Professional guideline versus product label selection for treatment with IV thrombolysis: an analysis from SITS registry

Introduction: Thrombolysis usage in ischaemic stroke varies across sites. Divergent advice from professional guidelines and product labels may contribute. Patients and methods: We analysed SITS-International registry patients enrolled January 2010 through June 2016. We grouped sites into organisational tertiles by number of patients arriving ≤2.5 h and treated ≤3 h, percentage arriving ≤2.5 h and treated ≤3 h, and numbers treated ≤3 h. We assigned scores of 1–3 (lower/middle/upper) per variable and 2 for onsite thrombectomy. We classified sites as lower efficiency (summed scores 3–5), medium efficiency (6–8) or higher efficiency (9–11). Sites were also grouped by adherence with European product label and ESO guideline: ‘label adherent’ (>95% on-label), ‘guideline adherent’ (≥5% off-label, ≥95% on-guideline) or ‘guideline non-adherent’ (>5% off-guideline). We cross-tabulated site-efficiency and adherence. We estimated the potential benefit of universally selecting by ESO guidance, using onset-to-treatment time-specific numbers needed to treat for day 90 mRS 0–1. Results: A total of 56,689 patients at 597 sites were included: 163 sites were higher efficiency, 204 medium efficiency and 230 lower efficiency. Fifty-six sites were ‘label adherent’, 204 ‘guideline adherent’ and 337 ‘guideline non-adherent’. There were strong associations between site-efficiency and adherence (P < 0.001). Almost all ‘label adherent’ sites (55, 98%) were lower efficiency. If all patients were treated by ESO guidelines, an additional 17,031 would receive alteplase, which translates into 1922 more patients with favourable three-month outcomes. Discussion: Adherence with product labels is highest in lower efficiency sites. Closer alignment with professional guidelines would increase patients treated and favourable outcomes. Conclusion: Product labels should be revised to allow treatment of patients ≤4.5 h from onset and aged ≥80 years

Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis

Cerebral edema (CED) is a severe complication of acute ischemic stroke. There is uncertainty regarding the predictors for the development of CED after cerebral infarction. We aimed to determine which baseline clinical and radiological parameters predict development of CED in patients treated with intravenous thrombolysis. We used an image-based classification of CED with 3 degrees of severity (less severe CED 1 and most severe CED 3) on postintravenous thrombolysis imaging scans. We extracted data from 42 187 patients recorded in the SITS International Register (Safe Implementation of Treatments in Stroke) during 2002 to 2011. We did univariate comparisons of baseline data between patients with or without CED. We used backward logistic regression to select a set of predictors for each CED severity. CED was detected in 9579/42 187 patients (22.7%: 12.5% CED 1, 4.9% CED 2, 5.3% CED 3). In patients with CED versus no CED, the baseline National Institutes of Health Stroke Scale score was higher (17 versus 10; P<0.001), signs of acute infarct was more common (27.9% versus 19.2%; P<0.001), hyperdense artery sign was more common (37.6% versus 14.6%; P<0.001), and blood glucose was higher (6.8 versus 6.4 mmol/L; P<0.001). Baseline National Institutes of Health Stroke Scale, hyperdense artery sign, blood glucose, impaired consciousness, and signs of acute infarct on imaging were independent predictors for all edema types. The most important baseline predictors for early CED are National Institutes of Health Stroke Scale, hyperdense artery sign, higher blood glucose, decreased level of consciousness, and signs of infarct at baseline. The findings can be used to improve selection and monitoring of patients for drug or surgical treatment

The SITS-UTMOST: a registry-based prospective study in Europe investigating the impact of regulatory approval of intravenous Actilyse in the extended time window (3–4.5 h) in acute ischaemic stroke

Introduction: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3–4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods: Inclusion of at least 1000 patients treated within 3–4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3–4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0–2, favourable outcome (mRS 0–1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N ¼ 1118 in the 3–4.5 h, N ¼ 3039 in the 0–3 h time window) and 3454 retrospective patients in the 0–3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3–4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3–4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion: Main weakness is the observational design of the study. Conclusion: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke

Are you suffering from a large arterial occlusion? Please raise your arm!

Background and purpose: Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke. Methods: Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined. Results: The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively. Conclusions: Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions

Stroke care indicators in the Republic of Moldova – the RES-Q registry

Introducere. Până la aderarea Moldovei in anul 2016 la platforma internațională RES-Q (Registry of Stroke Care Quality) - Registrul Calității Îngrijirii Accidentului Vascular Cerebral (AVC), nu au existat date privind indicatorii de calitate intraspitalicești ai ictusului. Scopul acestei lucrări a fost de a evalua calitatea asistenței medicale acordată pacienților cu AVC în Moldova în baza datelor registrului RES-Q. Material și metode. Au fost analizate datele tuturor pacienților cu ictus ischemic și hemoragic acut din registrul RES-Q din 15 spitale din Moldova. Datele au fost colectate timp de o lună pe an pe parcurs a 3 ani (2017-2019). Analiza datelor între spitale s-a realizat din considerentul accesului acestora la computer tomografia cerebrală. Adițional, datele din Moldova au fost comparate cu cele din trei țări ale proiectului ESO-EAST (European Stroke Organization Enhancing and Accelerating Stroke Treatment): România, Lituania și Georgia. Rezultate. Studiul a inclus un număr total de 1660 pacienți, cu vârsta medie de 68 ani (49% - bărbați). Moldova a înregistrat rezultate mai slabe la numărul de CT efectuate (81% [95% CI 79-84%]), la evaluarea disfagiei (29% [95% CI 27-32%]), efectuarea trombolizei intravenoase (3% [95% CI 2-4%]), administrarea de anticoagulante (44% [95% CI 39-49%]) și statine (42% [95% CI 39-45%]) la externare, la mortalitatea intraspitalicească prin AVC (17% [95% CI 15- 19%]). În interiorul Moldovei calitatea asistenței prin AVC s-a comparat reieșind din accesul la CT. Concluzii. Studiul nostru a identificat lacune serioase ale performanțelor asistenței intraspitalicești în ictus, cum ar fi lipsa scanărilor prin CT în multe spitale publice, absența unei rețele naționale centralizate în domeniul AVC, acces extrem de scăzut la tratamentul prin tromboliză și implementarea nesatisfăcătoare a tratamentului de profilaxie secundară a ictusului.Introduction. There were no data on in-hospital stroke care indicators until Moldova’s accession to the international Registry of Stroke Care Quality (RES-Q) platform in 2016. The aim of this paper was to assess the acute stroke care quality in Moldova based on the data of the RES-Q registry. Material and methods. We analyzed the data of all patients with acute ischemic and hemorrhagic stroke of the RES-Q from 15 Moldovan hospitals. Data were collected for one month each year, during a 3-year period (2017-2019). Data analysis was performed between hospitals according to their access to a brain CT facility for Moldovan participating hospitals. Additionally, Moldovan data were compared with other three ESO-EAST (European Stroke Organization Enhancing and Accelerating Stroke Treatment) project countries: Romania, Lithuania, and Georgia. Results. A total of 1660 patients were recruited in the study, mean age of 68 years (49% men). Moldova registered poorer results in number of brain CT performed (81% [95% CI 79-84%]), dysphagia screening (29% [95% CI 27-32%]), IV thrombolysis performed (3% [95% CI 2-4%]), administration of anticoagulants (44% [95% CI 39-49%]) and statins (42% [95% CI 39-45%]) at discharge, in-hospital stroke mortality (17% [95% CI 15- 19%]). Within Moldova the stroke care quality was driven by the access to CT scan. Conclusions. Our study highlighted some serious gaps of in-hospital stroke care performance in Moldova, such as the lack of CT scans in many public hospitals, the absence of a national stroke center network, extremely low accessibility of IV thrombolysis and unsatisfactory implementation of secondary stroke prevention treatment

How registry data are used to inform activities for stroke care quality improvement across 55 countries : A cross-sectional survey of Registry of Stroke Care Quality (RES-Q) hospitals

Background and purpose The Registry of Stroke Care Quality (RES-Q) is a worldwide quality improvement data platform that captures performance and quality measures, enabling standardized comparisons of hospital care. The aim of this study was to determine if, and how, RES-Q data are used to influence stroke quality improvement and identify the support and educational needs of clinicians using RES-Q data to improve stroke care. Methods A cross-sectional self-administered online survey was administered (October 2021–February 2022). Participants were RES-Q hospital local coordinators responsible for stroke data collection. Descriptive statistics are presented. Results Surveys were sent to 1463 hospitals in 74 countries; responses were received from 358 hospitals in 55 countries (response rate 25%). RES-Q data were used “always” or “often” to: develop quality improvement initiatives (n = 213, 60%); track stroke care quality over time (n = 207, 58%); improve local practice (n = 191, 53%); and benchmark against evidence-based policies, procedures and/or guidelines to identify practice gaps (n = 179, 50%). Formal training in the use of RES-Q tools and data were the most frequent support needs identified by respondents (n = 165, 46%). Over half “strongly agreed” or “agreed” that to support clinical practice change, education is needed on: (i) using data to identify evidence–practice gaps (n = 259, 72%) and change clinical practice (n = 263, 74%), and (ii) quality improvement science and methods (n = 255, 71%). Conclusion RES-Q data are used for monitoring stroke care performance. However, to facilitate their optimal use, effective quality improvement methods are needed. Educating staff in quality improvement science may develop competency and improve use of data in practice

Evaluation of miRNA detection methods for the analytical characteristics necessary for clinical utilization

miRNAs are promising biomarkers but methods for their measurement are not clear. We therefore examined three miRNA detection technologies and considered the analytical characteristics essential for clinical utilization. TaqMan assays, SplintR-qPCR and miREIA were compared for their absolute quantification bias, conformity and robustness. Absolute concentrations of miR-142-5p, miR-23a-3p and miR-93-5p were measured with all three methods using 30 samples. Robustness was evaluated by measurement of miR-21-5p in five uniform experiments. Correlations were miRNA-specific, but we observed a different absolute concentration range in RT-qPCR (fmol/mu l) and methods evading the RT process (amol/mu l). Consistently, RT-less methods reported better robustness (CV 8-19%) than RT-qPCR (CV 39-50%). The calibration curve in TaqMan Advanced assay was influenced by dilution media. Methods avoiding RT seem to be a promising future alternative for miRNA measurement. METHOD SUMMARY Three miRNA detection technologies were compared: 1) RT-qPCR where the RT step was performed with either a specific (TaqMan miRNA assay) or universal (TaqMan Advanced assay) priming strategy; 2) miREIA technology, using hybridization and specific antibody to DNA/RNA hybrids and 3) SplintR-qPCR, which utilizes a hybridization and ligation step followed by qPCR

Action Plan for Stroke in Europe 2018–2030

Two previous pan-European consensus meetings, the 1995 and 2006 Helsingborg meetings, were convened to review the scientific evidence and the state of current services to identify priorities for research and development and to set targets for the development of stroke care for the decade to follow. Adhering to the same format, the European Stroke Organisation (ESO) prepared a European Stroke Action Plan (ESAP) for the years 2018 to 2030, in cooperation with the Stroke Alliance for Europe (SAFE). The ESAP included seven domains: primary prevention, organisation of stroke services, management of acute stroke, secondary prevention, rehabilitation, evaluation of stroke outcome and quality assessment and life after stroke. Research priorities for translational stroke research were also identified. Documents were prepared by a working group and were open to public comments. The final document was prepared after a workshop in Munich on 21–23 March 2018. Four overarching targets for 2030 were identified: (1) to reduce the absolute number of strokes in Europe by 10%, (2) to treat 90% or more of all patients with stroke in Europe in a dedicated stroke unit as the first level of care, (3) to have national plans for stroke encompassing the entire chain of care, (4) to fully implement national strategies for multisector public health interventions. Overall, 30 targets and 72 research priorities were identified for the seven domains. The ESAP provides a basic road map and sets targets for the implementation of evidence-based preventive actions and stroke services to 2030

Global Stroke Statistics 2023: Availability of reperfusion services around the world

Background: Disparities in the availability of reperfusion services for acute ischaemic stroke are considerable globally, and require urgent attention. Contemporary data on the availability of reperfusion services in different countries provide the necessary evidence to prioritise where access to acute stroke treatment is needed. // Aims: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services. Methods: We searched PubMed to identify original papers, published up to January 2023, with the most recent, representative and relevant data for each country. Keywords included thrombolysis and telemedicine. We also screened reference lists of review papers, citation history of papers, and the grey literature. The information is provided as a narrative summary. // Results: Of 11,222 potentially eligible papers retrieved, 148 were included for review following de-duplications and full text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and Pre-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (6463% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulances services (80% in HICs) around the world. // Conclusion: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world

Supplemental material for Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study

Supplemental material, sj-docx-1-wso-10.1177_17474930221095965 for Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study by Irene Escudero-Martínez, Marius Matusevicius, Ana Pavia-Nunes, Petr Sevcik, Miroslava Nevsimalova, Viiu-Marika Rand, Janika Kõrv, Manuel Cappellari, Robert Mikulik, Danilo Toni and Niaz Ahmed in International Journal of Stroke.Boehringer Ingelheim.Peer reviewe