Risultati per: Approccio farmacologico al trattamento della stipsi indotta da oppioidi: focus su naldemedina

Objectives
Effective, real-time surveillance of dengue may provide early warning of outbreaks and support targeted disease-control intervention but requires widespread accurate diagnosis and timely case reporting. Research directing innovation in diagnostics for dengue surveillance is lacking. This study aimed to describe experience and requirements of relevant prospective users.

Design
A qualitative, focus group study was conducted.

Participants
Data were collected from 19 users of diagnostic technology who work across the Thai dengue surveillance system.

Data collection and analysis
Contextual knowledge, experience and needs were explored in focus groups. Discussions were translated, transcribed, analysed thematically and mapped to Consolidated Framework for Implementation Research domains.

Results
Participants expressed a need for rapid, accurate, serotype-specific tests which can be operated easily by non-expert users without laboratory equipment. They supported integration of diagnostics with surveillance systems and felt this would increase the quantity and speed of case reporting as well as provide healthcare professionals with up-to-date information about the number of cases locally, thereby aiding interpretation of test results. Concerns included those relating to data security and the cost of tests.

Conclusions
Engagement to understand prospective user experience and requirements can improve relevance and uptake of new technology, leading to system efficiencies. The present study highlights specific needs for accurate, serotype-specific, remote-connected diagnostics which are integrated with surveillance systems and support dengue case reporting at the point-of-care.

A Trieste 22/23 novembre. Confronto di esperienze sui progressi

A Trieste 22/23 novembre. Confronto di esperienze sui progressi

Circulation, Volume 150, Issue Suppl_1, Page A4138639-A4138639, November 12, 2024. Background:The anti-phagocytic molecule CD47 is upregulated in the atherosclerotic plaques of patients with cerebrovascular disease; however, the molecular mechanisms responsible for the development and progression of atherosclerotic lesions have not been fully established. In this study, we postulate how endothelial-specific CD47 promotes endothelial-to-mesenchymal transition (EndoMT) in potentiating atherosclerosis and assess the efficacy of the development of novel therapeutic interventions for cardiovascular disease.Methods:Using single-cell RNA sequencing (scRNA-seq), combined with molecular, cellular, and biochemical analyses, we investigated the role of endothelial CD47 in stimulating EndoMT using knock-out in ApoE-/- atherosclerotic mouse models.Results:ScRNA-seq revealed that CD47 promotes EndoMT, and the loss of endothelial CD47 inhibits EndoMT marker expression as well as transforming growth factor-beta signalingin vitroand atherosclerotic mice, which is associated with smaller lesions inApoe-/-mouse model. In endothelial cells, CD47 hinders efferocytosis of senescent ECs and represses macrophage’s efferocytotic capacity to propel arterial inflammation and atherogenesis. Mechanistically, the interaction between CD47 and efferocytic receptor MerTK exacerbates inflammation by inhibiting the process of efferocytosis in endothelial cells and macrophages under atherogenic conditions. In response to atherogenic stimuli, endothelial CD47 upregulates the endocytic adaptor protein epsin, causing fibroblast growth factor receptor-1 (FGFR1) signal attenuation that upregulates TGF-β signaling and promoting EndoMT and potentiating atherosclerosis.Conclusion:We conclude that endothelial CD47 potentiates EndoMT during atherogenesis by increasing TGF-β signaling through FGFR1 internalization and degradation and targeted manipulating CD47 expression with precision nanomedicine offering a novel approach for mitigating cardiovascular disease.

Circulation, Volume 150, Issue Suppl_1, Page A4144724-A4144724, November 12, 2024. Background:Paucity of evidence is available on sex-differences in the progression, left ventricular (LV) remodelling and long-term outcome in patients with native mild-to-moderate aortic stenosis (AS) and preserved LV ejection fraction (LVEF).Objectives:To assess the sex-differences in the progression, LV remodelling and long-term outcome of native AS.Methods:Baseline and follow-up echocardiographic data of patients with at least mild-to-moderate AS [aortic valve area(AVA)≤1.5 cm2, maximum aortic velocity(Vmax) ≥2.5 m/s or mean gradient(MG)≥25 mmHg] were prospectively collected between 2014 and 2019 and retrospectively analysed. Patients with LVEFmild were excluded. AS progression (analysed by annualized progression ratios in echocardiographic parameters), all-cause death, aortic valve replacement (AVR), were investigated stratifying for sex.Results:We included 677 patients with a mean age of 70.8±13.2 years, 258 (38.1%) women. During a median 5 years follow-up, 118(17.4%) deaths and 211(32.2%) AVR occurred. After inverse-propensity-weighting (IPW), men had faster progression rate of AS compared to women (MG: mean difference 1.77[1.10-2.43] mmHg/year, p

Objective
The collection of comprehensive data from post-authorisation trials for conditionally authorised anticancer medicines is frequently delayed. This raises questions about the feasibility of post-authorisation randomised controlled trials (RCTs) that aim to address remaining uncertainties. Therefore, this study explored factors that facilitate or impede the feasibility of post-authorisation RCTs from the perspective of stakeholders directly involved in the design, medical-ethical approval, and conduct of these RCTs.

Design
We conducted four qualitative focus groups (FGs).

Setting
FG discussions focused on the oncology setting in European context.

Participants
Twenty-eight European patients, physicians, medical ethicists and pharmaceutical industry representatives participated in the FGs.

Intervention
Respondents were informed about the topic and the purpose of the FGs before and at the start of FG discussions. An FG script was used to guide the discussion, which was informed by 14 semi-structured interviews with various stakeholders.

Results
We identified factors with the potential to impact feasibility related to trial design, trial conduct, factors external to a trial and post-authorisation interaction with regulators. Factors that may be particularly relevant for the post-authorisation setting include the choice of relevant endpoints and the inclusion of a fair comparator (trial design), strategies to increase patients’ and physicians’ willingness to participate (trial conduct), and external factors relating to a medicine’s commercial availability, the presence of competing medicines and trials and the perceptions about clinical equipoise. Post-authorisation interaction with regulators about how to obtain comprehensive data was deemed necessary in cases where a post-authorisation RCT seems infeasible.

Conclusions
Based on the identified factors, our findings suggest that patient recruitment and retention could be assessed more in-depth during regulatory feasibility assessments at the time of granting conditional marketing authorisation and that sponsors and regulators should better inform patients and physicians about the remaining uncertainties for conditionally authorised medicines and the necessity for post-authorisation RCTs. By enhancing the evaluation of trial feasibility, timely completion of post-authorisation RCTs may be facilitated to resolve the remaining uncertainties within a reasonable timeframe.

Introduction
Clinical guidelines recommend the use of the kidney failure risk equation (KFRE) to guide the referral of individuals with chronic kidney disease (CKD) to secondary kidney care services. People living with CKD frequently experience multiple long-term conditions (multimorbidity) and/or frailty. This may impact patients’ or carers’ perceptions of kidney failure in the context of other health problems and associated risks and emphasises the need for shared decision-making. This paper presents the research protocol for the exploration of patients’ and healthcare professionals’ perspectives on kidney failure risk and the use of the KFRE in the MULTIPle lOng-term condItions aNd frailTy study. This study aims to investigate patient and healthcare professionals’ perspectives and expectations of the use of KFRE in individuals with CKD and multimorbidity and/or frailty, with a focus on shared decision-making.

Methods and analysis
Analysis of semistructured interviews with adults who have CKD and multimorbidity and/or frailty and focus groups with healthcare professionals (who are involved in caring for patients with CKD). Framework analysis, underpinned by normalisation process theory, will be used to develop codes and explore themes from the interviews and focus groups. Patient and public involvement has been pivotal to the study conceptualisation and will continue to be embedded throughout the study.

Ethics and dissemination
The study protocol has undergone peer review by the NHS Greater Glasgow and Clyde Research and Innovation team and has been granted ethical approval in August 2023 by the NHS Health Research Authority following a favourable opinion from the West of Scotland Research Ethics Committee (REC) 3 (IRAS ID: 325848, REC reference: 23WS/0119, Protocol number GN22RE559).
The results of the research will be disseminated through peer-reviewed publications and conferences, as well as to patient and public involvement groups who have been involved in the study and through knowledge exchange events.

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