Discovery of orally bioavailable phenyltetrazolium derivatives for the acute treatment and the secondary prevention of ischemic stroke.

The potential for secondary stroke prevention, which can significantly reduce the risk of recurrent strokes by almost 90%, underscores its critical importance. N-butylphthalide (NBP) has emerged as a promising treatment for acute cerebral ischemia, yet its efficacy for secondary stroke prevention is hindered by inadequate pharmacokinetic properties. This study, driven by a comprehensive structural analysis, the iterative process of structure optimization culminated in the identification of compound B4, which demonstrated exceptional neuroprotective efficacy and remarkable oral exposure and oral bioavailability. Notably, in an in vivo transient middle cerebral artery occlusion (tMCAO) model, B4 substantially attenuated infarct volumes, surpassing the effectiveness of NBP. While oral treatment with B4 exhibited stronger prevention potency than NBP in photothrombotic (PT) model. In summary, compound B4, with its impressive oral bioavailability and potent neuroprotective effects, offers promise for both acute ischemic stroke treatment and secondary stroke prevention.

Medication Literacy in Chinese Patients with Stroke and Associated Factors: A Cross-Sectional Study.

In China, stroke is characterized by high incidence, recurrence, disability, economic burden, and mortality. Regular and effective medication therapy can reduce stroke recurrence. High medication literacy is vital for the success of tertiary prevention measures aimed at preventing recurrence and minimizing disability. A cross-sectional survey using a medication literacy questionnaire was conducted between January and May 2022 on 307 inpatients of a Class III Grade A hospital in Hefei, Anhui Province, China. The demographic and clinical data of the patients were obtained from medical records. The health literacy of the patients was moderate, with 36.8% exhibiting adequate medication literacy. Univariate analysis identified significant differences in the medication literacy of the patients, depending on education level, annual income, family history of stroke, number of health problems, age, daily medication times, and brain surgery history. Multiple regression analysis revealed that education level, annual income, family history of stroke, and number of health problems significantly influenced medication literacy. In patients with stroke who are older and have a low education level, more health problems, no history of surgery, or no family history of stroke or medication guidance, medication knowledge and attitude can be improved to enhance medication safety and guarantee tertiary-level prevention of stroke.

Cost-effectiveness of a photopethysmographic procedure for screening for atrial fibrillation in 6 European countries.

BACKGROUND: Strokes cause an estimated annual health care burden of 170 billion euros across Europe. Atrial fibrillation is one of the major risk factors for stroke and increases the individual risk 4.2-fold. But prevention with anticoagulants may reduce this risk by 70%. Screening methods are employed to detect previously undetected atrial fibrillation. Screening studies in various European countries show a high degree of undetected atrial fibrillation. This study aims to assess the cost-effectiveness of systematic screening with a smartphone application, named Preventicus Heartbeats. It is a hands-on screening tool for use on smartphone to diagnose AF with high sensitivity and specificity. METHODS: A previously published model for calculating screening cost-effectiveness was extended to 6 European countries covering a wide range in terms of treatment costs and epidemiologic parameters. RESULTS: The use of screening lowers the cost per case in countries with comparatively high levels of health care costs (Switzerland: -€75; UK: -€7). Moderate higher costs per case were observed in 4 countries (Greece: €6; Netherlands: €15). Low levels of health care costs result in less or no potential for further cost reduction (Poland: €20; Serbia: €33). In all countries considered, the model showed an increase in effectiveness measures both in the number of strokes avoided and the quality adjusted life years. The number of strokes avoided per 1000 participants ranged from 2.52 (Switzerland) to 4.44 (Poland). Quality-adjusted life-years per case gained from screening ranged from 0.0105 (Switzerland) to 0.0187 (Poland). The screening procedure dominated in two countries (Switzerland, UK). For the remaining countries, the incremental cost effectiveness ratio ranged from €489/QALY (Greece) to €2548/QALY (Serbia). CONCLUSION: The model results showed a strong dependence of the results on the country-specific costs for stroke treatment. The use of the investigated screening method is close to cost-neutral or cost-reducing in the Western European countries and Greece. In countries with low price levels, higher cost increases due to AF screening are to be expected. Lower costs of anticoagulation, which are expected due to the upcoming patent expiry of direct anticoagulants, have a positive effect on the cost result.

An accurate and explainable ensemble learning method for carotid plaque prediction in an asymptomatic population.

BACKGROUND AND OBJECTIVE: The identification of carotid plaque, one of the most crucial tasks in stroke screening, is of great significance in the assessment of subclinical atherosclerosis and preventing the onset of stroke. However, traditional ultrasound examination is not prevalent or cost-effective for asymptomatic people, particularly low-income individuals in rural areas. Thus, it is necessary to develop an accurate and explainable model for early identification of the risk of plaque prevalence that can help in the primary prevention of stroke. METHODS: We developed an ensemble learning method to predict the occurrence of carotid plaques. A dataset comprising 1440 subjects (50% with plaques and 50% without plaques) and ten-fold cross-validation were utilized to evaluate the model performance. Four machine learning methods (extreme gradient boosting (XGBoost), gradient boosting decision tree, random forest, and support vector machine) were evaluated. Subsequently, the interpretability of the XGBoost model, which provided the best performance, was analyzed from three aspects: feature importance, feature effect on prediction model, and feature effect on prediction decision for a specific subject. RESULTS: The XGBoost algorithm provided the best performance (sensitivity: 0.8678, specificity: 0.8592, accuracy: 0.8632, F1 score: 0.8621, area under the curve: 0.8635) in carotid plaque prediction and also had excellent performance under missing data circumstances. Further, interpretability analysis showed that the decisions of the XGBoost model were highly congruent with clinical knowledge. CONCLUSION: The model results are superior to those of state-of-the-art methods. Thus, it is a promising carotid plaque prediction tool that could be used in the primary prevention of stroke.

Vertebral artery occlusion associated with blunt traumatic cervical spine injury.

AIM: Vertebral artery injury associated with blunt traumatic cervical spine injury sometimes causes severe cerebellar and brain stem infarction. No treatment guidelines for vertebral artery injury aimed at preventing stroke have been decided. We have conducted endovascular embolization in patients with up to Denver grade IV cerebrovascular injury complicated by unstable cervical spine injury before open reduction and fixation surgery. The purpose of this study was to validate the clinical course of vertebral artery injury and especially endovascular treatment for grade IV patients in our hospital. METHODS: Participants comprised of patients diagnosed as having traumatic cervical spine injury in our hospital between January 2015 and April 2018. Among these patients, we selected those with vertebral artery injury and retrospectively examined the background characteristics of the patients, details of treatment, and complications with or without stroke. RESULTS: Traumatic cervical spine injury was diagnosed in 89 patients. Among these patients, 15 (16.7%) showed a complicating vertebral artery injury. Mean age was 62.6 years, and almost 50% of the patients were injured in falls. Three types of cervical spine injury caused vertebral artery injury: subluxation, Jefferson fracture, and fracture involving the foramen transversarium. Vertebral artery injury was classified as grade IV in 12 patients, of whom nine required spinal surgery. All patients who needed spinal surgery underwent endovascular therapy before surgery, and none experienced a stroke. CONCLUSION: Endovascular embolization of the vertebral artery occlusion in patients with unstable cervical spine injury before open reduction and fixation surgery can be a treatment option to prevent stroke.

The Epidemiology of Neurological Complications in Adults With Sickle Cell Disease: A Retrospective Cohort Study.

Introduction: Risk factors for neurological complications in sickle cell disease differ in the adult and pediatric populations. Here, we focused on neurological complications in adults with sickle cell disease. Methods: Patients were selected using the audit data from the St George's Hospital Red Cell Database. The genotyping, demographics, clinical data, and investigation findings were collected. Results: A total of 303 patients were enrolled in the study: hemoglobin S homozygosity (HbSS) genotype 56%, hemoglobin S and C coinheritance (HbSC) genotype 35%, and hemoglobin S and ß-thalassemia coinheritance (HbSß) thalassemia genotype 9%; the mean age was 38.8 years (±13.5 SD) with 46% males. The most common neurological complication was cerebrovascular disease (n = 37, 12%) including those with ischemic stroke (10%), cerebral vasculopathy (3%), and intracranial hemorrhage (1%). Ischemic stroke was common among the HbSS genotype compared with other genotypes (8 vs. 1.6%, p = 0.001). Comparing the patients with sickle cell disease who had suffered a stroke to those who had not, there was a higher proportion of intracranial vasculopathy (p = 0.001, in particular, Moyamoya) and cognitive dysfunction (p < 0.0001). Conclusion: Our cohort supports previous reports that the most common neurological complication in adult sickle cell patients is cerebrovascular disease. Strategies to prevent cerebral vasculopathy and cognitive impairment should be explored.

Temporary oral anticoagulation after MitraClip - a strategy to lower the incidence of post-procedural stroke?

Background: Incidence of stroke within 30 days after percutaneous mitral valve repair using the MitraClip varies from 0.7% and 2.6% between registries. Standard medical treatment after the MitraClip procedure, in the absence of risk factors requiring antithrombotic therapy such as atrial fibrillation, is dual antiplatelet therapy using aspirin and clopidogrel. ESC/EACTS and ACC/AHA surgical guidelines show a Class IIa indication for temporary antithrombotic therapy after mitral valve repair/bioprosthetic valve replacement within the first three months even in patients with no additional risk factors.Methods: 470 patients were treated with the MitraClip receiving oral anticoagulation (Coumadin: INR 2.0-3.0) instead of dual antiplatelet therapy for at least 30 days after the procedure. The incidence of stroke, as well as major adverse events such as bleeding, were analysed in comparison to large registries and multi-centre studies.Results: Incidence of stroke within 30 days was significantly reduced as compared to comparative cohorts (0.2% vs. Median 1.3% [0.7-2.6%]; p < .05). Cardiovascular risk factors such as age, atrial fibrillation, hypertension, diabetes, STS score and prior stroke did not differ significantly between cohorts (ns). Bleeding complications were not increased due to 30 days oral anticoagulation treatment (4.6% vs. Median 7.4% [3.4-13.6%]; ns).Conclusions: Temporary oral anticoagulation might be a strategy to reduce the incidence of stroke within the first 30 days after the MitraClip procedure. Bleeding events were not significantly altered due to temporary oral anticoagulation.

A cost-effectiveness analysis model of Preventicus atrial fibrillation screening from the point of view of statutory health insurance in Germany.

BACKGROUND: With atrial fibrillation (AF) the risk of stroke is 4.2-fold increased to a comparable population without AF. This risk decreases by up to 70% if AF is detected early enough and effective stroke preventive measures are taken as recommended by international guidelines. Long-term studies found large number of subjects with undiagnosed AF. Preventicus Heartbeats" is a hands-on screening tool for use on smartphone to diagnose AF with high sensitivity and specificity. The aim of this study is to research the cost-effectiveness of systematic screening for AF with this smartphone application. METHOD: Employing a Markov model we analysed the cost-effectiveness of the "Preventicus Heartbeats" screening for Germany, i.e. from the perspective of German statutory sick funds. RESULTS: For a cohort of 10,000 insured 75-year-old the use of the diagnostic app could avoid 60 strokes in the remaining lifetime thereof 32 strokes in the next four years. Former models have applied similar cohorts. The same cohort showed an increase in quality-adjusted life years (QALY) in the remaining lifetime of 165 QALYs in the scenario with screening versus. without screening and a decrease in discounted lifetime costs (including risk compensation effects) of €129 per participant (€148 for male, €114 for female participants). CONCLUSIONS: The modelling demonstrates the health benefits and economic effects of an implementation of a systematic screening on AF with "Preventicus Heartbeats", given the perspective of the German payer, the statutory health care system.

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible 'Bridging Function' of Acupuncture.

Worldwide, stroke is the leading cause of mortality and disability, with hypertension being an independent risk factor for a secondary stroke. Acupuncture for the treatment of hypertension gains more attention in alternative and complementary medicine, but the results are inconsistent. Few studies regarding the secondary prevention of stroke by managing hypertension with acupuncture have been carried out as there are some problems regarding the antihypertensive drug status in the secondary prevention of stroke. Still, the potential of acupuncture in regulating the blood pressure for secondary stroke prevention deserves our focus. This review is based on papers recorded in the PubMed, Embase, and Web of Science databases, from their inception until March 28, 2017, and retrieved with the following search terms: hypertension and acupuncture, limited in spontaneously hypertensive rats (SHRs), stress-induced (or cold-induced) hypertensive or pre-hypertensive models. We find that, in these hypertensive animals, acupuncture could mainly influence factors related to the nervous system, oxidative stress, the endocrine system, cardiovascular function, and hemorheology, which are closely associated with the stroke outcome. This trend may give us a hint that acupuncture might well participate in the secondary prevention of stroke through these pathways when used in the management of hypertension.

Long-term outcome in extracranial-intracranial bypass surgery for severe steno-occlusive disease of intracranial internal carotid or middle cerebral artery.

OBJECTIVES: We report the long-term outcome and rates of recurrent cerebral ischemic events in our cohort of carefully selected patients after STA-MCA bypass for severe steno-occlusive disease of intracranial ICA or MCA with exhausted cerebral vasodilatory reserve. PATIENTS AND METHODS: In this retrospective study, we reviewed the hospital records for all patients who underwent direct superficial temporal artery-middle cerebral artery bypass surgery at our institution from January 2010 to August 2017. Patients were included in the study if they presented with transient ischemic attack or non-disabling stroke due to a severe steno-occlusive lesions of the intracranial internal carotid artery or middle cerebral artery with abnormal cerebral vasodilatory reserve on imaging. The overall event rate is defined as transient ischemic attack, acute ischemic stroke, peri-operative stroke or death. RESULTS: 69 patients were included in the study. The median age of cohort was 57 years (inter-quartile range 36-78). Median follow up period in our study was 73 months (range 2-90 months). The overall event rate post-treatment during the follow up period is 20.2%. In contrast, previous studies have showed that patients who underwent best medical therapy had a higher recurrent ischemic stroke rate over a 2-3-year period. CONCLUSION: This study suggests that carefully selected patients with severe steno-occlusive disease and significantly abnormal cerebral hemodynamic reserve who undergo extracranial-intracranial bypass surgery, may benefit from long-term prevention of symptomatic cerebral ischemic events.

Acupuncture lowering blood pressure for secondary prevention of stroke: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. METHODS: This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. DISCUSSION: We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.

Carotid angioplasty with stenting versus endarterectomy: 10-year randomized trial in a community hospital.

OBJECTIVES: This single-center, randomized, clinical trial was designed to determine the 10-year comparative efficacy and durability of carotid angioplasty and stenting (CAS) versus carotid endarterectomy (CEA) in preventing ipsilateral ischemic stroke in symptomatic and asymptomatic patients with high-grade carotid artery stenosis. BACKGROUND: Modern clinical trials with short-term follow-up indicate CAS and CEA are equivalent in reducing the risk for ipsilateral ischemic stroke secondary to carotid stenosis. A paucity of data exists regarding long-term outcomes. METHODS: Patients of all surgical risks with symptomatic and asymptomatic carotid stenosis (>70%) were randomly selected for CEA or CAS and followed a minimum of 10 years. RESULTS: Long-term follow-up was achieved in 173 patients (91%). Eighty-seven (50.2%) died within this period, most commonly of nonvascular causes. No difference in the risk of stroke ipsilateral to the treated artery was noted among treatment groups (p > 0.05). Restenosis determined by sequential ultrasound was assessed only in the CAS group (3.3%) and remained asymptomatic. The combined risk of fatal or nonfatal heart attack over the 10-year period was highest in individuals with symptomatic versus asymptomatic stenosis (27.5% vs. 11.0%; hazard ratio [HR]: 2.32, 95% confidence interval [CI]: 1.298 to 4.146, p = 0.005) and was higher in all patients treated with CEA (HR: 2.27, 95% CI: 1.35 to 3.816, p = 0.002). CONCLUSIONS: Long-term protection against ipsilateral stroke provided by CAS and CEA did not differ in this trial. The 10-year risk of fatal/nonfatal myocardial infarction was highest in all patients harboring symptomatic carotid stenosis at enrollment. The risk of fatal/nonfatal heart attack was significantly more prevalent in those symptomatic or asymptomatic patients randomized to CEA.

Optimisation of secondary prevention of stroke: a qualitative study of stroke patients' beliefs, concerns and difficulties with their medicines.

OBJECTIVES: The objectives of this study are to explore stroke patients' and carers' beliefs and concerns about medicines and identify the barriers to medication adherence for secondary stroke prevention. METHODS: Qualitative semistructured one-on-one interviews were conducted with 30 patients with diagnosis of stroke. Interviews were analysed using the framework approach. KEY FINDINGS: The study suggests that stroke patients' and carers' perceptions of their medicines may influence medicine-taking behaviour. In some cases when beliefs outweighed concerns, practical barriers prevented participants taking their medicines. Negative beliefs about a medicine were strong enough to prevent some participants starting a new medicine. Participants' actions were influenced by the perceived consequences of not taking the medicine and the impact of the adverse effect on their quality of life. Concerns lessened with time with no adverse effects. The importance of the role of the carer and of a medicine-taking routine was evident. Participants reported the inadequacy of information provision and the desire to have more written and verbal information. Some reported total lack of contact with their general practitioner or community pharmacist after hospital discharge. CONCLUSIONS: Many of the difficulties stroke patients have adhering to secondary prevention strategies are potentially preventable with tailored information provision and appropriate monitoring and follow-up by primary healthcare professionals. We have designed an intervention addressing the identified barriers to medicine taking, the impact of which is currently being measured in a randomised controlled trial of a pharmacist-led home-based clinical medication review in stroke patients.

Left atrial appendage closure followed by 6 weeks of antithrombotic therapy: a prospective single-center experience.

BACKGROUND: Currently, 2 different left atrial appendage (LAA) closure systems are available for stroke prevention in nonvalvular atrial fibrillation but comparative data are lacking. OBJECTIVES: To prospectively compare procedural data and patient outcome for 2 contemporary LAA closure systems and to investigate an alternative antithrombotic treatment regimen in high-risk patients. METHODS: Patients with nonvalvular atrial fibrillation, with high risk for stroke, and who either had contraindication or were not willing to accept oral anticoagulation were prospectively enrolled. Watchman (Boston Scientific, Natick, MA; group A) or Amplatzer Cardiac Plug (St Jude Medical, Minneapolis, MN; group B) devices were implanted. All patients received antithrombotic therapy for 6 weeks. After repeat transesophageal echocardiography, patients were switched to aspirin. RESULTS: Eighty patients were enrolled. There was no statistical difference in patient characteristics in groups A and B: CHA2DS2VASC score: 4.1 ± 1.5 versus 4.5 ± 1.8; HASBLED score: 3.1 ± 1.1 versus 3.1 ± 1.1, respectively. LAA closure was achieved in 78 of 80 patients (98%) (group A: 38 of 40 [95%] vs group B: 40 of 40 [100%]). There was no difference in procedure time (group A: 48 ± 16 minutes vs group B: 47 ± 15 minutes; P = .69) and fluoroscopy time (group A: 6.0 ± 4.7 minutes vs group B: 7.3 ± 4.4 minutes; P = .25). Major complications included 1 air embolism and delayed tamponade in each group. After 6 weeks, 1 device dislodgment and 4 device-related thrombi were detected. Ninety-four percent of the patients (73 of 77) were switched to aspirin after 6 weeks. During a median follow-up of 364 days (Q1-Q3: 283-539 days), no systemic embolism occurred, but 3 patients died (heart failure: n = 2; bleeding: n = 1). CONCLUSIONS: Implantation of both LAA closure devices can be performed with high success rates in high-risk patients. Postprocedural 6 weeks antithrombotic therapy followed by aspirin therapy needs to be confirmed in a larger study.

Analysis of folic acid combined with vitamins on two primary prevention of stroke effect / 中国现代医生

Objective To study the analysis of folic acid combined with vitamin for level two ischemic stroke prevention effect. Methods From April 2013 to January 2014 in our hospital , selected the patients with stroke in 100 cases as the research object. In digital method were randomly divided into observation group (50 cases) and control group (50 cases). The patients in the observation group was taken folic acid combined with vitamin , the control group only was given vitamins, in all patients on admission and at discharge on the plasma levels of Hcy, D-two dimer, fibrinogen, three glycerol, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol level, the effect of folic acid combined with the vitamin was observed. Results No significant differences between the two groups before treatment, plasma Hcy levels (P>0.05) in different ways, the observation group after treatment, the plasma Hcy levels were significantly lower than the control group , with significant difference ( P<0 . 05 ) . Two groups by different ways of treatment, the observation group was best accounted for 70% (35/50), the excellent and good rate was as high as 98% (49/50), significantly higher than the control group 44% (22/50) and 74% (37/50), with significant difference (P<0.05). On two groups of different ways of treatment of cerebral was stroke recurrence and score in patients with SIAS were compared, the recurrence rate of the observation group was lower than the control group, with significant difference (P<0.05), the SIAS score was significantly higher than that of the control group, with significant difference (P<0.05). Conclusion For the patients with stroke, should the use of folic acid combine with vitamin two level of prevention. The combine uses of folic acid and vitamin , can effectively reduce the incidence of stroke and recurrence rate.

The Management of Cerebrovascular Accident

Most cerebrovascular diseases (CVA) are manifest by the abrupt onset of a focal neurologic deficit. The deficit may remain fixed or may rapidly improve or progressively worsen. Therefore, the main objective of treatment in cerebrovascular disease is the prevention of stroke. The current treatment of CVA may be divided into three parts : (1) management in the acute phase (restoration of the circulation and arrest of the pathologic process), (2) physical therapy and rehabilitation, and (3) prevention of the further recurrent strokes. When faced with an acute stroke, the clinician must differentiate between infarction and hemorrhage immediately, because the method of emergency treatment depends on the cause. The clinician should try to prevent or reverse acute brain injury with thrombolysis, and to inhibit the progression of cerebral infarction with anticoagulation or antiplatelet agents, and to prevent further neurologic injury with neuroprotection and attending to acute medical issues of airway, blood pressure, and concomitant organ failure. In addition, the clinician should remove or control the risk factors of stroke and must elaborate a proper strategy in order to prevent the secondary stroke.