[Midwives as influencers in skin care for newborns at risk of atopic diseases : Survey of midwives' current recommendations]. / Hebammen als Influencer bei der Hautpflege atopisch prädisponierter Neugeborener : Eine Umfrage zu den aktuellen Empfehlungen von Hebammen.

INTRODUCTION: The prevalence of atopic diseases remains high. Initial studies suggest that primary prevention with regular basic care may influence the incidence of atopic dermatitis in infants; however, data are unclear. Midwives play an important role in the care of women in the peripartum period and therefore also in providing advice on topics such as skin care, breastfeeding and nutrition of the newborn and young infant. The aim of this study was to determine the care recommendations for newborns by midwives. METHODS: We conducted a cross-sectional survey among German midwives using questionnaires on the topic of newborn skin care. RESULTS: A total of 128 questionnaires were analyzed. The most common recommendations were oil-based herbal topicals (34.9%) and plain water (34.0%). Approximately 70% of midwives reported recommending various options when there was a known family history of atopic diathesis. It was remarkable that most of the midwives' recommendations were identical regardless of the presence of an atopic diathesis. Essential care products are only used "when necessary". CONCLUSION: Training programs for midwives on the topic of "care and strengthening of the skin barrier", taking into account the current guidelines for allergy prevention, should be implemented.

Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts. / Atopische Keratokonjunktivitis: Pathophysiologie, Klinik und potenzielle neue Therapiekonzepte.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Burden of impaired sleep and its improvement through topical treatment in psoriasis and atopic dermatitis.

INTRODUCTION: Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. PATIENTS AND METHODS: Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2 weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. RESULTS: 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2 weeks (p < 0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r > 0.50, p < 0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r > 0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. CONCLUSIONS: Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2 weeks of topical treatment.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Bridging the gaps: management of lichen planus subtypes in a joint dermatology-oral surgery clinic.

Lichen planus (LP) presents with a range of clinical subtypes. It can affect the outer skin, involve the nails and present with alopecia and mucosal symptoms to varying degrees. LP of the outer skin mostly shows a self-limiting course; however, this is not the case for lichen planopilaris and the mucosa-affecting subtypes. The pathogenesis of LP is still incompletely understood. As a result, an effective, targeted therapy is currently lacking and different immunomodulatory approaches are being used in clinical practice. The management of patients with severe oral LP mucosae can be particularly challenging. Although the true risk remains controversial, oral LP is considered a risk factor for the development of squamous cell carcinoma and there is a need for regular screening. The quality of life in patients with LP is significantly impaired because of frequent clinical visits, pain, soreness, inability to eat certain foods, side effects to medication, frustrating therapy attempts and worry regarding cancer risk. We highlight here the advantages of an interdisciplinary dermatology and oral surgery clinic, which can address the domains of tooth status, nutrition, pain and malignant transformation and optimized patient management.

Sleep disorders in dermatology - a comprehensive review.

Sleep is a normal physiological process that accounts for approximately one third of a person's life. Disruption of the normal sleep cycle, which maintains physiological homeostasis, can lead to pathology. It is not known whether sleep disturbance causes skin disease or skin disease causes sleep impairment, but a bidirectional influence is suspected. We have compiled the data from published articles on "sleep disorders in dermatology" in PubMed Central from July 2010 to July 2022 (with the option "full text available") and provide an overview of sleep disorders associated with dermatological conditions and certain drugs used in dermatology as well as sleep disturbances for which some drugs used can cause itch or dermatological issues. Atopic dermatitis, eczema and psoriasis have been shown to be exacerbated by sleep problems and vice versa. Sleep deprivation, night-time pruritus and disrupted sleep cycles are often used to assess treatment response and quality of life in these conditions. Some medications used primarily for dermatological conditions have also been associated with alterations in the sleep-wake cycle. Addressing patients sleep disorders should be an integral part of the management of dermatological conditions. More studies are needed to further investigate the influence of sleep and skin disorders.

Oral Low-Dose Naltrexone in the Treatment of Frontal Fibrosing Alopecia and Lichen Planopilaris: An Uncontrolled Open-Label Prospective Study.

Background Frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) is scarring alopecias with limited evidence supporting their treatment options. We investigated the use of low-dose naltrexone (3 mg oral daily) as adjunctive therapy in the treatment of FFA and LPP. Methods A single-center, uncontrolled open-label prospective study was performed, with 26 patients who took low-dose naltrexone for one year included in the per-protocol analysis. Both patient-reported (pruritus and burning/pain) and physician-assessed (erythema, scale, and scalp involvement) outcomes were analyzed. Results There were decreases in erythema and scale for the overall longitudinal outcomes using linear mixed effects model analysis. However, only erythema had a significant decrease at 12 months compared with baseline. Mean erythema decreased by 0.93 at 12 months compared with baseline on a 0-3-point scale (p<0.0001, 95% mean CI [-1.32, -0.53]). There was no statistically significant difference comparing 12 months to baseline for the other outcomes including pruritus, burning/pain, and scalp involvement. Limitations include the possibility of spontaneous stabilization, concurrent medications, a small sample size with limited racial diversity, and mild subjective symptoms at baseline. Conclusion Our study supports further investigation of oral low-dose naltrexone as adjunctive therapy in the treatment of FFA and LPP if there is prominent erythema, and possibly scale.

Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure.

The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.

Neurobiological Correlates of Change in Adaptive Behavior in Autism.

OBJECTIVE: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of "personalized medicine" approaches is essential. However, this requires an understanding of the biological processes underpinning differences in clinical outcome, at both the individual and subgroup levels, across the lifespan. METHODS: The authors conducted a longitudinal follow-up study of 483 individuals (204 with ASD and 279 neurotypical individuals, ages 6-30 years), with assessment time points separated by ∼12-24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale-II), neuroanatomical data (structural MRI), and genetic data (DNA). Individuals with ASD were grouped into clinically meaningful "increasers," "no-changers," and "decreasers" in adaptive behavior. First, the authors compared neuroanatomy between outcome groups. Next, they examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level. Finally, they explored the observed neuroanatomical differences' potential genetic underpinnings. RESULTS: Outcome groups differed in neuroanatomical features (cortical volume and thickness, surface area), including in "social brain" regions previously implicated in ASD. Also, deviations of neuroanatomical features from the neurotypical profile predicted outcome at the individual level. Moreover, neuroanatomical differences were associated with genetic processes relevant to neuroanatomical phenotypes (e.g., synaptic development). CONCLUSIONS: This study demonstrates, for the first time, that variation in clinical (adaptive) outcome is associated with both group- and individual-level variation in anatomy of brain regions enriched for genes relevant to ASD. This may facilitate the move toward better targeted/precision medicine approaches.

Pathobiology of Second-Generation Antihistamines Related to Sleep in Urticaria Patients.

Background: Standard treatment options for urticaria are second-generation antihistamines; however, their effect on sleep is uncertain. This study measures the influence of different antihistamines on the biologic sleep pattern of urticaria patients and the relevance of sleep in urticaria patients. Methods: Ten patients with chronic spontaneous urticaria (CSU) and uncontrolled symptoms under a single dose of second-generation antihistamines were included. Two nights were monitored: the first night after 5 days on single dosage and the second night after 5 days on fourfold dosage. Patient-rated questionnaires were used and sleep was monitored using polygraphy. Results: The patients' rated daytime sleepiness decreased (p = 0.0319), as did their insomnia severity (p = 0.0349). The urticaria control (UCT) improved (p = 0.0007), as did the quality of life (p < 0.0001). There was no significant change of nightly pruritus (p = 0.1173), but there was an improvement of daytime pruritus (p = 0.0120). A significant increase in rapid eye movement (REM) sleep was seen (p = 0.0002) (from a mean of 3.9% to 14.3%). The deep sleep state (N3) also improved (8.7% to 12.3%) (p = 0.1172). Conclusion: This study has demonstrated an improvement of the sleep pattern in CSU patients under up-dosed second-generation antihistamines, without increased daytime sleepiness, alongside an improvement of urticaria symptoms and quality of life.

Severe chronic spontaneous urticaria in children - treatment options according to the guidelines and beyond - a 10 years review.

This is a retrospective study of 18 children with chronic spontaneous urticaria (CSU), where standard therapies, including up-dosing of antihistamines and omalizumab, were unable to cure the disease and where alternative strategies with experimental and off-label medication had to be used. MATERIALS: Being aware that our questionnaire is validated only for elder children or adults, we utilized the UAS7 to monitor disease control with the help of the parents. RESULTS: The UAS7 score decreased from a mean of 25 to an average of 13 after 8 weeks of therapy in 13 patients. Five patients had no significant reduction of UAS7 by week 8. In two of five patients, where periodic improvement was seen, omalizumab therapy was continued and showed complete response after 1-2 years. In three children, alternative treatments with cyclosporine and dupilumab, approved by the ethics committee, showed symptom improvement from a mean UAS7 of 29 to a mean value of 6. CONCLUSIONS: When omalizumab therapy including up-dosing strategies or shortened interval shows no symptom improvement, alternative therapies, sometimes off-label have to be considered in time.

Interindividual Differences in Cortical Thickness and Their Genomic Underpinnings in Autism Spectrum Disorder.

OBJECTIVE: Autism spectrum disorder (ASD) is accompanied by highly individualized neuroanatomical deviations that potentially map onto distinct genotypes and clinical phenotypes. This study aimed to link differences in brain anatomy to specific biological pathways to pave the way toward targeted therapeutic interventions. METHODS: The authors examined neurodevelopmental differences in cortical thickness and their genomic underpinnings in a large and clinically diverse sample of 360 individuals with ASD and 279 typically developing control subjects (ages 6-30 years) within the EU-AIMS Longitudinal European Autism Project (LEAP). The authors also examined neurodevelopmental differences and their potential pathophysiological mechanisms between clinical ASD subgroups that differed in the severity and pattern of sensory features. RESULTS: In addition to significant between-group differences in "core" ASD brain regions (i.e., fronto-temporal and cingulate regions), individuals with ASD manifested as neuroanatomical outliers within the neurotypical cortical thickness range in a wider neural system, which was enriched for genes known to be implicated in ASD on the genetic and/or transcriptomic level. Within these regions, the individuals' total (i.e., accumulated) degree of neuroanatomical atypicality was significantly correlated with higher polygenic scores for ASD and other psychiatric conditions, and it scaled with measures of symptom severity. Differences in cortical thickness deviations were also associated with distinct sensory subgroups, especially in brain regions expressing genes involved in excitatory rather than inhibitory neurotransmission. CONCLUSIONS: The study findings corroborate the link between macroscopic differences in brain anatomy and the molecular mechanisms underpinning heterogeneity in ASD, and provide future targets for stratification and subtyping.

Longitudinal Changes in Cortical Thickness in Adolescents with Autism Spectrum Disorder and Their Association with Restricted and Repetitive Behaviors.

The neuroanatomy of autism spectrum disorder (ASD) shows highly heterogeneous developmental trajectories across individuals. Mapping atypical brain development onto clinical phenotypes, and establishing their molecular underpinnings, is therefore crucial for patient stratification and subtyping. In this longitudinal study we examined intra- and inter-individual differences in the developmental trajectory of cortical thickness (CT) in childhood and adolescence, and their genomic underpinnings, in 33 individuals with ASD and 37 typically developing controls (aged 11-18 years). Moreover, we aimed to link regional atypical CT development to intra-individual variations in restricted and repetitive behavior (RRB) over a two-year time period. Individuals with ASD showed significantly reduced cortical thinning in several of the brain regions functionally related to wider autism symptoms and traits (e.g., fronto-temporal and cingulate cortices). The spatial patterns of the neuroanatomical differences in CT were enriched for genes known to be associated with ASD at a genetic and transcriptomic level. Further, intra-individual differences in CT correlated with within-subject variability in the severity of RRBs. Our findings represent an important step towards characterizing the neuroanatomical underpinnings of ASD across development based upon measures of CT. Moreover, our findings provide important novel insights into the link between microscopic and macroscopic pathology in ASD, as well as their relationship with different clinical ASD phenotypes.

Epidemiology of urticaria in German children.

BACKGROUND: To date, robust epidemiological metrics as well as data on comorbidity in pediatric urticaria are lacking. They form the basis for the design of efficient healthcare. METHODS: Retrospective study to analyze epidemiological data in pediatric urticaria. The analysis is based on routine data of a health insurance company operating throughout Germany (DAK-Gesundheit). Insured people under 18 years of age who received at least one confirmed outpatient or inpatient urticaria diagnosis according to the ICD-10 classification in the years 2010 to 2015 were included in the analysis and compared to children without a corresponding diagnosis. RESULTS: Of 2.3 million insured individuals, 313,581 (13.5 %) were under 18 years of age (153,214 female). Urticaria was diagnosed in 1.7 % of the 313,581 patients. The prevalence of urticaria decreased with age from 3.0 % in the 0-3-year age group to 1.0 % in the 14-18-year age group. Boys and girls were almost equally affected in all age groups. Atopic diseases as comorbidity occurred more frequently in children with urticaria than in the control group (16.0 % vs. 8.0 %). Autoimmune diseases, mental health problems, and obesity also occurred more frequently in children with urticaria than in the control group. CONCLUSIONS: The increased prevalence of specific comorbidities in children with urticaria suggests an increased need for screening. Multimodal treatment strategies need to be developed and interdisciplinary collaboration promoted.

Population-level mortality burden from novel coronavirus (COVID-19) in Europe and North America.

As of 31 January 2021, 63.9 million cases and 1.4 million deaths had been reported in Europe and North America, which accounted for 62.5% and 62.4% of the global total, respectively. Comparing the level of mortality across countries has proven difficult because of inherent limitations in the most commonly cited measures (e.g., case-fatality rates). We collected the cumulative number of confirmed deaths from COVID-19 by age in 2020 from the L'Institut National d'études Démographiques (INED) database and Statistics Canada for 15 European and North American countries. We calculated age-specific death rates and age-standardized death rates (ASDR) for each country over a 1-year period from 6 February 2020 (date of first COVID-19 death in Europe and North America) to 5 February 2021 using established demographic methods. We estimated that COVID-19 was the second leading cause of death behind cancer in England and Wales and France and the third leading cause of death behind cancer and heart disease in nine countries including the US. Countries with higher all-cause mortality prior to the COVID-19 experienced higher COVID-19 mortality than countries with lower all-cause mortality prior to the pandemic. The COVID-19 ASDR varied substantially within country (e.g., a 5-fold difference among the highest and lowest mortality states in Germany). Consistently strong public health measures may have lessened the level of mortality for some European and North American countries. In contrast, many of the largest countries and economies in these regions may continue to experience a high mortality level because of poor implementation and adherence to such measures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41118-021-00115-9.