Trans-epithelial migration is essential for neutrophil activation during RSV infection

The recruitment of neutrophils to the infected airway occurs early following respiratory syncytial virus (RSV) infection and high numbers of activated neutrophils in airway and blood is associated with the development of severe disease. The aim of this study was to investigate whether trans-epithelial migration is sufficient and necessary for neutrophil activation during RSV infection. Here, we used flow cytometry and novel live-cell fluorescent microscopy to track neutrophil movement during trans-epithelial migration and measure the expression of key activation markers in a human model of RSV infection. We found that when migration occurred, neutrophil expression of CD11b, CD62L, CD64, NE and MPO increased. However, the same increase did not occur on basolateral neutrophils when neutrophils were prevented from migrating, suggesting that activated neutrophils reverse migrate from the airway to the bloodstream side, as has been suggested by clinical observations. We then combined our findings with the temporal and spatial profiling and suggest three initial phases of neutrophil recruitment and behaviour in the airways during RSV infection; 1) initial chemotaxis; 2) neutrophil activation and reverse migration; 3) amplified chemotaxis and clustering, all of which occur within 20 minutes. This work and the novel outputs could be used to develop therapeutics and provide new insight into how neutrophil activation and a dysregulated neutrophil response to RSV mediates disease severity

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups

Effectiveness of Chest Physiotherapy in Infants Hospitalized with Acute Bronchiolitis: A Multicenter, Randomized, Controlled Trial

Vincent Gajdos and colleagues report results of a randomized trial conducted among hospitalized infants with bronchiolitis. They show that a physiotherapy technique (increased exhalation and assisted cough) commonly used in France does not reduce time to recovery in this population

Protective parents and permissive children: what qualitative interviews with parents and children can tell us about the feasibility of juvenile idiopathic arthritis trials

Background: Patient recruitment can be very challenging in paediatric studies, especially in relatively uncommon conditions, such as juvenile idiopathic arthritis (JIA). However, involving children and young people (CYP) in the design of such trials could promise a more rapid trajectory towards making evidence-based treatments available. Studies involving CYP are advocated in the literature but we are not aware of any early stage feasibility studies that have qualitatively accessed the perspectives of parents and CYP with a long term condition to inform design and conduct of a trial. In the context of a feasibility study to inform the design of a proposed randomised controlled trial of corticosteroid induction regimen in JIA, we explored families’ perspectives on the proposed trial and on JIA trials generally. Methods: We analysed interviews with 27 participants (8 CYP aged 8–16 years and 19 parents) from four UK paediatric rheumatology centres. CYP had recently received corticosteroids to treat JIA. Audio-recorded interviews were transcribed and analysed thematically, drawing on the Framework Method. Results: Both parents and CYP were capable of engaging with the logic of the proposed trial but pointed to challenges with its design. Treatment preferences influenced willingness to participate in the proposed trial. The preferences of older children and their parents often differed, with CYP being more willing to participate in the proposed trial than parents. Families’ current treatment preferences were largely informed by past positive and negative treatment experiences. Some participants also indicated that their treatment preferences were influenced by those of their clinicians. Conclusion: Previous research has typically focused on deficits in patients’ understandings of trials. We found that both parents and CYP understood trial concepts and were able to identify potential flaws in the proposed trial. We propose recommendations to optimise the design of a planned corticosteroid induction regimen trial in JIA. Accessing both parents’ and CYP’s perspectives helps to identify and address recruitment challenges, which will ultimately optimise informed consent and future recruitment

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Reporting standards for child health research were few and poorly Implemented.

OBJECTIVES This study aims to identify existing reporting standards for child health research, assess the robustness of the standards development process, and evaluate the dissemination of these standards. STUDY DESIGN AND SETTING We searched MEDLINE, the EQUATOR Network Library and Google to identify reporting standards for child health research studies. We assessed the adherence of the Guidance for Developers of Health Research Reporting Guidelines (GDHRG) by the identified reporting standards. We also assessed the use of the identified reporting standards by primary research studies, and the endorsement of the included reporting standards by journals. RESULTS We identified six reporting standards for child health research, including two under development. Among the four available standards, their median adherence to the 18 main steps of the GDHRG was 58.35% (range: 27.8%-83.3%). None of these four reporting standards had been endorsed by pediatric journals indexed by the Science Citation Index. Only 26 primary research studies declared that they followed one of the reporting standards. CONCLUSION There is a quantitative and qualitative paucity of well-developed reporting standards for child health research. The available standards are also poorly implemented. This situation demands an urgent need to develop robust standards and ensure their implementation

Trans-epithelial migration is essential for neutrophil activation during RSV infection

The recruitment of neutrophils to the infected airway occurs early following respiratory syncytial virus (RSV) infection, and high numbers of activated neutrophils in the airway and blood are associated with the development of severe disease. The aim of this study was to investigate whether trans-epithelial migration is sufficient and necessary for neutrophil activation during RSV infection. Here, we used flow cytometry and novel live-cell fluorescent microscopy to track neutrophil movement during trans-epithelial migration and measure the expression of key activation markers in a human model of RSV infection. We found that when migration occurred, neutrophil expression of CD11b, CD62L, CD64, NE, and MPO increased. However, the same increase did not occur on basolateral neutrophils when neutrophils were prevented from migrating, suggesting that activated neutrophils reverse migrate from the airway to the bloodstream side, as has been suggested by clinical observations. We then combined our findings with the temporal and spatial profiling and suggest 3 initial phases of neutrophil recruitment and behavior in the airways during RSV infection; (1) initial chemotaxis; (2) neutrophil activation and reverse migration; and (3) amplified chemotaxis and clustering, all of which occur within 20 min. This work and the novel outputs could be used to develop therapeutics and provide new insight into how neutrophil activation and a dysregulated neutrophil response to RSV mediates disease severity.</p

Reporting standards for child health research were few and poorly Implemented

OBJECTIVES: This study aims to identify existing reporting standards for child health research, assess the robustness of the standards development process, and evaluate the dissemination of these standards. STUDY DESIGN AND SETTING: We searched MEDLINE, the EQUATOR Network Library and Google to identify reporting standards for child health research studies. We assessed the adherence of the Guidance for Developers of Health Research Reporting Guidelines (GDHRG) by the identified reporting standards. We also assessed the use of the identified reporting standards by primary research studies, and the endorsement of the included reporting standards by journals. RESULTS: We identified six reporting standards for child health research, including two under development. Among the four available standards, their median adherence to the 18 main steps of the GDHRG was 58.35% (range: 27.8%-83.3%). None of these four reporting standards had been endorsed by pediatric journals indexed by the Science Citation Index. Only 26 primary research studies declared that they followed one of the reporting standards. CONCLUSION: There is a quantitative and qualitative paucity of well-developed reporting standards for child health research. The available standards are also poorly implemented. This situation demands an urgent need to develop robust standards and ensure their implementation

Flow chart of the development of the Liverpool ADR avoidability assesmsent tool.

<p>Flow chart of the development of the Liverpool ADR avoidability assesmsent tool.</p