Search Results for: Prima terapia farmacologica per l’apnea notturna (OSAS)

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Stroke, Volume 56, Issue Suppl_1, Page ATP358-ATP358, February 1, 2025. Introduction:Stroke is a well-established independent risk factor for the development of dementia. Most dementia patients exhibit mixed brain pathologies, with histological evidence of ischemia and Aβ plaque accumulation, observed at autopsy. It is known that apnea/breathing disorders are independent risk factors for cognitive dysfunction and the progression of dementia. Our previous work suggested stroke impairs breathing control in wildtype mice. Here we hypothesize that, in mice with pre-existing dementia, stroke will exacerbate their respiratory dysfunction and further impair cognitive function.Methods:We used Tg-SwDI mice as a model for cerebral amyloid angiopathy (CAA), a major type of dementia. Female (11 to 13 months old) Tg-SwDI mice underwent pd-MCAO (permanent distal middle cerebral artery occlusion surgery) with age and sex matched wildtype and sham controls. Barnes Maze and Novel Object Recognize Test (NORT) were used for cognitive assessment, while whole-body plethysmography captured respiratory metrics, including apnea rate at 6 weeks post-surgery. All data are presented as Mean±SEM.Results:Tg-SwDI mice without stroke showed significant increases in apnea rates (per min) compared to the wide-type mice without stroke (5.8±0.26 vs. 1.04±0.11,p=0.0003, n=7 and 5) and displayed worsen performance in Barnes Maze (escape latency 59.5±11.6 vs. 23.7±6.1,p=0.044, n=7 and 5) and NORT (percentage time spent with novel object 42.0±5.8% vs. 61.9±6.2%,p=0.019, n=7 and 5). pd-MCAO increased apnea events in Tg-SwDI group (9.5±0.91 vs. 5.8±0.26,p=0.0009, n=9 and 7) vs. Tg-SwDI mice without stroke. Tg-SwDI mice with pd-MCAO exhibited worsen performance in Barnes Maze escape latencies (93.7±10.4 vs. 59.5±11.6,p=0.027, n=9 and 7) compared with Tg-SwDI mice without stroke. There was also a non-significant reduced novel object interaction time in NORT (36.8%±3.54 vs. 42.0%±5.8,p=0.43, n=9 and 7).Conclusions:Stroke worsens both respiratory dysfunction and cognitive memory impairment in CAA mice. The increased breathing disorder may be a contributing factor for worsened cognition in CAA mice.

Stroke, Volume 56, Issue Suppl_1, Page ATP139-ATP139, February 1, 2025. Background:The Addressing Sleep Apnea Post-Stroke/TIA (ASAP) clinical trial aimed to enhance OSA management at six VA medical centers through a hybrid implementation trial, requiring coordination across hospital medicine, sleep medicine, nursing, and neurology in both inpatient and outpatient settings. This analysis evaluated the trial’s efforts to standardize early OSA screening in stroke/TIA patients.Methods:This mixed-methods evaluation used configurational comparative methods (CCMs) to identify key contextual factors for successful implementation, examining the joint effects of multiple factors. The stepped-wedge trial ran from May 2019 to January 2024 across three implementation waves. The primary outcome was the Group Organization (GO) score, which measured team cohesion in managing sleep apnea among cerebrovascular patients. Data sources included observational data, qualitative interviews, and administrative data across three periods (A, B, C), calibrated into dichotomous or multi-value categories for analysis.Results:Four key difference-makers distinguished more successful sites (GO score ≥6) from others: routines for ordering inpatient OSA tests, patient care coordination during hospitalization, involvement of field staff, and strong local champions. The ability to order and complete sleep studies was crucial for timely OSA diagnosis. Field staff (e.g., respiratory technicians, polysomnographic technologists, research) played a critical role in coordinating care during inpatient stays and post-discharge. Key pathways to success included active field staff engagement and strong champion support, particularly in the final phase. Less successful sites faced barriers like geographic separation and staff shortages. The figure describes the values for each of these factors at the 4 more successful versus 2 less successful sites.Conclusions:The study highlights the importance of flexibility in integrating new practices, particularly in stroke care requiring multi-specialty coordination. Findings provide a roadmap for healthcare systems implementing similar interventions, emphasizing leadership, coordinated care, and robust tracking for program success.

Stroke, Volume 56, Issue Suppl_1, Page AWP301-AWP301, February 1, 2025. Introduction:While intracranial hemorrhage (ICH) is uncommon in young adults (18-55), its incidence is on the rise. While the reasons for this increase are multifactorial, there is likely a contribution from the known rise in traditional vascular risk factors (VRFs) among the general young adult population. We aimed to examine the prevalence of VRFs among young patients with ICH and evaluate for racial and sex disparities in VRF burden.Methods:Data of patients hospitalized with stroke between January 2014 and December 2023 were collected by Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry. Young patients aged 18-55 with a diagnosis of ICH were included and separated into two age groups: 18-35 and 36-55. VRFs included hypertension, diabetes, kidney disease, smoking, drug or alcohol abuse, antithrombotic medication use, and sleep apnea. Polymorbidity was defined as the presence of three or more VRFs.Results:9541 young ICH patients were included (39% female, 41% White, 17% Hispanic, 33% non-Hispanic Black), and 1240 (13%) of these patients were aged 18-35. The prevalence of each VRF was higher among patients aged 36-55 vs 18-35 (all p values

Stroke, Volume 56, Issue Suppl_1, Page AWP47-AWP47, February 1, 2025. Introduction:The brain’s glymphatic system is crucial for clearing metabolic waste and maintaining balanced fluid circulation within the brain. Enlarged perivascular spaces in the basal ganglia (EPVS-BG) are markers of hypertensive cerebral small vessel disease (HTN-cSVD) due to glymphatic system dysfunction. Atrial fibrillation (AF) has been proposed to increase the wall shear stress and blood pressure in the lenticulostriate arteries (LSA), both potentially contributing to glymphatic dysfunction and cSVD development. We hypothesized that a higher AF burden is related to the presence of a severe degree EPVS-BG, potentially through the hemodynamic effects of AF on LSAs.Methods:We analyzed data from 641 AF patients who had no clinical history of stroke or neurodegenerative disease and received brain MRIs with appropriate sequences at a tertiary care center. Neuroimaging data were collected by a stroke neurologist blinded to the clinical data. AF load was classified as lower-burden (paroxysmal/persistent AF) or higher-burden (longstanding persistent/permanent AF). The imaging outcome variables were the presence of severe EPVS-BG ( >20 on one side of the brain), Fazekas score, atrophy score, lacunes and microbleeds (MB) in deep/lobar locations (FIGURE). The multivariable model was adjusted for all variables with p

Stroke, Volume 56, Issue Suppl_1, Page AWMP51-AWMP51, February 1, 2025. Background:Obstructive sleep apnea (OSA) is common among patients with ischemic stroke and transient ischemic attack (TIA) and has been associated with poor outcomes. Guidelines recommend evaluating eligible patients with cerebrovascular events for OSA.Objective:to examine whether a quality improvement (QI) intervention could increase OSA testing post-stroke/TIA.Methods:ASAP (NCT04322162) was a stepped-wedge cluster-randomized trial evaluating the effectiveness of a QI intervention to increase OSA testing among ischemic stroke or TIA patients at intervention (N=6) vs. control sites (N=30). Recruitment was at the facility level. The study involved 3 phases: baseline, implementation, and sustainability. The primary outcome was: 30-day OSA diagnostic testing rate. Secondary outcomes were: 30-day continuous positive airway pressure treatment rate, and 90-day recurrent vascular event and readmission rates. ASAP was powered to detect a difference in the primary outcome: baseline vs. implementation. Generalized linear mixed-effects models with binomial distribution and log link fit to patient-level data with site-level random effects were used. The QI intervention included: a virtual kickoff (teams reviewed data, identified improvement opportunities, considered barriers and solutions to diagnosing OSA post-stroke/TIA, and action plan development); monthly collaborative conferences; web-based platform displaying quality data and resource library; and external facilitation.Results:Among 1747 patients at 6 intervention sites the diagnostic rate increased from 2.1% (baseline, 20/952) to 29.1% (implementation, 189/650); among 7454 patients at 30 control sites the 30-day diagnostic rate varied (0.6%-2.2%; adjusted odds ratio (aOR) 16.90 (95%CI, 9.49-30.10). The diagnostic rate during sustainability was 11.7% (17/145); aOR 3.58 (1.59-8.04). The 30-day treatment rate varied (0.0%-0.4%) at control sites and increased at intervention sites: 0.3% (baseline, 3/952) to 2.8% (implementation, 18/650; OR 14.22 (2.40-84.40). The treatment rate during sustainability was 0.7% (1/145); aOR 2.66 (0.13-56.21). 90-day readmission and recurrent event rates were lower during implementation and sustainability (vs. baseline); these changes were not statistically significant.Conclusions:QI approaches can markedly increase OSA testing among patients with acute cerebrovascular events. Additional work should identify strategies to increase treatment rates among stroke/TIA patients with OSA.

Stroke, Volume 56, Issue Suppl_1, Page AWP346-AWP346, February 1, 2025. Dementia is associated with respiratory dysfunction. In mice models of dementia, there is increased astrogliosis in the brain stem retro-trapezoid nucleus (RTN), which is crucial for breathing control. Our previous work using a genetic approach suggested that increased transforming growth factor beta receptor (TGFβR) signaling may be responsible for RTN astrogliosis and contribute to respiratory and cognitive dysfunctions. Here we tested our hypothesis that pharmacological inhibition of TGFβR2 in mice models of dementia may reduce RTN gliosis, breathing disorder and cognitive impairment.We used male 16-month-old Tg-2576 and Tg-SwDI mice that model Alzheimer’s Disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively with WT controls. LY2109761, a selective TGF-β receptor inhibitor, was administered orally every day for 6 weeks at a 50 mg/kg dose. Barnes Maze and Novel Object Recognition Test (NORT) were used to measure cognitive strength, and plethysmography was used to measure respiratory metrics such as apnea rate after the 6 weeks of treatment. Immunofluorescence was used to quantify gliosis (GFAP) at RTN. All data is presented as Mean±SEM.Tg-2576 mice performed significantly worse than the WTs in the Barnes Maze (escape latency 184±20.99 vs. 119.4±12, p=.039, n=8-9/group), in the NORT (percentage time with the novel object 48.3±2.061 vs. 63.3±2.071, p=.0003, n=8-9/group), and showed increased apneas per minute (9±.9 vs 4.33±.81, p=.001, n=8-9/group). Similarly, Tg-SwDI mice showed impaired breathing and cognition function. In Tg-2576 mice, TGFβR2 inhibition improved performances in Barnes Maze (112±18.6 vs. 184±20.9, p= .02 n=8-9/group) and NORT (57.7±2.54 vs. 48.3±2.06, p=.023, n=8-9/group), and reduced apneas per minute (4.88±.058 vs. 9.0±.98, p=.004, n=8-9/group) compared with vehicle treatment. In Tg-SwDI mice, TGFβR2 inhibition also improved performance in Barnes Maze (43.8±2.72 vs. 58.2±5.16, p=.03 n=7/group) and NORT (59.1±3.28 vs. 46.6±3.32, p=.02, n=7/group), and reduced apneas per minute (5±1.06 vs. 9.71±1.71, p=.038 n=7/group) compared with vehicle group. TGFβR2 pharmacological inhibition additionally reduced astrogliosis in the RTN of Tg-2576 mice (drug 53.62±4.8 vs. vehicle 70.9±3.38, p=.018, n= 4/group).In conclusion, pharmacological inhibition of TGFβR2 improved cognition in AD and CAA mice. Improving breathing control via reducing gliosis at breathing center RTN may be the underlying mechanisms of the improvement.

Stroke, Volume 56, Issue Suppl_1, Page AWP164-AWP164, February 1, 2025. Introduction:Rates of guideline-concordant obstructive sleep apnea (OSA) testing among those with a recent cerebrovascular event are exceedingly low. Understanding the role contextual factors play is necessary to inform successful implementation of quality improvement (QI) initiatives designed to address this gap in stroke/transient ischemic attack (TIA) care.Methods:Longitudinal data was collected via questionnaires and semi-structured interviews to evaluate the implementation of QI initiatives conducted at six diverse VA Medical Centers (VAMCs) participating in Addressing Sleep Apnea Post-Stroke/TIA (ASAP), a Hybrid Type I, stepped-wedge cluster-randomized trial. Intervention components included a Systems Redesign Virtual Collaborative and data monitoring (Figure 1). Implementation strategies included external facilitation and audit and feedback. Provider- (e.g., clinical training) and systems-level contextual elements (e.g., Champion Team members and their roles) were collected. Select Consolidated Framework for Implementation Research (CFIR) constructs were rated in terms of magnitude and valence. The primary outcome of successful implementation was defined at the end of 21 months of active implementation as obtaining a Group Organizational (GO) score of ≥6 a measure of programmatic development and maturation. Comparisons of sites were conducted across contextual elements and stratified by those achieving a GO score of ≥6 (Figure 2).Results:ASAP Sites 1 through 4 obtained a GO score ≥6 (range: 7-9); across these sites, the Clinical Champion had: (1) field staff engaged in activities such as care coordination; (2) full to partial support of their local sleep personnel, and; (3) consistently positive CFIR scores values. These sites also received a greater amount of external facilitation and used a quality dashboard more often. All 4 sites created a change in health care personnel and medical center culture that stressed the importance of OSA testing soon after a cerebrovascular event occurred.Conclusions:Developing strong and consistent Champion teams who meaningfully engaged with local VAMC personnel within and across sleep medicine and stroke service lines was important for implementation success. Other key contextual factors for changing culture and creating a healthcare system wide approach to improving OSA testing for stroke/TIA patients included external facilitators and using performance data.Clinical Trials registration:NCT04322162

Stroke, Volume 56, Issue Suppl_1, Page ATP4-ATP4, February 1, 2025. Introduction:Current guidelines exclude patients with recent NOAC use from thrombolysis, even if they present during the 4.5hr timeframe. Emerging data suggest there may not be an increased risk of hemorrhagic conversion for patients who receive thrombolysis despite recent NOAC use. At a large urban Joint Commission certified comprehensive stroke center, a retrospective analysis was conducted to identify characteristics of patients excluded from thrombolytic due to NOAC use.Methods:The GWTG database was queried for patients with acute ischemic stroke presenting (time frame) within 4.5 of last known well. A total of 1,933 AIS patients were identified). A total of 5.0 % (n=96) of these patients were excluded due to recent NOAC use. A chi-squared analysis was performed to determine if there was a significant difference based on sex, race, age, history of heart disease and statin use. A pooled T-test analysis was also performed to determine if a significant difference exists between the mRS and NIHSS at baseline and at discharge within the excluded patients group.Results:Patients excluded from IVT due to recent NOAC use were more likely to take cholesterol reducer (67.1% vs 45.6%). The NOAC exclusion group were more likely to have medical co-morbidities including Afib/Aflutter, prosthetic heart valves, CAD/prior MI, heart failure, prior DVT/PE and sleep apnea (Table 1). Both groups had an equal probability of having a history of a previous stroke. There was no statistically significant difference in patient demographics (race, sex,etc.) between the two groups.Among the patients excluded from IVT due to recent NOAC use: 54.2% (n=52) had a normal EF, 10.8 % (n=10) had a thrombus visualized on TTE, 49.0 % (n=47) had a L.MCA stroke. 80.2% (n=77) had plans to restart their AC on discharge: Apixaban 45.8% (n=44), Rivaroxaban 11.5% (n=11) and Dabigatran 2.1 % (n=11). The median mRS at baseline was 1 and at discharge was 4.Conclusion:Patients excluded from IVT due to recent NOAC use were more likely to have cardiovascular co-morbidities. If NOAC exclusion is removed in the future, 1 in 20 patients could potentially become eligible for IVT, and MRS worsening due to stroke can potentially be avoided.