Global stroke statistics 2023: Availability of reperfusion services around the world.

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.

Intracranial Large Artery Disease is Independently Associated with Poor Functional Outcome in a Cohort of Ethnic South Asian Ischemic Stroke Patients.

BACKGROUND: Intracranial large artery disease (ICLAD) in ischemic stroke patients is associated with an increased risk for recurrent stroke; however, it is not known if ICLAD influences functional status following stroke. We studied the 6-month functional outcome in south Asian ischemic stroke patients and compared those with and without ICLAD. MATERIALS AND METHODS: This is a prospective cohort study of consecutive south Asian ischemic stroke patients. ICLAD was assessed with transcranial color-coded Doppler ultrasound or magnetic resonance angiography. Functional outcomes were obtained via telephone interviews with poor outcome defined as modified Rankin scale of 3-6. RESULTS: Of 216 ischemic stroke patients studied, 203 (93.9%) had follow-up data, of whom 50.7% (103) had ICLAD. Patients with ICLAD had a higher prevalence of hypertension (P < 0.001), hyperlipidemia (P = 0.047), ischemic heart disease (P = 0.030), and extracranial carotid disease (P = 0.005). A higher proportion of patients with ICLAD had poor functional outcome at 6 months (30.1%) versus those without ICLAD (13.0%) (P = 0.004). After adjusting for age, sex, hypertension, hyperlipidemia, diabetes, ischemic heart disease, atrial fibrillation, extracranial carotid stenosis, and recurrent vascular events, patients with ICLAD were 3.01 (95% confidence interval: 1.35-7.10) times more likely than those without ICLAD to have poor functional outcome. CONCLUSIONS: The presence of ICLAD rendered poorer functional prognosis after stroke. These findings support the specific evaluation of the benefits of known acute stroke treatments such as thrombolysis, as well as investigation of potential novel strategies such as acute stenting.

Stroke Rehabilitation Use and Caregiver Psychosocial Health Profiles in Singapore: A Latent Profile Transition Analysis.

OBJECTIVES: To identify and describe caregiver profiles based on their psychosocial health characteristics over a 12-month period and transitions among these profiles, to determine if stroke rehabilitation use at 12 months post-stroke differed by caregiver profile transition patterns, and to investigate if caregiver profiles at 3 months post-stroke moderate the association of stroke rehabilitation use at 3 months and 12 months post-stroke after accounting for covariates. DESIGN: Latent profile transition analysis of caregiver psychosocial health with stroke rehabilitation use at 12 month post-stroke as outcome. SETTING AND PARTICIPANTS: A total of 149 stroke patient-caregiver dyads from the Singapore Stroke Study. METHODS: Cross-sectional latent profile analyses were conducted on caregiver psychosocial health indicators of burden, depression, health status, quality of relationship with patient, and social support. Changes in latent profile classification over 3 time points (baseline, 3 months, and 12 months post-stroke) were analyzed using latent transition analysis. A transition model with stroke rehabilitation use at 12 months post-stroke as the outcome was tested after accounting for covariates. RESULTS: Two distinct caregiver psychosocial health latent profiles were found across time: nondistressed and distressed. Most caregivers were classified as nondistressed and remained nondistressed over time. Distressed caregivers at baseline were 76% likely to become nondistressed at 12 month post-stroke. Regardless of profile transition patterns, nondistressed caregivers at 12 months post-stroke tended to have cared for stroke rehabilitation nonusers at 12 months post-stroke. Patient depression explained profile classification at 3 months and 12 months post-stroke. After accounting for covariates, rehabilitation users at 3 months post-stroke tended to continue using rehabilitation at 12 months post-stroke only when they had nondistressed caregivers at 3 months post-stroke. CONCLUSIONS AND IMPLICATIONS: Whether caregiver adaptation explains the associations between the latent profile transition patterns and rehabilitation use at 12 months post-stroke should be examined. Early psychosocial health assessment and sustained support should be made available to stroke caregivers to enhance their well-being and subsequent patient rehabilitation participation.

Stroke Patients Without COVID-19 Symptoms: Is There a Need to Screen?

INTRODUCTION: COVID-19 patients who present with strokes but without typical COVID-19 symptoms have been described in small numbers. Despite the paucity of fever and respiratory symptoms, they remain capable of infecting others. The patient we discuss herein highlights the important issues of strokes as presenting events of COVID-19 infections, and how testing for COVID-19 in stroke patients, even when asymptomatic for COVID-19, can play an important role in infection control, clinical management and outcomes amidst this global pandemic. CASE REPORT: A 45-year-old male resident of a dormitory presented to our unit with acute vertigo and left-sided dysmetria. NIHSS was 2. The initial magnetic resonance imaging demonstrated infarction of the left cerebellar hemisphere, middle cerebellar peduncle and hemipons. An extensive work-up for stroke etiologies was unremarkable. Despite having no fever, respiratory symptoms, anosmia or ageusia, he was isolated and screened for COVID-19 due to his epidemiologic risks, with multiple residents from his dormitory being recently diagnosed with COVID-19. Confirming our suspicion, his respiratory samples returned positive for COVID-19. His D-dimer levels returned normal. Thereafter, the patient underwent posterior decompression surgery due to worsening edema caused by the cerebellar infarct. He was started on antiplatelet therapy and recovered significantly a month from presentation with an modified Rankin Sore of 2. He remained without typical COVID-19 symptoms. CONCLUSION: Our patient's case clearly supports the screening for COVID-19 in stroke patients who are without COVID-19 symptoms, appreciating the significant value it adds to infection control, clinical management, and outcomes amidst this global pandemic.

Home-based tele-rehabilitation presents comparable positive impact on self-reported functional outcomes as usual care: The Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) randomised controlled trial.

INTRODUCTION: The aim of this research was to evaluate the impact of a novel tele-rehabilitation system on self-reported functional outcomes compared to usual care during the first three months after stroke. METHODS: A parallel, two-arm, evaluator-blinded, randomised controlled trial was conducted. Adults aged ≥40 years who had suffered a stroke within four weeks of the start of the study were recruited from the general community. The intervention group received access to a novel tele-rehabilitation system and programme for three months. The primary outcome measures utilised were the frequency and limitation total scores of the Late-Life Function and Disability Instrument (LLFDI) at three months. RESULTS: A total of 124 individuals were recruited. The mean differences in the LLDFI frequency and limitation total scores at three months comparing the intervention and control groups were -3.30 (95% confidence interval (CI) -7.81 to 1.21) and -6.90 (95% CI -15.02 to 1.22), respectively. Adjusting for the respective baseline covariates and baseline Barthel Index also showed no significant difference between interventions in the LLFDI outcomes. DISCUSSION: The intervention and control groups self-reported similar improvements in functional outcomes. Tele-rehabilitation may be a viable option to provide post-stroke rehabilitation services in Singapore while reducing barriers to continue rehabilitation conventionally after discharge from hospital and encouraging more participation.

Association of Reperfusion After Thrombolysis With Clinical Outcome Across the 4.5- to 9-Hours and Wake-up Stroke Time Window: A Meta-Analysis of the EXTEND and EPITHET Randomized Clinical Trials.

Importance: Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain. Objective: To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials. Design, Setting, and Participants: Individual patient meta-analysis of randomized clinical trials performed from August 2001 to June 2018 with 3-month follow-up. Patients had acute ischemic stroke with 4.5-to 9-hours poststroke onset or with wake-up stroke were randomized to alteplase or placebo after perfusion mismatch imaging. Analysis began July 2019 and ended May 2020. Exposures: Reperfusion was defined as more than 90% reduction in time to maximum of more than 6 seconds' lesion volume at 24- to 72-hour follow-up. Main Outcomes and Measures: Ordinal logistic regression adjusted for baseline age and National Institutes of Health Stroke Scale score was used to analyze functional improvement in day 90 modified Rankin Scale score overall, including a reperfusion × time-to-randomization multiplicative interaction term, and in the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with a National Institutes of Health Stroke Scale score increase of 4 points or more. Results: Reperfusion was assessable in 270 of 295 patients (92%), 68 of 133 (51%) in the alteplase group, and 38 of 137 (28%) in the placebo reperfused group (P < .001). The median (interquartile range) age was 76 (66-81) years in the reperfusion group vs 74 (64.5-81.0) years in the group with no reperfusion. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (7-15) in the reperfusion group vs 12 (8.0-17.5) in the no reperfusion group. Overall, reperfusion was associated with improved functional outcome (common odds ratio, 7.7; 95% CI, 4.6-12.8; P < .001). Reperfusion was associated with significantly improved functional outcome in each of the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata, with no evidence of association between time to randomization and beneficial effect of reperfusion (P = .63). Symptomatic hemorrhage, assessed in all 294 patients, occurred in 3 of 51 (5.9%) in the 4.5- to 6-hours group, 2 of 28 (7.1%) in the 6- to 9-hours group, and 4 of 73 (5.5%) in the wake-up stroke in patients treated with alteplase (Fisher P = .91). Conclusions and Relevance: Strong benefits of reperfusion in all time strata without differential risk in symptomatic hemorrhage support the consistent treatment effect of alteplase in perfusion mismatch-selected patients throughout the 4.5- to 9-hours and wake-up stroke time window.

Ischaemic stroke.

Stroke is the second highest cause of death globally and a leading cause of disability, with an increasing incidence in developing countries. Ischaemic stroke caused by arterial occlusion is responsible for the majority of strokes. Management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy, which both reduce disability but are time-critical. Accordingly, improving the system of care to reduce treatment delays is key to maximizing the benefits of reperfusion therapies. Intravenous thrombolysis reduces disability when administered within 4.5 h of the onset of stroke. Thrombolysis also benefits selected patients with evidence from perfusion imaging of salvageable brain tissue for up to 9 h and in patients who awake with stroke symptoms. Endovascular thrombectomy reduces disability in a broad group of patients with large vessel occlusion when performed within 6 h of stroke onset and in patients selected by perfusion imaging up to 24 h following stroke onset. Secondary prevention of ischaemic stroke shares many common elements with cardiovascular risk management in other fields, including blood pressure control, cholesterol management and antithrombotic medications. Other preventative interventions are tailored to the mechanism of stroke, such as anticoagulation for atrial fibrillation and carotid endarterectomy for severe symptomatic carotid artery stenosis.

Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). INTERPRETATION: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. FUNDING: None.

Health-related quality of life loss associated with first-time stroke.

OBJECTIVES: This study aimed to quantify health-related quality of life (HRQoL) loss associated with first episode of stroke by comparing patient-reported HRQoL before and after stroke onset. The impact of stroke in local population was also evaluated by comparing the pre- and post-stroke HRQoL with that of the general population. METHODS: The HRQoL of stroke survivors was assessed with the EQ-5D-3L index score at recruitment, for recalled pre-stroke HRQoL, and at 3 and 12 month post-stroke. Change in HRQoL from pre-stroke to 3 and 12 month was self-reported by 285 and 238 patients, respectively. Mean EQ index score at each time point (baseline: 464 patients; 3 month post-stroke: 306 patients; 12 month post-stroke: 258 patients) was compared with published population norms for EQ-5D-3L. RESULTS: There was a significant decrease in HRQoL at 3 (0.25) and 12 month (0.09) post-stroke when compared to the retrospectively recalled patients' mean pre-stroke HRQoL level (0.87). The reduction at 3 month was associated with the reduction in all EQ-5D-3L health dimensions; reductions remaining at 12 month were limited to dimensions of mobility, self-care, usual activities, and anxiety/depression. Stroke patients had a lower mean EQ index than the general population by 0.07 points pre-stroke (0.87 vs. 0.94), 0.33 points at 3 month (0.61 vs. 0.94) and 0.18 points at 12 month (0.76 vs. 0.94) post-stroke. CONCLUSIONS: Stroke has a substantial impact on HRQoL in Singapore, especially in the first three months post-stroke. Compared to the general population, stroke survivors have lower HRQoL even before stroke onset. This pre-stroke deficit in HRQoL should be taken into account when quantifying health burden of stroke or setting goals for stroke rehabilitation.

Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.

BACKGROUND: Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke. METHODS: Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions. RESULTS: All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized ß = - 0.111; 12-month standardized ß = - 0.109) and mRS (3-month standardized ß = - 0.122; 12-month standardized ß = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D. CONCLUSIONS: HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.

The Relationship Between Ambient Air Pollution and Acute Ischemic Stroke: A Time-Stratified Case-Crossover Study in a City-State With Seasonal Exposure to the Southeast Asian Haze Problem.

STUDY OBJECTIVE: Studies are divided on the short-term association of air pollution with stroke. Singapore is exposed to seasonal transboundary haze. We aim to investigate the association between air pollution and stroke incidence in Singapore. METHODS: We performed a time-stratified case-crossover analysis on all ischemic stroke cases reported to the Singapore Stroke Registry from 2010 to 2015. Exposure on days was compared with control days on which exposure did not occur. Control days were chosen on the same day of the week earlier and later in the same month in the same year. We fitted a conditional Poisson regression model to daily stroke incidence that included Pollutant Standards Index and environmental confounders. The index was categorized according to established classification (0 to 50=good, 51 to 100=moderate, and ≥101=unhealthy). We assessed the relationship between stroke incidence and Pollutant Standards Index in the entire cohort and in predetermined subgroups of individual-level characteristics. RESULTS: There were 29,384 ischemic stroke cases. Moderate and unhealthy Pollutant Standards Index levels showed association with stroke occurrence, with incidence risk ratio 1.10 (95% confidence interval 1.06 to 1.13) and 1.14 (95% confidence interval 1.03 to 1.25), respectively. Subgroup analyses showed generally significant association, except in Indians and nonhypertensive patients. The association was significant in subgroups aged 65 years or older, women, Chinese, nonsmokers and those with history of diabetes, hypertension, and hyperlipidemia. Stratified by age and smoking, the risk diminished in smokers of all ages. Risk remained elevated for 5 days after exposure. CONCLUSION: We found a short-term elevated risk of ischemic stroke after exposure to air pollution. These findings have public health implications for stroke prevention and emergency health services delivery.

Two decades of nation-wide community-based stroke support - The Singapore National Stroke Association.

The Singapore National Stroke Association, registered in 1996, offers support and information to stroke survivors and caregivers, and aims to raise public stroke awareness. In the last 20 years, we have developed programs to equip stroke survivors and caregivers with knowledge, life skills, comfort, and opportunities for socialization and reintegration. We have on-going public education and advocacy initiatives. Obtaining funding, member recruitment, volunteer retention, and leadership renewal are on-going challenges. Singapore National Stroke Association will continue to strive for the betterment of stroke survivors, their caregivers, and the public.

Asian venous thromboembolism guidelines: updated recommendations for the prevention of venous thromboembolism.

The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.

Prognostic factors and treatment effect in the CHIMES study.

BACKGROUND: Stroke trials often analyze patients with heterogeneous prognoses using a single definition of outcome, which may not be applicable to all subgroups. We aimed to evaluate the treatment effects of MCL601 among patients stratified by prognosis in the Chinese Medicine Neuroaid Efficacy on Stroke Recovery (CHIMES) study. METHODS: Analyses were performed using data from the CHIMES study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. All subjects with baseline data and the modified Rankin Scale (mRS) score at 3 months were included. RESULTS: Data from 1006 subjects were analyzed. The predictive variables for mRS score greater than 1 at month 3 were age older than 60 years (P < .001), baseline National Institutes of Health Stroke Scale score 10-14 (P < .001), stroke onset to initiation of study treatment of more than 48 hours (P < .001), and female sex (P = .026). A higher number of predictors was associated with poorer mRS score at month 3 for both placebo (P < .001) and treatment (P < .001) groups. The odds ratio (OR) for achieving a good outcome increased with the number of predictors and reached statistical significance in favor of MLC601 among patients with 2 to 4 predictors combined (unadjusted OR = 1.44, 95% confidence interval, 1.02-2.03; adjusted OR = 1.60, 95% confidence interval, 1.10-2.34). CONCLUSIONS: Age, sex, baseline National Institutes of Health Stroke Scale score, and time to first dose are predictors of functional outcome in the CHIMES study. Stratification by prognosis showed that patients with 2 or more predictors of poorer outcome have better treatment effect with MLC601 than patients with single or no prognostic factor. These results have implications on designing future stroke trials.

Inflammatory markers and their association with post stroke cognitive decline.

BACKGROUND: Population-based studies have demonstrated the association of inflammation and cognitive impairment. However, few studies to date have examined this association in ischemic stroke patients. AIMS: The study aims to determine the association between inflammatory markers and cognitive impairment. METHODS: Ischemic stroke patients with baseline neuropsychological assessments at three-months poststroke were followed up with annual neuropsychological assessments for up to five-years. Inflammatory markers (C-reactive protein, interleukin 1ß, interleukin 6, interleukin 8, interleukin 10, interleukin 12, and tumor necrosis factor-α) were assayed, and logistic regression analyses were performed to determine associations between inflammatory markers and both baseline cognitive status and subsequent cognitive decline. RESULTS: There were 243 ischemic stroke patients in the study. In multivariable ordinal logistic regression analysis, age, education, ethnicity, stroke subtype, and interleukin 8 (OR 1.23 CI 1.05-1.44) levels were independently associated with baseline cognitive status. In multivariable logistic regression analyses, age, gender, recurrent strokes, and interleukin 12 (OR 25.02 CI 3.73 to 168.03) were independent predictors of subsequent cognitive decline. CONCLUSIONS: Following ischemic stroke, higher serum interleukin 8 is independently associated with baseline cognitive impairment while higher serum interleukin 12 is associated with subsequent cognitive decline.

Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation.

BACKGROUND: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. METHODS: Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. RESULTS: Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0.02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0.001), larger infarcts (median volume 75 vs. 23 ml, P = 0.001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0.03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0.03), and higher mortality (36% vs. 16%, P = 0·.3) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6.05, 95% confidence interval 1.60-22.83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0.99, 95% confidence interval 0.35-2.80) or mortality (odds ratio = 2.54, 95% confidence interval 0.86-7.49) three-months following stroke, after adjusting for other baseline imbalances. CONCLUSION: Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.

Disability impacts length of stay in general internal medicine patients.

BACKGROUND: Disability is prevalent among patients treated in Internal Medicine (IM), but its impact on length of inpatient stay (LOS) is unknown. Current systems of patient management and resource allocation are disease-focused with scant attention paid to functional impairment. Earlier studies in selected cohorts suggest that disability prolongs LOS. OBJECTIVE: To investigate the relationship of disability with LOS in IM, controlling for comorbidity. DESIGN: Prospective cohort study. PATIENTS: We charted 448 patients from an IM team admitted between 2008 and 2012 for sociodemographic, disease, biochemical and functional characteristics. Each IM team is on duty for one month annually, and patients were hence recruited for one month each year. MAIN MEASURES: Disability was measured using the Functional Independence Measure (FIM) recorded at discharge. Comorbidity was measured using the Charlson Comorbidity Index (CCI). KEY RESULTS: Of the 448 patients, 57.4 % were male with mean age 68.6 years. The mean LOS was 9.58 days. The mean motor and cognitive FIM scores were 57.1 and 25.7, respectively. The mean CCI score was 2.69. Thirty-four percent had major social issues impacting discharge plans. The five most common diagnoses for admission were pneumonia (8.9 %), urinary tract infection (7.8 %), cellulitis (7.6 %), heart failure (7.1 %) and falls (6.0 %). Both cognitive and motor FIM scores were negatively correlated with longer LOS (P < 0.001). On multivariate analysis, variables independently associated with longer LOS included the motor FIM score (P < 0.001), presence of social issues such as caregiver unavailability (P < 0.001), non-realistic patient expectations (P = 0.001) and administrative issues impeding discharge (P = 0.016). CONCLUSION: Disability predicts LOS in IM patients, and thus their comprehensive care should involve functional assessment. As social and administrative factors were also independently associated with LOS, there is a need to involve social workers and administrators in a multidisciplinary approach towards optimizing LOS.

Differing associations of white matter lesions and lacunar infarction with retinal microvascular signs.

BACKGROUND: White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear. AIM: Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI. METHODS: We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber. RESULTS: Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1·5, 95% confidence interval (CI) 1·1 to 2·1] and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·1 to 2·3); 200 patients with only LI were more likely to have arteriolar narrowing (OR 1·6, 95% CI 1·1 to 2·3) and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·0 to 2·4); and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1·7, 95% CI 1·1 to 2·6), enhanced arteriolar light reflex (OR 2·0, 95% CI 1·3 to 3·2) and wider venules (OR 2·3, 95% CI 1·4 to 3·6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors. CONCLUSION: Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.