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Introduction Lipid-lowering drugs and antihypertensive agents can be prescribed for the primary prevention of cardiovascular disease. In some cases, patients eligible for primary prevention of cardiovascular disease according to the European guidelines are not always started on preventive drugs. Existing research explores the attitudes of health professionals and patients towards cardiovascular preventive drugs but does not always differentiate between the attitudes towards drug initiation for primary or secondary prevention. We aim to systematically review qualitative studies assessing health professionals’ and patients’ attitudes and perceptions towards drug initiation for primary prevention of cardiovascular disease. Methods and analysis MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, CINAHL, Applied Social Sciences Index and Abstracts, Conference Proceedings Citation Index (Web of Science), Healthcare Management Information Consortium, and Open Grey will be searched without restrictions on date or language of publication. Searches will be limited to studies of qualitative design, standalone or in the context of a mixed-method design, focusing on cardiovascular drug initiation for primary prevention. The primary outcome is the attitudes of health professionals and patients towards drug initiation for primary prevention of cardiovascular disease. Two reviewers will independently carry out the study selection, data extraction and quality assessment. The Critical Appraisal Skills Programme Qualitative Research Checklist will be used to assess the quality of included studies. The findings will be analysed using Thomas and Harden’s thematic synthesis approach. Ethics and dissemination This systematic review 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. PROSPERO registration number CRD42018095346.

Summary of included studies. (DOCX 61 kb)

Excluded studies with reasons. (DOCX 24 kb)

Medline search. (DOCX 13 kb)

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.\ud \ud 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.\ud \ud 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.

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.\ud \ud 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.

Introduction: There is increasing evidence that electronic prescribing (ePrescribing) or computerised 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, qualitative approaches 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. 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 be searched for ongoing studies (ClinicalTrials.gov) and grey literature: Healthcare Management Information Consortium, Conference Proceedings Citation Index (Web of Science) and Sociological abstracts. Studies will be independently screened for eligibility by 2 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 2 reviewers using a piloted form. Quality appraisal will be based on criteria from the Critical Appraisal Skills Programme checklist and Standards for Reporting Qualitative Research. Studies will not be excluded based on quality assessment. A postsynthesis 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.

Introduction There is increasing evidence that electronic prescribing (ePrescribing) or computerised 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, qualitative approaches 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. 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 be searched for ongoing studies (ClinicalTrials.gov) and grey literature: Healthcare Management Information Consortium, Conference Proceedings Citation Index (Web of Science) and Sociological abstracts. Studies will be independently screened for eligibility by 2 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 2 reviewers using a piloted form. Quality appraisal will be based on criteria from the Critical Appraisal Skills Programme checklist and Standards for Reporting Qualitative Research. Studies will not be excluded based on quality assessment. A postsynthesis 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. Trial registration number CRD42016035552.

Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism and contribution of collagen modifications that occur outside the endoplasmic reticulum and Golgi are not understood. We discovered that VIPAR, with its partner proteins, regulate sorting of lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi collagen IV carriers and that VIPAR-dependent sorting is essential for modification of lysines in multiple collagen types. Identification of structural and functional collagen abnormalities in cells and tissues from patients and murine models of the autosomal recessive multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome caused by VIPAR and VPS33B deficiencies confirmed our findings. Thus, regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues. Lysine hydroxylation of procollagen precursors by LH3 is required for collagen fibril crosslinking and stabilization. Here the authors show that the trafficking protein VIPAR is required for correct sorting of LH3 into post-Golgi collagen carriers and for correct collagen modification and structure

Background Once-daily low-dose aspirin is routinely used for the prevention of secondary events in cardiovascular disease (CVD). The routine use of aspirin in primary prevention of CVD is less clear due to a finer balance between benefits and harms. In addition, the variability in benefit achievable from the prescription of aspirin has led to a growing interest in considering whether there are more effective aspirin regimens than once-daily dosing or whether effectiveness is influenced by the time of day aspirin is taken (chronotherapy). The proposed systematic review will evaluate the evidence on the effects of different aspirin regimens used in terms of number of doses (e.g. split or alternate dosing) or dosing time of aspirin (e.g. morning versus evening) in primary and secondary prevention of CVD. Methods/design Standard systematic review methodology will be employed for study identification, selection and data extraction. Electronic databases will be searched incorporating terms relating to population and the intervention. No date or language limitations will apply. Systematic reviews and controlled studies comparing different aspirin regimens—in terms of frequency or timing—for primary and/or secondary prevention of CVD will be included. No restrictions on outcome will apply. Quality assessment will be appropriate for each study design. The data will be tabulated and narratively synthesised. Meta-analysis may be undertaken where clinical and methodological homogeneity exists. Discussion There are a number of published and ongoing primary studies that investigate the cardiovascular protective effect of different aspirin regimens. However, no systematic review to date has attempted to review the evidence pertaining to aspirin dosing regimens differing in frequency and/or in timing. The proposed systematic review will cover both the above questions and could potentially be beneficial for reconsidering the current practice of managing patients with aspirin in primary care. Systematic review registration PROSPERO CRD42014010596 Electronic supplementary material The online version of this article (doi:10.1186/s13643-015-0078-3) contains supplementary material, which is available to authorized users.

Data collection form. (DOCX 30Â kb)

Sample search strategy for PubMed. (DOCX 15Â kb)

Warburg Micro syndrome and Martsolf syndrome are heterogenous autosomal-recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Causative biallelic germline mutations have been identified in RAB3GAP1, RAB3GAP2 or RAB18, each of which encode proteins involved in membrane trafficking. This report provides an up to date overview of all known disease variants identified in 29 previously published and 52 new families. 144 Micro and 9 Martsolf families were investigated, identifying mutations in RAB3GAP1 in 41% of cases, in RAB3GAP2 in 7% of cases and in RAB18 in 5% of cases. These are listed in Leiden Open source Variation Databases (LOVD) we created for all 3 genes. Genotype-phenotype correlations for these genes have now established that the clinical phenotype in Micro and Martsolf syndromes represent a phenotypic continuum related to the nature and severity of the mutations present in the disease genes with more deleterious mutations causing Micro syndrome and milder mutations causing Martsolf syndrome. RAB18 has not yet been linked to the RAB3 pathways, but mutations in all three genes cause an indistinguishable phenotype making it likely that there is some overlap. There is considerable genetic heterogeneity for these disorders and further gene identification will help delineate these pathways.