Elizabeth Keys

Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.

It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the inter-relationship between these players is completely unknown. We report several cellular events that led to enhanced trapping of bacteria in blood vessels: platelet TLR4 detected TLR4 ligands in blood and induced platelet binding to adherent neutrophils. This led to robust neutrophil activation and formation of neutrophil extracellular traps (NETs). Plasma from severely septic humans also induced TLR4-dependent platelet-neutrophil interactions, leading to the production of NETs. The NETs retained their integrity under flow conditions and ensnared bacteria within the vasculature. The entire event occurred primarily in the liver sinusoids and pulmonary capillaries, where NETs have the greatest capacity for bacterial trapping. We propose that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis.

How Well Do We Communicate Autopsy Findings to Next of Kin

CONTEXT A failure of communication among families, physicians, and pathologists is recognized as a major cause of declining autopsy rates and may be involved in increased litigation. OBJECTIVE To determine how effectively autopsy results are communicated to the next of kin and how satisfied families are with the process from consent to relaying of the results. DESIGN A retrospective telephone survey of next of kin of 106 consecutive patients autopsied at a major teaching hospital. The family was asked questions on the process of obtaining consent and the information they received back from health care providers. RESULTS Thirty-two percent of relatives indicated that they were not adequately informed as to the purpose of the autopsy. Eighty percent of respondents were notified of or obtained the results. The ways in which the autopsy findings were communicated varied, but 54% were involved in a discussion of the results with a medical professional. More than half of the families wished to have a copy of the results. Two-thirds felt they were satisfied with the explanation of the results, but an important cause of dissatisfaction was the use of unfamiliar medical terminology. When the familys understanding of the cause of death was compared with the diagnoses on the autopsy reports, 65% of families demonstrated an accurate knowledge of the autopsy findings, 28% had a general understanding, and for only 8% was their knowledge judged inaccurate. Overall, 92% of notified respondents felt the autopsy had served a useful purpose, mostly for personal reasons. CONCLUSIONS We conclude that the autopsy fulfills an important need for many families; however, the purpose of the autopsy and the findings need to be more effectively communicated.

Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug

BACKGROUND Airway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation. METHODS Surfactant was extracted from bronchial lavage fluid from children with CF and surface tension, and lipid content, inflammatory cells and microbial flora were determined. Dysfunctional surfactant samples were re-tested with a lipid-sequestering agent, methyl-β-cyclodextrin (MβCD). RESULTS CF surfactant samples were unable to sustain a normal low surface tension. MβCD restored surfactant function in a majority of samples.Mechanistic studies showed that the dysfunction was due to a combination of elevated cholesterol and an interaction with oxidized phospholipids and their pro-inflammatory hydrolysis products. CONCLUSION We confirm that CF patients have impaired airway surfactant function which could be restored with MβCD. These findings have implications for improving lung function and mitigating inflammation in patients with CF.

A Proposed Nursing Theory: Infant Sleep and Development

Although well positioned to work with families of young children, nurses do not yet have a theory that guides practice and research by relating infant sleep to child and family development. The authors of this paper describe a proposed theory that combines Bronfenbrenner’s bioecological theory of human development with the Barnard model of parent-child interaction to inform nursing practice and research related to infant sleep and optimizing child and family development. The theory focuses on sustainability of change in family processes and infant sleep, with a goal of optimizing family wellness as the proximal environment for child development.

Study Protocol: Determining Research Priorities of Young Albertan Families (The Family Research Agenda Initiative Setting Project—FRAISE)—Participatory Action Research

Introduction: Pregnancy and childrearing can be an exciting and stressful time for new parents. The maternal-child health landscape has changed dramatically over the last few decades and research priorities need to address these rapid changes. There have been limited attempts to engage and collaborate with members of the public to develop research priorities for families who are expecting or parenting an infant to age 24 months. The work that has been completed has attempted to identify parental preference for information delivery and barriers to uptake of parenting programs but has not investigated parental research priorities. Methods: In collaboration with provincial research units and strategic clinical networks (SCN), we will use principles of participatory action research (PAR) as our theoretical framework/method, and a modified James Lind Alliance priority setting approach to prioritize a list of research questions that parents/knowledge users believe will support the health of their families. This will result in a top 10 list of parent/knowledge user-identified research priorities. This project will consist of three phases. In the first phase, we developed a steering committee of parents/knowledge users, healthcare providers, community agencies, and researchers to design a survey about health priorities for families. In the second phase, we will distribute the survey to diverse groups of parents/knowledge users/providers and hold a series of meetings to identify and prioritize potential questions from new parents about health issues from conception to age 24 months. In the third phase, we will collaboratively disseminate and translate findings. Discussion: This study will highlight parental health concerns and recommend parent-identified research priorities to inform future research projects needed to support the health of families between conception to age 24 months. Understanding the health research priorities of families in the community will help ensure future research contributes to meaningful changes in the health of young children, parents/knowledge users, and families. Ethics: This study and protocol have received ethical approved from the Conjoint Health Research Ethics Board at the University of Calgary (REB17-0014). Dissemination: The top 10 research priorities will be published and additional findings from the study will be distributed through pamphlets and newsletters.

Using Play to Improve Infant Sleep: A Mixed Methods Protocol to Evaluate the Effectiveness of the Play2Sleep Intervention

Background One in four Canadian families struggle with infant sleep disturbances. The aim of this study is to evaluate Play2Sleep in families of infants with sleep disturbances. In addition to parental education on infant sleep, Play2Sleep uses examples from a video-recorded, structured play session with mothers and fathers separately to provide feedback on parent–infant interactions and their infant’s sleep-related social cues. The quantitative phase will answer the research question: Does one dose of Play2Sleep delivered during a home visit with mothers and fathers of infants aged 5 months reduce night wakings at age 7 months? The qualitative phase will answer the research question: What are parental perceptions of family experiences, processes, and contexts related to Play2Sleep and infant sleep? The overarching mixed methods research question is as follows: How do parental perceptions of family experiences, processes, and contexts related to infant sleep explain the effectiveness of Play2Sleep? Method and analysis An explanatory sequential mixed methods design will be used. In the quantitative phase, a randomized controlled trial and RM-ANOVA will compare night wakings in infants whose parents receive Play2Sleep versus standard public health nursing information. Sixty English-speaking families (mothers and fathers) of full-term, healthy, singleton, 5-month-old infants who perceive that their infant has sleep disturbances will be recruited. The primary outcome measure will be change in the number of night wakings reported by parents. The qualitative component will use thematic analysis of family interviews to describe parental perceptions and experiences of infant sleep. Mixed methods integration will use qualitative findings to explain quantitative results. Discussion Play2Sleep is a novel approach that combines information about infant sleep with personalized feedback on parent–infant interactions and infant cues. Including fathers and mixed methods should capture complex family experiences of infant sleep disturbances and Play2Sleep. If effective, Play2Sleep has possible application for preventing infant sleep disturbance and tailoring for other populations. Clinical Trial Registration www.ClinicalTrials.gov, identifier: NCT02742155. Registered on 2016 April 23.