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Stroke remains a global health challenge with high rates of mortality and rehospitalization placing significant demands on healthcare systems. Identifying factors that determine outcomes of post-hospitalization improves resource allocation. Traditional statistical prediction models are suboptimal for the analysis of complex, multi-dimensional datasets. The objective of our study is to define the extended list of clinical and non-clinical predictors, which we believe can be achieved using Explainable Machine Learning (XML) models as an expansion of conventional methods. We evaluated 11 established XML models that represent key ML methodologies to predict 90-day outcomes, namely mortality and rehospitalization among stroke survivors. The study population are 1,300 post-stroke individuals enrolled in the Transitions of Care Stroke Disparities Study (TCSD-S) (NIH/NIMH, NCT03452813) between June 2018 - October 2022. The care after transition data is sourced from participating comprehensive stroke centers and from the Florida Stroke Registry. The analysis incorporated clinical (e.g., age, stroke severity, comorbidities) and non-clinical factors including Social Drivers of Health (SDOH). A combined ranking approach, using Weighted Importance Scores and Frequency Counts, identified significant predictors across models. The resulting list of selected predictors included both established clinical factors and non-clinical factors, which enhanced prediction accuracy. Out of 38 identified predictors, 20 are non-clinical variables reflecting the importance of SDOH, environmental factors, and behavioral modifications beyond traditional clinical predictors of death/readmission. A secondary analysis restricted to ischemic stroke patients (n = 1,038) yielded virtually identical predictive performance, indicating robustness of the model within this subgroup. Integrating SDOH, environmental factors, and behavioral modifications alongside traditional clinical predictors enhances the predictive accuracy of post-stroke outcome models. This underscores the critical role of addressing socioeconomic disparities during post-stroke transitions of care. Moreover, XML models' ability to identify predictors spanning clinical and non-clinical domains suggests their potential to guide recovery. The resulting predictors are crucial for post-hospital care and hold strong potential for identifying individuals at risk of stroke, making them potentially significant across pre-stroke and hospitalization stages.

Objective The intracerebral hemorrhage (ICH) score was developed to enhance provider communication and facilitate early severity assessment. We examined the association of the ICH score with mortality and withdrawal of life‐sustaining treatment (WLST) in a large, multicenter stroke registry, and evaluated temporal trends in these associations. Methods We identified ICH patients from the Florida Stroke Registry from 2013 to 2022. Outcomes were WLST and in‐hospital mortality. ICH scores were grouped as 0–2, 3–4, and 5–6. Importance plots identified key predictors of WLST. Model performance was assessed using AUC‐ROC for logistic regression and random forest, adjusted for relevant confounders. Secondary analyses compared outcomes between 2015–2018 and 2019–2022 using stratified univariate logistic regression. Results In total, 12,426 patients were included (mean age 69, 55% male, 56% white). The most predictive factors associated with WLST were ICH score, age, state region, presenting level of consciousness, insurance status, and race (RF AUC = 0.94, LR AUC = 0.82). Mortality was 6.6%, 41.5%, and 66% for ICH score 0–2, 3–4, and 5–6. WLST occurred more frequently in higher ICH score groups (OR 9.35 [95% CI: 8.5–10.3] for scores 3–4; OR 18.64 [95% CI: 15.28–22.74] for scores 5–6). Early WLST (< 48 h) was more common in higher score groups (OR 2.97 [95% CI: 2.48–3.55] for 3–4; OR 9.51 [95% CI: 7.33–12.35] for 5–6). Interpretation Higher ICH scores were strongly associated with mortality and WLST, including early withdrawal decisions. These associations remained largely consistent over time. These observational findings underscore the need for continued attention to how prognostic scores may influence WLST decisions.

BackgroundIn ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase in patients who had a minor stroke enrolled in the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT) trial.MethodsThe AcT trial included individuals with ischaemic stroke, aged >18 years, who were eligible for standard-of-care intravenous thrombolysis. Participants were randomly assigned 1:1 to intravenous tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Patients with minor deficits pre-thrombolysis were included in this post-hoc exploratory analysis. The primary efficacy outcome was the proportion of patients with a modified Rankin Score (mRS) of 0–1 at 90–120 days. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH).ResultsOf the 378 patients enrolled in AcT with an NIHSS of ≤5, the median age was 71 years, 39.7% were women; 194 (51.3%) received tenecteplase and 184 (48.7%) alteplase. The primary outcome (mRS score 0–1) occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5 %) in the alteplase group (adjusted risk ratio (RR) 1.14 (95% CI 0.92 to 1.40)). There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group, unadjusted RR 0.79 (0.24 to 2.54)) and death within 90 days (5.5% in tenecteplase vs 11% in alteplase group, adjusted HR 0.99 (95% CI 0.96 to 1.02)).ConclusionIn this post-hoc analysis of patients with minor stroke enrolled in the AcT trial, safety and efficacy outcomes with tenecteplase 0.25 mg/kg were not different from alteplase 0.9 mg/kg.

Purpose To compare the association of different measures of intracranial thrombus permeability on non-contrast computerized tomography (NCCT) and computed tomography angiography (CTA) with recanalization with or without intravenous alteplase. Methods Patients with anterior circulation occlusion from the INTERRSeCT study were included. Thrombus permeability was measured on non-contrast CT and CTA using the following methods: [1] automated method, mean attenuation increase on co-registered thin (< 2.5 mm) CTA/NCCT; [2] semi-automated method, maximum attenuation increase on non-registered CTA/NCCT (ΔHUmax); [3] manual method, maximum attenuation on CTA (HUmax); and [4] visual method, residual flow grade. Primary outcome was recanalization with intravenous alteplase on the revised AOL scale (2b/3). Regression models were compared using C-statistic, Akaike (AIC), and Bayesian information criterion (BIC). Results Four hundred eighty patients were included in this analysis. Statistical models using methods 2, 3, and 4 were similar in their ability to discriminate recanalizers from non-recanalizers (C-statistic 0.667, 0.683, and 0.634, respectively); method 3 had the least information loss (AIC = 483.8; BIC = 492.2). A HU max ≥ 89 measured with method 3 provided optimal sensitivity and specificity in discriminating recanalizers from non-recanalizers [recanalization 55.4% (95%CI 46.2–64.6) when HU max > 89 vs. 16.8% (95%CI 13.0–20.6) when HU max ≤ 89]. In sensitivity analyses restricted to patients with co-registered CTA/NCCT ( n = 88), methods 1–4 predicted recanalization similarly (C-statistic 0.641, 0.688, 0.640, 0.648, respectively) with Method 2 having the least information loss (AIC 104.8, BIC 109.8). Conclusion Simple methods that measure thrombus permeability are as reliable as complex image processing methods in discriminating recanalizers from non-recanalizers.

In a trial involving patients with ischemic stroke due to medium-vessel occlusion, thrombectomy within 12 hours did not lead to a better functional outcome and lower mortality at 90 days than usual care.

In the ESCAPE-NA1 trial, treatment with nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, was associated with improved functional outcome among patients with acute ischaemic stroke due to large vessel occlusion undergoing endovascular thrombectomy without co-treatment with an intravenous thrombolytic agent. There was no benefit when intravenous thrombolytic agent co-treatment was used. We sought to confirm the clinical benefit of nerinetide in the absence of previous intravenous thrombolytic drug treatment. In this multicentre, randomised, double-blind, placebo-controlled study, done in 77 centres in Canada (16), the USA (16), Germany (21), Italy (four), the Netherlands (three), Norway (four), Switzerland (three), Australia (eight), and Singapore (two), we enrolled patients with acute ischaemic stroke due to anterior circulation large vessel occlusion within 12 h from onset. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation (baseline National Institutes of Health Stroke Scale [NIHSS] score >5), who had been functioning independently in the community (Barthel Index score >90) before the stroke, had Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and who were not treated with a plasminogen activator. Patients were randomly allocated (1:1) to receive intravenous infusion of nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, based upon estimated or actual weight (if known) or saline placebo using a real-time, dynamic, internet-based, stratified randomised minimisation procedure. All patients underwent endovascular thrombectomy. The primary outcome was a favourable functional outcome 90 days from randomisation, defined as a modified Rankin Scale (mRS) score of 0–2. The analysis was by intention to treat and adjusted for time from stroke onset to randomisation (≤4·5 h [yes or no]), age, sex, baseline NIHSS score, occlusion location, time from qualifying imaging to randomisation, baseline ASPECTS, and region. Secondary outcomes were measures of mortality, worsening of stroke, improved functional independence, and measures of neurological disability. This trial is registered with ClinicalTrials.gov, NCT04462536. From Dec 6, 2020, to Jan 31, 2023, 850 patients were assigned to receive nerinetide (n=454) or placebo (n=396). 206 (45%) participants in the nerinetide group and 181 (46%) participants in the placebo group achieved an mRS score of 0–2 at 90 days (odds ratio 0·97, 95% CI 0·72–1·30; p=0·82). Serious adverse events occurred equally between groups. While nerinetide did not improve outcomes in patients with acute ischaemic stroke, it was not associated with excess adverse events. Further study is needed to identify the ideal timing of treatment and the sub-population of stroke patients who might benefit from treatment combined with current reperfusion therapies. Canadian Institutes for Health Research and NoNO.

In three neuroprotection trials of nerinetide for acute ischaemic stroke, inconclusive results have been reported with respect to the prespecified primary outcome. However, none of the trials faithfully replicated the inclusion criteria of the animal studies that provided the rationale for the clinical trials—ie, treatment within 3 h of stroke onset and selected for reperfusion without previous thrombolysis. We aimed to investigate whether a clinical benefit of nerinetide might be seen in the subgroup of patients enrolled in these three clinical trials who met the criteria used in the animal studies. In this post-hoc individual patient data meta-analysis, we pooled data from the ESCAPE-NA1, ESCAPE-NEXT, and FRONTIER trials, which were done at 135 stroke centres in 13 countries (Canada, Australia, Germany, Ireland, Italy, the Netherlands, Norway, Singapore, South Korea, Sweden, Switzerland, the UK, and the USA). We included all participants who were enrolled within 3 h of acute ischaemic stroke onset, treated with study drug (nerinetide or placebo; randomised 1:1), and selected for reperfusion with thrombolysis, endovascular thrombectomy, or both. The primary endpoint was the number of responders at day 90, which was defined as people with a favourable outcome as per the primary endpoint prespecified in their respective trial. The primary endpoint was analysed by logistic regression, adjusted for age, stroke severity, and trial. Between March 26, 2015, and Jan 31, 2023, 2487 participants were enrolled in the three trials, of whom 690 met criteria for this pooled analysis (389 participants in the nerinetide group and 301 participants in the placebo group). 364 (53%) of 690 participants were men and 326 (47%) were women. The median age of participants was 76 years (IQR 66–83) and median baseline National Institutes of Health Stroke Scale score was 17 (11–21). 216 (56%) of 389 participants were responders at day 90 in the nerinetide group compared with 144 (48%) of 301 in the placebo group (adjusted odds ratio [aOR] 1·48, 95% CI 1·07–2·06; p=0·017). 62 (16%) of 389 people in the nerinetide group died compared with 55 (18%) of 301 people in the placebo group (aOR 0·81, 95% CI 0·53–1·24; p=0·34). No safety concerns were identified in either group. Nerinetide showed a clinically significant benefit over several outcome measures, including the modified Rankin Scale score, the incidence of stroke worsening, and infarction volumes. Neuroprotection with nerinetide might, therefore, be indicated for patients within 3 h of stroke onset and who are selected for reperfusion. These inclusion criteria should be tested in a future trial. None.

The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5-49.3) ml in the NTG group and 32.6 (8.6-96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7-44.2) ml) than the NTG group (3.2 (0.5-16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

BackgroundThe optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA).MethodsPatients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality.ResultsAmong 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups.ConclusionIn patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar.

Introduction: Patients who have undergone reperfusion treatments, like all ischemic stroke patients, are at risk of recurrent ischemic strokes in the first 90 days. Current guidelines recommend single antiplatelet therapy for secondary prevention at variable time points after the procedure. This study assessed the practices and perspectives of healthcare professionals on the use of dual antiplatelet therapy in patients with non-cardioembolic ischemic stroke who have undergone reperfusion therapy. Methods: We conducted a multinational cross-sectional web-based survey using Qualtrics involving neurologists and non-neurologist stroke physicians (including neurosurgeons, interventional neuroradiologists, and internal medicine physicians). Participants were asked about their current practices and presented with six structured case scenarios to determine their treatment preferences. In the case scenarios, we assessed their willingness to randomize to a clinical trial comparing single versus dual antiplatelets. Multinomial logistic regression analysis was performed to assess the relationship between demographic characteristics and willingness to randomize. Results: A total of 278 clinicians from 26 countries participated in the survey. The most common continent of practice was Asia (155/278; 55.9%). The most common area of practice was neurology (220/278; 79.1%), with most participants having 5–15 years of experience (115/278; 41.5%) and working in comprehensive stroke centers (205/278; 73.9%). Antiplatelet Choice: For a small infarct post-intravenous thrombolysis and endovascular thrombectomy (EVT), 194/278 (69.8%) preferred aspirin, and 49/278 (17.6%) chose a dual antiplatelet strategy with aspirin and clopidogrel. Loading of Antiplatelet: A total of 121/278 (43.5%) indicated they would not administer a loading dose in cases even with small final infarctions. Timing of Antiplatelet Initiation: Preferences varied; 61/278 (21.7%) considered early initiation immediately post-EVT, and 103/278 (37.2%) considered 24 h post-EVT. Willingness to Randomize: A total of 16/278 (77.7%) were willing or would consider randomizing in a clinical trial with dual antiplatelet. On regression analyses, the willingness to randomize was influenced by years of practice and the local volume of reperfusion therapy. Conclusion: Antiplatelet management for secondary stroke prevention in patients with non-cardioembolic ischemic stroke following reperfusion therapy is variable. However, more than three-fourths of participants were willing to consider randomization to a clinical trial exploring the prevention of recurrent stroke after reperfusion therapy.