A Rare Case of De Novo Beta-Thalassemia Diagnosed by Whole-Genome Sequencing in an Ethnically Danish Newborn.

In 2020, a 2-month-old ethnically Danish girl was diagnosed with ß-thalassemia after presenting with persistent jaundice. The peripheral blood smear showed significant aniso- and poikilocytosis, increased number of reticulocytes and erythroblastosis. Trio analysis of the index patient and both parents was performed by whole-genome sequencing. Here, both parents were found normal, however the analysis revealed an apparently de novo HBB:c.444A > C variant in the child. The child has recently been discharged three months after a successful bone marrow transplantation with a matched sibling-donor.

DAHEAN: A Danish nationwide study ensuring quality assurance through real-world data for suspected hereditary anemia patients.

BACKGROUND: Hereditary anemias are a group of genetic diseases prevalent worldwide and pose a significant health burden on patients and societies. The clinical phenotype of hereditary anemias varies from compensated hemolysis to life-threatening anemia. They can be roughly categorized into three broad categories: hemoglobinopathies, membranopathies, and enzymopathies. Traditional therapeutic approaches like blood transfusions, iron chelation, and splenectomy are witnessing a paradigm shift with the advent of targeted treatments. However, access to these treatments remains limited due to lacking or imprecise diagnoses. The primary objective of the study is to establish accurate diagnoses for patients with hereditary anemias, enabling optimal management. As a secondary objective, the study aims to enhance our diagnostic capabilities. RESULTS: The DAHEAN study is a nationwide cohort study that collects advanced phenotypic and genotypic data from patients suspected of having hereditary anemias from all pediatric and hematological departments in Denmark. The study deliberates monthly by a multidisciplinary anemia board involving experts from across Denmark. So far, fifty-seven patients have been thoroughly evaluated, and several have been given diagnoses not before seen in Denmark. CONCLUSIONS: The DAHEAN study and infrastructure harness recent advancements in diagnostic tools to offer precise diagnoses and improved management strategies for patients with hereditary anemias.

A survey on thromboprophylaxis and coagulation assessment in children and young adults with acute lymphoblastic leukaemia (ALL) in the Nordic and Baltic countries: Different practices of assessment and management.

Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk of coagulopathy, especially thromboembolism. We conducted a survey on practices in the assessment and management of coagulopathy during the new ALLTogether protocol in 29 (17 paediatric, 12 adult) Nordic and Baltic cancer centres. While 92% of adult centres used thromboprophylaxis with low-molecular-weight heparin, no paediatric centre did. Almost all providers performed baseline coagulation studies, but only 59% continued the assessment. Fibrinogen replacement was conducted in 59%, and antithrombin replacement in 28% of the centres. The survey highlights the need for guidelines in the management of coagulopathy during ALL therapy.

Twelve tips for postgraduate interprofessional case-based learning.

Based on developing, implementing, and evaluating postgraduate interprofessional case-based learning, we have written these twelve tips for health education planners who wish to apply case-based learning in the clinical setting. Interprofessional case-based learning engages participants in a structured manner towards uncovering decisions processes and patterns of action that resemble the clinical reality in which various healthcare professionals handle multifaceted tasks related to the optimal patient treatment. Postgraduate interprofessional case-based learning has the potential to break down traditional hierarchical structures as interactions generate respectful behaviour. We present two models of case-based learning to assist in standardising, structuring, and systematising postgraduate interprofessional case-based learning. We have created 12 practical tips for the design, implementation, and evaluation of successful postgraduate interprofessional case-based learning integrated into the existing clinical setting.

Postgraduate Interprofessional Case-Based Learning in Childhood Cancer: A Feasibility Study.

This paper presents a feasibility study assessing the acceptability, demand, implementation, and practicality of postgraduate interprofessional case-based learning in childhood cancer at Copenhagen University Hospital-Rigshospitalet. Healthcare professionals included nurses, doctors, social workers, physiotherapists, occupational therapists, pharmacists, pharmacologists, dieticians, nursing assistants, and professionals with a supportive function (teachers, secretaries, priests, and daycare workers). All participated in a postgraduate interprofessional case-based learning session. Feasibility was assessed using Bowen's focus areas of acceptability, demand, implementation, and practicality. Before and after the intervention session, three measurement tools were used 2-3 weeks before participation and 3-4 weeks after participation to collect data: Assessment of Interprofessional Team Collaboration Scale, Readiness for Interprofessional Learning Scale, and Safety Attitudes Questionnaire. Representing 13 occupational groups, 49 participants completed the case-based learning sessions, indicating acceptability and practicality. The pre- and post-intervention questionnaires were completed by 79% of the participants, 88% of whom rated the professional content as good or very good. A change over time was detected on all three scales measuring mean difference post-intervention scores. The outcome measures can be used to assess the effect of the intervention. Postgraduate interprofessional case-based learning in childhood cancer is feasible in terms of acceptability, demand, implementation, and practicality. Implementation requires leadership commitment at all levels.

Flow cytometric analysis of cerebrospinal fluid improves detection of leukaemic blasts in infants with acute lymphoblastic leukaemia.

Infants with acute lymphoblastic leukaemia (ALL) have a high frequency of central nervous system (CNS) involvement. Flow cytometric analysis of cerebrospinal fluid (CSF) was recently demonstrated to be a sensitive method for detecting CNS involvement in childhood ALL. In the present study, CSF from 14 infants was collected at routine lumbar punctures and analysed by multicolour flow cytometry. At initial diagnosis, leukaemic blasts were detected in CSF by flow cytometry in 11 patients (78·6%) compared to seven patients (50%) by cytospin. Larger studies are needed to determine if CSF flow cytometry has prognostic value in infant ALL.

Aspergillus flavus Infections in Children With Leukemia Despite Liposomal Amphotericin-B Prophylaxis.

Liposomal amphotericin-B (L-AmB) prophylaxis is used in children with leukemia when azoles are contraindicated, but its effect is debated. We reviewed cases of invasive aspergillosis despite L-AmB 2.5 mg/kg twice weekly in children with high-risk leukemia during 2012-2019. Ten (16%) of 62 children had proven or probable aspergillosis. Thus, L-AmB prophylaxis offered insufficient protection for Aspergillus, in particular for Aspergillus flavus.

[Challenges and advances in paediatric arterial ischaemic stroke].

Neurological sequelae occur in more than 50% of children with arterial ischemic stroke. Early recognition and treatment are essential in improving outcome. However, diagnostic delay in paediatric stroke often extends beyond 24 hours, and children rarely access hyperacute recanalisation therapies. This review describes clinical presentations, risk factors and treatment of paediatric ischaemic stroke. Additionally, we share our experience from a systematic paediatric stroke pathway implemented in Eastern Denmark since 2017.

Interprofessional versus monoprofessional case-based learning in childhood cancer and the effect on healthcare professionals' knowledge and attitudes: study protocol for a randomised trial.

BACKGROUND: Interprofessional education in childhood cancer is a multifaceted field involving multiple healthcare professionals with general and specialised knowledge and skills. Complex treatment, care and rehabilitation require continuous professional development and maintenance of healthcare professionals' competencies in their field of expertise. However, limited knowledge exists in comparing interprofessional and monoprofessional education. Only a few randomised studies have evaluated the effectiveness and efficiency of interprofessional education. The objective of this single-centre, investigator-initiated cluster randomised trial is to study the effect of interprofessional versus monoprofessional case-based learning on healthcare professionals' knowledge of gastrointestinal side effects and attitudes towards team collaboration. METHODS: This study will randomise healthcare professionals to participate in either the experimental interprofessional group or the control monoprofessional group of case-based learning. The topic of the case-based intervention will be gastrointestinal side effects, one of six categories identified in a three-round Scandinavian Delphi study as relevant for interprofessional education in childhood cancer. The primary outcome is the self-reported questionnaire Assessment of Interprofessional Team Collaboration Scale. Secondary outcomes are measured by the self-reported questionnaires Readiness for Interprofessional Learning Scale Questionnaire, Safety Attitudes Questionnaire, and knowledge will be evaluated using a multiple-choice quiz. Participants will receive the self-reported questionnaires about 2 weeks before and 1 month after the intervention. On the day of the intervention, participants will answer a multiple-choice quiz before and after the case-based learning. Linear mixed models will be used to compare differences between the two groups in mean scores postintervention, adjusting for preintervention scores. DISCUSSION: This study will provide insight into the differences between interprofessional and monoprofessional case-based learning and how it affects healthcare professionals' knowledge of gastrointestinal side effects and attitudes towards team collaboration. TRIAL REGISTRATION: The intervention was registered at Clinical Trials.gov : NCT04204109 on December 102,019 and with the National Committee on Health Research Ethics: H-19087506 December 112,019 and the Danish Data Protection Agency: P-2019-637 October 152,019.