Pleural Effusion and Chylothorax in Congenital Diaphragmatic Hernia-Risk Factors, Management and Outcome.

Background: Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax development in patients with CDH and to investigate the association of pleural effusion and chylothorax with neonatal morbidity and mortality. Methods: In this retrospective cohort study, we included 396 neonates with CDH treated at our institution between January 2013 and June 2019. Preoperative and postoperative chest radiographs and clinical data were evaluated and correlated with morbidity, complications and mortality. Results: Laboratory-confirmed chylothorax occurred in 58 (18.6%) of all CDH cases. Pleural effusion was frequently observed as a postoperative complication but also occurred as a pre-existing condition. Neonates with large defects of size C and D, patch repair, the need for presurgical and/or postsurgical ECMO support, pulmonary hypertension, liver-up phenomenon and lower relative fetal lung volume were associated with higher occurrences of chylothorax. After stepwise logistic regression, larger CDH defects (p < 0.0001) and the need for postsurgical ECMO (p = 0.0158) remained significant risk factors for CTX to occur (AUC 0.71). The same potential risk factors were used to assess their association with both presurgical and postsurgical pleural effusion. After stepwise logistic regression, only the need for presurgical ECMO remained significantly associated with presurgical PE (p < 0.01, AUC 0.65) and patch repair as the therapeutic intervention remained significantly associated with the occurrence of postsurgical PE (p < 0.0001, AUC 0.80). Patients with CTX had longer durations of both MV (p < 0.0001) and subsequent ventilatory assistance with spontaneous breathing (p = 0.0004), increased total lengths of hospitalization (p < 0.0001), increased durations of ECMO (p < 0.01) and increased incidences of CLD (p < 0.0001) compared to patients without CTX. No significant difference could be found for survival in both groups (p = 0.12). Conclusions: Our data suggest that the incidence of chylothorax is associated with large diaphragmatic defects, the need for postsurgical ECMO and the development of chronic lung disease, but not with survival.

Case Report: Fetoscopic Laparoschisis (FETO-LAP)-A New Therapeutic Route to Explore for Fetuses with Severe Diaphragmatic Hernias.

BACKGROUND: The purpose of this report is to describe the seminal case of a near-term human fetus with a life-threatening left diaphragmatic hernia that underwent fetoscopic tracheal occlusion (FETO) combined with fetoscopic partial removal of herniated bowel from the fetal chest by fetoscopic laparoschisis (FETO-LAP). CASE SUMMARY: A life-threatening left diaphragmatic hernia (liver-up; o/e LHR of ≤25%; MRI lung volume ≤ 20%) was observed in a human fetus at 34 weeks of gestation. After counselling the mother about the high risks of postnatal demise if left untreated, the expected limitations of fetoscopic tracheal occlusion (FETO), and the previously untested option of combining FETO with fetoscopic laparoschisis, i.e., partial removal of the herniated bowel from the fetal chest (FETO-LAP), she consented to the latter novel treatment approach. FETO-LAP was performed at 36 + 5 weeks of gestation under general maternofetal anesthesia. Mother and fetus tolerated the procedure well. The neonate was delivered and the balloon removed on placental support at 37 + 2 weeks of gestation. On ECMO, a rapid increase in tidal volume was seen over the next eight days. Unfortunately, after this period, blood clots obstructed the ECMO circuit and the neonate passed away. DISCUSSION: This seminal case shows that in a fetus with severe left diaphragmatic hernia, partial removal of the herniated organs from the fetal chest is not only possible by minimally invasive fetoscopic techniques but also well tolerated. As the effect of FETO alone is limited in saving severely affected fetuses, combining FETO with fetoscopic laparoschisis (FETO-LAP) offers a new therapeutic route with multiple, potentially life-saving implications.

Discovery and In Vitro Characterization of BAY 2686013, an Allosteric Small Molecule Antagonist of the Human Pituitary Adenylate Cyclase-Activating Polypeptide Receptor.

The human pituitary adenylate cyclase-activating polypeptide receptor (hPAC1-R), a class B G-protein-coupled receptor (GPCR) identified almost 30 years ago, represents an important pharmacological target in the areas of neuroscience, oncology, and immunology. Despite interest in this target, only a very limited number of small molecule modulators have been reported for this receptor. We herein describe the results of a drug discovery program aiming for the identification of a potent and selective hPAC1-R antagonist. An initial high-throughput screening (HTS) screen of 3.05 million compounds originating from the Bayer screening library failed to identify any tractable hits. A second, completely revised screen using native human embryonic kidney (HEK)293 cells yielded a small number of hits exhibiting antagonistic properties (4.2 million compounds screened). BAY 2686013 (1) emerged as a promising compound showing selective antagonistic activity in the submicromolar potency range. In-depth characterization supported the hypothesis that BAY 2686013 blocks receptor activity in a noncompetitive manner. Preclinical, pharmacokinetic profiling indicates that BAY 2686013 is a valuable tool compound for better understanding the signaling and function of hPAC1-R. SIGNIFICANCE STATEMENT: Although the human pituitary adenylate cyclase-activating polypeptide receptor (hPAC1-R) is of major significance as a therapeutic target with a well documented role in pain signaling, only a very limited number of small-molecule (SMOL) compounds are known to modulate its activity. We identified and thoroughly characterized a novel, potent, and selective SMOL antagonist of hPAC1-R (acting in an allosteric manner). These characteristics make BAY 2686013 an ideal tool for further studies.

Quality of life and mental health in children and adolescents during the first year of the COVID-19 pandemic: results of a two-wave nationwide population-based study.

BACKGROUND: The COVID-19 pandemic has disrupted the lives of children and adolescents worldwide. The German COPSY study is among the first population-based longitudinal studies to examine the mental health impact of the pandemic. The objective of the study was to assess changes in health-related quality of life (HRQoL) and mental health in children and adolescents and to identify the associated risk and resource factors during the pandemic. METHODS: A nationwide longitudinal survey was conducted with two waves during the pandemic (May/June 2020 and December 2020/January 2021). In total, n = 1923 children and adolescents aged 7 to 17 years and their parents participated (retention rate from wave 1 to wave 2: 85%). The self-report and parent-proxy surveys assessed HRQoL (KIDSCREEN-10), mental health problems (SDQ with the subscales emotional problems, conduct problems, hyperactivity, and peer problems), anxiety (SCARED), depressive symptoms (CES-DC, PHQ-2) and psychosomatic complaints (HBSC-SCL). Mixed model panel regression analyses were conducted to examine longitudinal changes in mental health and to identify risk and resource factors. RESULTS: The HRQoL of children and adolescents decreased during the pandemic, and emotional problems, peer-related mental health problems, anxiety, depressive and psychosomatic symptoms increased over time, however the change in global mental health problems from wave 1 to wave 2 was not significant, and some changes were negligible. Socially disadvantaged children and children of mentally burdened parents were at particular risk of impaired mental health, while female gender and older age were associated with fewer mental health problems. A positive family climate and social support supported the mental health of children and adolescents during the pandemic. DISCUSSION: Health promotion, prevention and intervention strategies could support children and adolescents in coping with the pandemic and protect and maintain their mental health.

The DADYS-Screen: Development and Evaluation of a Screening Tool for Affective Dysregulation in Children.

Affective dysregulation (AD) in children is characterized by persistent irritability and severe temper outbursts. This study developed and evaluated a screening questionnaire for AD in children. The development included the generation of an initial item pool from existing instruments, a Delphi rating of experts, focus groups with experts and parents, and psychometric analyses of clinical and population-based samples. Based on data of a large community-based study, the final screening questionnaire was developed (n = 771; 49.7 % female; age M = 10.02 years; SD = 1.34) and evaluated (n = 8,974; 48.7 % female; age M = 10.00 years; SD = 1.38) with methods from classical test theory and item response theory. The developed DADYS-Screen (Diagnostic Tool for Affective Dysregulation in Children-Screening Questionnaire) includes 12 items with good psychometric properties and scale characteristics including a good fit to a one-factorial model in comparison to the baseline model, although only a "mediocre" fit according to the root mean square error of approximation (RMSEA). Results could be confirmed using a second and larger data set. Overall, the DADYS-Screen is able to identify children with AD, although it needs further investigation using clinical data.

Impact of Time Point of Extracorporeal Membrane Oxygenation on Mortality and Morbidity in Congenital Diaphragmatic Hernia: A Single-Center Case Series.

Since there are no data available on the influence of the time point of ECMO initiation on morbidity and mortality in patients with congenital diaphragmatic hernia (CDH), we investigated whether early initiation of ECMO after birth is associated with a beneficial outcome in severe forms of CDH. All neonates with CDH admitted to our institution between 2010 until 2020 and undergoing ECMO treatment were included in this study and divided into four different groups: (1) ECMO initiation < 12 h after birth (n = 143), (2) ECMO initiation between 12−24 h after birth (n = 31), (3) ECMO initiation between 24−120 h after birth (n = 48) and (4) ECMO initiation > 120 h after birth (n = 14). The mortality rate in the first (34%) and fourth group (43%) was high and in the second group (23%) and third group (12%) rather low. The morbidity, characterized by chronic lung disease (CLD), did not differ significantly in the three groups; only patients in which ECMO was initiated >120 h after birth had an increased rate of severe CLD. Our data, although not randomized and limited due to small study groups, suggest that very early need for ECMO and ECMO initiation > 120 h after birth is associated with increased mortality.

The effects of prolactin receptor blockade in a murine endometriosis interna model.

Endometriosis in an estrogen-dependent disease that is characterized by the presence of endometrial tissue outside the uterine cavity leading to pain and infertility in many affected women. Highly efficient treatment options which create a hypo-estrogenic environment can cause side effects such as hot flushes and bone mass loss that are not favorable for premenopausal women. Previous work has demonstrated that increased local or systemic prolactin seems to be involved in the pathogenesis of endometriosis. Here we examined two prolactin receptor (PRLR) blocking antibodies in a murine endometriosis interna model which relies on the induction of systemic hyperprolactinemia in female SHN mice. The severity of the disease is determined by the degree of endometrial invasion into the myometrium. In this model, endometriosis was inhibited by clinical gold standards such as progestins and anti-estrogenic approaches. PRLR blockade completely inhibited endometriosis in this mouse model to the same extent as the anti-estrogen faslodex or the GnRH antagonist cetrorelix. In contrast to cetrorelix and faslodex, the PRLR antibodies did not decrease relative uterine weights and were thus devoid of anti-estrogenic effects. We therefore hypothesize that PRLR antibodies may present a novel and highly efficient treatment option for endometriosis with a good safety and tolerability profile. Clinical studies are on the way to test this hypothesis.

Assessing anger and irritability in children: psychometric evaluation and normative data for the German version of the PROMIS® Parent Proxy Anger Scale.

PURPOSE: Anger and irritability are common and impairing symptoms in children. The PROMIS Anger scales assess self- and parent-reported irritable and angry mood over the past 7 days. The aim of this study was to evaluate the psychometric properties of the German version of the PROMIS Parent Proxy Short Form v1.0-Anger and to provide normative data. METHODS: To evaluate the psychometric properties, data from the study ADOPT Epidemiology were used. In this study, the PROMIS Anger Scale was administered to a population-based sample of n = 8746 parents of children aged 8-12 years. Psychometric analyses were carried out including the investigation of distribution characteristics, factor structure, model fit, internal consistency, and congruent validity. Normative data were calculated as percentile ranks and T-scores. RESULTS: The PROMIS Anger Scale demonstrated good psychometric properties, including satisfactory distribution characteristics, unidimensionality, good internal consistency as well as congruent validity. German normative data for the PROMIS Anger Scale are presented. CONCLUSION: Based on first psychometric analyses, the German version of the PROMIS Anger Scale can be recommended for use in research and practice; however, further investigations using clinical data are needed. The normative data will allow researchers and clinicians an interpretation of the test scores in future applications.

Pharmacokinetics, Safety, and Tolerability of the α2C -Adrenoreceptor Antagonist BAY 1193397 in Healthy Male Subjects.

The α2C -adrenoreceptor antagonist BAY 1193397 is in development for the oral treatment of diabetic foot ulcers. Safety, tolerability, and pharmacokinetics of BAY 1193397 were investigated in 3 randomized, single-center phase 1 studies in healthy male subjects: a first-in-human study (single oral doses of 0.5-50 mg), a relative bioavailability and food effect study (single doses of 1 and 10 mg), and a multiple-dose escalation study (using 2 and 5 mg twice daily and 10 and 20 mg once daily for 9 consecutive days). BAY 1193397 was rapidly absorbed in the fasted state, peak concentrations were reached between 0.6 and 2 hours. The mean terminal half-life was in the range of 17 to 20 hours. Area under the plasma concentration-time curve and maximum concentration appeared to be dose proportional, with a negligible food effect. There were no high-accumulation effects of BAY 1193397 after repeated dosing. BAY 1193397 was safe and well tolerated. At supratherapeutic plasma concentrations, there were slight transient increases in norepinephrine levels, heart rate, and blood pressure that were more pronounced after a single dose compared to steady state and appeared to be maximum concentration dependent. The results of the presented studies support the conduct of subsequent clinical trials with BAY 1193397 in patients with diabetes and compromised microcirculation.

Impact of the COVID-19 pandemic on quality of life and mental health in children and adolescents in Germany.

The COVID-19 pandemic has caused unprecedented changes in the lives of 1.6 billion children and adolescents. First non-representative studies from China, India, Brazil, the US, Spain, Italy, and Germany pointed to a negative mental health impact. The current study is the first nationwide representative study to investigate the impact of the COVID-19 pandemic on health-related quality of life (HRQoL) and mental health of children and adolescents in Germany from the perspective of children themselves. A representative online survey was conducted among n = 1586 families with 7- to 17-year-old children and adolescents between May 26 and June 10. The survey included internationally established and validated instruments for measuring HRQoL (KIDSCREEN-10), mental health problems (SDQ), anxiety (SCARED), and depression (CES-DC). Results were compared with data from the nationwide, longitudinal, representative BELLA cohort study (n = 1556) conducted in Germany before the pandemic. Two-thirds of the children and adolescents reported being highly burdened by the COVID-19 pandemic. They experienced significantly lower HRQoL (40.2% vs. 15.3%), more mental health problems (17.8% vs. 9.9%) and higher anxiety levels (24.1% vs. 14.9%) than before the pandemic. Children with low socioeconomic status, migration background and limited living space were affected significantly more. Health promotion and prevention strategies need to be implemented to maintain children's and adolescents' mental health, improve their HRQoL, and mitigate the burden caused by COVID-19, particularly for children who are most at risk.

Measuring health-related quality of life in young children with physical illness: psychometric properties of the parent-reported KIDSCREEN-27.

PURPOSE: This study examined whether the KIDSCREEN-27 was reliable and valid in young children 2-7 years with chronic physical illnesses which included estimating inter-domain correlations and internal consistency; measurement invariance testing; and, discriminant and convergent validity assessments. METHODS: Data come from the Multimorbidity in Children and Youth across the Life-course; a longitudinal study of individuals aged 2-16 years with physical illness. The parent-reported KIDSCREEN-27 was administered. Children (2-7 years; n = 106) were compared to adolescents (8-16 years; n = 157). Reliability was estimated using Cronbach α for internal consistency. Multiple group confirmatory factor analysis tested for measurement invariance. Cohen's d and Pearson coefficient were used to assess discriminant validity by sex and age. Convergent validity was tested using Pearson coefficients with the WHODAS 2.0 (child functioning/impairment). Multiple regression examined associations between multimorbidity (co-occurring physical and mental illness) and HRQL. RESULTS: Internal consistency reliabilities were α = 0.74-0.88 (children) and α = 0.77-0.88 (adolescents). Inter-domain correlations were relatively low (children: r = 0.18-0.59; adolescents: r = 0.30-0.62) indicating that each KIDSCREEN-27 domain was measuring a unique aspect of health-related quality of life. Measurement invariance was demonstrated (scalar level). Parameter estimates of the invariant models were similar for children and adolescents. Small, non-significant correlations were found for sex and age for children and adolescents. Medium, significant correlations were found for both groups between the KIDSCREEN-27 and WHODAS 2.0. Children and adolescents with multimorbidity had significantly lower physical well-being, psychological well-being, and school environment scores compare to those without multimorbidity. Regression coefficients were similar between groups. CONCLUSION: Findings provide evidence of adequate psychometrics for the KIDSCREEN-27 in young children with chronic physical illness.

Risk and resource factors of antisocial behaviour in children and adolescents: results of the longitudinal BELLA study.

BACKGROUND: Antisocial behaviour is a common phenomenon in childhood and adolescence. Information on psychosocial risk and resource factors for antisocial behaviour are important for planning targeted prevention and early intervention programs. The current study explores risk and resource factors of antisocial behaviour in children and adolescents based on population-based longitudinal data. METHODS: We analysed longitudinal data from the German BELLA study (n = 1145; 11 to 17 year-olds) measured at three measurement points covering two years. Latent growth analysis, linear regression models and structural equation modelling were used to explore cross-sectional and longitudinal data. RESULTS: Based on baseline data, we found that stronger self-efficacy and worse family climate were each related to stronger antisocial behaviour. Longitudinal data revealed that more severe parental mental health problems, worse family climate at baseline, deteriorating family climate over time, and more social support were each associated with increasing antisocial behaviour over time. We further found a moderating effect for family climate. CONCLUSIONS: Our study provides important exploratory results on psychosocial risk, resource and protective factors in the context of antisocial behaviour in children and adolescents, which need confirmation by future research. Our exploratory results point in the direction that family-based interventions for antisocial behavior in children and adolescents may benefit from considering the family climate.

Health-related quality of life in children with and without physical-mental multimorbidity.

PURPOSE: This study examined health-related quality of life (HRQL) in children across different physical illnesses; estimated parent-child agreement on HRQL reports; compared HRQL between children with and without physical-mental multimorbidity; and tested if multimorbidity was associated with HRQL. METHODS: Children aged 6-16 years (mean = 11.1; n = 198) with one physical illness and their parents were recruited from a pediatric hospital. Physical illnesses were classified according to the International Statistical Classification of Diseases and Related Health Problems (ICD)-10, mental illnesses were assessed using the Mini International Neuropsychiatric Interview for Children and Adolescents, and HRQL was measured using the KIDSCREEN-27. Children who screened positive for ≥ 1 mental illness were classified as having physical-mental multimorbidity. χ2/t tests compared sample characteristics of children with vs. without multimorbidity; Kruskal-Wallis tests compared KIDSCREEN-27 scores across ICD-10 categories; interclass correlation coefficients estimated parent-child agreement; and multiple regression examined effects of the number of mental illnesses on HRQL. RESULTS: HRQL was similar across ICD-10 categories. Parent-child agreement was fair to good for all HRQL domains, regardless of multimorbidity status. Parent-reported HRQL was significantly lower for children with multimorbidity compared to norms across all domains, whereas child-reported HRQL was significantly lower for physical well-being, psychological well-being, and school environment. Number of mental illnesses was negatively associated with psychological well-being and school environment in a dose-response manner. CONCLUSION: Children with physical-mental multimorbidity are vulnerable to experiencing lower HRQL, particularly for psychological well-being and school environment. Longitudinal studies documenting trajectories of HRQL and school-based interventions that target these domains of HRQL for children with multimorbidity are warranted.

[Mental health and psychological burden of children and adolescents during the first wave of the COVID-19 pandemic-results of the COPSY study]. / Seelische Gesundheit und psychische Belastungen von Kindern und Jugendlichen in der ersten Welle der COVID-19-Pandemie ­ Ergebnisse der COPSY-Studie.

BACKGROUND: The drastic changes during the COVID-19 pandemic may have a negative impact on the psychological wellbeing of children and adolescents. OBJECTIVES: COPSY is the first national, representative German study to examine mental health and quality of life of children and adolescents during the pandemic. Results are compared with data of the representative longitudinal BELLA study conducted before the pandemic. MATERIALS AND METHODS: Internationally established instruments for measuring health-related quality of life and mental health (including anxiety and depressive symptoms) were administered to n = 1586 parents with 7­ to 17-year-old children and adolescents, of whom n = 1040 11- to 17-year-olds also provided self-reports, from 26 May to 10 June 2020. Data were analyzed using descriptive statistics and bivariate tests. RESULTS: Seventy-one percent of the children and adolescents and 75% of the parents felt burdened by the first wave of the COVID-19 pandemic. Compared to the time before the pandemic, the children and adolescents reported a lower health-related quality of life, the percentage of children and adolescents with mental health problems almost doubled, and their health behavior worsened. Socially disadvantaged children felt particularly burdened by the COVID-19 pandemic. Two-thirds of the parents would like to receive support in coping with their child during the pandemic. CONCLUSIONS: The COVID-19 pandemic poses a mental health risk to children and adolescents. Schools, doctors, and society are called to react by providing low-threshold and target-group-specific prevention and mental health promotion programs.

Trajectories of health-related quality of life in children of parents with mental health problems: results of the BELLA study.

PURPOSE: Children of parents with mental health problems (CPM) have an increased risk for impaired health-related quality of life (HRQoL). This study aims at investigating the age- and gender-specific course of HRQoL and at exploring predictors of HRQoL in CPM based on longitudinal data (baseline, 1-year and 2-year follow-up) of a German population-based sample. METHODS: Longitudinal data from the German BELLA study was analyzed (n = 1429; aged 11 to 17 years at baseline). The SCL-S-9 in combination with the cutoff for the General Severity Index (GSI) from the longer SCL-90-R served to identify CPM (n = 312). At first, we compared domain-specific HRQoL according to the KIDSCREEN-27 in CPM versus Non-CPM. Focusing on CPM, we used individual growth modeling to investigate the age and gender-specific course, and to explore effects of risk and (personal, familial and social) resource factors on self-reported HRQoL in CPM. RESULTS: Self-reported HRQoL was reduced in CPM compared to Non-CPM in all domains, but in social support & peers. However, a minimal important difference was only reached in girls for the domain autonomy & parent relation. Internalizing and externalizing mental health problems were associated with impaired HRQoL in CPM. Self-efficacy, social support and family climate were identified as significant resources, but parental mental health problems over time were not associated with any investigated domain of HRQoL in CPM. CONCLUSIONS: Adolescent female CPM may be especially at risk for reduced HRQoL. When developing support programs for CPM, self-efficacy, social support and family climate should be considered, HRQoL and mental health problems in CPM should be addressed.

[The Role of the Socioeconomic Status in Mental Health Care Utilization by Children and Adolescents in Germany: Results of the BELLA Study]. / Zur Rolle des sozioökonomischen Status bei der Inanspruchnahme fachspezifischer Versorgung von psychisch auffälligen Kindern und Jugendlichen in Deutschland: Ergebnisse der BELLA-Studie.

OBJECTIVE: Children and adolescents with a low socioeconomic status (SES) are significantly more often affected by mental health problems than their peers with a high SES. So far, little is known about the association between family's SES and utilization of mental health care. This study examines the mental health care utilization by children and adolescents depending on their SES and symptoms of mental health problems as well as the impact of mental health problems. METHODS: The analysis comprisesd data from the population-based BELLA-study, which investigates mental health in a representative subsample of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Between 2014 and 2017, 1,580 participants aged 7 to 17 years were examined. SES was measured by the indicators of household income, parental educational attainment and parental occupation status. Symptoms and impairment of mental health problems were measured using the Strength and Difficulties Questionnaire (SDQ and SDQ-Impact). To investigate mental health care, the consultation of child and adolescent psychiatrists, medical and psychological psychotherapists and psychologists was considered. A hierarchic binary logistic regression model was calculated predicting mental health care use. In addition, effects of SES-indicators on associations between symptoms and impairment as well as mental health care utilization (moderator analysis) were investigated. RESULTS: Children and adolescents with a low SES were more likely to utilize mental health care services than their peers with a high SES. Mental health care utilization was significantly predicted by symptoms of mental health problems (OR=1.15, p≤0.001) as well as by the impairment caused by these problems (OR=1.68, p≤0.001); we found no significant moderation effects for household income, parental education or parental occupation. CONCLUSION: The probability of mental health care utilization by children and adolescents is significantly predicted by the symptoms and the impairments caused by mental health problems, but not by household income, parental education or parental occupation.

Peer Relationships and Depressive Symptoms Among Adolescents: Results From the German BELLA Study.

Background: Poor mental health affects adolescent development and is associated with health and social outcomes in later life. The current study uses cross-sectional data to explore the understudied aspects of peer relationships as a predictor of depressive symptom severity of adolescents in Germany. Method: Data from the German BELLA study were analyzed. We focused on the most recent measurement point of the BELLA study and analyzed data of 446 adolescents (aged 14-17 years). Peer relationship was measured using four items from the internationally established Patient-Reported Outcome Measurement Information System (PROMIS). Depressive symptoms were assessed via seven items of the German version of the Centre for Epidemiological Studies Short Depression Scale (CES-D). Hierarchical linear regression models were computed to explore the association between depressive symptoms and peer relationships. Hierarchical linear regression models served to determine the added predictive effects of each aspect of peer relationships. Result: The regression model showed that 22% of the variance of the severity of depressive symptoms could be explained by the quality of adolescents' peer relationships (F(1,444) = 125.65, p < 0.001). Peer acceptance has the most substantial unique contribution to peer relationship as a predictor of depressive symptom severity (Change in R 2 = 0.05; Change in F = 27.01, p < 0.001). The gender-specific analysis shows different trends for boys and girls. Conclusion: The quality of peer relationships is a significant predictor of adolescents' depressive symptoms severity. Improved peer acceptance, dependability, and ease of making new friends are significantly associated with reduced depression symptoms for Germany's adolescent population.

Mental health and well-being from childhood to adulthood: design, methods and results of the 11-year follow-up of the BELLA study.

Mental health and well-being are of great interest in health policy and research. Longitudinal surveys are needed to provide solid population-based data. We describe the design and methods of an 11-year follow-up of the German BELLA study in children, adolescents and young adults, and we report on age- and gender-specific courses of general health and well-being, long-term health-related outcomes of mental health problems, and mental health care use. The BELLA study is the module on mental health and well-being within the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Standardised measures were used at each of the five measurement points of the BELLA study. In the 11-year follow-up, young people aged 7-31 years participated (n = 3492). Individual growth modelling, linear regression and descriptive analyses were conducted. Self-reported general health and well-being were both better in younger (vs. older) and in male (vs. female) participants according to the data from all five measurement points. Mental health problems in childhood and adolescence (measured at baseline) predicted impaired health outcomes at 6-year and 11-year follow-ups. Approximately one out of four children with a diagnosed mental disorder was not undergoing mental health treatment. With its 11-year follow-up, the prospective longitudinal BELLA study provides new and solid data on mental health and well-being from childhood to adulthood in Germany, and these data are important for health promotion and prevention practices. These results are consistent with previous findings. Promising future analyses are planned.

Effects of the chymase inhibitor fulacimstat in diabetic kidney disease-results from the CADA DIA trial.

BACKGROUND: The protease chymase generates multiple factors involved in tissue remodelling including angiotensin II (Ang II) and has been implicated in the pathophysiology of diabetic kidney disease (DKD). This study investigated the effects of the chymase inhibitor fulacimstat on albuminuria in patients with Type II diabetes mellitus and a clinical diagnosis of DKD. METHODS: In this double-blind, randomized, placebo-controlled trial, patients were on the maximum tolerated dose of either an Ang II receptor blocker or an Ang-converting enzyme inhibitor since at least 3 months before the screening visit. Eligible patients were randomized in a 2:1 ratio to treatment with either 25 mg fulacimstat (n = 99) or placebo (n = 48) twice daily on top of standard of care. RESULTS: The randomized patients had a mean urine albumin-creatinine ratio (UACR) of 131 mg/g (range: 29-2429 mg) and a mean (standard deviation) estimated glomerular filtration rate of 60.8 ± 16.9 mL/min/1.73 m2 before treatment start. Fulacimstat was safe and well tolerated, and achieved mean total trough concentrations that were ∼9-fold higher than those predicted to be required for minimal therapeutic activity. UACR increased by 27.4% [coefficient of variation (CV) 86%] and 3% (CV 88.9%) after 24 weeks of treatment with placebo or fulacimstat, respectively. Analysis of covariance revealed a least square mean UACR ratio (fulacimstat/placebo) of 0.804 (90% CI 0.627-1.030, P = 0.1477), indicating a statistically non-significant UACR reduction of 19.6% after fulacimstat treatment compared with placebo. CONCLUSIONS: Fulacimstat was safe and well tolerated but did not reduce albuminuria in patients with DKD. These findings do not support a therapeutic role for chymase inhibition in DKD.

Risk and resource factors for depressive symptoms during adolescence and emerging adulthood - A 5-year follow-up using population-based data of the BELLA study.

INTRODUCTION: Depression is one of the most common mental disorders in adolescents and young adults worldwide, and causes a high burden for both individuals and society. The present study aims to investigate the role of risk and resource factors for depressive symptoms during adolescence and emerging adulthood in a German population-based cohort. METHODS: Within the longitudinal BELLA study, data on risk and resource factors were collected among n = 632 children and adolescents aged 11 to 17 years. Depressive symptoms were measured five years later. Multivariate linear regression models served to investigate effects of risk and resource factors on depressive symptoms. Regression models were stratified by gender. Moreover, we explored potential interaction effects. RESULTS: A negative mother-child relationship predicted depressive symptoms in girls, whereas school stress served as a risk factor in boys. Peer competence was associated with fewer depressive symptoms in girls, and family cohesion was identified as a resource factor in boys. In addition, few moderating effects of resource factors on the association between risk factors and depressive symptoms were found. LIMITATIONS: As the BELLA study is a population-based observational study, we only identified associations between risk and resource factors and no cause-effect relationships. CONCLUSIONS: Findings provide evidence of gender-specific risk and resource factors for depression. Individuals who are exposed to risk factors must be monitored during the transition into adulthood. Gender-sensitive prevention and early intervention programs are needed.