bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 92: Tenecteplase Treatment And Thrombus Characteristics Associated With Early Reperfusion -
An EXTEND-IA TNK Trials Analysis
Authors: Yogendrakumar Vignan , Churilov Leonid , Guha Prodipta , Beharry James , Mitchell Peter J , Kleinig Timothy J , Yassi Nawaf , Thijs Vincent , Wu Teddy Y , Brown Helen , Dewey Helen M , Wijeratne Tissa H , Yan Bernard , Sharma Gagan , Desmond Patricia , Parsons Mark W , Donnan Geoffrey A , Davis Stephen , Campbell Bruce ,   EXTEND-IA TNK Investigators
Published: February 2023

Background:
Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trials.

Methods:
Patients with large vessel occlusion (LVO) were randomized to treatment with tenecteplase (0.25mg/kg or 0.4mg/kg) or alteplase (0.9mg/kg) prior to thrombectomy. The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on initial angiographic assessment. We compared the treatment effect of tenecteplase versus alteplase overall, and in subgroups based on intracranial occlusion site, the presence of contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores), whilst adjusting for relevant covariates using mixed effects logistic regression models.

Results:
Among the 465 patients in the primary analysis, early reperfusion occurred in 18% (84/465). Tenecteplase was associated with a higher odds of early reperfusion (tenecteplase: 75/369 [20%] vs. alteplase: 9/96 [9%], aOR: 2.18 [95%CI: 1.03-4.63]). The difference between thrombolytics was most notable in distal M1 or M2 occlusions (tenecteplase: 53/176 [30%] vs. alteplase: 4/42 [10%], aOR: 3.73 [95%CI: 1.25-11.11]), thrombi with contrast permeability (tenecteplase: 38/160 [24%] vs. alteplase: 5/48 [10%], aOR: 2.83 [95%CI: 1.00-8.05]), and in low clot burden occlusions (tenecteplase: 66/261 [25%] vs. alteplase: 5/67 [7%], aOR: 3.93 [95%CI: 1.50-10.33]). Both thrombolytics had limited early reperfusion efficacy in proximal occlusions (ICA: tenecteplase 1/73 [1%] vs. alteplase 1/19 [5%]) and in high clot burden occlusions (tenecteplase: 9/108 [8%] vs. alteplase: 4/29 [14%], aOR: 0.58 [95%CI: 0.16-2.06]).

Conclusions:
Tenecteplase demonstrates superior early reperfusion versus alteplase in distal LVO, in contrast-permeable thrombi, and in lesions with low clot burden. Reperfusion efficacy remains limited in ICA occlusions and lesions with high clot burden. Further improvements in intravenous thrombolytics are required.
Abstract TMP39: Receipt Of Intravenous Thrombolysis Is Strongly Associated With 90 Day Functional Outcomes For Large Vessel Occlusion Stroke Patients Undergoing Endovascular Therapy
Authors: Isenberg Derek , Herres Joseph P , Zhao Huaquing , Cooney Derek R , Kuc Alexander , Kraus Chadd K , Sigal Adam , Brandler Ethan S , Ackerman Daniel , Mullen Michael T , Nomura Jason T , Gentile Nina T ,   Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms
Published: February 2023

Introduction:
Endovascular thrombectomy (EVT) is the standard of care for the treatment of large vessel occlusion stroke (LVOS). Most patients arrive at an endovascular center (ESC) either directly by EMS or by transfer from a non-ESC hospital. Many LVOS patients receive intravenous thrombolysis (IVT) prior to EVT. However, the benefits of IVT in combination with EVT are uncertain. The effect of direct transport to an ESC for EVT (primary) versus patients transferred for EVT (secondary) is also uncertain. Our goal was to determine the association between the IVT, primary transport versus secondary transport, and 90-day functional outcomes in LVOS patients treated with EVT.

Methods:
This study is an analysis of the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigm (OPUS-REACH) registry. The registry includes 2400 LVOS patients who underwent EVT from nine health systems in the United States. We included all patients with LVOS who arrived by EMS and had a last known well time to EVT of less than 10 hours.

Results:
1171 patients were included in the analysis and 39.5% of patients had good outcomes at 90 days (mRS score of 0-2). We found a 9% improvement in good outcomes when patients received IVT prior to EVT (OR 1.65, 95% CI 1.31-2.07). This association held true up to 10 hours (Figure 1) and in both patients who were transported directly to an ESC and in those patients transferred from a non-ESC.

Conclusion:
This investigation supports the importance of LVOS patients receiving IVT prior to EVT treatment as it was associated with markedly better outcomes (NNT=9). Prehospital transport algorithms should maximize access to IVT even if it delays time to EVT.
Abstract TMP54: Increased Thrombectomy Time Saving From Melbourne Mobile Stroke Unit Operation During Covid-19 Pandemic
Authors: Menezes Candice , Haliem Ahmed , Churilov Leonid , Smith Karen L , Delardes Belinda , Coote Skye , Easton Damien , Langenberg Francesca , Beharry James , Yogendrakumar Vignan , Weir Louise C , Mitchell Peter J , Donnan Geoff A , Davis Stephen , Campbell Bruce , Zhao Henry ,   Melbourne Stroke Unit consortium
Published: February 2023

Introduction:
Mobile stroke units (MSU) have demonstrated major time savings for thrombolysis but mixed evidence for endovascular thrombectomy (EVT). COVID-19 precautions have dramatically slowed EVT workflows across Australia and we therefore aimed to examine the effect of the Melbourne MSU on thrombectomy times before and during the current pandemic.

Methods:
Patients receiving EVT facilitated by the Melbourne MSU from 2017-2021 were compared to non-MSU patients (metropolitan direct and secondary transfer for EVT) admitted to the largest Melbourne EVT centre. Quantile regression analysis was used to calculate the median time difference (50
th
quantile) between MSU and non-MSU patients before and during the pandemic, grouped by patients within an EVT centre ambulance catchment or those outside (who either received inter-hospital transfer or MSU-facilitated bypass to an EVT centre).

Results:
A total of 402 patients (112 MSU) were included. Pre-pandemic, no reduction in dispatch to arterial access time was seen for MSU patients within an EVT centre catchment (median 11min slower, p=0.38). However, a significant time saving was observed during the pandemic (median 29 min faster, p<0.001, p-interaction=0.0065). MSU care reduced hospital arrival to arterial access time by median 19min pre-pandemic vs 40 min during the pandemic, p-interaction<0.001). The pandemic did not alter MSU-related time savings for patients located outside of an EVT centre catchment.

Conclusions:
Melbourne MSU facilitation of EVT during the COVID-19 pandemic resulted in greater time savings for patients located close to a thrombectomy centre, while substantial time savings were maintained for those needing bypass from the local non-EVT hospital. This suggests that MSU operation enables streamlined EVT workflows during the pandemic by providing early pre-hospital notification and interventional angiography activation.
Abstract TMP80: Sex Is Associated With Location, Severity And Outcome Of Intracerebral Hemorrhage: A Combined Analysis Of Four Landmark Studies
Authors: Rivier Cyprien , Acosta Julian , Renedo Daniela , Marini Sandro , Magid-Bernstein Jessica , Rosand Jonathan , Hanley Daniel F , Ziai Wendy C , Mayer Stephan , Woo Daniel , Sansing Lauren H , Sheth Kevin N , Anderson Christopher D , Falcone Guido J
Published: February 2023

Background and objective:
Small, single-center studies point to biological and clinical differences in women and men who sustain a spontaneous, non-traumatic intracerebral hemorrhage (ICH). Leveraging data from four landmark studies of ICH, we investigated the impact of sex on risk factors, location, severity and outcome of ICH.

Design:
Individual patient data meta-analysis of four studies of ICH, including three randomized clinical trials and one multi-ethnic observational study.

Setting:
Academic medical centers in the United States.

Patients:
Patients with neuroimaging confirmed ICH.

Measurements:
We conducted an individual patient data meta-analysis of four landmark studies of ICH: ERICH, ATACH-II, FAST and MISTIE-III. We evaluated whether sex was associated with specific risk factor profiles, hemorrhage location (deep or lobar), neuroimaging severity (hematoma volume and expansion), and poor 90-day functional outcomes (defined as a modified Rankin scale 4 to 6).

Main Results:
A total of 4,812 ICH patients were evaluated (mean age 62, 60% males). Men with ICH were younger, more likely to be smokers and diabetics, and less likely to be on anticoagulants (all p<0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR], 1.69; 95% CI, 1.42-2.01; p<0.001), larger hemorrhages (beta, 0.21; 95% CI, 0.14-0.28; p<0.001) and a higher risk of hematoma expansion (OR, 1.31; 95% CI, 1.10-1.56; p=0.003). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 22% lower risk of poor outcomes (OR, 0.78; 95% CI, 0.67-0.91; p=0.001).

Conclusions:
Men with ICH are more likely to have vascular risk factors, have larger hemorrhage volumes, and have higher risk of hemorrhage expansion. They are also more likely to have a good outcome at 90 days compared to women.
Abstract TP37: Door-in-door-out Time Is Not Related To Outcomes In Large Vessel Occlusion Stroke
Authors: Isenberg Derek , Sigal Adam , Kraus Chadd K , Ackerman Daniel , Brandler Ethan S , Mullen Michael T , Kuc Alexander , Herres Joseph , Nomura Jason , Cooney Derek R , Zhao Huaquing , Gentile Nina T ,   Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH)
Published: February 2023

Endovascular thrombectomy (EVT) a significantly improves outcomes in large vessel occlusion (LVO) stroke. Time to thrombectomy is a major determinant of neurologic outcomes. When patients with LVO arrive at a stroke center that does not perform thrombectomy they require urgent transfer to an endovascular-capable stroke center (ESC) for EVT. The goal of this study was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in a large multi-center registry.

Methods:
We conducted a retrospective review of patients from the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry initially evaluated at non-ESC and then transferred to ESC for EVT. We determined the association between DIDO times and 90-day outcomes as measured by the modified Rankin scale (mRS).

Results:
The mean DIDO time for patients with good outcomes was 17 minutes shorter than patients with poor outcomes (122 minutes v. 139 minutes). DIDO cutoff times of cohorts of ≤ 60 minutes, ≤ 90 minutes, or ≤ 120 were not associated with improved functional outcomes for those undergoing EVT (46.4% vs 32.3% p=0.12; 38.6% vs 30.6%, p=0.10; and 36.4% vs 28.9%, p=0.10, respectively). This trend for time cohorts held even for those with hyperacute strokes of <4-hour onset. Lower baseline NIHSS (11.9 vs 18.2, p=<0.001) was associated with improved outcomes.

Conclusion:
Although the DIDO time was shorter for patients with a good outcome, no clear time cutoff was associated with improved outcomes for LVOS. Factors associated with improved outcomes were a lower stroke severity score at presentation. This study underscores the need to streamline DIDO times but not to set an artificial benchmark not supported by evidence.
Abstract TP76: Lost To Follow Up As A Missed Opportunity In ICH Survivors
Authors: Velasquez Francisco , Chada Deeksha , Kellner Christopher P , Majidi Shahram , Sheth Kevin N , Dams O'Connor Kristen , Dangayach Neha S ,   The NEMAT Lab
Published: February 2023

Introduction:
Improving rates of in-hospital survival in intracerebral hemorrhage (ICH) have led to opportunities to implement secondary prevention and recovery measures. Lost to follow up is not well characterized in this disabled population. The objective of this analysis was to describe the frequency of lost to follow up for ICH survivors from an urban comprehensive stroke center and thrombectomy capable center.

Methods:
We included n=409 ICH patients from December 2016 to February 2022. With chart review, we collected data regarding the admission, discharge and follow-up. Our primary outcome measure was a modified Rankin scale (mRS) score of 0 - 3 during their last recorded follow-up. Pearson correlation analyses were performed using R statistical software to determine if there was a significant correlation between the number of follow-ups a patient received and their final recorded mRS score.

Results:
Of 409 ICH patients, 80 died within the first month of their index hospitalization or had incomplete records that prevented further analysis. Of the 329 patients, 181 were minorities (83 blacks, 49 asian and 49 hispanics) and 90 were white. About 85% (279/329) had insurance. Only 162 received 3 or more follow-ups post-index hospitalization, with 47 patients never receiving any follow-ups after their initial discharge. Of those that received follow up, the average number of follow ups was 2.57, with an average time of 366.17 days between discharge and the last recorded follow-up. Among the 282 patients that received at least one follow-up, there was a significant negative correlation between the number of follow-ups a patient received and their final recorded mRS score (p = 0.0000339, r = -0.246). There was no significant differences related to age, race or insurance status for those who followed up versus those who were lost to follow up.

Conclusions:
In a large urban health system, 14% ICH survivors were lost to follow-up. ICH survivors with good functional outcomes received more follow-up. There is a need to improve systems of care to prevent ICH patients from getting lost to follow-up and improving long term outcomes.
Abstract WMP56: Selection Of Magnetic Resonance Imaging Or Computed Tomography Before Mechanical Thrombectomy For Acute Ischemic Stroke
Authors: Ohtsubo Haruki , Ueda Toshihiro , Hasegawa Yasuhiro , TAKEUCHI MASATAKA , MORIMOTO MASAFUMI , Tsuboi Yoshifumi , Yamamoto Ryoo , Kaku Shogo , Ayabe Junichi , Akiyama Takekazu , Ishima Daisuke ,   K-NET Registry Investigators
Published: February 2023

Introduction:
Evaluation of ischemic core and penumbra by magnetic resonance imaging (MRI) or computed tomography (CT) is useful in determining the indication for mechanical thrombectomy (MT) for acute ischemic stroke, however, it is still uncertain which imaging modality is superior. In this study, we compared the clinical outcomes after MT by imaging modality in the K-NET registry (Kanagawa intravenous and endovascular treatment of acute ischemic stroke registry).

Methods:
The K-NET registry (January 2018 to December 2021) is a Japanese multicenter prospective registry study of patients treated with Intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase), endovascular treatment of cerebral infarction, or both for acute ischemic stroke. Patients who were enrolled by December 2020 and underwent MT were included in the study. We compared the favorable outcome at 90 days (modified Rankin Scale [mRS] score 0-2 or mRS shift [prestroke - day 90] = 0) between the MRI group and the CT alone group.

Results:
Of the 2348 patients enrolled in K-NET, 1763 underwent MT. Median age was 77 years (70-84) and 745 (42.2%) were female. There were 1311 patients in the MRI group and 452 in the CT group. There were no notable differences in patient characteristics. Despise the time from presentation to imaging was significantly shorter in the CT group (MRI: 14 minutes [9-21]; CT: 8 minutes [4-15]; P<0.001), there was no difference in time from presentation to recanalization. The rate of favorable outcome at 90 days was higher in the MRI group (MRI: 46.4%; CT: 40.7%; P=0.03). There was no difference in outcome between the two groups within 6 hours of onset, however, after 6 hours, the MRI group had a better outcome (MR 41.1%; CT: 28.2%; P=0.05). Compared due to SSS-TOAST classification, the MRI group had a better outcome in atherothrombotic patients (MRI group: 53.8%; CT group: 40.3%; P=0.04), while other subtypes of stroke did not show any difference.

Conclusions:
MRI imaging before MT was associated with favorable outcome. In addition, patients after 6 hours of onset and those with atherothrombotic disease had more favorable outcomes in the MRI group, suggesting that MRI may be useful as an imaging modality before thrombus retrieval in these patients.
Abstract WMP71: Changes In Severity And Outcomes Of Ischemic Stroke Associated With Atrial Fibrillation In A Long-lasting Nationwide Hospital-based Registry: Japan Stroke Data Bank
Authors: Toyoda Kazunori , Yoshimura Sohei , Nakai Michikazu , Wada Shinichi , Sasahara Yusuke , Miwa Kaori , Koge Junpei , Ishigami Akiko , Iwanaga Yoshitaka , Miyamoto Yoshihiro , Minematsu Kazuo , Kobayashi Shotai , Koga Masatoshi ,   Japan Stroke Data Bank Investigators
Published: February 2023

Background:
To determine secular changes in severity and functional outcomes of acute atrial fibrillation (AF)-associated stroke patients using a large population.

Methods:
Ischemic stroke patients with known AF or AF diagnosed after stroke onset, who were registered within 7 days after symptom onset into a hospital-based prospective registry, Japan Stroke Data Bank, from Jan 2000 to Dec 2020 were compared with those without AF. The co-primary outcomes were the initial neurological severity assessed by NIHSS and favorable outcome assessed by mRS of 0 to 2 at hospital discharge. Secondary outcomes included unfavorable outcome assessed by mRS of 5 to 6 and in-hospital death.

Results:
Of 142,351 patients studied, 33,870 had AF (women 45.1%, median age 79 years, non-valvular 94.3%). Patients with AF had higher initial NIHSS score (median 9 vs. 3, adjusted coefficient 5.383, 95% CI 5.245 - 5.520) as compared to patients without AF (women 38.2%, median age 79 years). Anticoagulation prior to the index stroke showed a significant interaction with the frequency of the NIHSS score ≥10 in patients with AF relative to those without AF (aOR: 2.047 for anticoagulated patients vs. 4.189 for the others). The NIHSS score decreased over the 21-year period in AF patients (adjusted coefficient -0.104, 95% CI -0.133 - -0.074 per year). Favorable outcome was less common in patients with AF than those without AF in unadjusted analysis (48.4% vs. 70.4%) but was more common after multivariable adjustment including the initial NIHSS score (aOR 1.096, 95% CI 1.040 - 1.156). Unfavorable outcome (aOR 1.108) and in-hospital death (1.506) were also more common in AF patients. The proportion of favorable outcome showed an increase over time (aOR 1.018, 95% CI 1.009 - 1.026 per year) in AF patients but the increase was no longer significant after further adjustment by receiving reperfusion therapy (1.007, 0.998 - 1.016). The proportion of unfavorable outcome and that of in-hospital death showed a yearly decrease over time.

Conclusions:
AF patients showed favorable clinical outcome after ischemic stroke relative to patients without AF by adjustment using the NIHSS score and others. Initial stroke severity became milder and functional outcomes tended to improve in AF patients during the past 21 years.
Abstract WP166: CHA
2
DS
2
-VASc or CHA
2
DS
2
-VA: Do We Need An Additional Point To Anticoagulate Women?
Authors: Giudici Daria , Regina Rossana , Paciaroni Maurizio , Caso Valeria ,   RAF, RAF-NOAC, and RENO-Extend Investigators
Published: February 2023

Rationale
The prevalence of atrial fibrillation (AF) is higher in men than women, but women have a higher risk of stroke and death due to AF. The CHA2DS2-Vasc score measures the risk of stroke in patients with AF, recommending a score of ≥ 2 for males and ≥ 3 for women. The aims of this study were: 1) to determine if the female sex is an independent risk factor for stroke in secondary prevention; 2) to compare CHA2DS2-VASc and CHA2DS2-VA in the risk of recurrent ischemic stroke.

Methods:
We used pooled individual data from an international collaboration of prospective cohort studies (RAF, RAF-NOAC, and RENO-Extend studies) that included patients with acute ischemic stroke and AF. Primary outcome was ischemic stroke recurrence. A multivariable model was performed to evaluate independent predictors for primary outcome. The predictive value of the CHA2DS2-VASc and CHA2DS2-VA scores for primary outcome was evaluated by c-statistic difference (ROC curves).

Results:
The cohort for this analysis comprised 3,750 patients (mean age 77.3±9.5 years) with ischemic stroke and AF; of these, 1930 (51.5%) were female. After a mean follow-up of 7.5±9.1 months, 242 (6.5%) primary outcome events were recorded: 123/1930 (6.4%) in women and 119/1820 (6.5%) in men. On multivariable analysis, female sex was not associated with the primary outcome (OR 0.98; 95% CI 0.72-1.31). The predictive value of the CHA2DS2-VASc and CHA2DS2-VA scores for the primary outcome in the overall population was similar with areas under the curves of 0.571 (95% CI, 0.535-0.607; p<0.0001) and 0.581 (95% CI, 0.545-0.617; p<0.0001), respectively.

Conclusions:
Our study shows that sex is not a predictive factor for ischemic events and that CHA2DS2-VASc and CHA2DS2-VA scores have a similar predictive value for recurrent ischemic stroke.
Abstract WP170: Validation Of Magnetically Induced Physiological Response Assessment To Identify Patients Likely Harboring Silent Brain Infarcts
Authors: Saver Jeffrey L , Maynard James , Brill Silviu , Tanne David ,   DV-RSD Investigators
Published: February 2023

Background:
Silent brain infarcts (SBIs) are among the most potent risk factors for future symptomatic stroke and vascular cognitive impairment, increasing the hazard ratio up to 3.3-fold. But high costs make MRI screening for SBIs in asymptomatic patients cost-ineffective. The AHA/ASA 2017 Scientific Statement on silent cerebrovascular disease calls for research to develop techniques to identify people at higher risk of SBIs who could go on to targeted neuroimaging and intensive prevention intervention. We performed a derivation and validation study of such a tool, a magnetically induced physiological response assessment of brain network integrity.

Methods:
Multicenter international study conducted at 5 sites (3 US, 2 OUS), assessing direct electrophysiological imaging (DELPHI) technology that records brain network magnetically induced physiological response. One site recruited the derivation cohort and 4 the validation cohort. Healthy subjects ages 50-75 with at least one vascular RF underwent multiple evaluations including computerized cognitive testing, MR assessment of SBIs, gray matter volume, white matter integrity, and brain network physiological function using DELPHI measures of connectivity. MRI findings, including SBIs, were assessed by 3 blinded independent neuroradiologists.

Results:
The derivation cohort enrolled 220 subjects and validation cohort 264 subjects. Across both groups, age was 61.5 (±7.1), 57% were female, and leading vascular risk factors were obesity/overweight in 67%, hypertension in 51%, and dyslipidemia in 45%. Silent brain infarcts were present in 10.8% of individuals, among whom 92% had 1-4 SBIs and 8% had ≥ 5 SBIs. The validation cohort was tested using the DELPHI thresholds established in the derivation cohort. In the validation cohort, DELPHI assessment discriminated SBI positive patients with AUC=0.70, sensitivity 82%, specificity 65%, p=0.001.

Conclusion:
Brain network physiology evaluation using the DELPHI technology detects silent brain infarcts with substantial accuracy in the outpatient office setting. This system is a safe and reliable means to identify older individuals likely harboring silent brain infarcts who could go on to targeted neuroimaging and intensified prevention treatment.
Abstract WP173: Interaction Between CYP2C19 Allele Status And Outcome Following Ischemic Stroke In Patients Treated With Clopidogrel: A TARDIS Trial Substudy
Authors: McDermott John H , Woodhouse Lisa J , Sen Dwaipayan , Smith Craig J , Newman William G , Bath Philip M ,   TARDIS Investigators
Published: February 2023

Background:
Clopidogrel is routinely prescribed following ischaemic stroke (IS), or transient ischaemic attack (TIA), as secondary prevention. Conversion of clopidogrel to its active form involves several hepatic cytochrome P450 enzymes (CYP450), including P450-2C19 (CYP2C19). Previous evidence suggests that CYP2C19 loss of function (LoF) carriers prescribed clopidogrel are at increased risk of vascular events in comparison with non-carriers. We sought to test for interaction between CYP2C19 LoF status and treatment effects in the TARDIS trial.

Methods:
TARDIS was an international, randomised trial recruiting participants with acute IS/TIA. Participants were assigned to receive intensive antiplatelet therapy (aspirin, clopidogrel, and dipyridamole) or guideline therapy (clopidogrel alone or aspirin and dipyridamole). Blood samples for genotyping were taken from consented participants at a 70 of the 106 recruiting centres.

Results:
Of 3096 participants, 1361 (44%) had samples available for genotyping. Median age was 69.0 years and 65.1% were male. Of the 1361 with samples, 1071 (78.7%) were randomised to clopidogrel and 290 (21.3%) to aspirin plus dipyridamole. 387 (28.4%) participants were CYP2C19 LoF allele carriers. At 35 days, 64 participants (4.7%) had a further IS/TIA and the rate of major adverse cardiovascular events was 6.8%. In participants randomised to clopidogrel (monotherapy or intensive) the rates of further IS/TIA were 4.9% in LoF allele carriers and 4.2% in non-carriers. As for those taking clopidogrel monotherapy, the rates of further IS/TIA were 7.4% in LoF allele carriers compared to 3.8% in non-carriers, though this difference was non-significant (p=0.14). There were no significant differences, in outcome or bleeding risk, by treatment group and LoF carrier status.

Conclusions:
No significant interaction was found between CYP2C19 genotype and outcome following IS/TIA when prescribed clopidogrel, either as monotherapy or in combination with aspirin and dipyridamole. There was no observed interaction between LoF status, clinical outcome, and bleeding rates. A caveat is that this analysis was undertaken on a subgroup of TARDIS participants and so was underpowered to detect a difference in the monotherapy group.
Abstract WP177: Effects Of The Oral Factor XIa Inhibitor Asundexian On Intracranial Bleeding Among Patients With Acute Non-Cardioembolic Ischemic Stroke: PACIFIC-Stroke Randomized Trial
Authors: Khatri Pooja , Shoamanesh Ashkan , Mundl Hardi , Smith Eric , Saad Feryal , Xu Lizhen , Heenan Laura , Colorado Pablo , Kirsch Bodo , Neumann Christoph , Connolly Stuart J , HART Robert G ,   PACIFIC-Stroke Steering Committee and Investigators
Published: February 2023

Introduction:
The phase 2 PACIFIC-Stroke trial of patients with acute non-cardioembolic ischemic stroke assessed asundexian, the oral small molecule Factor XIa inhibitor, versus placebo administered within 48h of ischemic stroke to prevent recurrent stroke. This trial uniquely included moderate and severe strokes, which were excluded from other early timeframe, secondary prevention trials of escalated antithrombotic therapy. The primary results suggest a reduction in recurrent ischemic stroke and TIA when added to antiplatelet therapy without an overall increase in intracranial hemorrhage (ICH)(in press at the
Lancet
). In this
post-hoc
analysis, we will further characterize the observed ICH.

Methods:
PACIFIC-Stroke (NCT04304508) was an international, double-blind, placebo-controlled, phase 2 randomized trial enrolling 1808 participants and comparing three dosages (10mg, 20mg, or 50mg daily) of asundexian with placebo. Participants were randomized within 48h of the qualifying ischemic stroke, and all received background antiplatelet therapy chosen by the local investigator. Eligibility for Part A was limited to patients with NIHSS </=7 who did not receive thrombolysis or endovascular thrombectomy, and Part B allowed an NIHSS up to 15 and treatment with reperfusion therapy (if >24 hours prior to randomization). Participants underwent MRIs within 72 hours of randomization and after 6 months.

Results:
In this presentation, we will further characterize the ICHs observed in the 1808 participants (1334 asundexian, 452 placebo) of the PACIFIC-Stroke trial. Further characterization will include timing, baseline stroke severity, post-thrombolysis/endovascular therapy status, asundexian dosing, and associated symptoms and radiological subtypes will be presented.

Conclusions:
Early anticoagulation of ischemic stroke patients with asundexian added to antiplatelet therapy was not associated with an increase in ICH compared to placebo, supporting the premise that inhibition of Factor XIa may prevent thrombosis without increasing bleeding. Further characterization of the observed ICHs associated with this novel drug compared to placebo will be presented.
Abstract WP68: Rehabilitation Therapy Doses Are Low After Stroke And Predicted By Clinical Factors
Authors: Young Brittany M , Holman Alison , Cramer Steven C ,   the STRONG Study Investigators
Published: February 2023

Background:
Stroke is a leading cause of disability. Greater rehabilitation therapy after stroke improves functional outcomes but is often not provided. This study examined amount of rehabilitation therapy during the first year after stroke in the U.S. and identified factors that predict rehabilitation therapy dose.

Methods:
Adults with new radiologically confirmed stroke were enrolled in the STRONG Study 2-10 days after stroke onset at 28 acute care hospitals in the U.S. Following initial assessment during acute hospitalization, the number of PT, OT, and ST sessions was measured at 3-, 6-, and 12-months post-stroke. The 3-month visit included a live exam. Negative binomial regression was used to investigate relationships that clinical and demographic factors had with therapy dose. False discovery rate was used to correct for multiple comparisons.

Results:
Of 763 patients enrolled during the acute stroke admission, 510 were seen for follow-up. Rehabilitation therapy doses were overall low, with most therapy delivered within the first 3 months; 35.0% of patients received no PT; 48.8%, no OT, and 61.7%, no ST. Discharge destination was significantly related to cumulative therapy; the percentage of patients discharged to an inpatient rehabilitation facility varied from 0-71%. Most demographic factors did not predict therapy dose, though Hispanic patients received lower cumulative amounts of PT and OT. Acutely, severity of clinical factors (grip strength, NIHSS score, and NIHSS subscores for aphasia and neglect) predicted higher subsequent therapy doses. At 3 months post-stroke, measures of impairment and function (FM-UE, mRS, and SIS-ADL) predicted further therapy doses.

ConclusionS:
Rehabilitative therapy doses during the first year of stroke recovery are low in the U.S. Patients with more severe deficits receive higher doses. Multiple factors, particularly clinical measures assessed as early as acute stroke admission, predict rehabilitation doses. These findings suggest directions to address this unmet need.
Abstract WP98: Utilization Of Perfusion Imaging For Acute Ischemic Stroke: Secular Trends And Effects On Outcomes Of Endovascular Treatment
Authors: LEE Jeong-Yoon , Kang Kyusik , Kim Yong Soo , Lee Soo Joo , Kim Jae G , Cha Jae-kwan , Kim Dae Hyun , Yoon Byeol-A , Han Moon-Ku , Kim Beom J , Kang Jihoon , Kim Jun Y , Park Tai H , Park Sang-Soon , Choi Jin-Kyo , Lee Kyung Bok , LEE JUN , Kwon Doo Hyuk , Hong Keun-sik , Cho Yong-jin , Park Hong-kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi S , Lee Minwoo , Kim Joon-Tae , Choi Kangho , Kim Dong-Eog , Gwak Dong-Seok , Choi Jay Chol , Kim Joonggoo , Kang Chul-Hoo , Shin Dong-Ick , Yum Kyu Sun , Kim Baik Kyun , Chae Hee-Yoon , Kwon Jee-hyun , Kim Wook-Joo , Sohn Sung-il , Hong Jeong-Ho , Park Hyungjong , Jang Seong Hwa , Kim Chul Ho , Lee Sanghwa , LEE JUNEYOUNG , Lee Ji Sung , Park Jong-moo , BAE Hee-joon ,   CRCS-K Investigators.
Published: February 2023

Introduction:
Perfusion imaging (PI) could guide decision-making for endovascular treatment (EVT) of acute ischemic stroke (AIS). However, PI was underused even in the US before the pivotal EVT trials proved its usefulness in 2018. This study aimed to describe the secular trends of PI utilization and investigate the effectiveness of PI-based EVT in real-world practice.

Methods:
Using a prospective multicenter (n=17) stroke registry in South Korea, we identified patients with AIS who presented within 24 hours from onset between 2011 and 2021. The study period was divided into 3 epochs: 2011-2014, 2015-2017, and 2018-2021. The study population was divided into the early (arrival within 6 hours) and late window (6-24 hours) groups.

Results:
A total of 51,650 patients (15,654 patients in 2011-2014, 14,432 patients in 2015-2017, and 21,564 patients in 2018-2021) were analyzed. Utilization of PI decreased in the overall population and early window group (

P
trend

<0.001); 43.3% and 54.1% in 2011-2014, 40.1% and 44.1% in 2015-2017, and 38.4% and 40.2% in 2018-2021, respectively; but increased in the late window group (

P
trend

<0.001); 31.3% in 2011-2014, 35.7% in 2015-2017, and 36.5% in 2018-2021. Of 10,872 patients with anterior large-vessel occlusion (aLVO), the EVT rate was not different between patients with and without PI (48.7% vs. 46.6%,
P
=0.08) in the early window but higher in those with PI than without PI in the late window (29.8% vs. 18.7%,
P
<0.001). The EVT outcome (3-month mRS 0-2) was not different between patients with and without PI in the early window (44.1% vs. 41.8%,
P
=0.21) and late window (38.4% vs. 39.2%,
P
=0.81). Propensity score analysis and instrumental variable analysis with PI rate per center as an instrument will be performed to adjust imbalances between patients with and without PI.

Conclusion:
Between 2011 and 2021 in South Korea, PI utilization has decreased in patients arriving within 6 hours from onset but has increased in those arriving between 6 and 24 hours. Among patients with aLVO, PI likely increased the EVT rate in the late window but did not in the early window. PI utilization did not seem to affect the EVT outcomes, but in-depth analysis is required.
SOCIAL CONSTRUCTION OF THE GENDER FEATURES OF A DISABLED PERSON`S IMAGE (BASED ON THE CONTENT-ANALYSIS OF MEDIA ARTICLES)
Authors: Sobkin Vladimir S. , Emelin Gleb D. , Nikolaeva Zinaida G. , Savchenko Nina L. , Yakovleva Marina A.
Published: February 2023

Background. Media performs an important role in the social construction of an image of a disability. In its turn, that image infl uences the reader`s generated value orientation and behavioral attitudes towards the disabled persons. One of the main problems is that in most media articles disabled persons are not diff erentiated by sex. Th is raises the question of whether there is a description of the disabled persons` gender features in articles where their sex is specifi ed. Objective. To conduct a content-analysis of the news articles in order to reveal gender-specifi c features of the social construction of a disabled person`s image in aspects of behavior, social interaction and personality characteristics. Sample. 107 media articles published during the period from December 2020 to August 2021 in the RBC, RIA Novosti, Rossiyskaya Gazeta, TASS, Izvestia. Methods. Th e media article texts were analyzed using content-analysis. For this purpose, the authors selected 27 categories in a coordinated expert assessment. Th ese categories are related to three parameters: disabled person’s actions, interaction with a disabled person and personality characteristics. Contingency tables were constructed and frequency analysis of the categories used in the descriptions of the disabled men and women were conducted based on obtained data. Results and conclusion. Th e frequency distribution of the categories used in media articles shows that description of disabled persons corresponds to gender social role stereotypes. At the same time, the ways of social interaction of disabled men and women are diff erent. Disabled men are focused on communication with a principal-agent, while disabled women address those involved in some situation. When disabled women are described there are violations of the readers` expectations regarding their greater vulnerability. In other words disabled women are presented as more persistent compared to disabled men.
Evaluation of Aerosol Optical Depth Forecasts from NOAA’s Global Aerosol Forecast Model (GEFS-Aerosols)
Authors: Bhattacharjee Partha S. , Zhang Li , Baker Barry , Pan Li , Montuoro Raffaele , Grell Georg A. , McQueen Jeffery T.
Published: February 2023

The NWS/NCEP recently implemented a new global deterministic aerosol forecast model named the Global Ensemble Forecast Systems Aerosols (GEFS-Aerosols), which is based on the Finite Volume version 3 GFS (FV3GFS). It replaced the operational NOAA Environmental Modeling System (NEMS) GFS Aerosol Component version 2 (NGACv2), which was based on a global spectral model (GSM). GEFS-Aerosols uses aerosol modules from the GOCART previously integrated in the WRF Model with Chemistry (WRF-Chem), FENGSHA dust scheme, and several other updates. In this study, we have extensively evaluated aerosol optical depth (AOD) forecasts from GEFS-Aerosols against various observations over a timespan longer than one year (2019–20). The total AOD improvement (in terms of seasonal mean) in GEFS-Aerosols is about 40% compared to NGACv2 in the fall and winter season of 2019. In terms of aerosol species, the biggest improvement came from the enhanced representation of biomass burning aerosol species as GEFS-Aerosols is able to capture more fire events in southern Africa, South America, and Asia than its predecessor. Dust AODs reproduce the seasonal variation over Africa and the Middle East. We have found that correlation of total AOD over large regions of the globe remains consistent for forecast days 3–5. However, we have found that GEFS-Aerosols generates some systematic positive biases for organic carbon AOD near biomass burning regions and sulfate AOD over prediction over East Asia. The addition of a data assimilation capability to GEFS-Aerosols in the near future is expected to address these biases and provide a positive impact to aerosol forecasts by the model.

Significance Statement

The purpose of this study is to quantify improvements associated with the newly implemented global aerosol forecast model at NWS/NCEP. The monthly and seasonal variations of AOD forecasts of various aerosol regimes are overall consistent with the observations. Our results provide a guide to downstream regional air quality models like CMAQ that will use GEFS-Aerosols to provide lateral boundary conditions.
Public management, agility and innovation: The Swiss experience with the COVID-19 loan scheme
Authors: Pauletto Christian
Published: February 2023

Within only 10 days of March 2020, the Swiss administration had designed and implemented a loan guarantee scheme for enterprises. The implementation phase was also short: it lasted less than five months. This article examines how that was possible, considering the complexity of the institutional setting and the scheme's innovative form, especially in terms of IT, including breakthroughs for the Swiss e-administrative practice: the scheme used algorithms to verify clients’ applications, a unique identification number for companies was implemented on a large scale, Swiss banks were integrated into the project's preparation and implementation, and some of their client operations were centralised on a government e-platform. The salient features of the process are identified through an analysis of the unfolding of operations during those ten days. The circumstances and context leading to radically new forms of public governance are also identified. Besides, an output analysis was undertaken to single out the innovative features of the deliverable. The case under consideration was short, and came unpredictably, so that no data or observations could be collected before or during the case. Accordingly, the study is by and large based on ex-post enquiries. With no explicitly formalised mandates, structures, or roles, the project participants came up with an informal organisation system. A well-defined deliverable was a powerful driver of the process. Several characteristics of the project, such as efficient networks, real-time information flow, flexible roles, flat hierarchy, and swift iterative subprocesses were akin to those of ‘agile organisations’. Tasks were performed concomitantly instead of sequentially.

Points for practitioners

It is striking that not much scholarly research has been published so far with a view to collecting and sharing the ‘lessons learned’ from the unique experience of emergency support packages during the pandemic, including at intra-organisational level. Research could be done regarding replicability both for future emergencies and for adjusting normal-times public management practices. This proposal aims to contribute to this conversation with a view to inspiring practitioners in public administrations and government entities. It foregrounds the relationship between governmental crisis management and the digitalisation of public administration processes using computer-enabled tools.
Devotion of Dissent: Contesting Hindutva in Bhakti Tradition
Authors: Das Soma
Published: February 2023

In the past few years, India has witnessed cataclysmic incidents of intermittent violence under the banner of Hindutva. Hindutva is a political ideology which works on extremist agenda to establish a homogenized cultural hegemony by focussing on exclusivist interests of Hindu majoritarian. It advocates revisionist attitude towards Hindu mythical figures by projecting them as prototypes of hypermasculinity to coax common Hindus with pseudo-patriotism. This article discusses on how Hindutva uses the principle of masculinity as its conceptual framework and its ramification on the socio-cultural fabric of India. It also deliberates on the fundamental essence of bhakti tradition, which largely contests Hindutva on ideological plane. Furthermore, it demonstrates the significance of bhakti literature in the present social context by alluding to the rich repository of saint poets whose verses critique Hindutva with a message of humanism.
The Application of Organs-on-a-Chip in Dental, Oral, and Craniofacial Research
Authors: Huang C. , Sanaei F. , Verdurmen W.P.R. , Yang F. , Ji W. , Walboomers X. F.
Published: February 2023

The current development of microfluidics-based microphysiological systems (MPSs) will rapidly lead to a paradigm shift from traditional static 2-dimensional cell cultivation towards organized tissue culture within a dynamic cellular milieu. Especially organs-on-a-chip (OoCs) can very precisely re-create the mechanical and unique anatomical structures of the oral environment. This review provides an introduction to such technology, from commonly used chip materials and fabrication methods to the application of OoC in in vitro culture. OoCs are advantageous because of their small-scaled culture environment, the highly controlled dynamic experimental conditions, and the likeness to the in vivo structure. We specifically focus on current chip designs in dental, oral, and craniofacial (DOC) research. Also, future perspectives are discussed, like model standardization and the development of integrated platforms with advanced read-out functionality. By doing so, it will be possible for OoCs to serve as an alternative for animal testing and to develop highly predictive human models for clinical experiments and even personalized medicine.
AMPK Activation Restores Salivary Function Following Radiation Treatment
Authors: Meyer R.K. , Gilman K.E. , Rheinheimer B.A. , Meeks L. , Limesand K.H.
Published: February 2023

Head and neck cancers represent a significant portion of cancer diagnoses, with head and neck cancer incidence increasing in some parts of the world. Typical treatment of early-stage head and neck cancers includes either surgery or radiotherapy; however, advanced cases often require surgery followed by radiation and chemotherapy. Salivary gland damage following radiotherapy leads to severe and chronic hypofunction with decreased salivary output, xerostomia, impaired ability to chew and swallow, increased risk of developing oral mucositis, and malnutrition. There is currently no standard of care for radiation-induced salivary gland dysfunction, and treatment is often limited to palliative treatment that provides only temporary relief. Adenosine monophosphate (AMP)–activated protein kinase (AMPK) is an enzyme that activates catabolic processes and has been shown to influence the cell cycle, proliferation, and autophagy. In the present study, we found that radiation (IR) treatment decreases tissue levels of phosphorylated AMPK following radiation and decreases intracellular NAD+ and AMP while increasing intracellular adenosine triphosphate. Furthermore, expression of sirtuin 1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) was lower 5 d following IR. Treatment with AMPK activators, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and metformin, attenuated compensatory proliferation (days 6, 7, and 30) following IR and reversed chronic (day 30) salivary gland dysfunction post-IR. In addition, treatment with metformin or AICAR increased markers of apical/basolateral polarity (phosphorylated aPKCζT560-positive area) and differentiation (amylase-positive area) within irradiated parotid glands to levels similar to untreated controls. Taken together, these data suggest that AMPK may be a novel therapeutic target for treatment of radiation-induced salivary damage.
Rates of Developmental Disabilities Vary Across Birth Months in a Tropical Climate
Authors: Maylott Sarah E. , Fasano Regina M. , Moffitt Jacquelyn M. , Boland Cody L. , Burdette Evan T. , Nahin Erica R. , Simpson Elizabeth A. , Delgado Christine
Published: February 2023

Developmental disability rates may vary by the season or month in which children are born. However, the seasonal mechanisms, such as climate, underlying these variations are unclear. Previous studies focused on high-latitude regions, leaving this climate hypothesis only partially tested. We analyzed rates of developmental disabilities in 3- to 5-year-old children from a tropical climate—South Florida—from 2004 to 2015 ( N = 79,047) using a time-series analysis to identify peaks in diagnoses based on birth months. Children with speech impairments were more likely to be born in March, April, and September, a novel finding. Children with developmental delays were more likely to be born in September and October, consistent with studies in colder regions. In contrast to prior studies, there were no effects of birth month for language impairment or autism spectrum disorder. We highlight potential prenatal mechanisms that may contribute to the seasonal variations in some developmental disabilities.
The Editor’s Note: Stepping outside the little boxes
Authors: Preston Teresa
Published: February 2023

Editor-in-Chief Teresa Preston discusses the highlights of the February 2023 issue of Kappan, which puts the spotlight on suburban schools. The growing diversity of the suburbs has sparked conflict as some community members speak out against change. And this conflict has implications for schools. Instead of taking sides against each other, communities need to look together for solutions to their shared problems.