Modelling of patient journey in chronic spontaneous urticaria: Increasing awareness and education by shorten patients' disease journey in Germany.

BACKGROUND: Chronic spontaneous urticaria (CSU) is both physically and emotionally stressful, and guideline recommendations are often not optimally implemented in clinical practice. The objective of this study was to provide an overview on the patient journey in CSU and to develop a mathematical model based on solid data. METHODS: The journey of CSU patients in Germany was traced through literature review and expert meetings that included medical experts, pharmacists and representatives of patient organizations. The current situation's main challenges in the patient journey (education, collaboration and disease management) were discussed in depth. Then, a probabilistic model was developed in a co-creation approach to simulate the impact of three potential improvement strategies: (1) patient education campaign, (2) medical professional education programme and (3) implementation of a disease management programme (DMP). RESULTS: Chronic spontaneous urticaria patients are severely burdened by delays in diagnosis and optimal medical care. Our simulation indicates that in Germany, it takes on average of 3.8 years for patients to achieve disease control in Germany. Modelling all three optimization strategies resulted in a reduction to 2.5 years until CSU symptom control. On a population level, the proportion of CSU patients with disease control increased from 44.2% to 58.1%. CONCLUSION: In principle, effective CSU medications and a disease-specific guideline are available. However, implementation of recommendations is lagging in practice. The approach of quantitative modelling of the patient journey validates obstacles and shows a clear effect of multiple interventions on the patient journey. The data generated by our simulation can be used to identify strategies for improving patient care. Our approach might helping in understanding and improving the management of patients beyond CSU.

Obesity is linked to disease severity in moderate to severe atopic dermatitis-Data from the prospective observational TREATgermany registry.

BACKGROUND: There are conflicting data on a potential association between obesity and atopic dermatitis (AD). The purpose of this study was to investigate the relationship between obesity and AD disease severity. METHODS: Patients from the TREATgermany registry cohort were divided into three groups according to their body mass index (BMI). Due to low numbers, underweight patients (BMI <18.5 kg/m2) were excluded from the analysis. Physician- and patient-reported disease severity scores as well as additional phenotypic characteristics were evaluated for association with BMI. Generalized linear mixed models and multinomial logit models, respectively, were applied to investigate the association of BMI, age, sex and current systemic AD treatment with disease severity. RESULTS: This study encompassed 1416 patients, of which 234 (16.5%) were obese (BMI ≥30 kg/m2). Obesity was associated with lower educational background and smoking. Otherwise, obese and non-obese AD patients had similar baseline characteristics. Increased BMI was associated with higher oSCORAD (adjusted ß: 1.24, 95% CI: 1.05-1.46, p = 0.013) and Patient-oriented eczema measure (POEM) (adjusted ß: 1.09, 95% CI: 1.01-1.17, p = 0.038). However, the absolute difference in the overall oSCORAD was small between obese and non-obese AD patients (Δ oSCORAD = 2.5). Allergic comorbidity was comparable between all three groups, with the exception of asthma which was more pronounced in obese patients (p < 0.001). DISCUSSION: In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance. The overall prevalence of obesity among the German AD patients was lower than in studies on other AD cohorts from different countries, which confirms previous research on the German population and suggests regional differences in the interdependence of AD and obesity prevalence.

Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry. METHODS: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population-based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI). RESULTS: We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non-lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine. CONCLUSIONS: Systemic treatment with dupilumab but not cyclosporine tends to restore a healthy skin microbiome largely independent of the clinical response indicating potential effects of IL-4RA blockade on the microbiome.

Itching in Atopic Dermatitis: Patient- and Physician-reported Outcomes in the German Atopic Dermatitis Registry TREATgermany.

TREATgermany is an investigator-initiated prospective disease registry. It investigates physician- and patient-reported disease severity (Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator Global Assessment, Patient-Oriented Eczema Measure (POEM), Patient Global Assessment (PGA)), patient-reported symptoms (itch, sleep loss, depressive symptoms), therapy courses and dermatological quality of life (DLQI) in moderate-to-severe atopic dermatitis with SCORAD > 20. 1,134 atopic dermatitis patients (mean age 41.0 ± 14.7 years, 42.5% females) were enrolled by 40 German recruiting sites (dermatological clinics and practices) between June 2016 and April 2021. The current analysis focuses on itch scores obtained with a numerical rating scale (NRS)) documented for the previous 3 days prior to baseline visit. The results show that 97.2% (1,090 of 1,121) patients experienced itch. Itch severity correlated moderately with severity of atopic dermatitis oSCORAD (rho = 0.44 (0.39-0.48)) and EASI score (rho = 0.41 (0.36-0.46)). A strong correlation was found with self-reported disease severity as PGA (rho = 0.68 (0.65-0.71)), POEM sum score (rho = 0.66 (0.63-0.69)) and dermatological quality of life impairment DLQI (rho = 0.61 (0.57-0.65)). Itch as a subjective complaint is more closely correlated with patient-reported outcomes than with objective assessments by the physician.

Itch, sleep loss, depressive symptoms, fatigue, and productivity loss in patients with moderate-to-severe atopic dermatitis: Analyses of TREATgermany registry data.

BACKGROUND: TREATgermany is a multicenter registry including patients with moderate-to-severe atopic dermatitis (AD) from currently 74 study centers (university clinics, hospitals and practices) in Germany. As of August 31, 2021, 1,230 adult patients were enrolled. METHODS: In TREATgermany, patients and physicians fill in questionnaires pertaining to symptoms, disease severity, quality of life, depressiveness, and fatigue. In particular, limitations in work performance are assessed using the Work Limitations Questionnaire (WLQ). To assess associations between occupational performance/work limitations and symptoms, correlations and regression models were calculated. RESULTS: The examined sample of 228 employed patients reported an average of 6% at-work productivity loss within the past two weeks prior to enrolment in the registry. The WLQ productivity loss score was moderately associated with itch (r = 0.32) and sleep loss (r = 0.39) and strongly associated with depressive symptoms (r = 0.68) and fatigue (r = 0.60). CONCLUSIONS: The analyses of the registry data show that moderate-to-severe atopic dermatitis has a negative impact on the work productivity of the patients. The analyses further point out the relevant associations between work productivity, depressive symptoms, and fatigue highlighting the disease burden caused by the psychological components of AD.

Real-world data on the effectiveness, safety and drug survival of dupilumab: an analysis from the TREATgermany registry.

This interim analysis from the atopic dermatitis registry TREATgermany shows robust long-term efficacy, favourable safety and high persistence of dupilumab under real life conditions.

Perception of the coronavirus pandemic by patients with atopic dermatitis - Results from the TREATgermany registry.

BACKGROUND: TREATgermany, a registry for patients with moderate to severe atopic dermatitis (AD), established an additional questionnaire in spring 2020 to investigate the effects of the coronavirus pandemic on the daily life of patients with AD. MATERIAL AND METHODS: A questionnaire was used to analyze general information regarding a patient's experience of the coronavirus pandemic and, using the Inventory of Life-Changing Events, the resulting personal burden. To analyze possible associations between disease severity (EASI score, oSCORAD, IGA, PGA, POEM), quality of life (DLQI) and personal burden, t-tests, analyses of variance and correlations were evaluated, controlled for sex and age. RESULTS: 58 % (n = 233) of the included 400 registry patients reported high burden scores caused by the coronavirus pandemic, regardless of an actual infection. Men showed significantly higher burden scores than women, and younger than older respondents (both P = 0.03). There were no differences in burden scores related to the physician's assessment of disease severity. However, patients with higher quality of life impairments and higher disease severity perceived the burden of the coronavirus pandemic as less severe (DLQI P = 0.019, PGA P = 0.044). CONCLUSIONS: Our data show that registry patients considered the coronavirus pandemic as a life-changing event and perceived the burden differently. This should be taken into account in the treatment of patients with moderate to severe AD as well as in further studies.

Multicenter Analysis of Acquired Undescended Testis and Its Impact on the Timing of Orchidopexy.

OBJECTIVE: To assess whether late orchidopexy for undescended testis represents delayed treatment of primary undescended testis or later-occurring acquired undescended testis. STUDY DESIGN: We examined boys undergoing orchidopexy for cryptorchidism regarding age at surgery and entity of undescended testis. We characterized differences between primary undescended testis and acquired undescended testis and evaluated the knowledge regarding the diagnosis and management of acquired undescended testis among practicing physicians. We conducted an observational study using a mixed-method multicenter cross-sectional design. A total of 310 consecutive boys undergoing orchidopexy for undescended testis at 6 pediatric medical centers in Germany between April 2016 and June 2018 were investigated regarding testicular position at birth and age at surgery. In addition, a survey on acquired undescended testis management was carried out in 1017 multidisciplinary physicians and final-year medical students. RESULTS: Only 13% of all patients were operated on in their first year of life. Among patients with known previous testicular position (67%), primary undescended testis (n = 103) and acquired undescended testis (n = 104) were equally frequent. More than one-half (56%) of orchidopexies performed after the first year of life were due to acquired undescended testis. Remarkably, only 15% of physicians considered acquired undescended testis as an indication for late surgery. CONCLUSIONS: Acquired undescended testis is more common than previously perceived and accounts for a significant proportion of "late" orchidopexies in patients with undescended testis. Acquired undescended testis needs to be better recognized in clinical practice and screening should continue in older children with previously descended testes. TRIAL REGISTRATION: German Clinical Trials Registry: DRKS00015903.

Interparental conflict and early adolescents' aggression: is irregular sleep a vulnerability factor?

We investigated whether (a) short and irregular sleep are related to aggressive behavior in early adolescence and (b) whether they moderate the relation between interparental conflict and aggressive behavior. 176 early adolescents (mean age 11.6 years, 89 girls) reported their bed and wake times on weekdays and on weekends and their aggressive behavior. Interparental conflict was rated by their mothers and adolescents reported whether they felt threatened by the conflict. No direct association between early adolescents' sleep and aggression was found. However, short sleep duration on weekday nights, long sleep duration on weekends, and a large weekday to weekend difference in sleep duration moderated the relation between interparental conflict and early adolescents' aggression. Findings are consistent with the hypothesis that irregular sleep is a vulnerability factor for early adolescents' aggression and underscore the importance of sufficient and regular sleep for resilience.

Marital conflict and early adolescents' self-evaluation: the role of parenting quality and early adolescents' appraisals.

Cognitive appraisals and family dynamics have been identified as mediators of the relationship between marital conflict and children's adjustment. Surprisingly little research has investigated both meditational processes in the same study. Guided by the cognitive-contextual framework and the spillover hypothesis, the present study integrated factors from both theories early adolescents' appraisals of threat and self-blame, as well as perceived parenting quality as mediators of the link between early adolescents' perception of marital conflict and their self-evaluations (self-esteem and scholastic competence). Analyses were based on the first two waves of an ongoing longitudinal study. Participants were 176 two-parent families, and their early adolescents (50.5% girls) whose mean age was 10.61 years at Time 1 (SD =0.40) and 11.63 years at Time 2 (SD=0.39). Structural equation modeling analyses indicated that parenting quality and early adolescents' perceived threat provided indirect pathways between marital conflict and early adolescents' self-esteem 1 year later when controlling for their initial level of self-esteem. With respect to scholastic competence, only fathers' parenting was an indirect link. Self-blame did not play a role. Implications for understanding the mechanisms by which exposure to marital conflict predicts early adolescents' maladjustment are discussed.

Perceived interparental conflict and early adolescents' friendships: the role of attachment security and emotion regulation.

Although there is strong evidence for the effect of interparental conflict on adolescents' internalizing and externalizing problems, little is known about the effect on the quality of adolescents' relationships. The current study investigates the link between adolescents' friendships and interparental conflict as reported by both parents and adolescents. It considers early adolescents' emotion regulation ability and attachment security as mediators. The analysis is based on a longitudinal study with two waves separated by 12 months. The participants were 180 two-parent families and their adolescent children (50.5 % girls), the average age of the latter being 10.61 years (SD = 0.41) at the outset (Time 1). Binomial logistic regression analysis revealed that perceived interparental conflict increased the risk of instability in friendship relationships across the 1-year period. Structural equation modeling analysis indicated that the association between perceived interparental conflict and friendship quality was mediated by emotion regulation and attachment security. The discussion focuses on mechanisms whereby interparental conflict influences early adolescents' friendship relationships.

Long-term cosmetic results after minimally invasive video-assisted thyroidectomy.

BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) has been performed in the authors' department since 2004. Many authors have described some of its advantages over conventional surgery in terms of cosmetic results. The published literature on this topic variously describes the average central incision as 1 to 3 cm. The end point of the cosmetic results (e.g. the question of keloids) cannot be documented during the inpatient stay. This report describes the long-term cosmetic results for this method and analyzes the subjective and objective outcomes after MIVAT. METHODS: From January 2004 until March 2010, 116 patients underwent MIVAT in the authors' department. The authors included 96 patients in their subsequent examination, with a follow-up period of 22.4 months (range, 1-64 months). RESULTS: The measurable cervical scar length was 1.9 cm (range, 1-3 cm). The measurable wideness of the cervical scar was 0.17 cm (range, 0.05-1.5 cm). Keloids in 10 female patients (10.4%) had diverse proliferation. Of the 116 patients, 93 (96.8%) were very satisfied or satisfied with the cosmetic result. The Patient Scar Assessment Scale score was 9.7, and of the Observer Scar Assessment Scale score was 8.1. CONCLUSION: In terms of long-term results, MIVAT appears to provide excellent cosmetic outcomes. The problem with the development of keloids in the region of the cervical incision, especially in female patients, remains unresolved. The satisfaction of patients with the long-term outcome of MIVAT is high.

Parental conflict resolution styles and children's adjustment: children's appraisals and emotion regulation as mediators.

Guided by the emotional security hypothesis and the cognitive-contextual framework, the authors investigated whether the associations between negative parental conflict resolution styles and children's internalizing and externalizing problems were mediated by children's appraisals of threat and self-blame and their emotion regulation. Participants were 192 Swiss 2-parent families with children aged 9-12 years (M age = 10.62 years, SD = 0.41 years). Structural equation modeling was used to test the empirical validity of the theoretical model. Results indicated that children's maladaptive emotion regulation mediated the association between negative parental conflict resolution styles and children's internalizing as well as externalizing problems. Whereas perceived threat was related only to children's internalizing problems, self-blame did not mediate the links between negative parental conflict resolution styles and children's adjustment. Implications for understanding the mechanisms by which exposure to interparental conflict could lead to children's maladjustment and limitations of the study are discussed.

Be Careful Where You Smile: Culture Shapes Judgments of Intelligence and Honesty of Smiling Individuals.

Smiling individuals are usually perceived more favorably than non-smiling ones-they are judged as happier, more attractive, competent, and friendly. These seemingly clear and obvious consequences of smiling are assumed to be culturally universal, however most of the psychological research is carried out in WEIRD societies (Western, Educated, Industrialized, Rich, and Democratic) and the influence of culture on social perception of nonverbal behavior is still understudied. Here we show that a smiling individual may be judged as less intelligent than the same non-smiling individual in cultures low on the GLOBE's uncertainty avoidance dimension. Furthermore, we show that corruption at the societal level may undermine the prosocial perception of smiling-in societies with high corruption indicators, trust toward smiling individuals is reduced. This research fosters understanding of the cultural framework surrounding nonverbal communication processes and reveals that in some cultures smiling may lead to negative attributions.

The relation between attachment and intergenerational support.

This study investigated the relation between the internal representation of attachment and the perception of the actual exchange of intergenerational support within 100 dyads of adult daughters and their elderly mothers in Germany. Results showed relations between the daughters' preoccupation and avoidance with their perception of receiving emotional support from their parents and providing instrumental support to them. No relations were found between the mothers' attachment and the support they provided to the daughters. These results are discussed with respect to different conditions for emotional and instrumental support of adult daughters and their elderly mothers, and a relationship specific approach to attachment.

A three-year randomized trial in patients with dysplastic naevi treated with oral beta-carotene.

Ultraviolet irradiation provokes the development of new melanocytic naevi, or changes in existing naevi, leading to repeated surgery of atypical naevi and becoming a continual burden for individuals with many of these lesions. To determine the influence of long-term medication with the radical scavenger beta-carotene on newly developing atypical naevi, a single-centre, randomized, placebo-controlled study, prospective over 3 years, was started double-blind in 62 patients with numerous clinically atypical naevi. Beta-carotene (25 mg) was given twice daily for 36 months in the treatment group (n = 30) and saccharose capsules as placebo in the control group (n = 32). The total number of newly developed naevi in the beta-carotene group (n = 18) was 68 versus 88 in the placebo group (n=21) (not significant). Of 12 different locations on the human body evaluated separately, only in two, the lower arm (p = 0.03) and the feet (p = 0.03), was there a difference for the beta-carotene group in the quantification of naevi. Overall, it is concluded that beta-carotene does not reduce the development of new naevi in patients with numerous atypical naevi.