Ten Years of Improving Acute Stroke Management in a Metropolitan Area: A Population-Based Quantification of Quality Indicators.

BACKGROUND AND PURPOSE: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. METHODS: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. RESULTS: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). CONCLUSIONS: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

Association Between Adherence to Quality Indicators and 7-Day In-Hospital Mortality After Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Quality indicators (QI) are an accepted tool to measure performance of hospitals in routine care. We investigated the association between quality of acute stroke care defined by overall adherence to evidence-based QI and early outcome in German acute care hospitals. METHODS: Patients with ischemic stroke admitted to one of the hospitals cooperating within the ADSR (German Stroke Register Study Group) were analyzed. The ADSR is a voluntary network of 9 regional stroke registers monitoring quality of acute stroke care across 736 hospitals in Germany. Quality of stroke care was defined by adherence to 11 evidence-based indicators of early processes of stroke care. The correlation between overall adherence to QI with outcome was investigated by assessing the association between 7-day in-hospital mortality with the proportion of QI fulfilled from the total number of QI the individual patient was eligible for. Generalized linear mixed model analysis was performed adjusted for the variables age, sex, National Institutes of Health Stroke Scale and living will and as random effect for the variable hospital. RESULTS: Between 2015 and 2016, 388 012 patients with ischemic stroke were reported (median age 76 years, 52.4% male). Adherence to distinct QI ranged between 41.0% (thrombolysis in eligible patients) and 95.2% (early physiotherapy). Seven-day in-hospital mortality was 3.4%. The overall proportion of QI fulfilled was median 90% (interquartile range, 75%-100%). In multivariable analysis, a linear association between overall adherence to QI and 7-day in-hospital-mortality was observed (odds ratio adherence <50% versus 100%, 12.7 [95% CI, 11.8-13.7]; P<0.001). CONCLUSIONS: Higher quality of care measured by adherence to a set of evidence-based process QI for the early phase of stroke treatment was associated with lower in-hospital mortality.

[Quality of life and disability after severe stroke and early neurological rehabilitation]. / Lebensqualität und Behinderung nach schwerem Schlaganfall und neurologischer Frührehabilitation.

BACKGROUND: Data on the long-term effects on quality of life of patients after severe stroke and discharge from early institutional rehabilitation are important for guiding the early rehabilitation phase and the further outpatient care. OBJECTIVE: Analysis of the outcome of patients following severe stroke 3 and 12 months after discharge from early neurological rehabilitation. METHODS: Analysis of the Asklepios Hamburg multicenter early stroke rehabilitation registry (ICD 10: I61, I60, I63 and OPS 8­552). Structured interviews with documentation of disabilities using the early rehabilitation Barthel index (ERBI), modified Rankin scale (mRS) and quality of life (12-item short form health survey, SF-12). Assessment of further treatment and complications 3 and 12 months after discharge from the early rehabilitation departments by telephone interviews. RESULTS: Out of 1045 treated stroke patients 270 were enrolled between October 2015 and November 2017 and 200 and 151 patients could be followed up after 3 and 12 months, respectively. There was a significant improvement (p < 0.001) in the median ERBI (151 patients at 12 months). Factors influencing a poorer functional outcome (higher mRS) at 12 months were a higher mRS at discharge (OR 5.43 [1.18, 25.09], p = 0.03) and age (per decade OR 1.5 [1.09, 2.02]; p = 0.01). Female sex reduced the risk for a poorer outcome after 12 months (OR 0.49 [0.25, 0.96]; p = 0.04). Quality of life (SF-12) was not different over time. The mental quality of life showed no differences (p = 0.32) compared to a historical, significantly less (p<0.001) handicapped stroke collective. CONCLUSION: The surviving severe stroke patients recovered significantly up to 12 months after discharge. The mental quality of life did not differ from that of a historical less handicapped collective.

Stroke unit care in germany: the german stroke registers study group (ADSR).

BACKGROUND: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. METHODS: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. RESULTS: In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. CONCLUSIONS: Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low.

Safety of Endovascular Thrombectomy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants.

BACKGROUND AND PURPOSE: Prospective data on the safety of endovascular thrombectomy in acute stroke patients on non-vitamin K antagonist oral anticoagulants are lacking. METHODS: Prospective multicenter observational study. Patients with ischemic stroke undergoing thrombectomy with or without preceding thrombolysis were enrolled into the Registry of Acute Ischemic Stroke Under New Oral Anticoagulants. Baseline characteristics and functional outcome at 3 months were assessed. Hemorrhagic transformation and symptomatic intracranial hemorrhage were analyzed. Reperfusion was graded using the modified Thrombolysis in Cerebral Infarction score. RESULTS: Of 28 patients treated with thrombectomy, 5 had received also systemic thrombolysis (18%). Intracranial hemorrhage was observed in 46%, but symptomatic intracranial hemorrhage occurred only in 1 patient. Successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b-3) was achieved in 59%. At 3 months, 19% had a modified Rankin Scale score of 0 to 2, and mortality was 26%. CONCLUSIONS: Thrombectomy in non-vitamin K antagonist oral anticoagulant patients seems safe although a comparatively high rate of asymptomatic hemorrhagic transformation was noted. Confirmation in larger prospective controlled cohorts is necessary. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.

Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects.

3-Oxo-5-alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6-endo-dig cyclization reactions to furnish either 2-pyrones or 4-pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π-acid. This transformation is compatible with a variety of acid-sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4-pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co-solvent, which is thought to favor the protodeauration of the reactive alkenyl-gold intermediates as the likely rate-determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off-cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem-diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2-alkoxypyridine and 2-alkoxyisoquinoline derivatives starting from readily available imidate precursors.

The quality of acute stroke care- an analysis of evidence-based indicators in 260 000 patients.

BACKGROUND: Stroke patients should be cared for in accordance with evidence-based guidelines. The extent of implementation of guidelines for the acute care of stroke patients in Germany has been unclear to date. METHODS: The regional quality assurance projects that cooperate in the framework of the German Stroke Registers Study Group (Arbeitsgemeinschaft Deutscher Schlaganfall-Register, ADSR) collected data on the care of stroke patients in 627 hospitals in 2012. The quality of the acute hospital care of patients with stroke or transient ischemic attack (TIA) was assessed on the basis of 15 standardized, evidence-based quality indicators and compared across the nine participating regional quality assurance projects. RESULTS: Data were obtained on more than 260 000 patients nationwide. Intravenous thrombolysis was performed in 59.7% of eligible ischemic stroke patients patients (range among participating projects, 49.7-63.6%). Dysphagia screening was documented in 86.2% (range, 74.8-93.1%). For the following indicators, the defined targets were not reached for all of Germany: anti-aggregation within 48 hours, 93.4% (range, 86.6-96.4%); anticoagulation for atrial fibrillation, 77.6% (range, 72.4-80.1%); standardized dysphagia screening, 86.2% (range, 74.8-93.1%); oral and written information of the patients or their relatives, 86.1% (range, 75.4-91.5%). The rate of patients examined or treated by a speech therapist was in the target range. CONCLUSION: The defined targets were reached for most of the quality indicators. Some indicators, however, varied widely across regional quality assurance projects. This implies that the standardization of care for stroke patients in Germany has not yet been fully achieved.

Development of a new clot formation protocol for standardized in vitro investigations of sonothrombolysis.

BACKGROUND: Agreement about the most suitable clot formation protocol for sonothrombolysis investigations is lacking. Lysis rates vary strongly owing to different test conditions and, thus, cannot be compared. We aim to establish a simple but physiologically grounded protocol for in vitro coagulation to enable standardized sonothrombolysis investigations. METHOD: Clots were generated from platelet-rich plasma (PRP) obtained by centrifugation (10 min, 180 × g) of human venous blood (VB). PRP was mixed with the boundary layer formed between the supernatant and the erythrocyte layer. To achieve clots with different platelet counts, PRP was gradually substituted with platelet-free plasma (PFP), harvested from the supernatant of VB after centrifugation (10 min, 2570 × g). Clot types were examined for histological appearance, hydrodynamic resistance under physiological flows, and lysis rate measured by weight loss after a 2-h treatment with recombinant tissue plasminogen activator (rt-PA) (60 kU/ml). Lysis rates of the most suitable clot were measured after a 1-h treatment with rt-PA (60 kU/ml), and combined treatment with rt-PA and 2-MHz transcranial color-coded sonography (TCCS) (0.179 W/cm(2)) or 2-MHz transcranial Doppler (TCD) (0.457 W/cm(2)). RESULTS: With increased platelet count, the hydrodynamic resistance of the artificial clots increased, their histological appearance became more physiological, and lysis rates decreased. The most suitable clots consisted of 1.5-ml PRP, 2.0-ml PFP, and 0.5-ml boundary layer. Their lysis rates were 36.7 ± 7.8% (rt-PA), 40.8 ± 8.6% (rt-PA+TCCS), and 40.4 ± 8.3% (rt-PA+TCD). COMPARISON WITH EXISTING METHODS: These systemic investigations were conducted for the first time. CONCLUSION: This protocol should be used for standardized sonothrombolysis investigations.

Structure of a reactive gold carbenoid.

A formal gold-for-chromium transmetalation allowed the gold carbenoid species [Cy3 PAuCAr2 ]NTf2 (11) (Ar=pMeOC6 H4 -) to be obtained in crystalline form. The structure in the solid state suggests that there is only little back donation of electron density from gold to the carbene center of 11 and hence very modest AuC double-bond character; rather, it is the organic ligand framework that is responsible for stabilizing this species by resonance delocalization of the accumulated positive charge. Because 11 is capable of cyclopropanating p-methoxystyrene even at low temperature, the discussion of its structure is deemed relevant for a better understanding of the mechanisms of π-acid catalysis in general.

Gold carbenoids: lessons learnt from a transmetalation approach.

Carbophilic catalysts that are based on Au(I) allow a host of different nucleophiles to be added across various π systems. Although many of these reactions are thought to proceed via gold carbenoids, the challenge to observe and characterize these putative intermediates has basically been unmet. The current mechanistic interpretation therefore largely relies on indirect evidence and computational data, some of which are subject to debate. In an attempt to fill this gap, we pursued a potential route to gold carbenoids by formal transmetalation of chromium or tungsten Fischer carbene complexes with [LAu](+). Whereas this transformation proceeds with exceptional ease as long as a stabilizing heteroelement is present on the carbene center, it stops half-way in its absence. Rather unusual bimetallic arrays are formed, which allow the charge density to delocalize over several positions. The obvious difficulty of releasing an "unstabilized" gold carbenoid has potential mechanistic implications for the understanding of π-acid catalysis in general.

The prognostic impact of the stroke unit concept after transient ischemic attack.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) is associated with high short-term risk of stroke, especially in the early phase following the event. Data about the impact of the early hospitalization in a stroke unit on patients with TIA are sparse. This study compares the prognostic impact of the stroke unit concept with conventional care on patients with TIA. METHODS: During a 30-month period (beginning April 2005), 878 patients (mean age, 70±12years; 44.3% female) with TIA admitted within 24h of symptom onset were prospectively evaluated. The adjusted logistic regression analyses were used to estimate the odds ratio for the stroke risk during hospitalization and the 90-day mortality. RESULTS: Of 878 patients, 591 (67.3%) were treated in the stroke unit, and 287 (32.7%) underwent conventional care. Patients receiving stroke-unit care had significantly higher rates of cranial computed tomography (96.3% vs. 88.1%; P<.001) and brain-supplying artery ultrasound (97.1% vs. 91.3%; P<.001) investigations. The stroke risk during hospitalization was 1.7% in patients treated in stroke unit and 2.4% in patients received a conventional care. A relevant difference between the groups was not found (1.7% vs. 2.4%; P=.45). The 90-day mortality rate was 1.7% in the stroke unit group compared to 2.2% in the conventional care group (1.7% vs. 2.2%; P=.66). The adjusted logistic regression analyses revealed no difference in stroke rates (odds ratio, 0.68; 95% confidence interval, 0.24-1.9) and in the 90-day mortality (odds ratio, 0.63; 95% confidence interval, 0.2-1.96) between the stroke unit concept and conventional care. CONCLUSION: The prognostic impact of the stroke unit care for patients with transient ischemic attack appears to be similar to that of the conventional care. Further randomized studies are needed to investigate the impact of stroke-unit care on patients with transient ischemic attack.

Microvascular imaging in acute ischemic stroke.

BACKGROUND: Microvascular imaging (MVI), a new ultrasound technology, is used to analyze brain perfusion at the patient's bedside. This study aims to evaluate the diagnostic and prognostic value of MVI in patients with acute ischemic stroke (AIS). METHODS: Nineteen patients suffering from AIS (mean age, 70.9 ± 12.2 years; 47% female; mean NIHSS-score, 12 ± 8) were investigated within the first 12 hours after symptom onset. We used the iU22 (Philips) system (S5-1 probe; low-mechanical index; depth, 13 cm), and 2 bolus injections of an ultrasound contrast agent (2.4 mL SonoVue per injection). The area of maximal perfusion deficit (AMPD) was compared with infarction on follow-up cranial computed tomography (CT) and NIHSS score 24 hours after stroke onset. RESULTS: Of 19 patients, 15 patients (79%) had sufficient insonation conditions. Of these patients, 12 had infarctions. The sensitivity and specificity of detecting infarctions with ultrasound perfusion imaging were 91% and 67%, respectively. A significant correlation existed between the AMPD and NIHSS score at 24 hours after symptom onset (P= .023), and with occlusion of the internal carotid artery (P= .005). CONCLUSION: Performing bedside MVI in the early phase of AIS provides information on brain parenchyma perfusion and prognosis of AIS.

Optimized synthesis, structural investigations, ligand tuning and synthetic evaluation of silyloxy-based alkyne metathesis catalysts.

Nitride- and alkylidyne complexes of molybdenum endowed with triarylsilanolate ligands are excellent (pre)catalysts for alkyne-metathesis reactions of all sorts, since they combine high activity with an outstanding tolerance toward polar and/or sensitive functional groups. Structural and reactivity data suggest that this promising application profile results from a favorable match between the characteristics of the high-valent molybdenum center and the electronic and steric features of the chosen Ar(3)SiO groups. This interplay ensures a well-balanced level of Lewis acidity at the central atom, which is critical for high activity. Moreover, the bulky silanolates, while disfavoring bimolecular decomposition of the operative alkylidyne unit, do not obstruct substrate binding. In addition, Ar(3)SiO groups have the advantage that they are more stable within the coordination sphere of a high-valent molybdenum center than tert-alkoxides, which commonly served as ancillary ligands in previous generations of alkyne metathesis catalysts. From a practical point of view it is important to note that complexes of the general type [(Ar(3)SiO)(3)Mo≡X] (X = N, CR; R = aryl, alkyl, Ar = aryl) can be rendered air-stable with the aid of 1,10-phenanthroline, 2,2'-bipyridine or derivatives thereof. Although the resulting adducts are themselves catalytically inert, treatment with Lewis acidic additives such as ZnCl(2) or MnCl(2) removes the stabilizing N-donor ligand and gently releases the catalytically active template into the solution. This procedure gives excellent results in alkyne metathesis starting from air-stable and hence user-friendly precursor complexes. The thermal and hydrolytic stability of representative molybdenum alkylidyne and -nitride complexes of this series was investigated and the structure of several decomposition products elucidated.

Suzuki reactions of extended scope: the '9-MeO-9-BBN variant' as a complementary format for cross-coupling.

While the Suzuki coupling has gained paramount importance, the basic set-up of the reaction has remained essentially unchanged for decades. It consists of the palladium-catalyzed coupling of organoboron reagents with aryl- or alkenyl halides, -sulfonates or related electrophiles in the presence of a base. One of the few alternative formats for this transformation is the '9-MeO-9-BBN variant', which is distinguished by not requiring an added base as a promoter. Rather, polar organometallic reagents R-M (R = Me, alkyl, aryl, heteroaryl, alkenyl, alkynyl etc.) are first intercepted with 9-MeO-9-BBN to give the corresponding borinate complexes, which then pass the R-group onto an organopalladium complex generated in situ as the electrophilic partner. This procedure allowed the structural reach of the Suzuki coupling to be extended, and served in a host of advanced applications, most notably for elaborate sp-sp(2) and sp(3)-sp(2) coupling processes.

Introduction of a new model for time-continuous and non-contact investigations of in-vitro thrombolysis under physiological flow conditions.

BACKGROUND: Thrombolysis is a dynamic and time-dependent process influenced by the haemodynamic conditions. Currently there is no model that allows for time-continuous, non-contact measurements under physiological flow conditions. The aim of this work was to introduce such a model. METHODS: The model is based on a computer-controlled pump providing variable constant or pulsatile flows in a tube system filled with blood substitute. Clots can be fixed in a custom-built clot carrier within the tube system. The pressure decline at the clot carrier is measured as a novel way to measure lysis of the clot. With different experiments the hydrodynamic properties and reliability of the model were analyzed. Finally, the lysis rate of clots generated from human platelet rich plasma (PRP) was measured during a one hour combined application of diagnostic ultrasound (2 MHz, 0.179 W/cm2) and a thrombolytic agent (rt-PA) as it is commonly used for clinical sonothrombolysis treatments. RESULTS: All hydrodynamic parameters can be adjusted and measured with high accuracy. First experiments with sonothrombolysis demonstrated the feasibility of the model despite low lysis rates. CONCLUSIONS: The model allows to adjust accurately all hydrodynamic parameters affecting thrombolysis under physiological flow conditions and for non-contact, time-continuous measurements. Low lysis rates of first sonothrombolysis experiments are primarily attributable to the high stability of the used PRP-clots.

The platelet-rich plasma clot: a standardized in-vitro clot formation protocol for investigations of sonothrombolysis under physiological flows.

No agreement exists about which protocol for in-vitro clot formation is suitable for sonothrombolysis investigations. Lysis rates vary considerably because of different clotting processes and cannot be compared. We aim to establish a new protocol for in-vitro coagulation to permit standardized sonothrombolysis investigations. The proposed procedure is based upon clots prepared from platelet-rich plasma (PRP). This clot material (group A) was compared with the two most commonly used procedures, namely, recalcification of citrate-anticoagulated whole venous blood (group B) and spontaneous clotting of nonanticoagulated venous blood (group C). Histological examinations were performed and clot stability was tested under physiological flow conditions in vitro for all groups (each n = 10). Lysis rates measured by mass loss were compared using buffered plasma and recombinant tissue plasminogen activator (60 kU/ml), or buffered plasma alone. PRP clots displayed a high degree of similarity to emboli specimens in histological examinations and remained stable under pulsatile flow conditions. B and C clots were mechanically unstable and did not resist physiological flow and pressure. Measuring the lysis rate by weighing seems to be inaccurate, with lowest variability in PRP clots. PRP clots appeared more resistant to lysis. PRP clots should be used for standardized sonothrombolysis investigations.

Basal ganglia hyperechogenicity does not distinguish between patients with primary dystonia and healthy individuals.

Transcranial sonography (TCS) of the basal ganglia is a non-invasive tool to study movement disorders. Very few studies have addressed the question of whether TCS may detect specific echofeatures in patients with primary dystonia. The basal ganglia including the substantia nigra (SN) and the ventricular system were investigated by TCS in 84 primary dystonia patients and 43 neurologically healthy controls. Any hyperechogenicity of the lenticular nucleus was present in 57.5% of the patients and in 50.0% of the controls (p = 0.453). While marked hyperechogenicity was more frequently present in the patients (17.8 vs. 7.9%), this difference was not significant (p = 0.227). No differences in the occurrence of hyperechogenicity were detectable either in the caudate nucleus (21.6 vs. 39.5%, p = 0.122) or the thalamus (4.1 vs. 0%, p = 0.199). Marked hyperechogenicity of the caudate nucleus was rare in dystonia (4.1%) and absent in controls. There was no relationship between the side of basal ganglia hyperechogenicity and the clinically affected side of cervical dystonia. The area of SN echogenicity was similar in patients and controls (0.19 ± 0.14 vs. 0.20 ± 0.13 cm(2)), but correlated negatively with increasing disease duration in the dystonia patients (ρ = -0.257, p = 0.028). Width of the third ventricle correlated with increasing age (ρ = 0.511, p = 0.000) and, in patients, with disease duration (ρ = 0.244, p = 0.034) and severity of cervical dystonia (ρ = 0.281, p = 0.038). No characteristic abnormalities were found in the basal ganglia of primary dystonia patients. It remains to be explored whether this is due to a true absence of signal alterations in the basal ganglia of dystonia patients or to limitations of the current technology used.