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1.
Med Educ Online ; 29(1): 2316971, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38394053

RESUMO

INTRODUCTION: Given the complexity of teaching clinical reasoning to (future) healthcare professionals, the utilization of serious games has become popular for supporting clinical reasoning education. This scoping review outlines games designed to support teaching clinical reasoning in health professions education, with a specific emphasis on their alignment with the 8-step clinical reasoning cycle and the reflective practice framework, fundamental for effective learning. METHODS: A scoping review using systematic searches across seven databases (PubMed, CINAHL, ERIC, PsycINFO, Scopus, Web of Science, and Embase) was conducted. Game characteristics, technical requirements, and incorporation of clinical reasoning cycle steps were analyzed. Additional game information was obtained from the authors. RESULTS: Nineteen unique games emerged, primarily simulation and escape room genres. Most games incorporated the following clinical reasoning steps: patient consideration (step 1), cue collection (step 2), intervention (step 6), and outcome evaluation (step 7). Processing information (step 3) and understanding the patient's problem (step 4) were less prevalent, while goal setting (step 5) and reflection (step 8) were least integrated. CONCLUSION: All serious games reviewed show potential for improving clinical reasoning skills, but thoughtful alignment with learning objectives and contextual factors is vital. While this study aids health professions educators in understanding how games may support teaching of clinical reasoning, further research is needed to optimize their effective use in education. Notably, most games lack explicit incorporation of all clinical reasoning cycle steps, especially reflection, limiting its role in reflective practice. Hence, we recommend prioritizing a systematic clinical reasoning model with explicit reflective steps when using serious games for teaching clinical reasoning.


Assuntos
Aprendizagem , Resolução de Problemas , Humanos , Pensamento , Competência Clínica , Ocupações em Saúde
2.
Med Educ Online ; 28(1): 2231614, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37403584

RESUMO

PURPOSE: The unprecedented influx of patients in 2020 with COVID-19 to intensive care units (ICU) required redeployment of healthcare professionals without adequate previous ICU-training. In these extraordinary circumstances, pivotal elements of effective clinical supervision emerged. This study sets out to explore the nature, aspects and key features of supervision under highly demanding circumstances among certified and redeployed health-care professionals on COVID-19 ICUs. MATERIALS AND METHODS: A prospective qualitative, single center, semi-structured interview study among healthcare professionals at COVID-19 ICUs at University Medical Center Utrecht, the Netherlands between July and December 2020. Interview data were analyzed using an inductive coding style. RESULTS: A total of 13 certified and 13 redeployed health'hcare professionals, including physicians, nurses, and operation room technicians participated. Seven themes were identified as essential for both certified (supervisors) and redeployed (trainees) personnel: an open attitude, observing boundaries, gauging coworkers' capacities, being available, providing feedback, continuity in care and teams, and combining supervision with workload. CONCLUSIONS: This study provides seven recommendations for both supervisors and trainees to help optimize clinical supervision. They align with the known five factors determining entrustment and supervision (trainee, supervisor, task, context, and relationship). To ensure good clinical supervision, be it either during normal circumstances or under pressure, efforts should primarily focus on factors that are within a supervisor or trainee's span of control. MESH: Clinical supervision, interprofessional, COVID-19, Intensive Care.


Assuntos
COVID-19 , Internato e Residência , Mentores , Gestão de Recursos Humanos , Médicos , Humanos , Competência Clínica , COVID-19/epidemiologia , Unidades de Terapia Intensiva , Estudos Prospectivos , Pesquisa Qualitativa
3.
Med Teach ; 45(7): 701-707, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37027517

RESUMO

Entrustable professional activities (EPAs), units of professional practice that require proficient integration of multiple competencies and can be entrusted to a sufficiently competent learner, are increasingly being used to define and inform curricula of health care professionals. The process of developing EPAs can be challenging and requires a deep yet pragmatic understanding of the concepts underlying EPA construction. Based on recent literature and the authors' lessons learned, this article provides the following practical and more or less sequential recommendations for developing EPAs: [1] Assemble a core team; [2] Build up expertise; [3] Establish a shared understanding of the purpose of EPAs; [4] Draft preliminary EPAs; [5] Elaborate EPAs; [6] Adopt a framework of supervision; [7] Perform a structured quality check; [8] Use a Delphi approach for refinement and/or consensus; [9] Pilot test EPAs; [10] Attune EPAs to their feasibility in assessment; [11] Map EPAs to existing curriculum; [12] Build a revision plan.


Assuntos
Currículo , Internato e Residência , Humanos , Local de Trabalho , Pessoal de Saúde , Educação Baseada em Competências , Competência Clínica
4.
Teach Learn Med ; : 1-9, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071751

RESUMO

Phenomenon: Entrustable professional activities (EPAs) delineate major professional activities that an individual in a given specialty must be "entrusted" to perform, ultimately without supervision, to provide quality patient care. Until now, most EPA frameworks have been developed by professionals within the same specialty. As safe, effective, and sustainable health care ultimately depends on interprofessional collaboration, we hypothesized that members of interprofessional teams might have clear and possibly additional insight into which activities are essential to the professional work of a medical specialist. Approach: We recently employed a national modified Delphi study to develop and validate a set of EPAs for Dutch pediatric intensive care fellows. In this proof-of-concept study, we explored what pediatric intensive care physicians' non-physician team members (physician assistants, nurse practitioners, and nurses) constitute as essential professional activities for PICU physicians and how they regarded the newly developed set of nine EPAs. We compared their judgments with the PICU physicians' opinions. Findings: This study shows that non-physician team members share a mental model with physicians about which EPAs are indispensable for pediatric intensive care physicians. Despite this agreement however, descriptions of EPAs are not always clear for non-physician team members who have to work with them on a daily basis. Insights: Ambiguity as to what an EPA entails when qualifying a trainee can have implications for patient safety and trainees themselves. Input from non-physician team members may add to the clarity of EPA descriptions. This finding supports the involvement of non-physician team members in the developmental process of EPAs for (sub)specialty training programs.

5.
Educ Prim Care ; 34(2): 91-99, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36960834

RESUMO

BACKGROUND: The Irish General Practitioner Training (GP) Programme is currently moving to Competency-Based Medical Education (CBME), facilitated by Programmatic Assessment (PA) and Entrustable Professional Activities (EPAs). These new assessment and feedback mechanisms may provide a rich and much sought-after dataset. However, given the possible number of feedback and assessment events, and the variety of modalities used, aggregating and interpreting these can be costly and difficult. Dashboard implementations (DI) have been purposed as a solution to bridge the gap between the large datasets and the training community at all levels. AIMS: To explore the Irish GP training community's perceptions on how an EPAs DI could facilitate the delivery of GP training in Ireland. METHODS: A qualitative approach was taken, using a focus group representative of different groups in the training community. Concurrently, an EPAs DI was developed. Focus group transcripts were analysed in an iterative fashion using Template Analysis to generate themes and subthemes. RESULTS: Numerous advantages were seen in relation to the implementation of an EPAs DI around entrustment decisions, constructive alignment and summative decision-making. These advantages, however, need to be tempered with the realisation that the EPAs DI is not and should not be misinterpreted as being the learning analytic panacea for GP training. CONCLUSION: This paper outlines the perceptions from a postgraduate medical education training community on an EPAs DI, which would be applicable to other training communities considering introducing similar mechanisms.


Assuntos
Medicina Geral , Internato e Residência , Humanos , Irlanda , Educação Baseada em Competências , Currículo , Grupos Focais , Competência Clínica
6.
Med Educ ; 56(9): 881-891, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35388517

RESUMO

INTRODUCTION: Entrustable professional activities (EPAs), discrete profession-specific tasks requiring integration of multiple competencies, are increasingly used to help define and inform curricula of specialty training programmes. Although guidelines exist to help guide the developmental process, deciding what logic to use to draft a preliminary EPA framework poses a crucial but often difficult first step. The logic of an EPA framework can be defined as the perspective used by its developers to break down the practice of a profession into units of professional work. This study aimed to map dominant logics and their rationales across postgraduate medical education and fellowship programmes. METHODS: A scoping review using systematic searches within five electronic databases (Medline, Embase, Google Scholar, Scopus and Web of Science) was performed. Dominant logics of included papers were identified using inductive coding and iterative analysis. RESULTS: In total, 42 studies were included. Most studies were conducted in the United States (n = 22; 52%), Canada (n = 6; 14%) and the Netherlands (n = 4; 10%). Across the reported range of specialties, family medicine (n = 4; 10%), internal medicine (n = 4; 10%), paediatrics (n = 3; 7%) and psychiatry (n = 3; 7%) were the most common. Three dominant logics could be identified, namely, 'service provision', 'procedures' and/or 'disease or patient categories'. The majority of papers (n = 37; 88%) used two or more logics when developing EPA frameworks (median = 3, range = 1-4). Disease or patient groups and service provision were the most common logics used (39% and 37%, respectively). CONCLUSIONS: Most programmes used a combination of logics when trying to capture the essential tasks of a profession in EPAs. For each of the three dominant logics, the authors arrived at a definition and identified benefits, limitations and examples. These findings may potentially inform best practice guidelines for EPA development.


Assuntos
Educação Médica , Internato e Residência , Psiquiatria , Criança , Competência Clínica , Educação Baseada em Competências , Currículo , Humanos , Medicina Interna/educação , Lógica , Psiquiatria/educação , Estados Unidos
7.
Acad Med ; 97(3S): S28-S34, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34789660

RESUMO

PURPOSE: To better prepare for potential future large-scale redeployments, this study examines quality of supervision and care as perceived by redeployed residents, fellows, and attendings during a COVID-19 surge. METHOD: During April and May 2020, attendings, fellows, and residents redeployed at 2 teaching hospitals were invited to participate in a survey, which included questions on respondents' prior experience; redeployed role; amount of supervision needed and received; and perceptions of quality of supervision, patient care, and interprofessional collaboration. Frequencies, means, and P values were calculated to compare perceptions by experience and trainee status. Narrative responses to 2 open-ended questions were independently coded; themes were constructed. RESULTS: Overall, 152 of 297 (51.2%) individuals responded, including 64 of 142 attendings (45.1%), 40 of 79 fellows (50.6%), and 48 of 76 residents (63.2%). Fellows and attendings, regardless of prior experience, perceived supervision as adequate. In contrast, experienced residents reported receiving more supervision than needed, while inexperienced residents reported receiving less supervision than needed and rated overall supervision as poor. Attendings, fellows, and experienced residents rated the overall quality of care as acceptable to good, whereas inexperienced residents perceived overall quality of care as worse to much worse, particularly when compared with baseline. CONCLUSIONS: Narrative themes indicated that the quality of supervision and care was buffered by strong camaraderie, a culture of informal consultation, team composition (mixing experienced with inexperienced), and clinical decision aids. The markedly negative view of inexperienced residents suggests a higher risk for disillusionment, perhaps even moral injury, during future redeployments. Implications for planning are explored.


Assuntos
Atitude do Pessoal de Saúde , COVID-19 , Internato e Residência , Corpo Clínico Hospitalar , Qualidade da Assistência à Saúde , SARS-CoV-2 , Estudos Transversais , Hospitais de Ensino , Humanos , New York , Inquéritos e Questionários
8.
ATS Sch ; 2(3): 397-414, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34667989

RESUMO

Background: To meet coronavirus disease (COVID-19) demands in the spring of 2020, many intensive care (IC) units (ICUs) required help of redeployed personnel working outside their regular scope of practice, causing an expansion and change of staffing ratios. Objective: How did this composite alternative ICU workforce experience supervision, interprofessional collaboration, and quality and safety of care under the unprecedented clinical circumstances at the height of the first pandemic wave as lived experiences uniquely captured during the first peak of the pandemic? Methods: An international, cross-sectional survey was conducted among physicians, nurses, and allied personnel deployed or redeployed to ICUs in Utrecht, New York, and Dublin from April to May of 2020. Data were analyzed separately for the three sites. Quantitative data were treated for descriptive statistics; qualitative data were analyzed thematically and combined for general interpretations. Results: On the basis of 234, 83, and 34 responses (response rates of 68%, 48%, and 41% in Utrecht, New York, and Dublin, respectively), we found that the amount of supervision and the quality and safety of care were perceived as being lower than usual but still acceptable. The working atmosphere was overwhelmingly felt to be collaborative and supportive. Where IC-certified nurse-to-patient ratios had decreased most (Utrecht), nurses voiced criticism about supervision and quality of care. Continuity within the work environment, team composition, and informal ("curbside") consultations were critical mediators of success. Conclusion: In the exceptional circumstances encountered during the COVID-19 pandemic, many ICUs were managed by a composite workforce of IC-certified and redeployed personnel. Although supervision is critical for safe care, supervisory roles were not clearly related to the amount of prior ICU experience. Vital for satisfaction with the quality of care was the span of control for those who assumed supervisory roles (i.e., the ratio of certified to noncertified personnel). Stable teams that matched less experienced personnel with more experienced personnel; a strong, interprofessional, collaborative atmosphere; a robust culture of informal consultation; and judicious, more flexible use of rules and regulations proved to be essential.

9.
Acad Med ; 96(7S): S96-S104, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34183610

RESUMO

To establish a research and development agenda for Entrustable Professional Activities (EPAs) for the coming decade, the authors, all active in this area of investigation, reviewed recent research papers, seeking recommendations for future research. They pooled their knowledge and experience to identify 3 levels of potential research and development: the micro level of learning and teaching; the meso level of institutions, programs, and specialty domains; and the macro level of regional, national, and international dynamics. Within these levels, the authors categorized their recommendations for research and development. The authors identified 14 discrete themes, each including multiple questions or issues for potential exploration, that range from foundational and conceptual to practical. Much research to date has focused on a variety of issues regarding development and early implementation of EPAs. Future research should focus on large-scale implementation of EPAs to support competency-based medical education (CBME) and on its consequences at the 3 levels. In addition, emerging from the implementation phase, the authors call for rigorous studies focusing on conceptual issues. These issues include the nature of entrustment decisions and their relationship with education and learner progress and the use of EPAs across boundaries of training phases, disciplines and professions, including continuing professional development. International studies evaluating the value of EPAs across countries are another important consideration. Future studies should also remain alert for unintended consequences of the use of EPAs. EPAs were conceptualized to support CBME in its endeavor to improve outcomes of education and patient care, prompting creation of this agenda.


Assuntos
Competência Clínica , Educação Baseada em Competências/métodos , Tomada de Decisões , Educação Médica/métodos , Avaliação Educacional , Humanos , Pesquisa
10.
Med Teach ; 43(7): 817-823, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34043931

RESUMO

The COVID-19 pandemic has disrupted many societal institutions, including health care and education. Although the pandemic's impact was initially assumed to be temporary, there is growing conviction that medical education might change more permanently. The International Competency-based Medical Education (ICBME) collaborators, scholars devoted to improving physician training, deliberated how the pandemic raises questions about medical competence. We formulated 12 broad-reaching issues for discussion, grouped into micro-, meso-, and macro-level questions. At the individual micro level, we ask questions about adaptability, coping with uncertainty, and the value and limitations of clinical courage. At the institutional meso level, we question whether curricula could include more than core entrustable professional activities (EPAs) and focus on individualized, dynamic, and adaptable portfolios of EPAs that, at any moment, reflect current competence and preparedness for disasters. At the regulatory and societal macro level, should conditions for licensing be reconsidered? Should rules of liability be adapted to match the need for rapid redeployment? We do not propose a blueprint for the future of medical training but rather aim to provoke discussions needed to build a workforce that is competent to cope with future health care crises.


Assuntos
COVID-19 , Educação Médica , Internato e Residência , Competência Clínica , Educação Baseada em Competências , Currículo , Objetivos , Humanos , Pandemias , SARS-CoV-2
11.
PLoS One ; 16(3): e0248565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735195

RESUMO

Entrustable professional activities (EPAs), as a focus of learner assessment, are supported by validity evidence. An EPA is a unit of professional practice requiring proficiency in multiple competencies simultaneously, that can be entrusted to a sufficiently competent learner. Taken collectively, a set of EPAs define and inform the curriculum of a specialty training. The goal of this study was to develop a set of EPAs for Dutch PICU fellows. A multistage methodology was employed incorporating sequential input from task force members, a medical education expert, PICU fellowship program directors, and PICU physicians and fellows via a modified three-round Delphi study. In the first modified Delphi round, experts rated indispensability and clarity of preliminary EPAs. In the subsequent rounds, aggregated scores for each EPA and group comments were provided. In round two, respondents rated indispensability and clarity of revised EPAs. Round three was used to gain explicit confirmation of suitability to implement these EPAs. Based on median ratings and content validity index (CVI) analysis for indispensability in the first two rounds, all nine preliminary EPAs covered activities that were deemed essential to the clinical practice of PICU physicians. Based on median ratings and CVI analysis for clarity however, four EPAs needed revision. With an agreement percentage of 93-100% for all individual EPAs as well as the set as a whole, a high degree of consensus among experts was reached in the third round. The resulting nine PICU EPAs provide a succinct overview of the core tasks of Dutch PICU physicians. These EPAs were created as an essential first step towards developing an assessment system for PICU fellows, grounded in core professional activities. The robust methodology used, may have broad applicability for other (sub)specialty training programs aiming to develop specialty specific EPAs.


Assuntos
Competência Clínica/estatística & dados numéricos , Educação Baseada em Competências/métodos , Unidades de Terapia Intensiva Pediátrica , Internato e Residência/métodos , Adulto , Educação Baseada em Competências/organização & administração , Técnica Delfos , Feminino , Humanos , Internato e Residência/organização & administração , Internato e Residência/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos , Médicos/estatística & dados numéricos , Aprendizagem Baseada em Problemas , Inquéritos e Questionários
12.
Orphanet J Rare Dis ; 16(1): 137, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741030

RESUMO

We report five patients with lung disease immuno-deficiency and chromosome breakage syndrome (LICS) but without recurrent infections and severe immunodeficiency. One patient had extended survival to 6.5 years. Hematopoietic stem-cell transplantation failed to cure another patient. Our findings suggest that the immunological abnormalities can be limited and do not fully explain the LICS phenotype.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumopatias , Síndrome do Desconforto Respiratório , Quebra Cromossômica , Humanos , Fenótipo , Estudos Retrospectivos
15.
Clin Immunol ; 220: 108593, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920212

RESUMO

BACKGROUND: Neutrophils are the most abundant cell type infiltrating the airways during severe respiratory syncytial virus (RSV) infection. Their exact role in disease pathophysiology remains enigmatic. Therefore, we determined genome-wide RNA expression profiles of local and systemic neutrophils in RSV bronchiolitis to provide further insight into local neutrophil biology. METHODS: We performed a single-center analysis, in 16 infants, admitted to the pediatric intensive care unit with severe RSV bronchiolitis. Neutrophils were isolated from blood and tracheobronchial aspirates (sputum). After low input RNA sequencing, differential expression of genes was determined followed by gene set analysis. RESULTS: Paired transcriptomic analysis of airway versus blood neutrophils showed an inflammatory phenotype, characterized by NF-kB signaling and upregulated expression of IL-6 and interferon pathways. We observed distinct expression of neutrophil activation genes (TNFSF13B, FCER1G). DISCUSSION: Our data indicate that airway neutrophils regulate their function at the transcriptional level in response to viral infection. It also suggests that local interferon drives the neutrophil response of severe RSV bronchiolitis.


Assuntos
Bronquiolite/genética , Bronquiolite/imunologia , Neutrófilos/imunologia , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/imunologia , Transcriptoma , Fator Ativador de Células B/genética , Bronquiolite/sangue , Feminino , Humanos , Lactente , Interferons/imunologia , Pulmão/citologia , Pulmão/imunologia , Masculino , NF-kappa B/imunologia , RNA , Receptores Fc/genética , Infecções por Vírus Respiratório Sincicial/sangue
16.
BMC Infect Dis ; 20(1): 450, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591017

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age. METHODS: The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies. DISCUSSION: The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.


Assuntos
Genoma Viral , Epidemiologia Molecular/métodos , Polimorfismo Genético , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/genética , Anticorpos Monoclonais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Pré-Escolar , Farmacorresistência Bacteriana/genética , Feminino , Genótipo , Humanos , Imunização Passiva , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Clin Immunol ; 211: 108324, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31843567

RESUMO

During severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.


Assuntos
Neutrófilos/imunologia , Receptores Imunológicos/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Adulto , Armadilhas Extracelulares , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Explosão Respiratória , Escarro/citologia , Escarro/imunologia
18.
Front Immunol ; 10: 842, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080449

RESUMO

Neutrophils are crucial to antimicrobial defense, but excessive neutrophilic inflammation induces immune pathology. The mechanisms by which neutrophils are regulated to prevent injury and preserve tissue homeostasis are not completely understood. We recently identified the collagen receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1 as a functional inhibitory receptor on airway-infiltrated neutrophils in viral bronchiolitis patients. In the current study, we sought to examine the role of LAIR-1 in regulating airway neutrophil responses in vivo. LAIR-1-deficient (Lair1-/-) and wild-type mice were infected with respiratory syncytial virus (RSV) or exposed to cigarette smoke as commonly accepted models of neutrophil-driven lung inflammation. Mice were monitored for cellular airway influx, weight loss, cytokine production, and viral loads. After RSV infection, Lair1-/- mice show enhanced airway inflammation accompanied by increased neutrophil and lymphocyte recruitment to the airways, without effects on viral loads or cytokine production. LAIR-1-Fc administration in wild type mice, which blocks ligand induced LAIR-1 activation, augmented airway inflammation recapitulating the observations in Lair1-/- mice. Likewise, in the smoke-exposure model, LAIR-1 deficiency enhanced neutrophil recruitment to the airways and worsened disease severity. Intranasal CXCL1-mediated neutrophil recruitment to the airways was enhanced in mice lacking LAIR-1, supporting an intrinsic function of LAIR-1 on neutrophils. In conclusion, the immune inhibitory receptor LAIR-1 suppresses neutrophil tissue migration and acts as a negative regulator of neutrophil-driven airway inflammation during lung diseases. Following our recent observations in humans, this study provides crucial in-vivo evidence that LAIR-1 is a promising target for pharmacological intervention in such pathologies.


Assuntos
Movimento Celular/imunologia , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Pneumonia/imunologia , Receptores Imunológicos/imunologia , Animais , Bronquiolite Viral/imunologia , Bronquiolite Viral/patologia , Quimiocina CXCL1/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/patologia , Receptores Imunológicos/genética , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/imunologia , Fumaça/efeitos adversos , /toxicidade
19.
Vaccine ; 36(31): 4693-4700, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-29941327

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of infant mortality. Here, we estimated the potential impact of maternal vaccination against RSV on life-threatening RSV infection in infants. METHODS: We developed a mathematical model for maternal vaccine-induced antibody dynamics and used characteristics of a maternal RSV vaccine currently in phase 3 of clinical development. The model was applied to data from two cohorts of children younger than 12 months with RSV-related paediatric intensive care unit (PICU) admission in the United Kingdom (n = 370) and the Netherlands (n = 167), and a cohort of 211 children younger than 12 months with RSV-related in-hospital death from 20 countries worldwide. RESULTS: Our model predicted that, depending on vaccine efficiency, maternal vaccination at 30 weeks' gestational age could have prevented 62-75% of RSV-related PICU admissions in the United Kingdom and 76-87% in the Netherlands. For the global mortality cohort, the model predicted that maternal vaccination could have prevented 29-48% of RSV-related in-hospital deaths. Preterm children and children with comorbidities were predicted to benefit less than (healthy) term children. CONCLUSIONS: Maternal vaccination against RSV may substantially decrease life-threatening RSV infections in infants.


Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinação/métodos , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos , Países Baixos/epidemiologia , Gravidez , Infecções por Vírus Respiratório Sincicial/mortalidade , Análise de Sobrevida , Reino Unido/epidemiologia
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