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Background: Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed., Aims: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services., Methods: We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary., Results: Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and PRE-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (63% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulance services (80% in HICs) around the world., Conclusion: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available patient-level data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: India has a high burden of stroke, but there are limited data available on the characteristics of patients presenting with stroke in India., Aims: We aimed to document the clinical characteristics, practice patterns, and outcomes of patients presenting with acute stroke to Indian hospitals., Methods: A prospective registry study of patients admitted with acute clinical stroke was conducted in 62 centers across different regions in India between 2009 and 2013., Results: Of the 10,329 patients included in the prescribed registry, 71.4% had ischemic stroke, 25.2% had intracerebral hemorrhage (ICH), and 3.4% had an undetermined stroke subtype. Mean age was 60 years (SD = 14) with 19.9% younger than 50 years; 65% were male. A severe stroke at admission (modified-Rankin score 4-5) was seen in 62%, with 38.4% of patients having severe disability at discharge or dying during hospitalization. Cumulative mortality was 25% at 6 months. Neuroimaging was completed in 98%, 76% received physiotherapy, 17% speech and language therapy (SLT), 7.6% occupational therapy (OT), with variability among sites; 3.7% of ischemic stroke patients received thrombolysis. Receipt of physiotherapy (odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.33-0.52) and SLT (OR = 0.45, 95% CI: 0.32-0.65) was associated with lower mortality, while a history of atrial fibrillation (OR = 2.22, 95% CI: 1.37-3.58) and ICH (OR = 2.00, 95% CI: 1.66-2.40) were associated with higher mortality., Conclusion: In the INSPIRE (In Hospital Prospective Stroke Registry) study, one-in-five patients with acute stroke was under 50 years of age, and one-quarter of stroke was ICH. There was a low provision of thrombolysis and poor access to multidisciplinary rehabilitation highlighting how improvements are needed to reduce morbidity and mortality from stroke in India.

Rationale: The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary., Aim: To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity., Hypotheses: Compared with a prespecified reference arm, the optimal dose regimen(s) will result in more participants experiencing little or no disability (mRS 0-2) at 3 months post-stroke (primary), fewer deaths at 3 months, fewer and less severe complications during the intervention period, faster recovery of unassisted walking, and better quality of life at 3 months (secondary). We also hypothesize that these regimens will be more cost-effective., Sample Size Estimates: For the primary outcome, recruitment of 1300 mild and 1400 moderate participants will yield 80% power to detect a 10% risk difference., Methods and Design: Multi-arm multi-stage covariate-adjusted response-adaptive randomized trial of mobility training commenced within 48 h of stroke in mild (NIHSS < 7) and moderate (NIHSS 8-16) stroke patient strata, with analysis of blinded outcomes at 3 (primary) and 6 months. Eligibility criteria are broad, while excluding those with severe premorbid disability (mRS > 2) and hemorrhagic stroke. With four arms per stratum (reference arm retained throughout), only the single treatment arm demonstrating the highest proportion of favorable outcomes at the first stage will proceed to the second stage in each stratum, resulting in a final comparison with the reference arm. Three prognostic covariates of age, geographic region and reperfusion interventions, as well as previously observed mRS 0-2 responses inform the adaptive randomization procedure. Participants randomized receive prespecified mobility training regimens (functional task-specific), provided by physiotherapists/nurses until discharge or 14 days. Interventions replace usual mobility training. Fifty hospitals in seven countries (Australia, Malaysia, United Kingdom, Ireland, India, Brazil, Singapore) are expected to participate., Summary: Our novel adaptive trial design will evaluate a wider variety of mobility regimes than a traditional two-arm design. The data-driven adaptions during the trial will enable a more efficient evaluation to determine the optimal early mobility intervention for patients with mild and moderate ischemic stroke.

Background: Contemporary data on stroke epidemiology and the availability of national stroke clinical registries are important for providing evidence to improve practice and support policy decisions., Aims: To update the most current incidence, case-fatality, and mortality rates on stroke and identify national stroke clinical registries worldwide., Methods: We searched multiple databases (based on our existing search strategy) to identify new original papers, published between 1 November 2018 and 15 December 2021, that met ideal criteria for data on stroke incidence and case-fatality, and added these to the studies reported in our last review. To identify national stroke clinical registries, we updated our last search, using PubMed, from 6 February 2015 until 6 January 2022. We also screened reference lists of review papers, citation history of papers, and the gray literature. Mortality codes for International Classification of Diseases (ICD)-9 and ICD-10 were extracted from the World Health Organization (WHO) for each country providing these data. Population denominators were obtained from the United Nations (UN) or WHO (when data were unavailable in the UN database). Crude and adjusted stroke mortality rates were calculated using country-specific population denominators, and the most recent years of mortality data available for each country., Results: Since our last report in 2020, there were two countries (Chile and France) with new incidence studies meeting criteria for ideal population-based studies. New data on case-fatality were found for Chile and Kenya. The most current mortality data were available for the year 2014 (1 country), 2015 (2 countries), 2016 (11 countries), 2017 (10 countries), 2018 (19 countries), 2019 (36 countries), and 2020 (29 countries). Four countries (Libya, Solomon Islands, United Arab Emirates, and Lebanon) reported mortality data for the first time. Since our last report on registries in 2017, we identified seven more national stroke clinical registries, predominantly in high-income countries. These newly identified registries yielded limited information., Conclusions: Up-to-date data on stroke incidence, case-fatality, and mortality continue to provide evidence of disparities and the scale of burden in low- and middle-income countries. Although more national stroke clinical registries were identified, information from these newly identified registries was limited. Highlighting data scarcity or even where a country is ranked might help facilitate more research or greater policy attention in this field.

Stroke remains the second-leading cause of death and the third-leading cause of death and disability combined (as expressed by disability-adjusted life-years lost - DALYs) in the world. The estimated global cost of stroke is over US$721 billion (0.66% of the global GDP). From 1990 to 2019, the burden (in terms of the absolute number of cases) increased substantially (70.0% increase in incident strokes, 43.0% deaths from stroke, 102.0% prevalent strokes, and 143.0% DALYs), with the bulk of the global stroke burden (86.0% of deaths and 89.0% of DALYs) residing in lower-income and lower-middle-income countries (LMIC). This World Stroke Organisation (WSO) Global Stroke Fact Sheet 2022 provides the most updated information that can be used to inform communication with all internal and external stakeholders; all statistics have been reviewed and approved for use by the WSO Executive Committee as well as leaders from the Global Burden of Disease research group.

Background: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization-World Health Organization- Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries., Methods: Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019., Results: Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p < 0.001). Acute stroke treatments were offered in ∼ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol., Conclusions: There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.

Background: Data on stroke epidemiology and availability of hospital-based stroke services around the world are important for guiding policy decisions and healthcare planning., Aims: To provide the most current incidence, mortality and case-fatality data on stroke and describe current availability of stroke units around the world by country., Methods: We searched multiple databases (based on our existing search strategy) to identify new original manuscripts and review articles published between 1 June 2016 and 31 October 2018 that met the ideal criteria for data on stroke incidence and case-fatality. For data on the availability of hospital-based stroke services, we searched PubMed for all literature published up until 31 June 2018. We further screened reference lists, citation history of manuscripts and gray literature for this information. Mortality codes for International Classification of Diseases-9 and International Classification of Diseases-10 were extracted from the World Health Organization mortality database for each country providing these data. Population denominators were obtained from the World Health Organization, and when these were unavailable within a two-year period of mortality data, population denominators within a two-year period were obtained from the United Nations. Using country-specific population denominators and the most recent years of mortality data available for each country, we calculated both the crude mortality from stroke and mortality adjusted to the World Health Organization world population., Results: Since our last report in 2017, there were two countries with new incidence studies, China ( n  = 1) and India ( n  = 2) that met the ideal criteria. New data on case-fatality were found for Estonia and India. The most current mortality data were available for the year 2015 (39 countries), 2016 (43 countries), and 2017 (7 countries). No new data on mortality were available for six countries. Availability of stroke units was noted for 63 countries, and the proportion of patients treated in stroke units was reported for 35/63 countries., Conclusion: Up-to-date data on stroke incidence, case-fatality, and mortality statistics provide evidence of variation among countries and changing magnitudes of burden among high and low-middle income countries. Reporting of hospital-based stroke units remains limited and should be encouraged.

Background: India is a large country with geographically diverse populations and varying risk factors. Identification of regional differences can improve healthcare policy decisions., Aim: To study regional differences in stroke between North and South India., Methods: We analyzed data from the Indo-US Collaborative Stroke Project, a National Institute of Health-funded multicentre prospective study conducted in five academic centers in India with a US-based coordinating center. Risk factors, severity, mechanisms, management, complications, and outcomes among ischemic stroke patients were compared between North and South Indian centers., Results: Of the 2066 patients enrolled from North ( n  = 1060) and South India ( n  = 1006), North Indian patients were significantly older with fewer men and had lower rates of diabetes (32.8% vs. 38.7%, p  < 0.01), dyslipidemia (3.5% vs. 25.7%, p  < 0.01), tobacco use (27% vs. 38%, p  < 0.001), and alcohol use (30.1% vs. 38.6%, p  < 0.01). North Indian patients had higher median National Institute of Health stroke scale scores (10 vs. 9, p  < 0.01), more frequent large-artery atherosclerosis mechanism (34% vs. 25.6%, p  < 0.001), intravenous thrombolysis (14.0% vs. 6.1%, p  < 0.001), and lower rates of pneumonia (10.5% vs. 15.1%, p  = 0.02). The three-month outcome (modified Rankin Scale score 0-2, 45.8% vs. 50.3%, p  = 0.08) did not differ; however, North Indian patients had higher 90-day mortality (23.5% vs. 13.5%, p  < 0.0001)., Conclusions: The substantial regional differences in stroke risk factors and mechanisms may be partly explained by factors such as differing dietary habits and lifestyle, which can be addressed at a national level. Differences in acute and inpatient stroke care suggest a need for better adoption of national stroke management guidelines.

Conclusion: An effective primary stroke prevention strategy on a global scale should integrate pharmacological (polypill) and lifestyle modifications (motivational population-wide strategy) interventions. Side effects of such an integrative approach are expected to be minimal and the benefits among individuals at low-to-moderate risk of stroke could be significant. In the future, pragmatic field trials will provide more evidence.

Rationale: Controversy exists over the optimal dose of intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) and degree of blood pressure (BP) control in acute ischaemic stroke (AIS). Asian studies suggest low-dose (0·6 mg/kg) is more efficacious than standard-dose (0·9 mg/kg) i.v. rt-PA, and guidelines recommend reducing systolic BP to <185 mmHg before and <180 mmHg after use of i.v. rt-PA, despite observational studies indicating better outcomes at much lower (<140 mmHg) systolic BP levels in this patient group., Aims: The study aims to assess in thrombolysis-eligible AIS patients whether: (i) low-dose (0·6 mg/kg body weight; maximum 60 mg) i.v. rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage (sICH) compared to standard-dose (0·9 mg/kg body weight; maximum 90 mg) i.v. rt-PA; and (ii) early intensive BP lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of any ICH compared to guideline-recommended BP control (systolic target < 180 mmHg)., Design: The ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED) trial is an independent,2 × 2 quasi-factorial, active-comparison, prospective, randomized, open blinded endpoint (PROBE), clinical trial that is evaluating Arm [A] 'rt-PA dose' and/or Arm [B] 'BP control', using central Internet randomization and data collection in patients fulfilling local criteria for thrombolysis and clinician uncertainty over the study treatments. The treatment arms will be analyzed separately., Study Outcomes: The primary study outcome in both trial Arms is death or disability according to the modified Rankin scale (mRS, scores 2-6) assessed at 90 days. Secondary outcomes include sICH, any ICH, a shift ('improvement') in function across mRS scores, separately on death and disability, early neurological deterioration, recurrent major vascular events, health-related quality of life, length of hospital stay, need for permanent residential care, and health care costs., Results: Following launch of the trial in February 2012, the study has recruited more than 2500 patients across a global network of approximately 100 sites in 15 countries. The required sample sizes are 3300 for Arm [A] and 2300 for Arm [B], which will provide >90% power to detect non-inferiority of low-dose i.v. rt-PA and superiority of intensive BP lowering on the primary clinical outcome, respectively., Conclusions: Low-dose i.v. rt-PA and early intensive BP lowering could provide more affordable and safer use of thrombolysis treatment for patients with AIS worldwide., (© 2015 World Stroke Organization.)

Background: Over the past few decades, the burden of stroke in developing countries has grown to epidemic proportions. Two-thirds of global stroke occurs in low- and middle-income countries. We have found that little information is obtainable concerning the availability of thrombolysis therapy in developing countries., Summary of Review: The epidemiology of stroke is well investigated in the developed world; however, in the developing world stroke is less well documented. Most of the available stroke data from these countries are hospital-based. Stroke thrombolysis is currently used in few developing countries like Brazil, Argentina, Senegal, Iran, Pakistan, China, Thailand, and India. The two main barriers for implementation of thrombolysis therapy in developing countries are the high cost of tissue plasminogen activator and lack of proper infrastructure. Most of the centers with the infrastructure to deliver thrombolysis for stroke are predominantly private sector, and only available in urban areas., Conclusion: Until a more cost-effective thrombolytic agent and the proper infrastructure for widespread use of thrombolysis therapy are available, developing nations should focus on primary and secondary stroke prevention strategies and the establishment of stroke units wherever possible. Such multi-faceted approaches will be more cost-effective for developing countries than the use of thrombolysis.