Point-of-care tests, diagnostic uncertainty and antimicrobial stewardship in the ICU: procalcitonin or PCR to aid antibiotic-stop decisions - an observational cohort study.

Objectives: Intensive care unit (ICU) clinicians stop antibiotics more often, with a negative infection: point-of-care test (PCR-POCT). Simulated cases of diagnostic uncertainty regarding infection resolution led clinicians to choose options such as procalcitonin (PCT) and/or PCR-POCTs +/- de-escalation to aid stop decisions. We hypothesised that a direct infection indicator, PCR-POCT, would influence stop judgements more than indirect PCT.

Influences on safety of intrapartum electronic fetal heart rate monitoring practices: a scoping review.

Objectives: Suboptimal intrapartum electronic fetal heart rate monitoring using cardiotocography has remained a persistent problem (EFM-CTG). We aimed to identify the range of influences on the safety of using EFM-CTG in practice.

Design: Scoping review to identify influences related to the practice of intrapartum EFM.

Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012.

Introduction: Ewing sarcoma is a rare paediatric cancer. Currently, there is no way of accurately predicting these patients' survival at diagnosis. Disease type (ie, localised disease, lung/pleuropulmonary metastases and other metastases) is used to guide treatment decisions, with metastatic patients generally having worse outcomes than localised disease patients.

Cost efficiency of inpatient rehabilitation following acquired brain injury: the first international adaptation of the UK approach.

Objectives: To adapt and apply a model for evaluating the functional benefits and cost efficiency of specialist inpatient rehabilitation to the Australian context, comparing functional outcomes and savings in the cost of ongoing care after acquired brain injury.

Design: An observational cohort analysis of prospectively collected clinical data from admission to discharge, with follow-up to 3 years.

Setting: A newly established state-wide inpatient postacute rehabilitation unit in Victoria, Australia for patients with moderate to severe acquired brain injury.

Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol.

Introduction: Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test.

Experience, access and utilisation of fertility care for infertile men within the biomedical sector in urban Bangladesh: protocol for a qualitative study.

Introduction: One in six people of reproductive age experience infertility in their lifetime throughout the world, often with devastating consequences. Men are often invisible in infertility research and services, yet masculinity and reproductive agency intersect within social, cultural and religious contexts to shape their experiences of infertility and masculine expression. This study aims to provide insights into the lived experience of male infertility, the availability and access of infertility services for men within the biomedical sector in Bangladesh and the potential willingness of men to use home-based semen testing.

A phase II double-blind multicentre, placebo-controlled trial to assess the efficacy and safety of alpelisib (BYL719) in paediatric and adult patients with Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP): the SESAM study protocol.

Introduction: The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3Kα-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS).

Development of measures to assess listening-related effort and fatigue in daily life among hearing aid users: protocol for a quantitative field trial.

Introduction: Individuals with hearing loss and hearing aid users report higher levels of listening effort and fatigue in daily life compared with those with normal hearing. However, there is a lack of objective measures to evaluate these experiences in real-world settings. Recent studies have found that higher sound pressure levels (SPL) and lower signal-to-noise ratios (SNR) are linked to increased heart rate and decreased heart rate variability, reflecting the greater effort required to process auditory information.

Healthcare ethics and artificial intelligence: a UK doctor survey.

Objectives: To survey UK doctors on their uses of artificial intelligence (AI) and of their views on the ethics and regulation of AI in healthcare.

Design: Anonymous cross-sectional e-survey.

Setting: An online survey of UK General Medical Council (GMC) registered doctors.

Modified Delphi expert elicitation of the clinical and economic burden of obstructive hypertrophic cardiomyopathy in England and Northern Ireland.

Objective: To estimate the resource use of patients with obstructive hypertrophic cardiomyopathy (HCM), stratified by New York Heart Association (NYHA) class, in the English and Northern Irish healthcare systems via expert elicitation.

Design: Modified Delphi framework methodology.

Setting: UK HCM secondary care centres (n=24).

Heart-brain microvascular MRI study: protocol for a multicentre, observational, cohort study in the UK assessing associations between small vessel disease of the heart and brain.

Introduction: Ischaemic heart disease (IHD) and cerebrovascular disease are leading causes of morbidity and mortality worldwide. Cerebral small vessel disease (CSVD) is a leading cause of dementia and stroke. While coronary small vessel disease (coronary microvascular dysfunction) causes microvascular angina and is associated with increased morbidity and mortality.

Intersectionality factors and equitable end-of-life experiences: rapid review.

Background: Efforts to minimise inequity in palliative and end-of-life care (PEoLC) are well-researched. This is frequently explained by differences related to singular factors. The concept of intersectionality recognises that the combination of variables exacerbates disparities.

Editorial Perspective: What do we need to know about the manosphere and young people's mental health?

The manosphere is an international network of social media influencers and communities promoting male supremacy and antifeminist ideologies. Young men are engaging with this extremist content at high rates. Despite growing concerns among educators, policymakers and researchers, systematic data on the long-term impact of the manosphere on young people's mental health and behaviour remains limited.

Knee Anterior Laxity and Graft Maturation After Transphyseal Anterior Cruciate Ligament Reconstruction.

Background: The failure rate of anterior cruciate ligament (ACL) reconstruction in children and adolescents is a significant concern. Of the multitude of clinical factors that contribute to this risk, delayed maturation and graft laxity are potentially related and modifiable elements. The aim was to investigate knee anterior laxity and graft maturation in children and adolescents.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Risk prediction tools for pressure injury occurrence: an umbrella review of systematic reviews reporting model development and validation methods.

Background: Pressure injuries (PIs) place a substantial burden on healthcare systems worldwide. Risk stratification of those who are at risk of developing PIs allows preventive interventions to be focused on patients who are at the highest risk. The considerable number of risk assessment scales and prediction models available underscores the need for a thorough evaluation of their development, validation, and clinical utility.

North American avian species that migrate in flocks show greater long-term non-breeding range shift rates.

Background: Many species are exhibiting range shifts associated with anthropogenic change. For migratory species, colonisation of new areas can require novel migratory programmes that facilitate navigation between independently-shifting seasonal ranges. Therefore, in some cases range-shifts may be limited by the capacity for novel migratory programmes to be transferred between generations, which can be genetically and socially mediated.

Venous compression causes chronic cerebral ischaemia in normal pressure hydrocephalus patients.

Background: Cerebral autoregulation is a robust regulatory mechanism that stabilizes cerebral blood flow in response to reduced blood pressure, thereby preventing cerebral ischaemia. Scientists have long believed that cerebral autoregulation also stabilizes cerebral blood flow against increases in intracranial pressure, which is another component that determines cerebral perfusion pressure. However, this idea was inconsistent with the complex pathogenesis of normal pressure hydrocephalus, which includes components of chronic cerebral ischaemia due to mild increases in intracranial pressure.

Acceptability of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine plus dihydroartemisinin-piperaquine in Papua New Guinea: a qualitative study.

Background: In moderate-to-high malaria transmission regions, the World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) alongside insecticide-treated bed nets to reduce the adverse consequences of pregnancy-associated malaria. Due to high-grade Plasmodium falciparum resistance to SP, novel treatment regimens need to be evaluated for IPTp, but these increase pill burden and treatment days. The present qualitative study assessed the acceptability of IPTp-SP plus dihydroartemisinin-piperaquine (DP) in Papua New Guinea, where IPTp-SP was implemented in 2009.

Effectiveness and user experience of nose and throat swabbing techniques for SARS-CoV-2 detection: results from the UK COVID-19 National Testing Programme.

Background: The UK's National Health Service Test and Trace (NHSTT) program aimed to provide the most effective and accessible SARS-CoV-2 testing approach possible. Early user feedback indicated that there were accessibility issues associated with throat swabbing. We report the results of service evaluations performed by NHSTT to assess the effectiveness and user acceptance of swabbing approaches, as well as qualitative findings of user experiences from research reports, surveys, and incident reports.

Implementation strategies: lessons learned during an e-learning intervention to improve dietary behaviors and feeding practices in early childhood education and care.

Background: Early Childhood Education and Care (ECEC) centers play an important role in fostering healthy dietary habits. The Nutrition Now project focusing on improving dietary habits during the first 1000 days of life. Central to the project is the implementation of an e-learning resource aimed at promoting feeding practices among staff and healthy dietary behaviours for children aged 0-3 years in ECEC.

Prevalence and factors associated with childhood malaria and anaemia in Osun state, Nigeria: a baseline household malariometric study.

Background: Under-5 children have been known to bear a significant burden of malaria in endemic countries. Though significant progress has been made towards malaria prevention and control in Nigeria, it is expected that the addition of new malaria prevention strategy, such as perennial malaria chemoprevention (PMC) can contribute to a more rapid decline in malaria cases. This study aimed to determine the prevalence and factors associated with malaria and anaemia among children aged 2-18 months in Osun State.

Comparative effectiveness of physical activity interventions on cognitive functions in children and adolescents with Neurodevelopmental Disorders: a systematic review and network meta-analysis of randomized controlled trials.

Background: Physical activity (PA) interventions have been shown to yield positive effects on cognitive functions. However, it is unclear which type of PA intervention is the most effective in children and adolescents with Neurodevelopmental Disorders (NDDs). This study aimed to compare the effectiveness of different types of PA interventions on cognitive functions in children and adolescents with NDDs, with additional analyses examining intervention effects across specific NDD types including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

Fragmenstein: predicting protein-ligand structures of compounds derived from known crystallographic fragment hits using a strict conserved-binding-based methodology.

Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that 'stitches' the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode.