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In the earlier phases of the COVID-19 pandemic, studies in Germany and elsewhere found an overall reduction in health-related quality of life (HRQoL) among students. However, there is little evidence on later pandemic stages as well as socioeconomic influencing factors. We aimed to (1) describe HRQoL in a Berlin student cohort at two time points in mid-2021, and to (2) analyze the effects of household income and education. We assessed HRQoL of students from 24 randomly selected primary and secondary schools in Berlin, Germany, with the KIDSCREEN-10 index in June and September 2021. To adjust for non-response bias, inverse probability weighting was applied. The potential effects of both household income and education (lower vs. higher) were estimated in generalized linear mixed models, based on prior assumptions presented in directed acyclic graphs. Our cohort comprised 660 students aged 7-19 years. In June 2021, 11.3% [95% CI = 9.0% - 14.0%] reported low HRQoL, whereas in September 2021, this increased to 13.7% [95% CI = 11.1% - 16.5%], with adolescent girls more frequently reporting low HRQoL at both time points (20% [95% CI = 17.1% - 23.3%] and 29% [95% CI = 25.5% - 32.5%]) compared to boys and younger children. While there was no statistically significant total effect of lower household income on HRQoL, a negative effect of lower household education was statistically significant (β = -2.15, SE 0.95, 95% CI = -4.01 to -0.29, p = 0.024). In summary, students' HRQoL in mid-2021 was better than that documented in other studies conducted at pandemic onset using KIDSCREEN-10. Female adolescents reported low HRQoL more often, and lower household education significantly reduced children's HRQoL. Support strategies for psychosocial wellbeing should consider socioeconomically disadvantaged children as important target groups., Competing Interests: None of the authors had a conflict of interest related to the content of the study. Outside the work, TK reports to have received research grants from the Gemeinsamer Bundesausschuss (G-BA, Federal Joint Committee, Germany), the Bundesministerium für Gesundheit (BMG, Federal Ministry of Health, Germany). He further has received personal compensation from Eli Lilly and Company, Teva Pharmaceuticals, TotalEnergies S.E., The BMJ, and Frontiers. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Kern et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations., Methods and Analysis: A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes., Ethics and Dissemination: The study was approved by the Charité-Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations., Study Registration: First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021., Competing Interests: Competing interests: FE reports grants from German Research Foundation (DFG), grants from German Ministry of Education and Research, grants from the German Herta Foundation; during the conduct of the study; personal fees and non-financial support from Novartis, grants and personal fees from Boehringer Ingelheim, personal fees from CVRx, Pfizer, Medtronic, grants and personal fees from Servier, personal fees from MSD, personal fees from Merck & Co., grants from AstraZeneca, personal fees from Bayer, personal fees from Resmed, personal fees from Berlin Chemie, grants from Thermo Fischer, personal fees from Vifor Pharma, personal fees from PharmaCosmos outside the submitted work; ME reports grants from Bayer and fees paid to the Charité from Abbot, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, Sanofi, Novartis, Pfizer, all outside the submitted work. ME received funding from DFG under Germany’s Excellence Strategy – EXC-2049 – 390688087, Collaborative Research Center ReTune TRR 295- 424778381, BMBF, DZNE, DZHK, EU, Corona Foundation, and Fondation Leducq. HG reports grants from the DFG, the Leducq Foundation, the Federal Ministry of Education and Research (BMBF) and the DZHK during the conduct of the study, outside of the submitted work. UL reports research funding from DZHK; Fondation Leducq; research grants from Novartis, Bayer and Amgen. KM declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. DNM received funding for research from Bayer Healthcare, Deutsche Forschungsgemeinschaft and from BMBF. CHN received research grants from German Ministry of Research and Education, German Center for neurodegenerative Diseases (DZNE), DZHK, and speaker and/or consultation fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer Pharma, Abbott, Novartis, Daichii-Sankyo and Alexion all outside the submitted work. BP reports personal fees and other from Bayer Healthcare, personal fees and other from MSD, personal fees and other from Novartis, personal fees from Astrazeneca, grants and personal fees from Servier, personal fees from Medscape, outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work have exist beyond those listed. TP received grants from the BMBF, the Federal Ministry of Food and Agriculture (BMEL), the Federal Ministry for Economic Affairs and Energy (BMWi), the DFG, Deutsche Herzstiftung, German Academic Exchange Service (DAAD). KMSO reports having consultancy fees with BioPorto Diagnostics; having received license revenue related to the use of a neutrophil gelatinase-associated lipocalin assay via Columbia University; receiving research funding from FAST BioMedical, for being a principal investigator of the EMPAKT-CHF trial, and Quark Pharmaceuticals, for being the site principal investigator for QRK309 trial; and being an editorial board member for Kidney International and Kidney International Reports; each outside the submitted work. JSM reports grants from Bayer Healthcare, non-financial support from Siemens healthineers, non-financial support from Circle cardiovascular, non-financial support from Medis, outside the submitted work, and Bayer Healthcare, Advisor. Furthermore, funding for research from the EU, DZHK, Deutsche Herzstiftung. JS received funding for research from DFG and from BMBF. MW received funding for research from DFG, BMBF, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Foundation, Capnetz Foundation, International Max Planck Research School, Actelion, Bayer Health Care, Biotest, Boehringer Ingelheim, Noxxon, Pantherna, Quark Pharma, Vaxxilon, and for lectures and advisory from Actelion, Aptarion, Astra Zeneca, Bayer Health Care, Berlin Chemie, Biotest, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Novartis, Noxxon, Pantherna, Teva und Vaxxilon. All remaining authors MA, L-HB, K-UE, UG, NH, JK-H, DL, DNM, SKP, SR, GR, KS, OS, BS, SS, RV, JEW do not report potential conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The medial portrayal of migraine is often stereotypical and inaccurate but reflects how society perceives migraine. The discrepancy between others' views and the reality of affected individuals may negatively affect access to treatment and the disease course of patients with migraine. This study aimed to investigate whether images presented in the media as typical migraine attacks are perceived as realistic and representative by migraine patients in Rostock, a smaller town in rural Germany, and compare the results to those from Berlin, a large metropolis. We performed an online survey in Rostock. Migraine patients were shown ten images of migraine attacks, which were among the most downloaded stock pictures on the internet under the search term "migraine". They rated on a scale of 0-100 to what extent the pictures were realistic for migraine attacks (realism score), representative of their own migraine (representation score), or the society's view of migraine (society score). In addition, we compared our results with a recently published study from the metropolitan region of Berlin. A total of 174 migraine patients completed our survey. Mean (SD) realism, representation, and society scores were 59.9 (17.5), 56.7 (18.3), and 58.4 (17.1) respectively. Images of older patients were perceived as significantly more realistic and representative than those of younger patients (P < .001). Patients in Rostock (rural region) rated the images as significantly more realistic and representative than survey participants in Berlin (metropolis). Migraine patients in a rural region found typical migraine images only moderately realistic and representative but to a higher degree than their counterparts from a metropolis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: TH has nothing to disclose. JBH has nothing to disclose. KSL reports personal fees from Teva. LHO has nothing to disclose. PT has nothing to disclose. FR received honoraria for consulting and lectures from Allergan/Abbvie, Novartis, Teva, Lilly, Ipsen, Lundbeck, Hormosan. He has received royalties from Elsevier. TPJ has served on advisory boards and has received honoraria for lectures from Allergan, Abbvie, Grünenthal, Lilly, Lundbeck, Hormosan, Novartis, Pfizer, Sanofi, TEVA. He has received royalties from Elsevier. His research is supported by Grants from the Innovationsfonds/Gemeinsamer Bundesausschuss and the European Union (EFRE). PK received honoraria for consulting and lectures from Allergan, Lilly, Lundbeck, Novartis, and Takeda. UR received honoraria for consulting and lectures from Amgen, Allergan, Abbvie, Eli Lilly, Lundbeck, Novartis, electroCore, Medscape, StreaMedUp, and Teva. UR received research funding from the German Federal Ministry of Education and Research and Novartis. BR received honoraria for consulting and lectures from Abbvie/Allergan, Lilly, Novartis, and Teva as well as research funding from the German Research Foundation, the German Migraine and Headache Society and Novartis. All financial and non-financial support was received outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hamann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Elevated triglyceride and glucose levels are associated with an increased cardiovascular disease risk including ischemic stroke. It is not known whether the response to a combined oral triglyceride and glucose challenge after ischemic stroke improves identification of patients with increased risk for recurrent vascular events., Methods: The prospective, observational Berlin "Cream&Sugar" study was conducted at 3 different university hospital sites of the Charité-Universitätsmedizin Berlin, Germany, between January 24, 2009 and July 31, 2017. Patients with first-ever ischemic stroke were recruited 3 to 7 days after stroke. An oral triglyceride tolerance test (OTTT) and consecutive blood tests before (t 0 ) as well as 3 (t 1 ), 4 (t 2 ), and 5 hours (t 3 ) after OTTT were performed in fasting patients. An oral glucose tolerance test was performed in all nondiabetic patients 3 hours after the start of OTTT. Outcomes of the study were recurrent fatal or nonfatal stroke as well as a composite vascular end point including stroke, transient ischemic attack, myocardial infarction, coronary revascularization, and cardiovascular death assessed 1 year after stroke. Cox regression models were used to estimate hazard ratios and corresponding 95% CIs between patients with high versus low levels of triglyceride and glucose levels., Results: Overall 755 patients were included; 523 patients completed OTTT and 1-year follow-up. Patients were largely minor strokes patients with a median National Institutes of Health Stroke Scale score of 1 (0-3). Comparing highest versus lowest quartiles of triglyceride levels, neither fasting (adjusted hazard ratio t0 , 1.24 [95% CI, 0.45-3.42]) nor postprandial triglyceride levels (adjusted hazard ratio t3 , 0.44 [95% CI, 0.16-1.25]) were associated with recurrent stroke. With regard to recurrent vascular events, results were similar for fasting triglycerides (adjusted hazard ratio t0 , 1.09 [95% CI, 0.49-2.43]), however, higher postprandial triglyceride levels were significantly associated with a lower risk for recurrent vascular events (adjusted hazard ratio t3 , 0.42 [95% CI, 0.18-0.95]). No associations were observed between fasting and post-oral glucose tolerance test blood glucose levels and recurrent vascular risk. All findings were irrespective of the diabetic status of patients., Conclusions: In this cohort of patients with first-ever' minor ischemic stroke, fasting triglyceride or glucose levels were not associated with recurrent stroke at one year after stroke. However, higher postprandial triglyceride levels were associated with a lower risk of recurrent vascular events which requires further validation in future studies. Overall, our results do not support the routine use of a combined OTTT/oral glucose tolerance test to improve risk prediction for recurrent stroke.

Aims: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke., Methods: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke., Results: At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA 2 DS 2 -VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA 2 DS 2 -VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]., Conclusion: At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge., Clinical Trial Registration: NCT02306824., (© 2021. The Author(s).)

Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.

Background: Significant inequalities in caries distribution among children in Germany have been reported, but small-scale areas remain understudied., Aim: To examine spatio-temporal trends in children's dental caries at the small-area level in Berlin-Mitte., Design: Routinely collected data from Berlin's annual Health Examination Surveys were used, which also include information on age, sex, country of origin, and residential area. The study population consists of 14,866 children aged 5 to 7 between 2006 and 2014 in the district of Berlin-Mitte. Outcome variables are the dmft (decayed, missing, and filled teeth), the presence of any caries experience, untreated caries, and caries risk. The outcomes are summarized descriptively and graphically presented for 10 quarters and 41 communities within Berlin-Mitte., Results: Relevant gaps in children's dental caries were discovered between the quarters of Mitte. Three quarters in the northeast part of Mitte have consistently indicated the lowest oral health status in all four outcomes, and children having high caries risk have been increasingly concentrating in this area over time. Despite the continuous improvements in the southern part, the averages in total of Mitte for all outcomes have risen., Conclusion: Our findings confirm the spatiotemporally mounting disparities in children's oral health between the quarters in Berlin-Mitte and that particular quarters need urgent attention. The small-area approach made it easier and more effective to reveal the spatial distribution of children's dental caries at the local level. The small-area analysis should be strongly encouraged in future caries research to narrow the inequalities in children's oral health., (© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment., Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke., Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only)., Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794)., Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability., Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04)., Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

Aims: This study aimed to evaluate the impact of coronavirus disease 2019 (Covid-19) outbreak on admissions for acute myocardial infarction (AMI) and related mortality, severity of presentation, major cardiac complications and outcome in a tertiary-care university hospital in Berlin, Germany., Methods and Results: In a single-centre cross-sectional observational study, we included 355 patients with AMI containing ST-elevation or non-ST-elevation myocardial infarction (STEMI or NSTEMI), admitted for emergency cardiac catheterization between January and April 2020 and the equivalent time in 2019. During the early phase of the Covid-19 pandemic (e-COV) in Berlin (March and April 2020), admissions for AMI halved compared with those in the pre-Covid-19 time (January and February 2020; pre-COV) and with those in the corresponding months in 2019. However, mortality for AMI increased substantially from 5.2% pre-COV to 17.7% (P < 0.05) during e-COV. Severity of presentation for AMI was more pronounced during e-COV [increased levels of cardiac enzymes, reduced left ventricular ejection fraction (LVEF), an increase in the need of inotropic support by 25% (P < 0.01)], while patients' demographic and angiographic characteristics did not differ between pre-COV and e-COV. Time from symptom onset to first medical contact was prolonged in all AMI during e-COV (presentation > 72 h +21% in STEMI, p = 0.04 and presentation > 72 h in NSTEMI +22%, p = 0.02). Door to balloon time was similar in STEMI patients, while time from first medical contact to revascularization was significantly delayed in NSTEMI patients (p = 0.02). Major cardiac complications after AMI occurred significantly more often, and cardiac recovery was worse in e-COV than in pre-COV, demonstrated by a significantly lower LVEF (39 ± 16 vs. 46 ± 16, p < 0.05) at hospital discharge and substantially higher NTproBNP levels., Conclusions: The Covid-19 outbreak affects hospital admissions for acute coronary syndromes. During the first phase of the pandemia, significantly less patients with AMI were admitted, but those admitted presented with a more severe phenotype and had a higher mortality, more complications, and a worse short-term outcome. Therefore, our data indicate that Covid-19 had relevant impact on non-infectious disease states, such as acute coronary syndromes., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Efficacy and safety of different hemoglobin thresholds for transfusion of red blood cells (RBCs) in adults with an acute respiratory distress syndrome (ARDS) are unknown. We therefore assessed the effect of two transfusion thresholds on short-term outcome in patients with ARDS., Methods: Patients who received transfusions of RBCs were identified from a cohort of 1044 ARDS patients. After propensity score matching, patients transfused at a hemoglobin concentration of 8 g/dl or less (lower-threshold) were compared to patients transfused at a hemoglobin concentration of 10 g/dl or less (higher-threshold). The primary endpoint was 28-day mortality. Secondary endpoints included ECMO-free, ventilator-free, sedation-free, and organ dysfunction-free composites., Measurements and Main Results: One hundred ninety-two patients were eligible for analysis of the matched cohort. Patients in the lower-threshold group had similar baseline characteristics and hemoglobin levels at ARDS onset but received fewer RBC units and had lower hemoglobin levels compared with the higher-threshold group during the course on the ICU (9.1 [IQR, 8.7-9.7] vs. 10.4 [10-11] g/dl, P < 0.001). There was no difference in 28-day mortality between the lower-threshold group compared with the higher-threshold group (hazard ratio, 0.94 [95%-CI, 0.59-1.48], P = 0.78). Within 28 days, 36.5% (95%-CI, 27.0-46.9) of the patients in the lower-threshold group compared with 39.5% (29.9-50.1) of the patients in the higher-threshold group had died. While there were no differences in ECMO-free, sedation-free, and organ dysfunction-free composites, the chance for successful weaning from mechanical ventilation within 28 days after ARDS onset was lower in the lower-threshold group (subdistribution hazard ratio, 0.36 [95%-CI, 0.15-0.86], P = 0.02)., Conclusions: Transfusion at a hemoglobin concentration of 8 g/dl, as compared with a hemoglobin concentration of 10 g/dl, was not associated with an increase in 28-day mortality in adults with ARDS. However, a transfusion at a hemoglobin concentration of 8 g/dl was associated with a lower chance for successful weaning from the ventilator during the first 28 days after ARDS onset., Trial Registration: ClinicalTrials.gov NCT03871166.

Despite a growing body of knowledge about the morbidities and functional impairment that frequently lead to care dependency, the role of social determinants is not yet well understood. The purpose of this study was to examine the effect of social determinants on care dependency onset and progression. We used data from the Berlin Initiative Study, a prospective, population-based cohort study including 2,069 older participants living in Berlin. Care dependency was defined as requiring substantial assistance in at least two activities of daily living for 90 min daily (level 1) or 3+ hours daily (level 2). Multi-state time to event regression modeling was used to estimate the effects of social determinants (partnership status, education, income, and sex), morbidities, and health behaviors, characteristics, and conditions. During the study period, 556 participants (27.5%) changed their status of care dependency. Participants without a partner at baseline were at a higher risk to become care-dependent than participants with a partner (hazard ratio [HR], 95% confidence interval [CI]: 1.24 (1.02-1.51)). After adjustment for other social determinants, morbidities and health behaviors, characteristics, and conditions the risk decreased to a HR of 1.19 (95% CI: 0.79-1.79). Results indicate that older people without a partner may tend to be at higher risk of care dependency onset but not at higher risk of care dependency progression. Clinicians should inquire about and consider patients' partnership status as they evaluate care needs., (© 2020 The Authors. Research in Nursing & Health Published by Wiley Periodicals, Inc.)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients., Methods: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 μg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy., Results: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 μg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p <  0.001] were significantly associated with in-hospital mortality., Conclusions: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients., Clinical Trial Registration: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

Background: Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology., Methods: We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5-12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology., Results: Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress., Conclusion: The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.

Background: Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors., Objective: How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance?, Materials and Methods: This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model., Results: Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40-60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group., Conclusion: In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors.

Physical activity (PA) in youth tends to decline with increasing age, while sedentary behaviour including screen time (ST) increases. There are adolescents, however, whose PA and ST do not follow this pattern. The aim of this study is (i) to examine trajectories in PA and ST from grade 7-9 among students in Berlin, and (ii) to investigate the relationship of these trajectories with individual factors and school type. For the present analyses, changes in students' PA and ST across three time points from 7th to 9th grade were assessed via self-report questionnaires. Positive and negative trajectories were defined for both PA (positive: increasing or consistently high, negative: decreasing or consistently low) and ST (vice versa). Multivariable logistic regression analyses were performed to identify possible predictors of PA and ST trajectories. In total, 2122 students were included (50.2% girls, mean age 12.5 (standard deviation 0.7) years). Compared to grade 7, less students of grade 9 fulfilled PA and ST recommendations (PA: 9.4% vs. 13.2%; ST: 19.4% vs. 25.0%). The positive PA trajectory included 44% of all students (63% boys), while the positive ST trajectory included 21% of all students (30% boys). Being a boy was significantly associated with a positive PA trajectory, while being a girl, having a high socioeconomic status, and attending a high school, were significantly associated with a positive ST trajectory. Different PA and ST trajectories among adolescents should be taken into account when implementing prevention programs for this target group.

Aims: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke., Methods and Results: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively., Conclusion: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Liver transplantation is the only curative treatment option for patients with end-stage liver disease; however, the 40% decline of available organ donors in recent years in Germany necessitates the optimization of available resources and possibly extending the criteria to older donors., Material and Methods: All 2652 livers made available to the Charité Universitätsmedizin Berlin from 2010 to 2016 were retrospectively analyzed and the clinical outcome of 526 liver transplantations during this time frame were evaluated., Results: The median age of donors of transplanted organs increased from 49.3 years in 2010 to 57.3 years in 2016 (p = 0.02). Organs from donors ≥65 years were more frequently discarded than organs from younger donors (n = 344, 18.4% vs. n = 220, 28.1%; p = 0.005). Moreover, the older donors had higher rates of diabetes mellitus and hepatic steatosis. Organs from older donors had a higher donor risk index (2.8 vs. 2.2; p < 0.001) and were transplanted more often in patients with preserved liver function and hepatocellular carcinoma and liver cirrhosis (n = 121, 74.7% of indications). The 3‑year survival after liver transplantation from donors ≥65 and ≥80 years old was not significantly reduced in comparison to younger donors; however, there was an increased retransplantation rate (28.6%; p = 0.005) after transplantation of organs from donors ≥80 years old., Conclusion: Despite conservative organ acceptance there were higher rates of retransplantation after transplantation from very old donors. In the light of an increasing scarcity of suitable organs this mandates caution and highlights the need for adequate assessment instruments for marginal donor organs before transplantation.

Pregnancy-associated plasma protein-A2 (PAPP-A2), a metalloproteinase purportedly related to pregnancy, foetal growth and development, has recently been described essential for pre-adult growth. Thus, we measured PAPP-A2 in plasma of a non-pregnant population and determined its associations with lifestyle, anthropometric or biochemical factors. In this cross-sectional study of 387 participants (20-70 years) randomly drawn from registration offices near Berlin, Germany, socio-economic and lifestyle factors were assessed by questionnaires, and anthropometric measures and blood samples were taken by trained personnel. Blood was analysed for standard clinical parameters. PAPP-A2 concentration was measured by ELISA. Generalized linear models were used to estimate associations with anthropometric and biochemical factors adjusted for age, sex, and weight. Adjusted mean PAPP-A2 concentration was slightly higher in women (283 pg/mL) than in men (261 pg/mL, p = 0.05) and positively correlated with age (r = 0.17, p = 0.001). PAPP-A2 concentration was inversely associated with body mass index (-2.7 pg/mL per kg/m 2 , p = 0.03) and weight (-1.0 pg/mL per kg, p = 0.01) and positively associated with γ-glutamyl transferase (13.6 pg/mL per SD, p = 0.02), aspartate transaminase (18.5 pg/mL per SD, p = 0.002) and lactate dehydrogenase (14.9 pg/mL per SD, p = 0.02). Our results support that PAPP-A2, beyond its established role in early growth and development is relevant in adult metabolisms.

Rationale Prehospital stroke care in specialized ambulances increases thrombolysis rates, reduces alarm-to-treatment times, and improves the prehospital triage. Preliminary analyses suggest cost-effectiveness. However, scientific proof of better functional outcome compared to usual care is still lacking. Aim To prove better functional outcomes after deployment of the Stroke Emergency Mobile compared to regular ambulances. Sample size estimates A sample size of 686 patients will be required in each arm (Stroke Emergency Mobile group vs. regular care) to detect a difference regarding the primary outcome with 80% power at a two-sided significance level of 0.05. Methods and design This is a pragmatic, prospective study with blinded outcome assessment. Primary outcome will be functional status as defined by modified Rankin Scale score three months after the incident event. We will include cerebral ischemia patients within a predefined catchment area in Berlin, Germany. The study population consists of patients who might be candidates for acute recanalizing treatments, with onset-to-alarm time ≤4 h, symptoms not resolved at time of ambulance arrival, and able to walk without assistance prior to the qualifying incident. About 45% of Stroke Emergency Mobile dispatches are expected to be handled by regular ambulances, since Stroke Emergency Mobile will be already in operation creating the control group. Primary outcome Functional outcome after three months measured by the modified Rankin Scale over the entire range. Discussion The results will inform decision makers on the effectiveness of Stroke Emergency Mobile.