[ZSE-DUO - dual guidance structure at the centre for rare diseases]. / ZSE-DUO ­ duale Lotsenstruktur im Zentrum für Seltene Erkrankungen.

BACKGROUND: Patients with an unclear diagnosis and suspected rare disease pose special challenges to physicians, among others. AIM OF THE STUDY (RESEARCH QUESTION): The ZSE-DUO project aims to establish whether patient care under the joint supervision of a somatic expert and a mental health expert can improve diagnostic efficacy and precision, as well as shorten the time to diagnosis. MATERIAL AND METHODS: ZSE-DUO has successfully recruited more than 1000 patients at eleven national centres for rare diseases in a control and an intervention group. The findings are being analysed by three evaluating institutions. RESULTS AND DISCUSSION: The study is currently in its final phase. The results will be published in further papers.

Prevalence of pica and rumination behaviours in adults and associations with eating disorder and general psychopathology: findings form a population-based study.

AIMS: Pica and rumination disorder are known as feeding disorder diagnoses in childhood, but little is known about their occurrence in adulthood. This study aimed to assess prevalence rates of one-time and recurrent pica and rumination behaviours (PB and RB) in adults, including sociodemographic subgroups, and to examine associations with other eating disorder and general psychopathology. METHODS: The representative population sample (N = 2403) completed measures on PB and RB, symptoms of avoidant/restrictive food intake disorder (ARFID), body image and symptoms of depression and anxiety. RESULTS: Any PB and RB were reported in 5.33 and 5.49%, respectively, while recurrent PB or RB occurred in 1.08 and 0.71%, respectively. Co-occurrence was high, with 35.29% of recurrent PB in RB, and 23.08% vice versa. Prevalence rates of recurrent PB or RB did not differ by gender, weight status, educational or migration history from those without recurrent behaviours. Adults with v. without recurrent PB and RB showed more symptoms of ARFID, general eating disorders depression and anxiety, and behavioural symptoms of eating disorders (with the exception of compensatory behaviours in recurrent PB), and less positive body image. However, there were no differences regarding age and body mass index. CONCLUSIONS: Our findings highlight the clinical significance of PB and RB in adults regarding both prevalence and associations with other psychopathological symptoms. In particular, associations with body image need to be investigated further, as in contrast to other eating disorders, body image disturbance is not yet represented in the diagnostic criteria for pica and rumination disorder. In sum, the findings highlight the need for clinical attention for these disorders and related behaviours in adults.

How do patients with anorexia nervosa "process" psychotherapy between sessions? A comparison of cognitive-behavioral and psychodynamic interventions.

OBJECTIVE: Patients' processing of psychotherapy between sessions ("inter-session process" (ISP)) has been repeatedly shown to be related to outcome. The aim of this study was to compare ISP characteristics of cognitive-behavioral vs. psychodynamic psychotherapy in the treatment of anorexia nervosa (AN) and their relation to outcome. METHODS: Data of 106 patients participating in a randomized-controlled trial who received either 40 sessions of enhanced cognitive-behavioral therapy (CBT-E) or focal psychodynamic therapy (FPT) were analyzed. The ISP was measured with the Inter-session Experience Questionnaire (IEQ). Three outcome classes were distinguished: full recovery, partial recovery, and still fulfilling all AN criteria. RESULTS: Patients receiving CBT-E reported more on "applying therapy" in the initial and the final treatment phase compared to FPT patients. In terms of process-outcome relations, higher levels of "recreating the therapeutic dialogue between sessions," "recreating the therapeutic dialogue with negative emotions" as well as "applying therapy with negative emotions" in the final phase of treatment predicted negative outcome in FPT, whereas overall higher levels of negative emotions predicted negative outcome in CBT-E. CONCLUSIONS: In outpatient treatment in AN, the processing of therapy as measured by the IEQ showed surprisingly few differences between CBT-E and FPT. However, different ISP patterns were predictive of outcome, pointing to different mechanisms of change.

The KTx360°-study: a multicenter, multisectoral, multimodal, telemedicine-based follow-up care model to improve care and reduce health-care costs after kidney transplantation in children and adults.

BACKGROUND: Follow-up care after kidney transplantation is performed in transplant centers as well as in local nephrologist's practices in Germany. However, organized integrated care of these different sectors of the German health care system is missing. This organizational deficit as well as non-adherence of kidney recipients and longterm cardiovascular complications are major reasons for an impaired patient and graft survival. METHODS: The KTx360° study is supported by a grant from the Federal Joint Committee of the Federal Republic of Germany. The study will include 448 (39 children) incident patients of all ages with KTx after study start in May 2017 and 963 (83 children) prevalent patients with KTx between 2010 and 2016. The collaboration between transplant centers and nephrologists in private local practices will be supported by internet-based case-files and scheduled virtual visits (patient consultation via video conferencing). At specified points of the care process patients will receive cardiovascular and adherence assessments and respective interventions. Care will be coordinated by an additional case management. The goals of the study will be evaluated by an independent institute using claims data from the statutory health insurances and data collected from patients and their caregivers during study participation. To model longitudinal changes after transplantation and differences in changes and levels of immunosuppresive therapy after transplantation between study participants and historical data as well as data from control patients who do not participate in KTx360°, adjusted regression analyses, such as mixed models with repeated measures, will be used. Relevant confounders will be controlled in all analyses. DISCUSSION: The study aims to prolong patient and graft survival, to reduce avoidable hospitalizations, co-morbidities and health care costs, and to enhance quality of life of patients after kidney transplantation. TRIAL REGISTRATION: ISRCTN29416382 (retrospectively registered on 05.05.2017).

Large turbulent reservoirs of cold molecular gas around high-redshift starburst galaxies.

Starburst galaxies at the peak of cosmic star formation are among the most extreme star-forming engines in the Universe, producing stars over about 100 million years (ref. 2). The star-formation rates of these galaxies, which exceed 100 solar masses per year, require large reservoirs of cold molecular gas to be delivered to their cores, despite strong feedback from stars or active galactic nuclei. Consequently, starburst galaxies are ideal for studying the interplay between this feedback and the growth of a galaxy. The methylidyne cation, CH+, is a most useful molecule for such studies because it cannot form in cold gas without suprathermal energy input, so its presence indicates dissipation of mechanical energy or strong ultraviolet irradiation. Here we report the detection of CH+ (J = 1-0) emission and absorption lines in the spectra of six lensed starburst galaxies at redshifts near 2.5. This line has such a high critical density for excitation that it is emitted only in very dense gas, and is absorbed in low-density gas. We find that the CH+ emission lines, which are broader than 1,000 kilometres per second, originate in dense shock waves powered by hot galactic winds. The CH+ absorption lines reveal highly turbulent reservoirs of cool (about 100 kelvin), low-density gas, extending far (more than 10 kiloparsecs) outside the starburst galaxies (which have radii of less than 1 kiloparsec). We show that the galactic winds sustain turbulence in the 10-kiloparsec-scale environments of the galaxies, processing these environments into multiphase, gravitationally bound reservoirs. However, the mass outflow rates are found to be insufficient to balance the star-formation rates. Another mass input is therefore required for these reservoirs, which could be provided by ongoing mergers or cold-stream accretion. Our results suggest that galactic feedback, coupled jointly to turbulence and gravity, extends the starburst phase of a galaxy instead of quenching it.

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index.

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.

Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. METHOD: The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. RESULTS: Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

Caffeine intake is related to successful weight loss maintenance.

The effect of caffeine intake on weight loss maintenance has not been examined in humans. We compared the daily consumption of coffee and caffeinated beverages between 494 weight loss maintainers and 2129 individuals from the general population controlling for sociodemographic variables, body mass index and physical activity level. Weight loss maintainers reported to consume significantly more cups of coffee and caffeinated beverages compared with the participants in the general population sample. Thus, consumption of caffeinated beverages might support weight loss maintenance. Further studies should investigate possible mechanisms.

[Comment on Gender-Specific Aspects in Obesity and Metabolic Surgery--Analysis of Data from the German Bariatric Surgery Registry]. / Kommentar zu genderspezifischen Aspekten in der Adipositas- und metabolischen Chirurgie--Daten der Qualitätssicherungsstudie für operative Therapie der Adipositas.

BACKGROUND: The current situation in obesity and metabolic surgery since January 2005 has been investigated with the help of the quality assurance study on surgical therapy for obesity = German Bariatric Surgery Registry (GBSR). The data were acquired and analysed in cooperation with the Institute for Quality Assurance in Surgical Medicine at the Otto-von-Guericke University. METHODS: Data acquisition was done with the help of an online database. On a voluntary basis, all obesity and metabolic surgical interventions since 2005 have been recorded. In addition to the surgical data, the findings of the yearly follow-up investigations were recorded. RESULTS: Since 2005 there have been 1,263 gastric balloon procedures, 11,840 sleeve gastrectomies, 13,722 Roux-en-Y gastric bypasses and 3999 gastric banding operations. The average age of the male patients in all interventions was significantly higher. The average BMI of female patients who received a gastric banding or a gastric balloon procedure was significantly lower than that of the male patients. Men exhibited a higher incidence of comorbidities than women. CONCLUSION: The number of obesity and metabolic surgical interventions in Germany is continuously increasing. The results of the study on surgical therapy for obesity (GBSR) reveal significant differences in the gender-specific incidence of preoperative comorbidities. postoperative complications and mortality. Further studies on gender-specific aspects are necessary in order to optimise patient selection and reduce the incidence of postoperative complications.

[Factor structure of the German version of the BIS/BAS Scales in a population-based sample]. / Faktorenstruktur der deutschsprachigen version der BIS/BAS-Skalen in einer bevölkerungsstichprobe.

BACKGROUND: The Behavioural Inhibition System/Behavioural Activation System Scale (BIS/BAS-Scales) developed by Carver and White 1 is a self-rating instrument to assess the dispositional sensitivity to punishment and reward. The present work aims to examine the factor structure of the German version of the BIS/BAS-Scales. MATERIAL AND METHODS: In a large German population-based sample (n = 1881) the model fit of several factor models was tested by using confirmatory factor analyses. RESULTS: The best model fit was found for the 5-factor model with two BIS (anxiety, fear) and three BAS (drive, reward responsiveness, fun seeking) scales, whereas the BIS-fear, the BAS-reward responsiveness, and the BAS-fun seeking subscales showed low internal consistency. The BIS/BAS scales were negatively correlated with age, and women reported higher BIS subscale scores than men. CONCLUSION: Confirmatory factor analyses suggest a 5-factor model. However, due to the low internal reliability of some of the subscales the use of this model is questionable.

Cognitive-behavioural group therapy versus guided self-help for compulsive buying disorder: a preliminary study.

Compulsive buying (CB) is defined as extreme preoccupation with buying/shopping and frequent buying that causes substantial negative psychological, social, occupational and financial consequences. There exists preliminary evidence that group cognitive-behavioural therapy (CBT) is effective in the treatment of CB. The present pilot study made a first attempt to compare group CBT for CB with telephone-guided self-help (GSH). Fifty-six patients were allocated randomly to one of the three conditions: (1) group CBT (n = 22); (2) GSH (n = 20); and (3) a waiting list condition (n = 14). The results indicate that face-to-face group CBT is superior not only to the waiting list condition but also to GSH. Patients who received GSH tended to have more success in overcoming CB compared with the waiting list controls. Given the sample size, the results must be considered as preliminary and further research is needed to address the topic whether GSH also could be a helpful intervention in reducing CB.

Association of symptoms of attention-deficit/hyperactivity disorder with childhood overweight adjusted for confounding parental variables.

OBJECTIVE: There have been numerous reports on association between attention-deficit/hyperactivity disorder (ADHD) and overweight/obesity in children and adolescents; however, most studies adjusted only for a limited number of possible confounders. METHODS: We analyzed the data of 11,159 six through seventeen-year-old participants in the German Health Interview and Examination Survey for Children and Adolescents. We determined weight status based on measured anthropometry and national reference data by International Obesity Task Force criteria. The parent-rated hyperactivity/inattention subscale of the Strengths and Difficulties Questionnaire (SDQ-HI) was used as a continuous measure of ADHD symptoms. We examined whether the putative confounders socioeconomic status, migrant status, parental body mass index (BMI) and parental smoking were associated with both SDQ-HI and overweight/obesity. Associations between SDQ-HI and overweight/obesity vs normal weight were analyzed by binary logistic regression analyses. In the first model, we adjusted for age and sex only and in the second model also for the parental confounders. RESULTS: SDQ-HI was associated with an increased risk for overweight/obesity in both sexes adjusting for age and sex. However, after adjusting for all confounders SDQ-HI was associated with an increased risk for overweight/obesity only in adolescent females. Socioeconomic status, parental BMI and parental smoking each were relevant confounders. Migrant status was also significantly associated with both SDQ-HI and overweight/obesity, thus qualifying as a confounder but contributed only weakly to the association. CONCLUSIONS: The association between ADHD symptoms and overweight/obesity is due to confounding by family background variables in all but adolescent girls. Possible reasons for the increased risk for overweight/obesity in this subgroup are discussed. We also propose possible mechanisms for confounding by parental socioeconomic status, BMI and smoking.

[Resource activation in clinical psychology and psychotherapy: review of theoretical issues and current research]. / Ressourcenaktivierung in der klinischen Psychologie und Psychotherapie: Überblick über theoretische Hintergründe und aktuelle Forschungsansätze.

This review summarises theoretical issues and current research on working with clients' resources and strengths in clinical psychology and psychotherapy. Resource activation is considered as an important common factor in psychotherapy. In general, resource activation means an explicit focus on resources, strengths and potentials of the clients. After defining the term resources, considerations with regard to therapeutic attitude, principles of resource activation, approaches to resource diagnostics and different research strategies are presented. Current research focuses especially on the relation between resource activation and process variables in out-patient treatment.

[Diagnostic criteria for eating disorders: what will DSM-5 feature?]. / Diagnostik der Essstörungen : Was wird das DSM-5 bringen?

The diagnostic criteria of the classic eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by both a high validity and clinical utility. However, up to 50% of patients in specialized eating disorder centers do not meet the full diagnostic criteria and are relegated to the residual diagnosis "eating disorders not otherwise specified (EDNOS)". Eating disorders are more varied and variable than the ICD-10 or DSM-IV criteria suggest. This article describes the suggested modifications of the diagnostic criteria for eating disorders for the DSM-5. The DSM-5 abstains from setting a specific numerical standard for weight for AN and reduces the required minimum frequency for BN and binge eating disorder (BED) to once a week over the last 3 months. This will likely reduce the number of cases in the EDNOS category. In addition, the DSM-5 provides brief descriptions of several conditions of potential clinical significance without providing detailed criteria in order to stimulate additional research.

Screening for anorexia nervosa via measurement of serum leptin levels.

Due to their sub-normally low fat mass, leptin levels in patients with acute anorexia nervosa (AN) are well below reference levels for age and sex-matched controls. This hypoleptinemia entails endocrinological and behavioral characteristics observed in AN patients during starvation. We aimed to study the appropriateness of hypoleptinemia as a diagnostic marker for AN by assessing sensitivity, specificity and likelihood ratios for different referral serum leptin levels for predicting anorexia nervosa and healthy leanness. For prediction, we additionally generated a score based on a multivariate logistic model including body mass index (BMI; kg/m²) and leptin level. For this purpose, we measured leptin levels in 74 female patients with acute AN upon admission for inpatient or outpatient treatment. Adolescent and adult patients were recruited according to DSM-IV criteria from two multi-center studies. Additionally, leptin levels were measured in 65 female healthy, lean students. Mean serum leptin level was significantly decreased in patients with AN compared to underweight controls (0.87 ± 0.90 vs. 6.43 ± 3.55 µg/L, p < 0.001). Leptin predicted AN independently of BMI; we confirmed a cutoff value in the range of 2 µg/L as having both high specificity and sensitivity. Hypoleptinemia represents a state marker of acute AN and is useful for a laboratory-based diagnostic screening.

Psychometric evaluation of the German version of the impact of weight on Quality of Life-Lite (IWQOL-Lite) questionnaire.

OBJECTIVE: To evaluate the psychometric properties of a German version of the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. METHOD: IWQOL-Lite scores were obtained from 351 overweight/obese individuals and 127 lean adult volunteers. In addition, a subgroup of 126 obese subjects completed also the German versions of the 36-item short-form health survey (SF-36), the Beck Depression Inventory (BDI), the Eating Disorder Examination-Questionnaire (EDE-Q), and the German validated version of the Three-Factor Eating Questionnaire (TFEQ). RESULTS: The German version of the IWQOL-Lite has psychometric properties comparable to those found for the original version and demonstrates high internal consistency and excellent construct validity. Furthermore, the German IWQOL-Lite clearly discriminates between groups based on BMI on all subscales and the total score. CONCLUSION: The results of the present study suggest that the German IWQOL-Lite is a psychometrically validated instrument with which to measure weight-specific health related quality of life.

Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting.

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.

Congruence between clinical and research-based psychiatric assessment in bariatric surgical candidates.

BACKGROUND: Mental health professionals have become increasingly involved in working with bariatric surgical candidates, particularly in performing preoperative psychological evaluations to clear candidates for surgery. The objective of the present study was to examine the concordance of the psychiatric diagnoses obtained during routine clinical evaluation before bariatric surgery and the diagnoses obtained separately at a research facility using the Structured Clinical Interview for DSM (Diagnostic and Statistical Manual of Mental Disorders)-IV axis I disorders. METHODS: The study included 68 consecutively enrolled bariatric surgical candidates who had participated in the Longitudinal Assessment of Bariatric Surgery-3 study. The Structured Clinical Interview for DSM disorders data obtained from the research assessments were compared with the diagnostic data from the routine preoperative psychiatric evaluations. The congruence of the current and lifetime diagnoses was assessed using Cohen's coefficient kappa. RESULTS: Considerable variability was found among the major diagnostic categories, with generally poor agreement found for the current diagnoses. The kappa coefficients tended to be larger for the lifetime diagnoses. The agreement was moderate for any lifetime mood disorder, with a kappa value of 0.45. Regarding any lifetime anxiety, substance use, and eating disorder, the clinical diagnoses rarely concurred with the results from the Structured Clinical Interview for DSM disorders, with a kappa statistic of 0.30, 0.36, and 0.32, respectively. CONCLUSION: The congruence between the diagnoses assigned during the routine clinical psychiatric evaluations and research assessment using the Structured Clinical Interview for DSM disorders was surprisingly low. These conclusions should be considered tentative, given the interval and the possibility of treatment having occurred between the 2 evaluations. Overall, these data raise interesting questions concerning the use of unstructured psychiatric evaluations before bariatric surgery.