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Vascular territory mapping (VTM) software estimates which intracerebral vessel provides peak arterial flow to a brain voxel. This observational study was performed to assess the hypothesis that the VTM algorithm may correlate to visual measurements of leptomeningeal grading and stroke outcome measures in acute middle cerebral artery (MCA) occlusion. VTM software assigned regions of the brain to an estimated feeding intracerebral vessel. Whole brain dynamic CT angiography was used to visually grade the extent of flow in either anterior or posterior cerebral leptomeningeal arteries. The final dataset included 115 patients with MCA occlusion. The median age was 74 years (IQR 62–82). The time from onset of symptoms to scan was a median of 129 min (IQR 85–241) and the median National Institutes of Health Stroke Scale (NIHSS) was 15 (IQR 12–19). Baseline imaging revealed a median ischaemic core of 19 mL (IQR 6–39) and perfusion lesion of 92 mL (IQR 68–122). Ischaemic core and posterior cerebral artery VTM volume were significantly associated with less robust posterior collateral flow on visual grading. VTM variables were not predictive of anterior collateral grade or stroke outcome measures. There did not appear to be a significant relationship between VTM volumes and visualised leptomeningeal collateral flow direction. The clinical utility and diagnostic value of VTM software in predicting collateral flow patterns remain to be elucidated, and further validation studies are warranted to determine the potential applications in acute stroke assessment.

IntroductionRepeat imaging when regional and remote stroke patients arrive at a comprehensive stroke center (CSC) can delay endovascular thrombectomy (EVT). We examined which clinical and imaging parameters predict infarct progression and perfusion core growth during transport.MethodsWe included patients recruited from 2017 to 2023 in a prospective database who were transferred from remote sites with large vessel occlusion, had CT perfusion imaging at the primary stroke center (PSC), and had repeat CT on arrival at the CSC demonstrating persistent occlusion. The key imaging characteristics were perfusion core change (rCBF < 30%) and ASPECTS change. Multiple and ordinal logistic regression analyses were used to assess the relationship between background clinical and imaging variables and the CT-perfusion core and ASPECTS on arrival. DEFUSE 3 criteria (ASPECTS ≥ 6, perfusion core < 70 mL) were used to define “favorable imaging.”ResultsIn 90 patients with CT perfusion at both PSC and CSC and persistent occlusion, the median time from onset to PSC presentation was 279 min (IQR 143–702). The median time from PSC presentation to CSC arrival was 243.5 min (IQR 186–335), and the median distance traveled was 186.5 km (IQR 101–258). Lower baseline ASPECTS (per point) was associated with a 7 mL increase (95%CI 2–11 mL) in perfusion core between scans (p = 0.004). The time from onset, the time between PSC and CSC, and the distance traveled were not significantly associated with either ASPECTS or perfusion core growth during transport. In total, 11 out of 78 patients (14%) had deterioration of initially favorable imaging profiles during transport.ConclusionPerfusion core growth during transport was uncommon and most strongly associated with lower ASPECTS at the PSC. Initially, favorable PSC imaging May predict whether repeat imaging is necessary at the CSC.

Abstract This study explores the use of open educational resources (OERs) in studio-based learning and their influence on learning experiences. The research team conducted action research with 30 bachelor of arts students who were completing a video production subject. Students were required to learn from a website containing open online learning resources under a flipped classroom approach. A teaching schedule and website were designed according to several criteria. Research data were collected through observation, reflective journals, and interviews and were analyzed via thematic analysis. Participating students expressed their perceptions of benefits and hesitation in utilizing OERs in learning. They agreed that the use of OERs as flipped classroom learning materials could positively affect their learning, primarily through competence and learning autonomy as indicated in self-determination theory. This investigation provides teachers with valuable experience and suggestions for teaching and learning approaches that incorporate OERs into studio-based education. Students learn from OERs in which they can gain the most up-to-date technical knowledge in an autonomous environment. This experience indicates that this pedagogy greatly and positively influences students’ subject-learning experiences, learning outcomes, and self-learning skills.

Background Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta‐analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90‐day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. Methods and Results Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90‐day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random‐effects meta‐analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90‐day stroke recurrence was 8.6% (95% CI, 6.5–10.7), reducing by 0.60% (95% CI, 0.09–1.1; P=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5–8.0) when compared with non‐dual antiplatelet trial arms (7.2%, 95% CI, 4.7–9.6) and observational studies 10.6% (95% CI, 7.0–14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference – score ≤3: 8.6% (95% CI, 6.0–11.1), score ≤4: 8.4% (95% CI, 6.1–10.6), as did excluding studies with n

Objectives This study aims to investigate the cost incurred by people travelling to the neurology outpatient clinic of a large metropolitan hospital. As outpatients are a substantial portion of a hospital’s demographic, we aimed to understand the patient experience of various commuters.Methods We conducted an observational study collecting demographic details and travel information for how people attended the neurology clinic of Monash Medical Centre. Statistical analysis was performed using R. 165 participants were randomly selected and interviewed in-person. Data were collected via an anonymous questionnaire. The study was approved by the Monash Health Human Ethics Research Committee.Results 155 responses were included in the analysis. Patients paid an average of $A16.64 to travel to Monash Medical Centre. Drivers paid on average $A16.70 and those taking public transport paid on average $A9.64, with the maximum cost overall being $A120.00. For patients driving to hospital, parking accounted for 60% of their travel costs. The average to Monash Medical centre was 20.82 km with the maximum being 190.88 km. Distance from hospital was correlated with a higher cost of travel (p

The concept of 'pyramidal weakness' denotes that neurological examination findings can be localised to the central nervous system (CNS), and implying a specific pattern of motor weakness involving upper limb extensors and lower limb flexors. However, other weakness patterns have been observed in CNS lesions. We aim to investigate the pattern of weakness observed in CNS lesions and explore the use of the phrase 'pyramidal weakness' over time. We searched Medline, PubMed, and Google Scholar up to January 1st, 2022, using keywords such as ‘distal weakness,’ ‘upper limb flexion,’ ‘lower limb extension,’ ‘pyramidal weakness,’ and related terms. The inclusion criteria were papers relating to brain or spinal cord lesions and terms inferring their presence or the description of a motor weakness pattern. We identified 117 studies since 1889, of which 29.9% of publications described weakness in upper limb extensors and lower limb flexors, and 26.5% reported distal weakness. We found an early reference to 'pyramidal weakness' in 1922 in the context of unilateral weakness in encephalitis with no description of the upper limb extensor and lower limb flexor pattern. Since 1988, 'pyramidal weakness' has become associated with weakness in upper limb extensors and lower limb flexors. The phrase 'pyramidal weakness', used in its current format, has been more frequent since the 1980s. Distal weakness and upper limb extensor and lower limb flexor weakness have been associated with CNS lesions.

Background and aimRapid outpatient evaluation and treatment of TIA in structured clinics have been shown to reduce stroke recurrence. It is unclear whether short-term downtrends in TIA incidence and admissions have had enduring impact on TIA clinic activity. This study aims to measure the impact of the pandemic on hospitals with rapid TIA clinics.MethodsRelevant services were identified by literature search and contacted. Three years of monthly data were requested – a baseline pre-COVID period (April 2018 to March 2020) and an intra-COVID period (April 2020 to March 2021). TIA presentations, ischemic stroke presentations, and reperfusion trends inclusive of IV thrombolysis (IVT) and endovascular thrombectomy (EVT) were recorded. Pandemic impact was measured with interrupted time series analysis, a segmented regression approach to test an effect of an intervention on a time-dependent outcome using a defined impact model.ResultsSix centers provided data for a total of 6,231 TIA and 13,191 ischemic stroke presentations from Australia (52.1%), Canada (35.0%), Italy (7.6%), and England (5.4%). TIA clinic volumes remained constant during the pandemic (2.9, 95% CI –1.8 to 7.6, p = 0.24), as did ischemic stroke (2.9, 95% CI –7.8 to 1.9, p = 0.25), IVT (−14.3, 95% CI −36.7, 6.1, p

BackgroundMild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.MethodsIn this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCAResultsParticipants' (n = 119) MoCA scores improved from baseline to 3-months (pConclusionMore than half of mild-stroke survivors are at risk of cognitive decline one year after stroke, even when preceded by a significantly improving pattern in the first 3-months of recovery. Physical activity was the only modifiable factor independently associated with cognitive recovery. Individual-level prediction methods may inform the timing and personalized application of future interventions to maximize cognitive recovery post-stroke.

Background and purposeComputed tomography perfusion (CTP) has successfully extended the time window for reperfusion therapies in ischemic stroke. However, the published perfusion parameters and thresholds vary between studies. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines, we conducted a systematic review to investigate the accuracy of parameters and thresholds for identifying core and penumbra in adult stroke patients.MethodsWe searched Medline, Embase, the Cochrane Library, and reference lists of manuscripts up to April 2022 using the following terms “computed tomography perfusion,” “stroke,” “infarct,” and “penumbra.” Studies were included if they reported perfusion thresholds and undertook co-registration of CTP to reference standards. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and Standards for Reporting of Diagnostic Accuracy (STARD) guidelines.ResultsA total of 24 studies were included. A meta-analysis could not be performed due to insufficient data and significant heterogeneity in the study design. When reported, the mean age was 70.2 years (SD+/−3.69), and the median NIHSS on admission was 15 (IQR 13–17). The perfusion parameter identified for the core was relative cerebral blood flow (rCBF), with a median threshold of

Abstract The Nambu–Jona-Lasinio (NJL) model has been widely studied for investigating the chiral phase structure of strongly interacting matter. The study of the thermodynamics of field theories within the framework of Lattice Field Theory is limited by the sign problem, which prevents Monte Carlo evaluation of the functional integral at a finite chemical potential. Using the quantum imaginary time evolution (QITE) algorithm, we construct a quantum simulation for the (1 + 1) dimensional NJL model at finite temperature and finite chemical potential. We observe consistency among digital quantum simulation, exact diagonalization and analytical solution, indicating further applications of quantum computing in simulating QCD thermodynamics.

Abstract Coronavirus disease 2019 (COVID‐19) patients have increased thrombosis risk. With increasing age, there is an increase in COVID‐19 severity. Additionally, adults with a history of vasculopathy have the highest thrombotic risk in COVID‐19. The mechanisms of these clinical differences in risk remain unclear. Human umbilical vein endothelial cells (HUVECs) were infected with SARS‐CoV‐2, influenza A/Singapore/6/86 (H1N1) or mock‐infected prior to incubation with plasma from healthy children, healthy adults or vasculopathic adults. Fibrin on surface of cells was observed using scanning electron microscopy, and fibrin characteristics were quantified. This experiment was repeated in the presence of bivalirudin, defibrotide, low‐molecular‐weight‐heparin (LMWH) and unfractionated heparin (UFH). Fibrin formed on SARS‐CoV‐2 infected HUVECs was densely packed and contained more fibrin compared to mock‐infected cells. Fibrin generated from child plasma was the thicker than fibrin generated in vasculopathic adult plasma (p = 0.0165). Clot formation was inhibited by LMWH (0.5 U/ml) and UFH (0.1–0.7 U/ml). We show that in the context of the SARS‐CoV‐2 infection on an endothelial culture, plasma from vasculopathic adults produces fibrin clots with thinner fibrin, indicating that the plasma coagulation system may play a role in determining the thrombotic outcome of SARS‐CoV‐2 infection. Heparinoid anticoagulants were most effective at preventing clot formation.

Abstract Background There is an urgent need to understand the determinants (i.e., barriers and facilitators) of de-implementation. The purpose of this study was to develop a comprehensive list of determinants of the de-implementation of low-value care from the published literature and to compare this list to determinants identified by a group of stakeholders with lived experience with de-implementation. Methods This was a two-phase multi-method study. First, a systematic review examined published barriers and facilitators to de-implementation. Articles were identified through searches within electronic databases, reference lists and the grey literature. Citations were screened independently and in duplicate and included if they were: 1) written in English; and 2) described a barrier or facilitator to de-implementation of any clinical practice in adults (age ≥ 18 years). ‘Raw text’ determinants cited within included articles were extracted and synthesized into a list of representative determinants using conventional content analysis. Second, semi-structured interviews were conducted with decision-makers (unit managers and medical directors) and healthcare professionals working in adult critical care medicine to explore the overlap between the determinants found in the systematic review to those experienced in critical care medicine. Thematic content analysis was used to identify key themes emerging from the interviews. Results In the systematic review, reviewers included 172 articles from 35,368 unique citations. From 437 raw text barriers and 280 raw text facilitators, content analysis produced 29 distinct barriers and 24 distinct facilitators to de-implementation. Distinct barriers commonly cited within raw text included ‘lack of credible evidence to support de-implementation’ (n = 90, 21%), ‘entrenched norms and clinicians’ resistance to change (n = 43, 21%), and ‘patient demands and preferences’ (n = 28, 6%). Distinct facilitators commonly cited within raw text included ‘stakeholder collaboration and communication’ (n = 43, 15%), and ‘availability of credible evidence’ (n = 33, 12%). From stakeholder interviews, 23 of 29 distinct barriers and 20 of 24 distinct facilitators from the systematic review were cited as key themes relevant to de-implementation in critical care. Conclusions The availability and quality of evidence that identifies a clinical practice as low-value, as well as healthcare professional willingness to change, and stakeholder collaboration are common and important determinants of de-implementation and may serve as targets for future de-implementation initiatives. Trial registration The systematic review was registered in PROSPERO CRD42016050234 .

BackgroundThrombolytic agents such as tissue plasminogen activator (tPA) are the only drug class approved to treat ischemic stroke and are usually administered within 4.5 h. However, only ~20% of ischemic stroke patients are eligible to receive the therapy. We previously demonstrated that early intravenous administration of human amnion epithelial cells (hAECs) can limit brain inflammation and infarct growth in experimental stroke. Here, we have tested whether hAECs exert cerebroprotective effects in combination with tPA in mice.MethodsMale C57Bl/6 mice were subjected to middle cerebral artery occlusion for 60 min followed by reperfusion. Immediately following reperfusion, vehicle (saline, n = 31) or tPA (10 mg/kg; n = 73) was administered intravenously. After 30 min of reperfusion, tPA-treated mice were injected intravenously with either hAECs (1×106; n = 32) or vehicle (2% human serum albumin; n = 41). A further 15 sham-operated mice were treated with vehicle (n = 7) or tPA + vehicle (n = 8). Mice were designated to be euthanised at 3, 6 or 24 h post-stroke (n = 21, 31, and 52, respectively), and brains were collected to assess infarct volume, blood–brain barrier (BBB) disruption, intracerebral bleeding and inflammatory cell content.ResultsThere was no mortality within 6 h of stroke onset, but a high mortality occurred in tPA + saline-treated mice between 6 h and 24 h post-stroke in comparison to mice treated with tPA + hAECs (61% vs. 27%, p = 0.04). No mortality occurred within 24 h of sham surgery in mice treated with tPA + vehicle. We focused on early infarct expansion within 6 h of stroke and found that infarction was ~50% larger in tPA + saline- than in vehicle-treated mice (23 ± 3 mm3 vs. 15 ± 2 mm3, p = 0.02) but not in mice receiving tPA + hAECs (13 ± 2 mm3, p

BackgroundWe proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.MethodsThe design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.ResultsEight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.ConclusionOur Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.Clinical trial registrationClinicalTrials.gov, identifier ACTRN12618000076279P.

BackgroundThere is a growing interest in the topography of brain regions associated with disorders of consciousness. This has caused increased research output, yielding many publications investigating the topic with varying methodologies. The objective of this study was to ascertain the topographical regions of the brain most frequently associated with disorders of consciousness.MethodsWe performed a cross-sectional text-mining analysis of disorders of consciousness studies. A text mining algorithm built in the Python programming language searched documents for anatomical brain terminology. We reviewed primary PubMed studies between January 1st 2000 to 8th February 2023 for the search query “Disorders of Consciousness.” The frequency of brain regions mentioned in these articles was recorded, ranked, then built into a graphical network. Subgroup analysis was performed by evaluating the impact on our results if analyses were based on abstracts, full-texts, or topic-modeled groups (non-negative matrix factorization was used to create subgroups of each collection based on their key topics). Brain terms were ranked by their frequency and concordance was measured between subgroups. Graphical analysis was performed to explore relationships between the anatomical regions mentioned. The PageRank algorithm (used by Google to list search results in order of relevance) was used to determine global importance of the regions.ResultsThe PubMed search yielded 24,944 abstracts and 3,780 full texts. The topic-modeled subgroups contained 2015 abstracts and 283 full texts. Text Mining across all document groups concordantly ranked the thalamus the highest (Savage score = 11.716), followed by the precuneus (Savage score = 4.983), hippocampus (Savage score = 4.483). Graphical analysis had 5 clusters with the thalamus once again having the highest PageRank score (PageRank = 0.0344).ConclusionThe thalamus, precuneus and cingulate cortex are strongly associated with disorders of consciousness, likely due to the roles they play in maintaining awareness and involvement in the default mode network, respectively. The findings also suggest that other areas of the brain like the cerebellum, cuneus, amygdala and hippocampus also share connections to consciousness should be further investigated.

BackgroundPost-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute.MethodWe evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events.ResultsThe overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (pConclusionIn this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation.

Background Time to reperfusion is an important predictor of outcome in ischaemic stroke from large vessel occlusion (LVO). For patients requiring endovascular thrombectomy (EVT), the transfer times from peripheral hospitals in metropolitan and regional Victoria, Australia to comprehensive stroke centres (CSCs) have not been studied.Aims To determine transfer and journey times for patients with LVO stroke being transferred for consideration of EVT.Methods All patients transferred for consideration of EVT to three Victorian CSCs from January 2017 to December 2018 were included. Travel times were obtained from records matched to Ambulance Victoria and the referring centre via Victorian Stroke Telemedicine or hospital medical records. Metrics of interest included door-in-door-out time (DIDO), inbound journey time and outbound journey time.Results Data for 455 transferred patients were obtained, of which 395 (86.8%) underwent EVT. The median DIDO was 107 min (IQR 84–145) for metropolitan sites and 132 min (IQR 108–167) for regional sites. At metropolitan referring hospitals, faster DIDO was associated with use of the same ambulance crew to transport between hospitals (75 (63–90) vs 124 (99–156) min, p

BackgroundThere has been a decline in the stroke incidence across high income countries but such knowledge exists at Country or State rather than areal unit level such local government area (LGA). In this disease mapping study, we evaluate if there are local hot spots or temporal trends in TIA rate. Such knowledge will be of help in planning healthcare service delivery across regions.MethodsLinked hospital discharge data (Victorian Admitted Episodes Dataset or VAED) was used to collect TIA (defined by ICD-10-AM codes G450-G459) cases from 2001 to 2011. The State of Victoria is the second most populous state in Australia, with a population of 6.7 million and can be divided into 79 administrative units or LGA. The data is anonymized and contains residence of the patient in terms of LGA but not exact location. The date of the TIA event when the patient is admitted to hospital is provided in the dataset. The number of TIAs per year was aggregated for each LGA. Standardized TIA ratios were calculated by dividing actual over expected cases for each LGA per year. We used Integrated Nested Laplace Approximation (INLA) to perform spatial and spatiotemporal regression, adjusting for hypertension, sex and population, age (≥60), and socio-economic status (SES) decile within the LGA. The final model was chosen based on the lowest the Deviance Information Criterion (DIC) and Watanabe-Akaike information criteria (WAIC).ResultsChoropleth maps showed a higher standardized TIA ratios in North-West rural region. Compared to the baseline model (DIC 13,159, WAIC 13,261), adding in a spatial random effect significantly improved the model (DIC 6,463, WAIC 6,667). However, adding a temporal component did not lead to a significant improvement (DIC 6,483, WAIC 6,707).ConclusionOur finding suggests a statically significant spatial component to TIA rate over regional areas but no temporal changes or yearly trends. We propose that such exploratory method should be followed by evaluation of reasons for regional variations and which in turn can identify opportunities in primary prevention of stroke, and stroke care.

Abstract Introduction Correctly identifying people with suspected stroke is essential for ensuring rapid treatment. Our aims were to determine the sensitivity of emergency dispatcher and paramedic identification of patients with stroke, the factors associated with correct identification, and whether there were any implications for hospital arrival times. Methods Observational study using patient‐level data from the Australian Stroke Clinical Registry (2015–2017) linked with ambulance and emergency department records for the state of Victoria. The registry diagnosis was the reference standard to compare with the provisional diagnoses made by emergency services personnel classified as “suspected” and “not suspected” stroke/transient ischemic attack (TIA). Multivariable logistic and quintile regressions were used to determine factors associated with correct identification and timely arrival to hospital. Results Overall, 4717 (64%) were matched to ambulance transport records (median age: 73 years, 43% female). Stroke/TIA was suspected in 56% of registrants by call‐takers and 69% by paramedics. Older patients (75+ years) (adjusted odds ratio [aOR]: 0.61; 95% confidence interval [CI]: 0.49–0.75), females (aOR: 0.86; 95% CI: 0.75–0.99), those with severe stroke or intracerebral hemorrhage were less often suspected as stroke. Cases identified as stroke had a shorter arrival time to hospital (unadjusted median minutes: stroke, 54 [43, 72] vs not stroke, 66 [51, 89]). Conclusions Emergency dispatchers and paramedics identified over half of patients with stroke in the prehospital setting. Important patient characteristics, such as being female and those having a severe stroke, were found that may enable refinement of prehospital ambulance protocols and dispatcher/paramedic education. Those correctly identified as stroke, arrived earlier to hospital optimizing their chances of receiving time‐critical treatments.

Pre-pregnancy body mass index and weight gain management are associated with pregnancy outcomes in expecting women. Poor gestational weight gain (GWG) management could increase the risk of adverse complications. These risks can be alleviated by lifestyle-based interventions if an undesired GWG trend is detected early on in the pregnancy. Current literature lacks analysis of gestational weight gain data and tracking the pregnancy over time. In this work, we collected longitudinal gestational weight gain data from women during their pregnancy and model their weight measurements to predict the end-of-pregnancy weight gain and classify it in accordance with the medically recommended guidelines. The measurement frequency of the weights is often very variable such that segments of data can be missing and the need to predict early utilising few data points complicates data modelling. We propose a Bayesian approach to forecast weight gain while effectively dealing with the limited data availability for early prediction. We validate on diverse populations from Europe and China. We show that utilising individual’s data only up to mid-way through the pregnancy, our approach produces mean absolute errors of 2.45 kgs and 2.82 kgs in forecasting end-of-pregnancy weight gain on these populations respectively, whereas the best of state-of-the-art yields 8.17 and 6.60 kgs on respective populations. The proposed method can serve as a tool to keep track of an individual’s pregnancy and achieve GWG goals, thus supporting the prevention of excessive or insufficient weight gain during pregnancy.

Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection. VEEV-exposed macaques developed a biphasic fever after infection similar to that seen in humans. Maximum temperature deviation correlated with the inhaled dose, but fever duration did not. Neurological signs, suggestive of virus penetration into the central nervous system (CNS), were predominantly seen in the second febrile period. Electroencephalography data indicated a statistically significant decrease in all power bands and circadian index during the second febrile period that returned to normal after fever resolved. Intracranial pressure increased late in the second febrile period. On day 6 post-infection macaques had high levels of MCP-1 and IP-10 chemokines in the CNS, as well as a marked increase of T lymphocytes and activated microglia. More than four weeks after infection, VEEV genomic RNA was found in the brain, cerebrospinal fluid and cervical lymph nodes. Pro-inflammatory cytokines & chemokines, infiltrating leukocytes and pathological changes were seen in the CNS tissues of macaques euthanized at these times. These data are consistent with persistence of virus replication and/or genomic RNA and potentially, inflammatory sequelae in the central nervous system after resolution of acute VEEV disease.

BackgroundThis modeling study aimed to determine if helicopters may optimize the transportation of patients with symptoms of large vessel stroke in “intermediate density” areas, such as Denmark, by bringing them directly to the comprehensive stroke center.MethodsWe estimated the time for the treatment of patients requiring endovascular therapy or intravenous thrombolysis under four configurations: “drip and ship” with and without helicopter and “bypass” with and without helicopter. Time delays, stroke numbers per municipality, and helicopter dispatches for four helicopter bases from 2019 were obtained from the Danish Stroke and Helicopter Registries. Discrete event simulation (DES) was used to estimate the capacity of the helicopter fleet to meet patient transport requests, given the number of stroke codes per municipality.ResultsThe median onset-to-needle time at the comprehensive stroke center (CSC) for the bypass model with the helicopter was 115 min [interquartile range (IQR): 108, 124]; the median onset-to-groin time was 157 min (IQR: 150, 166). The median onset-to-needle time at the primary stroke center (PSC) by ground transport was 112 min (IQR: 101, 125) and the median onset-to-groin time when primary transport to the PSC was prioritized was 234 min (IQR: 209, 261).A linear correlation between travel time by ground and the number of patients transported by helicopter (rho = 0.69, p < 0.001) indicated that helicopters are being used to transport more remote patients. DES demonstrated that an increase in helicopter capture zone by 20 min increased the number of rejected patients by only 5%.ConclusionsOur model calculations suggest that using helicopters to transport patients with stroke directly to the CSC in intermediate density areas markedly reduce onset-to-groin time without affecting time to thrombolysis. In this setting, helicopter capacity is not challenged by increasing the capture zone.

Introduction Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients’ prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase.Objective In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion.Methods and analysis TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival.Ethics and dissemination The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences.Trial registration number NCT04071613.

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration.Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics.Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received “stat” (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4–3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2–20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0–16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (β 0.20 ± 0.03, SV = 3.2), nasogastric tube (β 19.8 ± 5.9, SV = −0.20), Alteplase (β 8.6 ± 3.6, SV = −1.9), stat dose antithrombotic (β −18.9 ± 2.9, SV = −10.8) and stroke code (β −5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if “stat” dose of antithrombotics was given (coefficient = −0.32).Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.

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.

Introduction and Purpose Chronic Disease Management (CDM) plans are used by general practitioners to manage chronic diseases such as stroke. However, there is limited evidence that being on these plans improve adherence to secondary prevention medications after stroke. We aimed to assess the association of the duration on a CDM plan in improving adherence to secondary prevention medications following stroke. Methods Australian survivors of stroke or transient ischaemic attack were participants from the STAND FIRM trial. Patients were individually linked with claims for CDM plans from Medicare and dispensings of secondary prevention medications from the Pharmaceutical Benefits Scheme. We estimated (1) duration on a CDM plan based on the timing and Medicare items claimed and (2) the proportion of days that patients would have been covered by these medications (PDC), while accounting for deaths and instances of over-supply. Dosage for each quantity of medication was determined by the regularity in which patients returned for a refill. Logistic regression was used to evaluate factors associated with ≥80% adherence, up to 3 years after stroke, for each of antihypertensive, antithrombotic and lipid-modifying drugs. Results The median PDC for 563 patients (median age 70yrs; 36% female) ranged from 92% to 95% among the three classes of medications. Approximately 27% did not take up a CDM plan, 33% were on plans for

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 (

Objective: 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.Design: Enhancing visual display of large volume of data.Setting: Worldwide estimates of the lifetime risk of stroke obtained from the GBD 2016.Participants: None.Intervention: None.Methods: 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.Outcomes: 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, R2 = 0.38, p < 0.01).Conclusion: 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.

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 (n = 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.

In the present research, structural analyses are conducted on Invar (64% Fe-36% Ni) samples manufactured by modulated laser powder bed fusion (LPBF) under different laser power regimes. Within the selected process window, the results obtained from X-ray computed tomography analysis indicate that the relative density of as-built samples increases with an increase in laser power. In addition, it is observed that irregular-shaped pores with the longest axis normal to the building direction are significantly reduced with increasing the laser power. Microstructural investigation suggests that with increasing the laser power, a transformation from conduction to transition and keyhole modes occurs. In X-ray diffraction patterns of the as-built samples, only fcc γ-phase is detected and no reflection of bcc α-phase is found. Texture measurements show that the intensity of 〈110〉 crystallographic orientation along the building direction of the as-built samples increases with increasing laser power. Coefficient of thermal expansion of the as-built samples is very low and comparable to that of conventionally manufactured Invar alloy. Furthermore, as-built samples fabricated at lowest (250 W) and highest (400 W) laser powers exhibit the lowest and highest thermal expansion displacement, respectively. Finally, the thermal expansion behavior and its correlation with structural integrity and texture are discussed. Keywords: Invar alloy, Laser powder bed fusion, Porosity, Microstructure, Thermal expansion

Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells (hAECs), which are placenta-derived stem cells. We recently assessed the effects of systemically delivered hAECs on stroke outcome using four animal models of stroke. We demonstrated that when injected intravenously after ischemia onset, hAECs migrate preferentially to the spleen and injured brain to limit apoptosis and inflammation, and attenuate early brain infiltration of immune cells, progression of infarction and systemic immunosuppression and to ultimately ameliorate functional deficits. When administration of hAECs is delayed by 1-3 days post-stroke, long-term functional recovery can still be enhanced in young and aged mice of either sex. Moreover, our proof-of-principle findings suggest that hAECs are effective at limiting post-stroke infarct development in non-human primates. Overall, the results suggest that hAECs could be a viable clinical stroke therapy.

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.

Background and purpose: The recent advances in stroke therapy have placed focus on delivering care within the first hour after stroke onset (golden hour), principally through the use of Mobile Stroke Unit (MSU) to bring the hospital to the patient. The aim of this project is to search the location of MSU hub in Sydney, Australia, optimizing for catchment, transport to nearest thrombolysis and endovascular clot retrieval (ECR)/thrombectomy capable hospital and population at risk.Methods: Traveling time was performed using ggmap package in R to interface with Google Maps application program interface (API). This analysis estimates the travel time from the centroids of each suburbs to five potential MSU hubs (Royal Prince Alfred, Prince of Wales, Royal North Shore, Liverpool, and Westmead hospitals) and eight thrombolysis capable hospitals. It is proposed that the MSU should be deployed at ECR hub to cover the suburbs, not well-covered by thrombolysis and ECR capable hospitals. This step was performed by assigning membership to hospitals within 30 min traveling time to the ECR hub. The base hub of the MSU was proposed as the closest hub (providing ECR) to the least well-served suburbs. The population serviceable by MSU was estimated using stroke incidence studies in Melbourne and Adelaide.Results: The largest population, serviceable by MSU within 30 min (4,606 cases), 45 min radius (8,918 cases), and 60 min (10,084 cases), was Royal North Shore followed by Royal Prince Alfred, Liverpool, Westmead, and Prince of Wales hospitals. Prince of Wales hospital has the smallest catchment within 30 min (3,078 cases), 45 min (7,721 cases), and 60 min (9,984 cases). Suburbs at the edge of metropolitan Sydney such as the Northern Suburbs are less well-served by thrombolysis and ECR capable hospitals. There are 10 suburbs within 30 min travel of one hospital. The remainders are within 30 min of two or more hospitals.Conclusions: Any of the five endovascular clot retrieval capable hospitals are capable of serving as a hub for MSU. We provide a method to identify the hub based on location of suburbs less well-served by other hospital.

Background and Purpose: Endovascular clot retrieval (ECR) has revolutionized acute stroke therapy but is expensive to run and staff with accredited interventional neuroradiologists 24/7; consequently, it is only feasible for each metropolitan city to have a minimum number of hubs that is adequate to service the population. This method is applied to search the minimum number of hospitals to be designated as ECR hubs in Sydney as well as the population at risk of stroke reachable within 30 min.Methods: Traveling time from the centroids of each suburbs to five ECR capable hubs [Royal Prince Alfred/RPA, Prince of Wales/POW, Royal North Shore/RNS, Liverpool/LH and Westmead/WH]. This step was performed using ggmap package in R to interface with Google Map application program interface (API). Next, we calculate the percentage of suburbs within each catchment in which traveling time to the ECR hub is

Background and purpose: Two hubs are designated to provide endovascular clot retrieval (ECR) for the State of Victoria, Australia. In an earlier study, Google Maps application programming interface (API) was used to perform modeling on the combination of hospitals optimizing for catchment in terms of current traveling time and road conditions. It is not known if these findings would remain the same if the modeling was performed with a large-scale transport demand model such as Victorian Integrated Transport Model (VITM). This model is developed by the Victorian State Government Transport has the capability to forecast travel demand into the future including future road conditions which is not possible with a Google Maps based applications. The aim of this study is to compare the travel time to potential ECR hubs using both VITM and the Google Maps API and model stability in the next 5 and 10 years.Methods: The VITM was used to generate travel time from randomly generated addresses to four existing ECR capable hubs in Melbourne city, Australia (i.e., Royal Melbourne Hospital/RMH, Monash Medical Center/MMC, Alfred Hospital/ALF, and Austin Hospital/AUS) and the optimal service boundaries given a delivering time threshold are then determined.Results: The strategic transport model and Google map methods were similar with the R2 of 0.86 (peak and off peak) and the Nash-Sutcliffe model of efficiency being 0.83 (peak) and 0.76 (off-peak travel). Futures modeling using VITM found that this proportion decreases to 82% after 5 years and 80% after 10 years. The combination of RMH and ALF provides coverage for 74% of cases, 68% by 5 years, and 66% by 10 years. The combination of RMH and AUS provides coverage for 70% of cases in the base case, 65% at 5 years, and 63% by 10 years.Discussion: The results from strategic transport model are similar to those from Google Maps. In this paper we illustrate how this method can be applied in designing and forecast stroke service model in different cities in Australia and around the world.

Stroke is the second leading cause of death and physical disability, with a global lifetime incidence rate of 1 in 6. Currently, the only FDA approved treatment for ischemic stroke is the administration of tissue plasminogen activator (tPA). Stem cell clinical trials for stroke have been underway for close to two decades, with data suggesting that cell therapies are safe, feasible, and potentially efficacious. However, clinical trials for stroke account for

Background: Mobile stroke units (MSU) have been proposed to expedite delivery of recombinant tissue plasminogen activator (tPA) and expedite endovascular clot retrieval (ECR). Unexplored questions in the use of MSU include: maximal distance from base, time limit with regards to the use CT imaging, CT Angiography, CT Perfusion, and Telemedicine. We developed a computational model as an app (https://gntem3.shinyapps.io/ambmc/), taking into account traveling time to explore this issue. The aim of this study was to define the operating parameters for an MSU in a large metropolitan city, based on the geography of Melbourne.Methods: There are 2 hospitals (Royal Melbourne Hospital/RMH, Monash Medical Center/MMC) designated to provide state-wide ECR services. In these spatial simulations, the MSU is based at RMH and delivers tPA at the patient's pick-up address and then takes the patient to the nearest ECR center. We extracted the geocode of suburbs in Melbourne and travel time to each hospital using ggmap, an interface to Google Map API. The app contains widgets for varying the processing time at the patient location (default = 30 min), performing CT angiography (default = 10 min), performing telemedicine consultation (default = 15 min). The data were compared against those for usual ambulance metrics (default traveling time = 15 min, processing time at patient's location = 20 min, door to tPA = 60 min, door to groin = 90 min). Varying the widgets allow the viewer to explore the trade-off between the variable of interest and time to therapy at a suburb level.Results: The MSU was superior for delivering tPA to all Melbourne suburbs (up to 76 min from RMH). If the CTA times or processing time at location increased by 20 min then it was superior for providing ECR to only 74.9% of suburbs if the return base was RMH. Addition of CT Perfusion or telemedicine consultation affect the ability of a single hospital to provide ECR but not tPA if these additions can be limited to 20 min. Conclusion: The app can help to define how best to deploy the MSU across Melbourne. This app can be modified and used to optimize operating characteristics of MSU in other centers around the world.

Background and Purpose: Post-stroke pneumonia is a feared complication of stroke as it is associated with greater mortality and disability than in those without pneumonia. Patients are often kept “Nil By Mouth” (NBM) after stroke until after receiving a screen for dysphagia and declared safe to resume oral intake. We aimed to assess the proportional contribution of stroke severity and dysphagia screen to pneumonia by borrowing idea from coalition game theory on fair distribution of marginal profit (Shapley value).Method: Retrospective study of admissions to the stroke unit at Monash Medical Center in 2015. Seventy-five percent of data were partitioned into training set and the remainder (25%) into validation set. Variables associated with pneumonia (p < 0.1) were entered into Shapley value regression and conditional decision tree analysis.Results: In 2015, there were 797 admissions and 617 patients with ischemic and hemorrhagic stroke (age 69.9 ± 16.2, male = 55.0%, National Institute of Health Stroke Scale/NIHSS 8.1 ± 7.9). The frequency of pneumonia was 6.6% (41/617). In univariable analyses NIHSS, time to dysphagia screen, Charlson comorbidity index (CCI), and age were significantly associated with pneumonia but not weekend admission. Shapley value regression showed that the largest contributor to the model was stroke severity (72.8%) followed by CCI (16.2%), dysphagia screen (3.8%), and age (7.2%). Decision tree analysis yielded an NIHSS threshold of 14 for classifying people with (27% of 75 patients) and without pneumonia (2.5% of 308 patients). The area under the ROC curve for training data was 0.83 (95% CI 0.75–0.91) with no detectable difference between the training and test data (p = 0.4). Results were similar when dysphagia was exchanged for the variable dysphagia screen.Conclusion: Stroke severity status, and not dysphagia or dysphagia screening contributed to the decision tree model of post stroke pneumonia. We cannot exclude the chance that using dysphagia screen in this cohort had minimized the impact of dysphagia on development of pneumonia.

Background. One in three survivors of stroke experience poststroke depression (PSD). PSD has been linked with poorer recovery of function and cognition, yet our understanding of potential mechanisms is currently limited. Alterations in resting-state functional MRI have been investigated to a limited extent. Fluctuations in low frequency signal are reported, but it is unknown if interactions are present between the level of depressive symptom score and intrinsic brain activity in varying brain regions. Objective. To investigate potential interaction effects between whole-brain resting-state activity and depressive symptoms in stroke survivors with low and high levels of depressive symptoms. Methods. A cross-sectional analysis of 63 stroke survivors who were assessed at 3 months poststroke for depression, using the Montgomery–Åsberg Depression Rating Scale (MÅDRS-SIGMA), and for brain activity using fMRI. A MÅDRS-SIGMA score of >8 was classified as high depressive symptoms. Fractional amplitude of frequency fluctuations (fALFF) data across three frequency bands (broadband, i.e., ~0.01–0.08; subbands, i.e., slow-5: ~0.01–0.027 Hz, slow-4: 0.027–0.07) was examined. Results. Of the 63 stroke survivors, 38 were classified as “low-depressive symptoms” and 25 as “high depressive symptoms.” Six had a past history of depression. We found interaction effects across frequency bands in several brain regions that differentiated the two groups. The broadband analysis revealed interaction effects in the left insula and the left superior temporal lobe. The subband analysis showed contrasting fALFF response between the two groups in the left thalamus, right caudate, and left cerebellum. Across the three frequency bands, we found contrasting fALFF response in areas within the fronto-limbic-thalamic network and cerebellum. Conclusions. We provide evidence that fALFF is sensitive to changes in poststroke depressive symptom severity and implicates frontostriatal and cerebellar regions, consistent with previous studies. The use of multiband analysis could be an effective method to examine neural correlates of depression after stroke. The START-PrePARE trial is registered with the Australian New Zealand Clinical Trial Registry, number ACTRN12610000987066.

BackgroundThere is increasing interest in stem cell therapy as another treatment modality in stroke, particularly for patients who are unable to receive endovascular clot retrieval or thrombolysis therapies, or for whom standard treatment has failed. We have recently shown that human amniotic epithelial cells (hAECs) are effective in reducing infarct volume in different animal models of ischemic stroke, including in non-human primates. hAEC therapy attenuated infarct growth and/or promoted functional recovery, even when administered 1–3 days after the onset of stroke.MethodsWe now propose an open label Phase 1 dose escalation trial to assess the safety of allogeneic hAECs in stroke patients with a view to providing an evidence platform for future Phase 2 efficacy trials. We propose a modified 3 + 3 dose escalation study design with additional components for measuring magnetic resonance signal of efficacy as well as the effect of hAECs on immunosuppression after stroke.ResultThe trial will commence in 2018. The findings will be published in a peer-reviewed journal.ConclusionThe trial is registered with ANZCTR (ACTRN12618000076279p).

BackgroundPrognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data.MethodThe inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003–2011). Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS), features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume) associates of severe disability and death. We used the area under the ROC (auROC) to determine accuracy of model. There were 41 (63.7% males) patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82–1.00). At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86–1.00).ConclusionOur findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

BackgroundEndovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.MethodsLarge vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014).ResultsThere were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00–0.91) in the alteplase-only versus 0.91 (0.65–1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2–8.7) versus 8.9 (4.7–13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2–13.1) versus 4.9 (0.3–8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3–11) days versus 8 (5–14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0–28) versus 27 (0–65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365.ConclusionThrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Clinical Trial Registrationhttp://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).

Background and aimThe availability and access of hospital administrative data [coding for Charlson comorbidity index (CCI)] in large data form has resulted in a surge of interest in using this information to predict mortality from stroke. The aims of this study were to determine the minimum clinical data set to be included in models for predicting disability after ischemic stroke adjusting for CCI and clinical variables and to evaluate the impact of CCI on prediction of outcome.MethodWe leverage anonymized clinical trial data in the Virtual International Stroke Trials Archive. This repository contains prospective data on stroke severity and outcome. The inclusion criteria were patients with available stroke severity score such as National Institutes of Health Stroke Scale (NIHSS), imaging data, and outcome disability score such as 90-day Rankin Scale. We calculate CCI based on comorbidity data in this data set. For logistic regression, we used these calibration statistics: Nagelkerke generalised R2 and Brier score; and for discrimination we used: area under the receiver operating characteristics curve (AUC) and integrated discrimination improvement (IDI). The IDI was used to evaluate improvement in disability prediction above baseline model containing age, sex, and CCI.ResultsThe clinical data among 5,206 patients (55% males) were as follows: mean age 69 ± 13 years, CCI 4.2 ± 0.8, and median NIHSS of 12 (IQR 8, 17) on admission and 9 (IQR 5, 15) at 24 h. In Model 2, adding admission NIHSS to the baseline model improved AUC from 0.67 (95% CI 0.65–0.68) to 0.79 (95% CI 0.78–0.81). In Model 3, adding 24-h NIHSS to the baseline model resulted in substantial improvement in AUC to 0.90 (95% CI 0.89–0.91) and increased IDI by 0.23 (95% CI 0.22–0.24). Adding the variable recombinant tissue plasminogen activator did not result in a further change in AUC or IDI to this regression model. In Model 3, the variable NIHSS at 24 h explains 87.3% of the variance of Model 3, follow by age (8.5%), comorbidity (3.7%), and male sex (0.5%).ConclusionOur results suggest that prediction of disability after ischemic stroke should at least include 24-h NIHSS and age. The variable CCI is less important for prediction of disability in this data set.

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.

Background: Lacunar infarcts have been characterized as small subcortical infarcts, resulting from in situ microatheroma or lipohyalinosis in small vessels. Based on this hypothesis, such infarcts should not be associated with large areas of perfusion deficits extending beyond subcortical regions to involve cortical regions. By contrast, selected small subcortical infarcts, as defined by MR imaging in the subacute or chronic stage, may initially have large perfusion deficits or related large vessel occlusions. These infarcts with ‘lacunar’ phenotype may also be caused by disease in the parent vessel and may have very different stroke mechanisms from small vessel disease. Our aim was to describe differences in imaging characteristics between patients with small subcortical infarction with ‘lacunar phenotype’ from those with lacunar mechanism. Methods: Patients undergoing acute CT Perfusion/angiography (CTP/CTA) within 6 hours of symptom onset and follow-up magnetic resonance imaging (MRI) for ischaemic stroke were included (2009-2013). A lacunar infarct was defined as a single subcortical infarct (SSI) ≤20 mm on follow-up MRI. Presence of perfusion deficits, vessel occlusion and infarct dimensions were compared between lacunar infarcts and other topographical infarct types. Results: Overall, 182 patients (mean age 66.4±15.3 years, 66% male) were included. SSI occurred in 31 (17%) patients. Of these, 12 (39%) patients had a perfusion deficit compared with those with any cortical infarction (120/142, 67%), and the smallest SSI with a perfusion deficit had a diameter of

Depression is a life-threatening psychiatric disorder characterized with a long-term hypercortisolemia in depressed patients. Based on this clinical feature, hypercortisolemia was mimicked in experimental animals to understand the neuropathogy of depression and to explore new therapeutic strategies. Wolfberry, also known as Lycium barbarum , is a type of common fruit produced in mainland China. Accumulated evidence has shown that the extracts from Lycium barbarum (LBP) had a wide range of neuroprotective effects in various neurogenerative models. However, the antidepressant effect of LBP on depression and its mechanism has not yet been explored. In the present study, we investigated the effects of LBP on counteracting depression using an animal model injected with moderate dose (40 mg/kg) or severe dose (50 mg/kg) of corticosterone (CORT) treatments for 14 days. The results showed that CORT significantly increased immobility time and decreased hippocampal cell proliferation. LBP treatment significantly decreased the immobility time in forced swimming test, a test for the intensity of depressive behaviors, both in 40 and 50 mg/kg CORT stressed rats. Moreover, LBP treatment restored the reduced proliferation of neuroprogentior cells in the hippocampus in 40 mg/kg CORT stressed rats and the neuronal differentiation but not the proliferation in 50 mg/kg CORT stressed rats. After ablation of adult neurogenesis with Ara-c infusion, the beneficial effect of LBP treatment in reducing immobility time was not affected in 40 and 50 mg/kg CORT stressed rats. Golgi staining and Western blotting detection showed that LBP treatment restored the reduced spine density and the decreased level of PSD-95 in the hippocampus caused by 40 and 50 mg/kg CORT, respectively, indicating enhanced synaptic plasticity in the hippocampus. The data showed a novel effect of LBP on reducing depression-like behavior and its antidepressant effect may be mediated by enhanced synaptic plasticity, but not hippocampal neurogenesis.