Search

Background: Recent research on boredom suggests that it can emerge in situations characterized by over- and under-challenge. In learning contexts, this implies that high boredom may be experienced both by low- and high-achieving students. Aims: This research aimed to explore the existence and prevalence of boredom due to being over- and under-challenged in mathematics, for which empirical evidence is lacking. Sample: We employed a sample of 1.407 students (fifth to ninth graders) from all three secondary school tracks (lower, middle and upper) in Bavaria (Germany). Methods: Boredom was assessed via self-report and achievement via a standardized mathematics test. We used latent profile analysis to identify groups characterized by different levels of boredom and achievement, and we additionally examined gender and school track as group membership predictors. Results: Results revealed four distinct groups, of which two showed considerably high boredom. One was coupled with low achievement on the test (i.e. 'over-challenged group', 13% of the total sample), and one was coupled with high achievement (i.e. 'under-challenged group', 21%). Furthermore, we found a low boredom and high achievement (i.e. 'well-off group', 27%) and a relatively low boredom low achievement group (i.e. 'indifferent group', 39%). Girls were overrepresented in the over-challenged group, and students from the upper school track were underrepresented in the under-challenged group. Conclusion: Our research emphasizes the need to openly discuss and further investigate boredom due to being over- and under-challenged.

Emotions influence processes of learning and thinking in all people. However, there is a lack of studies in the field of emotion research including people with intellectual disabilities (ID) addressing the existing diversity. The present study investigates the emotional competence of people with ID (N = 32). The first aim was to assess the emotional development using the Scale of Emotional Development (SEED). Based on these insights, the second objective was to replicate existing findings, validating the emotional reaction of people with ID to pictures of the International Affective Picture System (IAPS) based on self-reports. In an additional pilot-like analysis, the third aim was to investigate if these self-reported emotional reactions match the emotions expressed in their faces using the automated and video-based facial expression analysis software 'Affectiva (Affdex SDK)'. In the present study, the self-reported emotional reactions of participants with ID were in line with previous research. In addition, the present study shows the general potential of this innovative approach of using and applying commercially available automated emotion recognition software for the field of special needs and social science. [ABSTRACT FROM AUTHOR]

. Purpose: To characterize the temporal occurrence of retinal detachments (RD) after cataract surgery. Methods: In this retrospective, consecutive case series, we reviewed the charts of 798 pseudophakic patients with primary rhegmatogenous RD that underwent surgery between 1999 and 2009, at the Center of Ophthalmology, University of Cologne, Germany. Results: Twenty-five percent of all pseudophakic RDs occurred within 1 year after cataract surgery, 50% within 3.2 years and 90% within 9.9 years. Risk was increased for at least 11 years. The time interval was significantly shorter in vitrectomized eyes (2.49 versus 4.31 years, p = 0.016). Women showed a statistical trend towards longer time intervals (4.72 versus 3.93 years, p = 0.052), whereas myopic patients and different age groups showed no significant difference. Conclusions: After cataract surgery, the risk for RD was highest in the beginning and decreased continuously over time. However, the risk was increased for at least 11 years. Therefore, most studies have underestimated the incidence of RD after cataract surgery. [ABSTRACT FROM AUTHOR]

Clinics are, by definition, part of a country's critical infrastructure. In recent years, hospitals have increasingly become the target of cyber attacks, resulting in disruptions to their functionality lasting weeks to even months. According to the "National Strategy for the Protection of Critical Infrastructures (CRITIS Strategy)", clinics are legally obligated to take preventive measures against such incidents. This involves evaluating, defining, and developing failure concepts for IT-dependent processes within a clinic to be prepared for a cyber attack. Specifically tailored emergency plans for computer system failures should be created and maintained in all IT-dependent areas of a clinic.Additionally, paper-based alternative solutions, such as request forms for diagnostic or consultation services, department-specific emergency documents, and patient documentation charts, should be kept in a readily accessible location known to staff in the respective areas. The complete restoration of a clinic's network after a cyber attack often requires extensive recovery of numerous IT systems, which may take weeks to months in some cases.If the hospital has robust plans for cyber emergency preparedness, including regular scans and real-time backups, stabilization and a quicker resumption of operations may be possible., Competing Interests: E. Pfenninger ist Mitglied im BDA und DGAI, ehemaliger Leiter der Stabsstelle Katastrophenschutz am Universitätsklinikum Ulm. M. Königsdorfer ist Leiter der Stabsstelle Katastrophenschutz am Universitätsklinikum Ulm, (Thieme. All rights reserved.)

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.

Background: Recent research on boredom suggests that it can emerge in situations characterized by over- and under-challenge. In learning contexts, this implies that high boredom may be experienced both by low- and high-achieving students., Aims: This research aimed to explore the existence and prevalence of boredom due to being over- and under-challenged in mathematics, for which empirical evidence is lacking., Sample: We employed a sample of 1.407 students (fifth to ninth graders) from all three secondary school tracks (lower, middle and upper) in Bavaria (Germany)., Methods: Boredom was assessed via self-report and achievement via a standardized mathematics test. We used latent profile analysis to identify groups characterized by different levels of boredom and achievement, and we additionally examined gender and school track as group membership predictors., Results: Results revealed four distinct groups, of which two showed considerably high boredom. One was coupled with low achievement on the test (i.e. 'over-challenged group', 13% of the total sample), and one was coupled with high achievement (i.e. 'under-challenged group', 21%). Furthermore, we found a low boredom and high achievement (i.e. 'well-off group', 27%) and a relatively low boredom low achievement group (i.e. 'indifferent group', 39%). Girls were overrepresented in the over-challenged group, and students from the upper school track were underrepresented in the under-challenged group., Conclusion: Our research emphasizes the need to openly discuss and further investigate boredom due to being over- and under-challenged., (© 2024 The Author(s). British Journal of Educational Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Expanding in both scope and scale, ecosystem restoration needs to embrace complex social-ecological dynamics. To help scientists and practitioners navigate ever new demands on restoration, we propose the "social-ecological ladder of restoration ambition" as a conceptual model to approach dynamically shifting social and ecological restoration goals. The model focuses on three dynamic aspects of restoration, namely degrading processes, restoration goals and remedial actions. As these three change through time, new reinforcing and balancing feedback mechanisms characterize the restoration process. We illustrate our model through case studies in which restoration has become increasingly ambitious through time, namely forest landscape restoration in Rwanda and grassland restoration in Germany. The ladder of restoration ambition offers a new way of applying social-ecological systems thinking to ecosystem restoration. Additionally, it raises awareness of social-ecological trade-offs, power imbalances and conflicting goals in restoration projects, thereby laying an important foundation for finding more practicable and fairer solutions., (© 2024. The Author(s).)

Background: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking., Objectives: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders., Methods: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search., Results: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented., Conclusions: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams., (© 2024. The Author(s).)

Background: Healthcare associated infections (HAI) pose a major threat to healthcare systems resulting in an increased burden of disease. Surveillance plays a key role in rapidly identifying these infections and preventing further transmissions. Alas, in German hospitals, the majority of surveillance efforts have been heavily relying on labour intensive processes like manual chart review. In order to be able to identify further starting points for future digital tools and interventions to aid the surveillance of HAI we aimed to gain an understanding of the current state of digitalisation in the context of the general surveillance organisation in German clinics across all care-levels. The end user perspective of infection prevention and control (IPC) professionals was chosen to identify digital interventions that have the biggest impact on the daily surveillance work routines of IPC professionals. Perceived impediments in the advancement of surveillance digitalisation should be explored., Methods: Following the development of an interview guideline, eight IPC professionals from seven German hospitals of different care levels were questioned in semi- structured interviews between December 2022 and January 2023. These included questions about general surveillance organisation, access to digital data sources, software to aid the surveillance process as well as current issues in the surveillance process and implementation of software systems. Subsequently, after full transcription, the interview sections were categorized in code categories (first deductive then inductive coding) and analysed qualitatively., Results: Results were characterised by high heterogeneity in terms of general surveillance organisation and access to digital data sources. Software configuration of hospital and laboratory information systems (HIS/LIS) as well as patient data management systems (PDMS) varied not only between hospitals of different care levels but also between hospitals of the same care level. Outside research projects, neither fully automatic software nor solutions utilising artificial intelligence have currently been implemented in clinical routine in any of the hospitals., Conclusions: Access to digital data sources and software is increasingly available to aid surveillance of HAI. Nevertheless, surveillance processes in hospitals analysed in this study still heavily rely on manual processes. In the analysed hospitals, there is an implementation and funding gap of (semi-) automatic surveillance solutions in clinical practice, especially in healthcare facilities of lower care levels., (© 2024. The Author(s).)

Children all over the world learn language, yet the contexts in which they do so vary substantially. This variation needs to be systematically quantified to build robust and generalizable theories of language acquisition. We compared communicative interactions between parents and their 2-year-old children ( N = 99 families) during mealtime across five cultural settings (Brazil, Ecuador, Argentina, Germany, and Japan) and coded the amount of talk and gestures as well as their conversational embedding (interlocutors, function, and themes). We found a comparable pattern of communicative interactions across cultural settings, which were modified in ways that are consistent with local norms and values. These results suggest that children encounter similarly structured communicative environments across diverse cultural contexts and will inform theories of language learning. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using a novel German linked employer-employee dataset, we provide unique evidence about the consequences of working from home (WfH) on individual health and well-being. During the recent pandemic, this locational flexibility measure has been used extensively to promote health by hampering the spread of the virus and to secure jobs. However, its direct theoretical ambiguous effects on health and well-being as characterized by different potential channels have barely been empirically investigated to date despite WfH's increasing popularity in the years before the pandemic. To address concerns about selection into WfH in our dataset that is unaffected by the COVID-19 shock, our analysis relies on an identification strategy ruling out confounding effects by time-invariant unobservable variables. Moreover, we explain the remaining (intertemporal) variation in the individual WfH status by means of an instrumental variable strategy using variation in equipment with mobile devices among establishments. We find that subjective measures of individual health are partly affected by WfH, whereas no corresponding effect is present for an objective measure of individual health. In terms of individual well-being, we find that WfH leads to considerable improvement. By addressing the potential heterogeneity in our effect of interest, we find that men and middle-aged individuals particularly benefit from WfH., (© 2023. The Author(s).)

Background: The utilization of psychotherapeutic consultation at work (PT-A) has so far been investigated in large enterprises (LEs). These differ structurally from small(est) and medium-sized enterprises (SMEs). Differences in the user profiles of a PT‑A with regard to psychosomatic health, work-related self-efficacy, and work ability depending on company size have hardly been investigated. This study also examined differences in the employees' perception of the psychosocial safety climate (PSC) in the company, which represents management's efforts to promote mental health., Methods: As part of the Early Intervention in the Workplace intervention study called "friaa", employees from LEs and SMEs interested in a PT‑A were surveyed throughout Germany from September 2021 to January 2023. Using t‑ and χ 2 -tests, differences between employees in LEs (n = 439) and SMEs (n = 109) were examined with regard to the ICD-10 F diagnostic code ("International Statistical Classification of Diseases and Related Health Problems"; mental and behavioral disorders), depression (PHQ-9), anxiety (GAD-2), level of functioning (GAF), somatic symptom burden (SSS-8), health (VR-12), ability to work (WAI), self-efficacy (SOSES), and psychosocial safety climate (PSC-4). The association between these variables and especially the PSC‑4 were investigated using correlation analysis., Results: Both groups showed similar levels of stress. From the employees' perspective, psychosocial issues were addressed significantly more frequently in LEs than in SMEs with a medium effect size. The study provided initial indications that in LEs there were positive correlations of the PSC‑4 with SOSES and WAI and negative ones with PHQ‑9 and SSS‑8., Discussion: The comparable psychological strain on employees in LEs and SMEs points to the need for behavioral and structural preventive measures regardless of the company size. Mainly in SMEs, organizational communication of psychosocial health should be given greater priority., (© 2024. The Author(s).)

Background: Risk factors for mental health can be found in socio-economic-, gender- and migration-specific inequalities. These factors and the extent of depression, anxiety, and somatization among employees were examined in the present study., Methods: As part of the Early Intervention in the Workplace Study (friaa), mentally burdened employees at five locations in Germany were surveyed on socio-demographic-, work-, migration-, and health-related content. Regression analyses were used to examine the relationship between these factors and depression (Patient-Health-Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder-2, GAD-2), and somatization (Somatic Symptom Scale-8, SSS-8) in the entire sample and in people with migration background (MB). For the latter, acculturation (Frankfurt Acculturation Scale, FRACC) and the perception of burden in terms of demands of immigration (Demands of Immigration Scale, DIS) were also taken into account., Results: On average, the 550 employees (12% with MB) showed clinically relevant depression (M = 13.0, SD = 5.1) (PHQ-9 ≥ 10), anxiety (M = 3.5, SD = 1.7) (GAD ≥ 3) and somatization (M = 13.0, SD = 5.8) (SSS-8 ≥ 12). Female gender was associated with higher anxiety and somatization. Older age and night shift work were associated with higher somatization., Discussion: The results confirm the high level of mental burden among this sample of employees in Germany. In order to maintain their mental health, support measures should be offered, especially for vulnerable groups such as women, older employees, and night shift workers., (© 2024. The Author(s).)

Background: Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users' daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia)., Methods: In this hybrid effectiveness-implementation study, a parallel-group, assessor-blind, multi-centre cluster randomized controlled trial (cRCT) will be conducted, combined with a process and economic evaluation. In the cRCT, 24 clinical units (as the cluster and unit of randomization) at eight sites in four European countries will be randomly allocated using an unbalanced 2:1 ratio to one of two conditions: (a) the experimental condition, in which participants receive a Digital Mobile Mental Health intervention (DMMH) and other implementation strategies in addition to treatment as usual (TAU) or (b) the control condition, in which service users are provided with TAU. Outcome data in service users and clinicians will be collected at four time points: at baseline (t 0 ), 2-month post-baseline (t 1 ), 6-month post-baseline (t 2 ), and 12-month post-baseline (t 3 ). The primary outcome will be patient-reported service engagement assessed with the service attachment questionnaire at 2-month post-baseline. The process and economic evaluation will provide in-depth insights into in-vivo context-mechanism-outcome configurations and economic costs of the DMMH and other implementation strategies in routine care, respectively., Discussion: If this trial provides evidence on reach, effectiveness, adoption, implementation and maintenance of implementing ESM-based monitoring, reporting, and feedback, it will form the basis for establishing its public health impact and has significant potential to bridge the research-to-practice gap and contribute to swifter ecological translation of digital innovations to real-world delivery in routine mental health care., Trial Registration: ISRCTN15109760 (ISRCTN registry, date: 03/08/2022)., (© 2024. The Author(s).)

Objective: The number of hospitalized patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) does not differentiate between patients admitted due to coronavirus disease 2019 (COVID-19) (ie, primary cases) and incidental SARS-CoV-2 infection (ie, incidental cases). We developed an adaptable method to distinguish primary cases from incidental cases upon hospital admission., Design: Retrospective cohort study., Setting: Data were obtained from 3 German tertiary-care hospitals., Patients: The study included patients of all ages who tested positive for SARS-CoV-2 by a standard quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay upon admission between January and June 2022., Methods: We present 2 distinct models: (1) a point-of-care model that can be used shortly after admission based on a limited range of parameters and (2) a more extended point-of-care model based on parameters that are available within the first 24-48 hours after admission. We used regression and tree-based classification models with internal and external validation., Results: In total, 1,150 patients were included (mean age, 49.5±28.5 years; 46% female; 40% primary cases). Both point-of-care models showed good discrimination with area under the curve (AUC) values of 0.80 and 0.87, respectively. As main predictors, we used admission diagnosis codes (ICD-10-GM), ward of admission, and for the extended model, we included viral load, need for oxygen, leucocyte count, and C-reactive protein., Conclusions: We propose 2 predictive algorithms based on routine clinical data that differentiate primary COVID-19 from incidental SARS-CoV-2 infection. These algorithms can provide a precise surveillance tool that can contribute to pandemic preparedness. They can easily be modified to be used in future pandemic, epidemic, and endemic situations all over the world.

Prior research into bystander responses to hate speech has utilized variable-centered analyses - such approaches risk simplifying the complex nature of bystander behaviors. Hence, the present study used a person-centered analysis to investigate latent hate speech bystander profiles. In addition, individual and classroom-level correlates associated with the various profiles were studied. The sample included 3225 students in grades 7-9 (51.7% self-identified as female; 37.2% with immigrant background) from 215 classrooms in Germany and Switzerland. The latent profile analysis revealed that four distinct profiles could be distinguished: Passive Bystanders (34.2%), Defenders (47.3%), Revengers (9.8%), and Contributors (8.6%). Multilevel logistic regression models showed common and distinct correlates. For example, students who believed that certain social groups are superior were more likely to be Revengers and Contributors than Passive Bystanders, students who felt more connected with teachers were more likely to be Defenders, and students who were more open to diversity were less likely to be Contributors than Passive Bystanders. Students were less likely Defenders and more likely Revengers and Contributors than Passive Bystanders in classrooms with high rates of hate speech perpetration. Further, in classrooms with high hate speech intervention, students were more likely to be Defenders and less likely to be Contributors than Passive Bystanders. In classrooms with stronger cohesion, students were more likely to be Defenders and less likely to be Contributors than Passive Bystanders. In conclusion, the findings add to our understanding of bystander profiles concerning racist hate speech and the relevance of individual and classroom-level factors in explaining various profiles of bystander behavior., (© 2024. The Author(s).)

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals., (© 2024. The Author(s).)

Background: Due to their clinical training and secondary activities in the hospital, medical students are exposed to contact with SARS-CoV-2 infected people more often than the general population. We determined the seroprevalence of SARS-CoV-2 antibodies in medical students in clinical training at different times during the pandemic and asked participants about possible SARS-CoV-2 exposures in both medical and private settings., Methods: From May 2020 to June 2021, medical students each in their 3rd year of training at the University Hospital Würzburg participated in the cross-sectional survey. All SARS-CoV-2 unvaccinated students were offered a determination of their SARS-CoV-2 serostatus. The blood samples were tested by an immunoassay (Elecsys, Roche) for IgG/IgM/IgA antibodies against the SARS-CoV-2 N antigen. Demographic data, SARS-CoV-2 disease and vaccination status, as well as possible SARS-CoV-2 exposures were collected using a questionnaire., Results: Overall, 383 (86.1%) of 445 students took part in the cross-sectional survey (65% female; median age 22 years; IQR 21-24). Serostatus was determined in 223 (58.2% of 383) SARS-CoV-2 unvaccinated participants. In the period between the beginning of the pandemic in Germany (February 2020) and the time of the survey, 332 (86.7% of 383) students stated that they worked in the medical field, mainly in the context of clinical traineeships (76.8%) or secondary activities with patient contact (48.8%); 129 (33.7%) reported previous contact with a COVID-19 patient, of which 78.3% of contacts took place at a medical facility. Antibodies against SARS-CoV-2 were detected in 8 (3.6%) of the 223 unvaccinated participants tested, and in 3 infected persons an association between infection and contact in the course of medical activity seemed likely., Conclusion: Despite frequent patient contact and the associated increased risk of infection, medical students in their 3rd year of training did not show an increased seroprevalence compared to the general population and showed a lower or similar seroprevalence rate than medical students in other European countries in the first 18 months of the pandemic. This indicates sufficient protection of medical students at the beginning of clinical training through the hygiene and infection protection measures implemented at that time during medical activities., Competing Interests: MK erhält Beratungshonorare von Abbott, GSK und Pfizer ohne Verbindung zum Inhalt des Manuskripts. JL erhält Forschungsgelder von Pfizer, Janssen, GSK, Sanofi, und MSD, und Honorare für Vorträge/Advisory Boards von Astra Zeneca, Pfizer und MSD, ohne Verbindung zum Inhalt des Manuskriptes. AS erhält Forschungsgelder von Pfizer, Janssen, GSK, Sanofi, und MSD ohne Verbindung zum Inhalt des Manuskriptes. Die anderen Autoren geben an, dass kein Interessenskonflikt besteht., (Thieme. All rights reserved.)

Background: An infection with SARS-CoV-2 can lead to a variety of symptoms and complications, which can impair athletic activity., Objective: We aimed to assess the clinical symptom patterns, diagnostic findings, and the extent of impairment in sport practice in a large cohort of athletes infected with SARS-CoV-2, both initially after infection and at follow-up. Additionally, we investigated whether baseline factors that may contribute to reduced exercise tolerance at follow-up can be identified., Methods: In this prospective, observational, multicenter study, we recruited German COVID elite-athletes (cEAs, n = 444) and COVID non-elite athletes (cNEAs, n = 481) who tested positive for SARS-CoV-2 by PCR (polymerase chain reaction test). Athletes from the federal squad with no evidence of SARS-CoV-2 infection served as healthy controls (EAcon, n = 501). Questionnaires were used to assess load and duration of infectious symptoms, other complaints, exercise tolerance, and duration of training interruption at baseline and at follow-up 6 months after baseline. Diagnostic tests conducted at baseline included resting and exercise electrocardiogram (ECG), echocardiography, spirometry, and blood analyses., Results: Most acute and infection-related symptoms and other complaints were more prevalent in cNEA than in cEAs. Compared to cEAs, EAcon had a low symptom load. In cNEAs, female athletes had a higher prevalence of complaints such as palpitations, dizziness, chest pain, myalgia, sleeping disturbances, mood swings, and concentration problems compared to male athletes (p < 0.05). Until follow-up, leading symptoms were drop in performance, concentration problems, and dyspnea on exertion. Female athletes had significantly higher prevalence for symptoms until follow-up compared to male. Pathological findings in ECG, echocardiography, and spirometry, attributed to SARS-CoV-2 infection, were rare in infected athletes. Most athletes reported a training interruption between 2 and 4 weeks (cNEAs: 52.9%, cEAs: 52.4%), while more cNEAs (27.1%) compared to cEAs (5.1%) had a training interruption lasting more than 4 weeks (p < 0.001). At follow-up, 13.8% of cNEAs and 9.9% of cEAs (p = 0.24) reported their current exercise tolerance to be under 70% compared to pre-infection state. A persistent loss of exercise tolerance at follow-up was associated with persistent complaints at baseline, female sex, a longer break in training, and age > 38 years. Periodical dichotomization of the data set showed a higher prevalence of infectious symptoms such as cough, sore throat, and coryza in the second phase of the pandemic, while a number of neuropsychiatric symptoms as well as dyspnea on exertion were less frequent in this period., Conclusions: Compared to recreational athletes, elite athletes seem to be at lower risk of being or remaining symptomatic after SARS-CoV-2 infection. It remains to be determined whether persistent complaints after SARS-CoV-2 infection without evidence of accompanying organ damage may have a negative impact on further health and career in athletes. Identifying risk factors for an extended recovery period such as female sex and ongoing neuropsychological symptoms could help to identify athletes, who may require a more cautious approach to rebuilding their training regimen., Trial Registration Number: DRKS00023717; 06.15.2021-retrospectively registered., (© 2024. The Author(s).)

The spread of Homo sapiens into new habitats across Eurasia ~45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species' history. 'Transitional' technocomplexes, such as the Lincombian-Ranisian-Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to ~45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning ~12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold climates prevailed across LRJ occupations, with a temperature decrease culminating in a pronounced cold excursion at ~45,000-43,000 cal BP. Directly dated H. sapiens remains confirm that humans used the site even during this very cold phase. Together with recent evidence from the Initial Upper Palaeolithic, this demonstrates that humans operated in severe cold conditions during many distinct early dispersals into Europe and suggests pronounced adaptability., (© 2024. The Author(s).)

Ralstonia pickettii is a Gram-negative rod which may cause invasive infections when they contaminate liquid medical products. After R. pickettii was detected in blood cultures and a stem cell product from three patients in a tertiary care hospital in Germany, whole genome sequencing of these three isolates and two water isolates from the environment was performed. Core genome multilocus sequence typing analysis showed that the three patient isolates were closely related and there was a large distance to the environmental isolates. In a genomic comparison, the patients' isolates were distantly related to an R. pickettii strain from a cluster in Australia suspected to be caused by contaminated saline produced in India, while all liquid medical products with a link to all patients were produced in Europe or the United States. Our data point towards an ongoing risk by an unknown common source that could be traced back to medical products contaminated with R. pickettii and potentially distributed worldwide. Investigating invasive R. pickettii infections, identifying and testing medical products administered to the patients and timely whole genome sequencing may help identify the exact source of this potentially global outbreak.

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5 th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: The microscope is important in neurosurgery, but it is not exempt from limitations. The exoscope has emerged as an alternative because it offers better 3-dimensional (3D) visualization and better ergonomics. We present our initial experience in vascular pathology using 3D exoscopy at the Dos de Mayo National Hospital to show the viability of the 3D exoscope in vascular microsurgery. We also provide a review of the literature., Methods: In this work, the Kinevo 900 exoscope was used in 3 patients with cerebral (2) and spinal (1) vascular pathology. We evaluated the image quality, equipment management, ergonomics, educational utility, and 3D glasses and recorded the characteristics of the cases. We reviewed the experience of other authors as well., Results: Three patients underwent surgery: 1 occipital cavernoma, 1 cerebral dural fistula, and 1 spinal dural fistula. Excellent 3D visualization with Zeiss Kinevo 900 exoscope (Carl Zeiss, Germany), surgical comfort, and educational utility occurred, and there were no complications., Conclusions: Our experience and that of other authors suggests that the 3D exoscope shows excellent visualization, better ergonomics, and an innovative educational experience. Vascular microsurgery can be performed safely and effectively., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Although non-fracture-related syndesmotic injuries of the ankle are relatively rare, they may lead to poor clinical outcome if initially undiagnosed or managed improperly. Despite a variety of literature regarding possibilities for treatment of isolated syndesmotic injuries, little is known about effective applications of different therapeutic methods in day-to-day work. The aim of this study was to assess the current status of the treatment of isolated syndesmotic injuries in Germany., Materials and Methods: An online-questionnaire, capturing the routine diagnostic workup including clinical examination, radiologic assessment and treatment strategies, was sent to all members of the German Society of Orthopedic Surgery and Traumatology (DGOU) and Association of Arthroscopic and Joint Surgery (AGA). Statistical analysis was performed using Microsoft excel and SPSS., Results: Each question of the questionnaire was on average answered by 431 ± 113 respondents. External rotation stress test (66%), squeeze test (61%) and forced dorsiflexion test (40%) were most commonly used for the clinical examination. In the diagnostic workup, most clinicians relied on MRI (83%) and conventional X-ray analysis (anterior-posterior 58%, lateral 41%, mortise view 38%). Only 15% of the respondents stated that there is a role for arthroscopic evaluation for the assessment of isolated syndesmotic injuries. Most frequently used fixation techniques included syndesmotic screw fixation (80%, 42% one syndesmotic screw, 38% two syndesmotic screws), followed by suture-button devices in 13%. Syndesmotic screw fixation was mainly performed tricortically (78%). While 50% of the respondents stated that syndesmotic screw fixation and suture-button devices are equivalent in the treatment of isolated syndesmotic injuries with respect to clinical outcome, 36% answered that syndesmotic screw fixation is superior compared to suture-button devices., Conclusions: While arthroscopy and suture-button devices do not appear to be widely used, syndesmotic screw fixation after diagnostic work-up by MRI seems to be the common treatment algorithm for non-fracture-related syndesmotic injuries in Germany., (© 2022. The Author(s).)

Fraction understanding seems a double-edged sword. On the one hand, it is an important predictor of later mathematical achievement. On the other hand, it is also one of the topics students struggle most in secondary math education. To complement traditional instruction, digital learning games were developed and found to successfully foster fraction understanding. However, so far, it is not known to what degree different aspects of fraction understanding (e.g., part-whole relations, fraction magnitude, fraction arithmetic) may be conveyed by such games. The current study evaluated selective associations of in-game performance of the fraction learning game Semideus with specific aspects of fraction understanding assessed using a comprehensive paper-pencil test. In Semideus, seventh graders (M age =12.3years) from academic track secondary schools in Germany estimated the location of fractions on a number line and compared fractions according to their magnitude. Results replicated previous findings showing that in-game performance was significantly associated with mathematics achievement (i.e., math grades) and basic, whole number arithmetic skills. Moreover, we observed significant associations for aspects of fraction understanding closely matching mechanics of the learning game such as fraction number line estimation, fraction magnitude comparison and fraction ordering. These associations were observed for accuracy on the game's fraction learning tasks (e.g., estimation accuracy on the number line) but also generalized to game-based metrics such as virtual incentives (i.e., stars awarded in the game). This implies that the actual game mechanic may help to convey aspects of fraction understanding, substantiating ideas of intrinsic integration in game design., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The significant annual burden caused by seasonal influenza has led to global calls for increased influenza vaccination coverage rates (VCRs). We aimed to estimate the proportion of the German population at high risk of serious illness from influenza due to chronic conditions and to estimate age-specific VCRs of people with/without chronic conditions., Methods: Using health insurance claims data covering nine influenza seasons (2010-2019), we assessed up to 7 million insured individuals per season across all German regions. Individuals were classified according to age and presence of chronic health conditions. VCRs were estimated using outpatient healthcare utilization documentation., Results: In the 2018-2019 influenza season, 47.3% of individuals had ≥1 chronic condition. Most common were circulatory disorders, accounting for more than a third of individuals with ≥1 condition. Prevalence of chronic diseases, and therefore the proportion of high-risk individuals, increased slightly over time across most age groups. A downward trend in influenza VCRs was observed in all age groups until the 2017-2018 season, followed by a noticeable increase in the 2018-2019 season. Highest VCRs occurred among individuals of ≥60 years, with a 38.5% VCR for this age group in the 2018-2019 season. Several factors, including age, chronic condition type, and geographical location, affected VCRs., Conclusions: Influenza VCRs in individuals at high risk of severe complications from influenza infection are insufficient. Our results suggest that intensified public health efforts are necessary to reach the World Health Organization vaccination coverage target of 75%., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults., Methods and Findings: We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias., Conclusions: In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults., Trial Registration: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AV, FE, FT, JJ, JS, JW, MR, MS, and ON report institutional funding for parts of this project from the German BMBF. Unrelated to this study, FT reports payments for lectures from Dresden International University. JA reports grants from the Federal State of Saxony. Unrelated to this study, JS reports grants for investigator-initiated research from the German GBA, the BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings for Sanofi, Lilly, and ALK. MB reports payment for data analysis which is presented in this paper from DAK‐Gesundheit. Unrelated to this study, MB reports grants from German GBA and Sanofi Pasteur and consulting fees from Janssen‐Cilag. He participated in an advisory board for GSK. NT is member of the Steering Committee of the German Society for Pediatric Infectious Diseases (DGPI) and is the DGPI-mandated person for the pediatric expert group on long-COVID in children and adolescents. SB is Head of Analytics and Data Science at AOK PLUS, Dresden, Germany. Unrelated to this study, STSCH reports payments for a guest lecture at TU Berlin. The other authors declare that they have no competing interest., (Copyright: © 2022 Roessler 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: In Germany, winter sports are very popular. About 7 million people go skiing at least 6 days per season. The German national winter teams won about 50% of the Olympic medals for the last several Olympic games. The downside of winter sports is the everlasting high number of injuries. This affects both professionals and the large number of amateur skiers., Trend: The ASU institute of German insurances and skiing association find a decreasing number of injuries overall and a decreasing number of inpatient stays in hospitals. Still, the knee is the most injured region of the body. There is an increasing number of ACL ruptures within the knee lesions. The numbers in professional teams have been monitored with the FIS surveillance system since 2006. The highest rates of knee injuries (41.3%) are found with the ski world cup teams all over the world. The most common injury mechanism is the slip-catch mechanism. In current sports science examinations of the German skiing association there are extremely high forces of more than three times the body weight found on the body during skiing. Slalom skiing is especially affected. To understand the popular carving ski technology, you must know about the waist and the edge angle of the ski. There can be enormous forces coming along with the skis that can hardly be controlled by the skier., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Acute right heart failure is a life-threatening condition that can arise postoperatively. The options for symptomatic treatment have been markedly expanded in recent years through the introduction of percutaneously implantable mechanical cardiac support systems., Methods: This review is based on publications retrieved by a selective literature search in PubMed as well as on guidelines from Germany and abroad., Results: The diagnostic evaluation of right heart failure is chiefly based on echocardiography and pulmonary arterial catheteri - zation and is intended to lead to immediate treatment. Alongside treatment of the cause of the condition, supportive management is crucial to patient survival. A variety of ventilation strategies depending on the situation, catecholamine therapies, inhaled selective pulmonary vasodilators, and cardiac support systems are available for this purpose. The in-hospital mortality of postoperative right heart failure is 5-17 %. The results of the use of cardiac support systems reported in case series are dis - appointing, but nonetheless good compared to what these critically ill patients would face without such treatment. In one observational study, the 30-day survival rate was 73.3%., Conclusion: Survival is aided by the rapid recognition of right heart failure, targeted multidisciplinary treatment, and contact with an extracorporeal life support (ECLS) center for additional supportive treatment measures. Further studies on the use of pharmacological and mechanical cardiac support systems must be carried out to provide stronger evidence on which treatment recommendations can be based.

Importance: Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality., Objective: To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality., Design, Setting, and Participants: This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours., Interventions: A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol., Main Outcomes and Measures: The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay., Results: Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR, 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881 (33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5.9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 1.28; P = .91). None of the 19 prespecified secondary end points differed significantly., Conclusions and Relevance: Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT04016454.

Background: During the first waves of the COVID-19 pandemic, many cultural and sporting events were held without spectators or had to be cancelled. Therefore, several containment strategies to provide requirements for safe events were developed and tested. Nonetheless, every second (50.7%) is afraid of becoming infected on an event. We therefore investigated which hygiene and containment measures are perceived to be important from the visitor's point of view and thus might increase subjective sense of safety., Methods: This online study was carried out in November 2020. A total of 1,004 persons, who regularly attended events before the pandemic, took part in the study. The importance of different hygiene and containment measures was evaluated using a 5-point Likert-scale (1 "unimportant" to 5 "extremely important"). Potential statistical differences in socio-demographical aspects (age, gender, net disposable income for leisure activities) and attendance on events were tested with analyses of variance., Results: Participants perceived the use of disinfectant (M = 4.10) as the most important element of containment strategies, followed by transparent information on the hygiene strategy (M = 4.00), reduced occupancy (M = 3.98), and optimized ventilation (M = 3.97). Body temperature measurement at the entrance (M = 3.27), a negative SARS-CoV-2 test (M = 3.11), completion of a health questionnaire (M = 3.05), and abandoning breaks and catering (M = 2.98) were considered as less important. Analyses of group differences in socio-demographical aspects found abandoning breaks and catering to be more important to men than to women. This strategy is also more important to people aged 66 and above than to younger age groups (e.g., age 20-40). For women, the use of disinfectant is considerably more important. No other significant differences exist., Conclusion: Combining relevant measures appears to be important to provide a safe containment strategy. Measures aimed at positively influencing people's sense of safety do not fully correspond to researched knowledge of effectiveness. There are also target group-specific differences in the rating of measures, which should be considered while preparing containment strategies. To describe the dynamic development of changes in subjective rating of containment strategies, continuing research is needed., (© 2022. The Author(s).)

Objectives: This retrospective study evaluates intraoral surgical and conservative treatment need in patients with a chronic kidney end-stage disease, depending on the duration of dialysis treatment and the causative nephrological disease., Material and Methods: This study is based on data of patients referred to the Department of Oral and Maxillofacial Surgery of the University Hospital Erlangen, Germany, prior to kidney transplantation between January 2015 and March 2020. The necessity for oral surgical or dental therapy was determined by clinical and radiological examinations. Data on renal replacement therapy, cause of underlying renal disease, lifestyle, and general health were collected., Results: Data of N = 89 patients demonstrated that surgical treatment need depends on dialysis duration (p = 0.042). Patients, who had been dialyzing for 2 to 3 years showed the highest need for surgical intervention (80.0%; p = 0.024), followed by dialysis patients with a dialysis time of more than 3 years (48.1%). Similarly, dialysis patients in the second or third year of dialysis had the highest need for conservative treatment (73.3%; p > 0.05), followed by 55.6% of dialysis patients in the third year of dialysis., Conclusions: Operative and conservative treatment is essential to optimize subsequent kidney transplantation. The greatest necessity could be detected for patients in the second and third years of dialysis., Clinical Relevance: Oral health addressing surgical and conservative treatment need depends on the duration of dialysis in patients with a chronic kidney end-stage disease., (© 2021. The Author(s).)

Background: The rise of an infectious disease crisis such as the SARS-CoV‑2 pandemic posed significant challenges for the administrative structures of the public health service, which resulted in varying levels of efficiency in outbreak management as a function of staffing and digital resources. This substantially impeded the integration of innovative pandemic outbreak management tools. Innovative crisis management, such as cluster tracking, risk group testing, georeferencing, or the integration of wastewater surveillance recommended by the EU Commission, was made significantly more difficult., Aim: In this case study in Berchtesgadener Land, we present the integration of an area-wide georeferenced wastewater surveillance system that captured 95% of the entire population since November 2020., Methodology: Sampling occurred twice a week at nine municipal wastewater treatment plants and directly from the main sewer at three locations. Samples were pre-treated by centrifugation and subsequently analyzed by digital droplet polymerase chain reaction (PCR) targeting four specific genes of SARS-CoV‑2., Results: The integration of an area-wide georeferenced wastewater surveillance system was successful. Wastewater occurrences are plotted for each municipality against cumulative infections over seven days per 100,000 inhabitants. Changes in the infection pattern in individual communities are noticeable ten days ahead of the official case numbers with a sensitivity of approximately 20 in 100,000 inhabitants., Discussion: The integration of this innovative approach to provide a comprehensive overview of the situation by employing a digital dashboard and the use of an early warning system via quantitative wastewater surveillance resulted in very efficient, proactive management, which might serve as a blueprint for other municipalities in Germany., (© 2021. The Author(s).)

This retrospective cross-sectional epidemiological study deals with sport-specific injury patterns in show jumping. A total of 363 show jumpers of all levels (S) answered a retrospective questionnaire about injuries and overuse damages which occurred in the course of their careers. Demographic data and information on injuries in various body regions were collected. In addition to descriptive analysis, significance tests were performed. For better statistical comparability with other sports, exposure time was extrapolated with total career duration and weekly training hours, and injuries per 1000 jumping hours were calculated. The study included 251 (69%) women and 112 (31%) men, who were on average 26.9 ± 10.9 years old. The injury rate for the entire collective was 3.7 per 1000 h of exposure. The most frequently affected body region was the head (31%). Overuse complaints play a subordinate role and mainly affect the upper extremities (65%). The riders of the professional lower performance levels are less likely to injure themselves per 1000 h than riders of the higher performance levels. Riders who often or always wore a helmet suffered significantly fewer head injuries ( p = 0.008) and had a significantly lower total injury duration than riders who did not wear a helmet ( p = 0.006). Similarly, the study showed that riders who often or always wore a safety vest suffered significantly fewer spinal injuries ( p = 0.017) and had significantly fewer injuries per 1000 riding hours ( p = 0.031) than riders who did not wear a safety vest. Based on the present results, there should be an extension of the general helmet requirement and a requirement to wear safety vests in show jumping in general.

Introduction: Accumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion of autologous ex vivo expanded Treg in adults with ulcerative colitis., Methods and Analysis: The study is designed as a single-arm, fast-track dose-escalation trial. The study will include 10 patients with ulcerative colitis. The study intervention consists of (1) a baseline visit; (2) a second visit that includes a leukapheresis to generate the investigational medicinal product, (3) a third visit to infuse the investigational medicinal product and (4) five subsequent follow-up visits within the next 26 weeks to assess safety and tolerability. Patients will intravenously receive a single dose of 0.5×10 6 , 1×10 6 , 2×10 6 , 5×10 6  or 10×10 6 autologous Treg/kg body weight. The primary objective is to define the maximum tolerable dose of a single infusion of autologous ex vivo expanded Treg. Secondary objectives include the evaluation of safety of one single infusion of autologous ex vivo expanded Treg, efficacy assessment and accompanying immunomonitoring to measure Treg function in the peripheral blood and intestinal mucosa., Ethics and Dissemination: The study protocol was approved by the Ethics Committee of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany (number 417&#95;19 Az). In addition, the study was approved by the Paul-Ehrlich Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany (number 3652/01). The study is funded by the German Research Foundation (DFG, KFO 257 project 08 and SFB/TransRegio 241 project C04). The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki, Good Clinical Practice and Good Manufacturing Practice. The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media., Trial Registration Number: NCT04691232., Competing Interests: Competing interests: GS is inventor of granted patents related to the manuscript (publication number EP 1379625; CD4+CD25+ regulatory T cells from human blood)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Surgical departments are discredited as guardians of traditional structures of hierarchy. Hierarchy and working climate have a large share in human factor, being made responsible for 70% of avoidable errors in medicine. Aim of this study was the assessment of these topics amongst physicians in the field of orthopedics and traumatology., Material and Methods: A questionnaire of 10 questions was digitally handed to DGOU members. 799 questionnaires were answered., Results: We found significant differences in the assessment of hierarchy and working atmosphere amongst the physician groups. Working atmosphere was perceived as not appreciative by registrars only. All groups were in favor of a hierarchy rather close to, but nut absolutely on equal terms. All groups attach high influence of working atmosphere on quality of daily work., Discussion: Literature shows that hierarchic differentiation can increase performance of a team, while rigid hierarchy structures can lead to mistakes. Although hierarchy in orthopedics and traumatology seems to be less pronounced than assumed, hierarchy has great influence on daily work., Conclusion: In order to achieve a safety oriented medical environment, it will be of great importance to define hierarchy structures in clinics and to utilize them efficiently as a part of safety culture., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: Contradicting definitions of periprosthetic joint infection (PJI) are in use. Joint aspiration is performed before total hip arthroplasty (THA) revision. This study investigated the influence of PJI definition on PJI prevalence at THA revision. Test quality of prerevision aspiration was evaluated for the different PJI definitions., Methods: 256 THA revisions were retrospectively classified to be infected or not infected. Classification was performed according to the 4 different definitions proposed by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), the International Consensus Meeting (ICM), and the European Bone and Joint Infection Society (EBJIS). Only chronic PJIs were included., Results: PJI prevalence at revision significantly correlated with the applied PJI definition ( p = 0.01, Cramer's V = 0.093). PJI prevalence was 20.7% for the MSIS, 25.4% for the ICM, 28.1% for the IDSA, and 32.0% for the EBJIS definition. For synovial fluid white blood cell count, the best ROC-AUC for predicting PJI was 0.953 in combination with the MSIS definition., Conclusion: PJI definition significantly influences the rate of diagnosed PJIs at THA revision. Synovial fluid white blood cell count is a reliable means to rule out PJI. In cases with a borderline high synovial white blood cell count before THA revision as the only sign of chronic PJI, an extended diagnostic work-up should be considered., Competing Interests: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021 Sebastian Philipp Boelch et al.)

Background: Patients with coronavirus disease 2019 (COVID-19) who undergo surgery have impaired postoperative outcomes and increased mortality. Consequently, elective and semi-urgent operations on the increasing number of patients severely affected by COVID-19 have been indefinitely postponed.in many countries with unclear implications on disease progression and overall survival. The purpose of this study was to evaluate whether the establishment of a standardized screening program for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficient to ensure high-quality medical and surgical treatment of COVID-19 and non-COVID-19 patients while minimizing in-hospital SARS-CoV-2 transmission., Methods: The screening program comprised polymerase chain reaction (PCR) testing of nasopharyngeal swabs and a standardized questionnaire about potential symptoms for SARS-CoV-2 infection. All elective and emergency patients admitted to the surgical department of a tertiary-care hospital center in Lower Franconia, Germany, between March and May 2020 were included and their characteristics were recorded., Results: Out of the study population (n = 657), 509 patients (77.5%) had at least one risk factor for a potentially severe course of COVID-19 and 164 patients (25%) were active smokers. The average 7-day incidence in Lower Franconia was 24.0/100,000 during the observation period. Preoperative PCR testing revealed four asymptomatic positive patients out of the 657 tested patients. No postoperative SARS-CoV-2 infection or transmission could be detected., Conclusion: The implementation of a standardized preoperative screening program to both COVID-19 and non-COVID-19 patients can ensure high-quality surgical care while minimizing infection risk for healthcare workers and potential in-hospital transmission., (© 2021. The Author(s).)

Background: Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail., Methods: Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model., Results: Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both p adjust  < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (R A ) (p = 0.116), but diminished resistance of efferent arterioles (R E ) (p = 0.001). In M+I group R A was increased (p = 0.006) and R E remained unchanged (p = 0.538). The effects on R A (p adjust  < 0.05) and on R E (p adjust  < 0.05) differed between the groups., Conclusions: In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing R A and E+L predominantly decreasing R E , which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects., Trial Registration: The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016., (© 2021. The Author(s).)

Gene therapy can be used to restore cell function in monogenic disorders or to endow cells with new capabilities, such as improved killing of cancer cells, expression of suicide genes for controlled elimination of cell populations, or protection against chemotherapy or viral infection. While gene therapies were originally most often used to treat monogenic diseases and to improve hematopoietic stem cell transplantation outcome, the advent of genetically modified immune cell therapies, such as chimeric antigen receptor modified T cells, has contributed to the increased numbers of patients treated with gene and cell therapies. The advancement of gene therapy with integrating retroviral vectors continues to depend upon world-wide efforts. As the topic of this special issue is "Spotlight on Germany," the goal of this review is to provide an overview of contributions to this field made by German clinical and research institutions. Research groups in Germany made, and continue to make, important contributions to the development of gene therapy, including design of vectors and transduction protocols for improved cell modification, methods to assess gene therapy vector efficacy and safety (e.g., clonal imbalance, insertion sites), as well as in the design and conduction of clinical gene therapy trials., (© 2021. The Author(s).)

Background: Vaccines are an important tool to limit the health and economic damage of the Covid-19 pandemic. Several vaccine candidates already provided promising effectiveness data, but it is crucial for an effective vaccination campaign that people are willing and able to get vaccinated as soon as possible. Taking Germany as an example, we provide insights of using a mathematical approach for the planning and location of vaccination sites to optimally administer vaccines against Covid-19., Methods: We used mathematical programming for computing an optimal selection of vaccination sites out of a given set (i.e., university hospitals, health department related locations and general practices). Different patient-to-facility assignments and doctor-to-facility assignments and different constraints on the number of vaccinees per site or maximum travel time are used., Results: In order to minimize the barriers for people to get vaccinated, i.e., limit the one-way travel journey (airline distance) by around 35 km for 75% of the population (with a maximum of 70 km), around 80 well-positioned facilities can be enough. If only the 38 university hospitals are being used, the 75% distance increases to around 50 km (with a maximum of 145 km). Using all 400 health departments or all 56 000 general practices can decrease the journey length significantly, but comes at the price of more required staff and possibly wastage of only partially used vaccine containers., Conclusions: In the case of free assignments, the number of required physicians can in most scenarios be limited to 2 000, which is also the minimum with our assumptions. However, when travel distances for the patients are to be minimized, capacities of the facilities must be respected, or administrative assignments are prespecified, an increased number of physicians is unavoidable., (© 2021. The Author(s).)

Dual process theories suggest that the decision to be physically active is influenced by reflective and automatic processes. However, associations of automatic (affective) evaluations of exercise with physical activity and underlying basic motor competencies have not yet been investigated in children and young adolescents. Ninety-one participants (52 male; age: 10-14 years) were recruited from academic high schools in Germany and Switzerland. Automatic evaluations of exercise were measured with the Single-Target Implicit Association Test (ST-IAT) and a D-score was calculated. Moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) per day were determined via wrist-worn actigraphy over the course of seven days. Basic motor competencies were measured using the MOBAK-5 test battery. Pearson correlations showed non-significant associations of automatic evaluations of exercise with MVPA, but significant associations with VPA. Basic motor competencies were associated with automatic evaluations of exercise, and the MOBAK subscale of object movement was associated with both MVPA and VPA. Our results underscore the relevance of affective processes for physical activity behaviour. This could potentially be relevant for interventions targeting physical activity promotion. Longitudinal investigations and intervention studies are necessary to verify causal relationships and potential underlying mechanisms.

Introduction: So far there has been little evidence of the extent to which project steps can affect the timing and successful implementation of research projects in general practitioner (GP) practices. Using the example of an intervention study on palliative care, the aim of this article is to report a) how the overall course of the project turned out compared to the original planning, and b) what recommendations can be derived to promote efficient implementation of intervention studies in GP practices., Methods: In two workshops each, GP practice teams selected specific measures to improve their palliative care and tested them during a four-month implementation phase. In order to track the progress of the project, the times at which the practice teams reported their participation in the study, the individual project steps and the contacts were documented and descriptively analysed using Microsoft Excel., Results: Due to a high willingness of practice teams to participate in the intervention study, recruitment was completed on time. The overall duration of the project was extended due to an increased workload for the preparation of an unexpectedly high number of selected measures to improve palliative care., Discussion: Conducting intervention studies in GP practices is promising if practice teams take an active and co-determining role during the entire research process. Research projects can best be implemented if they involve minimal time commitment for the practice teams, and if continuous personal support from the study team is ensured., Conclusion: When planning future intervention studies with a high participatory share of GP practice teams, it is advisable to take into account potential additional work for the preparation and further development of intervention measures., (Copyright © 2021. Published by Elsevier GmbH.)

Three novel corynebacterial species were isolated from soil sampled at a paddock in Vilsendorf, North Rhine-Westphalia, Germany. The strains were coccoid or irregular rod-shaped, catalase-positive and pale white to yellow-orange in colour. By whole genome sequencing and comparison of the 16S rRNA genes as well as the whole genome structure, it was shown that all three strains represent novel species of the family Corynebacteriaceae , order Corynebacteriales , class Actinobacteria . This project describes the isolation, identification, sequencing, and phenotypic characterization of the three novel Corynebacterium species. We propose the names Corynebacterium kalinowskii sp. nov. (DSM 110639 T =LMG 31801 T ), Corynebacterium comes sp. nov. (DSM 110640 T =LMG 31802 T ), and Corynebacterium occultum sp. nov. (DSM 110642 T =LMG 31803 T ).

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10 -4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10  × 10 -7 ). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD., (© 2019. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Blood alcohol level (BAL) has previously been considered as a factor influencing the outcome of injured patients. Despite the well-known positive correlation between alcohol-influenced traffic participation and the risk of accidents, there is still no clear evidence of a positive correlation between blood alcohol levels and severity of injury. The aim of the study was to analyze data of the TraumaRegister DGU ® (TR-DGU), to find out whether the blood alcohol level has an influence on the type and severity of injuries as well as on the outcome of multiple-trauma patients., Methods: Datasets from 11,842 trauma patients of the TR-DGU from the years 2015 and 2016 were analyzed retrospectively and 6268 patients with a full dataset and an AIS ≥ 3 could be used for evaluation. Two groups were formed for data analysis. A control group with a BAL = 0 ‰ (BAL negative) was compared to an alcohol group with a BAL of ≥0.3‰ to < 4.0‰ (BAL positive). Patients with a BAL >  0‰ and <  0.3‰ were excluded. They were compared with regard to various preclinical, clinical and physiological parameters. Additionally, a subgroup analysis with a focus on patients with a traumatic brain injury (TBI) was performed. A total of 5271 cases were assigned to the control group and 832 cases to the BAL positive group. 70.3% (3704) of the patients in the control group were male. The collective of the control group was on average 5.7 years older than the patients in the BAL positive group (p < .001). The control group showed a mean ISS of 20.3 and the alcohol group of 18.9 (p = .007). In terms of the injury severity of head, the BAL positive group was significantly higher on average than the control group (p <  0.001), whereas the control group showed a higher AIS to thorax and extremities (p <  0.001). The mean Glasgow Coma Scale (GCS) was 10.8 in the BAL positive group and 12.0 in the control group (p <  0.001). Physiological parameters such as base excess (BE) and International Normalized Ratio (INR) showed reduced values ​​for the BAL positive group. However, neither the 24-h mortality nor the overall mortality showed a significant difference in either group (p = 0.19, p = 0.14). In a subgroup analysis, we found that patients with a relevant head injury (AIS: Abbreviated Injury Scale head ≥3) and positive BAL displayed a higher survival rate compared to patients in the control group with isolated TBI (p < 0.001)., Conclusions: This retrospective study analyzed the influence of the blood alcohol level in severely injured patients in a large national dataset. BAL positive patients showed worse results with regard to head injuries, the GCS and to some other physiological parameters. Finally, neither the 24-h mortality nor the overall mortality showed a significant difference in either group. Only in a subgroup analysis the mortality rate in BAL negative patients with TBI was significantly higher than the mortality rate of BAL positive patients with TBI. This mechanism is not yet fully understood and is discussed controversially in the literature., (© 2021. The Author(s).)

Background and Objective: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe illness with the hallmark symptom of Post-Exertional Malaise (PEM). Currently, no biomarkers or established diagnostic tests for ME/CFS exist. In Germany, it is estimated that over 300,000 people are affected by ME/CFS. Research from the United States and the UK shows that patients with ME/CFS are medically underserved, as they face barriers to medical care access and are dissatisfied with medical care. The first aim of the current research was to investigate whether patients with ME/CFS are medically underserved in Germany in terms of access to and satisfaction with medical care. Second, we aimed at providing a German-language version of the DePaul Symptom Questionnaire Short Form (DSQ-SF) as a tool for ME/CFS diagnostics and research in German-speaking countries. Materials and Methods: The current research conducted an online questionnaire study in Germany investigating the medical care situation of patients with ME/CFS. The questionnaire was completed by 499 participants who fulfilled the Canadian Consensus Criteria and reported PEM of 14 h or longer. Results: Participants frequently reported geographic and financial reasons for not using the available medical services. Furthermore, they reported low satisfaction with medical care by the physician they most frequently visited due to ME/CFS. The German version of the DSQ-SF showed good reliability, a one-factorial structure and construct validity, demonstrated by correlations with the SF-36 as a measure of functional status. Conclusions: Findings provide evidence that patients with ME/CFS in Germany are medically underserved. The German-language translation of the DSQ-SF provides a brief, reliable and valid instrument to assess ME/CFS symptoms to be used for research and clinical practice in German-speaking countries. Pathways to improve the medical care of patients with ME/CFS are discussed.

Background: Common mental disorders are one of the leading causes for sickness absence and early retirement due to reduced health. Furthermore, a treatment gap for common mental disorders has been described worldwide. Within this study, psychotherapeutic consultation at work defined as a tailored, module-based and work-related psychotherapeutic intervention will be applied to improve mental health care., Methods: This study comprises a randomised controlled multicentre trial with 1:1 allocation to an intervention and control group. In total, 520 employees with common mental disorders shall be recruited from companies being located around five study centres in Germany. Besides care as usual, the intervention group will receive up to 17 sessions of psychotherapy. The first session will include basics diagnostics and medical indication of treatment and the second session will include work-related diagnostics. Then, participants of the intervention group may receive work-related psychotherapeutic consultation for up to ten sessions. Further psychotherapeutic consultation during return to work for up to five sessions will be offered where appropriate. The control group will receive care as usual and the first intervention session of basic diagnostics and medical indication of treatment. After enrolment to the study, participants will be followed up after nine (first follow-up) and fifteen (second follow-up) months. Self-reported days of sickness absence within the last 6 months at the second follow-up will be used as the primary outcome and self-efficacy at the second follow-up as the secondary outcome. Furthermore, a cost-benefit assessment related to costs of common mental disorders for social insurances and companies will be performed., Discussion: Psychotherapeutic consultation at work represents a low threshold care model aiming to overcome treatment gaps for employees with common mental disorders. If successfully implemented and evaluated, it might serve as a role model to the care of employees with common mental disorders and might be adopted in standard care in cooperation with sickness and pension insurances in Germany., Trial Registration: The friaa project was registered at the German Clinical Trial Register (DRKS) at 01.03.2021 (DRKS00023049): https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00023049 .