The Diagnostic Assessment of Inherited Platelet Function Defects.

In this article, our goal is to offer an introduction and overview of the diagnostic approach to inherited platelet function defects (iPFDs) for clinicians and laboratory personnel who are beginning to engage in the field. We describe the most commonly used laboratory methods and propose a diagnostic four-step approach, wherein each stage requires a higher level of expertise and more specialized methods. It should be noted that our proposed approach differs from the ISTH Guidance on this topic in some points.

The Diagnostic Assessment of Platelet Function Defects.

Congenital platelet disorders are rare and targeted treatment is usually not possible. Inherited platelet function disorders (iPFDs) can affect surface receptors and multiple platelet responses such as defects of platelet granules, signal transduction, and procoagulant activity. If iPFDs are also associated with a reduced platelet count (thrombocytopenia), it is not uncommon to be misdiagnosed as immune thrombocytopenia.

Accounting for sampling heterogeneity suggests a low paleolatitude origin for dinosaurs.

Dinosaurs dominated Mesozoic terrestrial ecosystems for ∼160 million years, but their biogeographic origin remains poorly understood. The earliest unequivocal dinosaur fossils appear in the Carnian (∼230 Ma) of southern South America and Africa, leading most authors to propose southwestern Gondwana as the likely center of origin. However, the high taxonomic and morphological diversity of these earliest assemblages suggests a more ancient evolutionary history that is currently unsampled.

Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study.

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19).

A case study in statistical software development for advanced evidence synthesis: the combined value of analysts and research software engineers.

Background: Since 2015, the Complex Reviews Synthesis Unit (CRSU) has developed a suite of web-based applications (apps) that conduct complex evidence synthesis meta-analyses through point-and-click interfaces. This has been achieved in the R programming language by combining existing R packages that conduct meta-analysis with the shiny web-application package. The CRSU apps have evolved from two short-term student projects into a suite of eight apps that are used for more than 3,000 h per month.

The role of genetic sequencing in the diagnostic work-up for chronic immune thrombocytopenia.

Immune Thrombocytopenia (ITP) is a heterogenous autoimmune disorder diagnosed by excluding other conditions. Misdiagnosis of primary ITP occurs in patients with inherited thrombocytopenia and primary immunodeficiency syndromes. This study investigates whether genetic testing for inherited thrombocytopenia or primary immunodeficiency can enhance diagnostic accuracy in ITP, and guide treatment strategies.

Primary versus Secondary Immune Thrombocytopenia (ITP): A Meeting Report from the 2023 McMaster ITP Summit.

The McMaster Immune Thrombocytopenia (ITP) Summit, held on October 27, 2023, was an educational seminar from leading experts in immune thrombocytopenia and related disorders geared toward hematologists, internists, immunologists, and clinical and translational scientists. The focus of the Summit was to review the mechanisms, diagnosis, and treatment of primary versus secondary ITP. Specific objectives were to describe the unique features of secondary ITP, and to review its mechanisms in the context of autoimmune disease and infection.

Perception of Telemedicine and Remote Learning Following the COVID-19 Pandemic: A Health Education England Survey of London Obstetrics and Gynaecology Trainees.

Purpose: To determine the level of uptake of telemedicine among postgraduate obstetrics and gynaecology (O&G) trainees in London, and how they perceive its impact on their training.

Methods: A mixed-methods survey aimed at exploring trainee perspectives of telemedicine use in clinical practice and its implications for training. Study participants were O&G specialist doctors on the London (UK) training programme.

Evolution of sexual size dimorphism in tetrapods is driven by varying patterns of sex-specific selection on size.

Sexual size dimorphism (SSD) is highly prevalent in nature. Several hypotheses aim to explain its evolution including sexual selection, differential equilibrium and ecological niche divergence. Disentangling the causal mechanism behind the evolution of SSD is challenging, as selection arising from multiple pressures on fitness may act simultaneously to generate observed patterns.

Molecular diagnoses and candidate gene identification in the congenital heart disease cohorts of the 100,000 genomes project.

Congenital heart disease (CHD) describes a structural cardiac defect present from birth. A cohort of participants recruited to the 100,000 Genomes Project (100 kGP) with syndromic CHD (286 probands) and familial CHD (262 probands) were identified. "Tiering" following genome sequencing data analysis prioritised variants in gene panels linked to participant phenotype.

Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double-blind, placebo-controlled phase 3 studies and their open-label extension.

Primary immune thrombocytopenia (ITP) is an antiplatelet-antibody-mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti-FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24-week phase 3 studies (TP0003; TP0006), and their 52-week open-label extension (OLE).

Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review.

Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.

Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.

Kidney Beam-A Cost-Effective Digital Intervention to Improve Mental Health.

Introduction: There is inequity in the provision of physical rehabilitation services for people living with chronic kidney disease (CKD). The Kidney BEAM trial evaluated the clinical value and cost effectiveness of a physical activity digital health intervention (DHI) in CKD.

Methods: In a single-blind, 11 center, randomized controlled trial, 340 adult participants with CKD were randomly assigned to either the Kidney BEAM physical activity DHI or a waitlist control.

Tracking individual animals can reveal the mechanisms of species loss.

As biodiversity loss continues, targeted conservation interventions are increasingly necessary. Stemming species loss requires mechanistic understanding of the processes governing population dynamics. However, this information is unavailable for most animals because it requires data that are difficult to collect using traditional methods.

Well-being interventions for emergency department staff: 'necessary' but 'inadequate' - a phenomenographic study.

Introduction: Stress and burnout are prevalent among emergency department (ED) staff in the UK. The concept of well-being interventions for ED staff is a growing area of interest and research worldwide. Various interventions are described in the literature, yet little is known about the experience of ED staff in the UK of interventions designed to support their well-being.

Long-term coastal dynamics: The evolution of a mixed sediment mega-nourishment consisting of colliery spoil.

Mega-nourishments, where large volumes of sediment are deposited on coastlines, are increasingly employed to manage shoreline erosion, yet our understanding of their long-term behaviour is limited by the fact that most current schemes are less than 15 years old. However, on the County Durham coast, 39 million m of coal spoil was tipped onto beaches between the late 1800s and 1993, acting as a de facto mixed sediment mega-nourishment. Our findings reveal key insights into the long-term dynamics of mega-nourishment schemes, including evidence of effective sediment dispersal around headlands into normally disconnected units of coast.

Non-breeding conditions induce carry-over effects on survival of migratory birds.

Identifying the processes that limit populations is a foundational objective of ecology and an urgent need for conservation. For migratory animals, researchers must study individuals throughout their annual cycles to determine how environmental conditions limit demographic rates within each period of the annual cycle and also between periods through carry-over effects and seasonal interactions. Our poor understanding of the rates and causes of avian migration mortality hinders the identification of limiting factors and the reversal of widespread avian population declines.

Paradigmatic perspectives of research on the self-regulated learning of non-Western learners in health professions education: a scoping review protocol.

Objective: The objective of this review will be to explore the paradigmatic perspectives of research on self-regulated learning in non-Western learners in health professions education.

Introduction: Studies show that there are significant cultural differences in self-regulated learning. However, a predominantly positivistic research paradigm, attempting to fit cross-cultural populations into pre-defined Western conceptualizations of self-regulated learning, has led to the disregard of these differences.

The role of the supervisor in self-regulated learning in the clinical environment: BEME Guide No. 89.

Introduction: Self-regulated learning (SRL) in medical education is important for successful learning and safe patient care. However, supervisors may be unaware of behaviours that explicitly facilitate or inhibit their students' or residents' SRL, therefore this BEME review explores the role of the supervisor in SRL in clinical environments.

Methods: A qualitative systematic review using meta-aggregation was performed, seeking to draw on the knowledge of included studies and the participants those studies represent to create context-rich recommendations that are relevant and applicable to practice.

Baseline Cognition Is Not Associated With Depression Outcomes in Vortioxetine for Major Depressive Disorder: Findings From Placebo-Controlled Trials.

Major depressive disorder (MDD) is a common psychiatric disorder for which pharmacologic standard-of-care treatments have limited efficacy, particularly among individuals with cognitive dysfunction. Cognitive dysfunction is observed in approximately 25%-50% of those with MDD, wherein response to standard-of-care medications is reduced. Vortioxetine is an approved antidepressant that has shown evidence of procognitive effects in patients.

Sleep Behavior in Royal Australian Navy Shift Workers by Shift and Exposure to the SleepTank App.

Introduction: Rotating shiftwork schedules are known to disrupt sleep in a manner that can negatively impact safety. Consumer sleep technologies (CSTs) may be a useful tool for sleep tracking, but the standard feedback provided by CSTs may not be salient to shift-working populations. SleepTank is an app that uses the total sleep time data scored by a CST to compute a percentage that equates hours of sleep to the fuel in a car and warns the user to sleep when the "tank" is low.

Outpatient Hysteroscopy: (Green-top Guideline no. 59).

All gynaecology departments should provide a dedicated outpatient hysteroscopy service to aid care of women and people with abnormal uterine bleeding, reproductive problems, and insertion/retrieval of intrauterine devices. [Grade A] Written information should be provided to the woman prior to their appointment. This should include details about the procedure, the benefits and risks, advice regarding pre-operative analgesia, as well as alternative options for care and contact details for the hysteroscopy unit.

Health Needs Assessment of Unhoused Youth in Charleston, South Carolina.

Background: Over 35 000 youth experience homelessness on any given night in the United States (US). Unhoused youth experience unique physical and mental health challenges and face barriers in every social determinant of health (SDoH), which may be amplified in the LGBTQ+ population.

Objective: The objective of this study was to define characteristics of the unhoused youth population and their utilization of healthcare to inform programs to meet their needs.