460 results on '"Reinhard Berner"'
Search Results
2. Sex and age-related patterns in pediatric primary headaches: observations from an outpatient headache clinic
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Vanda Faria, Berit Höfer, Anna Klimova, Maja von der Hagen, Reinhard Berner, Rainer Sabatowski, Thea Koch, Anke Hübler, Matthias Richter, Eric A. Moulton, Scott A. Holmes, and Gudrun Gossrau
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migraine ,pediatric headache ,primary headache ,tension-type headache ,sex ,age ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
BackgroundAge reportedly affects headache prevalence differently in boys and girls. However, little empirical data exists regarding pediatric headache prevalence and headache-related burden in children and adolescents according to age and sex. In the present study, we considered age and sex while evaluating the distribution, characteristics, and impairment of primary headache disorders at a pediatric headache center in Germany.MethodsMedical records of children and adolescents attending the headache clinic of the Interdisciplinary Pain Center of the Carl Gustav Carus University Hospital in Dresden during the period 2015–2022 were retrospectively grouped and analyzed depending on age (< or ≥14 years) and sex.ResultsThe study population consisted of 652 children and adolescents, aged between 3 and 18 years. Almost two-thirds of the patients (≈60%) were females, and almost two-thirds of these females (58%) were ≥14 years of age. Generally, the most prevalent headache diagnoses as defined by the International Classification of Headache Disorders 3rd edition were episodic migraine without aura and the combination of tension-type headache and episodic migraine with or without aura i.e., mixed-type headache (each ≈27%). In the younger group (
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- 2024
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3. Prevalence of infectious diseases, immunity to vaccine-preventable diseases and chronic medical conditions among Ukrainian refugees in Germany – A cross sectional study from the German Network University Medicine (NUM)
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Folke Brinkmann, Anette Friedrichs, Georg MN Behrens, Pia Behrens, Reinhard Berner, Amke Caliebe, Claudia M. Denkinger, Katharina Giesbrecht, Alexander Gussew, Anna Theresa Hoffmann, Leonhard Hojenski, Olga Hovardovska, Alexandra Dopfer-Jablonka, Achim J. Kaasch, Robin Kobbe, Monika Kraus, Andreas Lindner, Christoph Maier, Lazar Mitrov, Matthias Nauck, Susana Nunes de Miranda, Margarete Scherer, Yvonne Schmiedel, Dana Stahl, Nina Timmesfeld, Nicole Toepfner, Janne Vehreschild, Walter A. Wohlgemuth, Astrid Petersmann, and Maria J.G.T. Vehreschild
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Infections ,Severe Acute Respiratory Syndrome Coronavirus-2 ,Infectious diseases ,refugees ,Ukraine ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Background: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. Methods: Using different media, we recruited Ukrainian refugees at 13 sites between 9–12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. Results: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children.Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. Conclusions: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.
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- 2024
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4. Resource utilization and costs of transitioning from pediatric to adult care for patients with chronic autoinflammatory and autoimmune disorders
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Daniela Choukair, Christian Patry, Ronny Lehmann, Dorothea Treiber, Georg F. Hoffmann, Corinna Grasemann, Normi Bruck, Reinhard Berner, Peter Burgard, Hanns-Martin Lorenz, and Burkhard Tönshoff
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Chronic autoinflammatory and autoimmune disorders ,Cost ,Empowerment ,Health literacy ,Transition from pediatric to adult care ,Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background A structured transition of adolescents and young adults with chronic autoinflammatory and autoimmune disorders from the pediatric to the adult health care system is important. To date, data on the time, processes, outcome, resources required for the necessary components of the transition process and the associated costs are lacking. Methods Evaluation of resource use and costs in a prospective cohort study of 58 adolescents with chronic autoinflammatory and autoimmune disorders, for the key elements of a structured transition pathway including (i) compilation of a summary of patient history, (ii) assessment of patients’ disease-related knowledge and needs, (iii) required education and counseling sessions, (iv) and a transfer appointment of the patient with the current pediatric and the future adult rheumatologist. Results Forty-nine of 58 enrolled patients (84.5%) completed the transition pathway and were transferred to adult care. The mean time from the decision to start the transition process to the final transfer consultation was 315 ± 147 days. Transfer consultations were performed in 49 patients, including 10 patients jointly with the future adult rheumatologist. Most consultations were performed by the multidisciplinary team with a median of three team members and lasted 65.5 ± 21.3 min. The cumulative cost of all consultation and education sessions performed including the transfer appointment was 283 ± 164 Euro per patient. In addition, the cost of coordinating the transition process was 57.3 ± 15.4 Euro. Conclusions A structured transition pathway for patients with chronic autoinflammatory and autoimmune disorders is resource and time consuming and should be adequately funded.
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- 2024
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5. Secondary use of patient data within decentralized studies using the example of rare diseases in Germany: A data scientist's exploration of process and lessons learned
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Michele Zoch, Christian Gierschner, Anne-Katrin Andreeff, Elisa Henke, Martin Sedlmayr, Gabriele Müller, Jenny Tippmann, Helge Hebestreit, Daniela Choukair, Georg F. Hoffmann, Fleur Fritz-Kebede, Nicole Toepfner, Reinhard Berner, Stephanie Biergans, Raphael Verbücheln, Jannik Schaaf, Julia Fleck, Felix Nikolaus Wirth, Josef Schepers, and Fabian Prasser
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Objective Unlocking the potential of routine medical data for clinical research requires the analysis of data from multiple healthcare institutions. However, according to German data protection regulations, data can often not leave the individual institutions and decentralized approaches are needed. Decentralized studies face challenges regarding coordination, technical infrastructure, interoperability and regulatory compliance. Rare diseases are an important prototype research focus for decentralized data analyses, as patients are rare by definition and adequate cohort sizes can only be reached if data from multiple sites is combined. Methods Within the project “Collaboration on Rare Diseases”, decentralized studies focusing on four rare diseases (cystic fibrosis, phenylketonuria, Kawasaki disease, multisystem inflammatory syndrome in children) were conducted at 17 German university hospitals. Therefore, a data management process for decentralized studies was developed by an interdisciplinary team of experts from medicine, public health and data science. Along the process, lessons learned were formulated and discussed. Results The process consists of eight steps and includes sub-processes for the definition of medical use cases, script development and data management. The lessons learned include on the one hand the organization and administration of the studies (collaboration of experts, use of standardized forms and publication of project information), and on the other hand the development of scripts and analysis (dependency on the database, use of standards and open source tools, feedback loops, anonymization). Conclusions This work captures central challenges and describes possible solutions and can hence serve as a solid basis for the implementation and conduction of similar decentralized studies.
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- 2024
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6. Epidemiology of 7375 children and adolescents hospitalized with COVID-19 in Germany, reported via a prospective, nationwide surveillance study in 2020–2022
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Maren Doenhardt, Markus Hufnagel, Natalie Diffloth, Johannes Hübner, René Mauer, Dominik T. Schneider, Arne Simon, Tobias Tenenbaum, Andreas Trotter, Jakob Armann, Reinhard Berner, and The DGPI COVID-19 working group
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Medicine ,Science - Abstract
Abstract By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020–November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1–4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1–4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines.
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- 2024
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7. Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection
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Julian Eder, Leonie Schumm, Jakob P. Armann, Milo A. Puhan, Felix Beuschlein, Clemens Kirschbaum, Reinhard Berner, and Nicole Toepfner
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Medicine ,Science - Abstract
Abstract Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.
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- 2023
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8. Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in children under 5 years
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Christoph Strumann, Otavio Ranzani, Jeanne Moor, Reinhard Berner, Nicole Töpfner, Cho-Ming Chao, and Matthias B. Moor
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Infectious disease ,Vaccines ,Medicine - Published
- 2023
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9. Transition for adolescents with a rare disease: results of a nationwide German project
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Corinna Grasemann, Jakob Höppner, Peter Burgard, Michael M. Schündeln, Nora Matar, Gabriele Müller, Heiko Krude, Reinhard Berner, Min Ae Lee-Kirsch, Fabian Hauck, Kerstin Wainwright, Sylvana Baumgarten, Janet Atinga, Jens J. Bauer, Eva Manka, Julia Körholz, Cordula Kiewert, André Heinen, Tanita Kretschmer, Tobias Kurth, Janna Mittnacht, Christoph Schramm, Christoph Klein, Holm Graessner, Olaf Hiort, Ania C. Muntau, Annette Grüters, Georg F. Hoffmann, and Daniela Choukair
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Transition ,Rare disease ,Pathway ,Empowerment ,Health literacy ,Adolescent health ,Medicine - Abstract
Abstract Purpose The transition process from paediatric/adolescent to adult medical care settings is of utmost importance for the future health of adolescents with chronic diseases and poses even more difficulties in the context of rare diseases (RDs). Paediatric care teams are challenged to deliver adolescent-appropriate information and structures. Here we present a structured transition pathway which is patient-focused and adoptable for different RDs. Methods The transition pathway for adolescents 16 years and older was developed and implemented as part of a multi-centre study in 10 university hospitals in Germany. Key elements of the pathway included: assessment of patients’ disease-related knowledge and needs, training/educational and counselling sessions, a structured epicrisis and a transfer appointment jointly with the paediatric and adult specialist. Specific care coordinators from the participating university hospitals were in charge of organization and coordination of the transition process. Results Of a total of 292 patients, 286 completed the pathway. Deficits in disease-specific knowledge were present in more than 90% of participants. A need for genetic or socio-legal counselling was indicated by > 60%. A mean of 2.1 training sessions per patient were provided over a period of almost 1 year, followed by the transfer to adult care in 267 cases. Twelve patients remained in paediatric care as no adult health care specialist could be identified. Targeted training and counselling resulted in improved disease-specific knowledge and contributed to empowering of patients. Conclusion The described transition pathway succeeds to improve health literacy in adolescents with RDs and can be implemented by paediatric care teams in any RD specialty. Patient empowerment was mainly achieved by individualized training and counselling.
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- 2023
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10. FamilyCoviDD19: results of a cross-sectional study—long-term outcomes of infected and uninfected household members
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Reinhard Berner, Alexander Dalpke, Christian Lück, Jakob P Armann, Theresa S Horst, Maren Doenhardt, Svenja Dreßen, Paula Czyborra, Josephine Schneider, Christin Gano, Annet Bluschke, Magdalena Wekenborg, and Judith Blankenburg
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Medicine (General) ,R5-920 - Abstract
Objective In this study, we aimed to compare long-term physical and mental health outcome between SARS-CoV-2 infected and uninfected household members to differentiate between infection-related and pandemic-related outcomes after about two and a half years of the pandemic. Furthermore, possible differences in the outcome of adults and children and young people (CYP) were of interest.Design In a cross-sectional study design, we compared the long-term physical and mental health outcome of between infected and uninfected as well as between adult and CYP (household members).Setting The FamilyCoviDD19 study—a serology study in households—was initially conducted to evaluate virus transmission in a close contact setting focusing on households with children and adolescents in Germany. At least 1 year after initial infection in the respective households, a follow-up took place in which the prevalence and type of possible long-term consequences were surveyed on the basis of self-reported information on physical and mental health.Participant In this study, a total of 533 household members of 146 families participated and responded to our survey, including 296 (55.5%) adults and 237 (44.5%) CYP.Result The difference in frequency of reported symptoms between infected and uninfected individuals was very moderate, suggesting that the vast majority of reported symptoms were not attributable to a previous SARS-CoV-2 infection. However, regardless of age and infection status, this study showed overall high rates of self-reported symptoms with CYP having fewer long-term sequelae than adults one year after infection. Furthermore, over 50% of those reporting symptoms were not affected in their daily life, with CYPs reporting an even lower percentage compared with adults.Conclusion CYP are at reduced risk not only to develop symptomatic infection or severe disease courses (previous analyses) but also to develop infection-associated long-term sequelae (this study). Independent of infection CYP reported high rates of neurocognitive, pain, somatic and mood symptoms, which makes the influence of the pandemic itself—including pandemic control measures—decisive.
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- 2023
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11. A comparison of pediatric inflammatory multisystem syndrome temporarily-associated with SARS-CoV-2 and Kawasaki disease
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Markus Hufnagel, Jakob Armann, André Jakob, Maren Doenhardt, Natalie Diffloth, Anton Hospach, Dominik T. Schneider, Andreas Trotter, Martin Roessler, Jochen Schmitt, Reinhard Berner, and The PIMS-DGPI Working Group
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Medicine ,Science - Abstract
Abstract The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4–11] vs. 3 [IQR 1–4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae—mainly cardiovascular—were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.
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- 2023
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12. Functional improvement in children and adolescents with primary headache after an interdisciplinary multimodal therapy program: the DreKiP study
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Hanna Sobe, Matthias Richter, Reinhard Berner, Maja von der Hagen, Antje Hähner, Ingo Röder, Thea Koch, Rainer Sabatowski, Anna Klimova, and Gudrun Gossrau
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Headache ,Children ,Therapy program ,Medicine - Abstract
Abstract Background More than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing. Methods One hundred eleven patients with frequent migraine and/or tension type headache were treated in a 15 hour group program in afternoons, parallel with school, parents received 7 hours of therapy. At the beginning of the program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were prospectively collected to investigate the effects of the therapy. Results Seventy-five patients (9-19 years, median = 14; 66.7% female) and their parents provided patient reported outcome measures showing at T1 (65 patients) and T2 (47 patients) reduced headache frequency (last 3 months headache days median T0: 30 days; T1: 18 days, reduction of median 12 days since T0; T2: 13 days, reduction of median 17 days since T0). Linear mixed models revealed significant reduction (T0/T1 p = 0,002; T0/T2 p = 0,001). Reduced headache disability has been reported at T1 and T2 (PedMidas median T0 = 30, T1 = 15, T2 = 7; p
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- 2022
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13. Interoperable, Domain-Specific Extensions for the German Corona Consensus (GECCO) COVID-19 Research Data Set Using an Interdisciplinary, Consensus-Based Workflow: Data Set Development Study
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Gregor Lichtner, Thomas Haese, Sally Brose, Larissa Röhrig, Liudmila Lysyakova, Stefanie Rudolph, Maria Uebe, Julian Sass, Alexander Bartschke, David Hillus, Florian Kurth, Leif Erik Sander, Falk Eckart, Nicole Toepfner, Reinhard Berner, Anna Frey, Marcus Dörr, Jörg Janne Vehreschild, Christof von Kalle, and Sylvia Thun
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundThe COVID-19 pandemic has spurred large-scale, interinstitutional research efforts. To enable these efforts, researchers must agree on data set definitions that not only cover all elements relevant to the respective medical specialty but also are syntactically and semantically interoperable. Therefore, the German Corona Consensus (GECCO) data set was developed as a harmonized, interoperable collection of the most relevant data elements for COVID-19–related patient research. As the GECCO data set is a compact core data set comprising data across all medical fields, the focused research within particular medical domains demands the definition of extension modules that include data elements that are the most relevant to the research performed in those individual medical specialties. ObjectiveWe aimed to (1) specify a workflow for the development of interoperable data set definitions that involves close collaboration between medical experts and information scientists and (2) apply the workflow to develop data set definitions that include data elements that are the most relevant to COVID-19–related patient research regarding immunization, pediatrics, and cardiology. MethodsWe developed a workflow to create data set definitions that were (1) content-wise as relevant as possible to a specific field of study and (2) universally usable across computer systems, institutions, and countries (ie, interoperable). We then gathered medical experts from 3 specialties—infectious diseases (with a focus on immunization), pediatrics, and cardiology—to select data elements that were the most relevant to COVID-19–related patient research in the respective specialty. We mapped the data elements to international standardized vocabularies and created data exchange specifications, using Health Level Seven International (HL7) Fast Healthcare Interoperability Resources (FHIR). All steps were performed in close interdisciplinary collaboration with medical domain experts and medical information specialists. Profiles and vocabulary mappings were syntactically and semantically validated in a 2-stage process. ResultsWe created GECCO extension modules for the immunization, pediatrics, and cardiology domains according to pandemic-related requests. The data elements included in each module were selected, according to the developed consensus-based workflow, by medical experts from these specialties to ensure that the contents aligned with their research needs. We defined data set specifications for 48 immunization, 150 pediatrics, and 52 cardiology data elements that complement the GECCO core data set. We created and published implementation guides, example implementations, and data set annotations for each extension module. ConclusionsThe GECCO extension modules, which contain data elements that are the most relevant to COVID-19–related patient research on infectious diseases (with a focus on immunization), pediatrics, and cardiology, were defined in an interdisciplinary, iterative, consensus-based workflow that may serve as a blueprint for developing further data set definitions. The GECCO extension modules provide standardized and harmonized definitions of specialty-related data sets that can help enable interinstitutional and cross-country COVID-19 research in these specialties.
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- 2023
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14. Restrictive prescription of antibiotics in preterm infants with premature rupture of membranes
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Jakob Armann, Mario Rüdiger, Reinhard Berner, and Lars Mense
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Early onset sepsis ,Antibiotic stewardship ,PPROM ,Pediatrics ,RJ1-570 - Abstract
Abstract Background In preterm infants with premature rupture of membranes, antibiotic treatment is frequently started but rates of early onset sepsis are lower. In line with national guidelines, a stratified approach in the decision to start antibiotic treatment using maternal history, clinical impression and biomarkers has been implemented in our level III neonatal center and its results are evaluated. Methods Retrospective cohort study of all preterm newborns with rupture of membranes at least 1 h prior to delivery admitted to our tertiary neonatal intensive care unit. Data on antibiotic exposure, mortality and major neonatal complications were extracted from the electronic patient charts to evaluate the effects and safety of our stratified approach. Results Four hundred fifty-six infants met the inclusion criteria. 120 (26%) received primary antibiotics whereas 336 (74%) did not. Of those receiving primary antibiotics, 13 (11%) had a blood culture positive sepsis, 46 (38%) met the criteria of clinical sepsis and in 61 (51%) sepsis was ruled out and antibiotics were stopped after 48-96 h. All infants with blood culture positive sepsis were identified and treated within the first 24 h of life using this approach. None of the 336 infants who were not started on antibiotics primarily needed antibiotic therapy within the first 5 days of life. There were no deaths or major neonatal complications in the group that did not receive empiric antibiotics. Conclusions Our stratified approach for preterm infants with premature rupture of membranes allows a safe reduction of antibiotic exposure even in this high risk population. As a result, only 25% of high risk preterm newborns are treated with antibiotics of which more than half receive less than 5 days of treatment. To treat one infant with blood culture positive sepsis, only 9 infants receive empiric antibiotics.
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- 2022
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15. Comparison of mental health outcomes in seropositive and seronegative adolescents during the COVID19 pandemic
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Judith Blankenburg, Magdalena K. Wekenborg, Jörg Reichert, Carolin Kirsten, Elisabeth Kahre, Luise Haag, Leonie Schumm, Paula Czyborra, Reinhard Berner, and Jakob P. Armann
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Medicine ,Science - Abstract
Abstract Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in young adolescents than the acute infection. To better understand the symptoms of long-term mental health outcomes in adolescents and distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a 12 question Long-COVID19 survey. Using this survey, we compared the responses on neurocognitive, general pain and mood symptoms from seropositive and seronegative adolescents in a cross-sectional study design. Since May 2020, students grade 8–12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Serostatus was assessed regularly in all participants. In March/April 2021, 1560 students with a median age of 15 years participated at the regular study visit after re-opening of the schools in mid-March and responded to our Long-COVID19 survey as part of this visit. 1365 (88%) students were seronegative, 188 (12%) were seropositive. Each symptom asked in the Long-COVID19 survey was present in at least 35% of the students within the last seven days before the survey. With the exception of seropositive students being less sad, there was no significant difference comparing the reported symptoms between seropositive students and seronegative students. The lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizes on the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents. Clinical Trial Registration: SchoolCoviDD19: Prospektive Erfassung der SARS-CoV-2 Seropositivität bei Schulkindern nach Ende der unterrichtsfreien Zeit aufgrund der Corona-Schutz-Verordnung (COVID-19), DRKS00022455, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022455
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- 2022
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16. An Integrated clinical pathway for diagnosis, treatment and care of rare diseases: model, operating procedures, and results of the project TRANSLATE-NAMSE funded by the German Federal Joint Committee
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Daniela Choukair, Fabian Hauck, Markus Bettendorf, Heiko Krude, Christoph Klein, Tobias Bäumer, Reinhard Berner, Min Ae Lee-Kirsch, Corinna Grasemann, Peter Burgard, and Georg F. Hoffmann
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Clinical pathway ,Rare diseases ,Diagnostic odyssey ,Evidence-based medicine ,Case management ,Medicine - Abstract
Abstract Background Diagnosis, treatment, and care of patients with rare diseases require multidisciplinary cooperation between medical and paramedical specialities and with patients and families. Innovative genetic diagnostics, whole exome and whole genome sequencing (WES, WGS) has enlarged the diagnostic toolkit but also increased the complexity of the endeavour. Structured multidisciplinary clinical pathways (CPW) can guide diagnosis, treatment, and care of patients with rare diseases, link scientific evidence to clinical practice and optimise clinical outcomes whilst maximising clinical efficiency. Results In contrast to the common approach of appending disease-specific CPWs to disease-specific guidelines, we suggest a generic CPW manoeuvring the patient along the way of finding the correct diagnosis by applying the best diagnostic strategy into an appropriate system of treatment and care. Available guidelines can be integrated into the generic CPW in the course of its application. The approach also applies to situations where a diagnosis remains unsolved. The backbone of the generic CPW is a set of multidisciplinary structured case conferences projecting and evaluating diagnostic and/or therapeutic steps, enforcing to integrate best scientific evidence with clinical experience. The generic CPW is stated as a flowchart and a checklist which can be used to record and document parsimoniously the structure, process and results of a patient’s pathway, but also as a data model for research. It was applied in a multicentre setting with 587 cases each with a presumptive diagnosis of a rare disease. In 369 cases (62.8%) a diagnosis could be confirmed, and multidisciplinary treatment and/or care was initiated. The median process time from first contact until confirmation of diagnosis by WES was 109 days and much shorter than diagnostic delays reported in the literature. Application of the CPW is illustrated by two case reports. Conclusions Our model is a tool to change the diagnostic odyssey into an organised and trackable route. It can also be used to inform patients and families about the stages of their individual route, to update health care providers only partially involved or attending specialised treatment and care, like the patient’s or family’s primary physician, and finally to train novices in the field.
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- 2021
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17. Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.
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Martin Roessler, Falko Tesch, Manuel Batram, Josephine Jacob, Friedrich Loser, Oliver Weidinger, Danny Wende, Annika Vivirito, Nicole Toepfner, Franz Ehm, Martin Seifert, Oliver Nagel, Christina König, Roland Jucknewitz, Jakob Peter Armann, Reinhard Berner, Marina Treskova-Schwarzbach, Dagmar Hertle, Stefan Scholz, Stefan Stern, Pedro Ballesteros, Stefan Baßler, Barbara Bertele, Uwe Repschläger, Nico Richter, Cordula Riederer, Franziska Sobik, Anja Schramm, Claudia Schulte, Lothar Wieler, Jochen Walker, Christa Scheidt-Nave, and Jochen Schmitt
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Medicine - Abstract
BackgroundLong-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 findingsWe 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.ConclusionsIn 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 registrationClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.
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- 2022
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18. Elevations in blood glucose before and after the appearance of islet autoantibodies in children
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Katharina Warncke, Andreas Weiss, Peter Achenbach, Thekla von dem Berge, Reinhard Berner, Kristina Casteels, Lidia Groele, Konstantinos Hatzikotoulas, Angela Hommel, Olga Kordonouri, Helena Elding Larsson, Markus Lundgren, Benjamin A. Marcus, Matthew D. Snape, Agnieszka Szypowska, John A. Todd, Ezio Bonifacio, Anette-G. Ziegler, and for the GPPAD and POInT Study Groups
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Immunology ,Medicine - Abstract
The etiology of type 1 diabetes has polygenic and environmental determinants that lead to autoimmune responses against pancreatic β cells and promote β cell death. The autoimmunity is considered silent without metabolic consequences until late preclinical stages,and it remains unknown how early in the disease process the pancreatic β cell is compromised. To address this, we investigated preprandial nonfasting and postprandial blood glucose concentrations and islet autoantibody development in 1,050 children with high genetic risk of type 1 diabetes. Pre- and postprandial blood glucose decreased between 4 and 18 months of age and gradually increased until the final measurements at 3.6 years of age. Determinants of blood glucose trajectories in the first year of life included sex, body mass index, glucose-related genetic risk scores, and the type 1 diabetes–susceptible INS gene. Children who developed islet autoantibodies had early elevations in blood glucose concentrations. A sharp and sustained rise in postprandial blood glucose was observed at around 2 months prior to autoantibody seroconversion, with further increases in postprandial and, subsequently, preprandial values after seroconversion. These findings show heterogeneity in blood glucose control in infancy and early childhood and suggest that islet autoimmunity is concurrent or subsequent to insults on the pancreatic islets.
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- 2022
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19. Reduced Humoral and Cellular Immune Response to Primary COVID-19 mRNA Vaccination in Kidney Transplanted Children Aged 5–11 Years
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Jasmin K. Lalia, Raphael Schild, Marc Lütgehetmann, Gabor A. Dunay, Tilmann Kallinich, Robin Kobbe, Mona Massoud, Jun Oh, Leonora Pietzsch, Ulf Schulze-Sturm, Catharina Schuetz, Freya Sibbertsen, Fabian Speth, Sebastian Thieme, Mario Witkowski, Reinhard Berner, Ania C. Muntau, Søren W. Gersting, Nicole Toepfner, Julia Pagel, and Kevin Paul
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T cell ,pediatric ,SARS-CoV-2 ,solid organ transplant ,glomerulonephritis ,Microbiology ,QR1-502 - Abstract
The situation of limited data concerning the response to COVID-19 mRNA vaccinations in immunocom-promised children hinders evidence-based recommendations. This prospective observational study investigated humoral and T cell responses after primary BNT162b2 vaccination in secondary immunocompromised and healthy children aged 5–11 years. Participants were categorized as: children after kidney transplantation (KTx, n = 9), proteinuric glomerulonephritis (GN, n = 4) and healthy children (controls, n = 8). Expression of activation-induced markers and cytokine secretion were determined to quantify the T cell response from PBMCs stimulated with peptide pools covering the spike glycoprotein of SARS-CoV-2 Wuhan Hu-1 and Omicron BA.5. Antibodies against SARS-CoV-2 spike receptor-binding domain were quantified in serum. Seroconversion was detected in 56% of KTx patients and in 100% of the GN patients and controls. Titer levels were significantly higher in GN patients and controls than in KTx patients. In Ktx patients, the humoral response increased after a third immunization. No differences in the frequency of antigen-specific CD4+ and CD8+ T cells between all groups were observed. T cells showed a predominant anti-viral capacity in their secreted cytokines; however, this capacity was reduced in KTx patients. This study provides missing evidence concerning the humoral and T cell response in immunocompromised children after COVID-19 vaccination.
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- 2023
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20. Kinetics and seroprevalence of SARS-CoV-2 antibodies: a comparison of 3 different assays
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Elisabeth Kahre, Lukas Galow, Manja Unrath, Luise Haag, Judith Blankenburg, Alexander H. Dalpke, Christian Lück, Reinhard Berner, and Jakob P. Armann
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Medicine ,Science - Abstract
Abstract Comparing seroprevalence and antibody kinetics in three different commercially available assays for SARS-CoV-2. Serostatus of COVID-19 patients was analyzed 5 months and 10 months after their infection, using three different assays: Diasorin LIAISON, Euroimmun, Abbott Diagnostics ARCHITECT. Seropositivity at baseline differed significantly depending on the assay (Diasorin 81%, Euroimmun 83%, Abbott 59%). At follow-up antibody levels detected in the Diasorin assay were stable, while there was a significant loss in seropositivity in the Euroimmun and Abbott assays. There are significant differences in SARS-CoV-2 antibody kinetics based on the specific assay used.
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- 2021
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21. Hyper-IgE and Carcinoma in CADINS Disease
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Leonora Pietzsch, Julia Körholz, Felix Boschann, Mildred Sergon, Batsukh Dorjbal, Debra Yee, Vanessa Gilly, Eva Kämmerer, Diana Paul, Clemens Kastl, Martin W. Laass, Reinhard Berner, Eva Maria Jacobsen, Joachim Roesler, Daniela Aust, Min A. Lee-Kirsch, Andrew L. Snow, and Catharina Schuetz
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CARD11 deficiency ,severe eczema ,dupilumab ,HPV driven carcinoma ,anal carcinoma ,mycosis fungoides ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundAtopic dermatitis (AD) affects up to 25% of children and 10% of adults in Western countries. When severe or recurrent infections and exceedingly elevated serum IgE levels occur in AD patients, an inborn error of immunity (IEI) may be suspected. The International Union of Immunological Societies classification lists variants in different genes responsible for so-called Hyper-IgE syndromes. Diagnosing an underlying IEI may influence treatment strategies.MethodsClinical and diagnostic workup of family members are presented including a detailed immunological description and histology of the carcinoma. Functional testing of the novel variant in CARD11 underlying ‘CARD11-associated atopy with dominant interference of NF-kB signaling’ (CADINS) was performed.ResultsWe report on an 18-year-old patient with a long-standing history of infections, accompanied by hypogammaglobulinemia, intermittent agranulocytosis, atopy, eosinophilia and colitis. The working diagnosis of common variable immunodeficiency was revised when a novel heterozygous CARD11 variant [c.223C>T; p.(Arg75Trp)] was identified. Functional studies confirmed this variant to have a dominant negative (DN) effect, as previously described in patients with CADINS. Five other family members were affected by severe atopy associated with the above variant, but not hypogammaglobulinemia. Malignancies occurred in two generations: an HPV-positive squamous cell carcinoma and a cutaneous T-cell lymphoma. So far, one patient is under treatment with dupilumab, which has shown marked benefit in controlling severe eczema.ConclusionThe phenotypic spectrum associated with heterozygous CARD11 DN mutations is broad. Partial T-cell deficiency, diminished IFN-γ cytokine and increased IL-4 production, were identified as disease-causing mechanisms. Malignant disease associated with germline CARD11 DN variants has only been reported sporadically. HPV vaccination in teenage years, and cytology screening analogous with routine cervical swabs may be recommended. Treatment with dupilumab, a monoclonal antibody blocking interleukin-4- and interleukin-13 signaling, may be of benefit in controlling severe and extended AD for some patients as reported for STAT3 loss-of-function.
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- 2022
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22. Social inequalities in the participation and activity of children and adolescents with leukemia, brain tumors, and sarcomas (SUPATEEN): a protocol for a multicenter longitudinal prospective observational study
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Julia Roick, Reinhard Berner, Toralf Bernig, Bernhard Erdlenbruch, Gabriele Escherich, Jörg Faber, Christoph Klein, Konrad Bochennek, Christian Kratz, Joachim Kühr, Alfred Längler, Holger N. Lode, Markus Metzler, Hermann Müller, Dirk Reinhardt, Axel Sauerbrey, Florian Schepper, Wolfram Scheurlen, Dominik Schneider, Georg Christof Schwabe, and Matthias Richter
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Children and adolescents ,Cancer ,Social participation ,Patient reported outcomes ,Brain tumors ,Leukemia ,Pediatrics ,RJ1-570 - Abstract
Abstract Background About 2000 children and adolescents under the age of 18 are diagnosed with cancer each year in Germany. Because of current medical treatment methods, a high survival rate can be reached for many types of the disease. Nevertheless, patients face a number of long-term effects related to the treatment. As a result, physical and psychological consequences have increasingly become the focus of research in recent years. Social dimensions of health have received little attention in health services research in oncology so far. Yet, there are no robust results that allow an estimation of whether and to what extent the disease and treatment impair the participation of children and adolescents and which factors mediate this effect. Social participation is of great importance especially because interactions with peers and experiences in different areas of life are essential for the development of children and adolescents. Methods Data are collected in a longitudinal, prospective, observational multicenter study. For this purpose, all patients and their parents who are being treated for cancer in one of the participating clinics throughout Germany will be interviewed within the first month after diagnosis (t1), after completion of intensive treatment (t2) and half a year after the end of intensive treatment (t3) using standardized questionnaires. Analysis will be done by descriptive and multivariate methods. Discussion The results can be used to identify children and adolescents in high-risk situations at an early stage in order to be able to initiate interventions tailored to the needs. Such tailored interventions will finally reduce the risk of impairments in the participation of children and adolescents and increase quality of life. Trial registration ClinicalTrials.gov: NCT04101123.
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- 2020
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23. Supplementation with Bifidobacterium longum subspecies infantis EVC001 for mitigation of type 1 diabetes autoimmunity: the GPPAD-SINT1A randomised controlled trial protocol
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Matthew D Snape, Melanie Gündert, Anette-Gabriele Ziegler, Peter Achenbach, Reinhard Berner, Kristina Casteels, Thomas Danne, Joerg Hasford, Olga Kordonouri, Karin Lange, Helena Elding Larsson, Markus Lundgren, Agnieszka Szypowska, John A Todd, Ezio Bonifacio, Nicole Zubizarreta, Christiane Winkler, Åke Lernmark, Daniel Agardh, Cigdem Gezginci, Claudia Ramminger, Marlon Scholz, Katharina Warncke, Carin Andrén Aronsson, Rasmus Bennet, Lina Fransson, Zeliha Mestan, Caroline Nilsson, Anita Ramelius, Carina Törn, Sarah Hogg, Catherine Owen, Lidia Groele, Florian Haupt, Claudia Matzke, Robin Assfalg, Matthew Snape, Felix Reschke, Marcin L Pekalski, Andreas Weiss, Andrew Johnston, Manja Jolink, Loredana Marcovecchio, Mariusz Ołtarzewski, Stefanie Arnolds, Annika Kölln, Markus Pfirrmann, Corinna Barz, Karina Blasius, Nadine Friedl, Adriano Gomez-Bantel, Martin Heigermoser, Bianca Höfelschweiger, Nadine Klein, Ramona Lickert, Rebecca Niewöhner, Katharina Schütte-Borkovec, Mira Taulien, Lara Vogel, Franziska Voß, José Maria Zapardiel Gonzalo, Philipp Sifft, Heidi Kapfelsberger, Merve Vurucu, Katharina Sarcletti, Stefanie Jacobson, Yulia Grinin, John A. Todd, Anette-G. Ziegler, Marcin L. Pekalski, Anette G. Ziegler, Annre Rochtus, An Jacobs, Hilde Morobé, Jasmin Paulus, Brontë Vrancken, Natalie Van den Driessche, Renka Van Heyste, Janne Houben, Veerle Vanhuyse, Sevina Dietz, Gita Gemulla, Manja Gottschalk-Schwarz, Sophie Heinke, Angela Hommel, Susann Kowal, Fabian Lander, Robert Morgenstern, Marc Weigelt, Sari Arabi, Raphael Hoffmann, Ruth Blechschmidt, Franziska Ehrlich, Anja Loff, Laura Galuschka, Ute Holtkamp, Nils Janzen, Sarah Landsberg, Erika Marquardt, Frank Roloff, Kerstin Semler, Thekla von dem Berge, Melanie Bunk, Simone Färber-Meisterjahn, Willi Grätz, Ines Greif, Melanie Herbst, Anna Hofelich, Benjamin Marcus, Annette Munzinger, Jasmin Ohli, Franziska Reinmüller, Tiziana Welzhofer, Sylwia Dybkowska, Katarzyna Dżygało, Dorota Owczarek, Katarzyna Popko, Agnieszka Skrobot, Anna Taczanowska, Beata Zduńczyk, Charlotte Brundin, Ida Jönsson, Sara Maroufkhani, Evelyn Tekum Amboh, Katarzyna Gajewska-Knapik, Elena Romero, Suzannah Twiss, Helen Gallon, Laura Gebbie, Fiona Jenkinson, Steven Pratt, Steve Robson, Claire Simmister, Evelyn Thomson, and Eileen Walton
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Medicine - Abstract
Introduction The Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 weeks until age 12 months to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.Methods and analysis Infants aged 7 days to 6 weeks from Germany, Poland, Belgium, UK and Sweden are eligible for study participation if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies by age 6 years as determined by genetic risk score or family history and HLA genotype. Infants are randomised 1:1 to daily administration of B. infantis EVC001 or placebo until age 12 months and followed for a maximum of 5.5 years thereafter. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies. Secondary outcomes are (1) Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including insulin autoantibodies, glutamic acid decarboxylase, islet tyrosine phosphatase 2 or zinc transporter 8, (2) Diabetes, (3) Transglutaminase autoantibodies associated with coeliac disease, (4) Respiratory infection rate in first year of life during supplementation and (5) Safety. Exploratory outcomes include allergy, antibody response to vaccines, alterations of the gut microbiome or blood metabolome, stool pH and calprotectin.Ethics and dissemination The study was approved by the local ethical committees of the Technical University Munich, Medical Faculty, the Technische Universität Dresden, the Medizinische Hochschule Hannover, the Medical University of Warsaw, EC Research UZ Leuven and the Swedish ethical review authority. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the study.Trial registration number NCT04769037.
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- 2021
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24. One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency
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Julia Körholz, Anastasia Gabrielyan, John M. Sowerby, Felix Boschann, Lan-Sun Chen, Diana Paul, David Brandt, Janina Kleymann, Martin Kolditz, Nicole Toepfner, Ralf Knöfler, Eva-Maria Jacobsen, Christine Wolf, Karsten Conrad, Nadja Röber, Min Ae Lee-Kirsch, Kenneth G. C. Smith, Stefan Mundlos, Reinhard Berner, Alexander H. Dalpke, Catharina Schuetz, and William Rae
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inborn error of immunity (IEI) ,SOCS1 ,Hyper-IgE syndrome ,autoimmunity ,genetic pleiotropy ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundInborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans.ObjectiveWe sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency.MethodsWe assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells.ResultsSOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients.ConclusionsSOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients.
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- 2021
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25. Burden of Pediatric SARS-CoV-2 Hospitalizations during the Omicron Wave in Germany
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Maren Doenhardt, Christin Gano, Anna-Lisa Sorg, Natalie Diffloth, Tobias Tenenbaum, Rüdiger von Kries, Reinhard Berner, and Jakob P. Armann
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SARS-CoV-2 ,COVID-19 ,Omicron ,children ,hospitalization ,Microbiology ,QR1-502 - Abstract
(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents were not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German healthcare system. (2) Methods: From 24 January 2022 to 31 July 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and the need for respiratory support, were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day was hospitalized in general wards, whereas a median of 0.1 cases (range 0–0.4 cases) was admitted to intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with the need for intensive care treatment and respiratory support due to symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.
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- 2022
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26. SARS-CoV-2 seroprevalence in students and teachers: a longitudinal study from May to October 2020 in German secondary schools
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Reinhard Berner, Carolin Kirsten, Christian Lück, Manja Unrath, and Alexander H Dalpke
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Medicine - Abstract
Objective To quantify the number of SARS-CoV-2 infections in secondary schools after their reopening in May 2020.Design Repeated SARS-CoV-2 seroprevalence study after the reopening of schools and 4 months later.Setting Secondary school in Dresden, Germany.Participants 1538 students grades 8–12 and 507 teachers from 13 schools.Interventions Serial blood sampling and SARS-CoV-2 IgG antibody assessment.Primary and secondary outcome measure Seroprevalence of SARS-CoV-2 antibodies in study population. Number of undetected cases.Results 1538 students and 507 teachers were initially enrolled, and 1334 students and 445 teachers completed both study visits. The seroprevalence for SARS-CoV-2 antibodies was 0.6% in May/June and the same in September/October. Even in schools with reported COVID-19 cases before the lockdown of 13 March, no clusters could be identified. Of 12 persons with positive serology five had a known history of confirmed COVID-19; 23 out of 24 participants with a household history of COVID-91 were seronegative.Conclusions Schools do not play a crucial role in driving the SARS-CoV-2 pandemic in a low-prevalence setting. Transmission in families occurs very infrequently, and the number of unreported cases is low in this age group. These observations do not support school closures as a strategy fighting the pandemic in a low-prevalence setting.Trial registration number DRKS00022455.
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- 2021
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27. Severe Bleeding Diathesis in Siblings with Platelet Dysfunction due to a Novel Nonsense RASGRP2 Mutation
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Julia Körholz, Nadja Lucas, Franziska Boiti, Karina Althaus, Oliver Tiebel, Mingyan Fang, Reinhard Berner, Min Ae Lee-Kirsch, and Ralf Knöfler
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bleeding diathesis ,platelet dysfunction ,rasgrp2 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Next-generation sequencing is increasingly applied during the diagnostic work-up of patients with bleeding diathesis and has facilitated the diagnosis of rare bleeding disorders such as inherited platelet function disorders. Mutations in RAS guanyl releasing protein 2 (RasGRP2), also known as calcium- and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), underlie a recently described platelet signal transduction abnormality. Here we present the case of a consanguineous family originating from Afghanistan with two siblings affected by recurrent severe mucocutaneous bleedings. Platelet function testing demonstrated a marked reduction of aggregation induced by collagen and adenosine diphosphate. Whole exome sequencing revealed a novel homozygous nonsense RASGRP2 mutation segregating with the bleeding disorder in the family.
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- 2020
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28. Orbital inflammation and colitis in pediatric IgG4-related disease: A case report and review of the literature
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Lissy Tille, Anja Schnabel, Martin W. Laass, Gabriele Hahn, Heike Taut, Anna Leszczynska, Jessica Pablik, Reinhard Berner, Normi Brück, and Christian M. Hedrich
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2020
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29. Hospitalization for Acute Respiratory Tract Infection in a Low-Antibiotic-Prescribing Setting: Cross-Sectional Data from General Practice
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Christin Löffler, Attila Altiner, Annette Diener, Reinhard Berner, Gregor Feldmeier, Christian Helbig, Winfried V. Kern, Anna Köchling, Michaela Schmid, Gerhard Schön, Helmut Schröder, Karl Wegscheider, and Anja Wollny
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anti-bacterial agents ,inappropriate prescribing ,drug prescriptions ,respiratory tract infections ,primary health care ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Acute respiratory tract infections (ARTI) are the main cause of inappropriate antibiotic prescribing. To date, there is limited evidence concerning whether low levels of antibiotic prescribing may impact patient safety. We investigate whether antibiotic prescribing for patients seeking primary care for ARTI correlates with the odds for hospitalization. Methods: Analysis of patient baseline data (n = 3669) within a cluster-randomized controlled trial. Adult patients suffering from ARTI in German primary care are included. The main outcome measure is acute hospitalization for respiratory infection and for any acute disease from 0 to 42 days after initial consultation. Results: Neither the antibiotic status of individual patients (OR 0.91; 95% CI: 0.49 to 1.69; p-value = 0.769) nor the physician-specific antibiotic prescription rates for ARTI (OR 1.22; 95% CI: 1.00 to 1.49; p-value = 0.054) had a significant effect on hospitalization. The following factors increased the odds for hospitalization: patient’s age, the ARTI being defined as lower respiratory tract infections (such as bronchitis) by the physician, the physician’s perception of disease severity, and being cared for within group practices (versus treated in single-handed practices). Conclusions: In a low-antibiotic-prescribing primary care setting such as Germany, lack of treatment with antibiotics for ARTI did not result in higher odds for hospitalization in an adult population.
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- 2020
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30. Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood
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Nicole Toepfner, Christoph Herold, Oliver Otto, Philipp Rosendahl, Angela Jacobi, Martin Kräter, Julia Stächele, Leonhard Menschner, Maik Herbig, Laura Ciuffreda, Lisa Ranford-Cartwright, Michal Grzybek, Ünal Coskun, Elisabeth Reithuber, Geneviève Garriss, Peter Mellroth, Birgitta Henriques-Normark, Nicola Tregay, Meinolf Suttorp, Martin Bornhäuser, Edwin R Chilvers, Reinhard Berner, and Jochen Guck
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real-time deformability cytometry ,cell mechanics ,spherocytosis ,malaria ,neutrophil activation ,leukemia ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of diluted whole blood, without labeling, enrichment or separation, at rates of 1000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in blood and adds a functional dimension to conventional blood analysis.
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- 2018
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31. Transition database for rare diseases and its use for clinical documentation.
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Michele Zoch, Christian Gierschner, Richard Gebler, Liz A. Leutner, Tanita Kretschmer, Adrian Danker, Min Ae Lee-Kirsch, Reinhard Berner, and Martin Sedlmayr
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- 2024
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32. Impfungen bei Risikoneugeborenen und -säuglingen
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Jakob Armann, Reinhard Berner, and Lukas Galow
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business.industry ,Medicine ,General Medicine ,business - Published
- 2022
33. Current articles relevant to general pediatrics
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Reinhold Kerbl, Reinhard Berner, Gesine Hansen, and Fred Zepp
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Pediatrics, Perinatology and Child Health ,Surgery - Published
- 2023
34. Vaccine effectiveness of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years in German Primary Care
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Christoph Strumann, Otavio Ranzani, Jeanne Moor, Reinhard Berner, Nicole Töpfner, Cho-Ming Chao, and Matthias B. Moor
- Abstract
BackgroundDespite the approval of BNT162b2 mRNA vaccine for children aged 6 months to 4 years by the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) in 2022, no data on vaccine effectiveness (VE) of BNT162b2 are available in this age group. We here report on the VE of BNT162b2 during an Omicron BA.1-2 dominant period.MethodsAn authentication-based retrospective survey was performed between April 14th 2022 and May 9th 2022 in individuals that had registered children for off-label SARS-CoV-2 vaccination in Germany. We used Cox regression to estimate relative VE of two BNT162b2 doses, with the period between first and second vaccine dose as reference period (24.8+-0.6 days) and >=7 days after Dose 2 to before Dose 3 as post-vaccination period (59.5+-23.6 days).ResultsThe present analysis included 4615 children aged 2.8+-1.2 years (mean+-standard deviation) who had received their first dose of BNT162b2 on January 1st 2022 or thereafter. VE was substantial for protection from any SARS-CoV-2 infection (VE: 53.1% [95% confidence interval (CI): 36.3-69.6%], pConclusionThis study offers a first industry-independent insight in the potential VE of two doses of the BNT162b2 vaccine in children aged below 5 years, as currently only immunogenicity data by the manufacturer Pfizer/BioNTech are available. Limitations include the retrospective study design, and that the reported VE does not necessarily correspond to currently circulating SARS-CoV-2 variants.
- Published
- 2023
35. Next-generation phenotyping integrated in a national framework for patients with ultra-rare disorders improves genetic diagnostics and yields new molecular findings
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Axel Schmidt, Magdalena Danyel, Kathrin Grundmann, Theresa Brunet, Hannah Klinkhammer, Tzung-Chien Hsieh, Hartmut Engels, Sophia Peters, Alexej Knaus, Shahida Moosa, Luisa Averdunk, Felix Boschann, Henrike Sczakiel, Sarina Schwartzmann, Martin Atta Mensah, Jean Tori Pantel, Manuel Holtgrewe, Annemarie Bösch, Claudia Weiß, Natalie Weinhold, Aude-Annick Suter, Corinna Stoltenburg, Julia Neugebauer, Tillmann Kallinich, Angela M. Kaindl, Susanne Holzhauer, Christoph Bührer, Philip Bufler, Uwe Kornak, Claus-Eric Ott, Markus Schülke, Hoa Huu Phuc Nguyen, Sabine Hoffjan, Corinna Grasemann, Tobias Rothoeft, Folke Brinkmann, Nora Matar, Sugirthan Sivalingam, Claudia Perne, Elisabeth Mangold, Martina Kreiss, Kirsten Cremer, Regina C. Betz, Tim Bender, Martin Mücke, Lorenz Grigull, Thomas Klockgether, Spier Isabel, Heimbach André, Bender Tim, Fabian Brand, Christiane Stieber, Alexandra Marzena Morawiec, Pantelis Karakostas, Valentin S. Schäfer, Sarah Bernsen, Patrick Weydt, Sergio Castro-Gomez, Ahmad Aziz, Marcus Grobe-Einsler, Okka Kimmich, Xenia Kobeleva, Demet Önder, Hellen Lesmann, Sheetal Kumar, Pawel Tacik, Min Ae Lee-Kirsch, Reinhard Berner, Catharina Schuetz, Julia Körholz, Tanita Kretschmer, Nataliya Di Donato, Evelin Schröck, André Heinen, Ulrike Reuner, Amalia-Mihaela Hanßke, Frank J. Kaiser, Eva Manka, Martin Munteanu, Alma Kuechler, Kiewert Cordula, Raphael Hirtz, Elena Schlapakow, Christian Schlein, Jasmin Lisfeld, Christian Kubisch, Theresia Herget, Maja Hempel, Christina Weiler-Normann, Kurt Ullrich, Christoph Schramm, Cornelia Rudolph, Franziska Rillig, Maximilian Groffmann, Ania Muntau, Alexandra Tibelius, Eva M. C. Schwaibold, Christian P. Schaaf, Michal Zawada, Lilian Kaufmann, Katrin Hinderhofer, Pamela M. Okun, Urania Kotzaeridou, Georg F. Hoffmann, Daniela Choukair, Markus Bettendorf, Malte Spielmann, Annekatrin Ripke, Martje Pauly, Alexander Münchau, Katja Lohmann, Irina Hüning, Britta Hanker, Tobias Bäumer, Rebecca Herzog, Yorck Hellenbroich, Dominik S. Westphal, Tim Strom, Reka Kovacs, Korbinian M. Riedhammer, Katharina Mayerhanser, Elisabeth Graf, Melanie Brugger, Julia Hoefele, Konrad Oexle, Nazanin Mirza-Schreiber, Riccardo Berutti, Ulrich Schatz, Martin Krenn, Christine Makowski, Heike Weigand, Sebastian Schröder, Meino Rohlfs, Vill Katharina, Fabian Hauck, Ingo Borggraefe, Wolfgang Müller-Felber, Ingo Kurth, Miriam Elbracht, Cordula Knopp, Matthias Begemann, Florian Kraft, Johannes R. Lemke, Julia Hentschel, Konrad Platzer, Vincent Strehlow, Rami Abou Jamra, Martin Kehrer, German Demidov, Stefanie Beck-Wödl, Holm Graessner, Marc Sturm, Lena Zeltner, Ludger J. Schöls, Janine Magg, Andrea Bevot, Christiane Kehrer, Nadja Kaiser, Denise Horn, Annette Grüters-Kieslich, Christoph Klein, Stefan Mundlos, Markus Nöthen, Olaf Riess, Thomas Meitinger, Heiko Krude, Peter M. Krawitz, Tobias Haack, Nadja Ehmke, and Matias Wagner
- Abstract
Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these challenges within Germany, a novel structured diagnostic concept, based on multidisciplinary expertise at established university hospital centers for rare diseases (CRDs), was evaluated in the three year prospective study TRANSLATE NAMSE. A key goal of TRANSLATE NAMSE was to assess the clinical value of exome sequencing (ES) in the ultra-rare disease population. The aims of the present study were to perform a systematic investigation of the phenotypic and molecular genetic data of TRANSLATE NAMSE patients who had undergone ES in order to determine the yield of both ultra-rare diagnoses and novel gene-disease associations; and determine whether the complementary use of machine learning and artificial intelligence (AI) tools improved diagnostic effectiveness and efficiency.ES was performed for 1,577 patients (268 adult and 1,309 pediatric). Molecular genetic diagnoses were established in 499 patients (74 adult and 425 pediatric). A total of 370 distinct molecular genetic causes were established. The majority of these concerned known disorders, most of which were ultra-rare. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were delineated, mainly in individuals with neurodevelopmental disorders.To determine the likelihood that ES will lead to a molecular diagnosis in a given patient, based on the respective clinical features only, we developed a statistical framework called YieldPred. The genetic data of a subcohort of 224 individuals that also gave consent to the computer-assisted analysis of their facial images were processed with the AI tool Prioritization of Exome Data by Image Analysis (PEDIA) and showed superior performance in variant prioritization.The present analyses demonstrated that the novel structured diagnostic concept facilitated the identification of ultra-rare genetic disorders and novel gene-disease associations on a national level and that the machine learning and AI tools improved diagnostic effectiveness and efficiency for ultra-rare genetic disorders.
- Published
- 2023
36. Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project
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Berit Lange, Veronika K Jaeger, Manuela Harries, Viktoria Rücker, Hendrik Streeck, Sabine Blaschke, Astrid Petersmann, Nicole Toepfner, Matthias Nauck, Max J Hassenstein, Maren Dreier, Isabell Von Holt, Axel Budde, Antonia Bartz, Julia Ortmann, Marc-André Kurosinski, Reinhard Berner, Max Borsche, Gunnar Brandhorst, Melanie Brinkmann, Kathrin Budde, Marek Deckena, Geraldine Engels, Marc Fenzlaff, Christoph Härtel, Olga Hovardovska, Alexander Katalinic, Katja Kehl, Mirjam Kohls, Stefan Krüger, Wolfgang Lieb, Kristin M Meyer-Schlinkmann, Tobias Pischon, Daniel Rosenkranz, Nicole Rübsamen, Jan Rupp, Christian Schäfer, Mario Schattschneider, Anne Schlegtendal, Simon Schlinkert, Lena Schmidbauer, Kai Schulze-Wundling, Stefan Störk, Carsten Tiemann, Henry Völzke, Theresa Winter, Christine Klein, Johannes Liese, Folke Brinkmann, Patrick F Ottensmeyer, Jens-Peter Reese, Peter Heuschmann, and André Karch
- Abstract
Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time.In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n=33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses (“confirmed exposures”). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest.Most participants were seropositive against the spike antigen; 37% of the participants ≥79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4%-28% of participants having less than three confirmed exposures.Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.
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- 2023
37. Comparing SARS-CoV-2 variants among children and adolescents in Germany: relative risk of COVID-19-related hospitalization, ICU admission and mortality
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Marietta Jank, Anna-Lisa Oechsle, Jakob Armann, Uta Behrends, Reinhard Berner, Cho-Ming Chao, Natalie Diffloth, Maren Doenhardt, Gesine Hansen, Markus Hufnagel, Fabian Lander, Johannes G. Liese, Ania C. Muntau, Tim Niehues, Ulrich von Both, Eva Verjans, Katharina Weil, Rüdiger von Kries, and Horst Schroten
- Subjects
Microbiology (medical) ,Infectious Diseases ,General Medicine - Abstract
Purpose SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. Methods Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. Results During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the Conclusion Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged.
- Published
- 2023
38. Kinder und Jugendliche auf der Flucht
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Reinhard Berner
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Pediatrics, Perinatology and Child Health ,Surgery - Published
- 2022
39. Aktuelle Projekte der versorgungsorientierten pädiatrischen Forschung
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Fred Zepp, Reinhard Berner, Gesine Hansen, and Reinhold Kerbl
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Pediatrics, Perinatology and Child Health ,Surgery - Published
- 2022
40. Seroprevalence of SARS-CoV-2 in German secondary schools from October 2020 to July 2021: a longitudinal study
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Carolin Kirsten, Elisabeth Kahre, Judith Blankenburg, Leonie Schumm, Luise Haag, Lukas Galow, Manja Unrath, Paula Czyborra, Josephine Schneider, Christian Lück, Alexander H. Dalpke, Reinhard Berner, and Jakob Armann
- Subjects
Microbiology (medical) ,Schools ,Infectious Diseases ,Adolescent ,SARS-CoV-2 ,Seroepidemiologic Studies ,Communicable Disease Control ,Humans ,COVID-19 ,Longitudinal Studies ,General Medicine ,Child - Abstract
Purpose To quantify the number of SARS-CoV-2 infections in students and teachers in 14 Secondary schools in eastern Saxony, Germany. Seroprevalence of SARS-CoV-2 antibodies in study population. Number of undetected cases. Methods Serial seroprevalence study. Results The role of educational settings in the SARS-CoV-2 Pandemic is still controversial. Seroprevalence increases from 0.8 to 5.9% from October to December when schools remained open and to 12.2% in March/April during a strict lockdown with closed schools. The ratio of undetected to detected cases decreased from 0.76 to 0.44 during the study period. Conclusion During the second and third wave of the pandemic in Germany, students and teachers are not overrepresented in SARS-CoV-2 infections. The percentage of undetected cases is moderate and decreases over time. The risk of contracting SARS-CoV-2 within the household is higher than contracting it in educational settings making school closures rather ineffective in terms of pandemic control measures or individual risk reduction in children and adolescents. Trial registration DRKS00022455 (July 23rd, 2020).
- Published
- 2022
41. High Diversity of emm Types and Marked Tetracycline Resistance of Group A Streptococci and Other ß-Hemolytic Streptococci in Gabon, Central Africa
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Benjamin, Arnold, Sabine, Bélard, Abraham, Alabi, Markus, Hufnagel, Reinhard, Berner, and Nicole, Toepfner
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Microbiology (medical) ,Antigens, Bacterial ,Streptococcus pyogenes ,Tetracycline Resistance ,Pharyngitis ,Cross-Sectional Studies ,Infectious Diseases ,Pyoderma ,Streptococcal Infections ,Pediatrics, Perinatology and Child Health ,Humans ,Gabon ,Prospective Studies ,Bacterial Outer Membrane Proteins - Abstract
Group A ß-hemolytic streptococcus (GABHS) is a leading pathogen worldwide and post-streptococcal sequelae is a major cause of morbidity and mortality in resource-limited countries. The M protein (coded by the emm gene) is a key virulence factor and a component of GABHS vaccine candidates. As data on BHS in Central Africa are scarce, antibiotic resistance, emm diversity and potential vaccine coverage were investigated.In a prospective cross-sectional study, 1014 Gabonese were screened for streptococcal throat carriage, tonsillopharyngitis and pyoderma by throat and skin smear tests. All BHS were isolated, species were identified and analysis of antibiotic resistance, emm types and emm clusters was performed.One hundred sixty-five BHS were detected, comprising 76 GABHS, 36 group C ß-hemolytic streptococcus (GCBHS) and 53 group G ß-hemolytic streptococcus (GGBHS) in 140 carrier, 9 tonsillopharyngitis and 16 pyoderma isolates. Eighty percentage of GABHS, 78% of GCBHS and 79% of GGBHS were tetracycline resistant. Forty-six emm types were identified. GABHS emm58, emm65 and emm81 were most prevalent (26%). Emm diversity of GABHS was the highest, GCBHS and GGBHS were less divers. Every second GABHS, every third GCBHS and every tenth GGBHS carrier was colonized with emm types detected in tonsillopharyngitis or pyoderma isolates.Tetracycline resistance and emm type diversity was high among BHS carriers in Gabon with a potential coverage of 58% by the 30-valent GABHS vaccine. A relevant overlap of carrier emm types with emm types found in tonsillopharyngitis and pyoderma characterizes a shared pool of circulating BHS strains.
- Published
- 2022
42. Streptokokken-Infektionen im Kindes- und Jugendalter
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Nicole Töpfner and Reinhard Berner
- Published
- 2022
43. Zwischen asymptomatischer Besiedelung und fulminanter Infektion
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Nicole Töpfner and Reinhard Berner
- Published
- 2022
44. SARS-CoV-2 in pediatric cancer: a systematic review
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Sandy Schlage, Thomas Lehrnbecher, Reinhard Berner, Arne Simon, and Nicole Toepfner
- Subjects
Pediatric ,Adolescent ,SARS-CoV-2 ,COVID-19 ,Malignancy ,Review ,Disease Outbreaks ,Neoplasms ,Pediatrics, Perinatology and Child Health ,Humans ,Chemotherapy ,Child ,Pandemics ,Cancer - Abstract
The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan challenges pediatric oncologists in an unexpected way. We provide a comprehensive overview, which systematically summarizes and grades evidence (QoE) on SARS-CoV-2 infections in pediatric cancer patients at 1.5 years of pandemic. A systematic literature search in PubMed combined with an additional exploratory literature review in other international databases was conducted to identify studies on children (aged Conclusion: Despite a favorable COVID-19 outcome in most pediatric cancer patients, the morbidity is reported higher than in children without comorbidities. However, no severe COVID-19 complications were associated to the continuation of chemotherapy in some cohort studies and reports on two patients. Therefore, the risk of cancer progress or relapse due to interruption of chemotherapy has carefully to be weighed against the risk of severe COVID-19 disease with potentially fatal outcome. What is Known:• Most of pediatric patients with malignant diseases show an asymptomatic, mild or moderate clinical course of SARS-CoV-2 infection. • Current need for a basis for decision-making, whether to stop or interrupt cancer treatment in a patient infected with SARS-CoV-2, and when to continue chemotherapy. What is New:• Review results comprising over 1000 pediatric COVID-19 cancer patients confirm mild courses of SARS-CoV-2 infection in most patients but also show the attributable mortality is at least 10 times higher compared to reports on hospitalized children without comorbidities.• Review identifies that chemotherapy was continued despite SARS-CoV-2 positivity in 18% of patients with individual chemotherapy modification according to the clinical course of SARS-CoV-2 infection and existing comorbidities. On this basis, no severe COVID-19 complications were associated to the continuation of chemotherapy in several cohort studies and two case reports.
- Published
- 2022
45. The Development of Interoperable, Domain-Specific Extensions for the German Corona Consensus (GECCO) COVID-19 Research Dataset Using an Interdisciplinary, Consensus-Based Workflow: Dataset Development Study (Preprint)
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Gregor Lichtner, Thomas Haese, Sally Brose, Larissa Röhrig, Liudmila Lysyakova, Stefanie Rudolph, Maria Uebe, Julian Sass, Alexander Bartschke, David Hillus, Florian Kurth, Leif Erik Sander, Falk Eckart, Nicole Toepfner, Reinhard Berner, Anna Frey, Marcus Dörr, Jörg Janne Vehreschild, Christof von Kalle, and Sylvia Thun
- Subjects
Health Information Management ,Health Informatics - Published
- 2023
46. Der klinische Versorgungspfad zur multiprofessionellen Versorgung seltener Erkrankungen in der Pädiatrie – Ergebnisse aus dem Projekt TRANSLATE-NAMSE
- Author
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Daniela Choukair, Min Ae Lee-Kirsch, Reinhard Berner, Corinna Grasemann, Olaf Hiort, Fabian Hauck, Christoph Klein, Diana Druschke, Georg F. Hoffmann, and Peter Burgard
- Subjects
Pediatrics, Perinatology and Child Health ,Surgery - Abstract
Zusammenfassung Hintergrund Seltene Erkrankungen (SE) manifestieren sich ganz überwiegend im Kindes- und Jugendalter, sind heterogen, multisystemisch, haben meist einen chronischen Verlauf und stellen eine große Herausforderung für alle Beteiligten dar. Finanziert durch den Innovationsfonds des G‑BA hatte das Versorgungsprojekt TRANSLATE-NAMSE das Ziel, Vorschläge zur besseren Versorgung von Menschen mit SE zu entwickeln und zu erproben. Fragestellung Für Patienten aller Altersgruppen mit einer Verdachtsdiagnose aus einer von 5 Gruppen definierter Indikatorerkrankungen (seltene Anämien, Endokrinopathien, Autoinflammationserkrankungen, primäre Immundefekte und Stoffwechselerkrankungen) sollte ein generischer Versorgungspfad entwickelt werden, der den Weg von der Konfirmationsdiagnostik bis hin zur Langzeitbetreuung dieser Patienten abbildet. Methodik Der Versorgungspfad wurde als allgemeines Ablaufschema dargelegt; die Prozessschritte wurden in eine Checkliste übertragen, inhaltlich ausformuliert und an 6 universitären Standorten an 587 Personen mit der Verdachtsdiagnose einer Indikatorerkrankungen erprobt. Ergebnisse Für 369 (62,9 %) Fälle mit der Verdachtsdiagnose einer Indikatorerkrankung konnte eine Diagnose gestellt werden, davon in 25,2 % mit innovativer genetischer Diagnostik; 104 (17,7 %) Verdachtsdiagnosen erwiesen sich als falsch-positiv; 114 (19,4 %) Fälle blieben ungeklärt. An Fallkonferenzen zur multiprofessionellen Versorgung nahmen im Median 4 Spezialisten teil. Die Versorgung (Diagnoseeröffnung, Schulung, Beratung, Information) begann im Median am Tag des Diagnostikergebnisses. In einer externen Evaluation erwies sich die Zufriedenheit der Sorgeberechtigten mit dem Versorgungspfad als hoch. Schlussfolgerungen Im bisher in Deutschland einzigartigen TRANSLATE-NAMSE-Projekt wurde ein Versorgungspfad für SE in der Pädiatrie entwickelt und erfolgreich erprobt. Zur Verstetigung dieser Versorgungsform ist eine auskömmliche Finanzierung in der Regelversorgung anzustreben.
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- 2021
47. Resource consumption of a structured transition of young people with rare diseases from pediatric to adult care in a German nationwide cohort : Effort and cost analysis from the TRANSLATE-NAMSE project
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C. Weiler-Normann, G. Müller, J. Höppner, Reinhard Berner, Daniela Choukair, Min Ae Lee-Kirsch, Georg F. Hoffmann, K. Wainwright, Corinna Grasemann, Peter Burgard, N. Matar, and S. Baumgarten
- Subjects
business.industry ,Pediatrics, Perinatology and Child Health ,Medizin ,Medicine ,Surgery ,business ,Humanities - Published
- 2021
48. Welche Rolle spielen Kinder in Schulen und Kindertagesstätten bei der Übertragung von SARS-CoV-2? – Eine evidenzbasierte Perspektive
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Reinhard Berner, Johannes Hübner, Herbert Renz-Polster, Anna Kern, Ingeborg Krägeloh-Mann, Freia De Bock, and Jessica Diebenbusch
- Subjects
Gynecology ,Adult ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Schule ,Schools ,Coronavirus disease 2019 (COVID-19) ,Pandemic ,Adolescent ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pandemie ,Public Health, Environmental and Occupational Health ,Kinder ,COVID-19 ,Political science ,Germany ,medicine ,Leitthema ,Humans ,Disease vector ,Child ,Vektor ,Children ,Pandemics - Abstract
Are children and adolescents relevant disease vectors when it comes to the transmission of SARS-CoV-2? Moreover, do they play a role as relevant disease vectors in a school or kindergarten setting? These questions could not be sufficiently answered at the beginning of the pandemic. Consequently, schools and childcare facilities were closed to stop the spread of SARS-CoV‑2. Over the past few months, researchers have gained a more detailed understanding of the overall pandemic situation. The SARS-CoV‑2 infection rate in children below 10 years of age in 2020 has been substantially lower than in adults. In addition, it showed that children had a milder course of disease.Although a majority of the analyses performed in schools and childcare facilities revealed that the virus is transmitted in these facilities, these transmissions did not, however, have a considerable influence on the overall rate of new infections. Despite these findings, German politicians continue to advocate for the closure of childcare facilities, including schools, to fight the pandemic, whereas many specialist societies such as the German Society for Pediatric Infectious Diseases (DGPI) have emphasized that such closures should be the measure of last resort in combating the pandemic. The same message is also conveyed by a German evidence-based S3 guideline established by an interdisciplinary expert group that had already put forward clear recommendations for high incidences in the general population at the beginning of February 2021, indicating that school closures were only required in exceptional cases.In this article, we would like to outline the situation based on the currently available data, try to predict the future, and discuss the circumstances necessary to realize normal classroom teaching without accepting the risk of an uncontrolled spread of SARS-CoV‑2.Sind Kinder und Jugendliche relevante Vektoren für die Übertragung von SARS-CoV-2? Und welche Rolle spielt es, wenn sie eine Schule oder Kindertagesstätte besuchen? Diese Fragen konnten zu Beginn der Pandemie nur unzureichend beantwortet werden. So wurden weltweit Schulen und Kinderbetreuungseinrichtungen geschlossen, um die Verbreitung von SARS-CoV‑2 einzudämmen. Inzwischen ist die Rolle von Kindern im Gesamtgeschehen der Pandemie jedoch klarer. Die Rate von SARS-CoV-2-Infektionen bei Kindern unter 10 Jahren war im Jahr 2020 deutlich niedriger als die bei Erwachsenen. Zudem zeigte sich bei Kindern ein deutlich milderer Verlauf der Erkrankung.Analysen zu Ausbrüchen an Schulen und Kinderbetreuungseinrichtungen kamen mehrheitlich zu dem Ergebnis, dass die Weitergabe des Virus in den Einrichtungen zwar stattfindet, jedoch das Infektionsgeschehen insgesamt nicht maßgeblich beeinflusst. Trotz dieser Erkenntnisse hält die deutsche Politik Schulschließungen weiterhin für einen integralen Baustein der Pandemiebekämpfung, wohingegen viele Fachgesellschaften, wie die Deutsche Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI), betonen, dass es sich um das letzte Mittel in der Bekämpfung der Pandemie handeln sollte. Diese Botschaft hat auch eine evidenzbasierte und auf interdisziplinärem Expertenkonsens aufgebaute S3-Leitlinie, die bereits Anfang Februar 2021 klare Empfehlungen für Zeiten hoher Inzidenzen in der Gesamtbevölkerung ausgesprochen hat, die Schulschließungen nur noch in Ausnahmefällen für notwendig erachten.In diesem Artikel möchten wir die Datenlage mit Stand Juni 2021 zu diesem Thema darlegen, einen Blick in die Zukunft wagen und diskutieren, unter welchen Umständen ein regulärer Präsenzunterricht gelingen kann, ohne das Risiko einer unkontrollierten Ausbreitung von SARS-CoV‑2 in Kauf nehmen zu müssen.
- Published
- 2021
49. High seroprevalence of SARS-CoV-2 in preschool children in July 2022
- Author
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Geraldine Engels, Katharina Hecker, Johannes Forster, Nicole Toepfner, Elena Hick, Franziska Pietsch, Peter Heuschmann, Reinhard Berner, Christoph Härtel, Oliver Kurzai, Astrid Petersmann, Andrea Streng, and Johannes Liese
- Subjects
General Medicine - Published
- 2022
50. Prevalence and Transmission of Severe Acute Respiratory Syndrome Coronavirus Type 2 in Childcare Facilities: A Longitudinal Study
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Reinhard Berner, Lukas Galow, Josephine Schneider, Alexander H. Dalpke, Judith Blankenburg, Jakob Peter Armann, Elisabeth Kahre, Christian Lück, Luise Haag, Leo Büttner, Manja Unrath, and Johanna Grabietz
- Subjects
Longitudinal study ,business.industry ,Transmission (medicine) ,viruses ,fungi ,Retrospective cohort study ,Asymptomatic ,body regions ,Environmental health ,Pediatrics, Perinatology and Child Health ,Pandemic ,Population study ,Medicine ,Seroprevalence ,medicine.symptom ,Viral shedding ,skin and connective tissue diseases ,business - Abstract
Objective To evaluate the role of childcare facilities in the transmission of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in a longitudinal study to gain further knowledge of SARS-CoV-2 prevalence, transmission, and spread among preschool children, their parents, and their caregivers. Study design Children aged 1-6 years, their parents, and their caregivers in 14 childcare facilities in Dresden, Saxony/Germany were invited to participate in the KiTaCoviDD19-study between July 2020 and January 2021. Seroprevalence of SARS-CoV-2 antibodies was assessed up to 4 times during the study period in all participating adults, and demographic characteristics, as well as epidemiologic information on personal SARS-CoV-2 history were obtained. Samples for stool virus shedding of SARS-CoV-2 were analyzed by polymerase chain reaction every 2-4 weeks in all participating children. Results In total, 318 children, 299 parents and 233 childcare workers were enrolled. By January 2021, 11% of the participating adults were found to be seropositive, whereas the percentage of children shedding SARS-CoV-2 was 6.8%. Overall, we detected 17 children with SARS-CoV-2 virus shedding in 8 different childcare facilities. In 4 facilities, there were a maximum of 3 connected cases in children. Approximately 50% of SARS-CoV-2 infections in the children could not be connected to a secondary case in our study population. Conclusions This study does not provide evidence of relevant asymptomatic (“silent”) spread of SARS-CoV-2 in childcare facilities in both low- and high-prevalence settings. Our findings add to the evidence that childcare and educational settings do not have a crucial role in driving the SARS-CoV-2 pandemic.
- Published
- 2021
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