The impact of non-pharmaceutical interventions on community non-SARS-CoV-2 respiratory infections in preschool children.

BACKGROUND: Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is related to infections which are not medically attended. The perspective on infections in the community setting is necessary to understand the effects of the pandemic on non-pharmaceutical interventions. METHODS: In the unique prospective LoewenKIDS cohort study, we compared the true monthly incidence of self-reported acute respiratory infections (ARI) in about 350 participants (aged 3-4 years old) between October 2019 to March 2020 (pre-pandemic period) and October 2020 to March 2021 (pandemic period). Parents reported children's symptoms using a diary. Parents were asked to take a nasal swab of their child during all respiratory symptoms. We analysed 718 swabs using Multiplex PCR for 25 common respiratory viruses and bacteria. RESULTS: During the pre-pandemic period, on average 44.6% (95% CI: 39.5-49.8%) of children acquired at least one ARI per month compared to 19.9% (95% CI: 11.1-28.7%) during the pandemic period (Incidence Rate Ratio = 0.47; 95% CI: 0.41-0.54). The detection of influenza virus decreased absolute by 96%, respiratory syncytial virus by 65%, metapneumovirus by 95%, parainfluenza virus by 100%, human enterovirus by 96% and human bocavirus by 70% when comparing the pre-pandemic to the pandemic period. However, rhinoviruses were nearly unaffected by NPI. Co-detection (detection of more than one virus in a single symptomatic swab) was common in the pre-pandemic period (222 of 390 samples with viral detection; 56.9%) and substantially less common during the pandemic period (46 of 216 samples; 21.3%). CONCLUSION: Non-pharmaceutical interventions strongly reduced the incidence of all respiratory infections in preschool children but did not affect rhinovirus.

T cell repertoire breadth is associated with the number of acute respiratory infections in the LoewenKIDS birth cohort.

We set out to gain insight into peripheral blood B and T cell repertoires from 120 infants of the LoewenKIDS birth cohort to investigate potential determinants of early life respiratory infections. Low antigen-dependent somatic hypermutation of B cell repertoires, as well as low T and B cell repertoire clonality, high diversity, and high richness especially in public T cell clonotypes reflected the immunological naivety at 12 months of age when high thymic and bone marrow output are associated with relatively few prior antigen encounters. Infants with inadequately low T cell repertoire diversity or high clonality showed higher numbers of acute respiratory infections over the first 4 years of life. No correlation of T or B cell repertoire metrics with other parameters such as sex, birth mode, older siblings, pets, the onset of daycare, or duration of breast feeding was noted. Together, this study supports that-regardless of T cell functionality-the breadth of the T cell repertoire is associated with the number of acute respiratory infections in the first 4 years of life. Moreover, this study provides a valuable resource of millions of T and B cell receptor sequences from infants with available metadata for researchers in the field.

Birth cohort studies using symptom diaries for assessing respiratory diseases-a scoping review.

BACKGROUND: Respiratory infections are the most frequent health problem in childhood leading to morbidity and socioeconomic burden. Studying symptoms of respiratory infections in home based settings requires dedicated prospective cohort studies using diaries. However, no information is available on which birth cohort studies using symptom diary data. A review of birth cohort studies with available symptom diary data, follow-up data, and bio samples is needed to support research collaborations and create potential synergies. METHODS: We conducted a scoping review of birth cohort studies using diaries for the collection of respiratory symptoms. The scoping review was conducted in accordance with the PRISMA Extension. We searched the electronic databases PubMed, Embase, Web of science and CINAHL (last search November 2020) resulting in 5872 records (based on title and abstract screening) eligible for further screening. RESULTS: We examined 735 records as full text articles and finally included 57 according to predefined inclusion criteria. We identified 22 birth cohort studies that collect(ed) data on respiratory symptoms using a symptom diary starting at birth. Numbers of participants ranged from 129 to 8677. Eight studies collected symptom diary information only for the first year of life, nine for the first two years or less and six between three and six years. Most of the cohorts collected biosamples (n = 18) and information on environmental exposures (n = 19). CONCLUSION: Information on respiratory symptoms with daily resolution was collected in several birth cohorts, often including related biosamples, and these data and samples can be used to study full spectrum of infections, particularly including those which did not require medical treatment.

Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Trends in radiotherapy inpatient admissions in Germany: a population-based study over a 10-year period.

OBJECTIVE: With the increasing complexity of oncological therapy, the number of inpatient admissions to radiotherapy and non-radiotherapy departments might have changed. In this study, we aim to quantify the number of inpatient cases and the number of radiotherapy fractions delivered under inpatient conditions in radiotherapy and non-radiotherapy departments. METHODS: The analysis is founded on data of all hospitalized cases in Germany based on Diagnosis-Related Group Statistics (G-DRG Statistics, delivered by the Research Data Centers of the Federal Statistical Office). The dataset includes information on the main diagnosis of cases (rather than patients) and the performed procedures during hospitalization based on claims of reimbursement. We used linear regression models to analyze temporal trends. The considered data encompass the period from 2008 to 2017. RESULTS: Overall, the number of patients treated with radiotherapy as inpatients remained constant between 2008 (N = 90,952) and 2017 (N = 88,998). Starting in January 2008, 48.9% of 4000 monthly cases received their treatment solely in a radiation oncology department. This figure decreased to 43.7% of 2971 monthly cases in October 2017. We found a stepwise decrease between December 2011 and January 2012 amounting to 4.3%. Fractions received in radiotherapy departments decreased slightly by 29.3 (95% CI: 14.0-44.5) fractions per month. The number of days hospitalized in radiotherapy departments decreased by 83.4 (95% CI: 59.7, 107.0) days per month, starting from a total of 64,842 days in January 2008 to 41,254 days in 2017. Days per case decreased from 16.2 in January 2008 to 13.9 days in October 2017. CONCLUSION: Our data give evidence to the notion that radiotherapy remains a discipline with an important inpatient component. Respecting reimbursement measures and despite older patients with more comorbidities, radiotherapy institutions could sustain a constant number of cases with limited temporal shifts.

The risk of indoor sports and culture events for the transmission of COVID-19.

Nearly all mass gathering events worldwide were banned at the beginning of the COVID-19 pandemic, as they were suspected of presenting a considerable risk for the transmission of SARS-CoV-2. We investigated the risk of transmitting SARS-CoV-2 by droplets and aerosols during an experimental indoor mass gathering event under three different hygiene practices, and used the data in a simulation study to estimate the resulting burden of disease under conditions of controlled epidemics. Our results show that the mean number of measured direct contacts per visitor was nine persons and this can be reduced substantially by appropriate hygiene practices. A comparison of two versions of ventilation with different air exchange rates and different airflows found that the system which performed worst allowed a ten-fold increase in the number of individuals exposed to infectious aerosols. The overall burden of infections resulting from indoor mass gatherings depends largely on the quality of the ventilation system and the hygiene practices. Presuming an effective ventilation system, indoor mass gathering events with suitable hygiene practices have a very small, if any, effect on epidemic spread.

Effect of Radiotherapy in Addition to Surgery in Early Stage Endometrial Cancer: A Population-Based Study.

BACKGROUND: The role of radiotherapy in the management of early (FIGO I) endometrial cancer is controversial with limited availability of prospective data from randomized trials. METHODS: German Epidemiologic Cancer Registries provided by the Robert Koch Institute. We considered FIGO I cases with recorded operative treatment (n = 12,718, 2000-2017). We computed hazard ratios (HR) from relative survival models in relation to the mortality of the general population with 95% confidence intervals (CI). Multivariate models were adjusted for age, stage (IA vs. IB), grading, and chemotherapy. Radiotherapy included external radiotherapy and brachytherapy. RESULTS: Cases with a favorable risk profile (FIGO IA, G1/G2) had a slightly lower survival rate, relative to the general population (FIGO IA: 0.9, G1: 0.91). The proportion of FIGO IA cases was lower in the radiotherapy group (52.6%) vs. cases without radiotherapy (78.6%). Additional treatment with radiotherapy was beneficial in FIGO IB (HR = 0.74) and all histopathological grades, but not FIGO IA cases (HR = 0.93) cases. Compared to IA tumors, IB cases had a HR of 1.51 (95% CI: 1.34-1.7). CONCLUSIONS: Radiotherapy in addition to surgery is beneficial for patients in a FIGO IB stage. Further studies need to address the impact of new techniques and risk assessment.

[Self-reported infections in the German National Cohort (GNC) in the context of the current research landscape]. / Selbst berichtete Infektionen in der NAKO Gesundheitsstudie ­ Einordnung in die gegenwärtige Forschungslandschaft.

BACKGROUND: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. OBJECTIVES: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. METHODS: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. RESULTS: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. OUTLOOK: The cross-sectional analyses of data and tools presented here - for example on determinants of susceptibility to self-reported infections - can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.

[Occurrence of bronchial asthma and age at initial asthma diagnosis-first results of the German National Cohort]. / Häufigkeit von Asthma bronchiale und Alter bei der Erstdiagnose ­ erste Ergebnisse der NAKO Gesundheitsstudie.

BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.

[Lung function in the German National Cohort: methods and initial results]. / Lungenfunktion in der NAKO Gesundheitsstudie: Methoden und erste Ergebnisse.

BACKGROUND: A nationwide assessment of the respiratory status on the basis of standardized lung function measurements has so far not been available in Germany. The present work describes the lung function tests in the German National Cohort (GNC) and presents initial results based on the GNC Midterm Baseline Dataset. MATERIAL AND METHODS: The assessment of lung function in the GNC comprised spirometry (level 1) and the determination of exhaled nitric oxide (FeNO, level 2). Our quality assurance concept included regular training of lung function test procedures at various GNC sites, interim evaluations of test quality, as well as regular calibration/measurement checks of test equipment. For spirometry, we established a stepwise procedure for offline quality control based on raw flow volume curves. RESULTS: In the present dataset (n = 101,734), spirometry was available for 86,893 study participants and FeNO was available for 15,228 participants. The average (±SD) FEV1 Z score (according to GLI 2012) was -0.321 ± 1.047, the FVC Z score was -0.153 ± 0.941, and the FEV1/FVC Z score was -0.337 ± 0.901. The difference in FEV1/FVC between current smokers and never-smokers increased with age. The average FeNO was 14.2 ÷ 2.0 ppb. Current smoking reduced FeNO levels by 43%, whereas respiratory allergy increased FeNO levels by 16% in nonsmokers. DISCUSSION: The results of spirometry and the FeNO measurements are in the expected range with regard to their distributions and correlates. The GNC provides a valuable basis for future investigations of respiratory health and its determinants as well as research into the prevention of respiratory diseases in Germany.

Medium- to Long-term Follow-up of Obstetric Anal Sphincter Injury.

BACKGROUND: Obstetric anal sphincter injury is the primary modifiable risk factor for anal incontinence in women. Currently, endoanal ultrasound is most commonly used to detect residual anal sphincter defects after childbirth. Translabial ultrasound has recently been introduced as a noninvasive alternative. OBJECTIVES: This study aimed to determine medium- to long-term outcomes in women after obstetric anal sphincter injuries diagnosed and repaired at delivery. DESIGN: This is a cross-sectional study. SETTINGS: This study was performed in a tertiary obstetric unit. PATIENTS: Between 2005 and 2015, 707 women were diagnosed with obstetric anal sphincter injuries; 146 followed an invitation for follow-up. INTERVENTIONS: Clinical examination, anal manometry, and translabial ultrasound were performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the St Mark incontinence score and the evidence of sphincter disruption on translabial ultrasound. RESULTS: Of 372 contactable patients, 146 attended at a mean follow-up of 6.6 years (1.7-11.9), of which 75 (51%) reported symptoms of anal incontinence with a median "bother score" of 6 (interquartile range, 3-8). Median St Mark score was 3 (interquartile range, 2-5). Twenty-four (16%) had a score of ≥5. Women who had been diagnosed with a 3c/4th degree tear had more symptoms (58% vs 44%), significantly lower mean maximal resting pressure (p < 0.001), maximal squeeze pressure (p < 0.001), and more residual external (p < 0.001) and internal (p = 0.012) sphincter defects in comparison with those who had a 3a/3b tear. Women with residual external sphincter defects had lower mean maximal squeeze pressure (p = 0.02). Residual internal sphincter defects (p = 0.001) and levator avulsion (p = 0.048) are independent risk factors for anal incontinence on multivariate modeling. LIMITATIONS: This study was limited by the lack of predelivery data of bowel symptoms and BMI and incomplete intrapartum documentation of tear grade. CONCLUSIONS: Symptoms of anal incontinence were highly prevalent (51%), with a high bother score of 6. St Mark scores were associated with residual internal anal sphincter defects and levator avulsion. Women who had a higher tear grade showed a higher incidence of residual sphincter defects and lower manometry pressures. See Video Abstract at http://links.lww.com/DCR/A824.