The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation

A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. The cortactin family of proteins (Cttn & HS1) are known to regulate WASp-Arp2/3-mediated actin polymerisation in other cell types and so here we address the role of these proteins in platelets using knockout mouse models. We generated mice lacking Cttn and HS1 in the megakaryocyte/platelet lineage. These mice had normal platelet production, with platelet number, size and surface receptor profile comparable to controls. Platelet function was also unaffected by loss of Cttn/HS1 with no differences observed in a range of platelet function assays including aggregation, secretion, spreading, clot retraction or tyrosine phosphorylation. No effect on tail bleeding time or in thrombosis models was observed. In addition, platelet actin nodules, and megakaryocyte podosomes, actin-based structures known to be dependent on WASp and the Arp2/3 complex, formed normally. We conclude that despite the importance of WASp and the Arp2/3 complex in regulating F-actin dynamics in many cells types, the role of cortactin in their regulation appears to be fulfilled by other proteins in platelets

How do stakeholders experience the adoption of electronic prescribing systems in hospitals? A systematic review and thematic synthesis of qualitative studies

Background: Electronic prescribing (ePrescribing) or computerised provider/physician order entry (CPOE) systems can improve the quality and safety of health services, but the translation of this into reduced harm for patients remains unclear. This review aimed to synthesise primary qualitative research relating to how stakeholders experience the adoption of ePrescribing/CPOE systems in hospitals, to help better understand why and how healthcare organisations have not yet realised the full potential of such systems and to inform future implementations and research. Methods: We systematically searched 10 bibliographic databases and additional sources for citation searching and grey literature, with no restriction on date or publication language. Qualitative studies exploring the perspectives/experiences of stakeholders with the implementation, management, use and/or optimisation of ePrescribing/CPOE systems in hospitals were included. Quality assessment combined criteria from the Critical Appraisal Skills Programme Qualitative Checklist and the Standards for Reporting Qualitative Research guidelines. Data were synthesised thematically. Results: 79 articles were included. Stakeholders’ perspectives reflected a mixed set of positive and negative implications of engaging in ePrescribing/CPOE as part of their work. These were underpinned by further-reaching change processes. Impacts reported were largely practice related rather than at the organisational level. Factors affecting the implementation process and actions undertaken prior to implementation were perceived as important in understanding ePrescribing/CPOE adoption and impact. Conclusions: Implementing organisations and teams should consider the breadth and depth of changes that ePrescribing/CPOE adoption can trigger rather than focus on discrete benefits/problems and favour implementation strategies that: consider the preimplementation context, are responsive to (and transparent about) organisational and stakeholder needs and agendas and which can be sustained effectively over time as implementations develop and gradually transition to routine use and system optimisation

Frequency and preventative interventions for non-suicidal self-injury and suicidal behaviour in primary school-age children : a scoping review protocol

Introduction: Non-suicidal self-injury (NSSI) and suicidal behaviour have been witnessed in children as young as 6–7 years of age, but while there are many reviews of preventative interventions for NSSI and suicide in adolescents, few have explored its prevalence in younger children and the potential impact of preventative interventions at this stage of life. NSSI and suicidal behaviour are an increasing concern in schools but school-based programmes can improve knowledge, attitudes and help-seeking behaviours and help prevent escalation of NSSI and later suicide. This scoping review will aim to explore the nature and extent of the evidence on the magnitude of NSSI and suicidal behaviour in primary school children, and to examine whether there are any primary school-based interventions available for the prevention of this phenomenon in 5 to 11-year-olds. Methods and analysis: A scoping review will be conducted using established methodology by Arksey and O’Malley and the Joanna Briggs Institute. Multiple bibliographic and indexing databases and grey literature will be searched using a combination of text words and index terms relating to NSSI, suicide, primary schools, frequency and intervention. Two reviewers will independently screen eligible studies for study selection and extract relevant data from included studies. A narrative summary of evidence will be conducted for all included studies with results presented in tables and/or diagrams. Inductive content analysis will be used to understand any narrative findings within the included studies. Ethics and dissemination: Ethical approval is not required for this scoping review. The results of this review will be disseminated though publication in a peer-reviewed journal and presented at relevant conferences

Improving health, well-being and parenting skills in parents of children with medical complexity::a scoping review protocol

IntroductionLess than 1% of children have complex medical conditions but account for one-third of all child health spending. The impact of suboptimal management of this group of children can have a considerable effect on families as well as services. Some families appear to cope more easily than others do, but there are compelling reasons to suggest that effective interventions may improve family coping and ultimately outcomes. Hospitalisation of their child presents a unique set of pressures and challenges for parents, but also an opportunity to intervene. However, the evidence is not well described in relation to this group of families. The primary objective of this scoping review is to identify parent and family-based interventions available to improve parental health, well-being, functioning or skills in the context of a child’s medically complex hospital admission and hospital care.Methods and analysisNine bibliographic databases will be searched spanning medicine, nursing, psychology, education, social work and the grey literature using a combination of index terms and text words related to parents, childhood, chronic illness and interventions. Study eligibility will be assessed by two researchers against preset inclusion and exclusion criteria. Key information from each study will be extracted and charted including year of publication, condition, severity, geographical setting, key concepts and definitions, aims, study population and sample size, methodology/methods, interventions, outcomes and key findings. Directed qualitative content analysis will be used to make sense of narrative findings within the included studies. Results will be presented which summarise the scope of the literature and identify key findings, potential areas for evidence synthesis and research gaps.Ethics and disseminationEthical approval is not required. The results of this review will be disseminated through publication in a peer-reviewed journal and feedback to stakeholders during the development of a hospital-based intervention.</jats:sec

Perceptions and experiences of the implementation, management, use and optimisation of electronic prescribing systems in hospital settings: protocol for a systematic review of qualitative studies

ABSTRACTIntroduction: There is increasing evidence that electronic prescribing (ePrescribing) or Computerized Provider/Physician Order Entry (CPOE) systems can improve the quality and safety of healthcare services. However, it has also become clear that their implementation is not straightforward and may create unintended or undesired consequences once in use. In this context, qualitativeapproaches have been particularly useful and their interpretative synthesis could make an important and timely contribution to the field. This review will aim to identify, appraise and synthesise qualitative studies on ePrescribing/CPOE in hospital settings, with or without clinical decision support (CDS).Methods and analysis: Data sources will include the following bibliographic databases: MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, Social Policy and Practice via Ovid, CINAHL via EBSCO, The Cochrane Library (CDSR, DARE and CENTRAL databases), Nursing and Allied Health Sources, Applied Social Sciences Index and Abstracts via ProQuest, and SCOPUS. In addition, other sources will besearched for ongoing studies (ClinicalTrials.gov) and grey literature: HMIC, Conference Proceedings Citation Index (Web of Science) and Sociological abstracts. Studies will be independently screened for eligibility by two reviewers. Qualitative studies, either standalone or in the context of mixed methods designs, reporting the perspectives of any actors involved in the implementation,management and use of ePrescribing/CPOE systems in hospital-based care settings will be included.Data extraction will be conducted by two reviewers using a piloted form. Quality appraisal will be based on criteria from the CASP and SRQR checklists. Studies will not be excluded based on quality assessment. A post-synthesis sensitivity analysis will be undertaken. Data analysis will follow the thematic synthesis method.Ethics and dissemination: The study does not require ethical approval as primary data will not be collected. The results of the study will be published in a peer-reviewed journal and presented at relevant conferences.Systematic review registration: PROSPERO CRD42016035552.STRENGTHS AND LIMITATIONS OF THIS STUDY• Although a number of systematic reviews have been conducted to date on ePrescribing or CPOE systems, only a few have focused on hospital settings.• According to the scoping searches conducted by the authors, only two existing reviews included qualitative studies, of which, only one focused on providers’ perceptions in a hospital setting.• To the best of the knowledge of the authors, this is the first systematic review of qualitative evidence relating to the management and use/optimisation of ePrescribing systems in hospital settings, not limited to the implementation process, and including any reported perspectives (i.e. not only health professionals, but also managers, commissioners, patients and relatives/carers).• The review will not address perceptions and experiences related to non-hospital based settings

Mice lacking the inhibitory collagen receptor LAIR-1 exhibit a mild thrombocytosis and hyperactive platelets

Objective— Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif–containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif–containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored. In this study, we investigate the role of LAIR-1 in megakaryocyte development and platelet production by generating LAIR-1–deficient mice. Approach and Results— Mice lacking LAIR-1 exhibit a significant increase in platelet counts, a prolonged platelet half-life in vivo, and increased proplatelet formation in vitro. Interestingly, platelets from LAIR-1–deficient mice exhibit an enhanced reactivity to collagen and the glycoprotein VI–specific agonist collagen-related peptide despite not expressing LAIR-1, and mice showed enhanced thrombus formation in the carotid artery after ferric chloride injury. Targeted deletion of LAIR-1 in mice results in an increase in signaling downstream of the glycoprotein VI–FcRγ-chain and integrin αIIbβ3 in megakaryocytes because of enhanced Src family kinase activity. Conclusions— Findings from this study demonstrate that ablation of LAIR-1 in megakaryocytes leads to increased Src family kinase activity and downstream signaling in response to collagen that is transmitted to platelets, rendering them hyper-reactive specifically to agonists that signal through Syk tyrosine kinases, but not to G-protein–coupled receptors. </jats:sec