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Background: The consortium project INTEGRATE-ADHD compared administrative data on the presence of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with the results of a parent survey and a comprehensive clinical assessment based on the S3 guideline of the Association of the Scientific Medical Societies in Germany (AWMF). Due to the COVID-19 pandemic, the clinical assessment was carried out online. Methods: The article describes how a guideline-based clinical assessment of ADHD can be implemented in an online setting. A specially developed diagnostic matrix is presented to illustrate the assessment procedures and the diagnostic decision-making process. The matrix is intended to help the diagnostician to gain an overview of the numerous individual findings that have been collected using different assessment perspectives and methods (e.g. diagnostic interviews, rating scales, performance tests) in order to make a well-founded and transparent diagnostic decision. Discussion: The consortium project INTEGRATE-ADHD has shown that an online assessment can be implemented in a guideline-compliant manner and allows a valid clinical decision. The diagnostic strategy is discussed with reference to international guidelines and recommendations for online diagnostics (e.g. aspects of feasibility, acceptability and safety of the assessment procedures). The challenges and opportunities of using online assessments in clinical practice are also described.

Background: This article examines discrepancies in the frequency of diagnoses of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in Germany using information on health care utilisation from both administrative and parent-reported survey data linked at person level. Methods: 5,461 parents of 0- to 17-year-olds insured with DAK-Gesundheit in 2020 and being registered with a confirmed administrative ADHD diagnosis (ICD-10 F90.0-9) in at least one quarter in 2020 (M1Q criterion) were surveyed online on their child’s ADHD diagnosis, utilisation of specialist care and therapeutic service providers. With regard to the presence of a parental report of the child’s documented ADHD diagnosis, administrative data and survey data were bi- and multivariately analysed. Results: The response rate was 21.5 %. ADHD diagnoses were given more frequently in the context of paediatric care, but in the multivariable model with the administrative data only the diagnosis made by mental health professionals (OR = 2.78), in the model with the survey data only utilisation of mental health professionals (OR = 2.99) positively predicted the parental diagnostic report. With regard to the utilisation of therapeutic service providers, only the utilisation of occupational therapy was associated with the parental report of the diagnosis in both data sources. Conclusions: Parental non-reporting of a child’s administrative ADHD diagnosis in survey studies can be in part be explained by utilisation characteristics.

Background: In the project INTEGRATE-ADHD, administrative and parent-reported ADHD diagnosis data of children and adolescents were linked at person level for the first time in Germany. This contribution analyses discrepancies between the data sources, considering sociodemographic characteristics. Methods: Parents of 5,461 0- to 17-year-olds insured with the German statutory health insurance company DAK-Gesundheit in 2020, who had a confirmed administrative diagnosis of ADHD (ICD-10 F90.0-9) in at least one quarter (M1Q criterion), were surveyed online about their child’s ADHD diagnosis and other health and care-related topics. Using logistic regression, associations between the presence of a parental report of the child’s administrative ADHD diagnosis and sociodemographic predictors were analysed. Results: 71.6 % of parents reported their child’s administrative diagnosis of ADHD in the survey. The diagnosis was significantly less likely to be reported by parents of girls, younger children, children with a migration background and children from nuclear families with both biological parents. There were no differences with regard to parental education, urbanisation (urban/rural) or density of care. Bivariate findings were confirmed in the multivariable model. Conclusions: Approximately one third of parents do not report their child’s administrative diagnosis of ADHD. The likelihood of parental reporting varies according to sociodemographic factors. This should be considered when contextualising the data sources in the future.

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased costs for the family, the health care system and the society. Previous cost-of-illness studies in Germany usually focused on prevalent ADHD. This study addressed the research gap on health care resource utilisation and costs of children and adolescents with incident ADHD diagnosis using nationwide claims data from the statutory health insurance DAK-Gesundheit. Methods: A matched-control design (propensity score matching, 1:3 ratio) was used to examine the health care costs of incident ADHD patients compared with a non-ADHD control group, considering an observation period of four quarters. Besides bivariate statistics, multivariate analyses of total costs were used to consider relevant covariates. Results: Total health care costs for children and adolescents with ADHD in the first year after diagnosis exceeded those of the control group by € 1,505.3. According to the multivariate analysis, the group with incident ADHD had significantly higher (2.86-fold) health care costs when compared with non-ADHD peers. Sensitivity analyses proved these findings. In addition, the analyses identified children’s age and comorbidity index to be significantly associated with increased costs. Conclusions: ADHD in children and adolescents is associated with a significant economic burden. The results emphasise the need for social awareness, prevention, appropriate treatment and research efforts.

Background: The study examines the psychometric properties of the ADHD section of the semi-structured diagnostic interview ILF-EXTERNAL, which was conducted online via video chat. Methods: As part of the INTEGRATE-ADHD research project, 202 children and adolescents (age M = 12.87 years, SD = 3.04, 28.2 % female) with an administrative diagnosis of ADHD registered with their health insurance company were clinically assessed for the presence of ADHD according to the German ADHD S3 guideline. Using the ILF-EXTERNAL, one parent and, from the age of eight, also the children themselves were interviewed. A proxy rating by a parent was made using the German FBB-ADHS rating scale. In a subsample (n = 65), an independent blind interviewer rated the videorecordings of the ILF-EXTERNAL parent interview to determine the interrater reliability of the ILF-EXTERNAL. Results: All ADHD symptom scales of the ILF-EXTERNAL showed good to excellent internal consistency (α = 0.89 to 0.93). Interrater reliability was high for both categorical and dimensional analyses (κ = 0.78 and κ = 0.81; ICC(1,1) = 0.97 and 0.98). High correlations of the ILF-EXTERNAL parent interview with the FBB-ADHS (r = 0.79 to r = 0.85) and with the ILF-EXTERNAL child interview (r = 0.60 to r = 0.71) demonstrated convergent validity. Conclusions: Sound psychometric properties of the ILF-EXTERNAL were also confirmed for its use in an online setting. High interrater reliabilities demonstrate the quality of the ADHD diagnostics carried out in the consortium project INTEGRATE-ADHD.

Background: The health-related quality of life (HRQoL) of individuals living with Attention-deficit/hyperactivity disorder (ADHD) is known to be impaired. Identifying factors that influence HRQoL can provide important information for the development of prevention and intervention programmes for affected children and adolescents. The aim of the present study was to investigate health care-related and psychosocial risk and protective factors for HRQoL in children and adolescents with an administrative ADHD diagnosis. Methods: In the consortium project INTEGRATE-ADHD, n = 4,809 parents of children and adolescents aged 7 to 17 years participated in an online survey between October 2021 and August 2022 and answered questions regarding HRQoL (KIDSCREEN-27), health care utilisation, and psychosocial risk and protective factors. Multiple linear regression analyses were conducted to assess the association between these factors and the five HRQoL dimensions of the KIDSCREEN-27. Results: Findings indicate that parental psychopathology and parental burden were risk factors for lower HRQoL in children and adolescents with ADHD. Further, a positive association was found between the five HRQoL dimensions and the psychosocial factors family climate and social support, indicating that these are protective factors. Conclusions: The results highlight the importance of prevention and intervention programmes for individuals with ADHD that consider parental mental health and aim to strengthen resources such as the availability of good family climate and social support.

Abstract Background Child maltreatment (CM) can have devastating and potentially lifelong effects for those affected and is a major contributor to mental health problems. To tackle public health problems it is crucial to have reliable data on CM. The aim of this study is to assess the prevalence and predictors of CM in a nationwide sample of the German population of young adults. Methods The study population (young adults aged 18 to 31 years) stems from the KiGGS Cohort study, the longitudinal branch of the German Health Interview and Examination Survey for children and adolescents. This sample meets the criteria of the United Nations Sustainable Development Goals (SDG) indicator 16.2.3. The data was collected between 2014 and 2017. CM were assessed with the Childhood Trauma Questionnaire (CTQ) in. In addition, socio-demographic variables and other known risk factors for CM were assessed. A total of 6433 (47.8% female) participants were included in the analyses. Binary logistic regression analyses were used to investigate predictors of maltreatment subtypes. Ordinal regression was used to examine their association with experience of multiple forms of CM. Results Overall, 18.4% (f: 20.9%, m: 16.1%) of the participants reported having experienced at least one type of CM; 6.7% (f: 8.8%, m: 4.8%) reported experiences of emotional abuse, 3.7% (f: 3.9%, m: 3.5%) physical abuse, 3.5% (f: 5.3%, m: 1.7%) sexual abuse, 9.0% (f: 9.9%, m: 8.2%) emotional neglect and 8.6% (f: 8.5%, m: 8.7%) physical neglect. Gender, subjective social status, education and household dysfunction (e.g. living with an individual who is using substances) emerged as significant predictors for different types of CM. Additionally, all these factors were significant risk factors for experiencing cumulative CM. Conclusions CM is common in the German population, with almost one in five people experiencing at least one type of CM. The results reveal important risk factors for the occurrence of CM. In particular, people with lower social status and those who grew up in dysfunctional households are at higher risk of CM. Greater support for this vulnerable population may reduce the prevalence of CM.

Abstract Background Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro. Epithelial cells can be immortalized, accomplished by using viral integration of immortalization factors. Viral approaches, however, might be impaired by regulatory and safety issues as well as random integration into regulatory genetic elements, modifying precise gene expression. We intend to use surgical specimen of prostate cancer patients to (i) prove for establishment of cancer cell lines, and (ii) perform non-viral, Sleeping Beauty (SB) transposase-based immortalization of prostate epithelial cells. Methods Radical prostatectomy samples of prostate cancer patients (n = 4) were dissociated and cultured in vitro. Cells were cultivated either without or after non-viral, Sleeping-Beauty transposase-based stable transfection with immortalization factors SV40LT and hTERT. Established cell lines were analyzed in vitro and in vivo for characteristics of prostate (cancer) cells. Results Initial cell cultures without genetic manipulation underwent senescence within ≤ 15 passages, demonstrating inability to successfully derive primary prostate cancer cell lines. By using SB transposase-based integration of immortalization factors, we were able to establish primary prostate cell lines. Three out of four cell lines displayed epithelial characteristics, however without expression of prostate (cancer) characteristics, e.g., androgen receptor. In vivo, one cell line exhibited tumorigenic potential, yet characteristics of prostate adenocarcinoma were absent. Conclusion Whereas no primary prostate cancer cell line could be established, we provide for the first-time immortalization of primary prostate cells using the SB transposase system, thereby preventing regulatory and molecular issues based on viral immortalization approaches. Although, none of the newly derived cell lines demonstrated prostate cancer characteristics, tumor formation was observed in one cell line. Given the non-prostate adenocarcinoma properties of the tumor, cells have presumably undergone oncogenic transformation rather than prostate cancer differentiation. Still, these cell lines might be used as a tool for research on prostate cancer initiation and early cancer progression.

Abstract Several bacterial toxins and viruses can deform membranes through multivalent binding to lipids for clathrin-independent endocytosis. However, it remains unclear, how membrane deformation and endocytic internalization are mechanistically linked. Here we show that many lipid-binding virions induce membrane deformation and clathrin-independent endocytosis, suggesting a common mechanism based on multivalent lipid binding by globular particles. We create a synthetic cellular system consisting of a lipid-anchored receptor in the form of GPI-anchored anti-GFP nanobodies and a multivalent globular binder exposing 180 regularly-spaced GFP molecules on its surface. We show that these globular, 40 nm diameter, particles bind to cells expressing the receptor, deform the plasma membrane upon adhesion and become endocytosed in a clathrin-independent manner. We explore the role of the membrane adhesion energy in endocytosis by using receptors with affinities varying over 7 orders of magnitude. Using this system, we find that once a threshold in adhesion energy is overcome to allow for membrane deformation, endocytosis occurs reliably. Multivalent, binding-induced membrane deformation by globular binders is thus sufficient for internalization to occur and we suggest it is the common, purely biophysical mechanism for lipid-binding mediated endocytosis of toxins and pathogens.

Gluten-related disorders are treated with a gluten-free diet. The “basic food basket” (BFB) consists of a list of basic foods consumed by low-income groups in society, including those lowest-cost versions within each food category. To evaluate the cost, availability, and nutritional quality of the BFB and gluten-free BFB (GF-BFB), foods were photographed, registering their cost, availability, and nutritional characteristics, in high quality and mid-range supermarkets, wholesalers, health shops, and corner shops, matching each regular BFB product with a gluten-free equivalent. Of the 1177 potential products, the selection of lowest-cost foods yielded 55 and 47 products (BFB and GF-BFB, respectively). Breads/cereals and drinks showed the highest differences (279% and 146%, respectively) while meats and sausages showed the lowest ones (18.6%). The GF-BFB cost represents 30.1% of the minimum wage, which covers the cost of 5.2 and 3.3 of the BFB and GF-BFB per month, respectively. Availability ranged between 22.7 and 42.4%. Lower availability was associated with poorer nutritional quality in the GF-BFB, which provides 5% less energy, 26% more fat, and 25% less protein than the BFB. Only 47% of gluten-free products declared their “gluten-free” condition. The results strongly suggest that the GF-BFB must be redesigned to be both gluten-free and nutritionally adequate.

Background: Child maltreatment (CM) can have devastating and potentially lifelong effects for those affected and is a major contributor to mental health problems. To tackle public health problems it is crucial to have reliable data on CM. The aim of this study is to assess the prevalence and predictors of CM in a nationwide sample of the German population of young adults. Methods: The study population (young adults aged 18 to 31 years) stems from the KiGGS Cohort study, the longitudinal branch of the German Health Interview and Examination Survey for children and adolescents. This sample meets the criteria of the United Nations Sustainable Development Goals (SDG) indicator 16.2.3. The data was collected between 2014 and 2017. CM were assessed with the Childhood Trauma Questionnaire (CTQ) in. In addition, socio-demographic variables and other known risk factors for CM were assessed. A total of 6433 (47.8% female) participants were included in the analyses. Binary logistic regression analyses were used to investigate predictors of maltreatment subtypes. Ordinal regression was used to examine their association with experience of multiple forms of CM. Results: Overall, 18.4% (f: 20.9%, m: 16.1%) of the participants reported having experienced at least one type of CM; 6.7% (f: 8.8%, m: 4.8%) reported experiences of emotional abuse, 3.7% (f: 3.9%, m: 3.5%) physical abuse, 3.5% (f: 5.3%, m: 1.7%) sexual abuse, 9.0% (f: 9.9%, m: 8.2%) emotional neglect and 8.6% (f: 8.5%, m: 8.7%) physical neglect. Gender, subjective social status, education and household dysfunction (e.g. living with an individual who is using substances) emerged as significant predictors for different types of CM. Additionally, all these factors were significant risk factors for experiencing cumulative CM. Conclusions: CM is common in the German population, with almost one in five people experiencing at least one type of CM. The results reveal important risk factors for the occurrence of CM. In particular, people with lower social status and those who grew up in dysfunctional households are at higher risk of CM. Greater support for this vulnerable population may reduce the prevalence of CM. [ABSTRACT FROM AUTHOR]

Simple Summary: ICI-based combinations have led to a significant change in mRCC medical treatment. However, data from real-world (RW) cohorts are rare. In this multicenter study, we evaluated the safety and effectiveness of cabozantinib plus nivolumab in real-world cohorts from centers in Germany, Switzerland, and Austria. The median PFS in the overall cohort was 18.6 months. We also analyzed subgroups in relation to the IMDC, histology, and with regard to the presence of bone metastasis. In summary, our real-word data support the promising efficacy data of the pivotal trials, particularly in patients with non-ccRCC and those without bone metastases at the start of the treatment. Introduction: Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients. Methods: Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria. Patients with advanced or mRCC were eligible. The investigator-based objective response rate (ORR) and progression free survival (PFS) were calculated from the start of the treatment to progression or death. Descriptive statistics and Kaplan–Meier (KM) plots were utilized where appropriate. Results: In total, 96 eligible patients (66.6% male) with a median age of 66.0 years were included. The most common histology was clear-cell RCC (ccRCC) in 63.4% (n = 61). A prior nephrectomy was performed in 60.4% (n = 58). ECOG 0-1 was 68.8% (n = 66). A partial response was documented in 43.8% of patients (n = 42), a stable disease in 32.3% (n = 31), and a progressive disease in 8.3% (n = 8) as the best overall response. Response data were not evaluable in 13.5% (n = 13). The median follow-up time was 12.7 months (95% CI, 10.0–15.3). The PFS rate at 6 months was 89.8% in the overall population (86.8% for ccRCC; 90.0% for non-ccRCC). Adverse events (AEs) were reported in 82.3% (n = 79) for all grades and 41.7% (n = 40) for grades 3–5. Elevated liver enzymes (34.4%), diarrhea (31.3%), and hand–foot syndrome (29.2%) were the three most frequent AEs of any grade and causality. Discussion/Conclusions: In this real-world cohort of mRCC patients, the application of cabozantinib plus nivolumab was shown to be safe and feasible. Our data support the use of cabozantinib plus nivolumab as a first-line standard therapy in mRCC patients. Major limitations were the retrospective data capture and short follow-up time of our study. [ABSTRACT FROM AUTHOR]