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Clinician's perceptions and experiences with tobacco treatment in people who use cannabis: a qualitative study
Full text linkCanabis; Política de salud; Servicios de atención sanitariaCannabis; Health policy; Healthcare servicesCànnabis; Política de salut; Serveis sanitarisGlobal demand for the treatment of cannabis use disorder has increased significantly, prompting a need to understand effective strategies for addressing concurrent cannabis and tobacco use. This study focuses on clinicians' experiences and perceptions in delivering tobacco cessation services to people who use cannabis.
Fifteen participants (12 females, 3 males) participated in three homogenous focus groups, including two groups with extensive experience in providing tobacco cessation among the substance use population in Catalonia, Spain, and one group of clinicians without such experience. Thematic analysis was conducted to identify key patterns and insights in their discourse, focusing on shared themes and divergences across groups.
Five main themes and 17 subthemes emerged: Individual characteristics, Clinician characteristics, Models of intervention, Organizational healthcare models, and Health policies. Clinicians stressed the importance of intervention models and the active role of professionals in addressing tobacco use within routine care, as tobacco cessation could mitigate social and chronic stigma among people who use cannabis, especially those engaged in polydrug use.
Recommendations included integrating tobacco cessation into all services, reducing healthcare service fragmentation, improving resource accessibility, enhancing clinical documentation, and advocating for stronger population-level tobacco control policies.
The ACT-ATAC project has been successfully registered at Clinicaltrials.gov [NCT04841655].This work was supported by the Instituto de Salud Carlos III (ISCIII) (Grant: PI18/01420) Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”. The Tobacco Control Research Group is partly supported by the Ministry of Business and Knowledge from the Government of Catalonia [2017SGR319] and by Instituto de Salud Carlos III, Government of Spain (CIBERES CB19/06/00004). CMM received funding for a research stay at the University of California San Francisco from the Ministry of Health in Spain (BAE: 20220021). We thank CERCA Programme/Generalitat de Catalunya for institutional support
Fetal Tracheal Occlusion Correlates with Normalized YAP Expression and Alveolar Epithelial Differentiation in Congenital Diaphragmatic Hernia
Full text linkAlveolar epithelial differentiation; Congenital diaphragmatic hernia; Fetal tracheal occlusionDiferenciació epitelial alveolar; Hèrnia diafragmàtica congènita; Oclusió traqueal fetalDiferenciación epitelial alveolar; Hernia diafragmática congénita; Oclusión traqueal fetalCongenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm. Although the ensuing compression to the fetal lung causes lung hypoplasia, specific cellular phenotypes and developmental signaling defects in the alveolar epithelium in CDH are not fully understood. Employing lung samples from human CDH, a surgical lamb model, and a nitrofen rat model, we investigated whether lung compression impairs alveolar epithelial differentiation and Yes-associated protein (YAP)-mediated mechanosensing. We showed that CDH in humans and lambs caused defective alveolar epithelial differentiation manifested by more alveolar epithelial type II (ATII) cells, fewer ATI cells, and the emergence of cells coexpressing ATI and ATII markers. Associated with these alveolar epithelial defects, we found a decrease in the level and nuclear localization of YAP. Reduced YAP and abnormal distal lung development were evident as early as 21 weeks of gestation in human CDH. In addition, rat fetuses with CDH also showed diminished nuclear YAP and more abundant ATII cells. In contrast, the littermates without the hernia had no such alveolar phenotypes. Furthermore, fetal tracheal occlusion in the surgical lamb model of CDH fully normalized nuclear YAP and rescued alveolar epithelial defects in a gestational age-dependent manner. Taken together, our findings across species indicate that lung compression in CDH is sufficient to disrupt alveolar epithelial differentiation and impair YAP signaling. Tracheal occlusion can restore nuclear YAP and rescue the alveolar defects in CDH, depending on the timing and the duration of this prenatal surgical intervention
Developing Allosteric Chaperones for GBA1-Associated Disorders-An Integrated Computational and Experimental Approach
Full text linkGaucher disease; Parkinson’s disease; GlucocerebrosidaseEnfermedad de Gaucher; Enfermedad de Parkinson; GlucocerebrosidasaMalaltia de Gaucher; Malaltia de Parkinson; GlucocerebrosidasaMutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are associated with Gaucher disease and increased risk of Parkinson’s disease. This study describes the discovery and characterization of novel allosteric pharmacological chaperones for GCase through an innovative computational approach combined with experimental validation. Utilizing virtual screening and structure-activity relationship optimization, researchers identified several compounds that significantly enhance GCase activity and stability across various cellular models, including patient-derived fibroblasts and neuronal cells harboring GBA1 mutations. Among these, compound 3 emerged as a lead candidate, demonstrating the ability to enhance GCase protein levels and enzymatic activity while effectively reducing the accumulation of toxic substrates in neuronal models. Importantly, pharmacokinetic studies revealed that compound 3 has favorable brain penetration, indicating its potential as a disease-modifying therapy for GBA1-related disorders affecting the central nervous system. This research not only offers a framework for developing allosteric GCase modulators but also unveils promising new therapeutic strategies for managing Gaucher disease and Parkinson’s disease. The ability of compound 3 to cross the blood-brain barrier emphasizes its potential significance in addressing neurological symptoms associated with these conditions.This study received funding from the Michael J. Fox Foundation, the Silverstein Foundation (MJFF 16182), and the Eurostars-2 joint program, which is co-funded by the European Union’s Horizon 2020 research initiative and Innosuisse—Swiss Innovation Agency (E! 113321–CHAPERONE; Ref.: 113321/21/Q). Additional support came from Eureka|Eurostars (https://eurekanetwork.org/programmes/eurostars/, accessed on 6 December 2022), Instituto de Salud Carlos III, EU/Spain (PI20/00728) to M.M-V. MM was supported by an FPU doctoral fellowship (FPU18/05595) from MINECO (Spain). The funders did not influence the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript
Management of Hemodynamic and Respiratory Instability and Anesthetic Approaches in Patients Undergoing Pulmonary Thrombectomy for Pulmonary Embolism
Full text linkHemodynamic instability; Pulmonary embolism; Pulmonary mechanical thrombectomyInestabilitat hemodinàmica; Embòlia pulmonar; Trombectomia mecànica pulmonarInestabilidad hemodinámica; Embolia pulmonar; Trombectomía mecánica pulmonarBackground/Objectives: The incidence, timing, and predictors of hemodynamic and respiratory deterioration in patients with high-risk or intermediate-high-risk pulmonary embolism (PE) undergoing pulmonary mechanical thrombectomy (PMT) remain poorly understood. This hemodynamic and respiratory instability can lead to modifications in the anesthetic management. This study investigates these key factors and quantifies the 30-day mortality following thrombectomy. Methods: A retrospective study was conducted on 98 patients aged ≥18 years who underwent PMT. Patients were categorized based on the occurrence of cardiac arrest (CA). Results: Of the 98 patients, 34 had high-risk PE, 62 intermediate/high-risk, and 2 low risk. There were 27 cases of CA, 17 pre- and 10 intra-PMT. An SBP < 90 mmHg increases the risk of CA by 33 (p < 0.001); men have an 8-fold higher risk than women (p = 0.004); SpO2 <90% by 6 (p = 0.012); and pre-existing respiratory conditions increase the risk by 4 (p = 0.047)). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 8206 ± 11660.86 and 2388.50 ± 5683.71 pg/mL (p = 0.035) in patients with and without CA, respectively. During PMT, 14% of patients required increased vasoactive drug use, and 38.77% were intubated, including 12 who required ECMO support. Sedation was administered in 64.3% of patients, while general anesthesia was used in 38.8%, with a preemptive indication in 23.5%. The survival rate of patients without CA before and/or during PMT was 96%. Conclusions: While PMT was successfully performed in all patients, hemodynamic and respiratory instability remained a significant concern. More than 10% of patients experienced severe hemodynamic instability, primarily during thrombus extraction, requiring conversion from sedation to general anesthesia. Male sex, pre-existing respiratory disease, SpO2 < 90%, and SBP < 90 mmHg were associated with an increased risk of CA. Additionally, elevated NT-proBNP levels were linked to a higher incidence of CA
Scientia: guia per a l’autoarxiu de documents
Full text linkRepositoris institucionals; Autoarxiu de documents; SalutRepositorios institucionales; Autoarchivo de documentos; SaludInstitutional repositories; Documents autoarchiving; HealthScientia és el dipòsit d'informació digital del Departament de Salut per a la gestió de la producció científica en ciències de la salut a Catalunya i l’accés obert als recursos digitals derivats d’aquesta producció científica. En aquesta guia s'especifiquen els requeriments per a l'autoarxiu de documents.Scientia es el repositorio de información digital del Departamento de Salud para la gestión de la producción científica en ciencias de la salud en Cataluña y el acceso abierto a los recursos digitales derivados de esta producción científica. En esta guía se especifican los requerimientos para el autoarchivo de documentos.Scientia is the digital information repository of the Department of Health for the management of scientific production in health sciences in Catalonia and open access to digital resources derived from this scientific production. This guide specifies the requirements for self-archiving documents
Proposal of an Integrated Patient Journey roadmap for the introduction of the first gene therapy for haemophilia B in Spain – The BHEMOGEN project
Full text linkGene therapy; Haemophilia B; Patient journey roadmapTeràpia gènica; Hemofília B; Full de ruta del recorregut del pacientTerapia genética; Hemofilia B; Hoja de ruta del recorrido del pacienteBackground
The approval of the first gene therapy for haemophilia B represents a disruptive innovation in its management. Its practical integration into the Spanish national healthcare system presents unique challenges and opportunities, requiring the development of a structured, coordinated and multidisciplinary patient journey roadmap to ensure high-quality patient care and outcomes measurement.
Methods
A multidisciplinary panel of 10 experts was established. The project involved a literature review, structured questionnaires, individual interviews, practical exercises and validation of results by focus group with nominal group methodology.
Results
No specific patient journey for haemophilia B or for gene therapy were identified in Spain. Associated changes required for current treatment of haemophilia B were identified and proposals made: 1) selection of candidates to receive gene therapy involves individualised assessment of eligibility criteria by a multidisciplinary committee including additional profiles; 2) providing adequate training on gene therapy to healthcare professionals is a must to ensure quality of care; 3) the generation of a specific informed consent document and processes involving hepatology and psychology are essential, with the patient association playing a crucial role; 4) centres without prior practical experience in gene therapy must adapt specific areas to ensure correct preparation and administration; 5) short- and long-term patient follow-up should incorporate continuous monitoring of the patient's liver health and inclusion in registries for evaluation of outcomes.This study was sponsored by CSL Behring
Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas
Full text linkImpact of CAR T-cell therapy; Efficacy; Refractory B-cell lymphomasTeràpia de cèl·lules T CAR; Eficàcia; Limfomes de cèl·lules B refractarisTerapia de células T CAR; Eficacia; Linfomas de células B refractariosMosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)–modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab. Thirty patients had paired samples at baseline and after 1 cycle of mosunetuzumab. The median time from CAR-T to mosunetuzumab was significantly longer for responding than for nonresponding patients (P = .006, unadjusted for multiple comparisons). Most patients (20/30) did not receive intervening therapy between CAR-T administration and mosunetuzumab. The remainder of patients received 1 intervening therapy after a protocol-mandated drug washout. After mosunetuzumab, responding patients had higher lymphocytes (995 vs 400 cells per μL; P = .02) and greater increases in CD4 and CD8 cells (median change, 73 vs –90 cells per μL [P = .005] and 243 vs –103 cells per μL [P = .004], respectively). Additionally, responding patients had an increase in activated CD8 cells (median fold change, 1.7; P = .02). Nonresponders had a relative decrease in CAR transgene levels (n = 16; P = .04). This is, to our knowledge, the first study to assess changes in lymphocytes, T cells, and CAR transgene levels in patients treated with BsAbs after CAR-T. These findings suggest an interaction between prior CAR-T and BsAb outcomes and have implications for optimal timing of BsAb after CAR-T. The trial was registered at www.ClinicalTrials.gov as #NCT02500407
Interoperability Framework of the European Health Data Space for the Secondary Use of Data: Interactive European Interoperability Framework-Based Standards Compliance Toolkit for AI-Driven Projects
Full text linkEuropean Health Data Space; European interoperability framework; artificial intelligence; healthcare standards interoperability; secondary use of health dataInteroperabilitat; Espai europeu de dades de salut; Intel·ligència artificialInteroperability; European Health Data Space; Artificial IntelligenceInteroperabilidad; Espacio europeo de datos de salud; Inteligencia artificialThe successful implementation of the European Health Data Space (EHDS) for the secondary use of data (known as EHDS2) hinges on overcoming significant challenges, including the proper implementation of interoperability standards, harmonization of diverse national approaches to data governance, and the integration of rapidly evolving AI technologies. This work addresses these challenges by developing an interactive toolkit that leverages insights from 7 leading cancer research projects (Integration of Heterogeneous Data and Evidence towards Regulatory and HTA Acceptance [IDERHA], European Federation for Cancer Images [EUCAIM], Artificial intelligence Supporting Cancer Patients across Europe [ASCAPE], Personalised Health Monitoring and Decision Support Based On Artificial Intelligence and Holistic Health Records [iHelp], Central repository for digital pathology [Bigpicture], Piloting an infrastructure for the secondary use of health data [HealthData@EU] pilot, and improving cancer diagnosis and prediction with AI and big data [INCISIVE]) to guide in shaping the EHDS2 interoperability framework. Building upon the foundations laid by the Towards the European Health Data Space (TEHDAS) joint action (JA) and the new European Interoperability Framework (EIF), the toolkit incorporates several key innovative features. First, it provides interactive and user-friendly entry modules to support European projects in creating their own interoperability frameworks aligned with the evolving EHDS2 requirements technical and governance requirements. Second, it guides projects in navigating the complex landscape of health data standards, emphasizing the need for a balanced approach to implementing the EHDS2 recommended standards for data discoverability and sharing. Third, the toolkit fosters collaboration and knowledge sharing among projects by enabling them to share their experiences and best practices in implementing standards and addressing interoperability challenges. Finally, the toolkit recognizes the dynamic nature of the EHDS2 and the evolving regulatory landscape, including the impact of AI regulations and related standards. This allows for continuous adaptation and improvement, ensuring the toolkit remains relevant and useful for future projects. In collaboration with HSbooster.eu, the toolkit will be disseminated to a wider audience of projects and experts, facilitating broader feedback and continuous improvement. This collaborative approach will foster harmonized standards implementation across projects that ultimately contribute to the development of a common EHDS2 interoperability framework
Large language models for diabetes training: a prospective study
Full text linkDiabetes training; Large language models; Primary diabetes careFormació en diabetis; Grans models de llenguatge; Atenció primària de diabetisFormación en diabetes; Grandes modelos de lenguaje; Atención primaria de diabetesDiabetes poses a considerable global health challenge, with varying levels of diabetes knowledge among healthcare professionals, highlighting the importance of diabetes training. Large Language Models (LLMs) provide new insights into diabetes training, but their performance in diabetes-related queries remains uncertain, especially outside the English language like Chinese. We first evaluated the performance of ten LLMs: ChatGPT-3.5, ChatGPT-4.0, Google Bard, LlaMA-7B, LlaMA2-7B, Baidu ERNIE Bot, Ali Tongyi Qianwen, MedGPT, HuatuoGPT, and Chinese LlaMA2-7B on diabetes-related queries, based on the Chinese National Certificate Examination for Primary Diabetes Care in China (NCE-CPDC) and the English Specialty Certificate Examination in Endocrinology and Diabetes of Membership of the Royal College of Physicians of the United Kingdom. Second, we assessed the training of primary care physicians (PCPs) without and with the assistance of ChatGPT-4.0 in the NCE-CPDC examination to ascertain the reliability of LLMs as medical assistants. We found that ChatGPT-4.0 outperformed other LLMs in the English examination, achieving a passing accuracy of 62.50%, which was significantly higher than that of Google Bard, LlaMA-7B, and LlaMA2-7B. For the NCE-CPFC examination, ChatGPT-4.0, Ali Tongyi Qianwen, Baidu ERNIE Bot, Google Bard, MedGPT, and ChatGPT-3.5 successfully passed, whereas LlaMA2-7B, HuatuoGPT, Chinese LLaMA2-7B, and LlaMA-7B failed. ChatGPT-4.0 (84.82%) surpassed all PCPs and assisted most PCPs in the NCE-CPDC examination (improving by 1 %–6.13%). In summary, LLMs demonstrated outstanding competence for diabetes-related questions in both the Chinese and English language, and hold great potential to assist future diabetes training for physicians globally.This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0509202 and 2023ZD0509201), National Natural Science Foundation of China (62077037,8238810007, 82022012, 81870598, 62272298 and 82388101), the National Key Research and Development Program of China (2022YFC2502800 and 2022YFC2407000), the Shanghai Municipal Key Clinical Specialty, Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002), the Chinese Academy of Engineering (2022-XY-08), the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212700) and Beijing Natural Science Foundation (IS23096)
Ab externo open conjunctiva XEN® 63 μm: a novel surgical alternative in uveitic glaucoma-a case report
Full text linkDecompression retinopathy; Minimally invasive glaucoma surgery; Uveitic glaucomaRetinopatía por descompresión; Cirugía de glaucoma mínimamente invasiva; Glaucoma uveíticoRetinopatia per descompressió; Cirurgia de glaucoma mínimament invasiva; Glaucoma uveíticPurpose
To describe the efficacy and safety of the ab externo open-conjunctiva XEN® 63 μm gel stent in uveitic glaucoma.
Case presentation
A case report of a 15-year-old patient with bilateral uncontrolled uveitic glaucoma secondary to chronic anterior uveitis was presented. Several medical ophthalmological and rheumatological evaluation visits were conducted. Preoperative intraocular pressure was 28 mmHg in the right eye and 32 mmHg in the left eye. She underwent a trabeculectomy in her right eye developing hypotonic maculopathy and decompression retinopathy, requiring surgical revision. Considering the complications endured in the right eye, it was decided to perform an ab externo open-conjunctiva XEN® 63 μm implant in her left eye with no postoperative complications. Postoperative course was uneventful with well-controlled intraocular pressure (11 mmHg) and no progression of glaucomatous damage, one year after the procedure. Anterior segment optical coherence tomography evidenced a well-functioning and non-encapsulated bleb along the follow up. Eventually, there were no postoperative uveitic episodes, with 40 mg Adalimumab as a steroid-sparing agent.
Conclusion
Uveitic glaucoma presents both clinical and therapeutic challenges. Traditional surgery such as trabeculectomy may entail postoperative complications such as hypotonic maculopathy and decompression retinopathy. This is the first case reporting the efficacy and safety of ab externo open-conjunctiva XEN® 63 μm implant in uveitic glaucoma, highlighting its potential usefulness in such clinical scenarios