[Early Detection Of Type 1 Diabetes By Islet Autoantibody Screening: A Position Paper Of The Fr1daplex Project Leaders And Training Centres, Bvkj Bavaria And Paednetz (Registered) Bavaria]. / Früherkennung von Typ-1-Diabetes durch Inselautoantikörper-Screening ­ ein Positionspapier der Fr1daPlex-Projektleiter und -Schulungszentren, des BVKJ Bayern und PaedNetz Bayern e.V.

This position paper is based on the authors' many years of clinical experience and basic science research on the diagnosis and treatment of children and adolescents with a presymptomatic early stage of type 1 diabetes. The benefits as well as potential disadvantages of early detection of type 1 diabetes by islet autoantibody screening are critically discussed. In addition, the perspectives of delaying the onset of the clinical metabolic disease through treatment with teplizumab are addressed. Today, we see the chance for a relevant improvement in therapeutic options and life perspectives of affected children and adolescents. Important next steps for the implementation of islet autoantibody screening in Germany are the training of pediatricians who should inform families about the screening, establishment of a few transregional laboratories that carry out the test, and expansion of regional capacities for the training and care of children with an early stage of type 1 diabetes.

Feasibility testing of the Core set of quality Indicators for Paediatric Primary Care in Europe, COSI-PPC-EU.

There is a need to measure and improve the quality of paediatric primary care in Europe where major differences in the delivery and outcomes of child health care exist. A collaborative panel of paediatric senior experts developed a Core Set of Indicators for Paediatric Primary Care in Europe by compiling 42 quality indicators in a modified consensus process following the RAND/UCLA appropriateness method. The aim of this study was to explore the feasibility of the quality indicator set in European paediatric primary care practices. Seventy-nine practices from eight countries participated in a detailed online interview. The practices rated the applicability, relevance, reliability and acceptance of the 42 quality indicator as well as the availability, technical feasibility and effort to retrieve the needed data from their medical records. Most quality indicators were considered applicable, available, reliable, acceptable and relevant for monitoring quality of care in paediatric primary care. Respondents rated feasibility and effort to retrieve the data lowest because of difficulties collecting the data from the medical records.Conclusion: European paediatric primary care practices generally agree with the proposed quality indicator set. They document most of the parameters. However, the collection of specific needed values from available routine patient-data is considered technically difficult and time-consuming. What is Known? • Paediatric primary care systems in Europe show striking differences in their performance. Pre-existing sets of quality indicators are predominantly limited to national populations, specific diseases and hospital care. • A Core Set of 42 quality indicators for paediatric primary care in Europe was developed by European paediatricians using a systematic literature review and a consensus process following a modified RAND/UCLA appropriateness method. What is New? • Paediatric primary care providers in Europe agree with the idea to use COSI-PPC-EU to monitor and improve the quality of care. The set was considered applicable, available, reliable, acceptable, and relevant for quality improvement. • The score for feasibility and effort to retrieve the data was low, because of technical reasons; the electronical or paper-based medical documentation in most cases does not allow convenient access to all necessary data.

Development of a core set of quality indicators for paediatric primary care practices in Europe, COSI-PPC-EU.

Paediatric ambulatory healthcare systems in Europe are, because of historical reasons, diverse and show strikingly different outcomes. All across Europe, the benchmarking of structures, processes and outcomes could reveal opportunities for improving Paediatric Primary Care (PPC). The aim of this study was to develop a set of Quality Indicators (QIs) to assess and monitor PPC in Europe. In a three-step process, we used the available external evidence and European expert consensus in a modified RAND/UCLA Appropriateness Method (RAM) to develop an indicator set. (1) A broad literature and online research of published QI and guidelines yielded an inventory of 1516 QI. (2) A collaborative panel of paediatric senior experts from the European Academy of Paediatrics (EAP) and the European Confederation of Primary Care Paediatricians (ECPCP) from 15 European countries participated in a first consensus process to reduce the initial indicator inventory by eliminating not PPC-focused indicators and duplicates. (3) In a second consensus process, the panel rated the QI regarding validity and feasibility. The final QI set "COSI-PPC-EU" consists of 42 indicators in five categories of PPC: (A) health promotion/prevention/screening (13 QI), (B) acute care (9 QI), (C) chronic care (8 QI), (D) practice management (3 QI) and (E) patient safety (9 QI). CONCLUSION: COSI-PPC-EU represents a consented set of a limited number of valid quality indicators for the application in paediatric primary care in different healthcare systems throughout Europe. What is Known: • Paediatric ambulatory healthcare systems in Europe are diverse and show strikingly different outcomes. • There are known gaps in quality performance measures of paediatric primary care in Europe. Pre-existing sets of quality indicators are predominantly limited to national populations, specific diseases and hospital care. What is New: • A set of 42 quality indicators for primary paediatric care in Europe was developed in a multi-country collaborative effort. The method combined a systematic literature review and a consensus process among European paediatric experts. • The quality indicator set can facilitate quality improvement of PPC. After studying the feasibility, providers can use COSI-PPC-EU to monitor, compare and improve performance of practices, regions and countries.

SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents From Colorado, USA, and Bavaria, Germany.

This study screens more than 50 000 youths in diverse populations of Colorado and Bavaria to assess whether previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.

SARS-CoV-2 Seroprevalence in Preschool and School-Age Children­Population Screening Findings From January 2020 to June 2022

BACKGROUND: The SARS-CoV-2 pandemic is ongoing in Germany. Children and adolescents are increasingly being infected, and many cases presumably remain undetected and unreported. Sero-epidemiological studies can help estimate the true number of infections. METHODS: From January 2020 to June 2022, 59 786 persons aged 1-17 years were tested for SARS-CoV-2 antibodies as part of a screening program for presymptomatic type 1 diabetes in the German federal state of Bavaria (the Fr1da study). RESULTS: In June 2022, the seroprevalence in the overall population was 73.5%. The seroprevalence was significantly higher in school-age children (from 5 to 10 years of age) than in preschool children (ages 1-4): 84.4% vs. 66.6%, p <0.001. In contrast, in November 2021, before the appearance of the omicron variant, the overall seroprevalence was 14.7% (16.2% of school-age children, 13.0% of preschool children, p = 0.06). In the overall collective, seroprevalence increased fivefold from the fall of 2021 to June 2022 (by a factor of 5.2 in school-age children and 5.1 in preschool children). Similar seroprevalences, with smaller case numbers, were observed in June 2022 in the corresponding Fr1da studies in Saxony and Northern Germany: 87.8% and 76.7%, respectively. CONCLUSION: Monthly case counts reveal a substantial rise in SARS-CoV-2-infections among children and adolescents from late 2021 to mid-2022. The high percentage of preschool and school-age children who have been infected with SARS-CoV-2, in a population that has low vaccination coverage, should be taken into account in the development of health policies.

Assessment of the quality of routine ambulatory healthcare for common disorders in children and adolescents in Germany: study protocol for a retrospective medical record review (QualiPäd).

INTRODUCTION: The quality of healthcare in childhood and adolescence is of key importance, in order to foster a healthy development and to avoid chronic health problems. Yet, data for Germany regarding the quality of healthcare for this patient group are lacking. The QualiPäd research project aims to estimate the quality of outpatient healthcare for children and adolescents in Germany, focusing on common psychiatric and physical disorders. METHODS AND ANALYSIS: Quality indicators for seven common physical and mental childhood and adolescent clinical conditions (attention deficit/hyperactivity disorder, asthma, atopic dermatitis, depression, otitis media, conduct disorder/oppositional defiant disorder, tonsillitis) will be developed and ratified by experts, using the RAND/UCLA Appropriateness Method.Initially, 1400 medical records of children and adolescents with one of the aforementioned clinical conditions will then be randomly drawn from 40 outpatient practices in the German federal state of Hessen. The records will then be assessed regarding their adherence to the respective quality indicators. Based on this, the percentage of appropriate and inappropriate (eg, wasteful) healthcare of all clinical conditions (primary endpoint) will be estimated. Additionally, possible factors influencing the quality of care (eg, patient characteristics, type of condition, type of practice) will be identified using generalised estimation equation models. ETHICS AND DISSEMINATION: This study will show for which of the studied clinical conditions and/or patients improvement of quality of care is necessary within the German health system. Also, the quality indicators designed for the study can afterwards be implemented in regular care and thus enable regular reporting of the outpatient care of this target group. The authors plan to disseminate their findings through international, peer-reviewed scientific publications, and through presentations at national and international paediatric and child psychiatric conferences. TRIAL REGISTRATION NUMBER: DRKS00022408.

Symptoms, SARS-CoV-2 Antibodies, and Neutralization Capacity in a Cross Sectional-Population of German Children.

Background: Children and youth are affected rather mildly in the acute phase of COVID-19 and thus, SARS-CoV-2 infection infection may easily be overlooked. In the light of current discussions on the vaccinations of children it seems necessary to better identify children who are immune against SARS-CoV-2 due to a previous infection and to better understand COVID-19 related immune reactions in children. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a) randomly, if they had an appointment for a regular health check-up or (b) if parents and children volunteered and actively wanted to participate in the study. Symptoms were recorded and two antibody tests were performed in parallel directed against S (in house test) and N (Roche Elecsys) viral proteins. In children with antibody response in either test, neutralization activity was determined. Results: We identified antibodies against SARS-CoV-2 in 162 of 2,832 eligible children (5.7%) between end of May and end of July 2020 in three, in part strongly affected regions of Bavaria in the first wave of the pandemic. Approximately 60% of antibody positive children (n = 97) showed high levels (>97th percentile) of antibodies against N-protein, and for the S-protein, similar results were found. Sufficient neutralizing activity was detected for only 135 antibody positive children (86%), irrespective of age and sex. Initial COVID-19 symptoms were unspecific in children except for the loss of smell and taste and unrelated to antibody responses or neutralization capacity. Approximately 30% of PCR positive children did not show seroconversion in our small subsample in which PCR tests were performed. Conclusions: Symptoms of SARS-CoV-2 infections are unspecific in children and antibody responses show a dichotomous structure with strong responses in many and no detectable antibodies in PCR positive children and missing neutralization activity in a relevant proportion of the young population.

A Public Health Antibody Screening Indicates a 6-Fold Higher SARS-CoV-2 Exposure Rate than Reported Cases in Children.

BACKGROUND: Antibody responses to virus reflect exposure and potential protection. METHODS: We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveillance. Antibody positivity was defined as a dual-positive response against both the receptor-binding domain and nucleocapsid proteins of SARS-CoV-2. Antibodies were measured by immunoprecipitation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (ClinicalTrials.gov: NCT04039945), in 1,916 dried blood spots from neonates in a Bavarian screening study (ClinicalTrials.gov: NCT03316261), and in 75 SARS-CoV-2-positive individuals. Virus positive incidence was obtained from the Bavarian health authority data. FINDINGS: Dual-antibody positivity was detected in none of the 3,887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2-positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June, and 0.91% in July. Antibody prevalence from April 2020 was 6-fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions (p < 0.0001), and was not associated with age or sex. Transmission in children with virus-positive family members was 35%. 47% of positive children were asymptomatic. No association with type 1 diabetes autoimmunity was observed. Antibody frequency in newborns was 0.47%. CONCLUSIONS: We demonstrate the value of population-based screening programs for pandemic monitoring. FUNDING: The work was supported by funding from the BMBF (FKZ01KX1818).

Dietary protein restriction throughout intrauterine and postnatal life results in potentially beneficial myocardial tissue remodeling in the adult mouse heart.

Diet composition impacts metabolic and cardiovascular health with high caloric diets contributing to obesity related disorders. Dietary interventions such as caloric restriction exert beneficial effects in the cardiovascular system, but alteration of which specific nutrient is responsible is less clear. This study investigates the effects of a low protein diet (LPD) on morphology, tissue composition and function of the neonatal and adult mouse heart. Mice were subjected to LPD (8.8% protein) or standard protein diet (SPD, 22% protein) throughout intrauterine and postnatal life. At birth LPD female but not male offspring exhibit reduced body weight whereas heart weight was unchanged in both sexes. Cardiomyocyte cross sectional area was increased in newborn LPD females compared to SPD, whereas proliferation, cellular tissue composition and vascularization were unaffected. Adult female mice on LPD exhibit reduced body weight but normal heart weight compared to SPD controls. Echocardiography revealed normal left ventricular contractility in LPD animals. Histology showed reduced interstitial fibrosis, lower cardiomyocyte volume and elevated numbers of cardiomyocyte and non-myocyte nuclei per tissue area in adult LPD versus SPD myocardium. Furthermore, capillary density was increased in LPD hearts. In conclusion, pre- and postnatal dietary protein restriction in mice causes a potentially beneficial myocardial remodeling.