[Educating Parents about Fever in Childhood Evaluation of the Effect of an Information Leaflet]. / Aufklärung von Eltern zu Fieber im Kindesalter Evaluation der Wirkung einer Informationsbroschüre.

BACKGROUND: Fever is an important immune reaction of the body in infections and plays a major role in childhood. Fear and uncertainty in dealing with fever are still widespread among parents. Information leaflets on the knowledge and handling of fever in childhood can serve as an educational tool for parents. It has not yet been investigated whether this type of information transfer is a suitable tool for educating parents. METHODS: 16 kindergartens in Saarland were visited. 481 parents of at least one child between the ages of 1 and 7 years answered a questionnaire on knowledge, approach and handling of fever in infections. Subsequently, an information leaflet on fever was handed out. On the following day, the questionnaire was answered again by the 190 parents who had read the information leaflet. The change due to reading the information leaflet was analyzed. RESULTS: 40% of the participants read the information leaflet. 87% mothers and 13% fathers participated in the follow-up survey. 10% of the post-survey respondents had a secondary school diploma and 34% had a university degree. After reading, fever was considered useful significantly more often and febrile convulsions and consequential damage were mentioned significantly less often as a reason for fever reduction. CONCLUSION: Information leaflets on fever can be a complementary tool for education, the short-term effect is confirmed, the sustainability needs to be further evaluated. There is also a need to reach the majority.

Media Awareness and Screen Time Reduction in Children, Youth or Families: A Systematic Literature Review.

Excessive use of screen media is a global public health issue and especially extensive screen exposure during very early childhood. This review was conducted in order to update previous reviews on the effectiveness of interventions to reduce screen time. An electronic literature search was carried out in MEDLINE, COCHRANE LIBRARY and CINAHL for articles indexed from June 2011 until October 2019. The search identified 933 publications of which 11 publications were included in this review. There are studies showing interventions with a positive influence on reduction of screen time and the participants' awareness and behavior concerning the use of screen media, as well as studies without such effects. No intervention was identified to be superior. This warrants further investigation of potentially effective combinations of intervention components and long-term follow-up.

Cyclically stretched ACL fibroblasts emigrating from spheroids adapt their cytoskeleton and ligament-related expression profile.

Mechanical stress of ligaments varies; hence, ligament fibroblasts must adapt their expression profile to novel mechanomilieus to ensure tissue resilience. Activation of the mechanoreceptors leads to a specific signal transduction, the so-called mechanotransduction. However, with regard to their natural three-dimensional (3D) microenvironment cell reaction to mechanical stimuli during emigrating from a 3D spheroid culture is still unclear. This study aims to provide a deeper understanding of the reaction profile of anterior cruciate ligament (ACL)-derived fibroblasts exposed to cyclic uniaxial strain in two-dimensional (2D) monolayer culture and during emigration from 3D spheroids with respect to cell survival, cell and cytoskeletal orientation, distribution, and expression profile. Monolayers and spheroids were cultured in crosslinked polydimethyl siloxane (PDMS) elastomeric chambers and uniaxially stretched (14% at 0.3 Hz) for 48 h. Cell vitality, their distribution, nuclear shape, stress fiber orientation, focal adhesions, proliferation, expression of ECM components such as sulfated glycosaminoglycans, collagen type I, decorin, tenascin C and cell-cell communication-related gap junctional connexin (CXN) 43, tendon-related markers Mohawk and tenomodulin (myodulin) were analyzed. In contrast to unstretched cells, stretched fibroblasts showed elongation of stress fibers, cell and cytoskeletal alignment perpendicular to strain direction, less rounded cell nuclei, increased numbers of focal adhesions, proliferation, amplified CXN43, and main ECM component expression in both cultures. The applied cyclic stretch protocol evoked an anabolic response and enhanced tendon-related marker expression in ACL-derived fibroblasts emigrating from 3D spheroids and seems also promising to support in future tissue formation in ACL scaffolds seeded in vitro with spheroids.

[The FeverApp Registry - A Way to Empower Parents through their Own Documentation to a Graduated Decision]. / Das FieberApp Register ­ ein Weg, um Eltern durch eigene Dokumentation zu einer abgestuften Entscheidung zu führen.

AIM OF THE STUDY: To demonstrate the feasibility and exemplarity of an app-based parent registry. METHODS: The app as an elaborated interactive electronic case report form and the underlying data structure of the registry are presented. The initial recruitment efforts are illustrated and the temperature distribution, as well as the distribution of fever events in 2020, are analyzed. RESULTS: The FeverApp successfully collects data into a central registry. Like every study, it also provides information on the current knowledge. The ecological momentary assessment can represent the illness situation at several levels (measurement, fever episode, individual, family, practice, country). Methods for data collection needed to be developed in a flexible manner due to pandemic conditions. The initial recruitment goal of 2400 fever phases in the first two years was met, with nationwide dissemination pending. It is shown that body temperature does not rise indefinitely; fevers reach an average of 39 degrees without antipyretics, although in rare cases temperatures beyond 41 degrees are reached without harm. Furthermore, a comparison with a reference practice shows that fever episodes can be recorded more comprehensively in the app, including infections that do not come to the presentation in a pediatrician's office. Thus, the FeverApp fulfills in a model-like fashion the use of registers in persons basically healthy and maps a multi-level diagnostics. CONCLUSION: The FeverApp could basically establish itself as a supporting tool, the registry can reliably collect data with the method used and maps the current infection situation. In researching the question of how infections develop in the post-Covid period, the app could perform an important task.

SV40 Transfected Human Anterior Cruciate Ligament Derived Ligamentocytes-Suitable as a Human in Vitro Model for Ligament Reconstruction?

Cultured human primary cells have a limited lifespan undergoing dedifferentiation or senescence. Anterior cruciate ligaments (ACL) are hypocellular but tissue engineering (TE) requires high cell numbers. Simian virus (SV) 40 tumor (T) antigen expression could extend the lifespan of cells. This study aimed to identify cellular changes induced by SV40 expression in human ACL ligamentocytes by comparing them with non-transfected ligamentocytes and tissue of the same donor to assess their applicability as TE model. Human ACL ligamentocytes (40-year-old female donor after ACL rupture) were either transfected with a SV40 plasmid or remained non-transfected (control) before monitored for SV40 expression, survival, and DNA content. Protein expression of cultured ligamentocytes was compared with the donor tissue. Ligamentocyte spheroids were seeded on scaffolds embroidered either from polylactic acid (PLA) threads solely or combined PLA and poly (L-lactide-co-ε-caprolactone) (P(LA-CL)) threads. These scaffolds were further functionalized with fluorination and fibrillated collagen foam. Cell distribution and survival were monitored for up to five weeks. The transfected cells expressed the SV40 antigen throughout the entire observation time, but often exhibited random and incomplete cell divisions with significantly more dying cells, significantly more DNA and more numerous nucleoli than controls. The expression profile of non-transfected and SV40-positive ligamentocytes was similar. In contrast to controls, SV40-positive cells formed larger spheroids, produced less vimentin and focal adhesions and died on the scaffolds after 21 d. Functionalized scaffolds supported human ligamentocyte growth. SV40 antigen expressing ligamentocytes share many properties with their non-transfected counterparts suggesting them as a model, however, applicability for TE is limited.

Human nasoseptal chondrocytes maintain their differentiated phenotype on PLLA scaffolds produced by thermally induced phase separation and supplemented with bioactive glass 1393.

Damage of hyaline cartilage such as nasoseptal cartilage requires proper reconstruction, which remains challenging due to its low intrinsic repair capacity. Implantation of autologous chondrocytes in combination with a biomimetic biomaterial represents a promising strategy to support cartilage repair. Despite so far mostly tested for bone tissue engineering, bioactive glass (BG) could exert stimulatory effects on chondrogenesis. The aim of this work was to produce and characterize composite porous poly(L-lactide) (PLLA)/1393BG scaffolds via thermally induced phase separation (TIPS) technique and assess their effects on chondrogenesis of nasoseptal chondrocytes. The PLLA scaffolds without or with 1, 2.5, 5% BG1393 were prepared via TIPS technique starting from a ternary solution (polymer/solvent/non-solvent) in a single step. Scaffolds were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetric analysis (DSC). Human nasoseptal chondrocytes were seeded on the scaffolds with 1 and 2.5% BG for 7 and 14 days and cell survival, attachment, morphology and expression of SOX9 and cartilage-specific extracellular cartilage matrix (ECM) components were monitored. The majority of chondrocytes survived on all PLLA scaffolds functionalized with BG for the whole culture period. Also inner parts of the scaffold were colonized by chondrocytes synthesizing an ECM which contained glycosaminoglycans. Type II collagen and aggrecan gene expression increased significantly in 1% BG scaffolds during the culture. Chondrocyte protein expression for cartilage ECM proteins indicated that the chondrocytes maintained their differentiated phenotype in the scaffolds. BG could serve as a cytocompatible basis for future scaffold composites for osteochondral cartilage defect repair. Abbreviations: AB: alcian blue ACAN: gene coding for aggrecan; BG: Bioactive glass; 2D: two-dimensional; 3D: three-dimensional; COL2A1: gene coding for type II collagen; DAPI: 4',6-diamidino-2-phenylindole; DMEM: Dulbecco's Modified Eagle's Medium; DMMB: dimethylmethylene blue; DSC: Differential scanning calorimetric analysis; ECM: extracellular matrix; EDTA: ethylenediaminetetraacetic acid; EtBr: ethidium bromide; FCS: fetal calf serum; FDA: fluorescein diacetate; GAG: glycosaminoglycans; HDPE: high density polyethylene; HE: hematoxylin and eosin staining; HCA: hydoxylapatite; PBE: phosphate buffered EDTA100 mM Na2HPO4 and 5 mM EDTA, pH8; PBS: phosphate buffered saline; PFA: paraformaldehyde; PG: proteoglycans; PI: propidium iodide; PLLA: Poly-L-Lactic Acid Scaffold; RT: room temperature; SD: standard deviation; SEM: scanning electron microscopy; sGAG: sulfated glycosaminoglycans; SOX9/Sox9: SRY (sex-determining region Y)-box 9 protein; TBS: TRIS buffered saline; TIPS: Thermally Induced Phase Separation; XRD: X-ray diffraction analysis.

Migrating Myofibroblastic Iliotibial Band-Derived Fibroblasts Represent a Promising Cell Source for Ligament Reconstruction.

The iliotibial band (ITB) is a suitable scaffold for anterior cruciate ligament (ACL) reconstruction, providing a sufficient mechanical resistance to loading. Hence, ITB-derived fibroblasts attract interest for ligament tissue engineering but have so far not been characterized. This present study aimed at characterizing ITB fibroblasts before, during, and after emigration from cadaveric ITB explants to decipher the emigration behavior and to utilize their migratory capacity for seeding biomaterials. ITB and, for comparison, ACL tissues were assessed for the content of alpha smooth muscle actin (αSMA) expressing fibroblasts and degeneration. The cell survival and αSMA expression were monitored in explants used for cell isolation, monolayer, self-assembled ITB spheroids, and spheroids seeded in polyglycolic acid (PGA) scaffolds. The protein expression profile of targets typically expressed by ligamentocytes (collagen types I-III, elastin, lubricin, decorin, aggrecan, fibronectin, tenascin C, CD44, ß1-integrins, vimentin, F-actin, αSMA, and vascular endothelial growth factor A [VEGFA]) was compared between ITB and ACL fibroblasts. A donor- and age-dependent differing percentage of αSMA positive cells could be detected, which was similar in ITB and ACL tissues despite the grade of degeneration being significantly higher in the ACL due to harvesting them from OA knees. ITB fibroblasts survived for several months in an explant culture, continuously forming monolayers with VEGFA and an increased αSMA expression. They shared their expression profile with ACL fibroblasts. αSMA decreased during the monolayer to spheroid/scaffold transition. Using self-assembled spheroids, the migratory capacity of reversible myofibroblastic ITB cells can be utilized for colonizing biomaterials for ACL tissue engineering and to support ligament healing.

IL-10 Could Play a Role in the Interrelation between Diabetes Mellitus and Osteoarthritis.

The association between osteoarthritis (OA), obesity and metabolic syndrome suggests an interrelation between OA and diabetes mellitus (DM). Little is known about the role of anti-inflammatory cytokine interleukin (IL)-10 in the interrelation between OA and DM. Hence, the effects of IL-10 under hyperglycemia (HG) and hyperinsulinemia (HI) in human articular chondrocytes (hAC) and chondrosarcoma cell line Okayama University Medical School (OUMS)-27 were examined. HAC and OUMS-27, cultured in normoglycemic (NG) and HG conditions were stimulated with insulin and/or IL-10. Cell survival, metabolic activity, proliferation and extracellular matrix (ECM) synthesis were immunocytochemically examined. No significant differences in vitality of hAC neither in pure NG (NGw/o) nor HG (HGw/o) conditions were found. Applying HI and/or IL-10 in both conditions reduced significantly the vitality of hAC but not of OUMS-27. HG impaired significantly hAC metabolism. When combined with HI + IL-10 or IL-10 alone it decreased also significantly hAC proliferation compared to NGw/o. In OUMS-27 it induced only a trend of impaired proliferation compared to NGw/o. hAC but not OUMS-27 reduced significantly their collagen type (col) I, SOX9 and proteoglycan (PG) synthesis in HG combined with HI +/- IL-10 compared to NGw/o. IL-10 could not moderate HI and HG effects. In contrast to hAC OUMS-27 showed limited sensitivity as DM model.

The distribution patterns of COMP and matrilin-3 in septal, alar and triangular cartilages of the human nose.

The biomechanical characteristics of septal cartilage depend strongly on the distinct extracellular matrix of cartilage tissue; therefore, it is essential that the components of this matrix are identified and understood. Cartilage oligomeric matrix protein (COMP) and matrilin-3 are localised in articular cartilage. This study was the first to examine all subtypes of mature human nasal cartilages (alar, triangular and septal) with specific attention to the distribution of COMP and matrilin-3. Three whole fresh-frozen noses from human donors were dissected, and exemplary biopsies were examined using histochemical staining (haematoxylin and eosin and Alcian blue) and immunohistochemistry (collagen II, COMP and matrilin-3). The following three zones within the nasal cartilage were identified: superficial, intermediate and central. COMP was detected as highest in the intermediate zones in all three subtypes of nasal cartilage, whereas matrilin-3 was detected with pericellular deposition mainly within septal cartilage predominantly in the superficial zones. The distinct staining patterns of COMP and matrilin-3 underscore the different functional roles of both proteins in nasal cartilage. According to the literature, COMP might be involved with collagen II in the formation of networks, whereas matrilin-3 is reported to prevent ossification or regulate mechanosensitivity. The predominant staining observed in septal cartilage suggests matrilin-3's modulatory role because of its presence in the osteochondral junctional zone and given that the biomechanical load in septal cartilage is different from that in alar or triangular cartilage. In conclusion, COMP and matrilin-3 were detected in mature human nasal cartilage but displayed different staining patterns that might be explained by the functional roles of the respective matrix protein; however, further research is necessary to identify and define the functional aspects of this morphological difference.

The interrelation of osteoarthritis and diabetes mellitus: considering the potential role of interleukin-10 and in vitro models for further analysis.

INTRODUCTION: Today, not only the existence of an interrelation between obesity/adipositas and osteoarthritis (OA) but also the association of OA and diabetes mellitus (DM) are widely recognized. Nevertheless, shared influence factors facilitating OA development in DM patients still remain speculative up until now. To supplement the analysis of clinical data, appropriate in vitro models could help to identify shared pathogenetic pathways. Informative in vitro studies could later be complemented by in vivo data obtained from suitable animal models. MATERIALS AND METHODS: Therefore, this detailed review of available literature was undertaken to discuss and compare the results of currently published in vitro studies focusing on the interrelation between OA, the metabolic syndrome and DM and to propose models to further study the molecular pathways. RESULTS: The survey of literature presented here supports the hypothesis that the pathogenesis of OA in DM is based on imbalanced molecular pathways with a putative crucial role of antiinflammatory cytokines such as IL-10. CONCLUSION: Future development of versatile micro-scaled in vitro models such as combining DM and OA on chip could allow the identification of common pathogenetic pathways and might help to develop novel therapeutic strategies.

Laser surface modification of decellularized extracellular cartilage matrix for cartilage tissue engineering.

The implantation of autologous cartilage as the gold standard operative procedure for the reconstruction of cartilage defects in the head and neck region unfortunately implicates a variety of negative effects at the donor site. Tissue-engineered cartilage appears to be a promising alternative. However, due to the complex requirements, the optimal material is yet to be determined. As demonstrated previously, decellularized porcine cartilage (DECM) might be a good option to engineer vital cartilage. As the dense structure of DECM limits cellular infiltration, we investigated surface modifications of the scaffolds by carbon dioxide (CO2) and Er:YAG laser application to facilitate the migration of chondrocytes inside the scaffold. After laser treatment, the scaffolds were seeded with human nasal septal chondrocytes and analyzed with respect to cell migration and formation of new extracellular matrix proteins. Histology, immunohistochemistry, SEM, and TEM examination revealed an increase of the scaffolds' surface area with proliferation of cell numbers on the scaffolds for both laser types. The lack of cytotoxic effects was demonstrated by standard cytotoxicity testing. However, a thermal denaturation area seemed to hinder the migration of the chondrocytes inside the scaffolds, even more so after CO2 laser treatment. Therefore, the Er:YAG laser seemed to be better suitable. Further modifications of the laser adjustments or the use of alternative laser systems might be advantageous for surface enlargement and to facilitate migration of chondrocytes into the scaffold in one step.

Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option.

Re-irradiation has been shown to be a meaningful option for recurrent high-grade glioma (HGG) patients. Furthermore, bevacizumab exerts certain activity in combination with chemotherapy/as monotherapy and was safely tested in combination with radiotherapy in several previous studies. To our knowledge, this is the largest cohort of patients treated with both re-irradiation and bevacizumab to date. After receiving standard radiotherapy (with or without TMZ) patients with recurrent HGG were treated with bevacizumab (10 mg/kg intravenously at d1 and d15) during re-irradiation. Median prescribed radiation dose during re-treatment was 36 Gy, conventionally fractionated. Datasets of 71 re-irradiated patients were retrospectively analyzed. Patients either received bevacizumab (N = 57) or not (N = 14; other substances (N = 4) and sole radiation (N = 10)). In patients receiving bevacizumab, both post-recurrence survival (PRS) (median 8.6 vs. 5.7 months; p = 0.003, log-rank test) and post-recurrence progression-free survival (PR-PFS, 5.6 vs. 2.5 months; p = 0.005, log-rank test; PFS-6 42.1 % for the bevacizumab group) were significantly increased which was confirmed by multivariate analysis. KPS, re-surgery, MGMT methylation status, sex, WHO grade, tumor volume and age were no significant predictors for neither PR-PFS nor PRS (univariate analysis). Re-irradiation with bevacizumab remains a feasible and highly effective treatment schedule. Studies on further salvage strategies and timing of sequential treatment options versus observation are warranted.

Biocompatibility evaluation of densified bacterial nanocellulose hydrogel as an implant material for auricular cartilage regeneration.

Bacterial nanocellulose (BNC), synthesized by the bacterium Gluconacetobacter xylinus, is composed of highly hydrated fibrils (99 % water) with high mechanical strength. These exceptional material properties make BNC a novel biomaterial for many potential medical and tissue engineering applications. Recently, BNC with cellulose content of 15 % has been proposed as an implant material for auricular cartilage replacement, since it matches the mechanical requirements of human auricular cartilage. This study investigates the biocompatibility of BNC with increased cellulose content (17 %) to evaluate its response in vitro and in vivo. Cylindrical BNC structures (Ø48 × 20 mm) were produced, purified in a built-in house perfusion system, and compressed to increase the cellulose content in BNC hydrogels. The reduction of endotoxicity of the material was quantified by bacterial endotoxin analysis throughout the purification process. Afterward, the biocompatibility of the purified BNC hydrogels with cellulose content of 17 % was assessed in vitro and in vivo, according to standards set forth in ISO 10993. The endotoxin content in non-purified BNC (2,390 endotoxin units (EU)/ml) was reduced to 0.10 EU/ml after the purification process, level well below the endotoxin threshold set for medical devices. Furthermore, the biocompatibility tests demonstrated that densified BNC hydrogels are non-cytotoxic and cause a minimal foreign body response. In support with our previous findings, this study concludes that BNC with increased cellulose content of 17 % is a promising non-resorbable biomaterial for auricular cartilage tissue engineering, due to its similarity with auricular cartilage in terms of mechanical strength and host tissue response.

[18F]fluoroethyltyrosine-positron emission tomography-based therapy monitoring after stereotactic iodine-125 brachytherapy in patients with recurrent high-grade glioma.

Therapy monitoring of glioma after stereotactic iodine-125 brachytherapy (SBT) remains challenging because posttherapeutic changes in magnetic resonance imaging can mimic tumor progression. We evaluated the prognostic value of serial [18F]fluoroethyltyrosine (FET)-positron emission tomographic (PET) scans for therapy monitoring of high-grade glioma (HGG) after SBT. Thirty-three patients with recurrent HGG were included. Serial FET-PET scans were performed prior to therapeutic intervention and at 3-month intervals during the first year after SBT. FET-PET evaluation was performed by both conventional data analysis and kinetic analysis. Prognostic factors were obtained from proportional hazard models. Median local progression-free survival (LPFS) was 11.1 months. Maximal standardized background uptake value (SUVmax/BG) and biologic tumor volume (BTV) differentiated accurately between therapeutic effects and local tumor progression at the 6-month and subsequent examinations. Increasing uptake kinetics at baseline (p < .05) and during follow-up (p < .01) were stringently associated with a longer LPFS. Early increase in FET uptake after SBT is not unequivocally associated with tumor progression; it might be induced by reactive changes and could easily lead to a misclassification of the tumor status (pseudoprogression). Six months after SBT (or later), however, increased SUVmax/BG and BTV values are associated with a worse prognosis. Multivariate analysis stresses the prognostic importance of dynamic studies.

Reliability of Data Collected via Ecological Momentary Assessment on the Example of FeverApp Registry.

The FeverApp registry is an ambulant ecological momentary assessment (EMA) model registry focusing on research of fever in children. Verification of EMA reliability is a challenge, due to absence of other source data. To ensure the reliability of EMA data, 973 families were invited to reassess their documentation in a survey. The survey contained questions (a) regarding the number of children, (b) genuineness of entries, (c) completeness of submitted fever episodes, (d) medication, (e) usefulness and further usage of the app. Of those invited, 438 families (45% response rate) participated in the survey. Of these, 363 (83%) families have registered all their children, 208 families have one child. The majority (n = 325, 74.2%) of families stated that they only made genuine entries in the app. Agreement between survey and app for fever episodes is 90% (Cohen's κ = 0.75 [0.66, 0.82]). Medication shows 73.7% agreement, κ = 0.49 [0.42; 0.54]. The majority (n = 245, 55.9%) consider the app as an additional benefit and 87.3% would like to use it further. Email surveys are a possible approach to evaluate EMA based registry data. The possible observation units (children and fever episodes) show an adequate reliability. With this approach, surveys of further samples and variables could help to improve the quality of EMA based registries.

Children's Symptoms with a Febrile Illness and a Positive or Negative Test of SARS-CoV-2 during the Omicron Wave.

Febrile infections are common in childhood. Children can be infected with SARS-CoV-2, but their course is milder than in adults. So far, a comparison between febrile infections with a positive or negative Corona test with the Omicron variant is missing. The data used are from the FeverApp registry, which collects parent-reported data on febrile infections in children and informs about fever management. A comparison of symptomatic differences between episodes with a positive or negative Corona test was performed using Χ2-tests. During the Omicron wave, reported tests doubled and positive test results nearly 12-folded. In episodes with positive Corona saliva tests, more cough, fatigue, disturbed smell/taste, limb pain, sore throat, signs of serious sickness, and touch sensitivity were reported. Children with a negative Corona test show more tonsillitis, teething, any pain symptoms, earaches, and rashes. Thus, there are some significant differences between febrile infections with a positive or negative Corona test, but symptoms are present on both sides. The omicron variant seems to be more infectious than the alpha or delta variants in children, but the symptoms remain mild and do not differ much from other febrile infections.

Predictors of sustained use of mobile health applications: Content analysis of user perspectives from a fever management app.

Objectives: Mobile health applications could be means of educating and changing behaviours of their users. Their features and qualities determine the sustainability of use. The FeverApp with two main features of information and documentation is a research-based app. In this observational cohort study, to evaluate the influential predictors of use, users' feedback on the FeverApp, were analyzed. Methods: Feedback is given using a structured questionnaire, four Likert items and two open questions regarding positive and negative impressions, available via app menu. Conventional content analysis (inductive approach) on the two open questions was performed. Comments were grouped into 12 codes. These codes were grouped hierarchically in an iterative process into nine subcategories and lastly into two main categories 'format' and 'content'. Descriptive and quantitative analysis were performed. Results: Out of 8243 users, 1804 of them answered the feedback questionnaire. The features of the app (N = 344), followed by the information aspect (N = 330) were most frequently mentioned. Documentation process (N = 226), request for new features or improvement of the current ones (N = 193), and functioning (N = 132) were also highlighted in users' feedback. App's ease of use, design and being informative were important for the users. The first impression of the app seems important as the majority of feedback were given during the first month of using the app. Conclusion: In-app feedback function could highlight shortcomings and strengths of mobile health apps. Taking users' feedback into consideration could increase the chance of sustained use. Besides ease of use and clear, likeable designs, users want apps that serve their needs while saving time.

Re-irradiation in recurrent malignant glioma: prognostic value of [18F]FET-PET.

The aim of the present study is to determine new positron emission tomography (PET) imaging-related factors predictive of progression-free survival as well as survival in patients with recurrent malignant glioma (MG) prior to and after re-irradiation. Fifty-six patients with recurrent MG who underwent re-irradiation treatment and pretherapeutic dynamic [(18)F]-fluoroethyl-L-tyrosine (FET)-PET scan were retrospectively analyzed. The prognostic value of different parameters, such as biological tumor volume, maximal tumor uptake (SUV(max)/BG), mean tumor uptake (SUV(mean)/BG), as well as uptake kinetics, was evaluated. [(18)F]FET uptake kinetics was classified according to a five-point rating as category G(1-2) (strongly/mainly increasing kinetics), G(3) (mixed 1:1), or G(4-5) (mainly/strongly decreasing kinetics). Patients within the pretherapeutic kinetic group G(4-5) had significantly worse survival than the other two groups (p = 0.01). Multivariate analysis revealed that histologic grade, Karnofsky Performance Score (KPS), and kinetic group were independent significant predictors for survival after re-irradiation. The uptake kinetics of [(18)F]FET-PET is an independent determinant of overall and to a lesser extent also progression-free survival. Thus, [(18)F]FET-PET kinetics may provide valuable additional prognostic information for treatment decisions.

Parental Confidence in Relation to Antipyretic Use, Warning Signs, Symptoms and Well-Being in Fever Management-Results from an App-Based Registry.

Parents' confidence regarding their children's fever is a key factor in its management and there is still unnecessary anxiety and associated antipyretic overuse. The FeverApp application collects naturalistic real-time data on febrile infections and educates parents on fever management. Logistic regression examined the associations between (1) parental confidence and (2) antipyretics use with fever relevant parameters. First entry data of 3721 children (mean age 21 months; SD 22.97) was assessed. A total of 58.0% of parents felt confident upon first fever documentation. Warning signs [OR = 0.49, 95% CI: 0.40-0.61], dehydration [OR = 0.65, 95% CI: 0.52-0.81], fever [OR = 0.67, 95% CI: 0.57-0.80] and having a female child [OR = 0.77, 95% CI: 0.66-0.90] had the highest negative association with parental confidence. Antipyretics were used initially in 14.7% of children. Fever had the highest positive [OR = 2.58, 95% CI: 1.89-3.50] and well-being the highest negative association with antipyretic use [OR = 0.37, 95% CI: 0.22-0.63). In the first entry data, parental confidence was related to children's health condition in a reasonable medical manner. The use of antipyretics was mostly associated with febrile temperature, but also low well-being. Thus, associations were partly in accordance with recent guidelines.