Browsing by Author "Lavados, Pablo"
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Item Accuracy of diffusion-weighted imaging in the diagnosis of stroke in patients with suspected cerebral infarct(American Heart Association, 2013) Brunser, Alejandro; Hoppe, Arnold; Illanes, Sergio; Díaz, Violeta; Muñoz, Paula; Cárcamo, Daniel; Olavarría, Verónica; Valenzuela, Marcela; Lavados, PabloBACKGROUND AND PURPOSE: The accuracy of diffusion-weighted imaging (DWI) for the diagnosis of acute cerebral ischemia among patients with suspected ischemic stroke arriving to an emergency room has not been studied in depth. METHODS: DWI was performed in 712 patients with acute or subacute focal symptoms that suggested an acute ischemic stroke (AIS), 609 of them with AIS. RESULTS: DWI demonstrated a sensitivity of 90% and specificity of 97%, a positive likelihood ratio of 31 and a negative likelihood ratio of 0.1 for detecting AIS. The overall accuracy was 95%. Of those patients who demonstrated abnormal DWI studies, 99.5% were AIS patients, and of those patients with normal DWI studies 63% were stroke mimics. CONCLUSIONS: DWI is accurate in detecting AIS in unselected patients with suspected AIS; a negative study should alert for nonischemic conditions.Item Accuracy of Power Mode TranscranialDoppler in the Diagnosis of Brain Death(2015) Brunser, Alejandro; Lavados, Pablo; Cárcamo, Daniel; Hoppe, Arnold; Olavarría, Verónica; López, Javiera; Muñoz, Paula; Rivas, RodrigoBackground:The diagnosis of brain death (BD) is complex. For this reason, we aimed toevaluate the accuracy of power mode transcranial Doppler (PMD-TCD) in diagnosing BD.Patients and methods:Patients admitted to an intensive care unit between December 2003and January 2012 were included in this study if they were in a structural coma, had nocraniectomy, and were evaluated blind by a neurologist using PMD-TCD. The diagnosis of BDwas based on an evaluation that took into consideration the absence of sedative drugs, amedian blood pressure>60 mmHg, a body temperature>35 C, and the absence of brainstemreflexes. A neurosonologist followed a protocol using PMD-TCD that considered the examina-tion as positive for brain circulatory arrest given the presence of reverberating, small systolicpeaks or the disappearance of a previous signal present in both middle cerebral arteries andintracranial vertebral arteries.Results:A total of 74 patients were evaluated. In 61 (82.4%) patients the interval betweenboth evaluations was less than 1 hour. The sensitivity and specificity for the diagnosis of BD with PMD-TCD were 100% and 98%, respectively. The positive and negative likelihood ratios forBD were 45 and 0, respectively.Conclusion:PMD-TCD is accurate for the diagnosis of BD.Item Additional Information Given to a Multimodal Imaging Stroke Protocol by Transcranial Doppler Ultrasound in the Emergency Room: A Prospective Observational Study(2010) Brunser, Alejandro M.; Lavados, Pablo; Cárcamo, Daniel A.; Hoppe, Arnold; Olavarría, Verónica; Diaz, Violeta; Rivas, RodrigoBackground: Transcranial Doppler (TCD) ultrasound can demonstrate dynamic information. We aimed to evaluate whether TCD generates useful additional information in the emergency room after a multimodal stroke imaging protocol and also whether this modified the management of patients with cerebral infarction. Methods: Patients admitted between April 2006 and June 2007 with ischemic stroke of less than 24 h were subjected to a protocol consisting of non-contrast brain CT, computed tomography angiography, diffusion-weighted magnetic resonance imaging and then TCD within the following 6 h by an observer blinded to the results of imaging studies. Results: Seventy-nine patients were included. The imaging protocol was performed 457 (+/-346) min after stroke symptoms and TCD after 572 (+/-376) min. TCD provided additional information in 28 cases (35.4%, 95% CI 25.7-46.4). More that one piece of additional information was obtained in 6 patients. The most frequent additional information was collateral pathways. Multivariate analysis demonstrated that intracranial vessel occlusion was the variable most associated with additional information. In 7 patients (8.8%, 95% CI 4.3-17.1), additional information changed management: in 4 an additional angiography was performed, in 2 patients angiography was suspended and in 1 aggressive neurocritical care was indicated. Patients with NIHSS >10 were significantly more likely to have their initial treatment changed (p = 0.004). Conclusions: TCD can provide additional information to a multimodal acute ischemic stroke imaging protocol in a third of patients. This can result in changes in the management in some of these patients.Item Applicability of ENCHANTED trial results to current acute ischemic stroke patients eligible for intravenous thrombolysis in England and Wales: Comparison with the Sentinel Stroke National Audit Programme registry(Sage Publishing, 2019-10) Robinson, Thompson; Bray, Benjamin; Paley, Lizz; Sprigg, Nikola; Wan, Xia; Arima, Hisatomi; Bath, Philip; Broderick, Joseph; Durham, Alice; Kim, Jong; Lavados, Pablo; Lee, Tsong-Hai; Martins, Sheila; Nguyen, Thang; Pandian, Jeyaraj; Parsons, Mark; Pontes-Neto, Octavio; Ricci, Stefano; Sharma, Vijay; Wang, Jiguang; Woodward, Mark; Rudd, Anthony; Chalmers, John; Anderson, Craig; ENCHANTED InvestigatorsBackground: Randomized controlled trials provide high-level evidence, but the necessity to include selected patients may limit the generalisability of their results. Methods: Comparisons were made of baseline and outcome data between patients with acute ischemic stroke (AIS) recruited into the alteplase-dose arm of the international, multi-center, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) in the United Kingdom (UK), and alteplase-treated AIS patients registered in the UK Sentinel Stroke National Audit Programme (SSNAP) registry, over the study period June 2012 to October 2015. Results: There were 770 AIS patients (41.2% female; mean age 72 years) included in ENCHANTED at sites in England and Wales, which was 19.5% of alteplase-treated AIS patients registered in the SSNAP registry. Trial participants were significantly older, had lower baseline neurological severity, less likely Asian, and had more premorbid symptoms, hypertension and atrial fibrillation. Although ENCHANTED participants had higher rates of symptomatic intracerebral hemorrhage than those in SSNAP, there were no differences in onset-to-treatment time, levels of disability (assessed by the modified Rankin scale) at hospital discharge, and mortality over 90 days between groups. Conclusions: Despite the high level of participation, equipoise over the dose of alteplase among UK clinician investigators favored the inclusion of older, frailer, milder AIS patients in the ENCHANTED trial.Publication Association of Dual-Phase Computed Tomography Angiography and CTPerfusion in Patients with Acute Ischemic Stroke Beyond the 6-Hour Window(2023) Gallardo, Andrés; Lavados, Pablo; Cox, Pablo; De la Barra, Camila; Cavada, Gabriel; Olavarria, VerónicaBackground: There is controversy regarding the need to use advanced imaging to select candidates for thrombectomy in late window acute ischemic stroke (AIS). Hypoattenuation on CT angiography source images (CTA-SI) in arterial phase has been shown to be more sensitive than Alberta Stroke Program Early CT score (ASPECTS) of brain parenchyma to determine tissue at risk of ischemia. Our hypothesis is that the addition of a second acquisition at 35-50 seconds could complement the assessment of hypoperfused tissue that fails to receive flow through pial vessels. Methods: Patients with large vessel occlusion and 6-16 hours from symptom onset, admitted between August 2019 and July 2022 were evaluated with dualphase CT angiography (CTA) and CT-perfusion. The association between automated CT-perfusion valuesand dual-phase CTA was assessed through a correlation coefficient. Results: Pearson's coefficient demonstrated a high correlation between ischemic core volume and delayed CTA-SI with an inverse association of -0.91 and between Tmax≥6 sec volume and arterial CTA-SI with a value of -0.83. Conclusion: CTA-derived source images (CTA-SI) in two phases may be useful in the selection of patients with AIS presenting beyond the 6-hour window.Publication Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis- Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study(2022) Wang, Xia; Minhas, Jatinder S.; Moullaali, Tom J.; Di Tanna, Gian Luca; Lindley, Richard I.; Chen, Xiaoying; Arima, Hisatomi; Chen, Guofang; Delcourt, Candice; Bath, Philip M.; Broderick, Joseph P.; Demchuk, Andrew M.; Donnan, Geoffrey A.; Durham, Alice C.; Lavados, Pablo; Lee, Tsong-Hai; Levi, Christopher; Martins, Sheila O.; Olavarría, Verónica V.; Pandian, Jeyaraj D.; Parsons, Mark W.; Pontes-Neto, Octavio M.; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K.; Silva, Federico; Thang, Nguyen H.; Wang, Ji-Guang; Woodward, Mark; Chalmers, John; Song, Lili; Anderson, Craig S.; Robinson, Thompson G.BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1–24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P<0.001 and 0.86 [95% CI, 0.76–0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93– 1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P=0.002 and 1.34 [1.11–1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients.Item Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies(BMJ Publishing Group, 2017) Delcourt, Candice; Zheng, Danni; Chen, Xiaoying; Hackett, Maree; Arima, Hisatomi; Hata, Jun; Heeley, Emma; Al-Shahi Salman, Rustam; Woodward, Mark; Huang, Yining; Robinson, Thompson; Lavados, Pablo; Lindley, Richard I; Stapf, Christian; Davies, Leo; Chalmers, John; Anderson, Craig; Sato, Shoichiro; INTERACT InvestigatorsBACKGROUND AND PURPOSE: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). METHODS: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL. RESULTS: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively. CONCLUSIONS: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score.Item Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial(Elsevier, 2014) Manning, Lisa; Hirakawa, Yoichiro; Arima, Hisatomi; Wang, Xia; Chalmers, John; Wang, Jiguang; Lindley, Richard; Heeley, Emma; Delcourt, Candice; Neal, Bruce; Lavados, Pablo; Davis, Stephen; Tzourio, Christophe; Huang, Yining; Stapf, Christian; Woodward, Mark; Rothwell, Peter; Robinson, Thompson; Anderson, CraigBackground: High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood pressure variability in participants of INTERACT2, an open-label randomised controlled trial (ClinicalTrials.gov number NCT00716079). Methods: INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150–220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mm Hg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2–7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles. Findings: We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05–1·90; ptrend=0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14–2·17; ptrend=0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14–1·80; ptrend=0·0014; for the acute phase OR 1·46, 95% CI 1·13–1·88; ptrend=0·0044). Interpretation: Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure. Funding: National Health and Medical Research Council of Australia.Item Blood pressure variability and outcome in acute ischemic and hemorrhagic stroke: a post hoc analysis of the HeadPoST study(2019) Minhas, Jatinder; Wang, Xia; Lavados, Pablo; Moullaali, Tom; Arima, Hisatomi; Billot, Laurent; Olavarria, Veronica; Middleton, Sandy; Pontes, Octavio; De Silva, H Asita; Lee, Tsong; Pandian, Jeyaraj; Mead, Gillian; Watkins, Caroline; Chalmers, John; Anderson, Craig S; Robinson, Thompson; HeadPoST InvestigatorsThe Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0°) or sitting-up (head elevated ≥30°) position. This post hoc analysis aimed to determine the association between blood pressure variability (BPV) and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to the standard criteria, with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 h. Outcome was ordinal 90-day Modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying flat vs. sitting up), and fixed period, random cluster, and random cluster-period, effects. Nine thousand one hundred and fifty six (8324 acute ischemic stroke and 817 intracerebral hemorrhage; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.11; P = 0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03-1.12; P = 0.001) over 24 h post stroke was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06-1.19) compared with lying-flat position (1.03, 0.98-1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, and the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability.Item Characteristics, management and response to alteplase in China versus non-China participants of the ENCHANTED trial(2017) Song, Lily; Wang, Xia; Robinson, Thompson; Lindley, Richard I; Arima, Hisatomi; Lavados, Pablo; Chen, Xiaoying; Chalmers, John; Anderson, Craig SBackground: The characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED), which tested different alteplase doses in AIS. Methods: ENCHANTED was an international, multicentre, open, blinded-endpoint trial of the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) in 3310 patients with AIS. Results: Participants (n=1419, 48%) in China were younger, and more often male, hypertensive and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared with non-China patients with AIS. Although China participants had more AIS due to large artery occlusion, were treated later and had differing ancillary management, there was no significant difference in 90-day modified Rankin scale scores 2-6 (55.6% vs 47.8%; OR, adjusted for baseline and management factors 0.87 (95% CI 0.71 to 1.07; p=0.20)) and risk of sICH (Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria: 1.4% vs 1.8%; p=0.12) compared with non-China participants. There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants. Conclusion: Patients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management factors to patients with AIS in other regions.Item Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial(2018) Kasner, Scott E.; Lavados, Pablo; Sharma, Mukul; Wang, Yongjun; Wang, Yilong; Dávalos, Antoni; Shamalov, Nikolay; Cunha, Luis; Lindgren, Arne; Mikulik, Robert; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens; Amarenco, Pierre; Ameriso, Sebastián F.; Tatlisumak, Turgut; Hart, Robert G.; NAVIGATE ESUS Steering Committee and InvestigatorsBackground: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Results: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.Item Clinical prediction algorithm (BRAIN) to determine risk of hematoma growth in acute intracerebral hemorrhage(American Heart Association, Inc., 2015) Wang, Xia; Arima, Hisatomi; Al-Shahi Salman, Rustam; Woodward, Mark; Heeley, Emma; Stapf, Christian; Lavados, Pablo; Thompson, Robinson; Huang, Yining; Wang, Jiguang; Delcourt, Candice; Anderson, Craig; INTERACT InvestigatorsBACKGROUND AND PURPOSE: We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients. METHODS: We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model. RESULTS: A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10-20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1-2=4, 2-3=3, 3-4=2, 4-5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer-Lemeshow P=0.82) in INTERACT1. CONCLUSIONS: The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice.Item Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke(Massachusetts Medical Society, 2017) Anderson, Craig; Arima, Hisatomi; Lavados, Pablo; Billot, Laurent; Hackett, Maree; Olavarría, Verónica; Muñoz Venturelli, Paula; Brunser, Alejandro; Peng, Bin; Cui, Liying; Song, Lily; Rogers, Kris; Middleton, Sandy; Lim, Joyce Y.; Forshaw, Denise; Lightbody, Elizabeth; Woodward, Mark; Pontes-Neto, Octavio; De Silva, Asita; Lin, Ruey-Tay; Lee, Tsong-Hai; Pandian, Jeyaraj D.; Mead, Gillian E.; Robinson, Thompson; Watkins, Caroline; HeadPoST Investigators and CoordinatorsBACKGROUND: The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS: In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS: The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P<0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P=0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P=0.83). There were no significant between-group differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS: Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours. (Funded by the National Health and Medical Research Council of Australia; HeadPoST ClinicalTrials.gov number, NCT02162017.)Publication Correlation between dual-phase CTA-SI ASPECTS and automated CT perfusion imaging in patients with acute ischemic stroke beyond the 6-hour window(2023) Gallardo, Andrés; Lavados, Pablo; Cox, Pablo; Barra, Camila de la; Cavada, Gabriel; Olavarría, Verónica V.Background/Objective: There is controversy regarding the need to use advanced imaging to select candidates for thrombectomy in late window acute ischemic stroke (AIS). Hypoattenuation on CT angiography source images (CTA-SI) in arterial phase has been shown to be more sensitive than Alberta Stroke Program Early CT Score (ASPECTS) of brain parenchyma to determine tissue at risk of ischemia. Our hypothesis is that the addition of a second acquisition at 35-50 seconds could complement the assessment of hypoperfused tissue that fails to receive flow through pial vessels. Methods: Patients with large vessel occlusion and 6-24 hours from symptom onset, admitted between August 2019 and July 2023, were evaluated with dual-phase CT angiography (CTA) and CT-Perfusion. A vascular neurologist estimated CTA-SI ASPECTS in both phases at the time of data entry into the RECCA registry. In contrast, the post-processing of CT-Perfusion images was performed in an automated way through RAPID© software. The association between automated CT-perfusion values and dual-phase CTA-SI ASPECTS was assessed through a correlation coefficient. Results: Pearson’s coefficient demonstrated a high correlation between ischemic core volume and delayed phase CTA (CTA-DP) ASPECTS with an inverse association of −0.93 and between Tmax ≥ 6 sec volume and arterial phase CTA (CTA-AP) ASPECTS with a value of −0.88. Conclusions: CTA-derived source images (CTA-SI) in two phases may be useful in the selection of patients with AIS presenting beyond the 6-hour window.Item COVID-19 Lockdown Effects on Acute Stroke Care in Latin America(2021) Pujol-Lereis, Virginia A.; Flores, Alan; Barboza, Miguel A.; Abanto-Argomedo, Carlos; Amaya, Pablo; Bayona, Hernán; Bonardo, Pablo; Díaz-Escobar, Luis; Gómez-Schneider, Maia; Góngora-Rivera, Fernando; Lavados, Pablo; León, Carolina; Luraschi, Adriana; Márquez-Romero, Juan Manuel; Ouriques-Martins, Sheila C.; Navia, Víctor; Ruiz-Franco, Angélica; Vences, Miguel Angel; Zurru, María Cristina; Arauz, Antonio; Ameriso, Sebastián; Latin American Stroke rEgistry (LASE) COVID-19 Collaborators.Objectives: COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America. Materials and Methods: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed. Results: Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0 5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-toCT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1 5 days vs. 0 9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period. Conclusions: In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.Item Degree and Timing of Intensive Blood Pressure Lowering on Hematoma Growth in Intracerebral Hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 Results(American Heart Association, Inc., 2016) Carcel, Cheryl; Wang, Xia; Sato, Shoichiro; Stapf, Christian; Sandset, Else; Delcourt, Candice; Arima, Hisatomi; Thompson, Robinson; Lavados, Pablo; Chalmers, John; Anderson, Craig; INTERACT2 InvestigatorsBACKGROUND AND PURPOSE: Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2). METHODS: INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], <140 mm Hg) versus guideline-recommended (SBP, <180 mm Hg) BP lowering in 2839 patients within 6 hours of spontaneous intracerebral hemorrhage and elevated SBP (150-220 mm Hg), in which 964 had repeat cranial computed tomography at 24 hours. ANCOVA models assessed categories of SBP reduction and time to target SBP on 24-hour hematoma growth. RESULTS: Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for <10, 10-20, and ≥20 mm Hg, respectively; P trend<0.001). In the intensive treatment group (n=491), the least mean hematoma growth was in patients who achieved target SBP <1 hour (2.6 mL) versus to those in target at 1 to 6 (4.7 mL) and >6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). CONCLUSIONS: Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079Item Demographics, socio-economic characteristics, and risk factor prevalence in patients with non-cardioembolic ischaemic stroke in low- and middle-income countries: the OPTIC registry.(Sage Publications, 2013) Abboud, Halim; Labreuche, Julien; Arauz, Antonio; Bryer, Alan; Lavados, Pablo; Massaro, Ayrton; Muñoz, Mario; Steg, Philippe; Yamout, Bassem; Vicaut, Eric; Amarenco, PierreBACKGROUND: There is a paucity of data on patients with stroke/transient ischaemic attack in low- and middle-income countries. We sought to describe the characteristics and management of patients with an ischaemic stroke and recent transient ischaemic attack or minor ischaemic strokes in low- or middle-income countries. METHODS: The Outcomes in Patients with TIA and Cerebrovascular disease registry is an international, prospective study. Patients ≥ 45 years who required secondary prevention of stroke (either following an acute transient ischaemic attack or minor ischaemic strokes (National Institutes of Health Stroke Scale <4) of <24 h duration, or recent (<6 months), stable, first-ever, non-disabling ischaemic stroke) were enrolled in 17 countries in Latin America, the Middle East, and Africa. The main measures of interest were risk factors, comorbidities, and socio-economic variables. RESULTS: Between January 2007 and December 2008, 3635 patients were enrolled in Latin America (n = 1543), the Middle East (n = 1041), North Africa (n = 834), and South Africa (n = 217). Of these, 63% had a stable, first-ever ischaemic stroke (median delay from symptom onset to inclusion, 25 days interquartile range, 7-77); 37% had an acute transient ischaemic attack or minor ischaemic stroke (median delay, two-days; interquartile range, 0-6). Prevalence of diabetes was 46% in the Middle East, 29% in Latin America, 35% in South Africa, and 38% in North Africa; 72% had abdominal obesity (range, 65-78%; adjusted P < 0.001); prevalence of metabolic syndrome was 78% (range, 72-84%, P < 0.001). Abnormal ankle brachial index (<0.9) was present in 22%, peripheral artery disease in 7.6%, and coronary artery disease in 13%. Overall, 24% of patients had no health insurance and 27% had a low educational level. INTERPRETATION: In this study, patients in low- and middle-income countries had a high burden of modifiable risk factors. High rates of low educational level and lack of health insurance in certain regions are potential obstacles to risk factor control. FUNDING: The Outcomes in Patients with TIA and Cerebrovascular disease registry is supported by Sanofi-Aventis, Paris, France.Item Determinantes del tiempo puerta-aguja en trombolisis endovenosa en el infarto cerebral, experiencia de un centro(2020) Brunser, Alejandro; Mazzon, Enrico; Muñoz, Paula; Hoppe, Arnold; Lavados, Pablo; Rojo, Alexis; Navia, Víctor; Cavada, Gabriel; Olavarría, Verónica; Mansilla, EloyBackground: Intravenous thrombolysis (IT) in acute ischemic stroke (AIS) is time dependent. The time elapsed from hospital admission to the thrombolytic bolus is named door to needle time (DNT) and is recommend to be of less than 60 min. Aim: To describe the DNT in our center and determine those factors associated with a DNT longer than 60 min. Material and Methods: Prospective analysis of patients treated with IT at a private hospital between June 2016 and June 2019. The percentage of patients with DNT exceeding 60 min, and the causes for this delay were evaluated. Results: IT was used in 205 patients. DNT was 43.6 ± 23.8 min. Forty patients (19.5% (95% CI, 14.4-25.7), had a DNT longer than 60 min. Uni-varied analysis demonstrated that AIS with infratentorial symptomatology (ITS), was significantly associated with DNTs exceeding 60 min. A history of hypertension, a higher NIH Stroke Scale score, the presence of an hyperdense sign in brain tomography (p = 0.001) and the need for endovascular therapy (p = 0.019), were associated with DNT shorter than 60 min. Multivariate analysis ratified the relationship between ITS and DNT longer than 60 min (Odds ratio: 3.19, 95% confidence intervals 1.26-8). Conclusions: The individual elements that correlated with a DNT longer than 60 min were the failure to detect the AIS during triage and doubts about its diagnosisItem Development of the standards of reporting of neurological disorders (STROND) checklist: a guideline for the reporting of incidence and prevalence studies in neuroepidemiology.(Springer International Publishing AG, 2015) Bennett, Derrick; Brayne, Carol; Feigin, Valery; Barker-Collo, Suzanne; Brinin, Michael; Davis, Daniel; Gallo, Valentina; Jetté, Nathalie; Karch, André; Kurtzke, John; Lavados, Pablo; Lagroscino, Giancarlo; Nagel, Gabriele; Preux, Pierre-Marie; Rothwell, Peter; Svenson, LawrenceIncidence and prevalence studies of neurological disorders play an important role in assessing the burden of disease and planning services. However, the assessment of disease estimates is hindered by problems in reporting for such studies. Despite a growth in published reports, existing guidelines relate to analytical rather than descriptive epidemiological studies. There are also no user-friendly tools (e.g., checklists) available for authors, editors and peer-reviewers to facilitate best practice in reporting of descriptive epidemiological studies for most neurological disorders. The Standards of Reporting of Neurological Disorders (STROND) is a guideline that consists of recommendations and a checklist to facilitate better reporting of published incidence and prevalence studies of neurological disorders. A review of previously developed guidance was used to produce a list of items required for incidence and prevalence studies in neurology. A three-round Delphi technique was used to identify the ‘basic minimum items’ important for reporting, as well as some additional ‘ideal reporting items’. An e-consultation process was then used in order to gauge opinion by external neuroepidemiological experts on the appropriateness of the items included in the checklist. Of 38 candidate items, 15 items and accompanying recommendations were developed along with a user-friendly checklist. The introduction and use of the STROND checklist should lead to more consistent, transparent and contextualised reporting of descriptive neuroepidemiological studies resulting in more applicable and comparable findings and ultimately support better healthcare decisions.Item Diagnostic accuracy of a simple clinical score to screen for vascular abnormalities in patients with intracerebral hemorrhage.(Elsevier, 2014) Olavarría, Verónica; Bustamante, Gonzalo; López, Mirta; Lavados, PabloBACKGROUND: Patients with intracerebral hemorrhage may have vascular abnormalities. There is no consensus about which patients should be studied with angiographic methods. Our aim was to derive a simple clinical score to screen for vascular abnormalities in intracerebral hemorrhage (ICH) and test its accuracy. METHODS: The data were extracted from 2 different registries of patients with ICH. Variables associated with a vascular abnormality were studied in the derivation cohort. We derived a scale by assigning scores to the degree of association. We applied the score to the validation cohort and calculated sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios (LRs), receiver operating curves (ROC) and area under the curve (AUC). RESULTS: The performance of the scale in the derivation cohort showed the maximum operating point (MOP) at ≥5 (sensitivity .77, specificity .5). In the validation cohort, the MOP was a cutoff point of ≥5 (sensitivity .76, specificity .467). The positive and negative LRs were 2.1 and .6, respectively. The ROC showed similar AUC for both cohorts: .7. The probability of a vascular malformation was 23% with scores ≤5 and 83% with scores ≥9 in the validation cohort. CONCLUSIONS: This simple clinical score can be used immediately on diagnosing an ICH to decide accurately whether to perform an angiographic study or not. Further studies using this simple score should be used to validate it in larger prospective unselected cohorts and consecutive patients.