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Background: The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany., Methods: We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence., Results: The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach., Discussion: BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care., Trial Registration: German Clinical Trial Register DRKS00028840. Registered on April 2022., Competing Interests: Declarations Ethics approval and consent to participate The study was approved in April 2022 by the central ethics committee in Würzburg (registry number 12/22-sc). All centres have obtained approval by the local ethics committees before recruitment. Written informed consent was obtained from all subjects before study participation. Consent for publication Not applicable. Competing interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AH, JW, IF, AB, TMD, PG, KiH, LH, KH, HM, VR, AS, CV declare that they or a family member have not had any economic or personal ties in the last 3 years. HB reports research grants from the Federal Joint Committee (G-BA) within the Innovationfond, during the conduct of the study; royalties or licenses from HelloBetter, consulting fees from Roche, speaker honoraria as a member of the digital agenda BPtK and for E-Mental-Health Lectures DRV-BW, SAMA, Medical Centre Göppingen, and Participation on a Data Safety Monitoring Board for IMMERSE EU-Project. EB reports Honoraria for a workshop at “6. Hamburger Tag der Psychoonkologie ´Krebs und Innovation´ “. SYB reports research grants from the Federal Joint Committee (G-BA) within the Innovationfond, during the conduct of the study; Advisory board honoraria and speaker fees received from Medtronic, Sanofi, Köhler, AstraZeneca, Lilly, MSD, Hologic, Roche. JeS reports speaker honoraria received from AstraZeneca, Clovis Oncology, Dajichi Sanko, GILEDA, GSK, Lilly, Novartis Pharma GmbH, Pfizer, SEAGEN; support for attending meetings and/or travel received from Dajichi Sanko, GILEDA, Lilly. MW reports research grants from the Federal Joint Committee (G-BA) within the Innovationfond, during the conduct of the study; personal fees, non-financial support, speaker fees, consultancy honoraria or grants received from Novartis, Pfizer, Roche, Celgene, Daiichi Sankyo, AstraZeneca. RP reports research grants from the Federal Joint Committee (G-BA) within the Innovationfond, during the conduct of the study. AW reports research grants from the Federal Joint Committee (G-BA) within the Innovationfond, during the conduct of the study; consulting fees received from AstraZeneca, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, MSD, Pierre Fabre, Clovis, Organon, Seagen, Exact Sciences, Gilead, Dajichi Sanko; speaker honoraria received from Aurikamed and Onkowissen; support for attending meetings and/or travel received from Pfizer, Dajichi Sanko, Seagan; leadership or fiduciary role in AGO, S3-Guideline Breast Cancer, German Society of Breast Cancer, BGGF. PUH reports research grants from the Federal Joint Committee (G-BA) within the Innovationfond, during the conduct of the study; research grants from the German Ministry of Research and Education, Federal Joint Committee (G-BA), European Union, German Parkinson Society, University Hospital Würzburg, German Heart Foundation, German Research Foundation, Bavarian State, German Cancer Aid, Charité – Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF randomised; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), outside the submitted work., (© 2024. The Author(s).)

As part of the Würzburg KiTa-CoV study series, SARS-CoV-2 pandemic-related attitudes/concerns of parents of preschool children attending day care centres were surveyed over a 21-month period. We expected associations between these parental attitudes/concerns and their change over the course of the pandemic, on the one hand, and the SARS-CoV-2 infection status of the children, on the other. Parents of children from nine day-care centres who completed a survey on pandemic-related attitudes/concerns in October 2020, July 2021 and July 2022, were included in the analysis. In July 2022, the children's infection status was determined by measuring nucleocapsid protein antibodies (N-AK) and, in the case of N-AK negative, unvaccinated children, the measurement results of spike protein antibodies (S-AK) against SARS-CoV-2 as indicators of previous infection were also taken into account. Changes in parental attitudes/concerns were analysed using trend tests, and their significance in predicting the child's infection status was analysed using multiple binomial regression analyses. Data were available from parents of 159 children (mean age 3.2 years). The overall group of parents showed an increasingly relaxed attitude towards the pandemic over the study period, although the parents' concerns towards a possible infection of their own increased. The infection status of the children could not be predicted from the initial attitudes and concerns of the parents. However, the subgroup of parents with an uninfected child tended to have a higher level of concerns over the course of the pandemic than the parents with an infected child and did not show the same increasing composure towards the pandemic event. The parents' increasing composure is understandable in the context of the reduced virulence of the virus variants prevailing over time, the increasing availability of testing strategies and vaccinations, and the withdrawal of pandemic-related restrictions. In addition, the mildness of most children's infections may have contributed to their parents' sense of security. The seemingly contradictory increase in parental concerns about infection may be related to the strong increase in the incidence due to omicron variant infections in the population since January 2022. It is possible that the higher level of concerns among parents of uninfected children had a protective effect behaviourally., Competing Interests: B. Weißbrich gab an, während der Durchführung der Studie Zuschüsse des Bundesministeriums für Bildung und Forschung erhalten zu haben. P. Heuschmann berichtete, dass er außerhalb der eingereichten Arbeit Zuschüsse vom Bundesministerium für Bildung und Forschung, der Europäischen Union, der Deutschen Parkinson Gesellschaft, der Deutschen Herzstiftung, dem Universitätsklinikum Würzburg, dem Robert-Koch-Institut, dem Gemeinsamen Bundesausschuss (G-BA) im Rahmen des Innovationsfonds, der Deutschen Forschungsgemeinschaft, der Charité-Universitätsmedizin Berlin (im Rahmen von Mondafis; Mondafis wird durch einen uneingeschränkten Forschungszuschuss an die Charité von Bayer unterstützt), der Universität Göttingen (im Rahmen von FIND-AF randomized; FIND-AF randomized wird durch einen uneingeschränkten Forschungszuschuss von Boehringer-Ingelheim an die Universität Göttingen unterstützt) und das Universitätsklinikum Heidelberg (im Rahmen von RASUNOA-prime; RASUNOA-prime wird durch einen uneingeschränkten Forschungszuschuss von Bayer, BMS, Boehringer-Ingelheim und Daiichi Sankyo an das Universitätsklinikum Heidelberg unterstützt) erhalten hat. O. Kurzai berichtete, dass er Zuschüsse vom Bundesministerium für Bildung und Forschung, vom Freistaat Bayern, aus COVID-Forschungsmitteln und vom Bayerischen Gesundheitsministerium über das Bayerische Landesamt für Gesundheit und Lebensmittelsicherheit erhalten hat, dass er von der Stadt Würzburg nicht-finanzielle Unterstützung in Form von Fahrzeugen für den Transport von Ausrüstung und Personal während der Durchführung der Studie erhalten hat, dass er Zuschüsse vom Bundesministerium für Bildung und Forschung und vom Bayerischen Gesundheitsministerium über das Bayerische Landesamt für Wissenschaft und Kunst außerhalb der eingereichten Arbeit erhalten hat und Mitglied des SARS-CoV-2-Expertengremien der Stadt und des Landkreises Würzburg ist. I. Gágyor gab an, während der Durchführung der Studie Förderung vom Bundesministerium für Bildung und Forschung Deutschland erhalten zu haben. M. Romanos gab an, während der Durchführung der Studie Zuschüsse vom Bundesministerium für Bildung und Forschung erhalten zu haben. J. Liese berichtete, dass er außerhalb der eingereichten Arbeit Zuschüsse vom Bundesministerium für Bildung und Forschung, GlaxoSmithKline, Janssen-Cilag, Pfizer, MSD und Sanofi-Pasteur erhalten hat. A. Streng gab an, außerhalb der eingereichten Arbeit Zuschüsse von GlaxoSmithKline, Janssen-Cilag, Pfizer Pharma, MSD und Sanofi Pasteur erhalten zu haben. Alle anderen Autoren sind sich keiner Einflüsse bewusst, die die Objektivität dieses Manuskripts beeinträchtigen könnten, und erklärten, dass sie keine konkurrierenden Interessen haben., (Thieme. All rights reserved.)

Background: Since the beginning of the corona pandemic in Germany in January 2020, day care centres (DCC) have faced the challenge of reliably detecting cases of SARS-CoV-2 infection as early and reliably as possible in order to avoid major outbreaks and closures. Conducting regular virological screening tests for asymptomatic DCC children and childcare workers requires a high level of acceptance among participants and should be as easy as possible to implement. The present study aimed to evaluate childcare workers' and parents' attitudes and experiences regarding the acceptance and feasibility of various screening methods. This assessment was conducted using additional qualitative interviews designed for home-based screening in the context of a screening study in DCCs., Method: From May to July 2021, childcare workers and parents of children in nine DCCs in Wuerzburg independently carried out screening tests for SARS-CoV-2 at home twice a week as part of the "Würzburg Child Care Study in the COVID-19 Pandemic 2.0". The participants were offered two self-sampling methods (mouth-rinsing fluid for pooled PCR tests and/or nasal rapid antigen self-tests). Before and after the 12-week test phase, telephone interviews were conducted with a selected sample of childcare workers and parents in order to ascertain initial attitudes and further experiences with the two self-sampling methods and their implementation. The interviews were fully transcribed for analysis and subjected to a qualitative content analysis according to Kuckartz., Results: Of the 1,026 eligible participants, 591 individuals, including 139 childcare workers and the parents of 452 children, agreed to take part in the screening tests. A total of 49 interviews were conducted with a specifically selected sample (20 before the start of the test, 29 after the end of the test). In the qualitative content analysis, three overarching topics emerged: 'aspects of the test performance', 'aspects of the perception of safety' and 'aspects of the testing in children'. Regardless of the fact that the various test methods and test features were perceived very differently, conducting the tests at home was found to be feasible., Discussion: The differentiated insights into the participants' perspectives provide valuable information about factors that influence the acceptance of self-testing. These should be taken into account before such a measure is introduced in DCCs if necessary., Conclusion: The assessment of test procedures is strongly influenced by individual preferences. Test concepts should be implemented with as little time and organisational effort as possible in order to promote willingness to participate. Clear study information and quick feedback on test results can enhance the sense of security among parents and childcare workers., (Copyright © 2024. Published by Elsevier GmbH.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F.A.M., V.R., K.U, A.P., D.M., B.H., M.G., W.N.W, C.K., A.M., and J.M. have nothing to disclose. S.W. reports grants from the German Ministry of Research and Education and Deutsche Herzstiftung e.V. C.M. is supported by the IZKF, University Hospital Würzburg (advanced clinician-scientist program, ADVCSP-3) and the German Research Foundation (Comprehensive Research Center 1525 “Cardio-immune interfaces,” #453989101, project C5). CM reports research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; travel grants, advisory and speakers honoraria from Amgen, Tomtec, Orion Pharma, Alnylam, AKCEA, Sobi, Alexion, Janssen, Pfizer, and EBR Systems; principal investigator in trials sponsored by Alnylam, AstraZeneca, and Bayer. St.St. reports grants, personal fees, non-financial support, and/or other from Boehringer, Bayer, Thermo Fisher, and Pfizer; AstraZeneca, Sanofi, Servier, Alnylam, Ionis, Akcea; and Novartis, outside the submitted work. S.F. reports grants from the German Ministry of Research and Education during the conduct of the study. KGH reports speaker’s honoraria, consulting fees, lecture honoraria, and/or study grants from Abbott, Amarin, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, W.L. Gore and Associates. P.U.H. reports grants from German Ministry of Research and Education, during the conduct of the study; grants from German Ministry of Research and Education, European Union, Charité-Universitätsmedizin Berlin, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, German Research Foundation, Bavarian State, German Cancer Aid, Charité-Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF randomized; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), outside the submitted work.

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., (© 2023. The Author(s).)

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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/and declare: support from Innovation Fund coordinated by the Innovation Committee of the Federal Joint Committee (G-BA) in Germany (grant no. 01VSF18053) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of interests CJS reports lecture fees and honoraria from b4c-Solutions, Elsevier, and Boehringer-Ingelheim. HJA reports speaker fees and consultancy honoraria from Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb, NovoNordisk, Pfizer, and Roche; and grants from the German Ministry of Research and Education, Pfizer, and the German Stroke Foundation for research in secondary stroke prevention. STE reports research support from Bristol-Myers Squibb MS, Pfizer, and Daiichi-Sankyo. KG reports personal fees and travel expenses from Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer outside the submitted work. KGH reports grants from Bayer and Sanofi-Aventis; and lecture fees and advisory board fees from Abbott, Alexion, Amarin, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, EIP Pharma, Medtronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W L Gore and Associates. AM reports grants, consulting fees, and lecturing fees from Argenx, Alexion, Octapharma, UCB, Argenx, Axunio, Adivo, Janssen, Merck, Boehringer, Desitin, Dierks, Grifols, Hormosan, Pfizer, Bristol Myers Squibb, and Xcenda. RV is an investigator of the NIHR Imperial Biomedical Research Centre and reports fees for consulting and speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Daichi Sankyo, Portola, Biogen, Medtronic, and Morphosys; and research grants from Bayer, Boehringer, Bristol Myers Squibb, Pfizer, Daiichi Sankyo, and Medtronic (RASUNOA-PRIME, ODEA-study), outside of the present work. PUH reports grants from the German Ministry of Research and Education, European Union, German Parkinson Society, University Hospital Würzburg, the German Heart Foundation, Federal Joint Committee within the Innovationfond, German Research Foundation, Bavarian State, German Cancer Aid, Charité–Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, and Daiichi Sankyo), outside the submitted work. FAE, VR, ALH, MK, SvB, DG, GFH, DS, MS, and AJG declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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 m 2 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&#95;web/; Unique identifier: DRKS00011615., (© 2022. The Author(s).)

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.

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., (Copyright © 2022 Brunssen, Rücker, Heuschmann, Held, Hermanek, Berlis, Hecht and Berger.)

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).

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gierszewski, Kurotschka, Krauthausen, Fröhlich, Forster, Pietsch, Streng, Rücker, Wallstabe, Hartmann, Jans, Engels, Romanos, Heuschmann, Härtel, Kurzai, Liese and Gágyor.)

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.

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., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00020389 ., (© 2021. The Author(s).)

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., (© European Stroke Organisation 2020.)

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., (© 2021 American Academy of Neurology.)

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., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., (© 2021 S. Karger AG, Basel.)

Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients., Competing Interests: PHeu reports grants from German Ministry of Research and Education, German Research Foundation, European Union, Charité—Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), Charité—Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF randomized; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), outside the submitted work. SF reports grants from DFG, BMBF, grants and personal fees from Abiomed, Amgen, Akzea, AstraZeneca, Bayer, Berlin-Chemie, Braun, Bristol-Myers Squibb, Boehringer, Daiichi Sankyo, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, Siemens, Zoll, outside the submitted work. GE reports grants and personal fees from Bayer, grants and personal fees from Novartis, grants and personal fees from Vifor Pharma Deutschland GmbH, outside the submitted work; PK reports other from FreseniusKabi, personal fees from BBraun, grants, personal fees and other from TEVARatiopharm, other from CSL Behring, other from Pajunk, other from APEPTICO Forschung und Entwicklung GmbH, outside the submitted work; KZ reports personal fees from Aesculap Akademie GmbH, personal fees from Affinites Sante, grants from Ashai Kasai Pharma, grants and personal fees from B. Braun AG, grants and personal fees from B. Braun Avitum AG, personal fees from Bayer AG, grants from Biotest AG, personal fees from Christian Doppler Stiftung, grants and personal fees from CSL Behring GmbH, personal fees from Cyto Sorbents GmbH, personal fees from Edward Lifescience Corporation, personal fees from Executive Insight AG, personal fees from Fresenius Kabi GmbH, personal fees from Fresenius Medical Care, personal fees from Haemonetics Corporation, personal fees from Hartmannbund Landesverband, personal fees from Health Adcances GmbH, personal fees from Heinen + Löwenstein GmbH, personal fees from Hexal AG, grants from INC Research, personal fees from Johnson and Johnson, personal fees from Josef Gassner, personal fees from Maquet GmbH, personal fees from Markus Lücke Kongress Organization, personal fees from Masimo International, personal fees from med Update GmbH, personal fees from Medizin and Markt Gesundheitswerk, personal fees from MSD Sharp and Dohme GmbH, personal fees from Nordic Group, personal fees from Nordic Pharma, grants from Novo Nordisc Pharma GmbH, grants from Pfizer Pharma GmbH, personal fees from Pharmacosmos, personal fees from Ratiopharm GmbH, personal fees from Salvia Medical GmbH, personal fees from Schering Stiftung, personal fees from Schöchl Medical Österreich, personal fees from Serumwerke, personal fees from Verlag für Printmedien und PR, Forum Sanitas, grants and personal fees from Vifor Pharma GmbH, personal fees from Wellington, personal fees from Werfen, outside the submitted work; HK served as a speaker and/or an Advisory Board Member for AbbVie, BMS, Gilead, Hexal, Janssen, MSD, Pfizer, ViiV and has received research funding from AbbVie, Arrowhaed, BMS, Gilead, Janssen, MSD, Novartis, German Liver Foundation, Hector Foundation, Virtual University of Bavaria, Federal Ministry of Education and Research, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Herrmann, Adam, Notz, Helmer, Sonntagbauer, Ungemach-Papenberg, Sanns, Zausig, Steinfeldt, Torje, Schmid, Schlesinger, Rolfes, Reyher, Kredel, Stumpner, Brack, Wurmb, Gill-Schuster, Kranke, Weismann, Klinker, Heuschmann, Rücker, Frantz, Ertl, Muellenbach, Mutlak, Meybohm, Zacharowski and Lotz.)

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.

Objectives: To date, no validated long or short telephone version of the German "Informant Questionnaire on Cognitive Decline in the Elderly" (IQCODE) exists for determining cognitive changes over a period of 10 years by interviewing relatives., Method: Sixty relatives of 60 ischemic stroke patients were interviewed both face-to-face and by phone with the 26-item German IQCODE version in randomized order. Inter-method reliability was calculated as between-method agreement and quantified by a weighted kappa with Fleiss-Cohen weights. A short telephone version of the IQCODE was developed with the Variance Inflation Factor (VIF). Its reliability in regard to the 26-item telephone ICQODE version was calculated by Spearman's correlation coefficient., Results: The weighted kappa between the telephone and face-to-face interview was 0.84 (95 % confidence interval: 0.72-0.97). The short version of the IQCODE consists of 10 items. Spearman's Correlation Coefficient in regard to the long and short telephone version of the IQCODE was 0.97 (95 % confidence interval 0.96-0.99)., Conclusions: A long and short telephone version of the IQ-CODE for detecting cognitive changes in the elderly within a period of 10 years was developed by interviewing relatives., Competing Interests: SE: keineSW: reports grants from German Ministry of Research and Education and Deutsche Herzstiftung e.V.VR: keinePK: keineDM: keineUM: keineSS: research grants from the German Ministry of Education and Research, European Union, University Hospital Würzburg; participation in Data Safety Monitoring and Event Adjudication Boards in trials sponsored MEDTRONIC; principal investigator in trials (co-)sponsored by BOEHRINGER, NOVARTIS, BAYER, SANOFI; scientific advisor in boards for BAYER, THERMO FISHER; speaker honaria by BOEHRINGER, SERVIER, NOVARTIS, ASTRA-ZENECA, PFIZER, BAYER; all outside the submitted work.CK: keinePH: reports grants from German Ministry of Research and Education, German Research Foundation, European Union, Charité – Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), Charité–Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF randomized; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), outside the submitted work., (Thieme. All rights reserved.)

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., (© 2020 Riegler et al.)

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.

Background: Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region., Methods: The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals., Results: Overall, 7881 patients were included (mean age 74.6 years ±12.8; 48.4% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31%), mainly in secondary stroke prevention; b) improvement over time (44%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period., Conclusion: The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.

Objective: Clinical evidence on giant intracranial aneurysms (GIAs), intracranial aneurysms with a diameter of at least 25 mm, is limited. The authors aimed to investigate the natural history, case fatality, and treatment outcomes of ruptured and unruptured GIAs., Methods: In this international observational registry study, patients with a ruptured or unruptured GIA received conservative management (CM), surgical management (SM), or endovascular management (EM). The authors investigated rupture rates and case fatality., Results: The retrospective cohort comprised 219 patients with GIAs (21.9% ruptured GIAs and 78.1% unruptured GIAs) whose index hospitalization occurred between January 2006 and November 2016. The index hospitalization in the prospective cohort (362 patients with GIAs [17.1% ruptured and 82.9% unruptured]) occurred between December 2008 and February 2017. In the retrospective cohort, the risk ratio for death at a mean follow-up of 4.8 years (SD 2.2 years) after CM, compared with EM and SM, was 1.63 (95% CI 1.23-2.16) in ruptured GIAs and 3.96 (95% CI 2.57-6.11) in unruptured GIAs. In the prospective cohort, the 1-year case fatality in ruptured GIAs/unruptured GIAs was 100%/22.0% during CM, 36.0%/3.0% after SM, and 39.0%/12.0% after EM. Corresponding 1-year rupture rates in unruptured GIAs were 25.0% during CM, 1.2% after SM, and 2.5% after EM. In unruptured GIAs, the HR for death within the 1st year in patients with posterior circulation GIAs was 6.7 (95% CI 1.5-30.4, p < 0.01), with patients with a GIA at the supraclinoid internal carotid artery as reference. Different sizes of unruptured GIAs were not associated with 1-year case fatality., Conclusions: Rupture rates for unruptured GIAs were high, and the natural history and treatment outcomes for ruptured GIAs were poor. Patients undergoing SM or EM showed lower case fatality and rupture rates than those undergoing CM. This difference in outcome may in part be influenced by patients in the CM group having been found poor candidates for SM or EM.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov).

Background. Effective antihypertensive treatment depends on patient compliance regarding prescribed medications. We assessed the impact of beliefs related towards antihypertensive medication on blood pressure control in a population-based sample treated for hypertension. Methods. We used data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) study investigating 5000 inhabitants aged 30 to 79 years from the general population of Würzburg, Germany. The Beliefs about Medicines Questionnaire German Version (BMQ-D) was provided in a subsample without established cardiovascular diseases (CVD) treated for hypertension. We evaluated the association between inadequately controlled hypertension (systolic RR >140/90 mmHg; >140/85 mmHg in diabetics) and reported concerns about and necessity of antihypertensive medication. Results. Data from 293 participants (49.5% women, median age 64 years [quartiles 56.0; 69.0]) entered the analysis. Despite medication, half of the participants (49.8%) were above the recommended blood pressure target. Stratified for sex, inadequately controlled hypertension was less frequent in women reporting higher levels of concerns (OR 0.36; 95%CI 0.17-0.74), whereas no such association was apparent in men. We found no association for specific-necessity in any model. Conclusion. Beliefs regarding the necessity of prescribed medication did not affect hypertension control. An inverse association between concerns about medication and inappropriately controlled hypertension was found for women only. Our findings highlight that medication-related beliefs constitute a serious barrier of successful implementation of treatment guidelines and underline the role of educational interventions taking into account sex-related differences., Competing Interests: Stefan Störk reports research grants from the German Ministry of Education and Research, European Union, University Hospital Würzburg, principal investigator in trials (cosponsored by BOEHRINGER, NOVARTIS, BAYER; speaker honoraria by BOEHRINGER, SERVIER, NOVARTIS, ASTRA-ZENECA, PFIZER, BAYER). Peter U. Heuschmann reports research grants from the German Ministry of Research and Education, German Research Foundation, European Union, Federal Joint Committee (G-BA) within the Innovationfond, Charité, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert-Koch-Institute, German Heart Foundation, Charité–Universitätsmedizin Berlin (within MonDAFIS; MonDAFIS is supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF-randomized; FIND-AF randomized is supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), and University Hospital Heidelberg (within RASUNOA-prime; RASUNOA-prime is supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), outside submitted work. Caroline Morbach reports a speakers honorarium from Amgen, a travel grant from Thermo Fisher, Orion Pharma, and Alnylam, and participation in Scientific Advisory and Patient Eligibility Boards sponsored by AKCEA, Alnylam, and EBR Systems outside the submitted work. Theresa Tiffe, Götz Gelbrich, Hermann Faller, Viktoria Rücker, and Martin Wagner declare that they have no conflicts of interest.

Rationale: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear., Objectives: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake ( V . o 2 peak) following rigorous adjustment for other predictors., Methods: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups., Measurements and Main Results: Cox regression showed, even after adjustment for sex, FEV 1 % predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that V . o 2 peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity., Conclusions: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.

Background: The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors., Methods: Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from Würzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT., Results: 2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA., Conclusions: As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual.