Publications by authors named "Henry Ma"

253 Publications

Does Intravenous Thrombolysis Within 4.5 to 9 Hours Increase Clot Migration Leading to Endovascular Inaccessibility?

Stroke 2021 Mar 16;52(3):1083-1086. Epub 2021 Feb 16.

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital (A.B., H.M., B.C.V.C., M.W.P., S.M.D., G.A.D., B.Y.), University of Melbourne, Parkville, Australia.

Background And Purpose: Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours.

Methods: We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data. Baseline and 12- to 24-hour follow-up clot location was determined on computed tomography angiogram or magnetic resonance angiogram. The incidence of clot migration leading to a change from retrievable to nonretrievable location was identified and compared between the two treatment groups (IVT versus placebo).

Results: Two hundred twenty patients were assessed. Clot migration from a retrievable to nonretrievable location occurred in 37 patients: 21 patients (19.3%) in the placebo group and 16 patients (14.4%) in the IVT group. No significant difference was identified in the incidence of clot migration leading to inaccessibility between groups (=0.336).

Conclusions: Our results did not show increased clot migration leading to clot inaccessibility in patients treated with IVT.
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http://dx.doi.org/10.1161/STROKEAHA.120.030661DOI Listing
March 2021

Influence of Thermal and Gustatory Stimulus in the Initiation of the Pharyngeal Swallow and Bolus Location Instroke.

J Stroke Cerebrovasc Dis 2021 Apr 5;30(4):105349. Epub 2021 Feb 5.

Department of Surgery, Sao Paulo State University - UNESP, Botucatu SP, Brazil.

Introduction/objective: The aim of this study is to analyze the influence of sour taste and cold temperature in the initiation of the pharyngeal swallow (IPS) and bolus location at pharyngeal swallow onset in individuals after stroke.

Methods: Cross-sectional prospective study. The study included 52 individuals with unilateral ischemic stroke. Each individual was assessed by videofluoroscopic swallowing study with 5ml of paste bolus offering four different stimuli (natural, cold, sour, and sour-cold). The individuals were divided into two groups according to the offer sequence. Group 1 (G1) - received a randomized sequence of stimuli (24 individuals), and Group 2 (G2) -the stimuli were offered in the following order: natural, cold, sour, and sour-cold(28 individuals). The IPS time and bolus location at pharyngeal swallow onset were analyzed. The bolus location at pharyngeal swallow onset was defined using six different levels.

Results: Individuals in G1 did not show a significant difference in IPS time between stimuli. However, individuals in G2 presented a significantly shorter IPS time with the sour and sour-cold stimuli than with natural or cold stimuli. The bolus location at pharyngeal swallow onset did not show significant difference between stimuli in both groups. On the other hand, in the G2 it was observed higher frequency of swallowing with sour-cold stimulus at level 1 (the bolus head was located in any region between the fauces pillar and the point where the tongue crosses the inferior border of the mandible).

Conclusion: The sour and sour-cold stimuli influenced the IPS time when they were offered in a sequential order. Moreover, both the IPS time and bolus location at pharyngeal swallow onset were not influenced by the sour and sour cold-bolus when offered in a random sequence.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105349DOI Listing
April 2021

Physiological and immunological changes in the brain associated with lethal eastern equine encephalitis virus in macaques.

PLoS Pathog 2021 Feb 3;17(2):e1009308. Epub 2021 Feb 3.

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Aerosol exposure to eastern equine encephalitis virus (EEEV) can trigger a lethal viral encephalitis in cynomolgus macaques which resembles severe human disease. Biomarkers indicative of central nervous system (CNS) infection by the virus and lethal outcome of disease would be useful in evaluating potential medical countermeasures, especially for therapeutic compounds. To meet requirements of the Animal Rule, a better understanding of the pathophysiology of EEEV-mediated disease in cynomolgus macaques is needed. In this study, macaques given a lethal dose of clone-derived EEEV strain V105 developed a fever between 2-3 days post infection (dpi) and succumbed to the disease by 6 dpi. At the peak of the febrile phase, there was a significant increase in the delta electroencephalography (EEG) power band associated with deep sleep as well as a sharp rise in intracranial pressure (ICP). Viremia peaked early after infection and was largely absent by the onset of fever. Granulocytosis and elevated plasma levels of IP-10 were found early after infection. At necropsy, there was a one hundred- to one thousand-fold increase in expression of traumatic brain injury genes (LIF, MMP-9) as well as inflammatory cytokines and chemokines (IFN-γ, IP-10, MCP-1, IL-8, IL-6) in the brain tissues. Phenotypic analysis of leukocytes entering the brain identified cells as primarily lymphoid (T, B, NK cells) with lower levels of infiltrating macrophages and activated microglia. Massive amounts of infectious virus were found in the brains of lethally-infected macaques. While no infectious virus was found in surviving macaques, quantitative PCR did find evidence of viral genomes in the brains of several survivors. These data are consistent with an overwhelming viral infection in the CNS coupled with a tremendous inflammatory response to the infection that may contribute to the disease outcome. Physiological monitoring of EEG and ICP represent novel methods for assessing efficacy of vaccines or therapeutics in the cynomolgus macaque model of EEEV encephalitis.
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http://dx.doi.org/10.1371/journal.ppat.1009308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886169PMC
February 2021

Where do low risk women live relative to maternity services across Victoria? Expanding access to public homebirth models across Victoria.

Women Birth 2021 Jan 12. Epub 2021 Jan 12.

Safer Care Victoria, Melbourne, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria 3168, Australia; The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia. Electronic address:

Problem: Currently <1% of Australian women give birth at home.

Background: In Australia there are very few options for women to access public funded homebirth.

Aim: We aimed to use geo-mapping to identify the number of women eligible for homebirth in Victoria, based on the criteria of uncomplicated pregnancies and residing within 15-25kms of suitable maternity services, to plan future maternity care options.

Methods: Retrospective study of births between 2015 and 2017 in Victoria, Australia. All women who were identified as having a low risk pregnancy at the beginning of pregnancy were included. The number of women within 15 and 25km of a suitable Victorian public maternity hospital and catchment boundaries around each hospital were determined.

Findings: Between 2015 and 2017, 126,830 low risk women gave birth in Victoria, of whom half live within 25km of seven Victorian hospitals. Currently, 2% of suitable women who live close to the current public homebirth models accessed them.

Discussion: We present a method to inform the expansion of maternity service options using Victoria as an example. On the basis of the maximum number of low risk women living close by, we have also identified the Victorian maternity services that would be most suitable for creation of public homebirth or low risk continuity of midwifery models.

Conclusion: This approach could can be used to plan other maternity care services.
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http://dx.doi.org/10.1016/j.wombi.2021.01.004DOI Listing
January 2021

Utility of Severity-Based Prehospital Triage for Endovascular Thrombectomy: ACT-FAST Validation Study.

Stroke 2021 01 22;52(1):70-79. Epub 2020 Dec 22.

Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital (H.Z., L.C., J.L.N., C.W., F.A., F.N., P.J.M., M.W.P., N.Y., S.M.D., B.C.V.C.), University of Melbourne, Australia.

Background And Purpose: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm.

Methods: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening.

Results: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0-61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region.

Conclusions: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.
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http://dx.doi.org/10.1161/STROKEAHA.120.031467DOI Listing
January 2021

Concurrent middle and posterior cerebral artery stroke: Question.

J Clin Neurosci 2021 Jan 13;83:123-124. Epub 2020 Dec 13.

Stroke & Ageing Research (STAR), Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia.

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http://dx.doi.org/10.1016/j.jocn.2020.09.010DOI Listing
January 2021

Concurrent middle and posterior cerebral artery stroke: Answer.

J Clin Neurosci 2021 Jan 13;83:152. Epub 2020 Dec 13.

Stroke & Ageing Research (STAR), Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia.

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http://dx.doi.org/10.1016/j.jocn.2020.11.015DOI Listing
January 2021

A Dye Tracer Approach for Quantifying Fluid and Solute Flux Across the Sediment-Water Interface.

Ground Water 2021 May 16;59(3):428-437. Epub 2020 Dec 16.

MHE Products, 3371 Sherman Road, East Tawas, MI, 48730, USA.

We propose a dye tracer method to characterize fluid and solute fluxes across the sediment-water interface. Zones of groundwater discharge within the streambed are first identified, and small volume slugs of 0.5 to 1 mL fluorescein dye are released at known subsurface depths. Fluorescein dye allows for visual identification of interface breakthrough locations and times, and dye concentrations at the point of discharge are recorded over time by a fluorometer to generate high resolution breakthrough curves. Groundwater velocities and dispersivities at the demonstration site are estimated by numerically fitting dye breakthroughs to the classical advection-dispersion equation, although the methodology is not limited to a specific transport model. Breakthroughs across the stream-sediment interface at the demonstration site are nonlinear with tracer release depth, and velocity estimates from breakthrough analysis are significantly more reliable than visual dye (time to first dye expression) and Darcy methods which tend to overestimate and underestimate groundwater velocity, respectively. The use of permanent injection points within the streambed and demonstrated reproducibility of dye breakthroughs allow for study of fluid and solute fluxes under seasonally varying hydrologic conditions. The proposed approach also provides a framework for field study of nonconservative, reactive solutes and allows for the determination of characteristic residence times at various depths in the streambed to better understand chemical and nutrient transformations.
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http://dx.doi.org/10.1111/gwat.13060DOI Listing
May 2021

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

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.

JAMA Neurol 2021 Feb;78(2):236-240

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

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.
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http://dx.doi.org/10.1001/jamaneurol.2020.4123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607491PMC
February 2021

Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial.

Lancet Neurol 2020 12 28;19(12):980-987. Epub 2020 Oct 28.

Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia.

Background: Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage.

Methods: We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of >7, intracerebral haemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636).

Findings: Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.

Interpretation: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.

Funding: National Health and Medical Research Council, Royal Melbourne Hospital Foundation.
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http://dx.doi.org/10.1016/S1474-4422(20)30369-0DOI Listing
December 2020

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

J Stroke Cerebrovasc Dis 2020 Dec 16;29(12):105321. Epub 2020 Sep 16.

Westchester Medical Center Health Network, Director of Neurocritical Care and Emergency Neurological Services, Valhalla, NY, USA; Westchester Medical Center Health Network, New York Medical College, Valhalla, NY, USA.

Background: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.

Methods: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.

Results: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001).

Conclusion: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494258PMC
December 2020

An International Report on the Adaptations of Rapid Transient Ischaemic Attack Pathways During the COVID-19 Pandemic.

J Stroke Cerebrovasc Dis 2020 Nov 18;29(11):105228. Epub 2020 Aug 18.

School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia; Department of Neurology, Monash Medical Centre, Melbourne, Australia. Electronic address:

Background: This report aims to describe changes that centres providing transient ischaemic attack (TIA) pathway services have made to stay operational in response to the SARS-CoV-2 pandemic.

Methods: An international cross-sectional description of the adaptions of TIA pathways between 30 March and 6 May 2020. Experience was reported from 18 centres with rapid TIA pathways in seven countries (Australia, France, UK, Canada, USA, New Zealand, Italy, Canada) from three continents.

Results: All pathways remained active (n = 18). Sixteen (89%) had TIA clinics. Six of these clinics (38%) continued to provide in-person assessment while the majority (63%) used telehealth exclusively. Of these, three reported PPE use and three did not. Five centres with clinics (31%) had adopted a different vascular imaging strategy.

Conclusion: The COVID pandemic has led TIA clinics around the world to adapt and move to the use of telemedicine for outpatient clinic review and modified investigation pathways. Despite the pandemic, all have remained operational.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434484PMC
November 2020

Experimental infection model with the bivalvulid Enteromyxum leei (Myxidiidae) in the sharpsnout seabream, Diplodus puntazzo (Sparidae), and evaluation of the antiparasitic efficacy of a functional diet.

Folia Parasitol (Praha) 2020 Sep 22;67. Epub 2020 Sep 22.

Institute of Marine Biology, Biotechnology and Aquaculture, Hellenic Centre for Marine Research, Anavissos, Attiki, Greece.

An infection model for sharpsnout seabream Diplodus puntazzo (Walbaum) challenged with the myxosporean Enteromyxum leei (Diamant, Lom et Dyková, 1994), resembling the natural infection conditions, was used to evaluate the antiparasitic efficacy of a functional diet. Fish of an average weight of 12.5 ± 1.2 g were delivered either a functional (included as feed supplement at 0.3% levels) or a control extruded diet. After four weeks of administration of the experimental diets, fish were challenged with the parasites (cohabitation with infected donors; donor: recipient ratio 1 : 1). The experiment was terminated four weeks after the start of the challenge. At the end of the experiment, growth and feeding (specific growth rate and feed efficiency), as well as immunological parameters (respiratory burst activity, antibacterial activities, hemoglobin concentration, anti-protease activity and ceruloplasmin activity) were measured along with cumulative mortality and total parasitic count in the gut. No significant difference was evident with regard to growth and feeding performance, mortality, gut parasitic load or immunological parameters as the parasitical challenge significantly affected both the performance of the control and functional diet fed fish. However, there was a less prominent impact on antibacterial, anti-protease and ceruloplasmin activity in fish fed with the functional diet. Overall, the present study validated the experimental cohabitation infection model and evaluated the efficacy of a functional ingredient as an antiparasitic agent, showing some potential effects on the fish immune response.
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http://dx.doi.org/10.14411/fp.2020.024DOI Listing
September 2020

Impact of Stress and Loneliness on Health-Related Quality of Life Among Low Income Senior African Americans.

J Racial Ethn Health Disparities 2020 Sep 17. Epub 2020 Sep 17.

Department of Psychology, University of Florida, Gainesville, FL, USA.

Low income senior African Americans are at risk for low health-related quality of life (HRQoL). Loneliness may exacerbate the effects of stress on health. The purpose of this study was to examine the impact of perceived stress and loneliness on the HRQoL of low income senior African Americans (N = 281). Results indicate that loneliness may exacerbate the inverse relationship of perceived stress with psychological HRQoL among this sample. Additionally, both loneliness and perceived stress were associated with poorer physical HRQoL. The present study has implications for interventions seeking to improve HRQoL among a similar sample of senior adults given that loneliness is a modifiable variable.
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http://dx.doi.org/10.1007/s40615-020-00865-wDOI Listing
September 2020

Acute Routine Leukocyte and Neutrophil Counts Are Predictive of Poststroke Recovery at 3 and 12 Months Poststroke: An Exploratory Study.

Neurorehabil Neural Repair 2020 09;34(9):844-855

La Trobe University, College of Science, Health and Engineering, Bundoora, Victoria, Australia.

. White blood cell (WBC) and neutrophil counts (NC) are common markers of inflammation and neurological stroke damage and could be expected to predict poststroke outcomes. . The aim of this study was to explore the prognostic value of early poststroke WBC and NC to predict cognition, mood, and disability outcomes at 3 and 12 months poststroke. . Routine clinical analyses WBC and NC were collected at 3 time points in the first 4 days of hospitalization from 156 acute stroke patients. Correlations using hierarchical or ordinal regressions were explored between acute WBC and NC and functional recovery, depression, and cognition at 3 and 12 months poststroke, after covarying for age and baseline stroke severity. . We found significant increases in NC between <12 hours and 24 to 48 hours time points ( = .05). Hierarchical regressions, covaried for age and baseline stroke severity, found that 24 to 48 hours WBC ( = .05) and NC ( = .04) significantly predicted 3-month cognition scores. Similarly, 24 to 48 hours WBC ( = .05) and NC ( = .02) predicted cognition scores at 12 months. Increases in WBC and NC were predictive of increased cognition scores at both 3 and 12 months (positive recovery) though there were no significant associations between WBC and NC and disability or depression scores. . Routine acute stroke clinical laboratory tests such as WBC and NC taken between 24 and 48 hours poststroke are predictive of cognition poststroke. It is interpreted that higher rapid immunological activation in the acute phase is an indicator for the trajectory of positive stroke recovery.
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http://dx.doi.org/10.1177/1545968320948607DOI Listing
September 2020

Leveraging Psychosocial Interventions to Motivate Instructor Participation in Teaching Professional Development.

CBE Life Sci Educ 2020 09;19(3):es10

Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, TN 37996.

To promote undergraduate education reform, teaching professional development (TPD) efforts aim to encourage instructors to adopt evidence-based practices. However, many instructors do not attend TPD. There may be many reasons for this, including low intrinsic motivation to participate in TPD. Psychologists have dealt with motivational barriers in educational contexts using psychosocial interventions, brief activities that draw on a rich history of psychological research to subtly alter key, self-reinforcing psychological processes to yield long-term intrinsic motivation and behavioral changes. Psychosocial interventions, for example, have been used to alter students' noncognitive attitudes and beliefs, such as attributions and mindset, which positively influence students' motivation and academic performance. Here, we propose that insights from research on psychosocial interventions may be leveraged to design interventions that will increase instructors' motivation to participate in TPD, thus enhancing existing pedagogical reform efforts. We discuss psychological principles and "best practices" underlying effective psychosocial interventions that could guide the development of interventions to increase instructors' motivation to attend TPD. We encourage new interdisciplinary research collaborations to explore the potential of these interventions, which could be a new approach to mitigating at least one barrier to undergraduate education reform.
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http://dx.doi.org/10.1187/cbe.19-11-0236DOI Listing
September 2020

Computer Modeling of Clot Retrieval-Circle of Willis.

Front Neurol 2020 7;11:773. Epub 2020 Aug 7.

Departments of Clinical Neuroscience and Radiology, Cummings School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

Endovascular clot retrieval, often referred to as mechanical thrombectomy, has transformed the treatment of patients with ischemic stroke based on an underlying large cerebral vessel occlusion, ranging from the extracranial internal carotid artery (ICA) to the M1 (proximal) segment of the middle cerebral artery (MCA). The aim of this study was to evaluate the effect of a progressive occlusion of the extracranial portion of the ICA on the cerebral blood flow either with a conventional guiding catheter or a balloon-guiding catheter, which enables the operator to completely occlude the parent artery by inflating the balloon around the tip of this type of guiding catheter. We evaluated the impact of flow reduction in the ICA in the setting of ipsilateral MCA occlusion given the different configurations of the circle of Willis (CoW). The computer model of cerebral arteries was based on anatomical works by Rhoton (1) and van der Eecken (2). The interactive experimental results are available on the web at https://gntem3.shinyapps.io/ecrsim. In the setting of left MCA occlusion, compensation from the anterior and posterior communicating artery preserved the flow in the left anterior cerebral artery (ACA) but not the left MCA branches. Under selected CoW configurations, such as classic, missing Acom, or missing A1 segment of the ACA and concurrent right ICA occlusion, there was a progressive decrease of flow in the left ACA to a minimum of 78% when the simulated catheter fully occluded the left ICA. Flow collapsed (<10%) in the left ACA and MCA branches under CoW configurations, such as bilateral fetal PCA. In summary, compensatory flow collapsed under certain clot retrieval scenarios and unusual configurations of CoW.
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http://dx.doi.org/10.3389/fneur.2020.00773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427049PMC
August 2020

Googling the Lifetime Risk of Stroke Around the World.

Front Neurol 2020 31;11:729. Epub 2020 Jul 31.

Department of Neurology, Monash Health, Melbourne, VIC, Australia.

We aimed to utilize the data on lifetime risk of stroke, from Global Burden of Disease (GBD) 2016, in combination with open data platforms to create an interactive map for use by clinicians and members of the public. Further, we explore the relationship between life expectancy and lifetime risk of stroke. Enhancing visual display of large volume of data. Worldwide estimates of the lifetime risk of stroke obtained from the GBD 2016. None. None. Data were extracted from a portable document format (pdf) copy of the GBD article on the lifetime risk of stroke and exported into the R programming environment (version 3.4.4). These data were merged with (i) the world map boundary, (ii) open data platforms from the World Bank (life expectancy and income), and (ii) open data from the United Nation Population Prospects 2017. Further we plotted the relationship between the adjusted lifetime risk of stroke and life expectancy. The map of the global burden of stroke shows a higher lifetime risk of stroke among high-income countries than in low-income countries (https://gntem3.shinyapps.io/strokeglobal/). The greatest risk was among upper-middle-income countries such as China and Eastern and Central European countries such as Latvia and Romania. The lifetime risk of stroke increased in countries with higher life expectancy (β = 0.48 ± 0.047, 95% confidence interval = 0.390-0.574, = 0.38, < 0.01). Overall life expectancy is a major driver of the lifetime risk of stroke. The interactive map enables clinicians to search information about the lifetime risk of stroke interactively and navigate by zooming in and out, while still retaining high resolution.
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http://dx.doi.org/10.3389/fneur.2020.00729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411741PMC
July 2020

Longitudinal Stroke Recovery Associated With Dysregulation of Complement System-A Proteomics Pathway Analysis.

Front Neurol 2020 28;11:692. Epub 2020 Jul 28.

Department of Occupational Therapy, La Trobe University, Bundoora, VIC, Australia.

Currently the longitudinal proteomic profile of post-ischemic stroke recovery is relatively unknown with few well-accepted biomarkers or understanding of the biological systems that underpin recovery. We aimed to characterize plasma derived biological pathways associated with recovery during the first year post event using a discovery proteomics workflow coupled with a topological pathway systems biology approach. Blood samples ( = 180, ethylenediaminetetraacetic acid plasma) were collected from a subgroup of 60 first episode stroke survivors from the Australian START study at 3 timepoints: 3-7 days (T1), 3-months (T2) and 12-months (T3) post-stroke. Samples were analyzed by liquid chromatography mass spectrometry using label-free quantification (data available at ProteomeXchange with identifier PXD015006). Differential expression analysis revealed that 29 proteins between T1 and T2, and 33 proteins between T1 and T3 were significantly different, with 18 proteins commonly differentially expressed across the two time periods. Pathway analysis was conducted using Gene Graph Enrichment Analysis on both the Kyoto Encyclopedia of Genes and Genomes and Reactome databases. Pathway analysis revealed that the significantly differentiated proteins between T1 and T2 were consistently found to belong to the complement pathway. Further correlational analyses utilized to examine the changes in regulatory effects of proteins over time identified significant inhibitory regulation of clusterin on complement component 9. Longitudinal post-stroke blood proteomics profiles suggest that the alternative pathway of complement activation remains in a state of higher activation from 3-7 days to 3 months post-stroke, while simultaneously being regulated by clusterin and vitronectin. These findings also suggest that post-stroke induced sterile inflammation and immunosuppression could inhibit recovery within the 3-month window post-stroke.
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http://dx.doi.org/10.3389/fneur.2020.00692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399641PMC
July 2020

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

J Stroke Cerebrovasc Dis 2020 Sep 8;29(9):104938. Epub 2020 May 8.

Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Background And Purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.

Methods: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.

Conclusion: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205703PMC
September 2020

Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.

PLoS One 2020 25;15(6):e0232381. Epub 2020 Jun 25.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naïve macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 - 4Hz); theta: [4 - 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316240PMC
August 2020

Undergraduate Biology Education Research Gordon Research Conference: A Meeting Report.

CBE Life Sci Educ 2020 06;19(2):mr1

Center for Research in Mathematics and Science Education, University of California, San Diego, and San Diego State University, San Diego, CA 92120.

The 2019 Undergraduate Biology Education Research Gordon Research Conference (UBER GRC), titled "Achieving Widespread Improvement in Undergraduate Education," brought together a diverse group of researchers and practitioners working to identify, promote, and understand widespread adoption of evidence-based teaching, learning, and success strategies in undergraduate biology. Graduate students and postdocs had the additional opportunity to present and discuss research during a Gordon Research Seminar (GRS) that preceded the GRC. This report provides a broad overview of the UBER GRC and GRS and highlights major themes that cut across invited talks, poster presentations, and informal discussions. Such themes include the importance of working in teams at multiple levels to achieve instructional improvement, the potential to use big data and analytics to inform instructional change, the need to customize change initiatives, and the importance of psychosocial supports in improving undergraduate student well-being and academic success. The report also discusses the future of the UBER GRC as an established meeting and describes aspects of the conference that make it unique, both in terms of facilitating dissemination of research and providing a welcoming environment for conferees.
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http://dx.doi.org/10.1187/cbe.19-09-0188DOI Listing
June 2020

Pre-existing Comorbidity Burden and Patient Perceived Stroke Impact.

Int J Stroke 2021 Apr 23;16(3):273-279. Epub 2020 Apr 23.

Department of Occupational Therapy, Social Work and Social Policy, School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Australia.

Background: Pre-existing comorbidities can compromise recovery post-stroke. However, the association between comorbidity burden and patient-rated perceived impact has not been systematically investigated. To date, only observer-rated outcome measures of function, disability, and dependence have been used, despite the complexity of the impact of stroke on an individual.

Aim: Our aim was to explore the association between comorbidity burden and patient-rated perceived impact and overall recovery, within the first-year post-stroke, after adjusting for stroke severity, age, and sex.

Methods: The sample comprised 177 stroke survivors from 18 hospitals throughout Australia and New Zealand. Comorbidity burden was calculated using the Charlson Comorbidity Index. Perceived impact and recovery were measured by the Stroke Impact Scale index and Stroke Impact Scale overall recovery scale. Quantile regression models were applied to investigate the association between comorbidity burden and perceived impact and recovery.

Results: Significant negative associations between the Charlson Comorbidity Index and the Stroke Impact Scale index were found at three months. At the .25 quantile, a one-point increase on the Charlson Comorbidity Index was associated with 6.80-points decrease on the Stroke Impact Scale index (95%CI: -11.26, -2.34; p = .003). At the median and .75 quantile, a one-point increase on the Charlson Comorbidity Index was associated, respectively, with 3.58-points decrease (95%CI: -5.62, -1.54; p = .001) and 1.76-points decrease (95%CI: -2.80, -0.73; p = .001) on the Stroke Impact Scale index. At 12 months, at the .25 and .75 quantiles, a one-point increase on the Charlson Comorbidity Index was associated, respectively, with 6.47-points decrease (95%CI: -11.05, -1.89; p = .006) and 1.26-points decrease (95%CI: -2.11, -0.42; p = .004) on the Stroke Impact Scale index. For the Stroke Impact Scale overall recovery measure, significant negative associations were found only at the median at three months and at the .75 quantile at 12 months.

Conclusion: Comorbidity burden is independently associated with patient-rated perceived impact within the first-year post-stroke. The addition of patient-rated impact measures in personalized rehabilitation may enhance the use of conventional observer-rated outcome measures.
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http://dx.doi.org/10.1177/1747493020920838DOI Listing
April 2021

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

JAMA 2020 04;323(13):1257-1265

Department of Medicine, Ballarat Base Hospital, Ballarat, Victoria, Australia.

Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase.

Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke.

Design, Setting, And Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria.

Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy.

Main Outcomes And Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death.

Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]).

Conclusions And Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned.

Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.
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http://dx.doi.org/10.1001/jama.2020.1511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139271PMC
April 2020

Melbourne Mobile Stroke Unit and Reperfusion Therapy: Greater Clinical Impact of Thrombectomy Than Thrombolysis.

Stroke 2020 03 12;51(3):922-930. Epub 2020 Feb 12.

From the Department of Neurology, Melbourne Brain Centre (H.Z., S.C., D.E., L.C., N.Y., B.Y., B.C.V.C., M.W.P., G.A.D., S.M.D.), Royal Melbourne Hospital, Victoria, Australia.

Background and Purpose- Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU. Methods- Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates. Results- In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was administered to 100 patients (mean age, 73.8 years; 62% men). The median time savings per MSU patient, compared with the control cohort, was 26 minutes (<0.001) for dispatch to hospital arrival and 15 minutes (<0.001) for hospital arrival to thrombolysis. The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes (95% CI, 36.0-49.0). In the same period, 41 MSU patients received EVT (mean age, 76 years; 61% men) with median dispatch-to-treatment time saving of 51 minutes ([95% CI, 30.1-71.9], <0.001). This included a median time saving of 17 minutes ([95% CI, 7.6-26.4], =0.001) for EVT hospital arrival to arterial puncture for MSU patients. Estimated median disability-adjusted life years saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT. Conclusions- The Melbourne MSU substantially reduced time to reperfusion therapies, with the greatest estimated disability avoidance driven by the more powerful impact of earlier EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.
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http://dx.doi.org/10.1161/STROKEAHA.119.027843DOI Listing
March 2020

Contralateral hyperhidrosis following lateral medullary infarction.

Pract Neurol 2020 08 30;20(4):330-331. Epub 2020 Jan 30.

Department of Neurology, Monash Health, Clayton, Victoria, Australia.

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http://dx.doi.org/10.1136/practneurol-2019-002346DOI Listing
August 2020

Current aspects of TIA management.

J Clin Neurosci 2020 Feb 5;72:20-25. Epub 2020 Jan 5.

Stroke Unit, Department of Neurosciences, Monash Medical Centre and Stroke and Aging Research Group, Department of Medicine, Monash University, Australia.

Transient Ischaemic Attack (TIA) if untreated carries a high risk of early stroke and is associated with poorer long-term survival [1]. There is emerging evidence of a reduction in stroke risk following TIA. Time critical investigations and management, as well as service organisation remain key to achieving good outcomes. Patients are diagnosed with TIA if they have transient, sudden-onset focal neurological symptoms which usually completely and rapidly resolve by presentation. The tissue based definition of TIA guides the fact that patients with residual symptoms should be considered as potentially having a stroke, with urgent evaluation regarding eligibility for thrombolysis and/or endovascular clot retrieval (ECR). Essential investigations for all patients with TIA should include early brain imaging, ECG, and carotid imaging in patients with anterior circulation symptoms. After brain imaging, exclusion of high risk indicators and immediate administration of an antiplatelet agent, subsequent attention to other mechanistic factors can be managed safely as part of a structured clinical pathway supervised by stroke specialists. This is in line with the recently revised Stroke Foundation Clinical Guidelines for Stroke Management (2017).
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http://dx.doi.org/10.1016/j.jocn.2019.12.032DOI Listing
February 2020

Electrocardiography Abnormalities in Macaques after Infection with Encephalitic Alphaviruses.

Pathogens 2019 11 16;8(4). Epub 2019 Nov 16.

Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Avenue, Ste. 9052, Pittsburgh, PA 15213, USA.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+) ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy.
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http://dx.doi.org/10.3390/pathogens8040240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969904PMC
November 2019

Stroke Severity, and Not Cerebral Infarct Location, Increases the Risk of Infection.

Transl Stroke Res 2020 06 10;11(3):387-401. Epub 2019 Nov 10.

Centre for Inflammatory Diseases, Department of Medicine at Monash Health, School of Clinical Sciences, Monash Medical Centre, Monash University, Clayton, VIC, 3168, Australia.

Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1 day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggestive of long-term immune impairment. At the acute phase, our data demonstrated an inverse relationship between infarct volume and the number of circulating leukocytes, indicating the elevated risk of infection in more severe stroke is associated with reduced cellularity in peripheral blood, owing predominately to markedly decreased lymphocyte numbers. In addition, the stroke-induced reduction of lymphocyte-to-neutrophil ratio was also evident in the lung of all post-stroke animals. To investigate the effect of infarct location on post-stroke infection, we additionally performed a photothrombotic (PT) model of stroke and using an innovative systematic approach of analysis, we found the location of cerebral infarct does not impact on the susceptibility of post-stroke infection, confirming the greater role of infarct volume over infarct location in the susceptibility to infection. Our experimental findings were validated in a clinical setting and reinforced that stroke severity, and not infarct location, influences the risk of infection after stroke.
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http://dx.doi.org/10.1007/s12975-019-00738-3DOI Listing
June 2020