local environmental conditions, which are more important for their growth than phenotypic traits. The variability in water availability determined by a latitudinal geographical gradient throughout the Macaronesian region influenced both the climatic response of the trees and their resilience to drought.

Engineered stone silicosis is an interstitial lung disease that progresses rapidly causing, in many cases, respiratory insufficiency and death. Metabolic activity in lungs and adenopathies and its relationships with systemic inflammation are unknown. Patients with complicated silicosis were enrolled. All had worked for at least 5 years in finishing and installing engineered stone and had ceased exposure for at least 7 years. Clinical data, positron emission tomography/computed tomography using ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG PET/CT), respiratory function tests and blood samples were collected. Patients’ mean age was 44 ± 5.4 years. The average exposure duration was 10.94 ± 3.2. Years from cessation of exposure was 11.6 ± 1.6. The average maximum standardized uptake value (SUVmax) of large opacities was 6.32 ± 3. All patients presented hypermetabolic mediastinal lymphadenopathies and 88.2% also extrathoracic lymphadenopathies. SUV max of large opacities was correlated with Fibrinogen (ρ = 0.717, P = 0.001), lymphocyte-to-monocyte ratio (ρ = -0.506, P = 0.038), systemic inflammatory response index (ρ = 0.559, P = 0.02) and CD4 + NKT cells. Large lung opacities and lymphadenopathies showed high metabolic activity even years after silica exposure ended. The relationships between metabolic activity and some inflammatory factors open a pathway for exploring new therapeutic targets.