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.

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.

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.

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.

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.

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.

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 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.

[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.

[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.

Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial.

BACKGROUND: Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. RESULTS: Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ±â€¯5.4%, placebo: 4.0% ±â€¯5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ±â€¯13.3 mL/m2, placebo: 5.1 ±â€¯18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ±â€¯11.2 mL/m2, placebo: 0.6 ±â€¯14.8 mL/m2, P = .56) were observed in both treatment arms. CONCLUSION: Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

Do 8- to 18-year-old children/adolescents with chronic physical health conditions have worse health-related quality of life than their healthy peers? a meta-analysis of studies using the KIDSCREEN questionnaires.

PURPOSE: This meta-analytic review aimed to estimate the magnitude of health-related quality of life (HrQoL) impairments, as assessed by the KIDSCREEN questionnaires, both self- and parent-reported, in 8- to 18-years-old children/adolescents with chronic health conditions. METHODS: To identify studies using the KIDSCREEN questionnaires, three electronic databases (PubMed, PsycINFO, EBSCOhost Psychology & Behavioral Sciences) were searched. The final search (February 14-15, 2018) revealed 528 non-duplicated articles, of which 23 papers (21 studies) directly compared the HrQoL of pediatric patients to community/healthy controls and were included in the meta-analysis. Pooled mean differences (MD) with 95% CIs were estimated using the inverse-variance random-effects method. RESULTS: Of the 21 studies, 16 used self-reports, one used parent-reports and four adopted a multi-informant approach. Self-reported data were retrieved from 20 studies (4852 cases/28,578 controls), and parent-reported data were retrieved from four studies (511 cases/433 controls). Pediatric patients presented significant HrQoL impairments in the domains of physical well-being (MD = - 4.84, 95% CI - 6.44/- 3.24 for self-reports; MD = - 6.86, 95% CI - 10.42/- 3.29 for parent-reports) and peers and social support (MD = - 1.29, 95% CI - 2.25/- 0.34 for self-reports; MD = - 3.90, 95% CI - 5.28/- 2.52 for parent-reports), compared to community/healthy peers. Between-studies heterogeneity was explained by diagnostic categories, instrument version and informants. CONCLUSIONS: The identification of significant HrQoL impairments among pediatric patients, specifically in the physical and social domains, highlights the importance of routine psychosocial assessment and intervention in primary pediatric healthcare services. Specific recommendations include the use of profile measures, both self- and parent-reports, and the prioritization of oncology, endocrinology and neurology services.

iNO Therapy in Patients with Congenital Diaphragmatic Hernia - Discrepancy between Widespread Use and Therapeutic Effects.

BACKGROUND: Despite recent studies failing to prove beneficial effects of iNO therapy in patients with CDH, its use is still widespread. The aim of this work was to analyze iNO use in a retrospective cohort focusing on outcome parameters. Patients 378 CDH patients born and treated in Mannheim University Medical Center, Department for Neonatology, between 2010 and 2017 constituted our cohort. Therapy was based on the standardized protocol of the CDH EURO Consortium. METHOD: General data (sex, birth weight, gestational age etc.) and therapy-related data (duration of iNO application, OI after 60 mins, need for ECMO support etc.) were collected from clinical reports and then conducted using SAS for both mono- and multivariate analyses. RESULTS: Out of 378 newborns with CDH, 265 received iNO (70.1%), of whom 82 (30.9%) showed a significant OI reduction of ≥5 pts after 60 mins (=responders), median OI improved by 1.85 pts overall. Among initial responders iNO, application reduced the need for ECMO support (p=0.0054), increased the time to ECMO initiation (p=0.005) and reduced mortality (p=0.0396). DISCUSSION: A group of 43 patients considerably benefited from iNO and thererfore as they did not need ECMO support. Even though iNO therapy has failed to prove significant beneficial effects for non-responders, the application is still to be considered an essential treatment method in the transitional period of CDH patients. CONCLUSIONS: A more critical approach towards iNO application in nonresponders should be promoted. Further extensive multicenter studies on treatment alternatives for CDH-PAH are desirable.

[Associations of maternal educational background with health and health behavior in infants]. / Der Bildungsstand von Müttern im Zusammenhang mit der Gesundheit und dem Gesundheitsverhalten ihrer Kleinkinder.

BACKGROUND: The basis for healthy development is established during the first years of one's life. In this early phase, parents can significantly influence the health conditions under which their child grows up. Parental education can play a key role in this regard. This study examines the association of maternal education with health and health behavior in infants. METHODS: A subsample of the representative German KiGGS study (Wave 1, 2009-2012) on the health of children and adolescents was investigated. Data from 1727 mothers who reported on health-specific characteristics of their infants (0 to 2 years), on their own educational background, and on characteristics of the family were analyzed. The influence of maternal education on indices of health and health behavior in infants was investigated by means of logistic regression; additional predictors were considered in regression models. RESULTS: Higher maternal education was associated with better health behavior, but not with overall infant health. The impact of maternal education on health behavior remained significant when considering other predictors (financial worries, low maternal age at childbirth, premature birth/low birth weight). Overall, low maternal education was accompanied by an accumulation of additional risks. CONCLUSIONS: Higher maternal education can help infants have a good start in their lives. The impact of poor health behavior on infant health may not become apparent until later in their lives. For prevention and intervention, it is important to identify sensitive stages of development during childhood and the underlying mechanisms of the relationship between maternal education and infant health behavior.

Predictors of self-reported health-related quality of life according to the EQ-5D-Y in chronically ill children and adolescents with asthma, diabetes, and juvenile arthritis: longitudinal results.

PURPOSE: Health-related quality of life (HRQoL) is an important patient-reported outcome in clinical and health research. The EQ-5D-Y assesses child and adolescent HRQoL by five items on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as a visual analogue scale (VAS) on the current health state. This study investigates predictors of self-reported HRQoL according to the EQ-5D-Y in chronically ill children and adolescents using longitudinal data. METHODS: Data from the German Kids-CAT study on children and adolescents with asthma, diabetes, and juvenile arthritis gathered over a period of six months were analyzed (n = 310; 7-17 years old; 48% female). Self-, parent-, and pediatrician-reported data were collected from June 2013 to October 2014. Generalized linear mixed models and linear mixed models served to examine effects of socio-demographic as well as disease- and health-specific predictors on the items as well as on the VAS of the EQ-5D-Y. RESULTS: Ceiling effects for the EQ-5D-Y indicated low burden of disease in the analyzed sample. Longitudinal analyses revealed associations between less health complaints and better HRQoL for all investigated HRQoL domains. Further, age- and gender-specific effects, and associations of better disease control, longer duration of the disease and less mental health problems with better HRQoL were found. CONCLUSIONS: Subjective health complaints and mental health problems should be considered in the care of children and adolescents with asthma, diabetes, and juvenile arthritis. Future research should suggest administering the items of the EQ-5D-Y with five instead of three response options, and investigate HRQoL over a longer period.

Trajectories of mental health problems in children of parents with mental health problems: results of the BELLA study.

Children of parents with mental health problems (CPM) have an increased risk for behavioral and psychological problems. This study investigated the age- and gender-specific course as well as predictors of mental health problems in CPM using the longitudinal data (baseline 1- and 2-year follow-ups) of a German general population sample from the BELLA study. Children and adolescents aged 11-17 years (at baseline) who had a parent with mental health problems (n = 325) were analyzed. The mental health problems of the children were assessed by the self-reported version of the strengths and difficulties questionnaire (SDQ). We used individual growth modeling to investigate the age- and gender-specific course, and the effects of risk as well as personal, familial and social protective factors on self-reported mental health problems in CPM. Additionally, data were examined differentiating internalizing and externalizing mental health problems in CPM. Results indicated that female compared to male CPM showed increasing mental health problems with increasing age. Mental health problems in CPM were associated with lower self-efficacy, worse family climate and less social competence over time. Internalizing problems were associated with lower self-efficacy, less social competence and more severe parental mental health problems. Externalizing problems were associated with lower self-efficacy, worse family climate and lower social competence. The main limitations of the study are the short time period (2 years) covered and the report of mental health problems by only one parent. Our findings should be considered in the development of treatment and prevention programs for mental health problems in CPM.

[Predictors of Health-related Quality of Life in Bavarian Preschool Children]. / Prädiktoren gesundheitsbezogener Lebensqualität bei bayerischen Einschulungskindern.

BACKGROUND: Little data are available on health-related quality of life (HRQOL) of children in Germany at the age of school enrollment. OBJECTIVE: Aim of this study was to investigate the HRQOL of children during school enrollment and to determine its predictors with special focus on environmental factors. METHODS: Data from the fifth survey of the Health-Monitoring-Units (GME) conducted in Bavaria (2010/2011) were analyzed. Parent-reported data on HRQOL using the KINDL-R(evised), the Strength and Difficulties Questionnaire (SDQ), socio-demographic characteristics and characteristics of the living environment were assessed. RESULTS: The sample included a total of 3,744 children (45.9% female; mean age: 6.0; SD=0.4). Girls had significantly higher values than boys in total HRQOL (83.7 vs. 82.4, p ≤0.0001) and in all KINDL-R subscales except "psychological well-being" and "physical well-being". For the latter, boys had significantly higher values than girls (84.1 vs. 82.9, p=0.0103). Multiple linear regression analysis showed that parental annoyance with air or noise pollution, possibility for children to safely play outside and the time a child is outside on weekdays in the summertime were significant predictors of total HRQOL measured by the KINDL-R. Obesity was not linked to HRQOL. Children with migration background had significantly higher values in the subscales "family" and "friends". CONCLUSIONS: Environmental factors are associated with HRQOL in children at the age of school enrollment but only partially of relevant use. Although they show significant associations, their explanatory power of the variability observed is rather limited.

Normative Data of the Self-Report Version of the German Strengths and Difficulties Questionnaire in an Epidemiological Setting.

OBJECTIVE: This study served to establish German norms for the Strengths and Difficulties Questionnaire self-report (SDQ-S) by using data from a representative epidemiological sample from the German National Health Interview and Examination Survey for Children and Adolescents (KiGGS study). Although the German version of the SDQ has been widely used and normative data for the parent version (SDQ-P) exist, no German norms for the self-report version have been reported, so that practitioners had to rely on the available British norms. In addition, we investigated whether sex- and age-specific norms are necessary. METHODS: At the baseline of the KiGGS study, SDQ-S ratings were collected from n = 6,726 children and adolescents between 11 and 17 years (n = 3,440 boys und n = 3,286 girls). We assessed the internal consistency and age/sex effects of the SDQ-S. Confirmatory factor analysis was conducted to assess the factor structure of the SDQ-S. Banding scores were developed to differentiate children and adolescents with levels of difficulties and categorized them as "normal," "borderline," and "abnormal." General as well as age- and sex-specific bandings were created for both total score and subscales of SDQ-S. In addition, the German norms of the SDQ-S were compared with those of the UK, Norway, and Thailand. RESULTS: The five-factor solution of the SDQ-S (including Emotional symptoms, Conduct problems, Hyperactivity/Inattention, Peer problems, and Prosocial behavior) provided a satisfactory fit to the data. Moderate internal consistencies (Cronbach's α) were observed for the scales Emotional symptoms, Hyperactivity/Inattention, and Total difficulties score, whereas insufficient internal consistency was found for the scales Peer problems and Conduct problems. However, using McDonald's ω as a more appropriate measure of homogeneity, internal consistencies were found to be satisfactory for all subscales and for Total difficulties. Normative banding scores were established conservatively to avoid producing too many false positives in the category "abnormal." In line with previous research, girls showed more emotional problems but fewer Peer problems than boys. German normative bandings of SDQ-S were similar to the original British bandings and those of other countries. CONCLUSIONS: This study of the German SDQ-S in a large representative epidemiological sample presents evidence of partly moderate to good psychometric properties. It also supports the usefulness of SDQ-S as an effective and efficient instrument for child and adolescent mental health problems in Germany. German normative banding scores of SDQ-S established in this study were comparable with the original British norms as well as with those of other countries, so that SDQ-S can be recommended as a psychopathological broadband-screening tool.

Risk and protective factors for the development of depressive symptoms in children and adolescents: results of the longitudinal BELLA study.

Mental health problems in children and adolescents are frequent, with a high risk of persistence into adulthood. Therefore, the investigation of determinants of onset and course of mental health problems is of high importance. The present paper investigates the impact of protective and risk factors on the development of depressive symptoms in children and adolescents. The BELLA study is the mental health module of the German National Health Interview and Examination Survey for children and adolescents (KIGGS). Based on the first three measurement points of the BELLA study (covering a period of 2 years), the present analysis focused on children and adolescents aged 11-17 years at baseline (n = 1,643; 50.6 % female). A longitudinal growth modelling approach was used. Mental health problems in parents (parent-reports) predicted depressive symptoms in children and adolescents (self-reports) as well as the development of these symptoms over time. Further, child-reported protective factors of self-efficacy, positive family climate and social support were associated with less depressive symptoms at baseline. Additionally, positive changes in protective factors were associated with the development of less depressive symptoms over time. Finally, family climate and social support moderated the detrimental influence of parental psychopathology on child's depressive symptoms. The addressed determinants for the development of depressive symptoms in children and adolescents are highly relevant for prevention and intervention strategies. Future research should investigate specific risk and protective factors focusing in detail on further mental health disorders and their development in children and adolescents.