Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Artrosi de genoll i artroplàstia
Full text linkArtroplàstia de genoll; Artrosi de genoll; CirurgiaArtroplastia de rodilla; Artrosis de rodilla; CirugíaKnee arthroplasty; Knee osteoarthritis; SurgeryEssencial és una iniciativa que identifica pràctiques clíniques d'escàs valor i promou recomanacions per a evitar la seva aplicació. En aquesta recomanació no es recomana l’artroplàstia de genoll com a primera línia de tractament en persones amb artrosi de genoll lleu o moderada.Essencial es una iniciativa que identifica prácticas clínicas de escaso valor y promueve recomendaciones para evitar su aplicación. En esta recomendación no se aconseja la artroplastia de rodilla como primera línea de tratamiento en personas con artrosis de rodilla leve o moderada.Essencial is an initiative that identifies low-value clinical practices and promotes recommendations to avoid their use. In this recommendation, knee arthroplasty is not advised as a first-line treatment for individuals with mild or moderate knee osteoarthritis
eHealth in geriatric rehabilitation: an international consensus study
Full text linkConsensus; Geriatric rehabilitation; eHealthConsenso; Rehabilitación geriátrica; eSaludConsens; Rehabilitació geriàtrica; eSalutPurpose: Current evidence on the use of eHealth in geriatric rehabilitation is limited. This aim of this study was to achieve international consensus on three key eHealth-related topics in geriatric rehabilitation: the use, domains, and scientific evaluation of eHealth. Additionally, we developed a model that provides insight into the use of eHealth in geriatric rehabilitation.
Methods: An international, two-round Delphi study was conducted. Two models served as a framework for the initial statement draft, with a total of 28 statements based on our systematic review results, an international survey, and expert opinion. Eligible healthcare professionals working in geriatric rehabilitation facilities were recruited across 10 countries.
Results: Eighty healthcare professionals participated in round one and 47 in round two. In the first round, consensus was obtained for 20 of the 28 statements (71%). Prior to round two, four statements were revised, two statements were combined, and one statement was removed. In round two, consensus was obtained on six statements, bringing the total to 26: three related to the use of eHealth, five to the domains of eHealth, and 18 related to the scientific evaluation of eHealth.
Conclusion: International consensus has been reached on the use, domains, and scientific evaluation of eHealth in geriatric rehabilitation. This first step in generating reliable knowledge and understandable information will help promote a consistent approach to the development, implementation, and scientific evaluation of eHealth in geriatric rehabilitation
Real-world adherence trajectories to direct oral anticoagulants in naive patients with atrial fibrillation in Spain
Full text linkAdherence trajectories; Atrial fibrillation; Direct oral anticoagulantsTrayectorias de adherencia; Fibrilación auricular; Anticoagulantes orales directosTrajectòries d'adherència; Fibril·lació auricular; Anticoagulants orals directesAims: This study aimed to identify adherence trajectories and associated factors in atrial fibrillation patients who initiated direct oral anticoagulant (DOAC) therapy, using population-based data from the Catalonia and Valencia regions in Spain during a 2-year follow-up.
Methods and results: Group-based trajectory modelling (GBTM) was applied to assess adherence patterns in cohorts comprising 14,641 patients in Catalonia and 13,211 in Valencia. Adherence trajectories were categorised based on prescription data, revealing three main trajectories in Valencia and five in Catalonia. Most patients in Valencia demonstrated high adherence, whereas Catalonia showed more varied patterns, including early, gradual, and late declines. Factors associated with non-adherence included high co-insurance levels, alcohol use, and specific DOACs, such as dabigatran.
Conclusion: Adherence trajectories differed between the two regions, with three identified in Valencia and five in Catalonia. Shared non-adherence patterns were observed across both cohorts, while Catalonia exhibited additional noncompliance trends. Key factors associated with non-adherence included socio-economic variables, clinical characteristics, and the type of DOAC prescribed. Understanding these patterns is essential for developing targeted intervention strategies to improve adherence and optimise treatment outcomes.The author(s) declare that financial support was received for the research and/or publication of this article. Francisco Sánchez-Sáez was partially funded by RICAPPS, ISCIII (grant number RD21/0016/0006, co-funded by European Union-ERDF)
First-in-human study of an EGFRvIII x CD3 T cell bispecific antibody in the treatment of newly diagnosed glioblastoma
Full text linkT cell bispecific antibody; Glioblastoma; Immune therapyAnticuerpo biespecífico de células T; Glioblastoma; InmunoterapiaAnticòs biespecífic de cèl·lules T; Glioblastoma; ImmunoteràpiaBackground
This first-in-human study evaluated EGFRvIII × CD3 TCB, a novel T cell bispecific antibody, in patients with newly diagnosed EGFRvIII-positive glioblastoma.
Methods
Patients with newly diagnosed glioblastoma received escalating doses of EGFRvIII × CD3 TCB following chemoradiation. The primary objectives were to evaluate safety/tolerability and define the maximum tolerated dose (MTD); secondary objectives included pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity.
Results
Thirty-six patients were enrolled, 32 with unmethylated and 4 with methylated MGMT promoter. EGFRvIII × CD3 TCB doses ranged from 0.004 to 10 mg Q3W, administered either on a flat or step-up dose schedule. One DLT occurred (grade 3 seizure). The MTD was not reached. Most adverse events (AEs) were of grade 1-2 severity, with headache being the most common treatment-related AE (22%). EGFRvIII × CD3 TCB showed dose-proportional PK in serum and cerebrospinal fluid (CSF), with a CSF/serum ratio of 0.08. At the highest dose tested, 10 mg Q3W, maximum serum concentrations remained 6-fold below the lower boundary of the predicted anticipated therapeutic dose.
Conclusions
The administration of EGFRvIII × CD3 TCB in a maintenance setting, following standard of care treatment, was safe and well tolerated up to the highest tested dose of 10 mg Q3W. However, evidence of efficacy was not observed at the evaluated doses, suggesting that a study of higher dose levels may be warranted.Funding for this study was provided by F. Hoffmann-La Roche, Basel, Switzerland. No grant numbers apply
Accelerating Drug Development for Neuroblastoma: Consensus Statement From the Third Neuroblastoma Drug Development Strategy Forum
Full text linkDrug development; Neuroblastoma; RelapseDesarrollo de medicamentos; Neuroblastoma; RecaídaDesenvolupament de medicaments; Neuroblastoma; RecaigudaHigh-risk neuroblastoma is a poor prognosis cancer of the sympathetic nervous system that accounts for a disproportionate number of childhood cancer deaths. Many viable biological targets have been identified, and the number of potential combinations is even larger. Several products have attained marketing authorization for treatment of patients with neuroblastoma. Patient outcomes remain poor, with approximately 50% of children with newly diagnosed high-risk neuroblastoma cured of their disease. International, multistakeholder Neuroblastoma Drug Development Strategy (NDDS) meetings were established more than a decade ago. This third NDDS meeting included academia, industry, regulatory, and patient advocacy representatives to prioritize agents and to address key challenges in drug development in this disease. Given the central role that anti-GD2 therapy plays, novel GD2-directed combinations were a key focus, including epigenetic enzymes such as EZH2 and immunologic targets such as IL15 and TIGIT as potential combination partners. GD2-directed chimeric antigen receptor (CAR)-T cells were a top priority, along with emerging CAR-T targets such as B7-H3 and GPC2. Recognizing that combination therapies are likely to be most impactful for patients and for advancing therapies to frontline, another key focus was on high priority combinations of targeted therapies, including Aurora A kinase plus BCL2 or ATR inhibitors. Additional targets and agents were prioritized or deprioritized based upon current data. Access to drugs for clinical trials was viewed as a major barrier to progress. Strategies to overcome this challenge focused on united efforts by the international scientific and advocacy community and early engagement by industry with regulatory authorities.This work was supported by Accelerate the Future Fund; Alex's Lemonade Stand Foundation; Dana-Farber Cancer Institute; and Friends for Life
Generalist Malaria Parasites and Host Imprinting: Unveiling Transcriptional Memory
Full text linkPlasmodium homocircumflexum; Adaptive strategies; Avian malariaPlasmodium homocircumflexum; Estrategias adaptativas; Malaria aviarPlasmodium homocircumflexum; Estratègies adaptatives; Malària aviarGeneralist parasites must adapt to diverse host environments to ensure their survival and transmission. These adaptations can involve fixed genetic responses, transcriptional plasticity, or epigenetic mechanisms. The avian malaria parasite Plasmodium homocircumflexum offers an ideal model for studying transcriptional variation across hosts. We experimentally inoculated P. homocircumflexum into different bird species, bypassing the vector, to assess whether gene expression remains stable across hosts, resets in response to new environments, or reflects epigenetic inheritance. We tested two alternative hypotheses: (i) universal gene expression profile (“one key fits all”), where parasite expression remains consistent across hosts. Our outcomes revealed that gene expression differed significantly depending on the host species and time postinfection, rejecting this hypothesis. (ii) Transcriptional plasticity, where gene expression is determined by the recipient host. Contrary to this hypothesis, we observed that gene expression was primarily influenced by the donor at 8 d postinfection (dpi), whereas gene expression was more aligned with the recipient host at 16 dpi. We also explored two mechanisms to explain these patterns: (i) epigenetic inheritance, whereby early transcription reflects the donor environment but adjusts over time, and (ii) genetic differentiation selecting for specific haplotypes. Our data support mechanism (i): 2,647 differentially expressed genes (DEGs) were associated with the donor at 8 dpi, while only 271 DEGs were linked to the recipient at 16 dpi. Single Nucleotide Polymorphism analyses revealed low genetic differentiation, rejecting mechanism (ii). These findings suggest that P. homocircumflexum undergoes a shift from donor-dependent to recipient-dependent gene expression, likely driven by epigenetic regulation and transcriptional plasticity.Funding was provided by the Junta de Extremadura (PO17024, postdoc grant) to L.G.-L., the Spanish Ministry of Science and Innovation (PID2022-140397NB-I00) to A.M., and LA4 (R + D + I program in the Biodiversity Area financed with the funds of the FEDER Extremadura 2021–2027 Operational Program of the Recovery, Transformation and Resilience Plan) to L.G.-L., and A.M. V.P. obtained funding from the Research Council of Lithuania (LMTLT) (project no. S-MIP-22-52). O.H. obtained funding from the Swedish Research Council (VR 2016-03419 and 2021-03663). All the authors would like to thank Ananias Escalante for taking the time to read the manuscript and for his inspiring ideas
First prospective, single-arm, multicenter study to evaluate safety and efficacy of the overall thrombectomy system -iNedit, iNdeep, and iNtercept- for acute ischemic stroke. Rationale beyond the study
Full text linkAcute ischemic stroke; Balloon guide catheter; Distal aspiration catheterIctus isquèmic agut; Catèter guia amb baló; Catèter d'aspiració distalIctus isquémico agudo; Catéter guía con balón; Catéter de aspiración distalRationale: The clinical impact of a novel mechanical thrombectomy strategy, which integrates distal access with flow reversal and flow arrest via a distal balloon, all within a single procedure [Safety and Efficacy of the overall throMbectomy system for sTroke (SEMTiC) strategy], has not been tested.
Aim: The SEMTiC-01 study is the first prospective, multicenter in vivo study evaluating the safety and efficacy of the combined thrombectomy system—iNedit, iNdeep, and iNtercept—in patients with acute ischemic stroke.
Sample size estimates: The study was designed with a sequential structure based on the efficacy endpoint (eTICI ≥2b) reported in the literature [71.1% with a 95% confidence interval of (68.5%, 73.8%)]. An interim analysis was set for 115 patients and a final analysis for 225 patients, ensuring 98% power at a one-sided 0.025 significance level, with a 2.6% non-inferiority margin and a 15% assumed withdrawal rate.
Design: SEMTiC-01 is a prospective, multicenter, single-arm, open-label clinical safety and efficacy investigation.
Outcome: Primary efficacy endpoint: expanded treatment in cerebral infarction score (eTICI) ≥2b revascularization within ≤ 3 stent retriever passes. Primary safety endpoint: monitoring serious adverse events within 24 h post-intervention and all-cause mortality at 90 days.This work has been sponsored by iVascular S.L.U., Sant Vicenç dels Horts, Spain
Cost-effectiveness analysis of universal hypothyroidism screening in the general population aged 30–65 years in Spain
Full text linkCost-effectiveness analysis; Spain; Hypothyroidism screeningAnálisis de costo-efectividad; España; Detección de hipotiroidismoAnàlisi de cost-efectivitat; Espanya; Detecció d'hipotiroïdismeAims
Hypothyroidism is an endocrine disorder that often begins in a subclinical form but can lead to non-specific symptoms and cardiovascular problems. Its prevalence is higher among women, and a significant proportion of cases remain undiagnosed. While previous studies assessed screening in specific populations (e.g. pregnant women, older adults), this study evaluates the cost-effectiveness of population-wide screening in adults aged 30–65 from the Spanish National Health System (NHS) perspective.
Materials and methods
A cost-effectiveness Markov model was developed, simulating seven health states: subclinical hypothyroidism (undiagnosed and controlled), overt hypothyroidism (undiagnosed and controlled), euthyroid state, cardiovascular event, and death. Two strategies were compared: population-based screening versus no screening. Model inputs-transition probabilities, prevalence, costs, utilities, and screening effectiveness-were obtained from published literature. A panel of four clinical experts validated the model structure and assumptions. Lifetime costs and quality-adjusted life-years (QALYs) were estimated, and the incremental cost-effectiveness ratio (ICER) was calculated. Probabilistic, sensitivity, and scenario analyses were conducted.
Results
Population-based screening for hypothyroidism in individuals aged 30–65 resulted in an incremental cost of €34.7 million and 6,037 QALYs gained over 35 years, yielding an ICER of €5,745/QALY, significantly below the Spanish willingness-to-pay threshold (€21,000/QALY). Screening also resulted in 33,215 additional diagnoses of subclinical hypothyroidism and 6,870 fewer cases of overt hypothyroidism. It was cost-effective in 99% of probabilistic simulations and under all tested screening intervals (1–5 years).
Limitations and conclusions
Key limitations include the use of constant transition probabilities and some inputs from international sources. Nonetheless, expert validation supports the model’s relevance. The analysis adopts a conservative approach, excluding potential additional benefits like hyperthyroidism detection or integration with routine bloodwork, which could improve cost-effectiveness. Overall, hypothyroidism screening is a cost-effective strategy for the Spanish NHS, improving early detection, preventing progression, and enhancing quality of life in a frequently underdiagnosed population.Project funded by Merck KGaA, CrossRef Funder ID: 10.13039/100009945
Managing lorlatinib together: An overview and practical guide for patients by ALK-positive NSCLC patients and medical experts
Full text linkAdverse event; Anaplastic lymphoma kinase; Non-small cell lung cancerEsdeveniment advers; Cinasa del limfoma anaplàsic; Càncer de pulmó de cèl·lules no petitesEvento adverso; Cinasa del linfoma anaplásico; Cáncer de pulmón de células no pequeñasLorlatinib is an oral treatment for patients with advanced ALK-positive non-small cell lung cancer (NSCLC). Its efficacy was demonstrated in the CROWN clinical study, in which data from 5 years of follow-up demonstrated effective long-term disease control in patients with advanced ALK-positive NSCLC. While lorlatinib has a distinct side effect profile, its side effects are generally manageable. Managing side effects successfully is critical to preserving patient quality of life and promoting adherence to treatment—both of which are key to maximizing the long-term benefits of lorlatinib. The CROWN study showed that lorlatinib-associated side effects can be managed with dose adjustments, such as lowering the daily dose, without sacrificing treatment effectiveness. This guide, developed collaboratively by patients living with advanced ALK-positive NSCLC and healthcare professionals experienced with managing lorlatinib treatment, aims to help patients understand what to expect from treatment and how to take an informed, active role in their care.Development of this report was funded by Pfizer
Severe invasive Streptococcus pyogenes infections: A 15-year observational study with molecular characterization of isolates among intensive care adults
Full text linkAntimicrobial stewardship; Clindamycin; MortalityAdministració antimicrobiana; Clindamicina; MortalitatAdministración antimicrobiana; Clindamicina; MortalidadBackground
Improving outcomes among patients with invasive group A Streptococcus pyogenes (iGAS) infections is an unmet clinical need. The main objective of this study was to analyze epidemiological and outcome differences in adults admitted to the intensive care unit (ICU) with iGAS infection over a 15-year period and to evaluate the impact of M1uk isolates and clindamycin optimization on patient outcomes.
Methods
This was a single-center observational study conducted at the ICU of Donostia University Hospital, located in Donostia, Spain. The recruitment of all consecutive adult patients admitted to the ICU by iGAS was carried out from January 2010 to May 2024 and divided into three periods: pre-pandemic (January 2010–2019), pandemic (2020–2021), and post-pandemic (May 2022–2024). The main outcome variables were ICU length of stay, hospital length of stay, and ICU mortality. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software (version 25; SPSS Inc., Chicago, IL, USA). A significance level of P <0.05 was considered for all analyses.
Results
Sixty-eight adults were enrolled, with a crude mortality in pre- and post-pandemic periods being 25.5% and 10.0% (P=0.200), respectively. Twenty (29.4%) were respiratory and 29 (41.2%) were soft tissue infections. The incidence had valleys (4/100,000 inhabitants) in 2014, 2019, and 2023. Pre-pandemic patients were significantly younger (median: 58.0 vs. 67.5 years, P <0.050), had lower Charlson scores (median: 0 vs. 2, P=0.009), and required more renal replacement therapy (48.9% vs. 15.0%, P=0.013). Emm1 type was the most frequent isolated strain, with the M1uk lineage being represented in 6 out of 7 Emm1 isolates in post-pandemic period. M1uk-infected patients were older (median: 67.0 vs. 50.0 years, P=0.073) but mortality was similar. Most patients (86.6%) received β-lactams plus clindamycin. Interestingly, time to clindamycin administration was earlier (median: 1 h vs. 24 h; P <0.050) in the post-pandemic period with a 5-fold increase in ICU mortality (5.6% to 26.5%, OR=6.14, 95% CI: 0.74 to 50.85; P=0.090) among those adults who did not receive clindamycin in the emergency department.
Conclusions
The incidence of iGAS infections requiring ICU admission showed no significant increase post-Coronavirus Disease-19 pandemic. The highly toxigenic M1uk strain became predominant, but it was not associated with worse mortality among adult ICU patients