Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

<p>Abstract</p> <p>Background</p> <p>This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous <b>s</b>tomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.</p> <p>Methods</p> <p>A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.</p> <p>Results</p> <p>Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.</p> <p>Conclusions</p> <p>Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.</p

Pediatric Autoinflammatory Diseases: Conceptual, Clinical, and Mechanistic Dimensions

This thesis focuses on three paediatric autoinflammatory diseases in Sweden today; familial Mediterranean fever (FMF), periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO). In addition to describing autoinflammation with reference to these diseases, the thesis explores the concept of autoinflammatory disease by examining four existing definitions. A modified definition is then proposed in the light of this analysis. The aim of the first study (paper I) was to characterize FMF in western Sweden. Patients with autoinflammatory diseases were continuously registered at five hospitals and case records were analysed retrospectively. Population data on immigration were retrieved from Statistics Sweden. Thirty-seven patients with FMF were identified in the records from the years 2000 to 2008. For the majority of patients, disease onset occurred during childhood. In western Sweden, the prevalence of FMF among immigrants from the eastern Mediterranean Basin was of the same order as for their country of origin. The second and third study (papers II and III) aimed to advance the pathophysiological understanding of PFAPA, as an initial step towards identification of molecular and cellular mechanisms important in disease pathogenesis, as well as facilitating the definition of biomarkers. Levels of blood cells, serum cytokines and functional features of neutrophils were investigated during afebrile and febrile phases in children with typical PFAPA episodes. The results show oscillations in the concentration of blood cells between the afebrile and febrile phases of PFAPA. Upon onset of fever, there were modest levels of pro-inflammatory serum cytokines, together with increased levels of the IFN-γ-induced chemokine IP10/CXCL10. Further, neutrophils were analysed for functional features such as apoptosis, production of reactive oxygen species (ROS) and priming status (paper III). The results show that neutrophils from patients with PFAPA are primed, show decreased apoptosis and generate increased amounts of intracellular ROS during febrile attacks, whereas the afebrile phase was characterized by increased apoptosis. How these molecular and cellular features may affect disease pathogenesis is discussed in the thesis. The fourth study (paper IV) investigated whether deficiency in neutrophil intracellular production of NADPH-oxidase-derived ROS is a disease mechanism in SAPHO, as suggested in a previous case report. Cells from four patients with SAPHO showed normal production of ROS, both intracellularly and extracellularly, contradicting the previous finding and showing that the SAPHO syndrome is not necessarily associated with deficient neutrophil intracellular ROS production. This thesis gives new insights into a group of diseases that has been largely overlooked in the context of immune function, as each disease involves newly defined mechanisms important for innate immune regulation. The thesis also attempts to advance the definition of autoinflammatory diseases, complementing the previous definitions with the possible activation of the adaptive immune system and an association with other immune dysfunctions

Toward an Inclusive, Congruent, and Precise Definition of Autoinflammatory Diseases

Autoinflammatory disease was introduced as a concept in 1999, demarcating an entirely new group of diseases in clinical, immunological, and conceptual terms. During recent years, the preconditions for the definition of autoinflammatory conditions have changed. This includes the recent discovery of a number of monogenic autoinflammatory conditions with complex phenotypes that combine autoinflammation with defects of the adaptive and/or innate immune system, resulting in the occurrence of infection, autoimmunity, and/or uncontrolled hyperinflammation in addition to autoinflammation. Further, there are strong indications that classical IL-1-driven autoinflammatory diseases are associated with activation of adaptive immunity. As suggested by this development, we are of the opinion that an all-encompassing definition of autoinflammatory diseases should regard autoinflammatory conditions and innate dysregulation as inseparable and integral parts of the immune system as a whole. Hence, in this article, we try to advance the conceptual understanding of autoinflammatory disease by, proposing a modification of the definition by Daniel Kastner et al., which allows for a congruent and precise description of conditions that expand the immunological spectrum of autoinflammatory disease

Combining learning for educators and participants in a paediatric CPD programme

Abstract Background Most continuing professional development (CPD) programmes do not include an educational training module. In our country, educational practice in the areas of CPD and continuing medical education relies traditionally on conventional lectures. This is in sharp contrast to the educational research that clearly demonstrates that educational programmes emphasising adult learning methods have greater potential to change physicians’ clinical practice. To investigate whether lecture-oriented educators were prepared to change their educational practice towards principles of adult learning, we decided to combine learning for educators and participants in a paediatric CPD programme. The aim of the study was to investigate educators’ reflections on their learning and educational practice after they have undergone an educational skills component integrated in the implementation of a CPD learning module for paediatricians and evaluate the results from the participants’ perspective. Methods The objectives of the educational skills component of the learning module were developed according to adult learning theories. The learning objectives for the CPD learning module were based on a pre-course needs assessment. Evaluations were made using questionnaires. Results Seven of 10 participants in the educational skills component of the learning module and all the participants, 13 paediatricians and 14 nurses, who participated in the learning module, answered the questionnaires. The results of this pilot study show that educators whose main experience of teaching was based on lectures were strengthened in their practice; they defined their competence and were prepared to move towards adult learning principles. The participants in the learning module expressed a high degree of satisfaction. Conclusions We conclude that it is feasible to combine learning for educators and participants in a paediatric CPD programme and that lecture-oriented educators are prepared to change their educational practice towards principles of adult learning

Paediatric on-call consultants’ learning within and beyond the objectives of a coherent CPD program

Background: Evaluations, using questionnaires, of a two-year long CPD program for on-call consultant paediatricians, showed that the overall objective of the program was largely met. We stipulate that the coherency of the CPD program contributed to the learning. To gains a deeper understanding of the participants learning within and beyond the overall objectives of the program, we decided to conduct an interview study enrolling participants from the frst two CPD courses. Methods: Nine experienced paediatric consultants were interviewed 1-4 years after completing a coherent two-year long CPD program, focusing on what and how they learned. The interviews were audio-recorded and transcribed as text, analysed, and categorised using qualitative content analysis. Results: What the participants learned: improved medical competences, greater confdence in the role of an on-call consultant, better understanding of the role of an on-call consultant and importance of professional networks. Several categories were outside the overall objective, at personal level: an understanding of one’s own and other’s competences, taking responsibility for one’s own CPD and managing things one does not know. At professional level: more secure as an individual and with colleagues.How it was learned: relevant objectives, preparatory material and case discussions were important. Participants learned by preparing, repeating, refecting, and participating actively, and by applying what they learned in clinical practice. The participants learned from one other over a period of two years, when they also got to know one another and created networks. A safe learning environment imposed demands and enabled participants to defne their competence and learn accordingly. Conclusions: This study describes what and how on-call consultant paediatricians learned during a coherent two year long CPD program. The learning took place within and beyond the framework of the overall objectives. The study suggests that evaluation methods based on objectives may be blind to important areas of learning and need to be combined with qualitative methods that examine a broad impact of learning. Taken together, the analysis of what and how the participants learned shows that they were better equipped to work as consultant on call and deal with the things they did not know.FundingThis research received fnancial support from: The Healthcare Board Region Västra Götaland and the Projekt: Pediatric and Pedagogic Continuing Professional Development (CPD) for Paediatricians, funded by the Human Resources Sub-Committee, Region Västra Götaland.© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.</p

Using scenario-based training to promote information literacy among on-call consultant pediatricians

Background: Traditionally, teaching hospital staff to search for medical information relies heavily on educator-defined search methods. In contrast, the authors describe our experiences using real-time scenarios to teach on-call consultant pediatricians information literacy skills as part of a two-year continuing professional development program. Case Presentation: Two information-searching workshops were held at Sahlgrenska University Hospital in Gothenburg, Sweden. During the workshops, pediatricians were presented with medical scenarios that were closely related to their clinical practice. Participants were initially encouraged to solve the problems using their own preferred search methods, followed by group discussions led by clinical educators and a medical librarian in which search problems were identified and overcome. The workshops were evaluated using questionnaires to assess participant satisfaction and the extent to which participants intended to implement changes in their clinical practice and reported actual change. Conclusions: A scenario-based approach to teaching clinicians how to search for medical information is an attractive alternative to traditional lectures. The relevance of such an approach was supported by a high level of participant engagement during the workshops and high scores for participant satisfaction, intended changes to clinical practice, and reported benefits in actual clinical practice

Decreased Memory Bias via a Mobile Application : A Symptom Tracker to Monitor Children's Periodic Fever.

Memory bias, the tendency to rely on certain events over others, can become an issue in chronic illnesses, especially when symptoms are reported retrospectively. This paper examines a case where continuous symptom registration can be facilitated, memory supported, and memory bias reduced by introducing a mobile application. The aim of the paper is to report on the design of an app for collecting subjective data over an extended period to continuously follow children with periodic fever. The research approach is qualitative, building on interview data. The design method is co-design, a collaborative and participatory approach involving researchers, physicians and other key stakeholders, with focus on the views of the parents. We argue that collecting data continuously through an app moves the discussion from memory to the specific data points, which is illustrated through trends shown in the visualizations of the data. Moreover, we highlight the importance of systematically collecting data over an extended period through a data-driven approach to both forward clinical practice and research on complex, often chronic topics such as periodic fever, which is genuinely under-researched to date

Strengthening paediatric competencies and educational skills among general paediatricians.

AIM: To develop a coherent programme that addresses the need for continuing professional development in general paediatrics and educational skills for senior paediatricians at outpatient clinics in Sweden today. METHODS: Educational needs in the target group were investigated using a questionnaire. Themes and sub-themes extracted from responses informed the curriculum formulation of the continuing professional development (CPD) programme, which was completed using a variety of learning, assessment and evaluation methods. RESULTS: Forty-six paediatricians identified 355 clinical situations. Competencies in general paediatrics and educational skills were incorporated in a CPD programme, implemented in western Sweden between 13 October 2016 and 23 May 2019, with 23 learning modules and 18 participants (male/female 3/15, median age 55 years). The participants' evaluation emphasised the importance of adult learning principles. Their responses to open reflective questions on 23 May 2109 suggested that the programme offered a learning environment in which they could develop their paediatric and educational practices and improve their mentorship, networks and work-based learning environment. They also described an enhanced feeling of joy at work. CONCLUSION: The involvement of experienced paediatricians in the programme formulation may be inspirational to clinicians and contribute to the definition, revitalisation and prioritisation of general paediatrics in Sweden in the future.This study was funded by the Healthcare Board, Region Västra Götaland</p

Digital Learning : Continuous Professional Development of Physicians

Continuous professional development (CPD) is an important, yet often overlooked, part of higher education. While a large body of literature exists on formal learning and e-training, aspects of self-directed and informal digital learning in CPD are still under-researched. The aim of this project was: i) to explore physicians informal learning (e.g., collegial communication, collaboration and knowledge sharing) when shifting to digital learning as part of a CPD course; ii) to identify features that enable and constrain interaction and networking; and; iii) to evaluate the effects of digital learning on the overall learning objectives and outcomes. This project was carried out in three steps, and the outcome is in a set of recommendations that can be used to capture and inform the design of future CPD programs, implemented in higher education, to better support informal learning in digital learning settings