Transport strategy for ischaemic stroke patients with large vessel occlusion.

INTRODUCTION: There are today two models of transporting patients with acute ischaemic stroke because of large artery occlusion (AIS-LVO): mothership (MS) and drip-and-ship (DS). Our aim was to evaluate our ongoing transport strategy (OT), which is an MS/DS hybrid. In our OT, the patient is transported directly to the CT of the Primary Stroke Centre (PSC), where intravenous thrombolysis (IVT) is administered. The patient then continues without delay to a Comprehensive Stroke Centre (CSC) with the same medical rescue team (MRT). The distance between our centres is 73 km. MATERIAL AND METHODS: We retrospectively analysed data of 100 consecutive AIS-LVO patients treated with mechanical thrombectomy (MT) between January 2017 and October 2019. OT, MS and DS groups were compared. 31 patients were transported as MS, 32 as DS, and 37 as OT. RESULTS: DS had significantly longer time to groin puncture (185 min) compared to OT and MS (p < 0.0001). OT shortened time almost to MS level (OT 124 min, MS 110 min, p = 0.002. Time to IVT administration (from MRT departure) differed statistically significantly in favour of OT (OT 27 min, MS 63 min, p < 0.0001). Logistical change in PSC had a significant effect on decreasing the door-to-needle time (DNT) median from 37 min to 11 min (p < 0.0001). DNT reduction also occurred in patients with AIS and without an indication for MT. CONCLUSIONS: OT is highly effective, significantly reducing the time to IVT administration, and combining all the benefits, while eliminating all the disadvantages, of DS and MS. The OT concept gives all indicated patients a chance for MT to be performed, and does not overload the performing centre.

Ultrashort Door-to-Needle Time for Intravenous Thrombolysis Is Safer and Improves Outcome in the Czech Republic: Nationwide Study 2004 to 2019.

Background The benefit of intravenous thrombolysis is time dependent. It remains unclear, however, whether dramatic shortening of door-to-needle time (DNT) among different types of hospitals nationwide does not compromise safety and still improves outcome. Methods and Results Multifaceted intervention to shorten DNT was introduced at a national level, and prospectively collected data from a registry between 2004 and 2019 were analyzed. Generalized estimating equation was used to identify the association between DNT and outcomes independently from prespecified baseline variables. The primary outcome was modified Rankin score 0 to 1 at 3 months, and secondary outcomes were parenchymal hemorrhage/intracerebral hemorrhage (ICH), any ICH, and death. Of 31 316 patients treated with intravenous thrombolysis alone, 18 861 (60%) had available data: age 70±13 years, National Institutes of Health Stroke Scale at baseline (median, 8; interquartile range, 5-14), and 45% men. DNT groups 0 to 20 minutes, 21 to 40 minutes, 41 to 60 minutes, and >60 minutes had 3536 (19%), 5333 (28%), 4856 (26%), and 5136 (27%) patients. National median DNT dropped from 74 minutes in 2004 to 22 minutes in 2019. Shorter DNT had proportional benefit: it increased the odds of achieving modified Rankin score 0 to 1 and decreased the odds of parenchymal hemorrhage/ICH, any ICH, and mortality. Patients with DNT ≤20 minutes, 21 to 40 minutes, and 41 to 60 minutes as compared with DNT >60 minutes had adjusted odds ratios for modified Rankin score 0 to 1 of the following: 1.30 (95% CI, 1.12-1.51), 1.33 (95% CI, 1.15-1.54), and 1.15 (95% CI, 1.02-1.29), and for parenchymal hemorrhage/ICH: 0.57 (95% CI, 0.45-0.71), 0.76 (95% CI, 0.61-0.94), 0.83 (95% CI, 0.70-0.99), respectively. Conclusions Ultrashort initiation of thrombolysis is feasible, improves outcome, and makes treatments safer because of fewer intracerebral hemorrhages. Stroke management should be optimized to initiate thrombolysis as soon as possible optimally within 20 minutes from arrival to a hospital.

Nationwide screening for Fabry disease in unselected stroke patients.

BACKGROUND AND AIMS: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients. METHODS: A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males-enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3. RESULTS: 986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02-0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08-2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables. CONCLUSIONS: The prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.

Stroke 20 20: Implementation goals for intravenous thrombolysis.

INTRODUCTION: Knowledge of the implementation gap would facilitate the use of intravenous thrombolysis in stroke, which is still low in many countries. The study was conducted to identify national implementation targets for the utilisation and logistics of intravenous thrombolysis. MATERIAL AND METHOD: Multicomponent interventions by stakeholders in health care to optimise prehospital and hospital management with the goal of fast and accessible intravenous thrombolysis for every candidate. Implementation results were documented from prospectively collected cases in all 45 stroke centres nationally. The thrombolytic rate was calculated from the total number of all ischemic strokes in the population of the Czech Republic since 2004. RESULTS: Thrombolytic rates of 1.3 (95%CI 1.1 to 1.4), 5.4 (95%CI 5.1 to 5.7), 13.6 (95%CI 13.1 to 14.0), 23.3 (95%CI 22.8 to 23.9), and 23.5% (95%CI 23.0 to 24.1%) were achieved in 2005, 2009, 2014, 2017, and 2018, respectively. National median door-to-needle times were 60-70 minutes before 2012 and then decreased progressively every year to 25 minutes (IQR 17 to 36) in 2018. In 2018, 33% of both university and non-university hospitals achieved median door-to-needle time ≤20 minutes. In 2018, door-to-needle times ≤20, ≤45, and ≤60 minutes were achieved in 39, 85, and 93% of patients. DISCUSSION: Thrombolysis can be provided to ≥ 20% of all ischemic strokes nationwide and it is realistic to achieve median door-to-needle time 20 minutes. CONCLUSION: Stroke 20-20 could serve as national implementation target for intravenous thrombolysis and country specific implementation policies should be applied to achieve such target.

Concentrating stroke care provision in the Czech Republic: The establishment of Stroke Centres in 2011 has led to improved outcomes.

This article describes policy processes that have led to the re-organisation of stroke care in the Czech Republic since 2011, which has been part of a broader process of care concentration in several medical fields. Currently, stroke care is provided by 13 Comprehensive and 32 Primary Stroke Centres. The paper explains factors that supported the reform implementation, reviews implications, and discusses future challenges. Mandatory reporting of quality indicators, the introduction of a benchmarking system, integration with pre-hospital emergency care, and the introduction of countrywide patient triage have supported more timely treatment for stroke patients and better quality of care. Data from the Stroke Care Quality Indicators of the Czech Stroke Society show positive trends in many areas: the number of patients treated with intravenous thrombolysis quadrupled in eight years, with 26.4 % of all acute stroke patients receiving thrombolysis in 2018. Czech Republic now ranks third in Europe in the number of thrombolysis per population and second in the number of mechanical thrombectomies per population. The Czech experience provides an example of positive outcomes of concentrated stroke care, while highlighting the importance of proper implementation processes. In particular, it is essential to involve stakeholders and to provide reputational incentives through continuous benchmarking.

Pharmacogenetic algorithm for predicting daily dose of warfarin in Caucasian patients of Czech origin.

OBJECTIVES: Warfarin use is limited by a low therapeutic index and significant interindividual variability of the daily dose. The most important factor predicting daily warfarin dose is individual genotype, polymorphisms of genes CYP2C9 (warfarin metabolism) and VKORC1 (sensitivity for warfarin). Algorithms using clinical and genetic variables could predict the daily dose before the initiation of therapy. The aim of this study was to develop and validate an algorithm for the prediction of warfarin daily dose in Czech patients. METHODS: Detailed clinical data of patients with known and stable warfarin daily dose were collected. All patients were genotyped for polymorphisms in genes CYP2C9 and VKORC1. RESULTS: Included patients were divided into derivation (n=175) and validation (n=223) cohorts. The final algorithm includes the following variables: Age, height, weight, treatment with amiodarone and presence of variant alleles of genes CYP2C9 and VKORC1. The adjusted coefficient of determination is 72.4% in the derivation and 62.3% in the validation cohort (p<0.001). CONCLUSIONS: Our validated algorithm for warfarin daily dose prediction in our Czech cohort had higher precision than other currently published algorithms. Pharmacogenetics of warfarin has the potential in the clinical practice in specialized centers.

Development of Czech National Stroke Guidelines.

Despite a significant transformation of ischaemic stroke management, it remains one of the leading causes of death, disability, functional impairment and cognitive deficits. With the advent of intravenous thrombolysis and mechanical thrombectomy, stroke is not an untreatable disease, mostly occurring in older people, any more. The most common cause of cardioembolic strokes is atrial fibrillation or flutter and atrial fibrillation is the most prevalent arrhythmia.The aim of this short communication is to describe the methodology of the Czech stroke guidelines development.High-quality 2017 Australian Stroke Foundation stroke guideline was considered for adaptation and a new guideline was developed and disseminated.

Impact of Transcranial Doppler Ultrasound on Logistics and Outcomes in Stroke Thrombolysis: Results From the SITS-ISTR.

BACKGROUND AND PURPOSE: Diagnostic transcranial Doppler ultrasound (TCD) is commonly used in patients with acute stroke before or during treatment with intravenous thrombolysis (IVT). We aimed to assess how much TCD delays IVT initiation and whether TCD influences outcomes. METHODS: We analyzed data from the SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) collected from December 2002 to December 2011. Outcomes were door-to-needle time, symptomatic intracerebral hemorrhage, functional outcome per the modified Rankin Scale, and mortality at 3 months. RESULTS: In hospitals performing any TCD pre-IVT, 1701 of 11 265 patients (15%) had TCD before IVT initiation. Door-to-needle time was higher in patients with pre-IVT TCD (74 versus 60 minutes; P<0.001). At hospitals performing any TCD during IVT infusion, of 9044 patients with IVT, 747 were examined with TCD during IVT. No treatment delay was seen with TCD during IVT. After multivariate adjustment, TCD during IVT was independently associated with modestly increased excellent functional outcome (modified Rankin Scale, 0-1; adjusted odds ratio, 1.28; 95% confidence interval, 1.06-1.55; P=0.012) and lower mortality (adjusted odds ratio, 0.73; 95% confidence interval, 0.55-0.95; P=0.022). CONCLUSIONS: We recommend that TCD, if performed, should be done during IVT infusion, to avoid treatment delay. The association of hyperacute TCD with beneficial outcomes suggests potential impact on patient management, which warrants further study.

The bleeding risk during warfarin therapy is associated with the number of variant alleles of CYP2C9 and VKORC1 genes.

BACKGROUND: Warfarin is commonly used for the treatment and prevention of arterial and venous thromboembolism but its use is hindered by the risk of bleeding. The main reason for this risk is a narrow therapeutic index and a wide response variability after warfarin treatment. These shortcomings affect clinical outcomes including bleeding complications and may be associated with variant polymorphisms in the CYP2C9 and VKORC1 genes. AIM: It was the aim of this study to assess the impact of the total variant allele count of CYP2C9 and VKORC1 genes on bleeding related to warfarin treatment. METHODS: In a retrospective cohort-design study, patients were genotyped for polymorphisms in genes CYP2C9 (*1, *2, *3) and VKORC1 (haplotype A, B). Extensive clinical data were obtained. Adjusted hazard ratios (HR) for the occurrence of major bleeding events (MBE) were counted separately for the induction and maintenance phases of warfarin therapy. RESULTS: Out of the 329 patients in our clinical database, 194 patients were eligible and included in the analysis. MBE occurred in 51 patients (26.3%) during a mean follow-up of 26 months: 6 patients (11.8%) experienced early MBE during warfarin initiation, and 45 MBE occurred during the maintenance phase. The adjusted HR for MBE risk for patients with any CYP2C9 variant allele was 1.962 [95% confidence interval (CI) 1.08-3.56, p = 0.027]; for the VKORC1 AA haplotype, HR was 1.841 (95% CI 0.97-3.48, p = 0.06), while for 3 variant allele carriers of both genes, HR was 4.34 (95% CI 1.95-9.65, p < 0.001). Despite the insignificant association of the VKORC1 genotype with bleeding in our study, we have noted a warfarin dose-dependent effect with risk significance ascending: CYP2C9 *1/*1 + VKORC1 B/B < CYP2C9 *1/*1 + VKORC1 A/B < CYP2C9 *1/*2 + VKORC1 B/B. CONCLUSION: Patients who are carriers of 3 variant alleles of the genes CYP2C9 and VKORC1 exhibited a significantly higher risk of MBE during the initiation and maintenance phases of warfarin therapy. Vigilant and careful management of patients with a higher variant allele count, including switching to newer anticoagulants, could be considered in this high-risk cohort.

Dosing of tissue plasminogen activator often differs from 0.9 mg/kg, but does not affect the outcome.

BACKGROUND: The safety and efficacy of low- and high-dose intravenous tissue plasminogen activator (t-PA) for the treatment of acute ischemic stroke are poorly understood. In this multicenter study, we examined the relationships between different doses of t-PA and outcome. METHODS: Between 2006 and 2010, patients were enrolled if they were treated with t-PA on the basis of estimated body weight and on the subsequent availability of actual body weight. Based on the actual weight, patients were divided into lower (<0.85 mg/kg), standard (0.85-0.95 mg/kg), and higher (>0.95 mg/kg) t-PA dose groups. Differences in the outcomes of these groups were compared in terms of functional recovery (modified Rankin Scale [mRS] 0-1) at 3 months and the incidence of parenchymal hemorrhages on follow-up computed tomographic scans. RESULTS: This cohort study included 272 patients: 171 (63%) patients received the standard t-PA dose, 62 (23%) a lower dose, and 39 (14%) a higher dose. At 3 months, 51% of the standard dose patients achieved a mRS score of 0 to 1, compared with 50% in the lower dose and 44% in the higher dose groups. Parenchymal hemorrhage occurred in 4.7%, 6.5%, and 7.7% of patients in standard, lower, and higher dose groups, respectively. Compared with standard dose groups, no significant differences in functional recovery and parenchymal hemorrhage were observed in the lower and higher dose groups. CONCLUSIONS: In clinical practice, the actual dose of t-PA often differs from the recommended dose of 0.9 mg/kg, but this has no significant impact on the outcome after t-PA treatment.