Risultati per: Analisi sull’uso dei farmaci anti-osteoporotici in sette database europei

Stroke, Volume 56, Issue Suppl_1, Page ATP214-ATP214, February 1, 2025. Background:Amyloid-related Imaging Abnormalities (ARIA) are adverse effects that occur during amyloid beta monoclonal antibody treatment for Alzheimer’s disease, including edema-type ARIA and hemorrhage-type ARIA. Few retrospective analysis have compared ARIA-H incidence among individual monoclonal antibodies, and a comprehensive comparison is currently lacking. After the approval of these antibodies, research has mainly focused on dosing frequency and drug dosage, leaving it unclear whether ARIA-H is associated with the specific characteristics of different monoclonal antibodies.Methods:1. For monoclonal antibodies targeting Aβ clearance, we selected seven: Aducanumab, Bapineuzumab, Crenezumab, Donanemab, Gantenerumab, Lecanemab, and Solanezumab. Our data is derived from systematic reviews and meta-analyses of Phase III clinical trials for these seven monoclonal antibodies. Data from Jeremic D et al. include six monoclonal antibodies (mAbs), while data from Qiao Y et al. include four mAbs. 2. For the evaluation variables, we selected the following factors: the form of monoclonal antibody binding to Aβ protein, binding affinity, binding epitope, Fc subtype of the monoclonal antibody, and the Aβ clearance rate. ARIA-H occurrence was used as a categorical variable for differential analysis. The odds ratio (OR) was utilized for data assessment, with an OR not equal to 1 and a 95% confidence interval excluding 1 used as the criterion for statistical significance. 3. We standardized the data for the seven monoclonal antibodies (mAbs). We compared the ARIA-H occurrence rates for the mAbs, taking into account other dimensional variables.Results:The risk of ARIA-H, from highest to lowest, is as follows: Donanemab, Aducanumab, Bapineuzumab, Lecanemab, Gantenerumab, Crenezumab, Solanezumab. Besides, ARIA-H is associated with the characteristics of mAb. (1)More mature Aβ clearance is associated with a higher risk of ARIA-H.(2)Lower clearance of Aβ oligomers is associated with a higher risk of ARIA-H.(3)Aβ clearance closer to the N-terminus is associated with a higher risk of ARIA-H.(4)mAb with an IgG4 structure are more likely to cause ARIA-H than those with an IgG1 structure.(5)Faster achievement of Aβ clearance thresholds is associated with a higher risk of ARIA-H.Conclusion:This research enhances our understanding of ARIA-H and may guide future monoclonal antibody drug development, which may improve the cognition and overall prognosis of Alzheimer’s disease patients.

Stroke, Volume 56, Issue Suppl_1, Page ATP273-ATP273, February 1, 2025. Introduction:Patients suffering from transient ischemic attack (TIA) are at high risk of ischemic stroke (IS). This study describes clinical characteristics and outcomes in patients with a first non-cardioembolic TIA.Methods:Using two US administrative claims databases (MarketScan and Optum’s de-identified Clinformatics® Data Mart Database [CDM]) converted to the Observational Medical Outcomes Partnership (OMOP) common data model, we conducted an observational, retrospective cohort study of adults with a first diagnosis of non-cardioembolic TIA between 2012 and 2022. Demographic and clinical characteristics were described at baseline, and incidence rates of IS, intracranial bleeding, and bleeding leading to hospitalization with sensitivity analyses at different time points were calculated.Results:Overall, 203,757 patients were included in the study, 97,481 from MarketScan, 106,276 from CDM. Mean age was 62 years in MarketScan and 72 years in CDM. Patients were mostly women (57.6% in MarketScan, 59.3% in CDM). At baseline, prevalence of comorbidities was high (hypertension 66% and 84%, hyperlipidemia 53% and 75%, coronary artery disease 18% and 31%, diabetes 25% and 38% in MarketScan and CDM, respectively). Median follow-up time was 569 days in MarketScan and 716 days in CDM. At 1 year follow-up, incidence rates per 100 person-years of IS, intracranial bleeding, and bleeding leading to hospitalization were 10.9, 0.9, and 4.2, respectively, in MarketScan and 20.2, 1.6, and 7.6 respectively, in CDM. Sensitivity analyses showed that most IS events occurred within 7 days of the index event. Additional event rates and sensitivity analyses are shown in Table 1.Conclusion:Results from two US claims databases show that the annual risk of IS is higher than expected following a first TIA diagnosis, especially when including the first 7 days in the ascertainment. Implementation of guideline directed antiplatelet therapies, or new antithrombotic strategies, is needed.

Stroke, Volume 56, Issue Suppl_1, Page ATP228-ATP228, February 1, 2025. Introduction:Cerebrovascular and cardiovascular diseases are major causes of global mortality, with significant impact in India. Clopidogrel, an antiplatelet prodrug, requires activation by CYP enzymes to inhibit platelet activation. Clopidogrel resistance, affecting 4-30% of patients, is often due to CYP2C19 gene variations, among other factors. This study explores genetic variants associated with clopidogrel resistance to improve personalized therapy for thrombotic conditions.Objective:To evaluate the relationship between CYP2C19 polymorphisms and recurrent thrombotic events in patients treated with clopidogrel for coronary artery disease and stroke.Methods:An ambispective observational study at a tertiary hospital over six months included 114 adults on clopidogrel for various ischemic conditions. Exclusion criteria were pregnancy, lactation, intracerebral hemorrhage, atrial fibrillation, left ventricular clot, and cardioembolic stroke. Data were collected from medical records. CYP2C192 and CYP2C193 polymorphisms were analyzed using PCR and gel electrophoresis. Statistical analysis was conducted with chi-square tests in IBM SPSS version 20.0 (p

Stroke, Volume 56, Issue Suppl_1, Page ATP281-ATP281, February 1, 2025. Introduction:We assess the risk of stroke in individuals with and without a migraine diagnosis, adjusting for demographic variables and stroke risk factors using participant information from the All of Us database.Method:Diagnoses of migraine, stroke and comorbidities were identified using ICD9 and ICD10 codes. A multivariable logistic regression analysis was performed to assess the association between migraine and risk of stroke adjusting for comorbidities including hypertension, atrial fibrillation, hyperlipidemia, diabetes, tobacco use, depression and demographics (age, sex at birth, race and ethnicity). To compare the prevalence of stroke between individuals with and without migraine, odds ratios using a 95% confidence interval (CI) were calculated.Results:Within theAll of Usdatabase, 31,444 individuals received a migraine diagnosis (female=25,374/81%, male=5,391/17%, other=679/2%; mean (std) age=54.9 (15.6)) and 379,283 did not have a migraine diagnosis (female=222,104/59%, male=149,182/39%, other=7,997/2%; mean (SD) age=55.9 (17.2)), see Figure 1 for detailed demographics.The migraine cohort had a greater proportion of women (81% vs 59%, p

Si è riunito il 29 gennaio per la prima seduta del 2025

Esperti, ‘da depressione ad Alzheimer si studiano nuovi usi”

Objectives
This study aims to report the trends in the certification of both sight impairment (SI) and severe sight impairment (SSI) in England and Wales during the period of 2010 to 2020, prior to the COVID-19 pandemic. The focus is on diabetic retinopathy/maculopathy as the key causative factor.

Design
Retrospective database analysis.

Setting
England and Wales.

Participants
Individuals certified as SI or SSI.

Outcome measures
Trends in certification of vision impairment in England and Wales due to any cause, with specific attention to diabetic retinopathy.

Methods
Certifications of vision impairment made by ophthalmologists in England and Wales were recorded and copies were sent to Moorfields Eye Hospital for epidemiological analysis. All certificates completed in England and Wales over an 11-year period, from April 2009 to March 2020, were queried and analysed on an annual basis. This analysis included all causes, and where both the main cause was diabetic eye disease or where diabetic eye disease was a contributory cause among multiple pathologies. Poisson regression was employed to analyse changes in trends over time for certifications of vision impairment.

Results
In England, from 2010 to 2020, there was a small but significant reduction (p

Rallenta la ricerca sui farmaci in Italia che con le sperimentazioni cliniche – passate nel 2023 a 611 dalle 663 dell’anno prima (-7,8%) – muove ogni anno 700-800 milioni di…

Nistico’, sistema italiano tiene ma -7,8% trial,1 su 3 oncologico

Background
Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.

Objective
We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.

Design
Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.

Results
Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.

Conclusion
Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.

Fujifilm Diosynth Biotechnologies costruirà i nuovi impianti nel sito danese di Hillerød in grado di produrre una maxi coltura di cellule per le terapie

Objective
This study planned to analyse the association between ondansetron use within 24 hours before intensive care unit (ICU) admission to within 48 hours after ICU admission and the risk of sepsis in ICU patients.

Design
A cohort study.

Setting and participants
Data of 65 366 participants in Medical Information Mart for Intensive Care IV from ICU in the Beth Israel Deaconess Medical Center.

Primary and secondary outcome measures
Sepsis was the primary outcome, which indicated patients with documented or suspected infection and acute change in total Sequential Organ Failure Assessment (SOFA) score ≥2 points. In-hospital mortality was the secondary outcome.

Results
There were 6737 patients with early ondansetron use. In total, 1646 patients suffered sepsis. According to the data from multivariate cox regression model, compared with participants without early ondansetron use, the risk of sepsis was reduced in participants with early ondansetron use relative to those without HR (HR=0.84, 95% CI: 0.76 to 0.93). The risk of in-hospital mortality was reduced in those with early ondansetron use (HR=0.63, 95% CI: 0.55 to 0.72). Subgroup analysis revealed that the association between early ondansetron use and decreased risk of sepsis was significant in participants aged

Multilingue, chiarirà dubbi e timori assunzione medicinali

This case series examines treatment with anti–programmed cell death 1 (PD1) immunotherapy for patients with basal cell nevus syndrome.

Objective
Heart rate serves as a critical prognostic factor in heart failure (HF) patients. We hypothesise that elevated heart rate in critically ill HF patients on discharge from the intensive care unit (ICU) could be linked to adverse outcomes.

Design
A single-centre retrospective cohort study.

Setting
This study used data collected between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (V.2.0) Database.

Participants
From the 76 943 ICU stays, we enrolled 2365 patients in this study.

Primary and secondary outcome measures
We observed correlations between in-hospital mortality and ICU discharge heart rate of 83.56±15.81 beats per minute (bpm) (survivors) vs 93.84±17.28 bpm (non-survivors, p