[Results of PCR Pool Testing In Primary and Special Needs Schools In Bavaria For The School Year 2021/2022: Sentinel Surveillance In Face-To-Face Teaching During The Sars-CoV-2 Pandemic]. / Ergebnisse von PCR-Pooltestungen an bayerischen Grund- und Förderschulen im Schuljahr 2021/2022 zur Surveillance im Präsenzunterricht während der SARS-CoV-2-Pandemie.

In the school years 2019/20 and 2020/21, children were physically, psychologically, and socially stressed by school closures caused by the SARS-CoV-2 pandemic. To ensure attendance with optimal infection protection, PCR pool testing was conducted during the 2021/22 school year at Bavarian elementary schools and schools for pupils with special needs for timely detection of SARS-CoV-2 infection. This study analyzes the results of PCR pool testing over time stratified by region, school type, and age of children. The data were obtained from classes in elementary and special needs schools, involving pupils aged 6 to 11 years, who participated in the Bavaria-wide PCR pool testing from 09/20/21 to 04/08/22. Samples were collected twice weekly, consisting of PCR pool samples and individual PCR samples, which were only evaluated in case of a positive pool test. A class was considered positive if at least one individual sample from that class was positive within a calendar week (CW). A school (class) was considered to be infection-prone if three or more classes in that school (students in that class) were positive within a CW. The data included 2,430 elementary schools (339 special needs schools) with 23,021 (2,711) classes and 456,478 (29,200) children. A total of 1,157,617 pools (of which 3.37% were positive) and 724,438 individual samples (6.76% positive) were analyzed. Larger schools exhibited higher PR compared to smaller schools. From January 2022, the Omicron variant led to a massive increase in PR across Bavaria. The incidence rates per 100,000 person-weeks within the individual school samples were significantly lower than the concurrently reported age-specific and general infection incidences in the overall Bavarian population. PCR pool testing revealed relatively few positive pools, with an average of four children per one hundred pools testing positive. Schools and classes were rarely considered infection-prone, even during periods of high incidences outside of schools. The combination of PCR pool testing and hygiene measures allowed for a largely safe in-person education for pupils in primary and special needs schools in the school year 2021/22.

Post-tuberculosis lung impairment: systematic review and meta-analysis of spirometry data from 14 621 people.

BACKGROUND: A substantial proportion of tuberculosis patients remain with pulmonary symptoms and reduced physical capacity despite successful treatment. We performed a systematic review to analyse the burden of post-tuberculosis lung impairment measured by lung function testing. METHODS: We searched the PubMed database for articles published between database inception and November 2020 and performed meta-analyses to estimate the prevalence, type and severity of lung impairment among drug-susceptible and multidrug-resistant tuberculosis survivors. Methodological quality of included studies was assessed using the Newcastle-Ottawa scale. RESULTS: 54 articles were included in this review. For subjects with former drug-susceptible tuberculosis, the combined estimated mean was 76.6% (95% CI 71.6-81.6) of predicted for forced expiratory volume in 1 s (FEV1) and 81.8% (95% CI 77.4-86.2) for forced vital capacity (FVC). In former patients with multidrug-resistant tuberculosis, it was 65.9% (95% CI 57.1-74.7) for FEV1 and 76.0% (95% CI 66.3-85.8) for FVC, respectively. The analysis of impairment types in former patients with drug-susceptible and multidrug-resistant tuberculosis showed that 22.0% versus 19.0% had obstructive, 23.0% versus 22.0% restrictive and 15.0% versus 43.0% had mixed impairment type, respectively. In the majority of studies, at least 10-15% of tuberculosis survivors had severe lung impairment. CONCLUSIONS: This systematic review showed long-term abnormal spirometry results in a significant proportion of tuberculosis survivors.

Landmark models to define the age-adjusted risk of developing stage 1 type 1 diabetes across childhood and adolescence.

BACKGROUND: Autoimmune diseases are often preceded by an asymptomatic autoantibody-positive phase. In type 1 diabetes, the detection of autoantibodies to pancreatic islet antigens in genetically at-risk children is prognostic for future clinical diabetes. Testing for islet autoantibodies is, therefore, performed in a range of clinical studies. Accurate risk estimates that consider the a priori genetic risk and other risk modifiers are an important component of screening. The age of an individual is an under-appreciated risk modifier. The aim of this study was to provide age-adjusted risk estimates for the development of autoantibodies across childhood in genetically at-risk children. METHODS: The prospective BABYDIAB and BABYDIET studies included 2441 children from birth who had a first-degree relative with type 1 diabetes. Children were born between 1989 and 2006 and were regularly followed from birth for the development of islet autoantibodies and diabetes. A landmark analysis was performed to estimate the risk of islet autoantibodies at birth and at the age 3.5, 6.5 and 12.5 years. Exponential decay curves were fitted for the risk by the age of 20 years. RESULTS: The risk of islet autoantibodies by the age of 20 years was 8%, 4.6%, 2.6% and 0.9%, at the landmark ages of birth, 3.5, 6.5 and 12.5 years, respectively. The short-term risks (within 6 years of follow-up) at these landmark ages were 5.3%, 2.9%, 1.8% and 1%, respectively. The decline in autoantibody risk with age was modelled using a one-phase exponential decay curve (r = 0.99) with a risk half-life of 3.7 years. This risk decay model was remarkably consistent when the outcome was defined as islet autoantibody-positive or multiple islet autoantibody-positive and when the study cohort was stratified by HLA risk genotype. A similar decay model was observed for coeliac disease-associated transglutaminase antibodies in the same cohort. Unlike the risk of developing islet autoantibodies, the rate of developing clinical diabetes in children who were islet autoantibody-positive did not decline with age. CONCLUSION: The risk of developing autoantibodies drops exponentially with age in children with a first-degree relative with type 1 diabetes.

Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol.

INTRODUCTION: The POInT study, an investigator initiated, randomised, placebo-controlled, double-blind, multicentre primary prevention trial is conducted to determine whether daily administration of oral insulin, from age 4.0 months to 7.0 months until age 36.0 months to children with elevated genetic risk for type 1 diabetes, reduces the incidence of beta-cell autoantibodies and diabetes. METHODS AND ANALYSIS: Infants aged 4.0 to 7.0 months from Germany, Poland, Belgium, UK and Sweden are eligible if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies as determined by genetic risk score or family history and human leucocyte antigen genotype. Infants are randomised 1:1 to daily oral insulin (7.5 mg for 2 months, 22.5 mg for 2 months, 67.5 mg until age 36.0 months) or placebo, and followed for a maximum of 7 years. Treatment and follow-up is stopped if a child develops diabetes. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies or diabetes. Other outcomes are: (1) Any persistent confirmed beta-cell autoantibody (glutamic acid decarboxylase (GADA), IA-2A, autoantibodies to insulin (IAA) and zinc transporter 8 or tetraspanin 7), or diabetes, (2) Persistent confirmed IAA, (3) Persistent confirmed GADA and (4) Abnormal glucose tolerance or diabetes. ETHICS AND DISSEMINATION: The study is approved by the ethical committees of all participating clinical sites. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the trial. TRIAL REGISTRATION NUMBER: NCT03364868.

[Ethical consideration of studies involving human subjects outside the regulatory framework: not mandatory, but of high relevance]. / Ethische Bewertung von Studien am Menschen außerhalb des regulatorischen Rahmens: nicht bindend, aber von großer Wichtigkeit.

According to the Declaration of Helsinki, ethics committees are obliged to evaluate any type of medical research involving human subjects in order to ensure an objective view on ethical considerations. This does not only mean considering whether the risks to study participants are ethically justifiable or not, but also checking whether the scientific quality of a study is sufficient. However, the role of ethics committees differs depending on whether the study to be considered is, for example, an approval study according to the German Medicines Act (AMG) or whether the study is outside the regulatory framework. For these so-called unregulated studies it is not always mandatory to obtain approval from an ethics committee or an institutional review board.In this paper, we first explain the term "unregulated studies" in detail and elaborate for which types of unregulated studies an application for ethical approval is required before we deal with the application for ethical approval as such and in particular with the study protocol as one of its major components. Registry studies, postmarketing surveillance studies, analyses of secondary data, surveys, intervention, and prognostic studies serve as examples to illustrate the broad range of unregulated studies.Finally, we discuss crucial aspects of the role of ethics committees with respect to the consideration of unregulated studies. In our conclusion, we point out the necessity of having ethics committees at each university in Germany that are also responsible for unregulated studies. In addition, the German legislature should define a stricter regulation such that unregulated studies also have to adhere to the vote of the ethics committee.

Factors influencing adherence in CML and ways to improvement: Results of a patient-driven survey of 2546 patients in 63 countries.

Optimal adherence to CML therapy is of key importance to maximize treatment effectiveness. Two clinical studies (ADAGIO and Hammersmith) have proven a clear correlation between adherence and achieving optimal treatment response and have revealed that non-adherence is common in CML patients (Marin et al. in J Clin Oncol 28(24):2381-2388, 2010, Noens et al. in Haematologica 99(33):437-447, 2014). The aim of this study is to assess the extent of suboptimal adherence and to investigate motivations and behavioural patterns of adherence in a worldwide patient sample. Questionnaires were provided by the CML Advocates Network and were filled in by patients online and offline. Patient characteristics, treatment and motivations were collected. Adherence was assessed by the 8-item Morisky Medication Adherence scale. Logistic regression models were fitted to investigate the influence of different factors on adherence. Overall, 2 546 questionnaires from 63 countries and 79 CML patient organisations were evaluable. 32.7% of participants were highly adherent, 46.5% were in the medium and 20.7% in the low adherence group. Factors increasing the probability of being in the high adherence group are older age, male sex, management of side effects, only one tablet per day and feeling well informed about CML by the doctor. More than 2 years since diagnosis were significantly lowering the chance as was the use of reminding tools. Living arrangements, multiple medication and personal payment obligations increased the probability to be at least in the medium adherent group. This is the most comprehensive study conducted to date to gain knowledge about factors causing non-adherence in CML. Better information on the disease, medication and management of side effects, supported by haematologists, is key to improve adherence.