Risultati per: Approccio pre-rete e Cure Palliative di base

The remarkable success of direct-acting antivirals in curing hepatitis C led to concerted efforts in developing a cure for hepatitis B. Unlike hepatitis C, it is accepted that a sterilising cure is not feasible in the foreseeable future. Instead, functional cure defined as hepatitis B surface antigen (HBsAg) loss (below detection) and HBV DNA suppression (below quantification) sustained for at least 24 weeks after completion of treatment has been embraced.1 Nucleos(t)ide analogues (NA) currently in use, entecavir and tenofovir, are highly effective in maintaining suppression of HBV DNA replication and yields substantial clinical benefits including reduced rates of cirrhosis and hepatocellular carcinoma, but HBsAg loss remains elusive. Yet, if a functional cure is achieved, the benefits are multiple, with further reductions in the risk for liver-related outcomes,2 elimination of the need for long-term monitoring and NA treatment and addressing the stigma associated with HBsAg-positivity. Strategies…

Vincitori programma Gianni Bonadonna 2024. All’estero per 1 anno

Per circa il 60% degli studenti delle scuole superiori di Milano che hanno partecipato all’incontro ‘Dal Laboratorio alla vita’

Objective
The primary study aims were to evaluate the implementation, mechanisms and context of a timely short-term specialised palliative care intervention for older people with frailty (Frailty+ intervention) as well as to assess the feasibility of a randomised controlled trial to evaluate Frailty+. Our secondary aim was to describe any preliminary effects of Frailty+.

Design
Pilot randomised controlled trial with process evaluation.

Setting/Participants
We aimed to recruit 50 adults (≥70 years) with Clinical Frailty Scale score 5–7, and complex care needs and their main family carer, if available, from two Belgian hospitals on discharge.

Interventions
Patients were randomised to the Frailty+ intervention alongside standard care or standard care alone.

Outcome measures
Implementation and trial feasibility were assessed through interviews, focus groups and quantitative data. The primary outcome to be used in a potential full-scale trial if the study is feasible and implementable was mean change in five palliative care symptoms over 8 weeks.

Results
We enrolled 37 patients (19 intervention, 18 control) and 26 family carers (15 intervention, 11 control). Patients and family carers valued the home visits from palliative care nurses, and nurses saw value in Frailty+. But most patients received only one visit over 8 weeks, and nurses did not organise foreseen multidisciplinary meetings, referring to absence of urgent needs. Many aspects of the trial methods were feasible, but recruitment was challenging. The baseline mean score on the five palliative care symptoms was 6.0 and 5.6 in intervention and control group, respectively; and 4.5 and 4.1 at 8 weeks (adjusted ratio 1.0, ie, no effects on symptoms).

Conclusions
While Frailty+ was generally welcomed by older people with frailty, families and palliative care nurses, our process evaluation uncovered multiple barriers, mostly rooted in the current organisation of specialised palliative care that is tailored to advanced stages of illness. Ensuring timely access requires efforts beyond timely referral alone, and implies profound organisational and cultural change.

Trial registration number
ISRCTN39282347.

Introduction
Pre-eclampsia is a condition associated with significant maternal and neonatal morbidity and mortality. The prediction of pre-eclampsia in high-risk populations using angiogenic markers, such as serum placental growth factor (PlGF) assessment, has been shown to improve maternal outcomes and is recommended by the National Institute for Health and Care Excellence (NICE). However, such tests are not yet available at the point of care (POC). Glycosylated fibronectin (GlyFn) level for the prediction of pre-eclampsia development is available as a POC test (Lumella) and has the potential to aid rapid clinical decision making. This study aimed to test the hypothesis that the sensitivity of the GlyFn test is not inferior to that of the current gold standard of soluble fms-like tyrosine kinase (sFlt)/PlGF-based laboratory testing for pre-eclampsia.

Methods and analysis
This is a multicentre prospective study. Women at risk for pre-eclampsia based on predefined clinical and/or obstetric risk factors will be invited to participate in the study. The recruitment target is 400 participants. Consenting participants will have paired samples for sFlt/PlGF together with POC GlyFn testing. Two follow-up visits are planned at 2 and 4 weeks after the initial recruitment where repeat testing with both tests will be performed. The clinical team will be blinded to the results of the GlyFn test but not that of the sFlt/PlGF test. Clinical care will be based on established protocols incorporating maternal/fetal evaluation and the results of sFlt/PlGF levels. Maternal and neonatal outcome data will be collected to compare the sensitivity and specificity of the tests, with the primary outcome being delivery for pre-eclampsia within 4 weeks.

Ethics and dissemination
Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales Ethics Committee. The results of this study will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number
ISRCTN13430018

Introduction
As one means to avoid waste in research investment, involving patients as full partners in research has become increasingly frequent. There is clearly a low level of investment in palliative care research. Following the guidance from the James Lind Alliance and the UK public consultation (‘Palliative and End of Life Care Research Priorities Project’), we developed a 3-step protocol aimed at prioritising 10 unanswered questions in palliative care (PC) research in France, from the viewpoint of patients, volunteers, healthcare professionals and family caregivers.

Methods and analysis
To identify unanswered questions in PC (stage 1), an unstructured questionnaire will be used. This questionnaire will be tested on patients and healthcare professionals and modified, if necessary, before being made available online for a period of 6 months. A multidisciplinary steering committee including board-certified PC physicians, methodologists, nurses, a sociologist, an anthropologist and an information specialist will analyse the data collected in order to delete duplicate questions, do a thematic and population classification of the responses, modify questions using the PICO (patient problem, intervention, comparison and outcome) format and perform a literature review on each question to identify any relevant systematic review.

Ethics and dissemination
We expect the results to have wide-ranging benefits, for example, by prompting investment in the 10 prioritised research questions. There are also potential benefits for patients and caregivers, by including them as partners in future research. Regarding the current bill being examined by the government planning to legalise euthanasia and assisted suicide in France, this study will provide new insights into how patients and caregivers are prioritising those themes. The major benefit of this study is to involve patients and family caregivers as partners in PC research. They will be consulted and their choices will be valuable resources and may prompt researchers to focus on different topics. In view of the limited funding available, PC research needs to prioritise major issues and raise its visibility.
The second stage of the study is the first-round prioritisation using a fixed format questionnaire, which will last 4 months. The third stage will consist of reaching a consensus regarding the top 10 unanswered questions in PC research, using the nominal group technique. A secondary objective during this third step is to study the reasons for the prioritisation.

The intensive care unit (ICU) may be the hospital’s unrecognized epicenter for people with palliative care needs. Several existing clinical trials have tested palliative care interventions for critically ill patients and their families. These trials aimed to improve communication about goals of care, support complex decision-making, and enhance palliative care involvement. Collectively, the results of these trials were variable and largely disappointing.

This randomized clinical trial evaluates the effect of a collaborative palliative care intervention compared to usual care among family members of patients in the intensive care unit.

Stroke, Volume 56, Issue Suppl_1, Page AWP187-AWP187, February 1, 2025. Introduction:3 to 5% of patients undergoing endovascular thrombectomy present impossible catheter access to the occlusion site from transfemoral access (TFA), largely attributed to complex arterial anatomy. Radial access can be an effective bailout strategy, but intraprocedural delays may negatively impact outcomes. Novel image processing algorithms allow for advanced characterization of vascular pathways from baseline neuroimaging, enabling the exploration of predictive models of impossible TFA before arterial puncture.Methods:A retrospective cohort of patients with an anterior large vessel occlusion who received thrombectomy from TFA between 2017 and 2023 were included in this study. A previously described automatic vascular analysis software was used to generate centerline graphs from the aorta to the intracranial occlusion site from baseline CTA. ArterialGNet, a graph neural network based on graph attention designed to integrate descriptors of centerline pathways extracted at three different distance scales, was trained for impossible TFA prediction. Five-fold cross validation was used for model derivation. The method was compared to a previously introduced random forest ensemble model with extreme gradient boosting (XGBRF) based on six vascular tortuosity descriptors of the aortic and supra-aortic regions.Results:A total of 745 patients (aged 78 years IQR 68-85, 56% women) were included in this study. Patients treated between 2017 to 2022 (n=568, 3.2% with impossible TFA) were used for model training and validation. Patients treated in 2023 (n=177, 3.4% with impossible TFA) were held out for testing. In validation, the best-performing configuration of ArterialGNet achieved a C-statistic of 0.82 (95%CI 0.74-0.90), similar to the baseline model (0.82, 95%CI 0.77-0.88). Comparable outcomes were observed in the final testing for ArterialGNet (0.84, 95%CI: 0.82–0.86). In contrast, the XGBRF model exhibited signs of overfitting (0.65, 95% CI: 0.53–0.78). In final testing, ArterialGNet predicted impossible TFA with a sensitivity of 0.80 (95%CI 0.66-0.94) and a specificity of 0.84 (95%CI 0.76-0.91). Median processing time for ArterialGNet was below 4 min.Conclusions:A novel model for impossible TFA prediction was validated with a large dataset. Impossible TFA prediction before arterial puncture may assist in decision support for initial access selection in thrombectomy, reducing intraprocedural delays and potentially improving clinical outcomes.

Stroke, Volume 56, Issue Suppl_1, Page ATMP76-ATMP76, February 1, 2025. Background and Purpose:In randomized trials, carotid artery stent (CAS) may have higher risk of periprocedural risk compared with carotid endarterectomy (CEA) if performed within the first 7 days after the onset of symptoms.Methods:We analyzed the data from Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). The time interval between the most recent qualifying ischemic event and CAS/CEA procedure was divided in four strata: 1-7 days, 8-14 days, 15-30 days and >30 days. We analyzed the effect of time interval strata between most recent qualifying ischemic event and procedure and procedure type (CEA versus CAS) on peri-procedural stroke and/or death after adjusting for age, gender, symptomatic status and initial severity of stenosis (≥70% versus 30 days (CAS 7.8% versus CAE 4.3%, p=0.12), after the most recent qualifying event. In the multivariate analysis, patients who underwent CAS had higher rate of peri-procedural stroke and/or death (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.25- 4.66) but timing of procedure were not associated with higher rate of peri-procedural stroke and/or death after adjustment for potential confounders. The interaction between procedure type and timing of procedure was not significant. The rate of peri-procedural stroke and/or death was significantly higher in CAS patients who received clopidogrel bolus (without 48-hour maintenance dose) among patients treated 7 days or less after the qualifying event compared with those undergoing CEA (6.6% versus 0%, p=0.012) but was not different between CAS patients who received 48 hours of clopidogrel maintenance and those undergoing CEA (0% versus 0%).Conclusions:The higher rate of peri-procedural stroke and/or death seen with CAS (compared with CEA) within the first 7 days may be attributed to factors such as inadequate pre-procedure antiplatelet medication use. The results of CAS and CEA may become comparable within the first 7 days after the qualifying ischemic event with use of newer generation P2Y12 platelet inhibitors that achieve rapid antiplatelet inhibition.

Stroke, Volume 56, Issue Suppl_1, Page ATMP115-ATMP115, February 1, 2025. Background/Aims:The Stroke Preclinical Assessment Network (SPAN) is a randomized, placebo-controlled, blinded, multi-laboratory preclinical study using a Multi-Arm Multi-Stage statistical design to select one or more putative stroke treatments with an implied high likelihood of success in future human clinical stroke trials.Methods:Through a rigorous NIH-managed peer review process, six independent research laboratories were selected for testing five promising cerebrovascular interventions. A Coordinating Center at the University of Southern California leads the trial. The Interventions, also selected through an NIH peer review process, included NanO2 (NuvOx) an oxygen delivery emulsion, tatCN19o (Neurexis) a CaM-kinase II inhibitor, GSK2256098 (GlaxoSmithKline/ETSU) a focal adhesion kinase inhibitor, GSK2256294 (GlaxoSmithKline/OHSU) a soluble epoxide hydrolase inhibitor, and BPN-27332 (Loxagen/MGH) a lipoxygenase inhibitor. After a pilot trial to evaluate several behavioral measures, we designated the primary endpoint for SPAN 2 to be a multi-item functional test battery, the Simplified SPAN Score. All other procedures, including behavior tests and magnetic resonance imaging were performed as they were in SPAN 1. Per the SPAN 2 pre-specified protocol, an interim analysis was performed after Stage 1, aka, SPAN 2.1.Results:SPAN 2.1 enrolled 774 subjects, divided among 4 animal co-morbid models in whom a transient filament MCAo was performed: young healthy mice (n=193), diet-induced obese mice (n=197), aged mice (n=192), and spontaneously hypertensive rats (192). Nine subjects were found ineligible, leaving an ITT population of 765, of whom 13 were dropped during the stroke procedure—the primary analysis population (mITT) included 751 subjects. Protocol compliance was evaluated: over 99% of subjects received the correct assigned intervention, but dose timing was protocol adherent in only 61%. Animals who did not receive all assigned doses (n=100) were excluded, leaving a Full Treatment population of 651. Mortality after treatment included 158 subjects, 21% of the mITT group. Among the animal comorbid models, mortality was greatest (40%) in aged mice.Conclusions:The feasibility and protocol compliance seen in SPAN 1 have been replicated in stage 1 of the second trial, SPAN 2.1. Mortality resembles previous experience, with an improved survival in aged mice. SPAN 2 has advanced to Stage 2 where improved dose timing is implemented.

Stroke, Volume 56, Issue Suppl_1, Page ATMP102-ATMP102, February 1, 2025. Background:Atrial Fibrillation (AF) occurs in about one-fourth of patients with Embolic Stroke of Undetermined Source (ESUS). Accurate prediction of post-stroke AF upon discharge from an index stroke admission informs a personalized post-stroke monitoring strategy of AF and interventions. While clinical risk scores predict AF, machine learning (ML) models have shown superior performance.However, traditional ML approaches only use expert-derived predictors available in an electronic health record (EHR) and thus may miss variables that would potentially increase the accuracy of prediction.Aims:This study aims to enhance AF prediction by augmenting expert-derived predictors with an unbiased selection of full diagnostic codes and medication histories up to index strokes. Through embedding learning with hypergraph neural networks, we generate compact representations of high-dimensional data to improve prediction accuracy by capturing complex feature interactions.Methods:We analyzed data from 510 ESUS patients (55.3% female, mean age 61.4 years) from 2015 to 2023 at Emory Healthcare. We focus on experiments using a logistic regression (LR) model to predict AF from different sets of features. At baseline, we use 58 clinically motivated predictors, including comorbidities characterized by 17 ICD codes manually extracted based on literature, and 41 other features extracted from lab results, echocardiographic and ECG. To directly model the full history of comorbidities and medications, another baseline uses the full 1530 ICD codes plus the 41 other features (1571 in total). In contrast, the embedding method uses the full 1530 ICD codes to generate condensed, informative embedding vectors (32-dimensional), eventually getting 32+41=73 features. To generate the embedding, a hypergraph neural network was trained on a larger stroke cohort (n=7956) to model the interactions between the 1530 ICD codes. A nested cross-validation approach was employed within 5-fold splits, and ROC-AUC scores were recorded.Result:Among 510 ESUS patients, 107 (21.0%) developed AF (mean age 67.9 years, 57% female). We compared the performance of LR model with different features from ICD codes (Table 1). The results show that the learned 32-dim embedding vectors improves the prediction of post-ESUS AF.Conclusion:The embedding technique can significantly enhance predictive performance by integrating comprehensive medical information, maximizing the use of available data for improved outcomes.

Stroke, Volume 56, Issue Suppl_1, Page AWMP53-AWMP53, February 1, 2025. Background:Treatment options and outcomes in stroke also depends on pre-hospital delays. The goal of this study is to describe onset-to-door times (ODT) across many countries and also investigate how the mode of arrival affects ODT.Methods:This is an analysis of the data from the Registry of Stroke Care Quality (RES-Q), years 2022&2023. RES-Q is used across the world for audit of clinical care. Data were stratified by the mode of arrival (EMS vs. non-EMS). Median ODT were analyzed, and 95% confidence intervals (CI) were calculated for each country and arrival mode.Results:Of 334,184 patients from 1,130 hospitals in 70 countries, 155,532 patients from 25 countries were diagnosed with acute ischemic stroke after excluding secondary transfers (n=32,349), cases from countries with fewer than 1,000 cases (n=128,660), and those with missing data or typing errors (n=17,643). The median ODT was 193 mins (95% CI: 164-223) for patients arriving by EMS and 309 mins (95% CI: 274-360) for those arriving by non-EMS. The percentage of EMS arrival by region was 34% (Africa), 30% (Asia), 39% (Latin America), and 87% (Europe). The percentage of EMS arrivals is shown in Figure 1. Compared to the patients who reached by non-EMS mode, patients who reached by EMS mode were more likely to receive intravenous thrombolysis (16% vs 44%,). The ODTs by mode of arrival and country are detailed in Figure 2.Conclusions:Transport via EMS was associated with a reduced arrival time nearly by 2 hours and tripled the chance of receiving thrombolysis as compared to non-EMS transportation. The percentage of patients arriving by EMS was higher in European countries as compared to Africa, Asia and Latin America and this is reflected by shorter ODT in many EU countries. Improvements in EMS infrastructure could improve stroke outcomes globally.

Stroke, Volume 56, Issue Suppl_1, Page AWMP54-AWMP54, February 1, 2025. Background and Objectives:Transportation to comprehensive stroke centers (CSCs) from primary stroke centers (PSCs) is key to achieving fast reperfusion in endovascular treatment (EVT)-eligible patients. We aimed to evaluate outcomes and workflow times of patients treated PSCs vs CSCs and additional key metrics for those transported from PSCs to CSCs for EVT.Methods:We performed a pre-specified analysis of the Alteplase compared to Tenecteplase (AcT) multicenter, randomized, controlled, trial in patients with acute ischemic stroke within 4.5 hours of onset. We compared baseline characteristics, workflow times, and clinical outcomes at 90 days between PSCs and CSCs. Mixed effects regression analyses were performed adjusting for age, sex, National Institute of Health Stroke Scale (NIHSS), location of intracranial occlusion, IVT drug and door-to-needle-time as fixed effects; and study site as a random effect.Results:Of 1,577 patients enrolled in the trial, 99 (6.27%) were treated in PSCs while 1,478 (93.72%) were treated in CSCs. Patients in both groups had similar age (median 72 [64 – 82] vs 74 [63 – 83] years), proportion of females (42.42% vs 48.24%), baseline stroke severity (median NIHSS 9 [6 – 16] vs 10 [6 – 16.5]), presence of large vessel occlusion (24.24% vs 24.70%; p=0.919) and EVT utilization (24.24% vs 32.61%). Patients treated in PSCs had longer onset-to-needle (median, 139 [100 – 190] vs 128 [94 – 185] minutes) and door-to-needle times (median, 56.5 [42 – 70] vs 35 [27 – 47] minutes) compared to those treated at CSCs. For patients transferred from PSCs to CSCs, patients who received tenecteplase had shorter needle-to-puncture times than those who received alteplase (median, 35.5 [21 – 58] vs 52 [18 – 74] minutes, p

Stroke, Volume 56, Issue Suppl_1, Page AWMP76-AWMP76, February 1, 2025. Importance:The COVID-19 pandemic significantly disrupted healthcare systems worldwide, impacting the management of acute ischemic stroke (AIS). Understanding changes in AIS admissions, treatment patterns&outcomes during the pandemic is essential for optimizing stroke care in future public health crises.Objective:To evaluate the impact of the COVID-19 pandemic on AIS admissions, treatment utilization, complications&outcomes in the U.S. from 2016 to 2021, focusing on the pre-pandemic (2016-2019)&peri-pandemic (2020-2021) periods.Methods:A retrospective observational cohort study utilizing the National Inpatient Sample (NIS) nationwide database, analyzing weighted hospital discharge records over 6 years, encompassing urban, rural, teaching &non-teaching hospitals.Participants were AIS patients aged 18 years&older (n=3,154,154), identified using ICD-10 codes. Sociodemographic characteristics such as age, sex, race&comorbidities were evaluated. The mean patient age was 70.0 ± 0.03 years, with an average length of stay of 5.1 ± 0.01 days&an adjusted mean cost of $16,765 ± 71. Men accounted for 50.5% of the cohort. AIS hospitalizations from 2016 to 2021 were collected, comparing pre-&peri-pandemic periods. Primary outcomes included AIS admission trends, while secondary outcomes included reperfusion therapy utilization, intubation&ventilation rates, discharge disposition&complications.Results:AIS admissions increased from 507,920 in 2016 to 535,694 in 2021. A demographic shift was observed, with the proportion of male patients rising from 49.8% to 51.4%&the mean age decreasing from 70.3 to 69.7 years (p < 0.0001). Most patients were White (69.5% in 2016), but their proportion decreased over time, while Black, Hispanic&Asian/Pacific Islander cases increased (p 0.5734). Reperfusion therapy usage increased, with mechanical thrombectomy (MT) rising from 2.2% to 5.6% in 6 years. Intubation/ventilation rates grew from 4.8% pre-COVID to 5.5% peri-COVID (p < 0.0001). Subarachnoid&intracerebral hemorrhage rates had increased throughout the 6 years in the group with MT-only intervention (p .011&.002, respectively).Conclusions:The COVID-19 pandemic led to significant shifts in AIS hospitalization patterns, including changes in age distribution, increased reperfusion therapy use&rising complications. These findings highlight the need for adaptive public health strategies&resource allocation to maintain stroke care during future crises.

Stroke, Volume 56, Issue Suppl_1, Page AWMP91-AWMP91, February 1, 2025. Background and Objective:Carotid artery stenting (CAS) is a procedure that has been established as a safe and effective alternative to carotid endarterectomy in high surgical risk patients. There are procedural questions that remain unanswered, specifically, the safety of pre-stent balloon angioplasty versus post-stent versus both. The objective of our study is to understand the risk and safety of these procedural techniques.Methods:Multicenter retrospective data related to angioplasty balloons, stents, complications due to pre and post-stent angioplasty along with the modified Rankin score (mRS) before and after the procedure were collected from January of 2015 until December of 2022. Statistical analysis was performed to correlate this data with risks of complications and clinical outcomes.Results:A total of 1355 patients were enrolled. We found that patients who underwent pre-stent angioplasty, or both (pre and post-stent angioplasty) had a higher risk of complications compared to those who only had post-stent angioplasty. There were more complications in patients who did not undergo post-stent angioplasty as compared to those who did undergo angioplasty (p=0.018, OR=0.513). Follow-up MRS at 30-90 days was higher if the balloons in both pre-stent angioplasty (p=0.016) and post-stent angioplasty (p=0.020) stent angioplasty were not inflated to nominal pressure. Follow up MRS was statistically higher (p=0.01) in patients with open-cell stents than closed-cell stents. Open-cell stents were more likely to undergo post-stent angioplasty (p