How professional and academic pre-qualifications relate to success in medical education: Results of a multicentre study in Germany.

OBJECTIVE: Every year, many applicants want to study medicine. Appropriate selection procedures are needed to identify suitable candidates for the demanding curriculum. Although research on medical school admissions has shown good predictive validity for cognitive selection methods (undergraduate GPA, aptitude tests), the literature on applicants with professional and/or academic experience prior to entering medical school remains slim. In our study, we therefore aimed to examine the association between academic success in medical school and having previously completed vocational training in the medical field, voluntary service (≥11 months) or an academic degree. METHODS: Data were collected in a multicentre, cross-sectional study at five medical schools in Germany (Baden-Wuerttemberg) from students during medical school (i.e. 3rd-, 6th-, and 10th-semester and final-year students). Academic success was assessed according to scores on the first and second state examinations, the total number of examinations repeated and the number of semesters beyond the standard period of study. For the analysis we calculated ordinal logistic regression models for each outcome variable of academic success. RESULTS: A total of N = 2,370 participants (response rate: RR = 47%) participated in the study. Having completed vocational training was associated with a higher amount of repeated examinations (small effect), while having an academic degree was associated with worse scores on the second state examination (medium effect). No significant association emerged between voluntary service and academic success. CONCLUSION: The results indicate that professional and academic pre-qualifications pose no advantage for academic success. Possible associations with the financing of study and living conditions of students with pre-qualifications were analysed and discussed in an exploratory manner. However, the operationalisation of academic success from objective and cognitive data should be critically discussed, as the benefits of prior experience may be captured by personal qualities rather than examination results.

SIESTA: a quick interprofessional learning activity fostering collaboration and communication between paediatric nursing trainees and medical students.

BACKGROUND: Interprofessional education has emerged as a key concept in education of health professionals over the last 20 years. Positive effects of interprofessional education have been shown, but it has proved to be more time-consuming than traditional teaching methods. We therefore developed a 30-minute interprofessional learning activity, using peer-teaching methods. We were interested in effects on and ways of interprofessional learning, including conditions and resources that make it successful despite limited time. METHODS: Speed InterprofESsional Peer Teaching PaediAtric (SIESTA) was developed in the context of an interprofessional training ward. 20 paediatric nursing trainees and 20 medical students were enrolled in the study. Two students from each profession participated in a total of four SIESTA sessions each, supervised by registered paediatric nurses and paediatricians. We used a mixed-methods approach of quantitative and qualitative data (questionnaires, semi-guided focus group interviews) to evaluate self-perceived interprofessional competencies, interprofessional learning gains and ways of interprofessional learning. RESULTS: Questionnaires were obtained from all participants (n = 40) and n = 26 took part in the group interviews. Participants from both professions reported an increase in self-perceived understanding of interprofessional roles and tasks. Communication and cooperation emerged as important aspects. The workplace-based nature of SIESTA promoted interprofessional learning, while peer teaching fostered a safe learning environment. Regarding time constraints participants suggested thorough preparation and structuring by facilitators as a solution. CONCLUSIONS: Our short interprofessional peer teaching activity showed promising results. Participants reported enhanced interprofessional competencies and provided suggestions for successful learning in limited time. Further studies should include an objective assessment of the interprofessional learning progress. The SIESTA concept can be easily adapted to other medical fields, providing interprofessional learning opportunities for many more health care professionals to come.

Cystic fibrosis in disguise - the wolf in sheep's clothing, a case report.

BACKGROUND: Childhood hypoglycemia in combination with hepatomegaly is suspicious for inborn errors of metabolism. Cystic fibrosis typically presents with failure to thrive, pulmonary and gastrointestinal symptoms. Hepatic involvement and hypoglycemia can occur in a significant number of patients, although hepatomegaly is uncommon. CASE PRESENTATION: A 28 months old boy was presented with recurrent upper airways infections, progressive lethargy and weight loss. Clinically hepatomegaly was the main presenting feature and hypoglycemia (minimum 1.4 mmol/l) was noted as were elevated transaminases. The patient did not produce enough sweat to analyze it. Infectious causes for hepatitis were excluded and a broad metabolic work-up initiated. A therapy with starch was initiated to control hypoglycemia. In further course loose stools were reported and pancreatic elastase was found to be reduced. A further sweat test yielded pathological chloride concentration and genetic testing confirmed the diagnosis of cystic fibrosis. CONCLUSIONS: Cystic fibrosis is a systemic disease and less common presentations need to be considered. Even in the age of CF-newborn screening in many countries CF needs to be ruled out in typical and atypical clinical presentations and diagnostics need to be repeated if inconclusive.

Pulmonary granulomatosis of genetic origin.

Granulomatous inflammation of the lung can be a manifestation of different conditions and can be caused by endogenous inflammation or external triggers. A multitude of different genetic mutations can either predispose patients to infections with granuloma-forming pathogens or cause autoinflammatory disorders, both leading to the phenotype of pulmonary granulomatosis. Based on a detailed patient history, physical examination and a diagnostic approach including laboratory workup, pulmonary function tests (PFTs), computed tomography (CT) scans, bronchoscopy with bronchoalveolar lavage (BAL), lung biopsies and specialised microbiological and immunological diagnostics, a correct diagnosis of an underlying cause of pulmonary granulomatosis of genetic origin can be made and appropriate therapy can be initiated. Depending on the underlying disorder, treatment approaches can include antimicrobial therapy, immunosuppression and even haematopoietic stem cell transplantation (HSCT). Patients with immunodeficiencies and autoinflammatory conditions are at the highest risk of developing pulmonary granulomatosis of genetic origin. Here we provide a review on these disorders and discuss pathogenesis, clinical presentation, diagnostic approach and treatment.

Interactive, case-based seminars in the digitized pediatrics block internship from the students' perspective.

We report on the pediatric block practice digitized due to the COVID-19 pandemic. Nineteen seminars were recorded, which represent the broad spectrum of pediatrics as comprehensively as possible, and made available on the learning platform ILIAS in a learning sequence. In order to increase attention and learning success formative questions were interspersed into the seminars. The evaluation of the students showed a high acceptance of this course. Especially the formative questions and the high time flexibility were appreciated. A major point of criticism was that not all questions were resolved immediately afterwards. The resolutions were inserted in the meantime. Parts of the digitized block practical course should therefore be used in the pediatric block practical course after the end of the corona restrictions after appropriate revision.

Nursing staff's and physicians' acquisition of competences and attitudes to interprofessional education and interprofessional collaboration in pediatrics.

BACKGROUND: Interprofessional education (IPE) is deemed essential for interprofessional collaboration (IPC) in healthcare systems. IPC has positive effects for both patients and healthcare professionals. Especially in pediatrics, IPC is paramount for adequate care of patients and their families though there is a lack of data on the attitudes towards IPE and IPC and acquisition of respective competences in pediatric nursing and medical staff. METHODS: Frequencies of interactions and attitudes towards IPE and IPC, with a focus on acquisition of competences for IPE and IPC, of nurses (N = 79) and physicians (N = 70) in a large pediatric university hospital were evaluated with an online questionnaire. RESULTS: All participants worked as part of interprofessional teams, mostly consisting of nurses and physicians. The majority (94.9% (n = 75) of nurses and 100% (n = 70) of physicians) highly valued IPC. Medical doctors acquired most competences important for IPC during day-to-day work and reported a substantial lack of IPE. Nursing staff on the other hand did report significant interprofessional education during their training as well as ongoing interprofessional learning during day-to-day work. Nurses also appreciated IPE more. CONCLUSIONS: Even though IPC is commonly reported in nurses and physicians working at a large pediatric university hospital there is a lack of structured IPE. A focus should be on IPE for nurses and physicians to enable them to effectively collaborate together. Political and local initiatives for IPE are gaining momentum but still need to be established nationally and internationally.

Non-CF Bronchiectasis as a Possible Indicator of a Primary Immunodeficiency: Diagnosis, Clinical Course, and Quality of Life in a Pediatric Cohort.

BACKGROUND: Non cystic fibrosis bronchiectasis (NCBE) is an increasingly recognized chronic, progressive respiratory disorder with significant morbidity also in children and adolescents. METHODS: We longitudinally assessed a cohort of 35 pediatric patients with NCBE and investigated underlying diagnosis, symptoms, clinical course, treatment, and quality of life. RESULTS: NCBE were diagnosed at a mean age of 9.5 (±5.3) years. In half of the children NCBE were found prior to identification of the causative diagnosis. Primary immunodeficiency (PID) was identified as the underlying diagnosis in 24/35 (68%) cases, of which two-thirds showed antibody deficiency. In the 11 non-PID cases ciliopathies were most common (n=7). Clinical aspects such as manifestation age, cough or dyspnea symptoms, and exacerbation frequency did not differ significantly between PID and non-PID patients. Likewise, quality of life (QoL) was equally reduced in both groups. Lung function test parameters were stable under appropriate therapy in all children. The majority in both groups was insufficiently vaccinated against influenza and pneumococci. CONCLUSION: Our data indicates that NCBE need to be especially appreciated as a presenting sign of PID in pediatric patients. Thus, occurrence of NCBE should warrant rigorous diagnostics to identify the underlying condition. In our cohort NCBE themselves rather than the causative diagnoses seem to dictate the clinical course of disease and reduce QoL in children. More intensive efforts have to be undertaken to vaccinate patients according to recommendations.

Student-perceived exam difficulty may trump the effects of different quality improvement measures regarding the students' evaluation of a pediatric lecture series.

BACKGROUND: Lectures are still an important part of today's medical education at many medical schools. The pediatric lecture series at the Center for Pediatrics, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany had been evaluated poorly in recent terms. METHODS: To improve lecture quality and possibly evaluation results a combination of measures consisting of peer lecturer coaching, use of an audience response system, in depth analysis of the end of term evaluation results and changes to the exam itself were implemented. RESULTS: Peer lecturer coaching was performed successfully and both the audience response system evaluation as well as the end of term evaluation results improved significantly in the following term. Analysis of the students' comments revealed more approval of lecture content and presentation after the organization of the lecture series was changed towards less lecturers and focus on less topics. Student-perceived high exam difficulty influenced the evaluation negatively. CONCLUSION: The student-perceived exam difficulty can supersede the effects of different measures to improve lecture quality measured via evaluation. Whether better evaluation of the lecture series after different improvement measures was due to better match of the curriculum with the exam content or that an improved curriculum led to better exam performance remains to be elucidated.

Nocturnal asthma is affected by genetic interactions between RORA and NPSR1.

BACKGROUND: Neuropeptide S Receptor 1 ( NPSR1) and Retinoid Acid Receptor-Related Orphan Receptor Alpha (RORA ) interact biologically, are both known candidate genes for asthma, and are involved in controlling circadian rhythm. Thus, we assessed (1) whether interactions between RORA and NPSR1 specifically affect the nocturnal asthma phenotype and (2) how this may differ from other asthma phenotypes. METHODS: Interaction effects between 24 single-nucleotide polymorphisms (SNPs) in RORA and 35 SNPs in NPSR1 on asthma and nocturnal asthma symptoms were determined in 1432 subjects (763 asthmatics [192 with nocturnal asthma symptoms]; 669 controls) from the Multicenter Asthma Genetic in Childhood/International Study of Asthma and Allergies in Childhood studies. The results were validated and extended in children from the Manchester Asthma and Allergy Study (N = 723) and the Children Allergy Milieu Stockholm and Epidemiological cohort (N = 1646). RESULTS: RORA* NPSR1 interactions seemed to affect both asthma and nocturnal asthma. In stratified analyses, however, interactions mainly affected nocturnal asthma and less so asthma without nocturnal symptoms or asthma severity. Results were replicated in two independent cohorts and seemed to remain constant over time throughout youth. CONCLUSION: RORA* NPSR1 interactions appear to be involved in mechanisms specific for nocturnal asthma. In contrast to previous studies focusing on the role of beta 2 receptor polymorphisms in nocturnal asthma as a feature of asthma control or severity in general, our data suggest that changes in circadian rhythm control are associated with nighttime asthma symptoms.

Efficacy, Safety, and Quality of Life in a Multicenter, Randomized, Placebo-Controlled Trial of Low-Dose Peanut Oral Immunotherapy in Children with Peanut Allergy.

BACKGROUND: Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published. OBJECTIVE: We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial. METHODS: A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT. RESULTS: Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL; 86% of children evaluated the BOT positively. DISCUSSION: Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development.

Work-Time Distribution of Physicians at a German University Hospital.

BACKGROUND: The effective utilization of staff resources is of decisive importance for the adequate, appropriate, and economical delivery of hospital services. The goal of this study was to determine the distribution of working time among doctors in a German university hospital-in particular, in terms of type of activities and time of day. METHODS: The distribution of working time was determined from 14-day samples taken in seven clinical departments of the Medical Center-University of Freiburg. In each 14-day sample, the activities being carried out at multiple, randomly chosen times were recorded. RESULTS: A total of 250 doctors (participation rate: 83%) took part in the study. A total of 20 715 hours of working time was analyzed, representing twelve years of full-time employment. Overall, 46% of working time in the inpatient sector was spent in direct contact with patients, with relevant differences among the participating clinical departments: for instance, the percentage of time taken up by patient contact was 35% in pediatrics and 60% in oral and maxillofacial surgery. Patient contact was highest (over 50% overall) in the period 8 a.m. to 12 noon. CONCLUSION: The amount of working time taken up by activities other than direct patient contact was found to be lower than in previous studies. It remains unclear what distribution of working time is best for patient care and whether it would be possible or desirable to increase the time that doctors spend in direct contact with patients.

A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma.

IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (ß = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.

Reduced PRF1 enhancer methylation in children with a history of severe RSV bronchiolitis in infancy: an association study.

BACKGROUND: Acute lower respiratory tract infection is the commonest disease affecting children under five worldwide. Respiratory syncytial virus (RSV) is among the most common causative pathogens. Epidemiological data suggest an association between severe viral respiratory infections in infancy and increased incidence of childhood wheeze and asthma. DNA methylation is involved in immune cell differentiation and identity. It provides an avenue for environmental influences on the genome and therefore has potential as a marker for sustained effects of infectious insults. In this study we investigated the association between DNA methylation patterns in the perforin gene (PRF1) in childhood and a history of hospitalisation for severe RSV disease in the first two years of life. METHODS: In this retrospective study, we explored patterns of whole blood DNA methylation at a methylation sensitive region of the proximal PRF1 enhancer in a group of children with a record of hospitalisation for severe RSV disease during infancy (n = 43) compared to healthy controls matched for age and sex with no similar hospitalisation history, no allergy and no persistent wheeze (n = 43). Univariate and bivariate conditional logistic regression analyses were conducted to test the association between PRF1 enhancer methylation and record of hospitalisation for RSV disease. RESULTS: Children with a record of hospitalisation for severe RSV bronchiolitis demonstrated markedly lower levels of DNA methylation at two cytosine-phosphate-guanine dinucleotide (CpG) loci of the PRF1 proximal enhancer, corresponding to a signal transducer and activator of transcription 5 (STAT5) responsive element, compared to controls, adjusted odds ratios of 0.82 (95% confidence interval [CI] 0.71, 0.94) and 0.73 (95% CI 0.58, 0.92) for each 1% increase in DNA methylation. Smoking in the household showed a significant influence on DNA methylation at the assayed positions. CONCLUSIONS: Our findings support an association between childhood DNA methylation patterns in PRF1 and a record of severe RSV infection in infancy. Longitudinal studies are required to establish the utility of PRF1 methylation as a marker of severe RSV disease.

Self-perceived attitudes toward interprofessional collaboration and interprofessional education among different health care professionals in pediatrics.

Interprofessional education (IPE) is the basis for interprofessional collaboration (IPC) in health care systems. It has beneficial effects for both patients and health care professionals. IPC is paramount for adequate care of patients and their families, especially in pediatrics. To determine the attitudes of medical doctors (n=121), nurses (n=15), psychologists (n=14), and social workers (n=19) toward IPE and IPC in a tertiary pediatric university teaching hospital, as well as the inpatient and outpatient settings in pediatrics, we developed a questionnaire with 21 items in four categories based on established questionnaires. All participants worked as part of interprofessional teams, and the overwhelming majority valued IPC highly. Most competencies important for IPC were acquired on the job. There was a substantial lack of interprofessional education, especially for medical doctors and psychologists. IPE still needs to be established as part of the undergraduate curriculum at German universities.

Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages.

BACKGROUND: Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. OBJECTIVE: We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. METHODS: Interactions between sex and polymorphisms on childhood asthma risk were evaluated in the Multicentre Asthma Genetics in Childhood Study (MAGICS)/Phase II International Study of Asthma and Allergies in Childhood (ISAAC II) population on a genome-wide level, and findings were validated in independent populations. Genetic fine mapping of sex-specific asthma association signals was performed, and putatively causal polymorphisms were characterized in vitro by using electrophoretic mobility shift and luciferase activity assays. Gene and protein expression of the identified gene doublesex and mab-3 related transcription factor 1 (DMRT1) were measured in different human tissues by using quantitative real-time PCR and immunohistochemistry. RESULTS: Polymorphisms in the testis-associated gene DMRT1 displayed interactions with sex on asthma status in a population of primarily clinically defined asthmatic children and nonasthmatic control subjects (lowest P = 5.21 × 10(-6)). Replication of this interaction was successful in 2 childhood populations clinically assessed for asthma but showed heterogeneous results in other population-based samples. Polymorphism rs3812523 located in the putative DMRT1 promoter was associated with allele-specific changes in transcription factor binding and promoter activity in vitro. DMRT1 expression was observed not only in the testis but also in lung macrophages. CONCLUSION: DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation.

Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.