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

Circulation, Volume 150, Issue Suppl_1, Page A4147962-A4147962, November 12, 2024. Introduction:Heart transplants (HT) and left ventricular assist devices (LVADs) are treatment options for advanced heart failure refractory to standard therapy. Historically, LVADs have been used as either destination therapy or a bridge to transplant. However, recent changes to the organ allocation system have deprioritized patients on LVADs as transplant recipients, leading to divisive views on the role of an LVAD. We sought to describe outcomes with each modality, highlighting each option’s strengths and clinical utility.Aim:To assess costs related to index hospitalization, 30-day (30DRC) and 90-day (90DRC) readmission categories for both subgroups.Method:We analyzed the National Readmission Database (NRD) from January 1, 2018, to December 31, 2021, identifying patients with HT and LVAD via ICD-10-CM codes. We selected this recent time frame to limit the influence of older LVAD technology and heart allocation schemes. We excluded patients

Circulation, Volume 150, Issue Suppl_1, Page A4119262-A4119262, November 12, 2024. Background:Impediment in the excretion of lipid deposits within SMC-derived foam cells (SMC-FCs) is one of the reasons for the continuous expansion of the plaque necrotic core. This study aims to explore the effect and underlying mechanimsm of exosomes secreted by M2 macrophage (M2-exos) on SMC-FCs lipid metabolism and plaque stability.Methods:First, immunofluorescence was used to detect the expression levels of CD45 (a recognized differentially expressed molecule of myeloid and SMC-FCs) and the key proteins of cholesterol efflux pathway, ABCA1 and ABCG1, in human early and late plaques. Exosomes derived from M0 and M2 macrophages were purified by sucrose density gradient centrifugation, and characterized based on specific morphology and surface markers. Western blot, Oil red O staining and cell total cholesterol assay were used to assess the effects of M2-exos on the lipid mechanism of SMC-FCs. RNA-seq was used to detect the miRNA profiles of M2-exos. Quantitative real-time PCR was used to identify candidate miRNAs. The dual-luciferase reporting system was utilized to assess the regulatory effect of candidate miRNA on target gene. Then, the effect of M2-exos on the progression and stability of plaques in ApoE-/-mice was evaluated using Oil red O, H&E, Masson, Movat and immunohistochemistry.Results:Immunofluorescence revealed that compared with early plaques, VSMC-FCs (CD45-) were significantly increased in late plaques, and the expression levels of ABCG1 and ABCA1 were marked lower than those in macrophage-derived foam cells (CD45+). Purified M2-exos treatment significantly promoted the cholesterol efflux of SMC-FCs in vitro. In high-fat-fed ApoE-/-mice, M2-exos significantly reduced the VSMC-FCs, delayed the progression of plaques, decreased necrotic core area and enhanced plaque stability. MiRNA profiling and comprehensive analysis of signaling pathways showed that M2-exos were rich in miR-7683-3p, which played a key role in regulating SMC-FCs lipid metabolism through PPARγ-LXRα-ABCA1/ABCG1 pathway. Dual-luciferase reporting assay showed that miR-7683-3p can specifically bind to the promoter region of homeobox genes A1(HoxA1), an inhibitor of PPARγ-LXRα-ABCA1/ABCG1 pathway.Conclusion:M2-exos exerted an obvious atherosclerotic protective effect, and the underlying mechanism was closely related to MiR-7683-3p, which targeted the 3’UTR of HoxA1 mRNA and activated the PPARγ-LXRα-ABCA1/ABCG1 mediated cholesterol efflux in SMC-FCs.

Circulation, Volume 150, Issue Suppl_1, Page A4147456-A4147456, November 12, 2024. Background:Cardiac fibrosis is a condition characterized by deposition of extracellular matrix proteins and myofibroblasts, leading to scar formation, cardiac dysfunction and arrhythmogenesis. Various cardiometabolic stressors can promote fibrosis and scarring, including MI, hypertension, diabetes and obesity. Targeted therapy to prevent cardiac fibrosis is therefore an important unmet medical need. In a mouse model of obesity-related atrial fibrillation (AF), inhibition of SGK1 reduced markers of inflammation and fibrosis, suggesting SGK1 as a novel target. Several SGK1 inhibitors are being evaluated in clinical studies for the treatment of long QT syndrome, paroxysmal AF, and heart failure.Hypothesis:SGK1 activation is a significant driver of inflammation and fibrosis, and its inhibition may offer a new therapeutic strategy for treating fibrotic diseases, including those of the cardiovascular system.Methods:Primary hepatic stellate cells, lung fibroblasts, and proximal tubule cells were treated with TGFβ for 24-48 hours to induce fibrosis and measure the effects of SGK1 inhibition on markers of fibrosis (alpha SMA and collagen 1). Three, selective and potent, SGK1 inhibitors (SGK1-I 1,2,3) were tested in a BioMAP fibrosis panel at concentrations ranging from 0.3 to 10 µM. The fibrosis panel includes three systems that model TGFβ and TNFα driven myofibroblast differentiation during chronic inflammation and wound healing. Markers of fibrosis, tissue remodeling, myofibroblast activation, and inflammation were measured quantitatively. IC50s were determined using GraphPad Prism.Results:In primary human stellate cells, SGK1-I,1,2,3 inhibited αSMA and collagen 1 mRNAs with IC50s ranging from 0.1- 0.8 µM and 1.0-3.0 µM, respectively. In primary lung fibroblasts, treatment with SGK1-I reduced the mRNA and protein expression of αSMA. Treatment of cells from different tissues with TGFβ resulted in a 1.5-to-3.0-fold increase in SGK1 mRNA and protein and this was blocked by the TGFβ receptor inhibitor SB525334. SGK1 inhibitors displayed anti-inflammatory and anti-fibrotic properties in the BioMAP panel, with inhibition of IL-6, IL-8, MCP-1, and αSMA, collagen 1, and TIMP1 respectively.Conclusion:SGK1 is an important effector of TGFβ signaling. The development of SGK1 inhibitors may represent a new therapeutic strategy for treating fibrotic diseases. Additional studies are warranted to further evaluate novel SGK1 inhibitors in cardiac fibrosis

Riccardi: ‘Maggiore efficienza, sicurezza e tempi più rapidi’

Riccardi: ‘Maggiore efficienza, sicurezza e tempi più rapidi’

Purpose
To study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary care since 2020. This cohort provides valuable data for researchers and policy-makers focused on diabetes management and public health strategies.

Participants
Diabetes was defined as having inpatient or outpatient encounters with a diagnosis of diabetes International Classification of Diseases-9/10 codes, any use of insulin or oral hypoglycaemic drugs, or one encounter with haemoglobin A1C >4.8 mmol/mol or 6.5%. Patients with diabetes have been continuously enrolled on hospitals and primary care in Nanjing since 2020. Demographic, medications and comorbidities data were extracted from clinical notes, diagnostic codes, labs, prescriptions and vital signs among different types of diabetes.

Findings to date
The NDC consisted of 1 033 904 patients from 1 January 2020 to 31 December 2022, the majority were male (50.62%) and from the Gulou district (30.79%). The clinical characteristics and medication usage of patients with type 1 diabetes, type 2 diabetes, gestational diabetes and other diabetes were assessed. The prevalences of hypertension, ischemic heart disease, and cerebrovascular disease were 49.72%, 17.85% and 24.90%, respectively.

Future plans
NDC will annually enrol eligible patients and include socioeconomic data in future updates. The data of NDC are maintained by the Department of Medical Informatics at Nanjing Medical University.

Background
Patient medication knowledge and health literacy affect patient safety. Taking angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin II receptor blockers (ARBs), with diuretics and non-steroidal anti-inflammatory medications (NSAIDs) is nephrotoxic. Patients may not know of this risk. An eHealth information package was developed to inform patients at risk of taking this combination of medication.

Objective
To assess the impact of the eHealth information package on patient knowledge and behaviour.

Design
This was a two-arm, parallel, randomised control trial. A knowledge quiz and NSAID use survey were undertaken at baseline, and repeated after two weeks. The intervention group accessed the information package after completing the baseline assessment. The control group received normal care.

Setting and participants
Primary healthcare patients prescribed an ACE-i or ARB plus a diuretic in Aotearoa New Zealand.

Intervention
A novel eHealth information package was made available to participants in the intervention group consisting of a downloadable PDF and online education activity. This took approximately 15 min for participants to complete.

Primary outcome measures
Change in knowledge scores and in NSAID use between pre-intervention and post-intervention assessment.

Secondary outcome measures
Self-reported patient intentions regarding future NSAID use

Results
The 201 participants who completed the study had high baseline NSAID medication knowledge, which did not substantially change at follow-up. The intervention group had a 0.35 (95% CI: -0.18, 0.88) higher knowledge score than the control group. NSAID use decreased over the study; the intervention group had 62% lower odds of NSAID use at follow-up assessment compared with the control group (OR=0.37, 95% CI: 0.14, 1.03). There was no substantial difference between study groups at follow-up for self-reported action. The information package was considered acceptable and useful.

Conclusion
This tailored eHealth information package may reduce NSAID use in patients at increased risk from NSAID-related harm.

Trial registration number
Australian New Zealand Clinical Trial Registry (ACTRN:12622001132730).

Per il numero uno delle imprese farmaceutiche il mancato rialzo del tetto della spesa fa alzare il payback a 2,5 miliardi nel 2025

Stroke, Ahead of Print. BACKGROUND:Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), aStachybotrys microsporatriprenyl phenol family member, may extend this therapeutic window.METHODS:In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence).RESULTS:Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42–87) and 8 (6–21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34–85) and 8 (6–22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0–12.1) and 10.0 (3.7–12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0–5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1–13.8]) for placebo (P=0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score

Obiettivo ridurre la spesa privata a carico dei cittadini

Obiettivo ridurre la spesa privata a carico dei cittadini

Pro Vita, con la Ru-486 si velocizza l’omicidio del nascituro

Con questa misura la ricetta medica dematerializzata entra definitivamente a regime, senza più bisogno di nuove proroghe