Adjusting for switches to multiple treatments: Should switches be handled separately or combined?

Treatment switching is common in randomised controlled trials (RCTs). Participants may switch onto a variety of different treatments, all of which may have different treatment effects. Adjustment analyses that target hypothetical estimands - estimating outcomes that would have been observed in the absence of treatment switching - have focused primarily on a single type of switch.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

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.

CIRCUS: CIRCUlating tumour cells in soft tissue Sarcoma - a short report.

Circulating tumour cells (CTCs) can be detected in peripheral blood using their physical properties (increased size and less deformable than normal circulating blood cells) or using cell surface markers. The study of these CTCs should provide important insights into tumour biology, including mechanisms of drug resistance. We performed a pilot study (IRAS ID: 235459) to evaluate if CTCs could be isolated from peripheral blood samples collected from soft tissue sarcoma (STS) patients.

Degeneration of the nucleus pulposus affects the internal volumetric strains and failure location of adjacent human metastatic vertebral bodies.

Intervertebral disc (IVD) degeneration is suspected to affect the distribution of stress and strain near the vertebral endplates and in the underlying bone. This scenario is worsened by the presence of metastatic lesions on the vertebrae (primarily thoracic vertebrae (60-80 %)) which increase the risk of fracture. As such, this study aimed to evaluate the effect of IVD degeneration on the internal volumetric strains and failure modes of human metastatic vertebral bodies.

Bone Turnover Markers Predict Changes in Bone Mineral Density in Men Treated with Abaloparatide: Results from ATOM.

Early increases in bone turnover markers (BTMs) in response to anabolic therapy correlate with 18-month bone mineral density (BMD) increases in postmenopausal women with osteoporosis; however, this relationship has not been assessed in men. In this analysis, the correlation between changes from baseline in fasting intact serum procollagen type I N propeptide (PINP) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at 1, 3, 6, and 12 months and percent increase from baseline in BMD at 12 months in men from the randomized phase 3 ATOM study (NCT03512262) were evaluated using Pearson's correlation coefficients. The uncoupling index (UI), a measure of the balance between markers of bone formation (PINP) and bone resorption (CTX), with positive UI favoring bone formation, was calculated.

A Psychosocial Critique of the Consequences of the COVID-19 Pandemic on UK Care Home Staff Attitudes to the Flu Vaccination: A Qualitative Longitudinal Study.

Vaccinating care home staff is essential to protect vulnerable residents by reducing infection risks and creating a safer care environment. However, vaccine hesitancy amongst staff remains a challenge, particularly since the COVID-19 pandemic raised concerns about side effects and vaccination mandates. This study examines how the pandemic influenced flu vaccine hesitancy amongst UK care home staff.

Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.

Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life.

Use of Magtrace as an Alternative Approach in Staging the Axilla in Early-Stage Breast Cancer: A Single-Center Experience.

Background The sentinel lymph node biopsy (SLNB) is the standard method used to determine the stage of breast cancer in patients with no clinical signs of axillary involvement. The current gold standard for the intraoperative assessment of the axilla involves the use of dual radioisotope and patent blue dye. However, researchers have been studying the use of superparamagnetic iron oxide Magtrace® (Endomagnetics Limited, Cambridge, United Kingdom) agents as an alternative to overcome the limitations of the standard SLNB technique.

Pharmacotherapeutic options for coronary thrombosis treatment: where are we today?

Introduction: Advances in pharmacotherapy for coronary thrombosis treatment and prevention have transformed the clinical outcomes of patients with coronary artery disease but increased the complexity of therapeutic decision-making. Improvements in percutaneous coronary intervention techniques and stent design have reduced the incidence of thrombotic complications, which consequently has increased the challenge of adequately powering clinical trials of novel antithrombotic strategies for efficacy outcomes. Knowledge of the pathophysiology of coronary thrombosis and the characteristics of antithrombotic drugs can help with therapeutic decisions.

Professional judgement: a social practice perspective on a multiple mini-interview for specialty training selection.

Background: Interviewers' judgements play a critical role in competency-based assessments for selection such as the multiple-mini-interview (MMI). Much of the published research focuses on the psychometrics of selection and the impact of rater subjectivity. Within the context of selecting for entry into specialty postgraduate training, we used an interpretivist and socio-constructivist approach to explore how and why interviewers make judgments in high stakes selection settings whilst taking part in an MMI.

Home Urine Dipstick Screening for Bladder and Kidney Cancer in High-Risk Populations in England: A Microsimulation Study of Long-Term Impact and Cost-Effectiveness.

Background: Testing high-risk populations for non-visible haematuria may enable earlier detection of bladder cancer, potentially decreasing mortality. This research aimed to assess the cost-effectiveness of urine dipstick screening for bladder cancer in high-risk populations in England.

Methods:  A microsimulation model developed in R software was calibrated to national incidence data by age, sex and stage, and validated against mortality data.

Bowel preparation for small bowel capsule endoscopy: standard regimen with 2 L polyethylene glycol versus 1 L polyethylene glycol plus ascorbate.

Background/aims: Optimization of bowel preparation for small bowel capsule endoscopy (SBCE) is debated. Guidelines recommend 2 L of iso-osmolar polyethylene glycol (PEG) to improve SBCE visibility. We compared the efficacy of the standard 2 L PEG solution with a 1 L PEG plus ascorbate (PEG-ASC) preparation, which has already been established for large-bowel preparation.

Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation.

Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC).

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

The psychometric properties of the EQ-HWB and EQ-HWB-S in patients with breast cancer: a comparative analysis with EQ-5D-5L, FACT-8D and SWEMWBS.

Objectives: The EQ Health and Well Being is a new generic measure that captures constructs beyond health-related quality of life, with a 25-item long form (EQ-HWB) and a shorter 9-item version (EQ-HWB-S). This study aims to assess the psychometric performance of both versions in breast cancer, which is the most prevalent cancer globally, and compare them to other instruments.

Methods: A longitudinal survey in Indonesia (2023-24) with 300 female patients used the EQ-HWB, EQ-5D-5L, Functional Assessment of Cancer Therapy-General (FACT-G, from which FACT-8D was derived), Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS, from which SWEMWBS was derived).

What is the Role of Measuring Urinary Gluten Immunogenic Peptides in Clinical Practice in Patients with Coeliac Disease?

Background And Aims: In coeliac disease, the clinical role of the urinary gluten immunogenic peptide is unclear. It has been suggested it can be a non-invasive marker of villous atrophy. Therefore, we present the largest cross-sectional clinical data in patients with coeliac disease to establish the diagnostic accuracy of the urinary gluten immunogenic peptide in identifying villous atrophy.

Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140.

Rationale & Objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study Design: Case series.

Impact of dementia and mild cognitive impairment on bone health in older people.

Mild cognitive impairment, dementia and osteoporosis are common diseases of ageing and, with the increasingly ageing global population, are increasing in prevalence. These conditions are closely associated, with shared risk factors, common underlying biological mechanisms and potential direct causal pathways. In this review, the epidemiological and mechanistic links between mild cognitive impairment, dementia and skeletal health are explored.

How to … Build a Peer Reviewer Community in Health Professions Education.

Peer review is the cornerstone of academic publishing that upholds the quality and integrity of scholarly work. However, there is an ever-growing struggle to recruit peer reviewers, termed the 'peer review crisis', driven by a shrinking academic workforce and increased workload. Additionally, there is a notable lack of standardised training for peer reviewers which poses a challenge in maintaining high-quality reviews.

"Are we ready to transition from the Global Alliance for Vaccines and Immunization support?" Perceptions from 15 Kenyan counties.

Introduction: Gavi, the Vaccine Alliance, defined a transition roadmap for countries receiving funding support based on their income status projections. According to the latest projections, Kenya will complete their transition from vaccine funding in 2029. While eligible countries are kept informed and supported for a smooth transition process, the extent to which countries understand the significant implications of a complete end of GAVI support on immunization service delivery varies.

Assessing Lung Ventilation and Bronchodilator Response in Asthma and Chronic Obstructive Pulmonary Disease with F MRI.

Background Pulmonary function tests are central to diagnosis and monitoring of respiratory diseases but do not provide information on regional lung function heterogeneity. Fluorine 19 (F) MRI of inhaled perfluoropropane permits quantitative and spatially localized assessment of pulmonary ventilation properties without tracer gas hyperpolarization. Purpose To assess regional lung ventilation properties using F MRI of inhaled perfluoropropane in participants with asthma, participants with chronic obstructive pulmonary disease (COPD), and healthy participants, including quantitative evaluation of bronchodilator response in participants with respiratory disease.

Next generation brain health: transforming global research and public health to promote prevention of dementia and reduce its risk in young adult populations.

Efforts to prevent dementia can benefit from precision interventions delivered to the right population at the right time; that is, when the potential to reduce risk is the highest. Young adults (aged 18-39 years) are a neglected population in dementia research and policy making despite being highly exposed to several known modifiable risk factors. The risk and protective factors that have the biggest effect on dementia outcomes in young adulthood, and how these associations differ across regions and groups, still remain unclear.