Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.

BACKGROUND AND AIMS: Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores. METHODS: We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset). RESULTS: Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance. DISCUSSION: Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.

Estimates of protection levels against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season: the IMMUNEBRIDGE project.

PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants ≥ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

Effects of a multimodal intervention in primary care to reduce second line antibiotic prescriptions for urinary tract infections in women: parallel, cluster randomised, controlled trial.

OBJECTIVES: To evaluate whether a multimodal intervention in general practice reduces the proportion of second line antibiotic prescriptions and the overall proportion of antibiotic prescriptions for uncomplicated urinary tract infections in women. DESIGN: Parallel, cluster randomised, controlled trial. SETTING: General practices in five regions in Germany. Data were collected between 1 April 2021 and 31 March 2022. PARTICIPANTS: General practitioners from 128 randomly assigned practices. INTERVENTIONS: Multimodal intervention consisting of guideline recommendations for general practitioners and patients, provision of regional data for antibiotic resistance, and quarterly feedback, which included individual first line and second line proportions of antibiotic prescribing, benchmarking with regional or supra-regional practices, and telephone counselling. Participants in the control group received no information on the intervention. MAIN OUTCOME MEASURES: Primary outcome was the proportion of second line antibiotics prescribed by general practices, in relation to all antibiotics prescribed, for uncomplicated urinary tract infections after one year between the intervention and control group. General practices were randomly assigned in blocks (1:1), with a block size of four, into the intervention or control group using SAS version 9.4; randomisation was stratified by region. The secondary outcome was the prescription proportion of all antibiotics, relative within all cases (instances of UTI diagnosis), for the treatment of urinary tract infections after one year between the groups. Adverse events were assessed as exploratory outcomes. RESULTS: 110 practices with full datasets identified 10 323 cases during five quarters (ie, 15 months). The mean proportion of second line antibiotics prescribed was 0.19 (standard deviation 0.20) in the intervention group and 0.35 (0.25) in the control group after 12 months. After adjustment for preintervention proportions, the mean difference was -0.13 (95% confidence interval -0.21 to -0.06, P<0.001). The overall proportion of all antibiotic prescriptions for urinary tract infections over 12 months was 0.74 (standard deviation 0.22) in the intervention and 0.80 (0.15) in the control group with a mean difference of -0.08 (95% confidence interval -0.15 to -0.02, P<0.029). No differences were noted in the number of complications (ie, pyelonephritis, admission to hospital, or fever) between the groups. CONCLUSIONS: The multimodal intervention in general practice significantly reduced the proportion of second line antibiotics and all antibiotic prescriptions for uncomplicated urinary tract infections in women. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00020389.

The structured ambulatory post-stroke care program for outpatient aftercare in patients with ischaemic stroke in Germany (SANO): an open-label, cluster-randomised controlled trial.

BACKGROUND: Patients with ischaemic stroke are at risk of recurrent stroke. In this study, we aimed to compare the effect of a structured ambulatory post-stroke care programme versus usual care on recurrent vascular events and death and control of cardiovascular risk factors. METHODS: We did a prospective, open-label, cluster-randomised controlled trial (SANO) at stroke centres in regions of Germany. A cluster was defined as a region in which acute stroke care is provided by a participating stroke centre. Patients were eligible for participation if they were aged 18 years or older, had no severe disabilities before the index stroke (modified Rankin scale 0-1), had at least one modifiable cardiovascular risk factor, and presented within 14 days of symptom onset of their first ischaemic stroke. The participating regions were randomly assigned (1:1) to the intervention and control group (usual care) by the statistician using block randomisation (block sizes of six), stratified by rural and urban regions. In intervention regions, a cross-sectoral multidisciplinary network was established to provide a 1-year organisational and patient-centred intervention. Due to the type of intervention, masking of participants and study physicians was not possible. Endpoint adjudication was performed by an independent endpoint adjudication committee who were masked to cluster allocation. The primary endpoint was a composite of recurrent stroke, myocardial infarction, and all-cause death within 12 months after baseline assessment, assessed in the modified intention-to-treat (mITT) population, which included all patients who did not withdraw consent and completed the primary endpoint assessment at 12 months. This study was registered with the German Clinical Trials Register, DRKS00015322. FINDINGS: Between Jan 1, 2019 and Dec 22, 2020, 36 clusters were assessed for eligibility, of which 30 were randomly assigned to the intervention group (n=15 clusters) or control group (n=15 clusters). No clusters dropped out of the study. 1203 (86%) of 1396 enrolled patients in the intervention group and 1283 (92%) of 1395 enrolled patients in the control group were included in the mITT population. The primary endpoint was confirmed in 64 (5·3%) of 1203 patients in the intervention group and 80 (6·2%) of 1283 patients in the control group (unadjusted odds ratio [OR] 0·80 [95% CI 0·49-1·30]; adjusted OR [aOR] 0·95 [95% CI 0·54-1·67]). All-cause deaths occurred in 31 (2·4%) of 1203 patients in the intervention group and 12 (1·0%) of 1283 patients in the control group. The incidence of serious adverse events was higher in the intervention group (266 [23·1%] of 1151) than the control group (106 [9·2%] of 1152). Falls (134 [11·4%] of 1203 patients in the intervention group; 39 [3·3%] of 1152 patients in the control group), hypertensive crisis (55 [4·7%]; 34 [2·8%]), and diagnosis of depression (51 [4·3%]; 13 [1·1%]) were the most frequent adverse events in both groups. No differences were identified in the rate of readmission to hospital between groups. INTERPRETATION: No differences were identified between patients with ischaemic stroke in the intervention group and control group with regard to the incidence of vascular events 1 year after baseline assessment, despite positive effects with regard to the control of some cardiovascular risk factors. Longer-term effects and other potentially favourable effects on stroke-related sequelae and quality of life require further evaluation. FUNDING: Innovation Fund of the Federal Joint Committee.

Cardiac dysfunction and high-sensitive C-reactive protein are associated with troponin T elevation in ischemic stroke: insights from the SICFAIL study.

BACKGROUND: Troponin elevation is common in ischemic stroke (IS) patients. The pathomechanisms involved are incompletely understood and comprise coronary and non-coronary causes, e.g. autonomic dysfunction. We investigated determinants of troponin elevation in acute IS patients including markers of autonomic dysfunction, assessed by heart rate variability (HRV) time domain variables. METHODS: Data were collected within the Stroke Induced Cardiac FAILure (SICFAIL) cohort study. IS patients admitted to the Department of Neurology, Würzburg University Hospital, underwent baseline investigation including cardiac history, physical examination, echocardiography, and blood sampling. Four HRV time domain variables were calculated in patients undergoing electrocardiographic Holter monitoring. Multivariable logistic regression with corresponding odds ratios (OR) and 95% confidence intervals (CI) was used to investigate the determinants of high-sensitive troponin T (hs-TnT) levels ≥14 ng/L. RESULTS: We report results from 543 IS patients recruited between 01/2014-02/2017. Of those, 203 (37%) had hs-TnT ≥14 ng/L, which was independently associated with older age (OR per year 1.05; 95% CI 1.02-1.08), male sex (OR 2.65; 95% CI 1.54-4.58), decreasing estimated glomerular filtration rate (OR per 10 mL/min/1.73 m2 0.71; 95% CI 0.61-0.84), systolic dysfunction (OR 2.79; 95% CI 1.22-6.37), diastolic dysfunction (OR 2.29; 95% CI 1.29-4.02), atrial fibrillation (OR 2.30; 95% CI 1.25-4.23), and increasing levels of C-reactive protein (OR 1.48 per log unit; 95% CI 1.22-1.79). We did not identify an independent association of troponin elevation with the investigated HRV variables. CONCLUSION: Cardiac dysfunction and elevated C-reactive protein, but not a reduced HRV as surrogate of autonomic dysfunction, were associated with increased hs-TnT levels in IS patients independent of established cardiovascular risk factors. Registration-URL: https://www.drks.de/drks_web/; Unique identifier: DRKS00011615.

Acceptance of Different Self-sampling Methods for Semiweekly SARS-CoV-2 Testing in Asymptomatic Children and Childcare Workers at German Day Care Centers: A Nonrandomized Controlled Trial.

Importance: Closure of day care centers (DCCs) to contain the COVID-19 pandemic has been associated with negative effects on children's health and well-being. Objective: To investigate the acceptance of self-sampling methods for continuous SARS-CoV-2 surveillance among asymptomatic children and childcare workers (CCWs) in DCCs. Design, Setting, and Participants: This nonrandomized pilot study included children and CCWs at 9 DCCs in Wuerzburg, Germany, from May to July 2021. Interventions: Twice weekly testing for SARS-CoV-2 was conducted by self-sampled mouth-rinsing fluid (saliva sampling [SAL], with subsequent pooled polymerase chain reaction test) plus nasal rapid antigen self-test (RAgT) (group 1), SAL only (group 2), or RAgT only (group 3) in children and CCWs. Main Outcomes and Measures: Main outcomes were rates for initial acceptance and successful (≥60% of scheduled samples) long-term participation. The probability of SARS-CoV-2 introduction into DCCs was modeled as a function of age-adjusted background incidence and DCC size. Results: Of 836 eligible children, 452 (54.1%; 95% CI, 50.7%-57.4%) participated (median [IQR] age: 4 [3-5] years; 213 [47.1%] girls), including 215 (47.6%) in group 1, 172 (38.1%) in group 2, and 65 (14.4%) in group 3. Of 190 CCWs, 139 (73.2%; 95% CI, 66.4%-79.0%) participated (median [IQR] age: 30 [25-46] years; 128 [92.1%] women), including 96 (69.1%) in group 1, 29 (20.9%) in group 2, and 14 (10.1%) in group 3. Overall, SARS-CoV-2 PCR tests on 5306 SAL samples and 2896 RAgTs were performed in children, with 1 asymptomatic child detected by PCR from SAL. Successful long-term participation was highest in group 2 (SAL only; children: 111 of 172 [64.5%]; CCWs: 18 of 29 [62.1%]). Weekly participation rates in children ranged from 54.0% to 83.8% for SAL and from 44.6% to 61.4% for RAgT. Participation rates decreased during the study course (P < .001). The probability of SARS-CoV-2 introduction into a DCC with 50 children was estimated to reach at most 5% for an age-adjusted SARS-CoV-2 incidence below 143. Conclusions and Relevance: Self-sampling for continuous SARS-CoV-2 testing was well accepted, with SAL being the preferred method. Given the high number of negative tests, thresholds for initiating continuous testing should be established based on age-adjusted SARS-CoV-2 incidence rates. Trial Registration: German Registry for Clinical Trials Identifier: DRKS00025546.

Stroke care during the COVID-19 pandemic: Case numbers, treatments, and mortality in two large German stroke registries.

Background and purpose: At the beginning of the SARS-CoV-2 pandemic, an alarming decline in hospitalizations for stroke was reported in several countries, including Germany. We assessed hospitalization numbers and indicators of the quality of stroke care in 2020 during the pandemic containment measures. Materials and methods: The analysis was based on data of two large stroke quality assurance registries in the north and the south of Germany (Qualitätssicherung Schlaganfall Nordwestdeutschland and Bayerische Arbeitsgemeinschaft für Qualitätssicherung in der stationären Versorgung). We included 395 hospitals with 467,931 documented cases in 2018-2020. The time interval between admission and thrombolysis, frequency of systemic thrombolysis and intra-arterial therapy (IAT), National Institutes of Health Stroke Scale (NIHSS) score on admission and in-hospital mortality were assessed. Changes in the second (Q2) and fourth (Q4) quarters of 2020 were compared to corresponding quarters in 2019 by chi-squared tests. Results: Hospitalization numbers decreased in the two stroke registries by 8% and 10% in Q2 of 2020 and by 5% and 15% in Q4 of 2020 compared to the same quarters in 2019, respectively. The decline was particularly seen in women and patients with transient ischemic attacks. In cases with cerebral infarction, no increase in NIHSS scores on admission was observed, and the proportion of patients with a time interval between admission and thrombolysis of ≤60 min was unchanged. No clear pattern was found in the frequency of systemic thrombolysis and IAT. In one of the registries, in-hospital mortality of patients with cerebral infarction increased in Q2 of 2020 compared to Q2 of 2019. Conclusion: Case numbers slightly decreased under pandemic conditions, while our quarterly analysis indicated that the quality of stroke care was largely unchanged throughout the year 2020.

Corrigendum: Parents' and childcare workers' perspectives toward SARS-CoV-2 test and surveillance protocols in pre-school children day care centers: A qualitative study within the german Wü-KiTa-CoV project.

[This corrects the article DOI: 10.3389/fmed.2022.897726.].

Parents' and Childcare Workers' Perspectives Toward SARS-CoV-2 Test and Surveillance Protocols in Pre-school Children Day Care Centers: A Qualitative Study Within the German Wü-KiTa-CoV Project.

Background: Feasibility of surveillance through continuous SARS-CoV-2 testing in pre-school children and childcare workers (CCWs) to prevent closure of day care centers (DCCs) was proven in the Wü-KiTa-CoV study. The purpose of this study was to describe the factors that facilitate or hinder the implementation of continuous SARS-CoV-2 testing from the perspective of parents and CCWs involved in the study. Methods: A total of 148 semi-structured telephone interviews, repeated before and after the implementation of the surveillance protocols, were conducted with parents and CCWs belonging to the DCCs involved in Wü-KiTa-CoV and analyzed using qualitative content analysis. Results: Five main topical categories that influences implementation of surveillance protocols for SARS-CoV-2 in DCCs emerged: Generating valuable knowledge, Impact on daily life, Communication and information, Children's wellbeing and the Sense of security. Smooth integration in daily routines, quickly delivered test results, and efficient communication and information between the study team and the participants were identified as factors that had a positive impact on implementation. To ensure children's wellbeing, the introduction of non-invasive testing procedures such as saliva testing, parental involvement to motivate, and prepare children for the procedure, the creation of a child-friendly environment for testing, and use of child-friendly explanations were considered critical. The surveillance was found to increase the sense of security during the pandemic. Conversely, reliability of tests in the surveillance protocols, low participation rates, non-transparent communication, the need to travel to testing sites, fear of quarantine in case of positive test results, concerns about higher workloads, the fear of unpleasant feelings for children, their young age, and changing test teams were considered as hindering factors. Conclusion: This qualitative study of parents of children in day care and DCC staff under surveillance through continuous testing for SARS-CoV-2 in nine German DCCs identified several factors that facilitate or hinder its implementation. These should be considered when planning screening interventions to prevent the spread of SARS-CoV-2 or other infectious diseases in pre-school children DCCs.

Feasibility of SARS-CoV-2 Surveillance Testing Among Children and Childcare Workers at German Day Care Centers: A Nonrandomized Controlled Trial.

Importance: Closure of day care centers has been implemented globally to contain the COVID-19 pandemic but has negative effects on children's health and psychosocial well-being. Objective: To investigate the feasibility of surveillance among children and childcare workers and to model the efficacy of surveillance on viral spread prevention. Design, Setting, and Participants: This nonrandomized controlled trial was conducted at 9 day care centers in Wuerzburg, Germany, from October 2020 to March 2021. Participants included children attending day care, childcare workers, and household members. Participating day care centers were assigned to different surveillance modules in a nonrandomized feasibility study. A mathematical model for SARS-CoV-2 spread in day care centers was developed to identify optimal surveillance. Interventions: Modules 1, 2, and 3 involved continuous surveillance of asymptomatic children and childcare workers by SARS-CoV-2 polymerase chain reaction testing of either midturbinate nasal swabs twice weekly (module 1) or once weekly (module 2) or self-sampled saliva samples twice weekly (module 3). Module 4 involved symptom-based, on-demand testing of children, childcare workers, and their household members by oropharyngeal swabs. All participants underwent SARS-CoV-2 antibody status testing before and after the sampling period. Questionnaires on attitudes and perception of the pandemic were administered in weeks 1, 6, and 12. Mathematical modeling was used to estimate SARS-CoV-2 spread in day care centers. Main Outcomes and Measures: The primary outcomes were acceptance of the respective surveillance protocols (feasibility study) and the estimated number of secondary infections (mathematical modeling). Results: Of 954 eligible individuals (772 children and 182 childcare workers), 592 (62%), including 442 children (median [IQR] age, 3 [2-4] years; 214 [48.6%] female) and 150 childcare workers (median [IQR] age, 29 [25-44] years; 129 [90.8%] female) participated in the surveillance. In total, 4755 tests for SARS-CoV-2 detected 2 infections (1 childcare worker and 1 adult household member). Acceptance for continuous surveillance was highest for biweekly saliva testing (150 of 221 eligible individuals [67.9%; 95% CI, 61.5%-73.7%]) compared with biweekly (51 of 117 individuals [43.6%; 95% CI, 35.0%-52.6%]) and weekly (44 of 128 individuals [34.4%; 95% CI, 26.7%-43.0%]) midturbinate swabbing (P < .001). Dropout rates were higher for midturbinate swabbing (biweekly, 11 of 62 participants [18%]; once weekly, 11 of 55 participants [20%]) than for saliva testing (6 of 156 participants [4%]). Mathematical modeling based on study and literature data identified biweekly testing of at least 50% of children and childcare workers as minimal requirements to limit secondary infections. Conclusions and Relevance: In this nonrandomized controlled trial, surveillance for SARS-CoV-2 in 9 German day care centers was feasible and well accepted. Mathematical modeling estimated that testing can minimize the spread of SARS-CoV-2 in day care centers. These findings enable setup of surveillance programs to maintain institutional childcare. Trial Registration: German Registry for Clinical Trials Identifier: DRKS00023721.

Feasibility of platelet marker analysis in ischemic stroke patients and their association with one-year outcome. A pilot project within a subsample of the Stroke Induced Cardiac Failure in Mice and Men (SICFAIL) cohort study.

Patients with ischemic stroke (IS) are at increased risk of mortality and recurrent cerebro- or cardiovascular events. Determining prognosis after IS remains challenging but blood-based biomarkers might provide additional prognostic information. As platelets are crucially involved in the pathophysiology of vascular diseases, platelet surface proteins (PSP) are promising candidates as prognostic markers in the hyperacute stage. In this pilot study, feasibility of PSP analysis by flow cytometry (HMGB1, CD84, CXCR4, CXCR7, CD62p with and without ADP-stimulation, CD41, CD61, CD40, GPVI) was investigated in 99 (median 66 years, 67.5% male) acute IS patients admitted to Stroke Unit within a substudy of the Stroke-Induced Cardiac FAILure in mice and men (SICFAIL) cohort study. Association between PSP expression and unfavorable one-year outcome (cerebro- or cardiovascular event, all-cause mortality and care dependency defined as Barthel Index <60) was explored. PSP measurements were feasible. Several process- (e.g. temperatures, processing times) and patient-related factors (e.g. prestroke ischemic events, surgery, blood pressure, antiplatelet therapy) were identified to be potentially associated with PSP expression. Elevated CD40 levels above study population's median were associated with unfavorable outcome. Standardized conditions during blood draw and processing within the hyperacute stroke unit setting are required and patient-related characteristics must be considered for valid measurements of PSP.Trial registration: German Clinical Trials Register (DRKS00011615).

REDuction of Antibiotic RESistance (REDARES) in urinary tract infections using treatments according to national clinical guidelines: study protocol for a pragmatic randomized controlled trial with a multimodal intervention in primary care.

BACKGROUND: Urinary tract infections (UTIs) are a common cause of prescribing antibiotics in family medicine. In Germany, about 40% of UTI-related prescriptions are second-line antibiotics, which contributes to emerging resistance rates. To achieve a change in the prescribing behaviour among family physicians (FPs), this trial aims to implement the guideline recommendations in German family medicine. METHODS/DESIGN: In a randomized controlled trial, a multimodal intervention will be developed and tested in family practices in four regions across Germany. The intervention will consist of three elements: information on guideline recommendations, information on regional resistance and feedback of prescribing behaviour for FPs on a quarterly basis. The effect of the intervention will be compared to usual practice. The primary endpoint is the absolute difference in the mean of prescribing rates of second-line antibiotics among the intervention and the control group after 12 months. To detect a 10% absolute difference in the prescribing rate after one year, with a significance level of 5% and a power of 86%, a sample size of 57 practices per group will be needed. Assuming a dropout rate of 10%, an overall number of 128 practices will be required. The accompanying process evaluation will provide information on feasibility and acceptance of the intervention. DISCUSSION: If proven effective and feasible, the components of the intervention can improve adherence to antibiotic prescribing guidelines and contribute to antimicrobial stewardship in ambulatory care.  Trial registration DRKS, DRKS00020389, Registered 30 January 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020389 .

Trial design and pilot phase results of a cluster-randomised intervention trial to improve stroke care after hospital discharge - The structured ambulatory post-stroke care program (SANO).

INTRODUCTION: Previous studies showed insufficient control of cardiovascular risk factors (CVRF) and high stroke recurrence rates among ischemic stroke patients in Germany. Currently, no structured secondary prevention program exists in clinical routine. We present the trial design and pilot phase results of a complex intervention to improve stroke care after hospital discharge in Germany. PATIENTS AND METHODS: SANO is a cluster-randomized trial with 30 participating regions across Germany aiming to enrol 2,790 patients (drks.de, DRKS00015322). Study intervention combines both structural and patient-centred elements. Study development was based on the Medical Research Council framework for complex interventions. In 15 intervention regions, a cross-sectoral multidisciplinary network is established to enhance CVRF control as well as detection and treatment of post-stroke complications. Recommendations on CVRF are based on high-quality secondary prevention guidelines. Study physicians use motivational interviewing and agree with patients on therapeutic targets. While hospitalised, patients also receive dietary counselling and a health-passport to track their progress. During regular visits, CVRF management and potential complications are monitored. The intervention is compared to 15 regions providing usual care. The primary endpoint is the combination of recurrent stroke, myocardial infarction and death assessed 12 months after enrolment and adjudicated in a blinded manner. RESULTS: Eighteen patients were enrolled in a pilot phase that demonstrated feasibility of patient recruitment and study procedures. CONCLUSION: SANO is investigating a program to reduce outcome events after ischemic stroke by implementing a complex intervention. If successful, the program may be implemented in routine care on national level in Germany.

Association of Infarct Volume Before Hemicraniectomy and Outcome After Malignant Infarction.

OBJECTIVE: To determine the impact of infarct volume before hemicraniectomy in malignant middle cerebral artery infarction (MMI) as an independent predictor for patient selection and outcome prediction, we retrospectively analyzed data of 140 patients from a prospective multicenter study. METHODS: Patients from the Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY) Registry who underwent hemicraniectomy after ischemic infarction of >50% of the middle cerebral artery territory were included. Functional outcome according to the modified Rankin Scale (mRS) was assessed at 12 months. Unfavorable outcome was defined as mRS score of 4 to 6. Infarct size was quantified semiautomatically from CT or MRI before hemicraniectomy. Subgroup analyses in patients fulfilling inclusion criteria of randomized trials in younger patients (age ≤60 years) were predefined. RESULTS: Among 140 patients with complete datasets (34% female, mean [SD] age 54 [11] years), 105 (75%) had an unfavorable outcome (mRS score >3). Mean (SD) infarct volume was 238 (63) mL. Multivariable logistic regression identified age (odds ratio [OR] 1.08 per 1-year increase, 95% confidence interval [CI] 1.02-1.13, p = 0.004), infarct size (OR 1.27 per 10-mL increase, 95% CI 1.12-1.44, p < 0.001), and NIH Stroke Scale score (OR 1.10, 95% CI 1.01-1.20, p = 0.030) before hemicraniectomy as independent predictors of unfavorable outcome. Findings were reproduced in patients fulfilling inclusion criteria of randomized trials in younger patients. Infarct volume thresholds for prediction of unfavorable outcome with high specificity (94% in overall cohort and 92% in younger patients) were >258 mL before hemicraniectomy. CONCLUSION: Outcome in MMI depends strongly on age and infarct size before hemicraniectomy. Standardized volumetry may be helpful in the process of decision-making concerning hemicraniectomy.

Stroke Angel: Effect of Telemedical Prenotification on In-Hospital Delays and Systemic Thrombolysis in Acute Stroke Patients.

INTRODUCTION: Door-to-CT scan time (DCT) and door-to-needle time (DNT) are important process measures in acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). We examined the impact of a telemedical prenotification by emergency medical service (EMS) (called the "Stroke Angel" program) on DCT and DNT and IVT rate compared to standard of care. PATIENTS AND METHODS: Two prospective observational studies including AIS patients admitted via EMS from 2011 to 2013 (cohort I; n = 496) and from January 1, 2015 to May 31, 2018 (cohort II; n = 349) were conducted. After cohort I, the 4-Item Stroke Scale and a digital thrombolysis protocol were added. Multivariable logistic and linear regression analysis was performed. RESULTS: In cohort I, DCT was lower in the intervention group (13 vs. 26 min using standard of care; p < 0.001), but no significant difference in median DNT (35 vs. 39 min; p = 0.24) was observed. In cohort II, a reduction of DCT (8 vs. 15 min; p < 0.001) and DNT (25 vs. 29 min p = 0.003) was observed in the intervention group. Compared to standard of care, the likelihood of DCT ≤10 min or DNT ≤20 min in the intervention group was 2.7 (adjusted odds ratio [aOR] 2.7; 95% CI: 2.1-3.5) and 1.8 (aOR 1.8; 95% CI: 1.1-2.9), respectively. In cohort II, IVT rate was higher (aOR 1.4; 95% CI: 1.1-1.9) in the intervention group. CONCLUSION: Although the positive effects of Stroke Angel in AIS provided a rationale for implementation in routine care, larger studies of practice implementation will be needed. Using Stroke Angel in the prehospital management of AIS impacts on important process measures of IVT delivery.

Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020.

BACKGROUND AND PURPOSE: The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. METHODS: In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in-hospital and (telemedical) stroke care during the pandemic was conducted. RESULTS: Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID-19 measures in May/June 2020 were observed. Compared to 2018-2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID-19, there were no relevant shortcomings reported regarding in-hospital stroke treatment or telemedical stroke care. CONCLUSIONS: Telemedical stroke care in Germany was able to provide full service despite the COVID-19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID-19 measures in Germany.

Prevalence and determinants of systolic and diastolic cardiac dysfunction and heart failure in acute ischemic stroke patients: The SICFAIL study.

AIMS: Ischaemic stroke (IS) might induce alterations of cardiac function. Prospective data on frequency of cardiac dysfunction and heart failure (HF) after IS are lacking. We assessed prevalence and determinants of diastolic dysfunction (DD), systolic dysfunction (SD), and HF in patients with acute IS. METHODS AND RESULTS: The Stroke-Induced Cardiac FAILure in mice and men (SICFAIL) study is a prospective, hospital-based cohort study. Patients with IS underwent a comprehensive assessment of cardiac function in the acute phase (median 4 days after IS) including clinical examination, standardized transthoracic echocardiography by expert sonographers, and determination of blood-based biomarkers. Information on demographics, lifestyle, risk factors, symptoms suggestive of HF, and medical history was collected by a standardized personal interview. Applying current guidelines, cardiac dysfunction was classified based on echocardiographic criteria into SD (left ventricular ejection fraction < 52% in men or <54% in women) and DD (≥3 signs of DD in patients without SD). Clinically overt HF was classified into HF with reduced, mid-range, or preserved ejection fraction. Between January 2014 and February 2017, 696 IS patients were enrolled. Of them, patients with sufficient echocardiographic data on SD were included in the analyses {n = 644 patients [median age 71 years (interquartile range 60-78), 61.5% male]}. In these patients, full assessment of DD was feasible in 549 patients without SD (94%). Prevalence of cardiac dysfunction and HF was as follows: SD 9.6% [95% confidence interval (CI) 7.6-12.2%]; DD in patients without SD 23.3% (95% CI 20.0-27.0%); and clinically overt HF 5.4% (95% CI 3.9-7.5%) with subcategories of HF with preserved ejection fraction 4.35%, HF with mid-range ejection fraction 0.31%, and HF with reduced ejection fraction 0.78%. In multivariable analysis, SD and fulfilment of HF criteria were associated with history of coronary heart disease [SD: odds ratio (OR) 3.87, 95% CI 1.93-7.75, P = 0.0001; HF: OR 2.29, 95% CI 1.04-5.05, P = 0.0406] and high-sensitive troponin T at baseline (SD: OR 1.78, 95% CI 1.31-2.42, P = 0.0003; HF: OR 1.66, 95% CI 1.17-2.33, P = 0.004); DD was associated with older age (OR 1.08, 95% CI 1.05-1.11, P < 0.0001) and treated hypertension vs. no hypertension (OR 2.84, 95% CI 1.23-6.54, P = 0.0405). CONCLUSIONS: A substantial proportion of the study population exhibited subclinical and clinical cardiac dysfunction. SICFAIL provides reliable data on prevalence and determinants of SD, DD, and clinically overt HF in patients with acute IS according to current guidelines, enabling further clarification of its aetiological and prognostic role.

A Self-administered Version of the Functioning Assessment Short Test for Use in Population-based Studies: A Pilot Study.

BACKGROUND: The Functioning Assessment Short Test (FAST) is an interviewer-administered scale assessing functional impairment originally developed for psychiatric patients. OBJECTIVES: To adapt the FAST for the general population, we developed a self-administered version of the scale and assessed its properties in a pilot study. METHODS: The original FAST scale was translated into German via forward and backward translation. Afterwards, we adjusted the scale for self-administered application and inquired participants from two ongoing studies in Germany, 'STAAB' (Würzburg) and 'BiDirect' (Münster), both recruiting subjects from the general population across a wide age range (STAAB: 30-79 years, BiDirect: 35-65 years). To assess reliability, agreement of self-assessment with proxy-assessment by partners was measured via intraclass correlation coefficient (ICC) over the FAST score. Construct validity was estimated by conducting correlations with validated scales of depression (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) and regression analyses using these scales besides potentially disabling comorbidities (e.g. Chronic Back Pain (CBP)). RESULTS: Participants (n=54) had a median age of 57.0 years (quartiles: 49.8, 65.3), 46.3% were female. Reliability was moderate: ICC 0.50 (95% CI 0.46-0.54). The FAST score significantly correlated with PHQ-9, GAD-7, and the mental sub-scale of SF-12. In univariable linear regression, all three scales and chronic back pain explained variance of the FAST score. In multivariable analysis, only CBP and the SF-12 remained significant predictors. CONCLUSION: The German self-administered version of the FAST yielded moderate psychometric properties in this pilot study, indicating its applicability to assess functional impairment in the general population.

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.

Twenty-Year Time Trends in Long-Term Case-Fatality and Recurrence Rates After Ischemic Stroke Stratified by Etiology.

BACKGROUND AND PURPOSE: Data on long-term survival and recurrence after stroke are lacking. We investigated time trends in ischemic stroke case-fatality and recurrence rates over 20-years stratified by etiological subtype according to the Trial of ORG 10172 in Acute Stroke Treatment classification within a population-based stroke register in Germany. METHODS: Data was collected within the Erlangen Stroke Project, a prospective, population-based stroke register covering a source population of 105 164 inhabitants (2010). Case fatality and recurrence rates for 3 months, 1 year, and 5 years were estimated with Kaplan-Meier estimates. Sex-specific time trends for case-fatality and recurrence rates were estimated with Cox regression. We adjusted for age, sex, and year of event and stratified for etiological subtypes. A sensitivity analysis with competing risk analysis for time trends in recurrence were performed. RESULTS: Between 1996 and 2015, 3346 patients with first ischemic stroke were included; age-standardized incidence per 100 000 was 75.8 in women and 131.6 in men (2015). Overall, 5-year survival probabilities were 50.4% (95% CI, 47.9-53.1) in women and 59.2% (95% CI, 56.4-62.0) in men; 5-year survival was highest in patients with first stroke due to small-artery occlusion (women, 71.8% [95% CI, 67.1-76.9]; men, 75.9% [95% CI, 71.3-80.9]) and lowest in cardioembolic stroke (women, 35.7% [95% CI, 31.0-41.1]; men, 47.8% [95% CI, 42.2-54.3]). Five-year recurrence rates were 20.1% (95% CI, 17.5-22.6) in women and 20.1% (95% CI, 17.5-22.7) in men; 5-year recurrence rate was lowest in women in stroke due to small artery occlusion 16.0% (95% CI, 11.7-20.1) and in men in large-artery atherosclerosis 16.6% (95% CI, 8.7-23.9); highest risk of recurrence was observed in undefined strokes (women, 22.3% [95% CI, 17.8-26.6]; men, 21.4% [95% CI, 16.7-25.9]). Cox regression revealed improvements in case-fatality rates over time with differences in stroke causes. No time trends in recurrence rates were observed. CONCLUSIONS: Long-term survival and recurrence varied substantially by first stroke cause. Survival probabilities improved over the past 2 decades; no major trends in stroke recurrence rates were observed.