Objectives: The prevalence of eating disorders is rising worldwide. The low body weight in anorexia nervosa as well as the increase in body mass index due to binge eating disorder are contributing to a strikingly high morbidity and mortality. In a similar pattern, the prevalence and burden of the disease of functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome is increasing. As gastrointestinal complaints are commonly reported by patients with eating disorders, the question arose whether there is a relationship between eating disorders and functional gastrointestinal disorders.

Methods: To address the need to better understand the interplay between eating disorders and functional gastrointestinal disorders as well as factors that might influence this connection, the data bases Medline, Web of Science and Embase were systematically searched.

Results: After removal of duplicates the search yielded 388 studies which were screened manually. As a result, 36 publications were selected for inclusion in this systematic review.

Conclusion: The occurrence of functional gastrointestinal disorders like irritable bowel syndrome and functional dyspepsia in patients with eating disorders is considerably high and often associated with psychological, hormonal and functional alterations. In the future, further research addressing the underlying mechanisms accounting for this relationship is required.

Objective: In focal epilepsy, data on the etiology-specific response to antiseizure medication (ASM) are surprisingly sparse. In this study, we sought to reappraise whether seizure outcome of pharmacological treatment is linked to the underlying etiology. Furthermore, we assessed ASM load with respect to the cause of epilepsy.

Methods: Data were retrospectively obtained from the electronic database of the three sites of an academic adult epilepsy outpatient clinic. For each patient, presumed cause of epilepsy was categorized into one of nine etiological groups. Individual drug loads were calculated according to the 2020 World Health Organization Center for Drug Statistics Methodology ATC/DDD Index. Univariate and multivariate analyses were conducted to explore the association between different etiologies and outcome regarding 12-month seizure freedom as well as ASM load.

Results: A total of 591 patients with focal epilepsy were included in the final analysis. Ischemic stroke was the etiology with the highest rate of 12-month terminal seizure freedom (71.2%, 95% confidence interval [CI] = 57.9-82.2) and, considering all etiological groups, was an independent predictor of seizure freedom (odds ratio = 2.093, 95% CI = 1.039-4.216). The lowest rates of seizure freedom were observed in patients with hippocampal sclerosis (28.2%, 95% CI = 15.0-44.9) and malformation of cortical development (16.7%, 95% CI = 2.1-48.4). In patients with ischemic stroke, median ASM load (1.0, interquartile range [IQR] = .5-1.8) was significantly lower compared to that in patients with hippocampal sclerosis (median = 1.8, IQR = 1.2-3.0, p = .008) and brain tumors (median = 1.7, IQR = .7-3.2, p = .049).

Significance: Response to treatment with ASM is highly etiology-specific and best in patients with epilepsy due to ischemic stroke. Interestingly, this most favorable treatment outcome can be achieved by the lowest ASM load considering all etiological groups. In focal epilepsy, etiology should be taken into account when counseling patients about their expected seizure outcome with pharmacological treatment and when tailoring initial ASM doses.

Background: "Classical" echocardiographic signs of Fabry cardiomyopathy (FC), such as left ventricular hypertrophy (LVH), posterolateral strain impairment (PLSI), and papillary muscle hypertrophy may be of limited diagnostic accuracy in clinical practice. Our aim was to evaluate the diagnostic value of left atrial (LA) strain impairment compared to "classical" echocardiographic findings to discriminate FC.

Methods: In standard echocardiographic assessments, we retrospectively analyzed the diagnostic value of the "classical" red flags of FC as well as LA strain in 20 FC patients and in 20 subjects with other causes of LVH. Receiver operating characteristic (ROC) curve analysis was performed to assess the respective diagnostic accuracy.

Results: FC was confirmed in 20 patients by genetic testing. In the LVH group, 12 patients were classified by biopsy to have hypertrophic cardiomyopathy, two had hypertensive heart disease, and six LVH combined with borderline myocarditis. Global and regional left ventricular (LV) strain was not significantly different between groups while LA strain was significantly impaired in FC (Left atrial reservoir strain (LASr) 19.1%±8.4 in FC and 25.6%±8.9 in LVH, p = 0.009; left atrial conduction strain (LAScd) -8.4%±4.9 in FC and -15.9%±8.4 in LVH, p < 0.01). LAScd, with an area under the curve (AUC) of .81 (95% confidence interval [CI] .66-.96) showed the highest diagnostic accuracy to discriminate FC. The PLSI pattern showed an AUC of .49, quantification of papillary muscle hypertrophy an AUC of .47.

Conclusion: Adding LA strain analysis to a comprehensive echocardiographic work-up of unclear LVH may be helpful to identify FC as a possible cause.

Hair samples are frequently analyzed in order to characterize consumption patterns of drugs. However, the interpretation of new psychoactive substance (NPS) findings in hair remains difficult because of lacking data for comparison. In this study, selected postmortem hair samples (n = 1203) from 2008 to 2020 were reanalyzed for synthetic cathinones, piperazines, phenethylamines, hallucinogens, benzodiazepines and opioids to evaluate prevalence data and concentration ranges. Hair samples were extracted using a two-step extraction procedure and analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Overall NPSs were detected in 381 cases (31.6%). Many cases were tested positive for more than one NPS in the same time span. A variety of NPS with a large range of concentrations was observed. For better comparability and interpretation of positive cases in routine work, quantitation data for 13 NPS were calculated as percentiles. The most frequently detected NPS in this study were N-ethylamphetamine, alpha-pyrrolidinovalerophenone, mephedrone, benzedrone, metamfepramone, and 4-fluoroamphetamine. In conclusion, a high prevalence of these drugs was observed from postmortem hair samples. The results show a growing use of many different NPSs by mainly young drug-using adults. Consequently, NPS screening procedures should be included in forensic toxicology. Our quantitative data may support other toxicologists in their assessment of NPS hair concentrations.

Introduction: The heavy drinking of others may negatively affect an individual on several dimensions of life. Until now, there is scarce research about how to judge the severity of various experiences of such harms. This study aims to empirically scale the severity of such harm items and to determine who is at most risk of these harms.

Methods: We used population-based survey data from 10 countries of the GENAHTO project (Gender and Alcohol's Harms to Others, data collection: 2011-2016). Questions about harms from others' drinking asked about verbal and physical harm, damage of belongings, traffic accidents, harassment, threatening behaviour, family and financial problems. We used item response theory methods (IRT) to scale severity of the aforementioned items. To acknowledge culturally based variations in different countries, we assessed 'differential item functioning'.

Results: The items 'family problems', 'financial problems' and 'clothes and property damage' as well as 'physical harm' were scaled as more severe in most countries compared to other items. Substantial differential item functioning was present in more than half of the country pairings. The item 'financial problems' was most often differentially scaled. Younger people who drank more, as well as women (compared to men), reported more harm.

Discussion and conclusions: Using IRT, we were able to evaluate grades of severity in harms from others' drinking. IRT scaling yielded in similar rankings of items as reported from other studies. However, empirical scaling allows for more differentiated severity scaling than simple summary scores and is more sensitive to cultural differences.

Aims: Several commercial and open-source automated insulin dosing (AID) systems have recently been developed and are now used by an increasing number of people with diabetes (PwD). This systematic review explored the current status of real-world evidence on the latest available AID systems in helping to understand their safety and effectiveness.

Methods: A systematic review of real-world studies on the effect of commercial and open-source AID system use on clinical outcomes was conducted employing a devised protocol (PROSPERO ID 257354).

Results: Of 441 initially identified studies, 21 published 2018-2021 were included: 12 for Medtronic 670G; one for Tandem Control-IQ; one for Diabeloop DBLG1; two for AndroidAPS; one for OpenAPS; one for Loop; three comparing various types of AID systems. These studies found that several types of AID systems improve Time-in-Range and haemoglobin A1c (HbA1c ) with minimal concerns around severe hypoglycaemia. These improvements were observed in open-source and commercially developed AID systems alike.

Conclusions: Commercially developed and open-source AID systems represent effective and safe treatment options for PwD of several age groups and genders. Alongside evidence from randomized clinical trials, real-world studies on AID systems and their effects on glycaemic outcomes are a helpful method for evaluating their safety and effectiveness.

Purpose: Age-related changes affect vitamin D absorption and metabolism. Low 25-hydroxyvitamin D concentrations have been reported as risk factor for the development of metabolic syndrome (MetS). However, recent evaluations suggest this association might be explained by obesity or insulin resistance (IR) in subjects with MetS. Our aim was to analyze associations between vitamin D insufficiency and MetS in a young cohort without diabetes and two senior cohorts with and without diabetes.

Methods: Four hundred sixteen young and 1357 older BASE-II participants were analyzed. Type 2 diabetes (T2D) was defined according to European Society of Cardiology (ESC) guidelines, MetS as suggested by International Diabetes Federation/American Heart Association/National Heart, Lung and Blood Institute (IDF/AHA/NHLBI 2009). Vitamin D insufficiency was defined as 25-hydroxyvitamin D concentrations <50 nmol/L. Among other confounders, BMI and IR were taken into account.

Results: MetS was prevalent in 7.7% of the young and in 35.6% of the older BASE-II participants and T2D occurred in 12.7% of the older participants. In young subjects without diabetes, vitamin D insufficiency was associated with an independent 3.2-fold increased odds of having MetS (OR: 3.2 CI: 1.0-8.7; p = 0.042). However, in the older participants, this association was lost once BMI was taken into account among those with diabetes, and once IR was taken into account among those without diabetes.

Conclusion: Independent associations between vitamin D insufficiency and MetS were only found among young subjects without diabetes. In the older adults, BMI annihilated these associations among subjects without diabetes as did HOMA-IR among subjects with diabetes.

Childhood is marked by profound changes in prosocial behaviour. The underlying motivational mechanisms remain poorly understood. We investigated the development of altruistically motivated helping in middle childhood and the neurocognitive and -affective mechanisms driving this development. One-hundred and twenty seven 6-12 year-old children performed a novel gustatory costly helping task designed to measure altruistic motivations of helping behaviour. Neurocognitive and -affective mechanisms including emotion regulation, emotional clarity and attentional reorienting were assessed experimentally through an extensive task-battery while functional brain activity and connectivity were measured during an empathy for taste paradigm and during rest. Altruistically motivated helping increased with age. Out of all mechanisms probed for, only emotional clarity increased with age and accounted for altruistically motivated helping. This was associated with greater functional integration of the empathy-related network with fronto-parietal brain regions at rest. We isolate a highly specific neuroaffective mechanism as the crucial driver of altruistically motivated helping during child development.

Myelination of axons in the neonatal brain is a highly complex process primarily achieved by oligodendroglial cells (OLs). OLs express receptors for gamma-aminobutyric acid (GABA) which is released from cortical interneurons on a basal level, while glial cells can be a source of GABA, too. We investigated GABA-induced oligodendroglial maturation, proliferation, apoptosis, and myelin production after pharmacological inhibition of GABA(A) and GABA(B) in the neonatal rat brain. Daily injections of the reverse GABA(A) receptor agonist (DMCM) and the GABA(B) receptor antagonist (CGP35348) were performed from postnatal day 6 (P6) to P11. MBP expression was examined by Western blots and immunohistochemistry. Furthermore, we determined the number of CC1(+)OLIG2(+) and CNP(+)OLIG2(+) cells to assess maturation, the number of PCNA(+)OLIG2(+) oligodendrocytes to assess proliferation, the number of oligodendrocyte precursor cells (PDGFR alpha(+)OLIG2(+)), and apoptosis of OLs (CASP3A(+)OLIG2(+)) as well as apoptotic cells in total (CASP3A(+)DAPI(+)) at P11 and P15. In addition, we analyzed the expression Pdgfr alpha and CNP. MBP expression was significantly reduced after CGP treatment at P15. In the same animal group, CNP expression and CNP(+)OLIG2(+) cells decreased temporarily at P11. At P15, the proliferation of PCNA(+)OLIG2(+) cells and the number of PDGFR alpha(+)OLIG2(+) cells increased after GABA(B) receptor antagonization whereas no significant differences were visible in the Pdgfr alpha gene expression. No changes in apoptotic cell death were observed. CGP treatment induced a transient maturational delay at P11 and deficits in myelin expression at P15 with increased oligodendroglial proliferation. Our in vivo study indicates GABA(B) receptor activity as a potential modulator of oligodendroglial development.

Objectives: Accurate radiological differentiation of parotid tumors remains challenging despite recent technical advances in quantitative medical imaging. Multifrequency magnetic resonance elastography (MRE) could provide additional information on viscoelastic properties of normal and abnormal biological tissues. This study investigates the feasibility of MRE of the parotid glands in healthy participants and provides first reference values.

Methods: 20 healthy participants underwent multifrequency MRE of both parotid glands at 3 Tesla. Shear waves at frequencies of 25, 30, 40, and 50 Hz were introduced into the participants' heads through the occiput using pressurized-air actuators. Shear wave speed (SWS) and loss angle of the shear modulus (φ) were reconstructed by tomoelastography post-processing as surrogate parameters for tissue stiffness and viscosity or fluidity. 10 participants underwent repeated MRE to determine test-retest reliability based on intraclass correlation coefficients.

Results: All MRE datasets acquired could be included in the analysis. Mean SWS was 0.97 ± 0.13 m/s, and mean φ was 0.59 ± 0.05 rad, each for both sides combined and without notable lateral difference (p = 0.88/0.87). Test-retest reliability was good for SWS (ICC = 0.84 for both sides/ICC = 0.77 for the right side/ICC = 0.79 for the left side) and good to excellent for φ(ICC = 0.94/0.86/0.90).

Conclusions: Multifrequency MRE of the parotid glands is feasible and reliable. This technique, therefore, is a promising method for investigating the viscoelastic properties of salivary gland tumors in future studies.

Objectives: The Neck Imaging Reporting and Data System (NI-RADS) is an increasingly utilized risk stratification tool for imaging surveillance after treatment for head and neck cancer. This study aims to measure the impact of supervision by subspecialized radiologists on diagnostic accuracy of NI-RADS when initial reading is performed by residents.

Methods: 150 CT and MRI datasets were initially read by two trained residents, and then supervised by two subspecialized radiologists. Recurrence rates by NI-RADS category were calculated, and receiver operating characteristic (ROC) curves were plotted. After dichotomization of the NI-RADS system (category 1 vs categories 2 + 3+4 and categories 1 + 2 vs 3 + 4), sensitivity, specificity, positive and negative predictive value were calculated.

Results: 26% of the reports were modified by the supervising radiologists. Area under the curve of ROC plots values of the supervision session were higher than those of the initial reading session for both the primary site (0.89 vs 0.86) and the neck (0.94 vs 0.91), but the difference was not statistically significant. For dichotomized NI-RADS category assignments, differences between the initial reading and the supervision session were statistically significant regarding specificity and PPV for the primary site (1 + 2 vs 3 + 4 and 1 vs 2 + 3+4) or even for both sites combined (1 vs 2 + 3+4).

Conclusion: NI-RADS enables trained resident radiologists to report surveillance imaging in patients with treated oral squamous cell carcinoma with high discriminatory power. Additional supervision by a subspecialized head and neck radiologist particularly improves specificity of radiological reports.

Following the arrival of over 1.2 million refugees and asylum seekers since the 2015 European refugee crisis, Germany has faced enormous humanitarian and societal challenges, with direct implications for participatory peace-building efforts at the local community level. A multitude of postmigration stressors and high prevalence of mental health conditions among refugees contribute to the substantial burden of daily conflicts in refugee shelters and communities. Ongoing exposure to a conflict-prone environment, psychological distress and stigmatization among community members can severely impair the quality of life and aggravate existing health-related, socio-economic and integrational challenges. Previous research has demonstrated the feasibility of individual alternative dispute resolution (ADR) and mental health literacy (MHL) interventions in refugee settings. As interpersonal conflict and psychological well-being constitute mutually interdependent phenomena, integrated methodologies combining ADR with MHL may offer unique value to affected vulnerable populations. However, systemic implementation of such mechanisms in refugee shelters has remained largely unexplored. In recognition of this unmet need and as part of the nonprofit organization R3SOLUTE, we have developed a tailored educational curriculum directed at equipping refugees in shelters and their local neighbor citizens with peer mediation-based ADR and MHL skills. In this multidisciplinary bottom-up approach, termed psychosocial peer mediation (PPM), participants learn to effectively manage and prevent conflicts in their own communities. Based on our field experience with implementing PPM in numerous refugee shelters across Germany between 2018 and 2021, we here provide relevant practical insights and discuss best practices, with a focus on addressing existing challenges and opportunities in the field.

Objective: Psychological disorders often take a long-term course, resulting in impairment in daily life and work. Treatment must therefore target not only symptoms of illness but also capacity limitations and context restrictions, as outlined in the International Classification of Functioning, Disability and Health (ICF). This includes sociomedical and interdisciplinary interventions like coordination with other specialists, contact to employers and employment agencies, social support agencies, debt counselling, self-help and leisure groups. There are no data on the spectrum, rate and unmet needs of sociomedical interventions in outpatient psychotherapy.

Method: Following a semistructured interview schedule, 131 psychotherapists in private practice were asked to report on unselected patients. The interviewer assessed to what degree 38 predefined sociomedical interventions were applied so far or should be considered in the future.

Result: Reports for 322 patients were gathered. All sociomedical interventions were applied, depending on the sick leave status and course of illness. Cognitive behaviour therapists used more sociomedical interventions than psychodynamic therapists.

Conclusion: The data show that sociomedical interventions are a frequent part of psychotherapy. They are used preferably in patients with participation restrictions. Psychotherapeutic concepts and education should include sociomedical aspects.

INTRODUCTION

Subthalamic DBS in Parkinson's disease has been associated with cognitive decline in few cases. Volume reduction of the nucleus basalis of Meynert (NBM) seems to precede cognitive impairment in Parkinson's disease. In this retrospective study, we evaluated NBM volume as a predictor of cognitive outcome 1 year after subthalamic DBS.

METHODS

NBM volumes were calculated from preoperative MRIs using voxel-based morphometry. Cognitive outcome was defined as the relative change of MMSE or DemTect scores from pre-to 1 year postoperatively. A multiple linear regression analysis adjusted for the number of cognitive domains affected in the preoperative neuropsychological testing and UPDRS III was conducted. To account for other variables and potential non-linear effects, an additional machine learning analysis using random forests was applied.

RESULTS

55 patients with Parkinson's disease (39 male, age 61.4 ± 7.5 years, disease duration 10.8 ± 4.7 years) who received bilateral subthalamic DBS electrodes at our center were included. Although overall cognition did not change significantly, individual change in cognitive abilities was variable. Cognitive outcome could be predicted based on NBM size (B = 208.98, p = 0.022*) in the regression model (F(3,49) = 2.869; R2 of 0.149; p = 0.046*). Using random forests with more variables, cognitive outcome could also be predicted (average root mean squared error between predicted and true cognitive change 11.28 ± 9.51, p = 0.039*). Also in this model, NBM volume was the most predictive variable.

CONCLUSION

NBM volume can be used as a simple non-invasive predictor for cognitive outcome after DBS in Parkinson's disease, especially when combined with other clinical parameters that are prognostically relevant.

Loss of function variants of GLI3 are associated with a variety of forms of polysyndactyly: Pallister-Hall syndrome (PHS), Greig-Cephalopolysyndactyly syndrome (GCPS), and isolated polysyndactyly (IPD). Variants affecting the N-terminal and C-terminal thirds of the GLI3 protein have been associated with GCPS, those within the central third with PHS. Cases of IPD have been attributed to variants affecting the C-terminal third of the GLI3 protein. In this study, we further investigate these genotype-phenotype correlations. Sequencing of GLI3 was performed in patients with clinical findings suggestive of a GLI3-associated syndrome. Additionally, we searched the literature for reported cases of either manifestation with mutations in the GLI3 gene. Here, we report 48 novel cases from 16 families with polysyndactyly in whom we found causative variants in GLI3 and a review on 314 previously reported GLI3 variants. No differences in location of variants causing either GCPS or IPD were found. Review of published data confirmed the association of PHS and variants affecting the GLI3 protein's central third. We conclude that the observed manifestations of GLI3 variants as GCPS or IPD display different phenotypic severities of the same disorder and propose a binary division of GLI3-associated disorders in either PHS or GCPS/polysyndactyly.

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are rare in both children and adults, and have been recently suggested to be an autoimmune neuroinflammatory group of disorders that are different from aquaporin-4 autoantibody-associated neuromyelitis optica spectrum disorder and from classic multiple sclerosis. In-vivo imaging of the MOGAD patient central nervous system has shown some distinguishing features when evaluating magnetic resonance imaging of the brain, spinal cord and optic nerves, as well as retinal imaging using optical coherence tomography. In this review, we discuss key clinical and neuroimaging characteristics of paediatric and adult MOGAD. We describe how these imaging techniques may be used to study this group of disorders and discuss how image analysis methods have led to recent insights for consideration in future studies.

Background: Allergen immunotherapy (AIT) is the only disease-modifying treatment in patients with seasonal allergic rhinoconjunctivitis (SAR). Its efficacy depends on the precise identification of the triggering allergen. However, diagnostics based on retrospective clinical history and sensitization to whole extracts (SWE) often leads to equivocal results.

Objectives: To assess the usability and impact of a recently established algorithm for a clinical decision support system (@IT2020-CDSS) for SAR and its diagnostic steps [anamnesis, SWE (skin prick test or serum IgE), component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary] on doctor's AIT prescription decisions.

Methods: After educational training on the @IT2020-CDSS algorithm, 46 doctors (18 allergy specialists, AS, and 28 general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the algorithm. The usability and perceived impact of the algorithm were evaluated.

Results: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p < .01). AIT prescription for pollen and Alternaria allergy based on anamnesis and SWE was heterogeneous but converged towards a consensus by integrating CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics.

Conclusions and clinical implications: The implementation of CRD and eDiary in the @IT2020-CDSS algorithm improved consensus on AIT prescription for SAR among AS and GP. The potential usefulness of a CDSS for aetiological diagnosis of SAR and AIT prescription in real-world clinical practice deserves further investigation.