A critical assessment of the current pharmacotherapy for the treatment of embolic strokes of undetermined source.

INTRODUCTION: 'Embolic stroke of undetermined source' (ESUS) is a term coined to identify non-lacunar stroke whose mechanism is likely to be embolic, and the source remains unidentified. The best antithrombotic treatment for preventing stroke recurrence in this population has not been delineated. AREAS COVERED: The authors summarize and critically appraise the currently available evidence about the antithrombotic treatment for preventing stroke recurrence in patients with ESUS. Randomized trials addressing this topic were identified through MEDLINE (accessed by PubMed, as of November 2021, week 4). EXPERT OPINION: Recent randomized trials have failed to demonstrate a significant benefit of direct oral anticoagulants over aspirin in reducing the recurrence of cerebral infarctions in unselected cohorts of patients with ESUS. The heterogeneity and often overlap of embolic sources may be possible explanations for the overall absence of a benefit of oral anticoagulants in ESUS as a single homogeneous entity. The results of these trials and their subgroup analyses have provided important cues to understand the pathophysiology of ESUS. They have, furthermore, increased in the interest in researchers in identifying distinct etiological phenotypes within this stroke population. There is a good rationale for ongoing and future investigations in order to tailor antithrombotic treatment according to individual features of patients with ESUS.

Incidence, prevalence and disability associated with neurological disorders in Italy between 1990 and 2019: an analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: Neurological conditions are highly prevalent and disabling, in particular in the elderly. The Italian population has witnessed sharp ageing and we can thus expect a rising trend in the incidence, prevalence and disability of these conditions. METHODS: We relied on the Global Burden of Disease 2019 study to extract Italian data on incidence, prevalence and years lived with a disability (YLDs) referred to a broad set of neurological disorders including, brain and nervous system cancers, stroke, encephalitis, meningitis, tetanus, traumatic brain injury, and spinal cord injury. We assessed changes between 1990 and 2019 in counts and age-standardized rates. RESULTS: The most prevalent conditions were tension-type headache, migraine, and dementias, whereas the most disabling were migraine, dementias and traumatic brain injury. YLDs associated with neurological conditions increased by 22.5%, but decreased by 2.3% in age-standardized rates. The overall increase in prevalence and YLDs counts was stronger for non-communicable diseases with onset in old age compared to young to adult-age onset ones. The same trends were in the opposite direction when age-standardized rates were taken into account. CONCLUSIONS: The increase in YLDs associated with neurological conditions is mostly due to population ageing and growth: nevertheless, lived disability and, as a consequence, impact on health systems has increased. Actions are needed to improve outcome and mitigate disability associated with neurological conditions, spanning among diagnosis, treatment, care pathways and workplace interventions.

Trends in cardiovascular diseases burden and vascular risk factors in Italy: The Global Burden of Disease study 1990-2017.

AIMS: An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries. METHODS: All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries. RESULTS: Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function. CONCLUSIONS: Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.

Enhancing and accelerating stroke treatment in Eastern European region: Methods and achievement of the ESO EAST program.

INTRODUCTION: Despite the availability of prevention and therapies of stroke, their implementation in clinical practice, even of low-cost ones, remains poor. In 2015, the European Stroke Organisation (ESO) initiated the ESO Enhancing and Accelerating Stroke Treatment (EAST) program, which aims to improve stroke care quality, primarily in Eastern Europe. Here, we describe its methods and milestones. PATIENTS AND METHODS: The ESO EAST program is using an implementation strategy based on a 'detecting-understanding-reducing disparities' conceptual framework: stroke care quality is first measured (after developing a platform for data collection), gaps are identified in the current service delivery, and ultimately feedback is provided to participating hospitals, followed by the application of interventions to reduce disparities. The ESO EAST program is carried out by establishing a stroke quality registry, stroke management infrastructure, and creating education and training opportunities for healthcare professionals. RESULTS: Program management and leadership infrastructure has been established in 19 countries (Country Representatives in 22 countries, National Steering Committee in 19 countries). A software platform for data collection and analysis: Registry of Stroke Care Quality was developed, and launched in 2016, and has been used to collect data from over 90,000 patients from >750 hospitals and 56 countries between September 2016 and May 2019. Training in thrombolysis, nursing and research skills has been initiated. DISCUSSION: ESO EAST is the first pan-Eastern European (and beyond) multifaceted quality improvement intervention putting evidence-informed policies into practice. Continuous monitoring of stroke care quality allows hospital-to-hospital and country-to-country benchmarking and identification of the gaps and needs in health care.

Preserving stroke care during the COVID-19 pandemic: Potential issues and solutions.

The coronavirus 2019 (COVID-19) pandemic requires drastic changes in allocation of resources, which can affect the delivery of stroke care, and many providers are seeking guidance. As caregivers, we are guided by 3 distinct principles that will occasionally conflict during the pandemic: (1) we must ensure the best care for those stricken with COVID-19, (2) we must provide excellent care and advocacy for patients with cerebrovascular disease and their families, and (3) we must advocate for the safety of health care personnel managing patients with stroke, with particular attention to those most vulnerable, including trainees. This descriptive review by a diverse group of experts in stroke care aims to provide advice by specifically addressing the potential impact of this pandemic on (1) the quality of the stroke care delivered, (2) ethical considerations in stroke care, (3) safety and logistic issues for providers of patients with stroke, and (4) stroke research. Our recommendations on these issues represent our best opinions given the available information, but are subject to revision as the situation related to the COVID-19 pandemic continues to evolve. We expect that ongoing emergent research will offer additional insights that will provide evidence that could prompt the modification or removal of some of these recommendations.

Access to and delivery of acute ischaemic stroke treatments: A survey of national scientific societies and stroke experts in 44 European countries.

INTRODUCTION: Acute stroke unit care, intravenous thrombolysis and endovascular treatment significantly improve the outcome for patients with ischaemic stroke, but data on access and delivery throughout Europe are lacking. We assessed best available data on access and delivery of acute stroke unit care, intravenous thrombolysis and endovascular treatment throughout Europe. METHODS: A survey, drafted by stroke professionals (ESO, ESMINT, EAN) and a patient organisation (SAFE), was sent to national stroke societies and experts in 51 European countries (World Health Organization definition) requesting experts to provide national data on stroke unit, intravenous thrombolysis and endovascular treatment rates. We compared both pooled and individual national data per one million inhabitants and per 1000 annual incident ischaemic strokes with highest country rates. Population estimates were based on United Nations data, stroke incidences on the Global Burden of Disease Report. RESULTS: We obtained data from 44 European countries. The estimated mean number of stroke units was 2.9 per million inhabitants (95% CI 2.3-3.6) and 1.5 per 1000 annual incident strokes (95% CI 1.1-1.9), highest country rates were 9.2 and 5.8. Intravenous thrombolysis was provided in 42/44 countries. The estimated mean annual number of intravenous thrombolysis was 142.0 per million inhabitants (95% CI 107.4-176.7) and 72.7 per 1000 annual incident strokes (95% CI 54.2-91.2), highest country rates were 412.2 and 205.5. Endovascular treatment was provided in 40/44 countries. The estimated mean annual number of endovascular treatments was 37.1 per million inhabitants (95% CI 26.7-47.5) and 19.3 per 1000 annual incident strokes (95% CI 13.5-25.1), highest country rates were 111.5 and 55.9. Overall, 7.3% of incident ischaemic stroke patients received intravenous thrombolysis (95% CI 5.4-9.1) and 1.9% received endovascular treatment (95% CI 1.3-2.5), highest country rates were 20.6% and 5.6%. CONCLUSION: We observed major inequalities in acute stroke treatment between and within 44 European countries. Our data will assist decision makers implementing tailored stroke care programmes for reducing stroke-related morbidity and mortality in Europe.

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Countries with women inequalities have higher stroke mortality.

Background Stroke outcomes can differ by women's legal or socioeconomic status. Aim We investigated whether differences in women's rights or gender inequalities were associated with stroke mortality at the country-level. Methods We used age-standardized stroke mortality data from 2008 obtained from the World Health Organization. We compared female-to-male stroke mortality ratio and stroke mortality rates in women and men between countries according to 50 indices of women's rights from Women, Business and the Law 2016 and Gender Inequality Index from the Human Development Report by the United Nations Development Programme. We also compared stroke mortality rate and income at the country-level. Results In our study, 176 countries with data available on stroke mortality rate in 2008 and indices of women's rights were included. There were 46 (26.1%) countries where stroke mortality in women was higher than stroke mortality in men. Among them, 29 (63%) countries were located in Sub-Saharan African region. After adjusting by country income level, higher female-to-male stroke mortality ratio was associated with 14 indices of women's rights, including differences in getting a job or opening a bank account, existence of domestic violence legislation, and inequalities in ownership right to property. Moreover, there was a higher female-to-male stroke mortality ratio among countries with higher Gender Inequality Index (r = 0.397, p < 0.001). Gender Inequality Index was more likely to be associated with stroke mortality rate in women than that in men (p < 0.001). Conclusions Our study suggested that the gender inequality status is associated with women's stroke outcomes.

Stroke in women - from evidence to inequalities.

Stroke is the second largest cause of disability-adjusted life-years lost worldwide. The prevalence of stroke in women is predicted to rise rapidly, owing to the increasing average age of the global female population. Vascular risk factors differ between women and men in terms of prevalence, and evidence increasingly supports the clinical importance of sex differences in stroke. The influence of some risk factors for stroke - including diabetes mellitus and atrial fibrillation - are stronger in women, and hypertensive disorders of pregnancy also affect the risk of stroke decades after pregnancy. However, in an era of evidence-based medicine, women are notably under-represented in clinical trials - despite governmental actions highlighting the need to include both men and women in clinical trials - resulting in a reduced generalizability of study results to women. The aim of this Review is to highlight new insights into specificities of stroke in women, to plan future research priorities, and to influence public health policies to decrease the worldwide burden of stroke in women.

Acute stroke symptoms: do differences exist between sexes?

BACKGROUND: Previous studies have reported that women with stroke often present different stroke symptoms than men. The aim of our study was to assess for the relevance of these differences from a large case series. METHODS: Consecutive patients admitted to the Stroke Unit at the University of Perugia, with acute stroke or transient ischemic attack between 1 June, 2005, and May 2012, and recorded in Perugia Stroke Registry were prospectively included. Associations between the recorded symptoms and sex were assessed by preliminary cross-tabulations with the Chi-square test or Fisher exact test with Yate correction when appropriate. Multivariable regression analysis was used to identify independent predictors of a single symptom including sex as an independent variable. RESULTS: Overall, 1072 men and 811 women were included in this study. Women had a higher average age at onset (75.40 ± 12.90 years in women and 70.14 ± 12.61 years in men) and presented more severe strokes with higher National Institute of Health Stroke Scale scores than men, whereas men were more likely to have a posterior stroke.Regarding symptoms, multivariate analysis revealed correlations between postural instability and male sex and between dysphagia and female sex. CONCLUSIONS: We found no differences in the clinical presentation of stroke between the sexes, except that men were more likely to have postural instability and females were more likely to have dysphagia. These findings suggest that stroke locations and stroke severity were associated with sex.

Women Stroke Association Statement on Stroke.

We describe the current and future objectives of the Women Stroke Association, a nonprofit multidisciplinary organization promoting research awareness on medical, psychological, and social issues concerning women affected by cerebrocardiovascular disease. In this paper, we deal with only cerebrovascular disease, whereas cardiovascular disorders will be addressed in a future paper. Gender differences in the clinical presentation of cerebrovascular diseases have been repeatedly suggested, and some treatment options may not be as effective and safe in men and women. For many years, women have either been underrepresented or excluded from randomized clinical trials, and the majority of therapeutic research has been carried on predominantly male populations. Furthermore, gender differences have been shown to contribute to different responses to cerebrovascular drugs in women when compared with men, regarding pharmacokinetics, pharmacodynamics, and physiology. In this statement, we discuss main research fields relevant to Women Stroke Association's mission and commitment, highlighting opportunities and critical from the women's health perspective. Future directions and goals of the Women Stroke Association arise from these considerations and represent the association's commitment to combating stroke.