Viral infections in hospitalized children in Germany during the COVID-19 pandemic: Association with non-pharmaceutical interventions.

Background: Non-pharmaceutical interventions (NPI) during the COVID-19 pandemic aimed at prevention of SARS-CoV-2 transmission also influenced transmission of viruses other than SARS-CoV-2. The aim of this study was to describe and compare the burden of common viral respiratory and gastrointestinal infections in children admitted to Berlin University Children's Hospital (BCH) before and during the COVID-19 pandemic at different levels of public NPI measures. Methods: In this retrospective study, we analyzed the frequency of detection of common human respiratory and gastrointestinal viruses from January 2016 through January 2022 in all patients admitted to BCH. We compared virus detection before and during the COVID-19 pandemic at different levels of public NPI measures. Results: The frequency of detection of seasonal enveloped and non-enveloped viruses [Boca-, Corona-, Influenza-, Metapneumo-, Parainfluenza-, Rota-, and Respiratory Syncytial Viruses (RSV)] was diminished during the COVID-19 pandemic, whereas detection rates of non-seasonal viruses (Rhino-/Entero-, and Adenoviruses) were stable during the pandemic. After withdrawal of major NPI measures, we observed an out of season surge of the detection rates of Boca-, Corona-, Parainfluenzaviruses, and RSV. In contrast, no increased detection frequency was observed for Influenza-, Metapneumo-, and Rotaviruses as of January 2022. Conclusion: Corona-, Boca-, Parainfluenzaviruses, and RSV returned as frequently detected pathogens after withdrawal of major NPI measures. The out of season rise might be attributed to an "immune-debt" due to missing contact to viral antigens resulting in waning of population immunity during the COVID-19 pandemic.

A Case Report: First Long-Term Treatment With Burosumab in a Patient With Cutaneous-Skeletal Hypophosphatemia Syndrome.

Epidermal nevus syndromes encompass a highly heterogeneous group of systemic disorders, characterized by epidermal nevi, and a spectrum of neuromuscular, ocular, and bone abnormalities. Cutaneous-skeletal hypophosphatemia syndrome (CSHS) constitutes a specific sub-entity in which elevated levels of fibroblast growth factor-23 cause hypophosphatemic rickets that are, to date, not amenable to causal therapy. Here, we report the first long-term follow-up of causal treatment with burosumab in a 3-year-old female patient with CSHS. 4 weeks after initiation of burosumab treatment, serum phosphate normalized to age-appropriate levels. Furthermore, long-term follow-up of 42 months revealed significant improvement of linear growth and gross physical functions, including respiratory insufficiency. Radiographic rickets severity as well as subjective bone pain were strongly reduced, and no side effects were observed over the course of treatment. In summary, we, here, report about a successful treatment of hypophosphatemic rickets in CSHS with burosumab over the time course of 42 months. In our patient, burosumab showed convincing efficacy and safety profile, without any loss of effect or increase of dose.

Maintenance of Elective Patient Care at Berlin University Children's Hospital During the COVID-19 Pandemic.

Background: In Germany, so far the COVID-19 pandemic evolved in two distinct waves, the first beginning in February and the second in July, 2020. The Berlin University Children's Hospital at Charité (BCH) had to ensure treatment for children not infected and infected with SARS-CoV-2. Prevention of nosocomial SARS-CoV-2 infection of patients and staff was a paramount goal. Pediatric hospitals worldwide discontinued elective treatments and established a centralized admission process. Methods: The response of BCH to the pandemic adapted to emerging evidence. This resulted in centralized admission via one ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatment during the first wave, but maintenance of elective care and decentralized admissions during the second wave. We report numbers of patients treated and of nosocomial SARS-CoV-2 infections during the two waves of the pandemic. Results: During the first wave, weekly numbers of inpatient and outpatient cases declined by 37% (p < 0.001) and 29% (p = 0.003), respectively. During the second wave, however, inpatient case numbers were 7% higher (p = 0.06) and outpatient case numbers only 6% lower (p = 0.25), compared to the previous year. Only a minority of inpatients were tested positive for SARS-CoV-2 by RT-PCR (0.47% during the first, 0.63% during the second wave). No nosocomial infection of pediatric patients by SARS-CoV-2 occurred. Conclusion: In contrast to centralized admission via a ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatments, maintenance of elective care and decentralized admission allowed the almost normal use of hospital resources, yet without increased risk of nosocomial infections with SARS-CoV-2. By this approach unwanted sequelae of withheld specialized pediatric non-emergency treatment to child and adolescent health may be avoided.

Geographical Accessibility of Pediatric Inpatient, Nephrology, and Urology Services in Europe.

Background: Although many children with diseases of the kidneys and the urinary tract may not tolerate long journeys, the number of facilities that provide specialized care for these patients is limited. Therefore, the geographical accessibility of the required health services is critical especially in this patient group. We have analyzed the geographical accessibility of pediatric inpatient and nephro-urology services in Germany, Ireland, and the United Kingdom (UK). Methods: This study introduces a model to compare countries or regions regarding the geographical accessibility of their health services. We calculated the geodesic distances, travel distances, and travel time by car from evenly distributed random points to the nearest facilities that provide pediatric inpatient or nephro-urology outpatient services (pediatric inpatient ward, urology clinic, nephrology clinic, hemodialysis unit). The results were weighted by population density. We compared the three countries with regard to the accessibility of the named services. Results: Weighted median travel times from the random points to the nearest pediatric inpatient ward are < 30 min in all countries. Weighted travel times to the nearest point of pediatric service are shortest in the UK (median <50 min) and longest in Ireland (median <90 min), regardless of the type of service (p < 0.0001). Non-weighted travel times to the nearest pediatric inpatient ward and hemodialysis unit, however, are shorter in Germany than in the UK (p < 0.0001). Conclusions: There is a surprising disparity between the travel times to the nearest facility with pediatric nephro-urology service in these three industrialized European countries. Reasons may be differences in the geographical distribution of the population, the focus of the health care system, and a different degree of clinical networking.

Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage.

BACKGROUND: This study aims to establish age- and gender-specific cystatin C (CysC) reference values for healthy infants, children, and adolescents and to relate them to pubertal stage, height, weight, and body mass index (BMI). METHODS: Serum CysC and creatinine levels of 6217 fasting, morning venous blood samples from 2803 healthy participants of the LIFE Child study (age 3 months to 18 years) were analyzed by an immunoassay. Recruitment started in 2011; 1636 participants provided at least one follow-up measurement. Percentiles for CysC were calculated. Age- and gender-related effects of height, weight, BMI, and puberty status were assessed through linear regression models. RESULTS: Over the first 2 years of life, median CysC levels decrease depending on height (ß = - 0.010 mg/l/cm, p < 0.001) and weight (ß = - 0.033 mg/l/kg, p < 0.001) from 1.06 to 0.88 mg/l for males and from 1.04 to 0.87 mg/l for females. Following the second year of age, the levels remain stable for eight years. From 11 to 14 years of age, there is an increase of median CysC levels in males to 0.98 mg/l and a decrease in females to 0.86 mg/l. The change is associated with puberty (ß = 0.105 mg/l/Tanner stage, p < 0.001 in males and ß = - 0.093 mg/l/Tanner stage, p < 0.01 in females) and in males with height (ß = 0.003 mg/l/cm, p < 0.001). CONCLUSIONS: CysC levels depend on age, gender, and height, especially during infancy and puberty. We recommend the use of age- and gender-specific reference values for CysC serum levels for estimating kidney function in clinical practice.

Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function.

BACKGROUND: Impaired glucose metabolism and cystic fibrosis (CF)-related diabetes (CFRD) are associated with insufficient weight gain and impaired lung function in children and adolescents with CF. We have asked whether imminent CFRD may be a cause of poor growth in children and adolescents. METHODS: A retrospective case control study including 32 patients with CF with or without diabetes was conducted. Sixteen pairs, matched according to age, gender and exocrine pancreatic insufficiency, were analysed. Standard deviation scores (SDS) of height, growth, weight, body mass index (BMI), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and forced expiratory flow at 75% of expired FVC (FEF75) were recorded during a mean observation period of 13 years per patient. RESULTS: SDS of height and weight were reduced in CF patients with diabetes compared to those without, not only at the point of diagnosis (both p<0.05) but years before the evidence of diabetes. Afterwards there was a significant decline in height (p<0.001) and weight (p<0.01) SDS in CFRD patients and an increasing difference between the height and weight of CF patients with or without diabetes. In contrast, no significant reduction of BMI-SDS was observed in CFRD patients. All analysed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to the diagnosis of diabetes. CONCLUSIONS: Deteriorating growth, reduced weight and impaired lung function are related to the development of CFRD and are obvious several years before the actual diagnosis of diabetes.

Adherence to transfusion guidelines: are we prepared for the Smarter Medicine or Choosing Wisely initiative?

OBJECTIVE: To determine, whether a restrictive transfusion strategy is followed in our hospital and to identify differences in activities within departments and patient groups. METHOD: Over a period of 15 months, RBC transfusions were prospectively recorded including the haemoglobin level prior to transfusion and were grouped in the different departments of our hospital (internal medicine ward, department of surgery, emergency room, intensive care unit, gynaecology ward, medical outpatient clinic and oncology outpatient clinic). Indications and co-morbidities were assessed retrospectively by reviewing the patient's charts. RESULTS: There were 1,832 RBC products transfused in total. The overall mean level of haemoglobin before transfusion was 7.61 g/dl (±1.1). These haemoglobin levels differed significantly between the departments (p <0.001), with the lowest threshold in the internal medicine ward (7.30 g/dl ± 1.0) compared to the surgery ward (7.73 g/dl ± 1.0) and to the intensive care unit (7.82 g/dl ± 0.9). In general, mean pre-transfusion haemoglobin levels did not differ significantly between patients with coronary artery disease (CAD) and patients without (7.64 g/dl ± 1.0 vs 7.59 g/dl ± 1.1, p = 0.48). In transfusions for patients with acute coronary syndrome a tendency to a higher transfusion threshold than in patients with stable CAD could be found (7.84 g/dl ± 0.7 vs 7.58 g/dl ± 1.0, p = 0.05). Patients with haematological disorders were transfused at a higher threshold when compared to patients without (7.77 g/dl vs 7.56 g/dl, p = 0.006). CONCLUSION: All wards in our analysis are following the current guidelines based on restrictive transfusion strategies. At the same time, we were able to detect significant differences between different departments and patient characteristics.