SLC6A1 variant pathogenicity, molecular function and phenotype: a genetic and clinical analysis.

Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains 1, 6 and extracellular loop 4 (EL4) were enriched for patient over population variants. Across functionally tested missense variants (n = 156), the spatial proximity from the ligand was associated with loss-of-function in the GAT1 transporter activity. For variants with complete loss of in vitro GABA uptake, we found a 4.6-fold enrichment in patients having severe disease versus non-severe disease (P = 2.9 × 10-3, 95% confidence interval: 1.5-15.3). In summary, we delineated associations between the 3D structure and variant pathogenicity, variant function and phenotype in SLC6A1-related disorders. This knowledge supports biology-informed variant interpretation and research on GAT1 function. All our data can be interactively explored in the SLC6A1 portal (https://slc6a1-portal.broadinstitute.org/).

Exploring formal and informal learning opportunities during morning report: a qualitative study.

BACKGROUND: Morning reports are an essential component of physicians' daily work. Attending morning reports is prioritized by junior doctors as it provides them with an opportunity to learn diagnostic reasoning through discussion of cases. While teaching formats during morning reports have previously been reported, an in-depth analysis of what learning opportunities exist, e.g., how teaching is enacted during morning reports, is lacking. This qualitative study explores learning opportunities during morning reports. METHODS: We used an explorative design based on video-recordings of 23 morning reports from two surgical departments, an internal medicine department and an emergency department. We used thematic analysis combined with and inspired by Eraut's theoretical framework of workplace learning. RESULTS: Both formal and informal learning opportunities were identified. Formal learning opportunities had the character of planned teaching activities, and we identified four themes: (1) modes of teaching, (2) structure, (3) presenter role, and (4) participant involvement. Informal learning, on the other hand, was often implicit and reactive, while deliberate learning opportunities were rare. The data showed many missed opportunities for learning. CONCLUSION: Both formal and informal learning opportunities are present during morning reports. However, a prevalent focus on medical topics exists, leaving other important aspects of the medical role under-discussed. Pedagogical methods could be employed more optimally, and harnessing the potential of missed opportunities should be encouraged.

The Child Health System in Denmark: Current Problems and Successes.

In Denmark, child primary care is taken care of by general practitioners who have 6 months of pediatric training as part of their specialty training and, therefore, are qualified to work as gatekeepers for the secondary health care at the hospitals. As new, more expensive, drugs are increasingly prescribed, corresponding expenses pose serious threats to the economy at 18 pediatric departments. We will highlight the new developments in pediatric education: skills training and training of clinical reasoning.

Combining bimodal presentation schemes and buzz groups improves clinical reasoning and learning at morning report.

Morning reports offer opportunities for intensive work-based learning. In this controlled study, we measured learning processes and outcomes with the report of paediatric emergency room patients. Twelve specialists and 12 residents were randomised into four groups and discussed the same two paediatric cases. The groups differed in their presentation modality (verbal only vs. verbal + text) and the use of buzz groups (with vs. without). The verbal interactions were analysed for clinical reasoning processes. Perceptions of learning and judgment of learning were reported in a questionnaire. Diagnostic accuracy was assessed by a 20-item multiple-choice test. Combined bimodal presentation and buzz groups increased the odds ratio of clinical reasoning to occur in the discussion of cases by a factor of 1.90 (p = 0.013), indicating superior reasoning for buzz groups working with bimodal materials. For specialists, a positive effect of bimodal presentation was found on perceptions of learning (p < 0.05), and for residents, a positive effect of buzz groups was found on judgment of learning (p < 0.005). A positive effect of bimodal presentation on diagnostic accuracy was noted in the specialists (p < 0.05). Combined bimodal presentation and buzz group discussion of emergency cases improves clinicians' clinical reasoning and learning.

Use of patient video cases in medical education.

Patient video cases (PVCs) are brief video recordings of patients during spontaneous or instructed activity. PVCs are true to life and can be replayed, enabling the establishment of highly interactive, contextual and safe learning environments, with a minimum of facilitation. This article describes the use of workshops in which PVCs are used to assist with the development of observational skills and clinical reasoning in medical students and postgraduates. We describe why PVCs are a valuable addition to an educator's portfolio of resources, what evidence there is for their effectiveness, how to use videos for teaching, and some practical advice and tips on their collection and storage.

Arterial ischemic stroke as a complication to disseminated infection with Fusobacterium necrophorum.

Lemierre syndrome (LS) is a rare complication of oropharyngeal and odontogenic infections in otherwise healthy young individuals. It is characterized by septic internal jugular vein thrombophlebitis and disseminated metastatic abscesses. Cerebral arterial ischemic stroke is rarely seen in LS. The authors present a 14-year-old, previously healthy girl, who developed cerebral arterial infarction following acute tonsillitis and abscess formations due to Fusobacterium necrophorum.

Co-regulation of learning in a department of paediatrics.

INTRODUCTION: Co-regulated learning (CRL) is a process in which the learner's regulation of learning is guided by social transactions. The change in learning techniques during the transition from university to workplace learning and the rapidly changing learning environment make awareness of CRL extremely relevant. This study examined CRL among medical students and residents and identified the factors affecting CRL. METHODS: We applied an explorative approach using direct observation and semi-structured focus group discussions (FGD). The first author made direct observations that produced explorative data about actual behaviour. However, this was not sufficiently sensitive to capture the participants' full perceptions of CRL. Therefore, we conducted semi-structured FGD that involved interactions and reflections among the participants. RESULTS: This study suggests that CRL occurred in multiple situations and was affected by many factors. The stimulating factors identified were a supportive learning environment, feedback based on observations and questioning by a supervisor, dyad work and interactive, bimodal presentation of emergency cases at the morning conference. Time pressure, heavy workload and shortage of specialists were inhibiting factors. CONCLUSION: We identified several factors affecting CRL. A focus on the augmentation of stimulating factors and reduction of inhibiting factors may help medical students and residents develop CRL. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Splenic Abscess in an Adolescent due to Salmonella enterica Conservatively Treated with Ultrasound-Guided Fine-Needle Aspiration.

Background: Splenic abscesses are rare and potentially fatal. Diagnosis is often delayed due to vague symptoms, and laboratory findings are varying and often nonspecific. Ultrasound and computed tomography have a high sensitivity in detecting splenic abscesses. Splenectomy was previously considered the gold standard for treatment, but in recent years, a shift has been seen towards a more conservative approach, i.e., ultrasound-guided aspiration or drainage in combination with adequate antibiotics in selected cases. Case Report. A previously healthy adolescent complained of left-sided chest pain, pain in the left clavicular region for three weeks, and recent fever. Ultrasound and computed tomography demonstrated an intrasplenic abscess. The patient was successfully treated with two percutaneous fine-needle punctures and adequate antibiotics for six weeks. Salmonella enterica serotype Poona was grown from the aspirate. At one-year follow-up, the patient remained healthy without signs of recurrence. Conclusion: The present case report demonstrates that ultrasound-guided aspiration and subsequent treatment with antibiotics may be an effective alternative to splenectomy in patients with a splenic abscess.

How doctors build community and socialize into a clinical department through morning reports. A positioning theory study.

PHENOMENON: The morning report is one of the longest surviving hospital practices. Most studies of the morning report focus on the effectiveness of formal medical training, while focus on social and communicative aspects is rarer. This study explores the social interactions and communication in morning reports, examining the ways in which they contribute to the construction of professional identity and socialization into the community of the clinical department. APPROACH: We used a qualitative explorative design with video observations of morning reports. Our data consisted of 43 video-recorded observations (in all, 15.5 hours) from four different hospital departments in Denmark. These were analyzed using the theoretical framework of positioning theory. FINDINGS: A key finding was that each department followed its own individual structure. This order was not articulated as such but played out implictly. Two alternative storylines unfolded in the elements of the morning report: 1) being equal members of the specialty and department, and 2) preserving the hierarchical community and its inherent positions. INSIGHTS: The morning report can be seen as playing an important role in community making. It unfolds as a "dance" of repeated elements in a complex collegial space. Within this complexity, the morning report is a space for positioning oneself and others as a collegial "we", i.e., equal members of a department and specialty, at the same time as "having a place" in a hierarchal community. Thus, morning reports contribute to developing professional identity and socialization into the medical community.

Growth hormone treatment, final height, insulin-like growth factors, ghrelin, and adiponectin in four siblings with Seckel syndrome.

OBJECTIVE: To report on the effect of growth hormone (GH) treatment on final height (FH) and to describe the insulin-like growth factor (IGF) system, ghrelin, and adiponectin (ADPN) in children with Seckel syndrome. SUBJECTS AND RESULTS: Four severely growth-retarded Iraqi siblings (two girls and two boys) with Seckel syndrome were referred at ages 16.5, 14.4, 12.4, and 10.4 years. They were born at term, but their growth was retarded and birth weight ranged between 1 and 1.5 kg. The children were healthy and had a normal response to GH provocative test. Long-term GH treatment of the youngest brother and sister increased the FH by 7.2 and 3.4 cm, respectively, compared with their older brother and sister. At FH, body mass index standard deviation scores (BMISDS) ranged from -3.0 to -3.9. Serum levels of immunoreactive IGF-1, bioactive IGF-1, and IGF-binding protein 3 were all within normal to high range before GH treatment and increased after GH treatment. Fasting plasma ghrelin remained severely reduced. Despite low BMISDS, plasma ADPN was moderately reduced and showed an almost complete absence of the low-molecular-weight subform. CONCLUSION: This is the first report on the effect of GH treatment on FH in children with Seckel syndrome. GH may have increased FH. In addition to growth defects and reduced BMISDS, patients with Seckel syndrome are characterized by low fasting ghrelin levels, low total ADPN, and near deficiency of the low-molecular-weight ADPN subform. The possible significance of the hormonal changes requires further investigations.

[Functional disorders in previously healthy children during the COVID-19 pandemic].

Functional disorders may involve neurological symptoms, which are triggered by stressful situations. This case report describes two otherwise healthy children with sudden onset of functional symptoms in the days preceding the reopening of their schools after a suspension due to the COVID-19 pandemic outbreak. Little treatment was necessary, and both patients made fast recoveries. We correlate these symptoms with the stress associated with the COVID-19 pandemic and the suspension of normal education.

Identifying and prioritising technical procedures for simulation-based curriculum in paediatrics: a Delphi-based general needs assessment.

OBJECTIVES: To identify and prioritise technical procedures that should be integrated in a curriculum of simulation-based procedural training in paediatrics using the Delphi method. STUDY DESIGN: National general needs assessment using a Delphi process was completed among 93 key opinion leaders in paediatrics in Denmark. Delphi round 1 identified technical procedures. Round 2 explored frequency of procedures, number of paediatricians performing the procedures, risks and/or discomfort for patients and feasibility for simulation-based training. Round 3 included final elimination and reprioritisation. RESULTS: Response rates in the Delphi rounds were 73%, 71% and 72%. We identified 37 procedures in Delphi round 1, preprioritised in round 2, resulting in a final list of 19 procedures in round 3. Strong correlation between the prioritisation from the second and third Delphi rounds was identified, Spearman's r of 0.94 (p<0.0001). Top five on the final list were acute neonatal airway management, acute non-neonatal airway management, non-neonatal peripheral intravenous and intraosseous access, neonatal vascular access and advanced heart lung resuscitation. CONCLUSION: We identified and prioritised 19 technical procedures in paediatrics that are suitable for simulation and may be used as a guide for the development of simulation-based curriculum in paediatrics.

Selection and ranking of patient video cases in paediatric neurology in relation to learner levels.

BACKGROUND: Teaching and learning with patient video cases may add authenticity, enhance diagnostic accuracy and improve chances of early diagnosis. The aim of this study is firstly to identify selection criteria for key Patient video cases (PVCs), secondly to identify trends in relevance of PVCs for learner levels and thirdly, to rank PVCs for learner levels. METHODS: Based on a literature review, we identified criteria for key PVCs for use in paediatric neurology. We then performed a multi-round Delphi analysis to obtain agreement between 28 expert clinician teachers concerning key PVCs for four learner levels. RESULTS: We identified two major criteria: key PVCs should demonstrate key movements, and these movements should be subtle and/or difficult to note. The expert clinician teachers subsequently assessed a list of 14 topics for key PVCs. We found a clear, increasing trend in relevance scores, from medical students to young residents to experienced residents and specialists. For medical students and residents, epileptic spasms, Down syndrome, developmental delay, cerebral palsy and absence epilepsy were highly ranked. For specialists, conditions like chorea, focal seizures or eye movement disorders topped the ranking list, although ranking was less clear for this group of advanced learners. DISCUSSION AND CONCLUSION: Key PVCs should demonstrate movements that are difficult to note for learners. Ranked lists of key PVCs for teaching and learning at different learner levels are now available and may help institutions build validated local libraries of PVCs.

[Intervertebral discitis in children].

Intervertebral discitis is a rare disorder which is easily missed. It presents with non-specific symptoms such as irritability, abdominal pain, decreased appetite and limping. The infection parameters can be normal, and blood cultures are often negative. The pathogenesis is not established but infectious, and inflammatory aetiologies have been suggested. Diagnostic golden standard is magnetic resonance imaging. The treatment is immobilization, anti-inflammatory drugs and often antibiotics. Early treatment is important to reduce the risk of complications such as nerve damage and spine fusion.

[Arthrogryposis multiplex congenita]. / Arthrogryposis multiplex congenita

Arthrogryposis multiplex congenita (AMC) is a sign rather than a diagnosis. It implies contractures in multiple body areas and occurs in 1:3,000-5,000 live births. Primary aetiologies include neuropathic, myopathic, metabolic, end plate and vascular disorder affecting the developing foetus, including limitation of foetal space. Amyoplasia is the most common type of AMC after central nervous system disorders. Knowledge about the classification of AMC is essential to make a correct diagnosis and treatment plans. We recommend follow-up by experienced paediatric orthopaedic surgeons and neurologists.

[MR scanning of cerebrum in the investigation of delayed development in children. Syntelencephaly--is it really so rare?]. / MR-scanning af cerebrum i udredning af udviklingsforsinkelse hos børn. Syntelencefali--er det så sjaeldent endda?

A 14-month-old boy presented with a mild global developmental delay, plagiocephaly, and a mild mid-face dysmorphology, including hypertelorism. At 24 months of age, early signs of a spastic diplegic cerebral palsy were noted. MRI of the brain showed middle interhemispheric fusion: syntelencephaly.

[The 180 degree study is a simple examination of the motor development of infants]. / 180-gradersundersøgelsen er en enkel undersøgelse af spædbørns motoriske udvikling.

In this article we present The 180 degree study, a systematic and simple approach to examination of the motor development in infants aged 2-10 month. The examination is simple to learn, easy to practice and gives rich opportunity to generate diagnostic hypotheses.

[Multiple mini interviews before the occupation of main training posts in paediatrics]. / Multiple miniinterview før besættelse af pædiatriske hoveduddannelsesstillinger er gennemførlige.

Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.

Learning to diagnose using patient video case in paediatrics: perceptive and cognitive processes.

Thomas Balslev, a paediatric neurologist and educational researcher, defended his thesis on 24 November 2011. The thesis included five published papers, and investigated learning with authentic, brief patient video cases. With analysis of a video case in a small group, learning processes and sharing of knowledge was intensely stimulated. Small group discussion and subsequent listening to an expert's think-aloud were particularly effective approaches to enhance diagnostic accuracy among non-experts. In a descriptive study, expertise-related differences during analysis of patient video cases were characterized, and in a controlled study, different types of visual modelling were tested.

Visual expertise in paediatric neurology.

BACKGROUND: Visual expertise relies on perceptive as well as cognitive processes. At present, knowledge of these processes when diagnosing clinical cases mainly stems from studies with still pictures. In contrast, patient video cases constitute a dynamic diagnostic challenge that may simulate seeing and diagnosing a patient in person. AIMS: This study investigates visual attention and the concomitant cognitive processes of clinicians diagnosing authentic paediatric video cases. METHODS: A total of 43 clinicians with varying levels of expertise took part in this cross-sectional study. They diagnosed four brief video recordings of children: two with seizures and two with disorders imitating seizures. We used eye tracking to investigate time looking at relevant areas in the video cases and a concurrent think-aloud procedure to explore the associated clinical reasoning processes. RESULTS: More experienced clinicians were more accurate in visual diagnosis and spent more of their time looking at relevant areas. At the same time, they explored data less, yet they built and evaluated more diagnostic hypotheses. CONCLUSIONS: Clinicians of varying expertise analyse patient video cases differently. Clinical teachers should take these differences into account when optimising educational formats with patient video cases.