Stroke in Asia.

Background There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition. Summary In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy and cerebral venous thrombosis. Key Messages The review of selected literature and recent updates, call for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.

STENOSIS: Long-term single versus dual antiplatelet therapy in patients with ischaemic stroke due to intracranial atherosclerotic disease - a randomised trial.

Rationale: Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications. Aim: The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD. Sample size: Using 80% power and an alpha error of 5 %, presuming a 10%-15% drop-out rate, a total of 2200 patients will be recruited for the study. Methodology: This is a prospective, randomised, double-blind, placebo controlled trial. Study outcomes: The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase. Discussion: The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.

Secondary prevention by structured semi-interactive stroke prevention package in INDIA (SPRINT INDIA): Findings from the process evaluation of a randomized controlled trial.

INTRODUCTION: Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in INDIA Trial delivered secondary stroke awareness intervention to sub-acute stroke patients in form of workbook, videos and SMS across 31 centres in 12 languages. Trial was stopped for futility due to fewer vascular outcomes than anticipated. Trial results indicated that trial intervention, did not lead to reduction in vascular events. We carried out process evaluation, to evaluate trial implementation and participant's perspectives, to comprehend the trial's futile outcomes. MATERIALS AND METHODS: Using mixed methods approach, qualitative interviews and quantitative data from case report forms, workbooks and questionnaires were analysed to measure intervention fidelity and contamination. Using purposive sampling, 115 interviews of patient-caregiver dyads and health professionals at 11 centres and 2 focus group discussions were held. RESULTS AND DISCUSSION: Iterative thematic analysis of qualitative data was done with RE-AIM and realist models. There was good fidelity to intervention and adherence to protocol; however, there was dilution of inclusion criteria by randomly enrolling uneducated and caregiver-dependent patients. Centre coordinators provided counselling to both arms, not specified by protocol, causing bias. Coordinators found it difficult to keep patients motivated to view intervention which was corroborated by fidelity questionnaire showing decreased viewing of intervention for a year. Cardiovascular protection improved in routine care by virtue of participating in trial. No contamination of intervention was reported. CONCLUSION: The intervention was acceptable by patients and caregivers, which could be made a community-based programme. Reasons identified for decreased viewing were repetitive content and non-availability of personal cellular device.

Six years of the Angels Initiative: Aims, achievements, and future directions to improve stroke care worldwide.

The rate of stroke-related death and disability is four times higher in low- and middle-income countries (LMICs) than in high-income countries (HICs), yet stroke units exist in only 18% of LMICs, compared with 91% of HICs. In order to ensure universal and equitable access to timely, guideline-recommended stroke care, multidisciplinary stroke-ready hospitals with coordinated teams of healthcare professionals and appropriate facilities are essential.Established in 2016, the Angels Initiative is an international, not-for-profit, public-private partnership. It is run in collaboration with the World Stroke Organization, European Stroke Organisation, and regional and national stroke societies in over 50 countries. The Angels Initiative aims to increase the global number of stroke-ready hospitals and to optimize the quality of existing stroke units. It does this through the work of dedicated consultants, who help to standardize care procedures and build coordinated, informed communities of stroke professionals. Angels consultants also establish quality monitoring frameworks using online audit platforms such as the Registry of Stroke Care Quality (RES-Q), which forms the basis of the Angels award system (gold/platinum/diamond) for all stroke-ready hospitals across the world.The Angels Initiative has supported over 1700 hospitals (>1000 in LMICs) that did not previously treat stroke patients to become "stroke ready." Since its inception in 2016, the Angels Initiative has impacted the health outcomes of an estimated 7.46 million stroke patients globally (including an estimated 4.68 million patients in LMICs). The Angels Initiative has increased the number of stroke-ready hospitals in many countries (e.g. in South Africa: 5 stroke-ready hospitals in 2015 vs 185 in 2021), reduced "door to treatment time" (e.g. in Egypt: 50% reduction vs baseline), and increased quality monitoring substantially.The focus of the work of the Angels Initiative has now expanded from the hyperacute phase of stroke treatment to the pre-hospital setting, as well as to the early post-acute setting. A continued and coordinated global effort is needed to achieve the target of the Angels Initiative of >10,000 stroke-ready hospitals by 2030, and >7500 of these in LMICs.

Community health volunteer for blood pressure control in rural people with stroke in India: Pilot randomised trial.

OBJECTIVE: To test the hypothesis that an Accredited social health activist (ASHA), a community health volunteer in a task-sharing model can help in sustained control of systolic blood pressure (BP) in rural people with Stroke and hypertension at 6 months follow up. METHODS: In this randomized trial two rural areas (Pakhowal and Sidhwan bet) with 70 and 94 villages respectively were screened for people with stroke and hypertension. They were assigned to either ASHA-assisted BP control in addition to standard-of-care (Pakhowal-intervention Group) or standard-of-care alone (Sidhwan bet- Control Group). Assessors blinded to intervention conducted the baseline and 6 months follow-up visits to measure risk factors in both the rural areas. RESULTS: A total of 140 people with stroke with mean age of 63.7 ± 11.5 years and 44.3% females were randomised. The baseline systolic BP was higher in the intervention group (n = 65,173.5 ± 22.9 mmHg) compared to the control group (n = 75,163 ± 18.7 mmHg, p = 0.004). The follow-up systolic BP was lower in the intervention group compared to the control group 145 ± 17.2 mmHg and 166.6 ± 25.7 mmHg respectively (p < 0.0001). According to the intention-to-treat analysis a total of 69.2% of patients in the intervention group achieved systolic BP control compared to 18.9% in the control group patients (OR 9, 95% CI 3.9-20.3; p < 0.0001). CONCLUSION: Task sharing with ASHA a community health volunteer can improve BP control in rural people with stroke and hypertension. They can also help in the adoption of healthy behaviour. CLINICAL TRIAL REGISTRATION NUMBER: ctri.nic.in, CTRI/2018/09/015709.

A Scoping Review of Recent Advancements in Intervention and Outcome Measures for Post-Stroke Cognitive Impairments.

Background: Cognitive deficit is one of the common impairments that occur post stroke and have a major effect on the quality of life of stroke survivors. However, the intervention and outcome measures used to remediate post-stroke cognitive impairments are diverse and highly heterogeneous. Therefore, a review of intervention and outcome measures for post-stroke cognitive impairments was carried out. Objectives: To review all available information on the recent advancements in intervention and outcome measures for post-stroke cognitive impairments. Methods: An electronic database search was conducted in PubMed, Medline, Google Scholar, and the Cochrane Library with key search terms between 2001 and 2021. The search results were systematically screened, and data was independently extracted by three reviewers. The data was thematically analyzed and narratively synthesized. Results: The search retrieved 2018 records, and we included 12 studies that met the inclusion criteria. Most of the studies targeted global cognitive deficits in ischemic stroke patients in the chronic phase. We categorized data based on the type of cognitive impairment, cognitive- domain targeted, intervention, and available outcome measures for post-stroke cognitive rehabilitation. Attention, memory, executive function, and global cognition were the common cognitive components targeted, managed, and assessed using an outcome measure. We found that technology is replacing conventional approaches to improve cognitive impairment. Conclusion: Regardless of many new developments in post-stroke cognitive rehabilitation interventions driven by technology, there is limited data available on actual implementation as a scalable solution. There is an extensive need for future research for evidence-based assessment and management of cognitive impairments in post-stroke rehabilitation.

Ayurvedic Treatment in the Rehabilitation of Ischemic Stroke Patients in India: A Randomized Controlled Trial Study Protocol.

In patients with ischemic stroke, motor and sensory impairments are common and are associated with functional disability. Conventional physiotherapy (CP) is the primary modality of rehabilitation for post-stroke sensorimotor dysfunction. Ayurveda is a commonly practiced alternative system of medicine that offers unique rehabilitative measures for post-stroke recovery. We hypothesize that Ayurvedic rehabilitative treatment (ART) is superior to similar duration CP in improving the sensorimotor recovery of patients with ischemic stroke at 90 days after enrollment. AyuRvedic TrEatment in the Rehabilitation of Ischemic STrOke Patients in India: A Randomized controllEd trial (RESTORE) is an investigator-initiated, multicenter, prospective, randomized, controlled, parallel-arm, blinded outcome assessment trial being conducted under the Indian Stroke Clinical Trial (INSTRuCT) Network across the four comprehensive stroke centers in India. Consecutive hemodynamically stable adult patients with their first acute ischemic stroke between 1 and 3 months from stroke onset are being randomized (1:1) into two treatment groups to receive either 1 month of ART or 1 month of CP. The primary outcome measure is the Fugl Meyer Assessment-upper extremity for physical performance at 90 days. The secondary outcomes are the modified Rankin Scale, Barthel Index, Berg Balance, and SF-36 at 90 days. The safety outcomes include a composite of irreversible morbidity and mortality. A sample size of 140 (70 in each group) patients with ischemic stroke will allow us to detect a minimal clinical important difference of 9.4 (standard deviation) with superiority margin of 5, an attrition rate of 10%, alpha of 5%, and power of 80%. This randomized trial will systematically assess the efficacy and safety of traditional ART compared to CP. The trial has been registered in the Clinical Trial Registry India (CTRI/2018/04/013379).

Reliability of Instant Messaging-Based Evaluation of Brain Imaging in Acute Stroke.

BACKGROUND: The use of instant messenger applications among physicians has become common in acute stroke management, especially in developing countries. Photos or video sequences of brain computed tomography (CT) scans are being sent to receive real-time support in assessing radiological findings. We analyzed whether instant messaging-based evaluation is precise enough to extract relevant information from the images. METHODS: In this prospective study, anonymized videos and photos of CT and CT angiography scans of patients with symptoms of acute stroke were recorded from the diagnostic monitor using a smartphone. Two neurologists and 2 neuroradiologists performed evaluation of the images using WhatsApp. The gold standard was set by 2 experienced neuroradiologists who evaluated the CT images with their full radiological equipment. Statistical analysis included the calculation of Cohen kappa (κ). RESULTS: A total of 104 brain images (derived from 81 patients) were included. All 4 raters performed with a perfect (κ=1) interobserver reliability in diagnosing intracerebral hemorrhage. For subarachnoid hemorrhage, interobserver reliability was slightly lower (raters 1, 2, and 3, κ=1; rater 4, κ=0.88). For diagnosing stroke mimics, interobserver reliability showed considerable variations (κ between 0.32 and 1). Alberta Stroke Program Early CT Score differences overall were comparable between raters and did not exceed 3 to 4 points without noticeable outliers. All raters performed with a moderate-to-substantial interobserver reliability for detecting large vessel occlusions (κ=0.48 in rater 1, κ=0.62 in rater 2, and κ=0.63 in raters 3 and 4). CONCLUSIONS: Stroke neurologists can reliably extract information on intracerebral hemorrhage from CT images recorded via smartphone and sent through instant messaging tools. Remote diagnosis of early infarct signs and stroke mimics was less reliable. We developed a standard for the acquisition of images, taking data protection into account.

Regional and national differences in stroke thrombolysis use and disparities in pricing, treatment availability, and coverage.

BACKGROUND: Major disparities have been reported in recombinant tissue plasminogen activator (rtPA) availability among countries of different socioeconomic status. AIMS: To characterize variability of rtPA price, its availability, and its association with and impact on each country's health expenditure (HE) resources. METHODS: We conducted a global survey to obtain information on rtPA price (50 mg vial, 2020 US Dollars) and availability. Country-specific data, including low, lower middle (LMIC), upper middle (UMIC), and high-income country (HIC) classifications, and gross domestic product (GDP) and HE, both nominally and adjusted for purchasing power parity (PPP), were obtained from World Bank Open Data. To assess the impact of rtPA cost, we computed the rtPA price as percentage of per capita GDP and HE and examined its association with the country income classification. RESULTS: rtPA is approved and available in 109 countries. We received surveys from 59 countries: 27 (46%) HIC, 20 (34%) UMIC, and 12 (20%) LMIC. Although HIC have significantly higher per capita GDP and HE compared to UMIC and LMIC (p < 0.0001), the median price of rtPA is non-significantly higher in LMICs (USD 755, interquartile range, IQR (575-1300)) compared to UMICs (USD 544, IQR (400-815)) and HICs (USD 600, IQR (526-1000)). In LMIC, rtPA cost accounts for 217.4% (IQR, 27.1-340.6%) of PPP-adjusted per capita HE, compared to 17.6% (IQR (11.2-28.7%), p < 0.0001) for HICs. CONCLUSION: We documented significant variability in rtPA availability and price among countries. Relative costs are higher in lower income countries, exceeding the available HE. Concerted efforts to improve rtPA affordability in low-income settings are necessary.

Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India.

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Case-Fatality and Functional Outcome after Subarachnoid Hemorrhage (SAH) in INternational STRoke oUtComes sTudy (INSTRUCT).

BACKGROUND: There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. METHODS: We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. RESULTS: Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. CONCLUSION: Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial.

BACKGROUND: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. METHODS: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1-7.8 mmol/L and 7.8-10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. DISCUSSION: As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established. TRIAL REGISTRATION: ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017.

Preventing the Next Pandemic: The Case for Investing in Circulatory Health - A Global Coalition for Circulatory Health Position Paper.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

Serum GFAP for stroke diagnosis in regions with limited access to brain imaging (BE FAST India).

INTRODUCTION: Despite a high burden of stroke, access to rapid brain imaging is limited in many middle- and low-income countries. Previous studies have described the astroglial protein GFAP (glial fibrillary acidic protein) as a biomarker of intracerebral hemorrhage. The aim of this study was to test the diagnostic accuracy of GFAP for ruling out intracranial hemorrhage in a prospective cohort of Indian stroke patients. PATIENTS AND METHODS: This study was conducted in an Indian tertiary hospital (Christian Medical College, Ludhiana). Patients with symptoms suggestive of acute stroke admitted within 12 h of symptom onset were enrolled. Blood samples were collected at hospital admission. Single Molecule Array technology was used for determining serum GFAP concentrations. RESULTS: A total number of 155 patients were included (70 intracranial hemorrhage, 75 ischemic stroke, 10 stroke mimics). GFAP serum concentrations were elevated in intracranial hemorrhage patients compared to ischemic stroke patients [median (interquartile range) 2.36 µg/L (0.61-7.16) vs. 0.18 µg/L (0.11-0.38), p < 0.001]. Stroke mimics patients had a median GFAP serum level of 0.14 µg/L (0.09-0.26). GFAP values below the cut-off of 0.33 µg/L (area under the curve 0.871) ruled out intracranial hemorrhage with a negative predictive value of 89.7%, (at a sensitivity for detecting intracranial hemorrhage of 90.0%). DISCUSSION: The high negative predictive value of a GFAP test system allows ruling out patients with intracranial hemorrhage. CONCLUSION: In settings where immediate brain imaging is not available, this would enable to implement secondary prevention (e.g., aspirin) in suspected ischemic stroke patients as soon as possible.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Influence of Including Patients with Premorbid Disability in Acute Stroke Trials: The HeadPoST Experience.

BACKGROUND: Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. METHODS: Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 ("early ΔmRS"), and poor outcome (mRS score 3-6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0-1 versus 2-5. RESULTS: Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2-5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14-1.27; p < 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend p < 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. CONCLUSIONS: Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. CLINICAL TRIAL REGISTRATION: HeadPoST is registered at http://www.ClinicalTrials.gov (NCT02162017).

Systematic Development of Structured Semi-interactive Stroke Prevention Package for Secondary Stroke Prevention.

BACKGROUND: Lack of compliance to medication and uncontrolled risk factors are associated with increased risk of recurrent stroke and acute coronary syndrome in patients with recent stroke. Multimodal patient education may be a strategy to improve the compliance to medication and early adoption of nonpharmacological measures to reduce the vascular risk factor burden in patients with stroke. We thus aim to develop multilingual short messaging services (SMS), print, and audio-visual secondary stroke prevention patient education package. The efficacy of the package will be tested in a randomized control trial to prevent major cardiovascular and cerebrovascular events. METHODS: In the formative stage, intervention materials (SMS, video, and workbook) were developed. In the acceptability stage, the package was independently assessed and modified by the stakeholders involved in the stroke patient care and local language experts. The modified stroke prevention package was tested for implementation issues (implementation stage). RESULTS: Sixty-nine SMS, six videos, and workbook with 11 chapters with 15 activities were developed in English language with a mean ± SD SMOG index of 9.1 ± 0.4. A total of 355 stakeholders including patients (24.8%), caregivers (24.8%), doctors (10.4%), nurses (14.1%), local language experts (2.8%), physiotherapists (13.2%), and research coordinators (9.8%) participated in 10 acceptability stage meetings. The mean Patient Education Material Assessment Tool understandability score in all languages for SMS, video scripts, and workbook was 95.2 ± 2.6%, 95.2 ± 4.4%, and 95.3 ± 3.6%, respectively. The patients [n = 20, mean age of 70.3 ± 10.6 years and median interquartile range (IQR) baseline NIHSS 1 (0-3)] or the research coordinators (n = 2) noted no implementation issues at the end of 1 month. CONCLUSION: An implementable complex multilingual patient education material could be developed in a stepwise manner. The efficacy of the package to prevent major adverse cardiovascular events is being tested in the SPRINT INDIA study.