Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort.

Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-beta maintenance, yielded promising survival rates even after adapting total radiation doses to tumor response. The outcome of 45 patients in the NPC-2003 study was reassessed after a median follow-up of 85 months. In addition, we analyzed 21 further patients after closure of the NPC-2003 study, recruited between 2011 and 2017, and treated as per the NPC-2003 study protocol. The EFS and OS of 66 patients with locoregionally advanced NPC were 93.6% and 96.7%, respectively, after a median follow-up of 73 months. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy; none relapsed. In young patients with advanced locoregional NPC, excellent long-term survival rates can be achieved by multimodal treatment, including interferon-beta. Radiation doses may be reduced in patients with complete remission after induction chemotherapy and may limit radiogenic late effects.

[The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3 - clinical guideline]. / Diagnostik von Autismus- Spektrum-Störungen im Kindes-, Jugend- und Erwachsenenalter: Überblick zu den wesentlichen Fragestellungen und Ergebnissen des ersten Teils der S3-Leitlinie.

The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3 - clinical guideline Abstract. Background: Autism spectrum disorders (ASD) include ICD-10 diagnoses of childhood autism, Asperger syndrome, and atypical autism; there is a lifetime prevalence of ~1 %. The aim of the evidence-based clinical guideline (AWMF-S3-Guideline) is to summarize the current evidence concerning diagnostic and therapeutic processes for professionals working in healthcare and social welfare and to provide consensus on clinical recommendations. The present study summarizes the most important results of the diagnostic part of this guideline. Method: The guideline group comprised 14 clinical and scientific expert associations from the German healthcare system, in addition to representatives of relatives and patients. Recommendations were based on results of a systematic literature search, data extraction, the evaluation of study quality, and, if possible, meta-analytic aggregation of included data in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. Results: The AWMF-S3-Clinical Guideline, Diagnostic Part, summarizes current research on this topic. The main focus is put on the question of obligatory versus redundant diagnostic procedures. After a general introduction to the clinical picture of ASD, essential aspects like obtaining the medical history, the effective use of screening and diagnostic instruments, medical examination, the full diagnostic work-up as well as communicating the diagnostic results to relatives and patients are described in detail. We also conducted a meta-analysis on the stability of early diagnosis. Conclusion: This first part of the ASD guideline offers users the opportunity to inform themselves about the background of ASD as well as evidence-based and broadly consented information on the correct diagnostic process of ASD from infancy to adulthood.

Psychotherapeutic Treatment for Anorexia Nervosa: A Systematic Review and Network Meta-Analysis.

Background: The aim of the study was a systematic review of studies evaluating psychotherapeutic treatment approaches in anorexia nervosa and to compare their efficacy. Weight gain was chosen as the primary outcome criterion. We also aimed to compare treatment effects according to service level (inpatient vs. outpatient) and age group (adolescents vs. adults). Methods:The data bases PubMed, Cochrane Library, Web of Science, Cinahl, and PsychInfo were used for a systematic literature search (until Feb 2017). Search terms were adapted for data base, combining versions of the search terms anorexia, treat*/therap* and controlled trial. Studies were selected using pre-defined in- and exclusion criteria. Data were extracted by two independent coders using piloted forms. Network-meta-analyses were conducted on all RCTs. For a comparison of service levels and age groups, standard mean change (SMC) statistics were used and naturalistic, non-randomized studies included. Results: Eighteen RCTs (trials on adults: 622 participants; trials on adolescents: 625 participants) were included in the network meta-analysis. SMC analyses were conducted with 38 studies (1,164 participants). While family-based approaches dominate interventions for adolescents, individual psychotherapy dominates in adults. There was no superiority of a specific approach. Weight gains were more rapid in adolescents and inpatient treatment. Conclusions: Several specialized psychotherapeutic interventions have been developed and can be recommended for AN. However, adult and adolescent patients should be distinguished, as groups differ in terms of treatment approaches considered suitable as well as treatment response. Future trials should replicate previous findings and be multi-center trials with large sample sizes to allow for subgroup analyses. Patient assessment should include variables that can be considered relevant moderators of treatment outcome. It is desirable to explore adaptive treatment strategies for subgroups of patients with AN. Identifying and addressing maintaining factors in AN remains a major challenge.

Day-patient treatment after short inpatient care versus continued inpatient treatment in adolescents with anorexia nervosa (ANDI): a multicentre, randomised, open-label, non-inferiority trial.

BACKGROUND: In-patient treatment (IP) is the treatment setting of choice for moderately-to-severely ill adolescents with anorexia nervosa, but it is costly, and the risks of relapse and readmissions are high. Day patient treatment (DP) is less expensive and might avoid problems of relapse and readmission by easing the transition from hospital to home. We investigated the safety and efficacy of DP after short inpatient care compared with continued IP. METHODS: For this multicentre, randomised, open-label, non-inferiority trial, we enrolled female patients (aged 11-18 years) with anorexia nervosa from six centres in Germany. Patients were eligible if they had a body-mass index (BMI) below the tenth percentile and it was their first admission to hospital for anorexia nervosa. We used a computer-generated randomisation sequence to randomly assign patients to continued IP or DP after 3 weeks of inpatient care (1:1; stratified for age and BMI at admission). The treatment programme and treatment intensity in both study groups were identical. The primary outcome was the increase in BMI between the time of admission and a 12-month follow-up adjusted for age and duration of illness (non-inferiority margin of 0·75 kg/m(2)). Analysis was done by modified intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN67783402, and the Deutsches Register Klinischer Studien, number DRKS00000101. FINDINGS: Between Feb 2, 2007, to April 27, 2010, we screened 660 patients for eligibility, 172 of whom we randomly allocated to treatment: 85 to IP and 87 to DP. DP was non-inferior to IP with respect to the primary outcome, BMI at the 12-month follow-up (mean difference 0·46 kg/m(2) in favour of DP (95% CI, -0·11 to 1·02; pnon-inferiority<0·0001). The number of treatment-related serious adverse events was similar in both study groups (eight in the IP group, seven in the DP group). Three serious adverse events in the IP group and two in the DP group were related to suicidal ideation; one patient in the DP attempted suicide 3 months after she was discharged. INTERPRETATION: DP after short inpatient care in adolescent patients with non-chronic anorexia nervosa seems no less effective than IP for weight restoration and maintenance during the first year after admission. Thus, DP might be a safe and less costly alternative to IP. Our results justify the broad implementation of this approach. FUNDING: German Ministry for Education and Research.

[Hematological changes in adolescent anorexia nervosa]. / Hämatologische Veränderungen bei Anorexia nervosa im Kindes- und Jugendalter.

OBJECTIVE: Hematological changes often occur in patients with acute anorexia nervosa (AN). However, the relationship between these disturbances and other clinical parameters remains unclear. METHOD: Leucocyte, erythrocyte, and thrombocyte counts as well as hematocrit, hemoglobin, and differential blood counts were collected at admission and after weight restoration in 88 female adolescent patients with the diagnosis of AN according to DSM-IV. These were then compared to clinical parameters. RESULTS: At admission, there were mild changes in the blood count, most of which, however, were reversible after weight gain. Patients with a greater weight loss, a lower age-adjusted BMI, and a history of taking psychotropic drugs were more likely to develop hematological abnormalities. CONCLUSIONS: Although most of the hematological changes in adolescent patients with AN were mild, patients with high weight loss and/or low age-adjusted BMI as well as those on psychotropic medication should be monitored carefully in order to avoid severe medical complications. An altered immune function in adult patients with chronic AN might contribute to a higher rate of infections and thus to an increased mortality.

Migration background and juvenile mental health: a descriptive retrospective analysis of diagnostic rates of psychiatric disorders in young people.

INTRODUCTION: This article presents diagnostic rates for specific mental disorders in a German pediatric inpatient population over a period of 20 years with respect to migration background and socioeconomic status (SES). METHODS: Diagnostic data were obtained over a period of 20 years from 8,904 patients who visited a child and adolescent psychiatry mental health service in Germany. Data from 5,985 diagnosed patients (ICD-9 and ICD-10 criteria) were included with respect to gender, migration background, and SES. RESULTS: Migration- and gender-specific effects were found for both periods of assessment. The group of boys with a migration background showed significantly higher rates of reactions to severe stress, adjustment disorders, and posttraumatic stress disorder compared to their male, non-migrant counterparts. Conversely, boys without a migration background showed a significantly higher percentage rate of hyperkinetic disorders than male migrants. Similar results were found for female migrants in the latter assessment period (ICD-10). In addition, female migrants showed lower rates of emotional disorders whose onset occurs in childhood compared to their non-migrant counterparts. CONCLUSIONS: Data from this investigation provide preliminary evidence that the prevalence of various psychiatric disorders in children and adolescents is influenced by migration background and SES.

The diagnosis and treatment of eating disorders.

BACKGROUND: Eating disorders are of major significance both in clinical medicine and in society at large. Anorexia and bulimia nervosa almost exclusively afflict young persons, severely impairing their physical and mental health. The peak ages for these diseases are in late adolescence and young adulthood; patients therefore suffer setbacks both in school and/or in their occupational careers. This scientifically based S3 guideline was developed with the intention of improving the treatment of eating disorders and motivating future research in this area. METHODS: The existing national and international guidelines on the three types of eating disorders were synoptically compared, the literature on the subject was systematically searched, and meta-analyses on bulimia nervosa and binge-eating disorder were carried out. 15 consensus conferences were held, as a result of which 44 evidence-based recommendations were issued. RESULTS: Anorexia and bulimia nervosa are diagnosed according to the ICD-10 criteria (International Classification of Diseases), binge-eating disorder according to those of the DSM (Diagnostic and Statistical Manual of Mental Disorders). Psychotherapy is the mainstay of treatment for all three disorders, and cognitive behavioral therapy is the form of psychotherapy best supported by the available evidence. The administration of selective serotonin reuptake inhibitors (SSRI) can be recommended as a flanking measure in the treatment of bulimia nervosa only. The evidence does not support any type of pharmacotherapy for anorexia nervosa or binge-eating disorder. Bulimia nervosa and binge-eating disorder can usually be treated on an outpatient basis, as long as they are no more than moderately severe; full-fledged anorexia nervosa is generally an indication for in-hospital treatment. CONCLUSION: This guideline contains evidence- and consensus-based recommendations for the diagnosis and treatment of eating disorders. If strictly implemented, it should result in improved care for the affected patients.

[Pharmacotherapy in bipolar disorders during childhood and adolescence]. / Pharmakotherapie bipolarer Störungen im Kindes- und Jugendalter.

OBJECTIVE: Bipolar disorders during childhood and adolescence are rare, but serious and highly recurrent disorders, often associated with negative outcome. Pharmacotherapy, including Lithium, other mood stabilizers and typical antipsychotic agents, is the first-line treatment in bipolar disorders and often necessary for many months or years. METHOD: A computerized medline-search (Pubmed) was made for prospective studies and reviews of bipolar disorder in this age-group published during the last 10 years, which were then reviewed for their relevance. RESULTS: Despite the widespread use of substances whose efficacy for adults is well-established, there is a substantial lack of empirical data regarding the efficacy and safety in the treatment of bipolar disorder in children and adolescents. Placebo-controlled studies are very rare, and the interpretation of the existing data is complicated by the diagnostic controversy about bipolar disorder in children. Side-effects are more common in children and adolescents than in adults. CONCLUSIONS: Combination therapy may be favoured in cases of severe and psychotic bipolar disorder. Needed are more placebo-controlled studies and long-term studies on the efficacy and safety of mood stabilizers and atypical antipsychotic agents in the treatment of children and adolescents with bipolar disorder.

Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study.

OBJECTIVE: The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders. METHOD: Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting. RESULTS: Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events. CONCLUSIONS: In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.

[Adolescent eating disorders]. / Essstörungen in der Adoleszenz.

Anorexia and Bulimia nervosa are common psychiatric disorders in adolescent girls. In discrepancy to ICD-10 and DSM-IV we would propose the 10th BMI percentile as weight criterium for anorexia nervosa. Both disorders have a high somatic and psychiatric comorbidity; the most severe complication at long term follow-up is osteoporosis. The most prevalent psychiatric disorders are affective disorders, anxiety and obsessive-compulsive disorder and substance abuse. There is undoubtedly a genetic predisposition and a range of general and personal environmental risk factors. Treatment of adolescent eating disorders mostly requires a multimodal approach which consists of several components, e.g. weight rehabilitation, nutritional counselling, individual and family psychotherapy, and treatment of comorbid psychiatric disorders.

[Parent psychoeducation groups in the treatment of adolescents with eating disorders]. / Psychoedukation für Eltern in der Behandlung essgestörter Jugendlicher.

Parents of adolescents with eating disorders show high levels of emotional distress, which may contribute to less functional coping with the illness of their child. In our department a psychoeducational group program is been offered to the parents of 153 children and adolescents with anorexia and bulimia nervosa. According to their own reports parents are highly interested in gaining information about the eating disorder and appreciate this means of support to help them to cope with the illness of their child.

Group psychoeducation for parents of adolescents with eating disorders: the Aachen program.

Family-based treatment in adolescents and individual psychoeducation in adults are accepted components in a multimodal treatment of eating disorders. However, only few studies have been conducted on the use of parent-based psychoeducation. This paper presents the structure and content, as well as a preliminary evaluation, of a group psychoeducation program for parents of adolescent patients with eating disorders. The program is limited to five 90-minute sessions and aimed at increasing the parents' understanding of the disorder and promoting high transparency with regard to our treatment principles. The vast majority of parents rated the group psychoeducation as helpful in coping with their child's disorder and would recommend others to take part in the program.