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.
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.
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.
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.
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.
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.
Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to ...xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan. To test this idea, we experimentally increased resistance of Drosophila to the xenobiotic dichlordiphenyltrichlorethan (DDT), by artificial selection or by transgenic expression of a gene encoding a cytochrome P450. Although both interventions increased DDT resistance, neither increased lifespan. Furthermore, dietary restriction increased lifespan without increasing xenobiotic resistance, confirming that the two traits can be uncoupled. Reduced activity of the insulin/Igf signaling (IIS) pathway increases resistance to xenobiotics and extends lifespan in Drosophila, and can also increase longevity in C. elegans, mice, and possibly humans. We identified a nuclear hormone receptor, DHR96, as an essential mediator of the increased xenobiotic resistance of IIS mutant flies. However, the IIS mutants remained long-lived in the absence of DHR96 and the xenobiotic resistance that it conferred. Thus, in Drosophila IIS mutants, increased xenobiotic resistance and enhanced longevity are not causally connected. The frequent co-occurrence of the two traits may instead have evolved because, in nature, lowered IIS can signal the presence of pathogens. It will be important to determine whether enhanced xenobiotic metabolism is also a correlated, rather than a causal, trait in long-lived mice.
BackgroundComplex treatment, care and rehabilitation require continuous healthcare professional development and maintenance of competencies in collaboration with other professionals. ...Interprofessional education in childhood cancer involves several groups of healthcare professionals with both general and specific knowledge and skills.ObjectiveTo establish consensus on content and interprofessional learning objectives for an interprofessional education in childhood cancer.DesignA three-round Delphi survey in Scandinavian childhood cancer departments.ParticipantsHealthcare professionals appointed by their head of departments and head nurses based on their profession and their involvement in continuing professional development.Main outcome measuresA prioritised list of interprofessional learning objectives with a mean score of ≥3 on a five-point scale (1=not relevant, 5=extremely relevant).Results12 childhood cancer departments participated with 30 healthcare professionals: 11 nurses, 10 medical doctors, 5 social workers, 2 physiotherapists and 2 pedagogues. In total, 28 (93%), 25 (83%) and 22 (73%) completed the first, second and third round, respectively. In the first round, we asked open-ended questions and used directed content analysis to analyse 386 statements. We formulated 170 interprofessional learning objectives in six categories: (1) acute life-threatening situations, (2) gastrointestinal toxicities and side effects, (3) pain, (4) palliation, (5) play and activity, and (6) prescription and administration of medicine. The second round resulted in 168 interprofessional learning objectives receiving a mean score of ≥3 on a five-point scale. Final agreement in the third round resulted in a prioritised list of 168 learning objectives.ConclusionsConsensus on content and interprofessional learning objectives for an interprofessional education in childhood cancer was established across five groups of healthcare professionals in three countries. Some learning objectives are generic and can be applied in settings other than childhood cancer, where healthcare professionals collaborate to provide patients and families optimal treatment and care.
Health during aging can be improved by genetic, dietary and pharmacological interventions. Many of these increase resistance to various stressors, including xenobiotics. Up-regulation of xenobiotic ...detoxification genes is a transcriptomic signature shared by long-lived nematodes, flies and mice, suggesting that protection of cells from toxicity of xenobiotics may contribute to longevity. Expression of genes involved in xenobiotic detoxification is controlled by evolutionarily conserved transcriptional regulators. Three closely related subgroups of nuclear hormone receptors (NHRs) have a major role, and these include DAF-12 and NHR-8 in C. elegans, DHR96 in Drosophila and FXR, LXRs, PXR, CAR and VDR in mammals. In the invertebrates, these NHRs have been experimentally demonstrated to play a role in extension of lifespan by genetic and environmental interventions. NHRs represent critical hubs in that they regulate detoxification enzymes with broad substrate specificities, metabolizing both endo- and xeno-biotics. They also modulate homeostasis of steroid hormones and other endogenous cholesterol derivatives and lipid metabolism, and these roles, as well as xenobiotic detoxification, may contribute to the effects of NHRs on lifespan and health during aging, an issue that is being increasingly addressed in C. elegans and Drosophila. Disentangling the contribution of these processes to longevity will require more precise understanding of the molecular mechanisms by which each is effected, including identification of ligands and co-regulators of NHRs, patterns of tissue-specificity and mechanisms of interaction between tissues. The roles of vertebrate NHRs in determination of health during aging and lifespan have yet to be investigated.
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.
In 2020, a 2-month-old ethnically Danish girl was diagnosed with β-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.In 2020, a 2-month-old ethnically Danish girl was diagnosed with β-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.
Summary
The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is less known. This study ...aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH. We conducted a multicentre retrospective and prospective study that included 33 haemophilia centres from 20 countries. Inclusion criteria were children and adolescents born between 1993 and 2014, with severe haemophilia A or B without inhibitors. Participants were categorized by prophylaxis regimen: full, partial or none, based on dose and dose frequency of regular infusions. The cohort study included 1515 children: 29 cases of ICH over 8038 patient years were reported. The incidence of ICH in the prophylaxis group, 0·00033 cases of ICH/patient year, was significantly lower compared to the no prophylaxis group, 0·017 cases of ICH/patient year (RR 50·06; P < 0·001) and the partial prophylaxis group, 0·0050 cases of ICH/patient year (RR 14·92; P = 0·007). In the on‐demand‐group, 8% (2/24) children with ICH died and 33% had long‐term sequelae, including intellectual and behavioural problems, paresis and epilepsy. Children on regular, frequent prophylaxis have a low risk of ICH compared to those using non‐frequent or no prophylaxis.
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