IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Added Value of [18F]PSMA-1007 PET/CT and PET/MRI in Patients With Biochemically Recurrent Prostate Cancer: Impact on Detection Rates and Clinical Management.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR). PURPOSE: To investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management. STUDY TYPE: Retrospective. SUBJECTS: 41 patients with BCR (median age [range]: 68 [55-78]). FIELD STRENGTH/SEQUENCE: 3T, including T1-weighted gradient echo (GRE), T2-weighted turbo spin echo (TSE) and dynamic contrast-enhanced GRE sequences, diffusion-weighted echo-planar imaging, and a T1-weighted TSE spine sequence. In addition to MRI, [18F]PSMA-1007 PET and low-dose CT were acquired on the same day. ASSESSMENT: Images were reported using a five-point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT. Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed. STATISTICAL TESTS: McNemar test, Cohen's κ, and intraclass correlation coefficients. A P-value <0.05 was considered significant. RESULTS: 7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients. DATA CONCLUSION: The addition of [18F]PSMA-1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Childhood and adolescence factors and multiple sclerosis: results from the German National Cohort (NAKO).

BACKGROUND: Multiple Sclerosis (MS) represents the most common inflammatory neurological disease causing disability in early adulthood. Childhood and adolescence factors might be of relevance in the development of MS. We aimed to investigate the association between various factors (e.g., prematurity, breastfeeding, daycare attendance, weight history) and MS risk. METHODS: Data from the baseline assessment of the German National Cohort (NAKO) were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between childhood and adolescence factors and risk of MS. Analyses stratified by sex were conducted. RESULTS: Among a total of 204,273 participants, 858 reported an MS diagnosis. Male sex was associated with a decreased MS risk (HR 0.48; 95% CI 0.41-0.56), while overweight (HR 2.03; 95% CI 1.41-2.94) and obesity (HR 1.89; 95% CI 1.02-3.48) at 18 years of age compared to normal weight were associated with increased MS risk. Having been breastfed for ≤ 4 months was associated with a decreased MS risk in men (HR 0.59; 95% CI 0.40-0.86) compared to no breastfeeding. No association with MS risk was observed for the remaining factors. CONCLUSIONS: Apart from overweight and obesity at the age of 18 years, we did not observe considerable associations with MS risk. The proportion of cases that can be explained by childhood and adolescence factors examined in this study was low. Further investigations of the association between the onset of overweight and obesity in childhood and adolescence and its interaction with physical activity and MS risk seem worthwhile.

Evaluation of a Multimodal Stress Management and Comprehensive Lifestyle Modification Program on Quality of Life and Gastrointestinal Symptoms in Patients with Crohn's Disease: A Randomized Controlled Pilot Trial with 9-Month Follow-Up.

INTRODUCTION: Stress and lifestyle factors impact the course of Crohn's disease (CD). Our primary objective was to assess whether patients with CD benefit from a mind-body-medicine stress management and lifestyle modification (MBM) program. METHODS: This 9-month two-arm pilot trial was conducted in Bamberg, Germany (2020-2021). Patients (18-75 years) with mild to moderate activity of CD and stable medication were enrolled and randomly assigned to either a 10-week MBM program (intervention group, IG) or a single 90-min education session (waiting list control group, CG). Primary endpoints were quality of life (IBDQ) and disease activity (HBI). Secondary endpoints were emotional distress, core self-evaluation, and inflammatory biomarkers 3 and 9 months after baseline assessment. RESULTS: We analyzed data from 37 patients (IG: n = 19, mean ± SD age 49.6 ± 13.1 years, 68% female; CG: 18, 46.8 ± 11.4, 67% female). Immediately after the intervention, 79% (IG) and 44% (CG) experienced a clinically relevant improvement (IBDQ score ≥16 points). This was similar after 9 months (63% vs. 44%). There was no difference in disease activity (3 months: p = 0.082, 95% CI -1.3 to 2.6; 9 months: p = 0.251, 95% CI -1.2 to 2.5). Secondary outcomes indicated improvements in emotional distress, core self-evaluation, erythrocyte sedimentation rate after three and in emotional distress, T-cell profiling in the blood, and fecal lactoferrin and calprotectin group after 9 months in the IG. CONCLUSION: Our study suggested benefits of a multimodal stress management and lifestyle modification program for patients with CD. Larger trials are needed to determine if the program can supplement or at least partially replace pharmacological treatment approaches.

Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS­CoV­2 infection: an analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort.

PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free. METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled ≥ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free. RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection. CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.

Grip strength values and cut-off points based on over 200,000 adults of the German National Cohort - a comparison to the EWGSOP2 cut-off points.

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies. OBJECTIVE: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample. METHODS: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality. RESULTS: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality. CONCLUSIONS: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed.

Past attachment experiences, the potential link of mentalization and the transmission of behavior to the child by mothers with mental health problems: cross-sectional analysis of a clinical sample.

Maternal capacity to mentalize (= reflective functioning, RF), secure attachment and emotionally available parenting has an impact on the child's development. The transmission of mothers' past attachment experiences gained with both her caregivers in her own childhood and the impact on current mother-child interaction is part of the 'transmission gap.' This study explores the transgenerational transmission mechanisms and the potential moderating effect of RF in a clinical sample of 113 mother-child dyads suffering from mental health problems. In a cross-sectional study, the associations between maternal attachment experiences, RF (coded based on Adult Attachment Interviews) and current mother-child interaction (Emotional Availability Scales) were examined with univariate correlation, moderator analyses, and structural equation models. We found relationships between attachment experiences and mother-child interaction, but RF had no moderating effect. Past loving experiences and perceived neglection, particularly with the own father in childhood, were predictors for the present mother-child interaction. There seems to be an intergenerational transmission of attachment experiences to the ongoing generation. Particularly past adverse childhood experiences with the own father seem to explain currently disruptive interactions with the child.Trial registration: DRKS00017008 and DRKS00016353.

Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy.

BACKGROUND: A genetic defect in the epidermal barrier protein filaggrin (FLG) plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in FLG contribute to the development and persistence of food allergies. OBJECTIVES: This study tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. METHODS: This study recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the 4 most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as the control population. RESULTS: FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. CONCLUSIONS: Using the gold standard for food allergy diagnosis, this study demonstrates that FLG LOF mutations confer a risk of any food allergy independent of eczema. These mutations predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.

[How Common are Complementary Medicine Procedures in Bavarian Acute Care Hospitals? Results of A Bavarian-wide Website Screening]. / Wie verbreitet sind komplementärmedizinische Verfahren in bayerischen Krankenhäusern? Eine Vollerhebung für Bayern mittels Website-Screening.

BACKGROUND: In Germany, complementary medicine is used by up to 62% of patients, but type and extent of in-patient complementary care are not known. The objective of this study was, therefore, to conduct a survey on complementary medicine procedures in Bavarian acute care hospitals by screening the websites of all respective facilities in order to cover a broad range of complementary procedures. METHODS: In 2020, an independent and comprehensive website screening of all 389 Bavarian acute hospitals, including all departments, was conducted by two independent raters. Complementary medicine procedures offered were analysed in total as well as separately by specialty. RESULTS: Among all 389 Bavarian acute care hospitals, 82% offered at least one and 66% at least three different complementary procedures on their website. Relaxation techniques (52%), acupuncture (44%), massage (41%), movement-, art-, and music therapy (33%, 30%, and 28%), meditative movement therapies like yoga (30%), and aromatherapy (29%) were offered most frequently. Separated by specialty, complementary procedures were most common in psychiatry/psychosomatics (relaxation techniques 69%, movement and art therapy 60% each) at 87%, and in gynaecology/obstetrics (most common acupuncture 64%, homeopathy 60%, and aromatherapy 41%) at 72%. CONCLUSION: The vast majority of Bavarian acute care hospitals also seem to conduct complementary medicine procedures in therapy, especially for psychological indications and in obstetrics and gynaecology, according to the hospital websites. How often these procedures are used in inpatient or outpatient settings as well as evidence on effectiveness of the applied procedures should be investigated in further studies.

[Bavarian online database for corona screening tests-development and use of a digital solution in the pandemic]. / Bayerisches Meldeportal für Corona-Reihenuntersuchungen ­ Entwicklung und Einsatz einer digitalen Lösung in der Pandemie.

During the SARS-CoV­2 pandemic, various data had to be collected to support political decisions for pandemic preparedness and response. Nevertheless, using analogue tools like paper and pencil as well as sending files with media discontinuity that have to be merged later are not useful and can hardly provide usable data in real time. With the selected system architecture, the Bavarian Online Database for Corona Screening Tests (BayCoRei) is a central, Bavaria-wide, consistent digital solution that is agile and easy to use. BayCoRei uses established technical components and interfaces. Apart from this, the support of the individual stakeholders (e.g., health authorities, service providers, and district governments) plays a decisive role in the success of the solution. The present article describes BayCoRei and two other online databases as examples that comprise the technology and architecture that have proven to be (rapidly) deployable and points out the gap between intention and reality regarding pandemic management.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

A singleplex IgE test to a mixture of molecules from multiple airborne allergen sources: Innovating in vitro screening of respiratory allergies.

BACKGROUND: In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. TARGET: To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (µl) of serum. METHODS: We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank-order correlation coefficient and Bland-Altmann plots. RESULTS: The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE-Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p < .001), (rho 0.87, p < .001), (rho 0.84, p < .001), respectively. The novel molecular SX01 test detected IgE-Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. DISCUSSION: Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1.

Der p 23-specific IgE response throughout childhood and its association with allergic disease: A birth cohort study.

BACKGROUND: The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross-sectional studies. We longitudinally analysed the trajectory of Der p 23-specific IgE antibody (sIgE) levels throughout childhood and youth, their early-life determinants and their clinical relevance for allergic rhinitis and asthma. METHODS: We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. RESULTS: Der p 23-sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23-sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. CONCLUSIONS: Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23-sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.

Framework and baseline examination of the German National Cohort (NAKO).

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.

Development and evaluation of a patient education programme for children, adolescents, and young adults with differences of sex development (DSD) and their parents: study protocol of Empower-DSD.

BACKGROUND: Differences in sexual development (DSD) are rare diseases, which affect the chromosomal, anatomical or gonadal sex differentiation. Although patient education is recommended as essential in a holistic care approach, standardised programmes are still lacking. The present protocol describes the aims, study design and methods of the Empower-DSD project, which developed an age-adapted multidisciplinary education programme to improve the diagnosis-specific knowledge, skills and empowerment of patients and their parents. METHODS: The new patient education programme was developed for children, adolescents and young adults with congenital adrenal hyperplasia, Turner syndrome, Klinefelter syndrome or XX-/or XY-DSD and their parents. The quantitative and qualitative evaluation methods include standardised questionnaires, semi-structured interviews, and participatory observation. The main outcomes (assessed three and six months after the end of the programme) are health-related quality of life, disease burden, coping, and diagnosis-specific knowledge. The qualitative evaluation examines individual expectations and perceptions of the programme. The results of the quantitative and qualitative evaluation will be triangulated. DISCUSSION: The study Empower-DSD was designed to reduce knowledge gaps regarding the feasibility, acceptance and effects of standardised patient education programmes for children and youth with DSD and their parents. A modular structured patient education programme with four generic and three diagnosis-specific modules based on the ModuS concept previously established for other chronic diseases was developed. The topics, learning objectives and recommended teaching methods are summarised in the structured curricula, one for each diagnosis and age group. At five study centres, 56 trainers were qualified for the implementation of the training programmes. A total of 336 subjects have been already enrolled in the study. The recruitment will go on until August 2022, the last follow-up survey is scheduled for February 2023. The results will help improve multidisciplinary and integrated care for children and youth with DSD and their families. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00023096 . Registered 8 October 2020 - Retrospectively registered.

Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

BACKGROUND: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children. METHODS: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. RESULTS: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors. CONCLUSION: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies.

Efficacy of parent-infant psychotherapy compared to care as usual in children with regulatory disorders in clinical and outpatient settings: study protocol of a randomised controlled trial as part of the SKKIPPI project.

BACKGROUND: The first years of life are a significant period for child development, when children are particularly sensitive and prone to crises. This early phase lays the foundation for healthy growth. Clinical assessment of psychological symptoms in early infancy and adequate treatment are both important in improving the diagnostic outcome and preventing later long-term developmental consequences. The most common psychological problems in the first 3 years of life are regulatory disorders. The aim of this trial is to investigate the efficacy of Parent-Infant Psychotherapy (PIP) for infants and young children (aged 0-36 months, diagnosed with at least one regulatory disorder) and their mothers, compared to care as usual (CAU). METHODS: In this open multicentre randomised controlled trial, 160 mother-infant dyads are randomised to receive PIP or CAU for 6 weeks of intervention in clinical or outpatient (including home treatment) settings. The primary outcome is the maternal sensitivity (sensitivity scale of the Emotional Availability Scales (EAS)) after 6 weeks. Secondary outcomes include assessment of interaction, mental health problems, attachment, development, psychological factors, treatment adherence, health care system utilisation, and costs, after 6 weeks and 12 months. DISCUSSION: This study will evaluate whether a manualised focus-based short-term psychodynamic psychotherapeutic intervention in mother-child dyads improves the care situation for families of children diagnosed with regulatory disorders, and helps prevent long-term psychopathologies. Assessment of the intervention in different settings will support the development of more tailored interventions for affected infants and their mothers. TRIAL REGISTRATION: German Clinical Trial Register, ID: DRKS00017008 . Registered 03/20/2019.

Self-reported health and life satisfaction in older emergency department patients: sociodemographic, disease-related and care-specific associated factors.

BACKGROUND: Self-reported health (SRH) and life satisfaction (LS) are patient-reported outcomes (PROs) that independently predict mortality and morbidity in older adults. Emergency department (ED) visits due to serious health problems or accidents might pose critical life events for patients. This study aimed (a) to characterize older patients' SRH and LS during the distinct event of an ED stay, and (b) to analyze concomitant associations of PROs with ED patients' sociodemographic, disease-specific and care-related variables. METHODS: Study personnel recruited mostly older ED patients from three disease groups during a two-year period (2017-2019) in eight EDs in central Berlin, Germany, in the context of the health services research network EMANet. Cross-sectional data from the baseline patient survey and associated secondary data from hospital information systems were analyzed. Multilevel linear regression models with random intercept were applied to assess concomitant associations with SRH (scale: 0 (worst) to 100 (best)) and LS (scale: 0 (not at all satisfied) to 10 (completely satisfied)) as outcomes, including sensitivity analyses. RESULTS: The final sample comprised N = 1435 participants. Mean age was 65.18 (SD: 16.72) and 50.9% were male. Mean ratings of SRH were 50.10 (SD: 23.62) while mean LS scores amounted to 7.15 (SD: 2.50). Better SRH and higher LS were found in patients with cardiac symptoms (SRH: ß = 4.35, p = .036; LS: ß = 0.53, p = .006). Worse SRH and lower LS were associated with being in need of nursing care (SRH: ß = - 7.52, p < .001; LS: ß = - 0.59, p = .003) and being unemployed (SRH: ß = - 8.54, p = .002; LS: ß = - 1.27, p < .001). Sex, age, number of close social contacts, and hospital stays in the previous 6 months were additionally related to the outcomes. Sensitivity analyses largely supported results of the main sample. CONCLUSIONS: SRH and LS were associated with different sociodemographic and disease-related variables in older ED patients. Nursing care dependency and unemployment emerged as significant factors relating to both outcomes. Being able to identify especially vulnerable patients in the ED setting might facilitate patient-centered care and prevent negative health outcomes. However, further longitudinal research needs to analyze trajectories in both outcomes and suitable intervention possibilities in the ED setting. TRIAL REGISTRATION: EMANet sub-studies were registered separately: German Clinical Trials Register (EMAAge: DRKS00014273, registration date: May 16, 2018; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00014273; EMACROSS: DRKS00011930, registration date: April 25, 2017; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011930); ClinicalTrials.gov (EMASPOT: NCT03188861, registration date: June 16, 2017; https://clinicaltrials.gov/ct2/show/NCT03188861?term=NCT03188861&draw=2&rank=1).

State-level trends in sudden unexpected infant death and immunization in the United States: an ecological study.

BACKGROUND: Sudden unexpected infant death (SUID) continues to be a major contributor to infant mortality in the United States. The objective was to analyze time trends in SUID and their association with immunization coverage. METHODS: The number of deaths and live births per year and per state (1992-2015) was obtained from the Centers for Disease Control and Prevention (CDC). We calculated infant mortality rates (i.e., deaths below one year of age) per 1000 live births for SUID. We obtained data on immunization in children aged 19-35 months with three doses or more of diphtheria-tetanus-pertussis (3+ DTP), polio (3+ Polio), and Haemophilus influenzae type b (3+ Hib) as well as four doses or more of DTP (4+ DTP) from the National Immunization Survey, and data on infant sleep position from the Pregnancy Risk Assessment Monitoring System (PRAMS) Study. Data on poverty and race were derived from the Current Population and American Community Surveys of the U.S. Census Bureau. We calculated mean SUID mortality rates with 95% confidence interval (CI) as well as the annual percentage change using breakpoint analysis. We used Poisson regression with random effects to examine the dependence of SUID rates on immunization coverage, adjusting for sleep position and poverty (1996-2015). In a second model, we additionally adjusted for race (2000-2015). RESULTS: Overall, SUID mortality decreased in the United States. The mean annual percent change was - 9.6 (95% CI = - 10.5, - 8.6) between 1992 and 1996, and - 0.3 (95% CI = - 0.4, - 0.1) from 1996 onwards. The adjusted rate ratios for SUID mortality were 0.91 (95% CI = 0.80, 1.03) per 10% increase for 3+ DTP, 0.88 (95% CI = 0.83, 0.95) for 4+ DTP, 1.00 (95% CI = 0.90, 1.10) for 3+ polio, and 0.95 (95% CI = 0.89, 1.02) for 3+ Hib. After additionally adjusting for race, the rate ratios were 0.76 (95% CI = 0.67, 0.85) for 3+ DTP, 0.83 (95% CI = 0.78, 0.89) for 4+ DTP, 0.81 (95% CI = 0.73, 0.90) for 3+ polio, and 0.94 (95% CI = 0.88, 1.00) for 3+ Hib. CONCLUSIONS: SUID mortality is decreasing, and inversely related to immunization coverage. However, since 1996, the decline has slowed down.