Stroke risk following traumatic brain injury: Systematic review and meta-analysis.

Background: Traumatic brain injury is a global health problem; worldwide, >60 million people experience a traumatic brain injury each year and incidence is rising. Traumatic brain injury has been proposed as an independent risk factor for stroke.

Aims: To investigate the association between traumatic brain injury and stroke risk.

The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review.

Background: Patients with chronic kidney disease, especially those receiving hemodialysis (HD), are at risk of hyperkalemia (HK). This systematic review aimed to evaluate the prevalence of HK in patients with renal disease receiving HD and collate evidence on the effect of HK and differing HD patterns (i.e.

Patients' and health professionals' attitudes and perceptions towards the initiation of preventive drugs for primary prevention of cardiovascular disease: a systematic review of qualitative studies.

Background: Statins and antihypertensive agents are recommended for primary prevention of cardiovascular disease (CVD), but they are not always prescribed to eligible patients.

Design & Setting: A systematic review of qualitative studies.

Aim: To explore health professionals' and patients' attitudes towards cardiovascular preventive drugs.

Clinicians' views and experiences of prescribing oral anticoagulants for stroke prevention in atrial fibrillation: A qualitative meta-synthesis.

Background: Globally, over 33 million people have atrial fibrillation (AF). In eligible patients, oral anticoagulation (OAC) is recommended for stroke risk reduction. Despite recent increases in OAC prescribing, global under-prescription to high-risk AF patients and inappropriate prescription to low-risk patients is leading to unnecessary risk of stroke and haemorrhage.

Improving health, wellbeing and parenting skills in parents of children with special health care needs and medical complexity - a scoping review.

Background: Parenting children with special health care needs can be challenging particularly if children have complex conditions. Parents may struggle to manage their child's health and their own emotions, contributing to poorer health outcomes for the family. Frequent healthcare contact presents opportunities to intervene, but current evidence review is limited.

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.

Patients' and health professionals' attitudes and perceptions towards the initiation of preventive drugs for primary prevention of cardiovascular disease: protocol for a systematic review of qualitative studies.

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.

Transcatheter aortic valve implantation for aortic stenosis in high surgical risk patients: A systematic review and meta-analysis.

Background: Symptomatic aortic stenosis has a poor prognosis. Many patients are considered inoperable or at high surgical risk for surgical aortic valve replacement (SAVR), reflecting their age, comorbidities and frailty. The clinical effectiveness and safety of TAVI have not been reviewed systematically for these high levels of surgical risk.

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

Introduction: Less 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.

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.

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.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited.

Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis.

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.

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.

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.

Pre-clinical evaluation of therapies to prevent or treat bone non-union: a systematic review protocol.

Background: Non-union of fractured bone is a major cause of morbidity in the orthopaedic population. Despite this, optimal management of non-union is still unclear and remains a significant clinical challenge. Research continues in animal models in an attempt to identify an effective clinical treatment.

SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects.

Inherited thrombocytopenias are a group of disorders that are characterized by a low platelet count and are sometimes associated with excessive bleeding that ranges from mild to severe. We evaluated 36 unrelated patients and 17 family members displaying thrombocytopenia that were recruited to the UK Genotyping and Phenotyping of Platelets (GAPP) study. All patients had a history of excessive bleeding of unknown etiology.

Investigating the effectiveness of different aspirin dosing regimens and the timing of aspirin intake in primary and secondary prevention of cardiovascular disease: protocol for a systematic review.

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).

VPS33B regulates protein sorting into and maturation of α-granule progenitor organelles in mouse megakaryocytes.

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is caused by deficiencies in the trafficking proteins VPS33B or VIPAR, and is associated with a bleeding diathesis and a marked reduction in platelet α-granules. We generated a tamoxifen-inducible mouse model of VPS33B deficiency, Vps33b(fl/fl)-ER(T2), and studied the platelet phenotype and α-granule biogenesis. Ultrastructural analysis of Vps33b(fl/fl)-ER(T2) platelets identified a marked reduction in α-granule count and the presence of small granule-like structures in agreement with the platelet phenotype observed in ARC patients.

Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay.

Up to 1% of the population have mild bleeding disorders, but these remain poorly characterized, particularly with regard to the roles of platelets. We have compared the usefulness of Optimul, a 96-well plate-based assay of 7 distinct pathways of platelet activation to characterize inherited platelet defects in comparison with light transmission aggregometry (LTA). Using Optimul and LTA, concentration-response curves were generated for arachidonic acid, ADP, collagen, epinephrine, Thrombin receptor activating-peptide, U46619, and ristocetin in samples from (1) healthy volunteers (n = 50), (2) healthy volunteers treated with antiplatelet agents in vitro (n = 10), and (3) patients with bleeding of unknown origin (n = 65).

Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects.

We analyzed candidate platelet function disorder genes in 13 index cases with a history of excessive bleeding in association with a significant reduction in dense granule secretion and impaired aggregation to a panel of platelet agonists. Five of the index cases also had mild thrombocytopenia. Heterozygous alterations in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related transcription factor 1, respectively, which have a fundamental role in megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild thrombocytopenia.

Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.

Warburg Micro syndrome and Martsolf syndrome (MS) are heterogeneous 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 families and 52 new families.