[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.

Seborrheic keratosis.

Seborrheic keratosis (SK) is the most common benign epidermal tumor in clinical dermatological practice. This review summarizes current knowledge about the clinical and histological appearance, epidemiology, pathogenesis, and treatment of SK. There are different subtypes of SK based on clinical presentation and histologic findings. Several factors, including age, genetic predisposition, and possibly also exposure to ultraviolet radiation, are thought to contribute to the development of SK. The lesions can occur on all areas of the body except for the palms and soles, but the most common sites are the face and upper trunk. The diagnosis is usually made clinically, and in some cases by dermatoscopy or histology. Many patients prefer to have the lesions removed for cosmetic reasons although there is no medical indication. Treatment options include surgical therapy, laser therapy, electrocautery, cryotherapy, and topical drug therapy, which is currently in development. Treatment should be individualized depending on the clinical picture and patient preference.

Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product.

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process's milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300-400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 "IMI-Gel" batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability.

[Multidisciplinarity as the key to success : Cooperation between dermatology and rheumatology to optimize patient care]. / Multidisziplinarität als Schlüssel zum Erfolg : Zusammenarbeit zwischen Dermatologie und Rheumatologie zur Optimierung der Patientenversorgung.

BACKGROUND: Treatment of patients with systemic autoimmune and/or autoinflammatory diseases (AI/AInf) often requires multidisciplinary collaboration of various medical specialties. OBJECTIVES: We evaluated whether the establishment of a multidisciplinary board, which we termed rheuma board (RB), can contribute to optimization of care for patients with psoriatic arthritis (PsA) or other AI/AInf. MATERIALS AND METHODS: A total of 272 patients were included in the study. Patients were divided into three groups-group 1: 41 patients with or with suspected PsA, initially assessed in the dermatology department and afterwards presented for consultation in the rheumatology department; group 2: 166 patients with or with suspected PsA presenting in the dermatology department and afterwards discussed by RB; group 3: 65 patients with other AI/AInf presenting in the dermatology department and afterwards discussed by RB. We evaluated the average duration from initial presentation to therapy initiation after completing evaluation and diagnostics by both specialties. In addition, diagnosis confirmation/verification and therapy continuation/optimization were analyzed for all three groups. RESULTS: The average duration from initial presentation until therapy initiation was 85 ± 42.24 (5-173) days in group 1, 15 ± 13.09 (0-78) days in group 2, and 20 ± 16.71 (1-75) days in group 3. In addition, in groups 2 and 3 confirmation of diagnosis was faster and waiting time for diagnosis and therapy initiation was significantly reduced. CONCLUSIONS: Establishment of a RB results in a significant reduction in the time duration between first presentation and initiation of therapy, and an improvement of care for patients with AI/AInf including confirmation of diagnosis and therapy optimization.

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.

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.

Effective treatment of disseminated superficial actinic porokeratosis with chemical peels - customary treatment for a rare disease.

Background: Disseminated superficial actinic porokeratosis (DSAP) is a rare dermatologic disorder of the epidermis. Often misdiagnosed as chronic UV-damage or actinic keratoses, patients are treated for years with different therapeutic options with little success. Current treatment options include imiquimod, ingenol mebutate, cryosurgery, photodynamic therapy and topical or systemic therapy with retinoids. Since those approaches show only little success or come along with major side effects, therapeutic alternatives are strongly requested. Methods: We report a series of five female patients with history of DSAP that were successfully treated with chemical peels. Results: All patients suffered from the disease for 14.4 years on average and all were refractory to at least two therapeutic options, mostly imiquimod and topical tretinoin. Patients were treated with glycolic acid 50% and salicylic acid 25% in a two-layer-technique. After a mean of three cycles every 6 weeks a clear reduction in lesion was assessed by physicians. Patients were highly satisfied with outcome and rare occurrence of side effects as assessed by TSQM questionnaire. Conclusion: Chemical peels are safe and well tolerated treatment options for patients with refractory porokeratosis. As characteristic for chronic diseases, frequent repetition of treatment is needed in order to control disease activity.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 2: Treatment, Prevention and Follow-up.

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 1: Epidemiology, Genetics and Diagnosis.

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.

Extemporaneous formulations in Germany - relevance for everyday clinical practice.

BACKGROUND: Extemporaneous formulations broaden the spectrum of therapeutic options for topical treatment in particular and thus improve patient care. The latest amendment to the Regulation on the Operation of Pharmacies issued in 2012 brought about changes in prescribing and manufacturing practices. The aim of the present study was to assess the relevance of extemporaneous formulations in everyday clinical practice. METHODS: We used data from the German Institute for Drug Use Evaluation (DAPI) to analyze the prescribing practice for compounded preparations in Germany between the fourth quarter of 2011 and the third quarter of 2014. In doing so, we determined the total cost associated with extemporaneous formulations covered by statutory health insurance funds in the outpatient setting. RESULTS: Approximately three out of ten prescriptions (30.54 %) by German dermatologists during the observation period were extemporaneous formulations. While dermatologists make up only 2.7 % of physicians working in the statutory health care system in Germany, they prescribe more than half of all compounded preparations (53.6 %). Each dermatologist prescribed an average of 270.4 formulations per quarter; that number was 13.5 (1.3 %) for all other medical specialties. On average, 1,983,687 extemporaneous formulations overall (1.3 % of all prescriptions) were prescribed per quarter, corresponding to a total cost of € 40,944,982 (0.55 %). CONCLUSIONS: Apart from finished medicinal products, extemporaneous formulations play a key role in outpatient care. Based on the principles of evidence-based and patient-oriented medicine, the quality of compounded preparations and the prescribing practice of physicians (standardized vs. individual formulations) should be further investigated to optimize the quality of these preparations.

Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy.

Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit.We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health).Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: disease-free health and melanoma recurrence (with or without previous use of IFNα-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects.Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer.On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.

Checkpoint-Inhibitoren in der Immuntherapie: Ein Meilenstein in der Behandlung des malignen Melanoms.

Seit Jahrzehnten ist bekannt, dass Tumoren vom Immunsystem erkannt und zerstört werden können. Diese, vor allem in Tierversuchen gewonnene Erkenntnis konnte jedoch in der Vergangenheit nicht zum Nutzen unserer Patienten umgesetzt werden, da immunonkologische Therapieansätze in den letzten Jahrzehnten in der Anwendung beim Menschen stets versagt haben. Daher hat, mit Ausnahme der adjuvanten Interferontherapie, keines dieser Verfahren den Einzug in die klinische Versorgung gefunden. Langzeitüberleben unter guter Lebensqualität war dabei sehr wenigen Patienten vorbehalten. Mit den neuen immunologischen Therapieansätzen wird jedoch sowohl das Langzeitüberleben als auch die Lebensqualität onkologischer Patienten neu definiert. Auf die neuen "Immun-Checkpoint-Inhibitoren" spricht erstmals ein relevanter Teil der behandelten Patienten an und diese zeigen in der Regel langandauernde Remissionen bis hin zur Heilung. Schon jetzt ist klar, dass die Immuntherapie in Zukunft eine der wesentlichen Therapiesäulen bei der Behandlung des metastasierten Melanoms und auch vieler anderer fortgeschrittener Tumoren bilden wird. In dieser Übersicht werden die wichtigsten neuen Therapiemodalitäten besprochen und sowohl deren Wirkprinzip als auch klinische Daten zum Therapieansprechen und zu erwartenden Nebenwirkungen der Therapie referiert.

Immune checkpoint inhibitors: a milestone in the treatment of melanoma.

It has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge - mostly acquired through animal experiments - could not be used to benefit our patients, because immuno-oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life. With the advent of novel immunological approaches, the meaning of long-term survival as well as quality of life has been redefined for oncological patients. For the first time, a significant percentage of patients responds to treatment with immune checkpoint inhibitors, showing long-term remission and even cure. It has already become apparent that immunotherapy will in the future be one of the therapeutic mainstays in the treatment of metastatic melanoma as well as many other tumor types. The present review article presents the most important new treatment modalities, their mechanism of action, clinical data regarding treatment response, and adverse events to be expected.