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Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship.In a pooled, patient-level analysis of EXTEND-IA trials and SELECT study, we employed a mediation analysis framework to quantify infarct growth and cerebral edema(midline shift) mediation effect on successful reperfusion(mTICI≥2b) association with functional outcome(mRS distribution). Further, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift.542/665(81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful vs unsuccessful reperfusion. Median(IQR) infarct growth was 12.3(1.8-48.4)ml and median(IQR) midline shift was 0(0,2.2)mm. Of 249(37%) demonstrating a midline shift of ≥1mm, median(IQR) shift was 2.75(1.89, 4.21)mm). Successful reperfusion was associated with reductions in both predefined mediators; infarct growth (β, -1.19; 95%CI, -1.51to-0.88;p0.001) and midline shift (aOR:0.36,95%CI:0.23-0.57,p0.001). Successful reperfusion association with improved functional outcome (acOR:2.68; 95%CI:1.86-3.88,p0.001), became insignificant (acOR:1.39, 95%CI:0.95-2.04,p=0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect. Analysis considering alternative hypothesis demonstrated consistent results.In this mediation analysis from a pooled, patient-level cohort, a significant proportion(~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect and identify novel therapeutic targets to further enhance reperfusion benefits. This article is protected by copyright. All rights reserved.

Background: Stroke education is a key factor in minimising secondary stroke risk, yet worldwide stroke education rates are low. Technology has the potential to increase stroke education accessibility. One technology that could be beneficial is augmented reality (AR). We developed and trialled a stroke education lesson using an AR application with stroke patients and significant others. Methods: A feasibility study design was used. Following development of the AR stroke education lesson, 19 people with stroke and three significant others trialled the lesson then completed a customised mixed method questionnaire. The lesson involved narrated audio while participants interacted with a model brain via a tablet. Information about participant recruitment and retention, usage, and perceptions were collected. Results: Fifty-eight percent (n = 22) of eligible individuals consented to participate. Once recruited, 100% of participants (n = 22) were retained. Ninety percent of participants used the lesson once. Most participants used the application independently (81.82%, n = 18), had positive views about the lesson (over 80% across items including enjoyment, usefulness and perception of the application as a good learning tool) and reported improved confidence in stroke knowledge (72.73%, n = 16). Confidence in stroke knowledge post-lesson was associated with comfort using the application (p = 0.046, Fisher’s exact test) and perception of the application as a good learning tool (p = 0.009, Fisher’s exact test). Conclusions: Technology-enhanced instruction in the form of AR is feasible for educating patients and significant others about stroke. Further research following refinement of the lesson is required.

PURPOSE OF REVIEW: There have been many attempts to use variations in tibial polyethylene design to better recreate normal knee kinematics in the total knee arthroplasty. The goal of this review is to provide an overview of the various types of tibial inserts that exist and review the theoretical mechanics versus what was demonstrated in vivo. RECENT FINDINGS: Many polyethylene inserts have been attempted to re-create normal knee kinematics, but none have been able to successfully do so. Previously the only two types of inserts were posterior stabilized (PS) and cruciate retaining (CR) polyethylene inserts. Both of these have shown excellent long-term survival but neither has demonstrated native kinematics. Initially, it was thought that retention of the posterior cruciate ligament (PCL) would allow for more native kinematics, but fluoroscopic evidence has shown that the PCL alone cannot accomplish this. Newer inserts try to restore femoral roll back and the screw home mechanism. The bicruciate retaining total knee inserts are having the most “normal” kinematics, suggesting the importance of both the ACL and PCL in knee biomechanics. SUMMARY: Modern polyethylene inserts show favorable short-term data with bicruciate retaining inserts having the best kinematics; however, long-term studies are still needed to determine if survivorship and patient outcomes remain favorable.

India witnessed its first case of coronavirus infection (COVID-19) on January 27, 2020, in Kerala, India. Since then, the infection has spread rapidly across the country and the pandemic outbreak has affected all industries severely including the construction sector. This study aims to understand the effect of the COVID-19 pandemic on the construction sector, particularly the ready-mix concrete (RMC) industry. An attempt was made to investigate the liabilities and the losses incurred by the RMC industry in terms of income and change in the production of concrete during the coronavirus outbreak. A preliminary survey was carried out to create a database of the RMC plants located nearby the study area i.e., Ahmedabad City in the state of Gujarat, and to prepare a questionnaire using google forms. The RMC plants were visited and from the inputs of RMC officials, statistical insights were drawn. The study reveals that during the COVID-19 lockdown period there was almost a 40% loss in concrete production60% loss in the income generated by the ready-mix concrete industry. In addition to this, it was also found that the industry had to pay off liabilities like land rent, electricity bills, staff salaries, etc. during the time of the pandemic. This study provides the opportunity for RMC plants to identify the vital elements involved in the operation of the plant which can be affected due to such pandemic and provides guidelines to reduce the effect of any such pandemic on the plant's productionsales by ensuring the stability of all assets involved in its supply chain.

Background and ObjectivesThe relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging.MethodsIn a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial (EXTEND-IA; ClinicalTrials.govNCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion.ResultsRegions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%–70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%–32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%–28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median −3.3%, interquartile range −11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32–15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22–16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = −4.06, 95% CI 6.78–1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35–10.20, p = 0.011) in multivariable analysis.DiscussionCerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted.Classification of EvidenceThis study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.

The optimal general anesthetic (GA) technique for stroke patients undergoing endovascular thrombectomy (ET) is unclear. We compared favorable outcomes and mortality in patients receiving propofol or volatile GA during ET and assessed associations between mean arterial pressure (MAP) and outcome.Ninety-three patients with anterior circulation stroke who received propofol or volatile GA during ET between February 2015 and February 2018 were included in this retrospective study. Ninety-day modified Rankin scores were compared and mortality was adjusted for intravenous thrombolysis and diabetes. We performed ordinal logistic regression analyses containing MAP time/exposure thresholds.There was no difference in the rate of favorable outcome (modified Rankin scores 0-2) in the volatile and propofol groups (48.8% vs. 55.8%, respectively; P=0.5). Ninety-day mortality was lower in patients receiving propofol (11.5%) than in those receiving volatile GA (29.3%) (odds ratio, 0.32; 95% confidence interval, 0.11 to 0.94; P=0.03); this mortality benefit was greater in patients that did not receive intravenous thrombolysis before ET (odds ratio for survival, 6; 95% confidence interval, 1.13 to 31.74). There was no difference in MAP between groups and a (nonsignificant) trend towards the benefit of MAP90 mm Hg but not70 mm Hg.Favorable outcome rates were similar in stroke patients receiving propofol or volatile GA during ET. Propofol was associated with lower mortality, an effect magnified in patients that did not receive intravenous thrombolysis. MAP time/exposure thresholds were associated with outcome but independent of the anesthetic agent. Our data suggest that a difference in outcome related to an anesthetic agent may exist; this hypothesis needs to be tested in a prospective study.

Technological advancement over the year has contributed immensely to the enhancement of quality of life through various new products and services. One such revolution in the field of construction industry is the pre-engineered buildings (PEB). Pre-engineered building concept involves the steel building system which are predesigned and prefabricated. Pre-engineered building structure brings optimization technique and faster construction technology. PEB are designed according to the analytical results so the section of this particular elements is tapered according to the results and this concept makes the structure light weight and also provide the best possible sections according to the optimum requirements and cost effectiveness. In current scenario pre-engineered building (PEB) construction is used for multi storey building having large span. In the present work, the study of pre-engineered building (PEB) with conventional steel building (CSB) has been carried out, in this study pre-engineered building (PEB) and conventional steel building (CSB) were designed as per IS 800:2007. Comparative assessment will be conducted between PEB system and CSB system by using STAAD Pro V8i software. I have taken different plan and different material specifications also different height (G+10, G+20) and different span (3880 mm, 4850 mm) for plans for study of material consumption. After the study result of PEB and CSB structures observed that the PEB structures reduce the material consumption.

The relationship between reperfusion and edema is unclear, with experimental and clinical data yielding conflicting results. We investigated whether the extent of salvageable and irreversibly-injured tissue at baseline influenced the effect of therapeutic reperfusion on cerebral edema. In a pooled analysis of 415 patients with anterior circulation large vessel occlusion from the Tenecteplase-versus-Alteplase-before-Endovascular-Therapy-for-Ischemic-Stroke (EXTEND-IA TNK) part 1 and 2 trials, associations between core and mismatch volume on pre-treatment CT-Perfusion with cerebral edema at 24-hours, and their interactions with reperfusion were tested. Core volume was associated with increased edema (p

Despite evidence that stroke education is important and effective, low rates of stroke education are reported worldwide. Many stroke survivors and carers report that current stroke information does not meet their needs. The aim of the current study was to explore the perceptions of stroke survivors and carers towards stroke education in an Australian health context. A qualitative descriptive approach using focus groups was used to explore education received and preferred content, format and timing of education. Data were analysed inductively using qualitative content analysis to identify key categories, sub-categories and an overarching theme. Fifteen stroke survivors and four carers participated. Four categories emerged: the timing of stroke education, the content of stroke education, the format of stroke education, and reactions to stroke education. Each category contained a number of sub-categories. One overarching theme was woven through the transcripts: everyone is different and has different needs. Overall, participants generally expressed positive attitudes towards stroke education. Participants reported that education should occur at multiple timepoints and in a mixed format. All participants reported receiving stroke education in hospital, but not in the community. Stroke survivors preferred group education, while carers did not share this preference. Both stroke survivors and carers desired information about post-stroke physical changes and computer use; however, stroke survivors desired additional information spanning a variety of areas such as motivation and driving. Tailoring of stroke education for each individual is critical to ensure that education meets the needs of stroke survivors and carers from the hospital to the community.

Objective The urethral gap in pelvic fracture urethral injury (PFUI) is traditionally assessed using voiding cystourethrogram (VCUG) and retrograde urethrogram (RGU). Magnetic resonance imaging (MRI) is performed in complex cases. We assessed the refined "Joshi" MRI protocol to evaluate complex urethral defects after PFUI. Material and methods A prospective study was conducted at our center from January 2018 to January 2020, involving patients aged >18 years with PFUI, suitable for MRI, and those who gave consent to perform standard RGU, VCUG, and MRI using standard and "Joshi" protocol. Forty men were included in the study. Distance between urethral/prostatic stumps was measured. Image quality was scored by four radiologists and four urologists. The surgical approach and type of PFUI repair were noted. We also established the need for inferior pubectomy by assessing the position of the posterior urethra (membranous) in relation to a horizontal line drawn from the lower edge of the pubic bone anteriorly to the rectum posteriorly in a sagittal image. Results The mean age was 30 years (SD, 5.25; range, 21-43), and the time from injury to imaging was 4 months (3-10 months); 40% of the men underwent crural separation, 57.5%, inferior pubectomy, and 2.5%, crural rerouting. There was a difference of 0.3 to 1.1 cm in the urethral gap measurements between MR images using the standard versus "Joshi" technique. MRI identified complex injuries such as rectourethral fistula, the need for inferior pubectomy, and the orientation of the posterior urethra. Urologists' and radiologists' satisfaction scores for the MR images were satisfactory to excellent. If the posterior urethra was over the defined mark, there was a 100% likelihood of inferior pubectomy (23/40 patients). Conclusion MR image acquisition using the "Joshi" protocol provided high-quality anatomical information in PFUI cases to assist with surgical planning.

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.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 of7, intracerebral haemorrhage volume70 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 or6 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).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.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.National Health and Medical Research Council, Royal Melbourne Hospital Foundation.

To examine associations between in utero marijuana exposure and birth outcomes. In two separate cohorts (Appalachian, Rocky Mountain), data were collected from medical records. Marijuana exposure was positive based on urine drug screening at delivery, with nonexposed controls matched on multiple factors including other substance exposure. Marijuana-exposed newborns (n = 531) had significantly worse birth outcomes than controls (n = 531), weighing 218 g less, 82%, 79%, and 43% more likely to be low birth weight, preterm, or admitted to the NICU, respectively, and significantly lower Apgar scores. Marijuana exposure in utero predicted newborn factors linked to longer-term health and development issues. Effects were not attributable to other comorbidities in this study due to rigorous matching and biochemical verification of marijuana and other drug use. Findings add to growing evidence linking marijuana exposure to adverse birth and longer-term outcomes. Women should be encouraged to avoid marijuana use during pregnancy.

Late rupture of the posterior cruciate ligament (PCL) in cruciate-retaining total knee arthroplasty (TKA) can lead to increased AP instability. This results in increased stress on the medial hamstrings resulting in hamstring-based pain. We looked to identify patients with late PCL failure using a lateral stress radiograph.A prospective cohort analysis was completed at a single institution. Eligible patients were divided into two groups based on the amount of anterior knee pain. Pain was defined as a visual analog scale of greater than or equal to 3. Each group completed a visual analog scale, Knee Injury and Osteoarthritis Outcome Score Junior, Patient-Reported Outcome Measurement Information System score and underwent a lateral posterior stress/nonstress radiograph. Amount of posterior translation and posterior tibial slope was measured.Patients who had painful TKAs at the follow-up had lower Knee Injury and Osteoarthritis Outcome Score Junior (45.86 ± 13.52 versus 78.00 ± 13.26 P0.001). Those patients were also found to have significantly higher posterior tibial translation with stress radiograph (6.89 ± 1.874 versus 3.91 ± 2.15 mm P0.001) and significantly increased tibial slope (6.51 ± 2.37° versus 3.98 ± 1.79°, P = 0.004). Seven of the 14 patients in the pain group underwent revision surgery, with 6 patients found to have incompetent PCLs.Patients with increased AP translation and increased posterior tibial slope after cruciate-retaining TKA are likely to have worse pain and outcome measures.

Introduction: Anticoagulation reduces recurrent ischemic stroke based on clinical definitions in patients with atrial fibrillation (AF). However, neuroimaging registries suggested a significant proportion developed ischemic lesions on magnetic resonance imaging (MRI) at 12 months follow up. The rate of early recurrent ischemic stroke identified by MRI remains unclear. ATTUNE (Atrial fibrillation in stroke - Utility of Neuroimaging Evaluation) is a prospective, multicentre study of clinical and radiological outcomes in patients commenced on anticoagulation after ischaemic stroke or TIA. We aimed to investigate the incidence of early ischemic stroke on MRI in this group of patients who were anticoagulated. Aims/Methods: We performed an interim analysis of the ATTUNE database to determine the proportion of patients with radiological evidence of infarction and haemorrhage on (MRI), one month after index ischemic stroke or transient ischemic attack (TIA). MRIs performed at one month were analysed independently by two experienced neuroimage assessors and the number of new infarcts and haemorrhages determined for each patient. Results: A total of 216 patients were analysed. The median age was 74 (IQR 68-81). Anticoagulation was commenced a median of 4 days after index event (IQR 2-6). Twenty-eight patients had new infarcts on follow-up MRI (13%). Fifty-six had new haemorrhage on follow up MRI (26%). Of these, 41 patients had hemorrhagic transformation of the initial infarct and 15 had a remote haemorrhage. Conclusion: There is a high rate of recurrent ischemic lesions and haemorrhages on MRI in patients commenced on anticoagulation within 30 days of index stroke or TIA.

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods: In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT Functional outcomes (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes. Results: Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22], non-GA 16[11-20], p Conclusion: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.

The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity.In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity.We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds.In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.

Introduction: Electromagnetic imaging is an emerging technology which promises to provide a mobile, and rapid neuroimaging modality for pre-hospital and bedside evaluation of stroke patients based on the dielectric properties of the tissue. It is now possible due to technological advancements in materials, antennae design and manufacture, rapid portable computing power and network analyses and development of processing algorithms for image reconstruction. The purpose of this report is to introduce images from a novel, portable electromagnetic scanner being trialed for bedside and mobile imaging of ischaemic and haemorrhagic stroke.Methods: A prospective convenience study enrolled patients (January 2020 to August 2020) with known stroke to have brain electromagnetic imaging, in addition to usual imaging and medical care. The images are obtained by processing signals from encircling transceiver antennae which emit and detect low energy signals in the microwave frequency spectrum between 0.5 and 2.0 GHz. The purpose of the study was to refine the imaging algorithms.Results: Examples are presented of haemorrhagic and ischaemic stroke and comparison is made with CT, perfusion and MRI T2 FAIR sequence images.Conclusion: Due to speed of imaging, size and mobility of the device and negligible environmental risks, development of electromagnetic scanning scanner provides a promising additional modality for mobile and bedside neuroimaging.

The prevalence of opioid use disorder has increased across the United States, but the rural population of Appalachia has been disproportionately impacted. Concurrently, the slow, but steady progress in the legalization of marijuana may be affecting perception of marijuana use in pregnancy. However, marijuana use in pregnancy has been associated with adverse perinatal outcomes. Concomitant use of opioids and marijuana in pregnancy has not been evaluated.The primary aim of the study was to evaluate the association between confirmed marijuana use in late pregnancy and preterm birth in opioid-exposed pregnancies.A retrospective chart review was conducted that included all births from July 2011 to June 2016 from 6 delivery hospitals in South-Central Appalachia. Out of 18,732 births, 2368 singleton pregnancies indicated opioid use and met remaining inclusion criteria, with 108 of these mothers testing positive for marijuana at delivery. Independent sampleNeonates born to marijuana-positive women in opioid-exposed pregnancy were more likely to be born preterm, small for gestational age, have low birth weight, and be admitted to NICU. After statistically controlling for parity, marital status, tobacco and benzodiazepine use, preterm birth and low birth weight remained statistically significant with aOR of 2.35 (1.30-4.24) and 2.01 (1.18-3.44), respectively.Maternal use of marijuana in any opioid-exposed pregnancy may increase risk of preterm birth and low-birth weight infants. Prospective studies need to examine the dose and timing of marijuana and opioid use in pregnancy to better delineate perinatal effects. Nonetheless, pregnant women using opioids, including recommended medication assisted treatment for opioid use disorder, should be educated about the risks of concurrent marijuana use during pregnancy and may need to be counseled to abstain from marijuana use during pregnancy for an optimal outcome.

Background Local endovascular services for acute stroke in rural and remote regions remain a significant challenge despite higher rates of stroke in these regions. Objectives We present time metrics, logistics, safety and outcome data on stroke patients with large vessel occlusion (LVO) that were aero-medically transferred from rural and remote ‘spoke’ sites to the Gold Coast University Hospital (GCUH) ‘hub’ for endovascular thrombectomy (EVT). Methods This is a retrospective observational study utilizing prospectively collected stroke database from December 2018 to March 2020. Aeromedical transfers from ten rural and remote Queensland sites and one Northern New South Wales site were included, covering more than 1.8 million km² catchment area. Results Over the period of 16 months, 20 out of 26 transferred patients underwent EVT. Mean distance was 1350 km, median time of ictus to recanalization was 928 minutes and TICI 2b-3 was achieved in 90% of the patients. One out of 20 patients (5%) had symptomatic intracranial hemorrhage (sICH), and 9 out of 20 (45%) achieved functional independence (mRS 0-2) at 90 days; similar to the recent pivotal trials. Conclusions Our 12-center network experience confirms real world reproducibility of trial results, including ultra-long transfers, and supports such transfers at other centers worldwide.

This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of "omics" technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health.

Objective:To determine accessibility of the primary healthcare system for patients with stroke recently discharged from hospital.Methods:This project mapped retrospective patient location data and the location of primary healthcare services in the same region. Patient location data were from all patients with stroke (N = 1595: January 2011–January 2017) discharged from one metropolitan hospital to the local Primary Health Network. Geographic Information System technology was used to map the patient discharge locations and the spatial distribution of primary healthcare services (general practitioner, pharmacy, allied health) across the region. Road network data were used to measure the level of access from each patient’s discharge location to the services.Results:Access to primary healthcare services was variable. Areas with larger proportions of patients with stroke did not necessarily have good service access. With an increase in travel time, the number of services accessible to patients also increased. However, the spatial variation of access to services remained largely unchanged.Conclusion:Access to primary healthcare services for patients with stroke varies spatially, with a trend towards relatively low levels of accessibility for many patients. There is an urgent need for future planning to consider geographical access to primary healthcare services for patients with stroke.

Background and Purpose Changes to hospital systems were implemented from March 2020 in Australia in response to the coronavirus disease 2019 pandemic, including decreased resources allocated to stroke units. We investigate changes in the quality of acute care for patients with stroke or transient ischemic attack during the pandemic according to patients’ treatment setting (stroke unit or alternate ward).Methods We conducted a retrospective cohort study of patients admitted with stroke or transient ischemic attack between January 2019 and June 2020 in the Australian Stroke Clinical Registry (AuSCR). The AuSCR monitors patients’ treatment setting, provision of allied health and nursing interventions, prescription of secondary prevention medications, and discharge destination. Weekly trends in the quality of care before and during the pandemic period were assessed using interrupted time series analyses.Results In total, 18,662 patients in 2019 and 8,850 patients in 2020 were included. Overall, 75% were treated in stroke units. Before the pandemic, treatment in a stroke unit was superior to alternate wards for the provision of all evidence-based therapies assessed. During the pandemic period, the proportion of patients receiving a swallow screen or assessment, being discharged to rehabilitation, and being prescribed secondary prevention medications decreased by 0.58% to 1.08% per week in patients treated in other ward settings relative to patients treated in stroke units. This change represented a 9% to 17% increase in the care gap between these treatment settings during the period of the pandemic that was evaluated (16 weeks).Conclusions During the first 6 months of the pandemic, widening care disparities between stroke units and alternate wards have occurred.

The application of telestroke has matured considerably since its inception in 1999. The use of telestroke is now recommended in several published guidelines. Consequently, jurisdictions without a telestroke service are seeking practical information on the best approach to implement telestroke. French et al. (2013) reviewed the challenges of implementing a telestroke network including studies between 2000 and 2010. At the time, telestroke networks were largely limited to the UK, USA, Canada and Europe and only one process evaluation had been conducted. Given the prolific expansion of telestroke services since 2010, we conducted a systematic review to determine factors associated with successful establishment, management, and sustainability of a contemporary telestroke services. A comprehensive search of telestroke studies was conducted in July 2021. Empirical studies published between 2010 and 2021 were included if they contained descriptive, evaluation or operational data on the implementation of a telestroke network. Studies were subsequently evaluated using the Consolidated Framework for Implementation Research (CFIR). The initial literature search revealed a total of 7415 potential studies; 38 of which met the inclusion criteria. The past decade of process evaluation studies has enabled a more nuanced investigations into how to implement and sustain a telestroke network. Pre-implementation planning is crucial to ensure clear telestroke processes, governance structures and stakeholder engagement. Sustainability of networks relies on securing long-term investment, providing adequate resources, and maintaining staff motivation and willingness. Recommendations are provided to overcome commonly identified barriers related to technology, staffing, planning and standardisation of processes, evaluation, and sustainability and scale-up. Further research needs to explore how new advancements in stroke care such as endovascular clot retrieval (EVT) and advanced brain imaging can be considered and planned for during the implementation of a new telestroke service.

Background: Our 10-hospital network (2 CSCs, 2PSCs, 6 non-SCs) switched our standard stroke thrombolytic from alteplase (ALT) to tenecteplase (TNK; 0.25 mg/kg) in September 2019. Methods: We designed a two-year prospective cohort analysis of key processes and clinical outcomes for TNK-treated patients with planned quarterly assessments of feasibility and safety. The TNK cohort is compared to the retrospective historical cohort of all unique patients at these hospitals treated with ALT during the prior 2-year period (n=354). Analysis were taken from a local REDcap registry that recorded data fields required for Stroke Center certification and submission to Get-With-The Guidelines (GWTG). Interim results through three quarters ending June 30, 2020. Results: 151 patients were treated with TNK. The samples TNK v ALT were well matched on age (median, IQR) 66.0 (55.0, 76.0) v 67.0 (55.0, 78.8) and NIHSS at admission (median, IQR), 8 (4, 13) v 8 (4, 15). Symptomatic ICH (ECASS 3 definition) occurred in 2.0% of TNK and 2.3% of ALT treated patients; all but one symptomatic ICH occurred in patients treated with both thrombolytic and endovascular therapies. All cause in-hospital mortality was 3.3% and 6.8%, respectively. No differences were observed in early outcomes of discharge to home (52%, 53%) or independent ambulation (46%, 45%). Day 90 Rankin Score (last observation carried forward for missing values) was available only for TNK: mRS 0-1 in 46.4% (95%CI 38.6%-54.3%), 0-2 in 55.6% (95%CI 47.7%-63.3%). A significantly greater proportion of patients were treated with the lytic within 45 minutes of hospital arrival after the switch to TNK using Get-With-The-Guidelines DTN time criteria (Table), most notably at the primary stroke centers. Conclusions: To date, the transition to TNK was associated with reductions in DTN times and in Drip-and-Ship transfer times (see related abstract). No differences were seen on early indices of safety or efficacy.

Background: Local endovascular services for acute stroke in rural and remote regions remain a significant challenge despite higher rates of stroke in these regions. Aim: We present time metrics, logistical, safety and outcome data on large vessel occlusion (LVO) patients receiving endovascular thrombectomy (EVT) that were aeromedically transferred from rural and remote “spoke” sites to the Gold Coast University Hospital (GCUH) “hub”. Methods: This is a retrospective observational study utilizing prospectively collected stroke database from December 2018 to March 2020. Aeromedical transfers from ten rural and remote Queensland sites and one northern New South Wales site were included, covering more than 1.853 million km 2 catchment. Results: 20 out of 26 transferred patients underwent EVT over this period. Mean distance was 1380.5 km, median time of ictus to re-canalization was 928 minutes and TICI 2b-3 was achieved in 90% of the patients. One out of 20 patients (5%) had symptomatic ICH (sICH), and 9 out of 20 (45%) achieved functional independence (mRS 0-2) at 90 days; similar to the recent pivotal trials. Conclusions: Our 12-center network experience confirms real world reproducibility of trial results including ultra-long transfers and supports such transfers at other centers worldwide.

ObjectiveTo investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO).MethodsTo determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated.ResultsWe included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7–32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3–12; p = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40–71] minutes) vs alteplase-treated patients (110 [IQR 51–185] minutes; p = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; p = 0.9).ConclusionsTNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted.Clinicaltrials.gov IdentifiersNCT02388061 and NCT03340493.Classification of EvidenceThis study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.

Directed cell migration plays a crucial role in physiological and pathological conditions. One important mechanical cue, known to influence cell migration, is the gradient of substrate elastic modulus (E). However, the cellular microenvironment is viscoelastic and hence the elastic property alone is not sufficient to define its material characteristics. To bridge this gap, in this study, we investigated the influence of the gradient of viscous property of the substrate, as defined by loss modulus (G″) on cell migration. We cultured human mesenchymal stem cells (hMSCs) on a collagen-coated polyacrylamide gel with constant storage modulus (G') but with a gradient in the loss modulus (G″). We found hMSCs to migrate from high to low loss modulus. We have termed this form of directional cellular migration as "Viscotaxis". We hypothesize that the high loss modulus regime deforms more due to creep in the long timescale when subjected to cellular traction. Such differential deformation drives the observed Viscotaxis. To verify our hypothesis, we disrupted the actomyosin contractility with myosin inhibitor blebbistatin and ROCK inhibitor Y27632, and found the directional migration to disappear. Further, such time-dependent creep of the high loss material should lead to lower traction, shorter lifetime of the focal adhesions, and dynamic cell morphology, which was indeed found to be the case. Together, findings in this paper highlight the importance of considering the viscous modulus while preparing stiffness-based substrates for the field of tissue engineering. STATEMENT OF SIGNIFICANCE: While the effect of substrate elastic modulus has been investigated extensively in the context of cell biology, the role of substrate viscoelasticity is poorly understood. This omission is surprising as our body is not elastic, but viscoelastic. Hence, the role of viscoelasticity needs to be investigated at depth in various cellular contexts. One such important context is cell migration. Cell migration is important in morphogenesis, immune response, wound healing, and cancer, to name a few. While it is known that cells migrate when presented with a substrate with a rigidity gradient, cellular behavior in response to viscoelastic gradient has never been investigated. The findings of this paper not only reveal a completely novel cellular taxis or directed migration, it also improves our understanding of cell mechanics significantly.

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.

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

Background: Mechanical thrombectomy (MT) became standard care in 2015 after positive trials in patients presenting with acute ischemic stroke and large vessel occlusion (LVO) 0-6h and in 2018 for selected patients up to 24h from symptom onset. Objective: To evaluate whether patients receiving MT at our center would have comparable outcomes in patients presenting to our comprehensive stroke center (direct) vs transfer patients (drip-and-ship) Methods: This is a retrospective observational study utilising prospectively collected stroke database for patients receiving MT for LVO in anterior and posterior circulation in South Brisbane network of 7 hospitals (6 drip-and-ship centers and 1 MT-capable center), Australia which serves 1.6 million. Day 90 modified Rankin scale (mRS) was used to assess functional outcomes via outpatient follow up at direct or referral center. The association of drip and ship versus mothership treatment with day 90 mRS was tested in ordinal logistic regression adjusted for age, baseline NIHSS and IV thrombolysis. Results: Of 191 patients who underwent Mechanical Thrombectomy from 2015 to June 2018 at our center, 22 patients were excluded from analysis as either their baseline mRS was >1 (13) or follow up data was missing (9). The mean age was 64.4 years. Median (inter-quartile range, IQR) NIHSS was 16 (9-21) on admission and 7 (2-18) on day 1. Thrombolysis in Cerebral Infarction (TICI) ≥2b was achieved in 88.9%. At 90 days, 50.9% achieved excellent functional outcome (mRS 0-1), 61.4% achieved good functional outcome (mRS 0-2) and 69% achieved favorable outcome (mRS 0-3). Median mRS was 1 (IQR 0-5) in 96 patients presenting directly to the endovascular center and 1 (IQR 1-4) in 73 drip-and-ship patients (common odds ratio 1.07 (95%CI 0.62-1.83), p=0.82) Conclusion: Our 7-center network experience confirms real world reproducibility of trial results, interestingly with no difference in functional outcomes for direct vs drip-and-ship patients.