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Introduction: Dysphagia is common after acute ischemic stroke and entails considerable morbidity and mortality. Here, we investigated the impact of intensified care on swallowing recovery after stroke., Patients and Methods: In this secondary analysis of STROKE-CARD, a randomized intervention trial of intensified post-stroke care, dysphagia was assessed by speech therapists at admission for acute ischemic stroke, at hospital discharge, and after 12-months. Patients randomized to STROKE-CARD care additionally received a detailed dysphagia follow-up at 3-months, including a standardized dysphagia examination, instructions on further exercises and compensation mechanisms and, if necessary, referral for further speech therapy., Results: Dysphagia was present initially after stroke in 236 (16.6%; median age 82 (73-88), 44.1% female) of 1419 patients, with similar prevalence in both study groups at hospital admission ( p  = 0.239) and discharge ( p  = 0.870). At follow up, 14 (9.5%) of 147 in the intervention group and 18 (20.2%) of 89 in the control group suffered from persistent dysphagia ( p  = 0.020). There was better dysphagia recovery in the intervention group also under multivariable adjustment for age, sex, functional disability at 12-months, severe dysphagia at hospitalization, mode of feeding, cognitive impairment, thrombolysis, and stroke localization (odds ratio, 0.41, 95% confidence interval: 0.17 to 0.96)., Discussion and Conclusion: Intensified post-stroke care improved dysphagia recovery within 1 year after acute ischemic stroke, highlighting the potential of targeted interventions for enhancing stroke outcomes., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PW reports consultancy fees from Novartis Pharmaceuticals unrelated to this manuscript. The remaining authors report no disclosures relevant to this research.

Background: Pre-existing comorbidities increase the likelihood of post-stroke dysphagia. This study investigates comorbidity prevalence in patients with dysphagia after ischemic stroke., Methods: The data of patients with acute ischemic stroke from two large representative cohorts (STROKE-CARD trial 2014-2019 and STROKE-CARD registry 2020-2022 - both study center Innsbruck, Austria) were analyzed for the presence of dysphagia at hospital admission (clinical swallowing examination). Comorbidities were assessed using the Charlson Comorbidity Index (CCI)., Results: Of 2054 patients with ischemic stroke, 17.2% showed dysphagia at hospital admission. Patients with dysphagia were older (77.8 ± 11.9 vs. 73.6 ± 14.3 years, p < 0.001), had more severe strokes (NIHSS 7(4-12) vs. 2(1-4), p < 0.001) and had higher CCI scores (4.7 ± 2.1 vs. 3.8 ± 2.0, p < 0.001) than those without swallowing impairment. Dysphagia correlated with hypertension (p = 0.034), atrial fibrillation (p < 0.001), diabetes (p = 0.002), non-smoking status (p = 0.014), myocardial infarction (p = 0.002), heart failure (p = 0.002), peripheral arterial disease (p < 0.001), severe chronic liver disease (p = 0.002) and kidney disease (p = 0.010). After adjusting for relevant factors, the associations with dysphagia remained significant for diabetes (p = 0.005), peripheral arterial disease (p = 0.007), kidney disease (p = 0.014), liver disease (p = 0.003) and overall CCI (p < 0.001)., Conclusions: Patients with multiple comorbidities have a higher risk of developing post-stroke dysphagia. Therefore, early and thorough screening for swallowing impairment after acute ischemic stroke is crucial especially in those with multiple concomitant diseases., Trial Registration: Stroke Card Registry (NCT04582825), Stroke Card Trial (NCT02156778)., (© 2024. The Author(s).)

Introduction: There is increasing demand for accurate early fetal cardiac disease (FCD). We assessed the accuracy of early fetal echo (EFE) conducted in our high-volume fetal cardiac program and reviewed the spectrum of FCD, associated genetic anomalies, and outcomes encountered., Methods: We identified all EFEs performed from 10 +0 to 15 +6  weeks of gestation from 2009 to 2021. We compared findings at EFE to fetal echo at ≥18 +0  weeks or autopsy and documented genetic testing results for all FCD cases. For those with discrepancy between EFE and later exam, the discrepancy impact was reviewed. A score was used to quantify the anatomy assessed., Results: A total of 1,662 EFEs were performed in 1,387 pregnancies; all but 41 were considered diagnostic. Fetal cardiac disease was diagnosed at EFE in 130, including 101 major, 12 minor, 13 other FCD, and 4 arrhythmias. In 14/130 with FCD, endovaginal imaging was undertaken, which increased the score (1.6/9 vs 3.5/9; P = .049). Thirty-five of 130 had repeat EFE, which increased the score (5.2/9 vs 7.4/9, P < .0001). Fetal loss occurred before confirmation of FCD in 16 and termination in 64, and 11 were lost to follow-up. Thirty-nine had autopsy and/or fetal echo ≥18 +0 : 35 had FCD confirmed, and 4 had resolution. Of the 35 confirmed FCD, 27 had no, 7 minor, and 1 major change. Of 1,489 with normal EFE, later echo demonstrated FCD in 14: 3 major and 11 minor. In 16, FCD evolved, including 4 arrhythmias and 12 with progressive FCD. Sensitivity, specificity, and positive and negative predictive values of EFE in identifying major FCD were 92.9%, 100%, 100%, and 99.7%, respectively. In cases with FCD, 85.4% had genetic testing, of whom 71% (60.8% of the total) had abnormal results., Conclusions: In our experience, EFE permits accurate diagnosis and exclusion of most FCD. Endovaginal imaging and repeat EFE studies improved the ability to visualize structures adequately., Competing Interests: Conflicts of Interest None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: High-sensitivity cardiac troponin T (hs-cTnT) is associated with cardiovascular disease (CVD) risk in general and various high-risk populations., Objectives: The purpose of this study was to precisely characterize the association of hs-cTnT with CVD risk in patients following acute ischemic stroke or transient ischemic attack., Methods: We conducted post hoc analyses of data from the STROKE-CARD trial (NCT02156778), a pragmatic randomized controlled trial of a disease management program in patients with acute ischemic stroke or transient ischemic attack (ABCD 2 score ≥3). We measured hs-cTnT on admission (Roche Elecsys, detection limit 5 ng/L) and quantified HRs for a composite CVD outcome (ie, stroke, myocardial infarction, CVD death) adjusted for age, sex, prior coronary heart disease, prior heart failure, diabetes, smoking, systolic blood pressure, and low- and high-density-lipoprotein cholesterol., Results: Among 1,687 patients (mean age, 69.3 ± 13.7 years; 40.7% female), hs-cTnT was detectable in 80.7%. Median hs-cTnT was 10 ng/L (IQR: 6-18 ng/L). Over a median follow-up of 12.1 months, 110 patients had a CVD event. The association of hs-cTnT level with CVD risk was of log-linear shape, with a multivariable-adjusted HR of 1.40 (95% CI: 1.15-1.70; P  < 0.001) per 1-SD higher log-transformed hs-cTnT value. The strength of association was similar when further adjusted for other potential confounders and across clinically relevant subgroups. Corresponding outcome-specific HRs were 1.33 (95% CI: 1.06-1.68; P  = 0.016) for stroke, 1.28 (95% CI: 0.69-2.37; P  = 0.430) for myocardial infarction, 1.98 (95% CI: 1.43-2.73; P  < 0.001) for CVD death, and 1.93 (95% CI: 1.54-2.41; P  < 0.001) for all-cause death., Conclusions: High hs-cTnT is associated with increased CVD risk in ischemic stroke and transient ischemic attack patients., Competing Interests: The STROKE-CARD trial was financially supported by the University Hospital (Tirol Kliniken), Tyrolean Health Insurance Company (TGKK), the Tyrol Health Care Funds (TGF), and unrestricted research grants from Boehringer Ingelheim, Bayer Healthcare, Nstim Services, and Sanofi. Komarek, Lang, Knoflach, and Kiechl were supported by VASCage-Research Centre on Clinical Stroke Research. VASCage is a COMET Centre within the Competence Centers for Excellent Technologies (COMET) program and funded by the Federal Ministry for Climate Action, Environment, Energy, Mobility, Innovation and Technology, the Federal Ministry of Labor and Economy, and the federal states of Tyrol, Salzburg, and Vienna. COMET is managed by the Austrian Research Promotion Agency (Österreichische Forschungsförderungsgesellschaft). FFG Project number: 898252. Prof P. Willeit reports personal fees from Novartis Pharmaceuticals outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: This study suggests a graded association between elevated high-sensitivity cardiac troponin T concentration and cardiovascular risk in patients after ischemic stroke or transient ischemic attack. TRANSLATIONAL OUTLOOK: Future research is needed to clarify whether patients with elevated high-sensitivity cardiac troponin T benefit from additional targeted preventive measures, including a tailored cardiac workup., (© 2024 The Authors.)

The systemic inflammatory response following acute ischaemic stroke remains incompletely understood. We characterised the circulating inflammatory profile in 173 acute ischaemic stroke patients by measuring 65 cytokines and chemokines in plasma. Participants were grouped based on their inflammatory response, determined by high-sensitivity C-reactive protein levels in the acute phase. We compared stroke patients' profiles with 42 people experiencing spontaneous cervical artery dissection without stroke. Furthermore, variations in cytokine levels among stroke aetiologies were analysed. Follow-up samples were collected in a subgroup of ischaemic stroke patients at three and twelve months. Ischaemic stroke patients had elevated plasma levels of HGF and SDF-1α, and lower IL-4 levels, compared to spontaneous cervical artery dissection patients without stroke. Aetiology-subgroup analysis revealed reduced levels of nine cytokines/chemokines (HGF, SDF-1α, IL-2R, CD30, TNF-RII, IL-16, MIF, APRIL, SCF), and elevated levels of IL-4 and MIP-1β, in spontaneous cervical artery dissection (with or without ischaemic stroke as levels were comparable between both groups) compared to other aetiologies. The majority of cytokine/chemokine levels remained stable across the study period. Our research indicates that stroke due to large artery atherosclerosis, cardioembolism, and small vessel occlusion triggers a stronger inflammatory response than spontaneous cervical artery dissection., (© 2024. The Author(s).)

Background and Purpose: Dysphagia is associated with poor outcome, higher mortality, reduced quality of life, and social isolation. We investigate the relationship between swallowing impairment and symptoms of anxiety and depression after ischemic stroke., Methods: Consecutive patients with ischemic stroke participating in the prospective STROKE-CARD Registry study from 2020 to 2022 were assessed for dysphagia on hospital admission (clinical swallowing assessment) and for persistence until discharge and 3-month follow-up (SINGER Independency Index). Anxiety and depression symptoms were recorded using Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS) at 3-month follow-up., Results: Of 648 patients, 19.3% had dysphagia on admission, persisting in 14.8% at discharge and 6.8% at 3-month follow-up. With the presence or duration of dysphagia (no dysphagia, dysphagia at baseline, at discharge, at 3 months), score (mean ± SD) increased on the BDI (7.9 ± 6.7, 12.5 ± 8.7, 13.5 ± 9.0, 16.5 ± 10.2), HADS-D (4.4 ± 3.7, 7.1 ± 4.2, 7.7 ± 4.4, 9.8 ± 4.3), and HADS-A (4.4 ± 3.5, 5.4 ± 3.6, 6.0 ± 3.6, 7.0 ± 3.6). In linear regression analysis adjusting for age, sex, diabetes, dementia, and either functional disability or stroke severity, BDI and HADS-D scores were significantly higher in patients with dysphagia across all points in time (admission, discharge, 3-month follow-up). An independent association with HADS-A scores was only evident in patients with persisting dysphagia after 3 months. Patients with dysphagia were more likely to receive antidepressants, antipsychotics, or benzodiazepines at discharge and 3-month follow-up., Conclusions: Dysphagia after stroke is common and severely affects psychosocial functioning of individuals. Our results highlight swallowing impairment as an independent predictor for poststroke depressive and, to a lesser extent, anxiety symptoms., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Initiation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus type 2) vaccinations aroused scepticism within the general-public about risks including stroke. Our aim was to explore temporal associations between vaccination and cerebrovascular events through an analysis of a prospective large-scale cohort of consecutive stroke and high-risk TIA (transitory ischaemic attack) patients., Methods: We prospectively recruited a cohort of consecutive ischaemic stroke and high-risk TIA (ABCD2-Score ≥ 4) patients treated at the Innsbruck University Hospital (STROKE-CARD Registry Study, NCT04582825) from December 2020 until February 2022. SARS-CoV-2 vaccination status and the time of administration was ascertained by electronic health-data. A Cox model with vaccination status as time-dependent co-variable was employed to examine its association with ischaemic events., Results: Data on 572 participants were available with 355 (62.1%) vaccinated against SARS-CoV-2 before suffering cerebral ischaemia. In our cohort, no temporal association between vaccination and cerebrovascular event was detected (HR 1.06 [0.85-1.34; p = 0.60]) and this also applies to TIA (HR [0.82 0.37-1.85; p = 0.64]) or minor stroke (HR 1.18 [0.89-1.56; p = 0.26]) and subgroups defined by sex and age. Neither vector-based (HR 1.11 [0.79-1.56; p = 0.55]) nor mRNA-based (HR 1.06 [0.84-1.34; p = 0.61]) vaccinations were associated with the occurrence of cerebral ischaemia., Conclusion: Among patients with stroke or high-risk TIA, SARS-CoV-2 vaccination was not associated with cerebral ischaemia., Competing Interests: Declaration of Competing Interest The authors have no competing interests to report., (Copyright © 2023. Published by Elsevier B.V.)

Abstract: Platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4/polyanion enzyme-immunoassays and negative/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile). We tested these patients by a standard chemiluminescence assay that detects anti-PF4/heparin antibodies found in HIT (HemosIL AcuStar HIT-IgG(PF4-H)) as well as a novel chemiluminescence assay for anti-PF4 antibodies found in VITT. Representative control sera included an exploratory anti-PF4 antibody-positive but HIPA-negative/weak cohort obtained before 2020 (n = 188). We identified 9 patients with a clinical-pathological profile of a VITT-like disorder in the absence of proximate heparin or vaccination, with a high frequency of stroke (arterial, n = 3; cerebral venous sinus thrombosis, n = 4), thrombocytopenia (median platelet count nadir, 49 × 109/L), and hypercoagulability (greatly elevated D-dimer levels). VITT-like serological features included strong reactivity by PIPA (aggregation <10 minutes in 9/9 sera) and positive testing in the novel anti-PF4 chemiluminescence assay (3/9 also tested positive in the anti-PF4/heparin chemiluminescence assay). Our exploratory cohort identified 13 additional patient sera obtained before 2020 with VITT-like anti-PF4 antibodies. Platelet-activating VITT-like anti-PF4 antibodies should be considered in patients with thrombocytopenia, thrombosis, and very high D-dimer levels, even without a proximate exposure to heparin or adenovirus vector vaccines., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Spinels of the general formula Li 2-δ M 2 O 4 are an essential class of cathode materials for Li-ion batteries, and their optimization in terms of electrode potential, accessible capacity, and charge/discharge kinetics relies on an accurate understanding of the underlying solid-state mass and charge transport processes. In this work, we report a comprehensive impedance study of sputter-deposited epitaxial Li 2-δ Mn 2 O 4 thin films as a function of state-of-charge for almost the entire tetrahedral-site regime (1 ≤ δ ≤ 1.9) and provide a complete set of electrochemical properties, consisting of the charge-transfer resistance, ionic conductivity, volume-specific chemical capacitance, and chemical diffusivity. The obtained properties vary by up to three orders of magnitude and provide essential insights into the point defect concentration dependences of the overall electrode potential. We introduce a defect chemical model based on simple concentration dependences of the Li chemical potential, considering the tetrahedral and octahedral lattice site restrictions defined by the spinel crystal structure. The proposed model is in excellent qualitative and quantitative agreement with the experimental data, excluding the two-phase regime around 4.15 V. It can easily be adapted for other transition metal stoichiometries and doping states and is thus applicable to the defect chemical analysis of all spinel-type cathode materials., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: Continuous analysis of key epidemiologic data is irremissible to adapt health-care systems to trends in stroke epidemiology. We present data from 2015 to 2019 on quality indicators of stroke care, including rates on hospitalization, stroke unit care and recurrence rates using medical record-linkage of in-patient routine documentation., Patients and Methods: We included stroke/TIA patients admitted to Austrian hospitals between 2015 and 2019 aged ⩾20 years using medical record-linkage., Results: In our cohort of 102,107 patients with 107,055 treatment episodes, we could show a significant decrease in 1-year cumulative age-adjusted hospitalization rates per 100,000 in TIA (86.3 [95% CI 84.1-88.5] vs 75.4 [95% CI 73.4-77.4], RR 0.87 [95% CI 0.85-0.90]), ischemic stroke (187.3 [95% CI 184.0-190.5] vs 173.4 [95% CI 170.4-176.5], RR 0.93 [95% CI 0.91-0.94]), and intracerebral hemorrhage (28.5 [95% CI 27.3-29.8] vs 22.8 [95% CI 21.7-23.9], RR 0.80 [95% CI 0.76-0.84]). In ischemic stroke the rate of stroke unit care increased significantly (55.7% vs 69.3%; RR 1.14 [95% CI 1.12-1.17]), and acute 1-year recurrences decreased significantly., Discussion: We found a decline of the annual age-adjusted cumulative hospitalization rates in stroke/TIA, a higher age of disease manifestation and less severe strokes, which is probably attributable to improved primary and secondary prevention in Austria. The proportion of patients treated at stroke units increased significantly, however a geographical and age-dependency is still evident., Conclusion: Age-adjusted hospitalization rates of stroke/TIA patients decreased, and stroke unit care is increasing but the goal of the Stroke Action Plan for Europe is yet to be reached., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Introduction: Administrative health data are increasingly used for disease surveillance, quality assurance and research purposes. In Austria, reporting of a standardized dataset is mandatory for each patient., Patients and Methods: Routine documentation includes administrative and medical data, including admission and discharge characteristics, disease-diagnosis using ICD-10, medical procedure codes, and coding of involved hospital departments. Since 2015, a three-step pseudonymization on these data is provided including a pseudonym using secure hash algorithm 256, a non-recalculable record-ID, and age-groups of 5 years, allowing the reconstruction of individual patient-trajectories. We included persons aged ⩾20 years with an in-patient treatment in Austrian hospitals for acute stroke or transient ischemic attack (TIA) between 01.01.2015 and 31.12.2019 using medical record-linkage., Results: This totals 102,107 patients (49.3% women) with 107,055 treatment episodes. An ischemic stroke (IS) occurred in 60.9% ( n  = 65,133), 27.1% ( n  = 29,019) had a TIA, 3.3% ( n  = 3488) a subarachnoid hemorrhage, and 8.8% ( n  = 9415) an intracerebral hemorrhage (ICH). The study period covers 35.2 million person-years at risk, with a hospitalization rate for acute stroke of 221.8 per 100,000 person-years (95% CI 220.2-223.3), and 185.1 per 100,000 person-years (95% CI 183.7-186.5) for IS. Unscheduled re-admissions within 1 year occurred in 29.2% (95% CI 28.8-29.7) after IS, and 41.7% (95% CI 40.0-43.3) after ICH. Recurrent stroke occurred in 5.3% (95% CI 5.1-5.5) after IS, and 5.6% (95% CI 4.9-6.4) after ICH., Discussion: We present herein the details of a novel methodology to establish a nation-wide unselected Austrian stroke cohort, and to reconstruct pseudonymized individual longitudinal patient-trajectories on a national level. This approach shows potential applications in epidemiological research, quality assessment and outcome measurement., Conclusion: This novel approach opens new research fields, facilitates international comparison, and is needed for national benchmarking to assess the achievement of goals according to the Stroke Action Plan for Europe and augment the quality of Austria's integrated stroke care., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Background: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted., Methods: We aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3-6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management., Discussion: This long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run. Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019., (© 2022. The Author(s).)

Objective: Head/neck pain is one of the primary symptoms associated with spontaneous cervical artery dissection. Still, data on pain quality, intensity, and long-term dynamics are scarce., Methods: Spontaneous cervical artery dissection subjects were included if mural hematoma was visualised through T1 fat-saturated MRI at baseline. All available medical records were evaluated and patients were invited to standardised clinical follow-up visits at least 1 year after the index event., Results: In total, 279 subjects were included in the ReSect-study with head/neck pain being the most frequent symptom of spontaneous cervical artery dissection (220 of 273, 80.6%). Pain was of pulling nature in 107 of 218 (49.1%), and extended to the neck area in 145 of 218 (66.5%). In those with prior headache history, pain was novel in quality in 75.4% (42 of 55). Median patient-reported pain intensity was 5 out of 10 with thunderclap-type headache being uncommon (12 of 218, 5.5%). Prior to hospital admission, head/neck pain rarely responded to self-medication (32 of 218, 14.7%). Characteristics did not differ between subjects with and without cerebral ischemia. Pain resolved completely in all subjects within a median of 13.5 days (IQR 12). Upon follow-up in 42 of 164 (25.6%) novel recurring headache occurred, heterogeneous in quality, localisation and intensity., Conclusion: We present an in-depth analysis of spontaneous cervical artery dissection-related head/neck pain characteristics and its long-term dynamics.

Background: The aim of this study was to examine the diagnostic yield of current fetal echocardiography (FE) indications representing a recent era., Methods: FE reports of all pregnancies referred to two provincial FE programs from 2009 to 2018 were examined, identifying the indication for FE (14 categories), gestational age at referral, and whether there was no fetal heart disease (FHD), mild or possible FHD (e.g., simple ventricular septal defect, possible coarctation), or moderate or severe FHD., Results: Over the study period, there were 19,310 unique FE referrals in Alberta (23.3 ± 5.4 weeks' gestation), including 1,907 (9.9%) with moderate or severe and 654 (3.4%) with mild or possible FHD. The most common referral indications included extracardiac pathology or markers (29.7%), maternal diabetes (18.3%), suspected FHD (17.7%), and family history of heart defects (17.7%). The highest yield for moderate or severe FHD was suspected FHD (41.1%; 95% CI, 39.4%-42.7%), followed by suspected or confirmed genetic disorder (15.4%; 95% CI, 12.6%-18.2%), twins or multiples (10.6%; 95% CI, 8.7%-12.5%), oligohydramnios (8.0%; 95% CI, 4.1%-11.9%), extracardiac pathology or markers (6.4%; 95% CI, 5.8%-7.1%), and heart not well seen (5.8%; 95% CI, 4.0%-7.6%). Lowest yields were observed for maternal diabetes (2.2%; 95% CI, 1.7%-2.7%) and family history of heart defects (1.7%; 95% CI, 1.3%-2.2%). Excluding suspected FHD, with two or more FE indications, all other indications demonstrated significant increases in yield of mild or possible (3.5% vs 1.9%, P < .001) and moderate or severe (7.2% vs 2.9%, P < .001) FHD., Conclusions: Suspected FHD provides the highest diagnostic yield of moderate or severe FHD. In contrast, maternal diabetes and family history of heart defects, among the most common referral indications, had diagnostic yields approaching general population risks. Even in the absence of suspected FHD, having two or more referral indications importantly increases the diagnostic yield of all other FE indications., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

High- T c molecular magnets have amassed much promise; however, the long-standing obstacle for its practical applications is the inaccessibility of high-temperature molecular magnets showing dynamic and nonvolatile magnetization control. In addition, its functional durability is prone to degradation in oxygen and heat. Here, we introduce a rapid prototyping and stabilizing strategy for high T c (360 K) molecular magnets with precise spatial control in geometry. The printed molecular magnets are thermally stable up to 400 K and air-stable for over 300 days, a significant improvement in its lifetime and durability. X-ray magnetic circular dichroism and computational modeling reveal the water ligands controlling magnetic exchange interaction of molecular magnets. The molecular magnets also show dynamical and reversible tunability of magnetic exchange interactions, enabling a colossal working temperature window of 86 K (from 258 to 344 K). This study provides a pathway to flexible, lightweight, and durable molecular magnetic devices through additive manufacturing.

Short- to mid-term functional outcome in spontaneous cervical artery dissection is favorable, but the concomitant psychosocial impact is underreported. We aimed to determine these possible sequelae, with a special focus on sex differences, in our cohort of spontaneous cervical artery dissection subjects. During a standardized prospective in-house follow-up visit we, among other values, evaluated functional outcome (modified Rankin Scale [mRS]), psychosocial measures (return to work-, divorce rate) and health-related quality of life (WHO-QoL-BREF and SF-36-questionnaires). 145 patients participated in the long-term prospective follow-up. Median follow-up time was 6.5 years and excellent functional outcome (mRS ≤ 1) was achieved in 89.0% subjects. 87.6% returned to work and 17.6% married patients had a divorce during follow-up. Even though relevant baseline-/discharge characteristics and functional outcome did not differ between the sexes, women were less likely to return to work compared to men (79.7% vs. 93.8%; P = 0.010) and divorce rate was considerably higher in women (30.2% vs. 9.2%; P = 0.022). Health related quality of life did not differ significantly between the sexes, but women consistently reported lower values. Even though functional outcome is beneficial in most patients, measures to prevent poor psychosocial outcome should be considered in the long-term care of patients with spontaneous cervical artery dissection, especially women., (© 2022. The Author(s).)

Background: Recent advances in acute stroke therapy have been shown to improve clinical outcome and therefore reduce long-term disability. Acute therapy procedures in stroke have a limited time frame after onset of symptoms; thus, rapid emergency management is critical. The Tyrolean Stroke Pathway was developed to optimize the entire treatment pathway from stroke onset to outpatient rehabilitation., Objectives: The description of the Tyrolean Stroke Pathway as an example to optimize the entire treatment pathway of stroke patients in a central European alpine region with a focus on prehospital management., Materials and Methods: In four subprojects from the prehospital phase up to outpatient rehabilitation, the project optimized intersections between different phases of care and evaluated the care processes using quality assurance measures., Results: After implementation, thrombolysis rates doubled and functional outcome of stroke patients after 3 months improved and complications, e.g., pneumonia, declined. Access to rehabilitation improved, particularly because of the establishment of quality assured and funded outpatient rehabilitation., Conclusions: The project showed that a holistic standardized stroke pathway from acute management up to outpatient rehabilitation can be successfully implemented in clinical routine. The project improved the entire health care pathway of stroke patients. The Stroke Action Plan for Europe 2018-2030 recommends to have national plans for stroke that encompass the entire chain of care., (© The Author(s) 2022.)

Background and Purpose: The polypill approach has been proposed to reduce patients' pill burden, increase medication adherence and lower stroke incidence. However, little is known about patients' attitudes towards polypills for cerebrovascular medication., Methods: Based on the European Organization for Research and Treatment of Cancer Quality of Life Group questionnaire development guidelines, a questionnaire to measure patients' attitudes towards polypills for the secondary prevention of stroke (phase I-III) was developed. In phase I, issues were generated via literature review and interviews with patients and healthcare professionals. The issues were operationalized into items in phase II. In phase III the questionnaire was validated in a large single-centre sample, and test-retest and internal validity were evaluated., Results: In phase I, 34 relevant issues were identified through literature search and interviews. Pre-testing the questionnaire indicated high applicability and comprehensibility. The final Attitudes towards Polypills Questionnaire was tested in N = 260 patients and showed a two-factor structure. The factors were labelled 'concerns' and 'benefits'. The scales showed acceptable and good internal validity (concerns, Cronbach's α = 0.85; benefits, α = 0.93), but the scales' test-retest validity was ambiguous. On a 0 to 3 rating scale, concerns were rated lower than benefits (mean 1.07, SD 0.69 vs. mean 1.87, SD 0.89)., Conclusions: The Attitudes towards Polypills Questionnaire showed high comprehensibility and content validity to assess German language patients' attitudes towards a polypill medication. Our data and questionnaire may aid the implementation of polypill treatments in clinical practice and can be used in the design of future clinical trials on polypill therapy. Further validation of the questionnaire is advised., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Competing Interests: Declaration of interests TD declares minor shareholdings and an unpaid directorship at CapeRay Medical, which was an institution-based activity. WC declares he is the chief executive officer of a telemedicine company providing general medical consultation. All other authors declare no competing interests.

Background: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance., Methods: We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra., Results: Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis , of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF., Conclusion: We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays., Competing Interests: Conflict of interest: A. Penn-Nicholson reports grants from Bill and Melinda Gates Foundation, during the conduct of the study; reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: S.N. Gomathi reports grants from Indian Council of Medical Research - India TB Research Consortium, during the conduct of the study. Conflict of interest: C. Ugarte-Gil has nothing to disclose. Conflict of interest: A. Meaza has nothing to disclose. Conflict of interest: E. Lavu has nothing to disclose. Conflict of interest: P. Patel reports grants from the Indian Council of Medical Research through the National Institute for Research in Tuberculosis Chennai, during the conduct of the study. Conflict of interest: B. Choudhury reports grants from Indian Council of Medical Research – India TB Research Consortium through the National Institute for Research in Tuberculosis Chennai, during the conduct of the study. Conflict of interest: C. Rodrigues has nothing to disclose. Conflict of interest: S. Chadha reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: M. Kazi has nothing to disclose. Conflict of interest: A. Macé reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: P. Nabeta reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: C. Boehme reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: R.R. Gangakhedkar has nothing to disclose. Conflict of interest: S. Sarin reports grants from Bill and Melinda Gates Foundation, during the conduct of the study; and reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: E. Tesfaye has nothing to disclose. Conflict of interest: E. Gotuzzo has nothing to disclose. Conflict of interest: P. du Cros reports grants from FIND and the Australian Dept of Foreign Affairs and Trade during the conduct of the study; other (consultancy) from TB Alliance, outside the submitted work; and is a member of the steering committee for the MSF Sponsored TB PRACTECAL Clinical Trial for novel regimens for MDR-TB treatment. Conflict of interest: S. Tripathy reports grants from ICMR-India TB Research Consortium (ICMR-ITRC), during the conduct of the study. Conflict of interest: M. Ruhwald reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Conflict of interest: M. Singh has nothing to disclose. Conflict of interest: C.M. Denkinger reports grants from the Bill and Melinda Gates Foundation, during the conduct of the study; and reports working for FIND until April 2019. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. Since leaving FIND, C.M. Denkinger continues to hold a collaborative agreement with FIND. Conflict of interest: S.G. Schumacher reports working for FIND. FIND conducts multiple clinical research projects to evaluate multiple new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access., (Copyright ©The authors 2021.)