Stroke systems of care in low-income and middle-income countries: challenges and opportunities.

The burden of stroke is higher in low-income and middle-income countries (LMICs) than in high-income countries and is rising. Even though there are global policies and guidelines for implementing stroke care, there are many challenges in setting up stroke services in LMICs. Despite these challenges, there are many models of stroke care available in LMICs-eg, multidisciplinary team care led by a stroke neurologist, specialist-led care by neurologists, physician-led care, hub and spoke models incorporating stroke telemedicine (ie, telestroke), and task sharing involving community health workers. Alternative strategies have been developed, such as reorganising the existing hospital infrastructure by training health professionals to implement protocol-driven care. The future challenge is to identify what elements of organised stroke care can be implemented to make the largest gain. Simple interventions such as swallowing assessments, bowel and bladder care, mobility assessments, and consistent secondary prevention can prove to be key elements to improving post-discharge morbidity and mortality in LMICs.

Increased Vascular Pathology in Older Veterans With a Purple Heart Commendation or Chronic Post-Traumatic Stress Disorder.

The goal of this retrospective cohort study was to determine whether stressors related to military service, determined by a diagnosis of chronic post-traumatic stress disorder (cPTSD) or receiving a Purple Heart (PH), are associated with an increased risk of vascular risk factors and disease, which are of great concern for veterans, who constitute a significant portion of the aging US population. The Veterans Integrated Service Network (VISN) 16 administrative database was searched for individuals 65 years or older between October 1, 1997 to September 30, 1999 who either received a PH but did not have cPTSD (PH+/cPTSD-; n = 1499), had cPTSD without a PH (PH-/cPTSD+; n = 3593), had neither (PH-/cPTSD-; n = 5010), or had both (PH+/cPTSD+; n = 153). In comparison to the control group (PH-/cPTSD-), the PH+/cPTSD- group had increased odds ratios for incidence and prevalence of diabetes mellitus, hypertension, and hyperlipidemia. The PH-/cPTSD+ group had increased odds ratios for prevalence of diabetes mellitus and for the incidence and prevalence of hyperlipidemia. The PH-/cPTSD+ and PH+/cPTSD- groups were associated with ischemic heart disease and cerebrovascular disease, but not independently of the other risk factors. The PH+/cPTSD+ group was associated only with an increase in the incidence and prevalence of hyperlipidemia, though this group's much smaller sample size may limit the reliability of this finding. We conclude that certain physical and psychological stressors related to military service are associated with a greater incidence of several vascular risk factors in veterans aged 65 years or older, which in turn are associated with greater rates of ischemic heart disease and cerebrovascular disease.

High Prevalence of Stroke in Rural Gadchiroli, India: A Community-Based Study.

BACKGROUND: In the near future, a majority of strokes are projected to occur in developing countries. However, population-level information on the prevalence of stroke from rural areas of developing countries, including India, is rare. We estimated the prevalence of stroke in a rural area of one of the most underdeveloped districts of India. METHODS: Trained surveyors conducted a house-to-house survey using a validated screening questionnaire in a well-defined population of 45,053 living in 39 villages in a demographic surveillance site in Gadchiroli district. A trained physician and a neurologist evaluated screen-positive patients and diagnosed stroke using the World Health Organization's criteria. RESULTS: In the screened population, 175 patients had stroke. The mean age of patients with stroke was 60.9 ± 14.7 years and 32.5% were women. The crude prevalence rate of stroke was 388.43 (95% CI 335.04-450.33) and the age-standardized prevalence rate of stroke was 535.58 (95% CI 492.41-583.01) per 100,000 population. The crude prevalence rate of stroke was significantly higher among men than among women (520 vs. 255/100,000 population, p < 0.05). CONCLUSION: In this prevalence study, conducted after a gap of 20 years in rural India, the prevalence of stroke was high and was more than twice the prevalence reported from the previous study. The prevalence was double among men compared to women. Stroke is emerging as a public health priority in rural India.

Stroke Is the Leading Cause of Death in Rural Gadchiroli, India: A Prospective Community-Based Study.

BACKGROUND AND PURPOSE: Stroke is an important cause of death and disability worldwide. However, information on stroke deaths in rural India is scarce. To measure the mortality burden of stroke, we conducted a community-based study in a rural area of Gadchiroli, one of the most backward districts of India. METHODS: We prospectively collected information on all deaths from April 2011 to March 2013 and assigned causes of death using a well-validated verbal autopsy tool in a rural population of 94 154 individuals residing in 86 villages. Two trained physicians independently assigned the cause of death, and the disagreements were resolved by a third physician. RESULTS: Of 1599 deaths during the study period, 229 (14.3%) deaths were caused by stroke. Stroke was the most frequent cause of death. For those who died because of stroke, the mean age was 67.47±11.8 years and 48.47% were women. Crude stroke mortality rate was 121.6 (95% confidence interval, 106.4-138.4), and age-standardized stroke mortality rate was 191.9 (95% confidence interval, 165.8-221.1) per 100,000 population. Of total stroke deaths, 87.3% stroke deaths occurred at home and 46.3% occurred within the first month from the onset of symptoms. CONCLUSIONS: Stroke is the leading cause of death and accounted for 1 in 7 deaths in this rural community in Gadchiroli. There was high early mortality, and the mortality rate because of stroke was higher than that reported from previous studies from India. Stroke is emerging as a public health priority in rural India.

Protocol for an evaluation of the initiation of an integrated longitudinal outpatient care model for severe chronic non-communicable diseases (PEN-Plus) at secondary care facilities (district hospitals) in 10 lower-income countries.

INTRODUCTION: The Package of Essential Noncommunicable Disease Interventions-Plus (PEN-Plus) is a strategy decentralising care for severe non-communicable diseases (NCDs) including type 1 diabetes, rheumatic heart disease and sickle cell disease, to increase access to care. In the PEN-Plus model, mid-level clinicians in intermediary facilities in low and lower middle income countries are trained to provide integrated care for conditions where services traditionally were only available at tertiary referral facilities. For the upcoming phase of activities, 18 first-level hospitals in 9 countries and 1 state in India were selected for PEN-Plus expansion and will treat a variety of severe NCDs. Over 3 years, the countries and state are expected to: (1) establish PEN-Plus clinics in one or two district hospitals, (2) support these clinics to mature into training sites in preparation for national or state-level scale-up, and (3) work with the national or state-level stakeholders to describe, measure and advocate for PEN-Plus to support development of a national operational plan for scale-up. METHODS AND ANALYSIS: Guided by Proctor outcomes for implementation research, we are conducting a mixed-method evaluation consisting of 10 components to understand outcomes in clinical implementation, training and policy development. Data will be collected through a mix of quantitative surveys, routine reporting, routine clinical data and qualitative interviews. ETHICS AND DISSEMINATION: This protocol has been considered exempt or covered by central and local institutional review boards. Findings will be disseminated throughout the project's course, including through quarterly M&E discussions, semiannual formative assessments, dashboard mapping of progress, quarterly newsletters, regular feedback loops with national stakeholders and publication in peer-reviewed journals.

Why are so many indigenous Pando people dying? Using observations from Chhattisgarh, India, to conduct structural assessment and identify solutions.

Health challenges of communities are often assessed using biomedical or individual risk-based frameworks which are often inadequate for understanding their full extent. We use observations from the global South to demonstrate the usefulness of structural assessment to evaluate a public health problem and spur action. Following newspaper reports of excessive deaths in the marginalised indigenous or Adivasi community of the Pando people in Northern Chhattisgarh in central India, we were asked by the state government's public health authorities to identify root causes of these deaths. In this rapidly evolving situation, we used a combination of public health, social medicine, and structural vulnerability frameworks to conduct biomedical investigation, social inquiry, and structural assessment. After biomedical investigations, we identified scrub typhus, a neglected tropical disease, as the most likely cause for some of the deaths which was unrecognised by the treating physicians. In the social inquiry, the community members identified the lack of Adivasi status certificates, education, and jobs as the three major social factors leading to these deaths. During the structural assessment of these deaths, we inductively identified the following ten structures- political, administrative, legal, economic, social, cultural, material, technical, biological, and environmental. We recommended improving the diagnosis and treatment of scrub typhus, making the hospitals more friendly for Adivasi people, and tracking the health status of the Adivasi communities as some of the measures. We suggest that a combination of biomedical, social,and structural assessments can be used to comprehensively evaluate a complex public health problem to spur action..

Surveillance of stroke: a South-East Asia Region (SEAR) perspective.

Surveillance of stroke is critical to track its burden and assess progress in prevention and treatment. We reviewed the literature to evaluate stroke surveillance efforts in the South-East Asia Region (SEAR) countries, identify progress and assess gaps. Epidemiological data on all the major parameters such as the incidence, prevalence and mortality of stroke were available for India and Thailand but for none of the other SEAR countries. Most of the epidemiological data came from investigator-initiated studies. National stroke surveillance was present only in India in the form of a National Stroke Registry Programme and Thailand has a national database that was used to obtain epidemiological data for stroke. Research on novel methods for stroke registration, such as using information technology, was absent. This review identified serious gaps in the monitoring and surveillance of stroke in SEAR countries. Systematic efforts are needed to fill those gaps.

The burden, risk factors and unique etiologies of stroke in South-East Asia Region (SEAR).

The World Health Organization (WHO) South East Asia Region (SEAR) comprises 11 countries, which are one of the most culturally, topographically, and socially diverse areas worldwide, undergoing an epidemiological transition towards non-communicable diseases, including stroke and other cardiovascular diseases (CVDs). This region accounts for over 40% of the global stroke mortality. Few well-designed population-based epidemiological studies on stroke are available from SEAR countries, with considerable variations among them. Ischemic stroke, a common stroke subtype, has higher frequencies of intracerebral hemorrhage in many countries. Along with an aging population, the increased prevalence of risk factors such as hypertension, diabetes mellitus, tobacco and alcohol consumption, lack of physical activity, high ambient pollution, heat, and humidity contribute to the high burden of stroke in this region. SEAR's many unique and uncommon stroke etiologies include cerebral venous thrombosis, tuberculosis, dengue, scrub typhus, falciparum malaria, snake bite, scorpion sting, etc. Current data on stroke burden and risk factors is lacking, compelling an urgent need for high-quality hospital-level and population-level data in all SEAR countries. Strategies towards a consolidated approach for implementing improved stroke prevention measures, stroke surveillance, and established stroke systems of care are the path to bridging the gaps in stroke care.

Stroke systems of care in South-East Asia Region (SEAR): commonalities and diversities.

The Southeast Asia Region (SEAR) accounts for nearly 50% of the developing world's stroke burden. With various commonalities across its countries concerning health services, user awareness, and healthcare-seeking behavior, SEAR still presents profound diversities in stroke-related services across the continuum of care. This review highlights the numerous systems and challenges in access to stroke care, acute stroke care services, and health care systems, including rehabilitation. The paper has also attempted to compile information on the availability of stroke specialized centers, Intravenous thrombolysis (IVT) ready centers, Endovascular therapy (EVT) ready centers, rehabilitation centers, and workforce against a backdrop of each country's population. Lastly, the efforts of WHO (SEARO)-CMCL (World Health Organization-South East Asia region, Christian Medical College & Hospital Ludhiana) collaboration towards improving stroke services and capacity among the SEAR have been described.

Medical and environmental risk factors associated with frontotemporal dementia: a case-control study in a veteran population.

BACKGROUND: Compared with other major dementias, very little is known about the medical and environmental risk factors associated with frontotemporal dementia (FTD). In this study, we evaluated medical and environmental disorders associated with FTD in a veteran population. METHODS: The medical records of 845 consecutive veterans who were evaluated for cognitive and/or behavioral complaints at a cognitive disorders clinic in an academic medical center between March 1, 2003, and June 30, 2008, were reviewed and 554 patients received a diagnosis of dementia. Medical disorders and environmental risk factors in 63 patients with behavioral variant of FTD were compared with 491 patients with non-FTD dementias. RESULTS: The prevalence of traumatic brain injury (TBI) was significantly greater in patients with FTD versus those with non-FTD dementias (12.7% vs 3.5%; P < .05). The FTD group also had a lower prevalence of heart disease (19.0% vs 36.7%; P < .05) and cerebrovascular diseases (12.7% vs 26.1%; P < .05), although the prevalence of vascular risk factors was comparable between FTD and non-FTD dementia groups: hypertension (65.1% vs 68.2%), diabetes (31.7% vs 26.9%), hyperlipidemia (42.9% vs 48.9%), and tobacco use (7.9% vs 8.8%; P > .05 for all). In multivariate analysis, the risk for FTD was increased in patients with TBI (OR, 4.4; 95% CI, 1.6-11.8). The risk for FTD was marginally decreased in patients with heart disease (OR, 0.4; 95% CI, 0.3-0.96). CONCLUSIONS: In a clinical sample of veterans, risk of FTD was increased in patients with TBI and marginally decreased in patients with heart disease. Prospective studies are needed to confirm these associations temporally and to identify their underlying mechanisms.

Clinical features, management, and mortality because of COVID-19 in an intensive care unit in Surguja, a tribal district in Central India: A single-centre descriptive study.

Background: The clinical features and management of severe coronavirus disease 2019 (COVID-19) have been well documented in urban India. However, little data exist on the management and outcomes of severe COVID-19 in rural and tribal areas. Methods: This was a retrospective chart review of the patients admitted in a 20-bedded COVID-19 intensive care unit (ICU) set up at the Government District Hospital, Ambikapur, Chhattisgarh, between 17 May and 17 July 2021 during the second wave of COVID-19 in India. The ICU was managed by a team of primary care providers, family physicians, and nurses under the supervision of three specialists. Data related to socio-demographic, clinical, laboratory, and treatment profiles were extracted using a data extraction tool and analysed. Results: A total of 55 of the 63 (87.3%) patients admitted in the ICU during the study period were eligible for the study. The mean age of the patients was 50.95 [standard deviation (SD) 15.76] years; 66% were < 60 years of age, and 63.6% were men. The mean duration of symptoms before ICU admission was 7.52 (SD 4.16) days. Breathlessness (63.6%), fever (58.2%), cough (52.7%), and altered sensorium (38.2%) were the most common presenting symptoms. 67% of the patients had any co-morbidity, and 43% had two or more co-morbidities. 32.7% patients needed non-invasive (14 out of 55) or invasive ventilation (4 out of 55). 12.7% of the patients (7 out of 55) needed dialysis. The intra-ICU mortality was 47%. Patients who died had higher prevalence of heart disease, hypoxia, and altered sensorium. Conclusion: Our study highlights the need for critical care services in Government District Hospitals in India and the feasibility of providing such care by primary care providers through specialist mentoring.

Cross-cultural adaptation, reliability and validity of the Marathi versions of the Back Beliefs Questionnaire and Pain Self-Efficacy Questionnaire in people living with chronic low back pain.

PURPOSE: To translate and cross-culturally adapt the Back Beliefs Questionnaire (BBQ) and Pain Self-Efficacy Questionnaire (PSEQ) into Marathi, and to evaluate their clinimetric properties in a native Marathi speaking population with chronic low back pain. MATERIAL AND METHODS: The BBQ and PSEQ were translated into Marathi using international published guidelines. Fifty native Marathi speakers were recruited. Reliability (n = 43) was evaluated in terms of internal consistency (Cronbach α) and test-retest reliability [intra class correlation coefficient, ICC (2, 1)] and 95% confidence interval (CI). Convergent validity (n = 50) was assessed by correlating the Marathi versions of BBQ and PSEQ with the Marathi version of Roland Morris Disability Questionnaire (RMDQ). RESULTS: Internal consistency of BBQ (Cronbach α  =  0.67) was good and that for PSEQ (Cronbach α  =  0.93) was high. Test-retest reliability for BBQ (ICC =  0.80; 95% CI: 0.66 to 0.89) was good and PSEQ (ICC = 0.85; 95% CI: 0.74 to 0.92) was excellent. A significant, low negative correlation was found between RMDQ and BBQ scores (r = -0.298; p = 0.036) and PSEQ (r = -0.28; p = 0.049). CONCLUSIONS: The BBQ and PSEQ were successfully cross-culturally adapted into Marathi. Clinimetric evaluation of these questionnaires in a sample of native Marathi speaking populations with chronic low back pain demonstrated good acceptability, acceptable internal consistency, and high test-retest reliability.Implications for rehabilitationThe Back Beliefs Questionnaire (BBQ) and Pain Self Efficacy Questionnaire (PSEQ) were successfully cross-culturally adapted into Marathi.The Marathi versions of BBQ and PSEQ have good acceptability, acceptable internal consistency, and high test-retest reliability.They can be used by clinicians and researchers to evaluate beliefs about back pain and pain self-efficacy in Marathi speaking patients with chronic low back pain.

Informal Providers-Ground Realities in South Asian Association for Regional Cooperation Nations: Toward Better Cancer Primary Care: A Narrative Review.

PURPOSE: South Asian Association for Regional Cooperation (SAARC) nations are a group of eight countries with low to medium Human Development Index values. They lack trained human resources in primary health care to achieve the WHO-stated goal of Universal Health Coverage. An unregulated service sector of informal health care providers (IPs) has been serving these underserved communities. The aim is to summarize the role of IPs in primary cancer care, compare quality with formal providers, quantify distribution in urban and rural settings, and present the socioeconomic milieu that sustains their existence. METHODS: A narrative review of the published literature in English from January 2000 to December 2021 was performed using MeSH Terms Informal Health Care Provider/Informal Provider and Primary Health Care across databases such as Medline (PubMed), Google Scholar, and Cochrane database of systematic reviews, as well as World Bank, Center for Global Development, American Economic Review, Journal Storage, and Web of Science. In addition, citation lists from the primary articles, gray literature in English, and policy blogs were included. We present a descriptive overview of our findings as applicable to SAARC. RESULTS: IPs across the rural landscape often comprise more than 75% of primary caregivers. They provide accessible and affordable, but often substandard quality of care. However, their network would be suitable for prompt cancer referrals. Care delivery and accountability correlate with prevalent standards of formal health care. CONCLUSION: Acknowledgment and upskilling of IPs could be a cost-effective bridge toward universal health coverage and early cancer diagnosis in SAARC nations, whereas state capacity for training formal health care providers is ramped up simultaneously. This must be achieved without compromising investment in the critical resource of qualified doctors and allied health professionals who form the core of the rural public primary health care system.

Stroke in India: A systematic review of the incidence, prevalence, and case fatality.

BACKGROUND: The burden of stroke is increasing in India; stroke is now the fourth leading cause of death and the fifth leading cause of disability. Previous research suggests that the incidence of stroke in India ranges between 105 and 152/100,000 people per year. However, there is a paucity of available data and a lack of uniform methods across published studies. AIM: To identify high-quality prospective studies reporting the epidemiology of stroke in India. SUMMARY OF REVIEW: A search strategy was modified from the Cochrane Stroke Strategy and adapted for a range of bibliographic databases from January 1997 to August 2020. From 7717 identified records, nine studies were selected for inclusion; three population-based registries, a further three population-based registries also using community-based ascertainment and three community-based door-to-door surveys. Studies represented the four cities of Mumbai, Trivandrum, Ludhiana, Kolkata, the state of Punjab, and 12 villages of Baruipur in the state of West Bengal. The total population denominator was 22,479,509 and 11,654 (mean 1294 SD 1710) people were identified with incident stroke. Crude incidence of stroke ranged from 108 to 172/100,000 people per year, crude prevalence from 26 to 757/100,000 people per year, and one-month case fatality rates from 18% to 42%. CONCLUSIONS: Further high-quality evidence is needed across India to guide stroke policy and inform the development and organization of stroke services. Future researchers should consider the World Health Organization STEPwise approach to Surveillance framework, including longitudinal data collection, the inclusion of census population data, and a combination of hospital-registry and comprehensive community ascertainment strategies to ensure complete stroke identification.

Control of scabies in a tribal community using mass screening and treatment with oral ivermectin -A cluster randomized controlled trial in Gadchiroli, India.

BACKGROUND: Scabies is often endemic in tribal communities and difficult to control. We assessed the efficacy of a community-based intervention using mass screening and treatment with oral ivermectin in controlling scabies. METHODS/ FINDINGS: In this cluster randomised controlled trial, 12 villages were randomly selected from a cluster of 42 tribal villages in Gadchiroli district. In these villages, trained community health workers (CHWs) conducted mass screening for scabies. The diagnosis was confirmed by a physician. Six villages each were randomly allocated to the intervention and usual care arm (control arm). In the intervention arm (population 1184) CHWs provided directly observed oral ivermectin to scabies cases and their household contacts. In the usual care arm (population 1567) scabies cases were referred to the nearest clinic for topical treatment as per the standard practice. The primary outcome was prevalence of scabies two months after the treatment. Secondary outcomes were prevalence of scabies after twelve months of treatment and prevalence of impetigo after two and twelve months of treatment. Outcomes were measured by the team in a similar way as the baseline. The trial was registered with the clinical trial registry of India, number CTRI/2017/01/007704. In the baseline, 2 months and 12 months assessments 92.4%, 96% and 94% of the eligible individuals were screened in intervention villages and 91.4%, 91.3% and 95% in the usual care villages. The prevalence of scabies in the intervention and usual care arm was 8.4% vs 8.1% at the baseline, 2.8% vs 8.8% at two months [adjusted relative risk (ARR) 0.21, 95% CI 0.11-0.38] and 7.3% vs 14.1% (ARR 0.49, 95% CI 0.25-0.98) at twelve months The prevalence of impetigo in the intervention and usual care arm was 1.7% vs 0.6% at baseline, 0.6% vs 1% at two months (ARR 0.55, 95% CI 0.22-1.37) and 0.3% vs 0.7% at 12 months (ARR 0.42, 95% CI 0.06-2.74). Adverse effects due to ivermectin occurred in 12.1% of patients and were mild. CONCLUSIONS: Mass screening and treatment in the community with oral ivermectin delivered by the CHWs is superior to mass screening followed by usual care involving referral to clinic for topical treatment in controlling scabies in this tribal community in Gadchiroli.

Clinical patterns and their prevalence among adult population with back pain: A community-based cross-sectional study in rural Gadchiroli, India.

BACKGROUND: Evaluating clinical patterns and their prevalence of back pain, a common problem in rural areas, can help develop treatment strategies to address this leading cause of disability. METHODS: We conducted a population-based study in rural Gadchiroli, India. In this, two-phase study, trained surveyors conducted a door to door survey (Phase 1) to identify individuals with pain in the back and extremities in two villages randomly selected using pre-defined criteria. Those with pain were evaluated by a team of spine surgeons and rheumatologists to diagnose clinical conditions among these patients (Phase 2). RESULTS: Of the 2535 eligible adults, 2259 (89%) were screened, 1247 (55%) reported pain in back and limb and were referred to the specialist clinic. Out of the 906 (73%) participants who attended the clinics, 783 (89%) had back/neck pain. The point prevalence of back/neck pain among adults was 49% (95% confidence interval (CI) = 49%-51%), non-specific low back pain 45% (95% CI = 43.4%-47.5%); non-specific neck pain 21% (95% CI = 18.9-22.4), radiculopathy 12 (95% CI = 10.4-13.1), myelopathy 0.4 (95% CI = 0.1-0.7) and other serious spinal disorders 0.2 (95% CI 0.048-0.45). The prevalence of non-specific back/neck pain and radiculopathy was higher among females. CONCLUSIONS: Non-specific back and neck pain are the commonest diagnoses among those with pain in the back and extremities, followed by radiculopathy. Serious disorders are rare. Given the high prevalence of non-specific back and neck pain, community health workers and physicians working in rural areas need to be trained systematically to manage these conditions.

A matching algorithm to address imbalances in study populations: application to the National Institute of Neurological Diseases and Stroke Recombinant Tissue Plasminogen Activator acute stroke trial.

BACKGROUND AND PURPOSE: Outcome from stroke is highly dependent on baseline conditions. Patients with stroke have a wide range of severities, ages, and etiologies and it has proven difficult to achieve randomization of key variables in clinical trials. We present a new post hoc approach to achieve balance among selected variables. To illustrate the approach, we rebalanced the National Institute of Neurological Diseases and Stroke Recombinant Tissue Plasminogen Activator trial, in which the contribution of baseline imbalances continues to be debated. METHODS: We selected baseline stroke severity (National Institutes of Health Stroke Scale), age, and glucose as matching criteria. The closest matched placebo and treated subjects were identified based on nearness to each other in 3-dimensional Euclidean space. Matching was performed within the quintiles of National Institutes of Health Stroke Scale that have been previously used to assess balance. Subjects who could not be matched were eliminated. Outcomes were assessed using the original specified National Institute of Neurological Diseases and Stroke trial measures. RESULTS: We successfully matched the 2 arms resulting in nearly identical baseline characteristics and distribution among quintiles. Despite fewer subjects after outlier elimination, the primary outcome measures remained significantly improved. After rebalancing, the magnitude of benefit was reduced by 13% to 23%. Benefit was apparent mostly in the large vessel occlusion subtype. CONCLUSION: This study demonstrated the feasibility of rebalancing individual subjects within a randomized trial. After rebalancing and outlier elimination, recombinant tissue plasminogen activator continued to demonstrate improved outcome. That the apparent treatment effect was reduced suggests that imbalances contributed to the magnitude of the original National Institute of Neurological Diseases and Stroke outcomes. This method could in theory be applied to any data set to find matched subjects for outcome or other analyses.