Key considerations for digital decentralised clinical trials from a feasibility study assessing pacing interventions for long COVID.

Post COVID-19 condition or long COVID is highly prevalent and often debilitating, with key symptoms including fatigue, breathlessness, and brain fog. There is currently a lack of evidence-based treatments for this highly complex syndrome. There is a need for clinical trial platforms to rapidly evaluate nonpharmacological treatments to support affected individuals with symptom management.

Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial.

Background: Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration.

Critical care unit bed availability and postoperative outcomes: a multinational cohort study.

Background: Critical care beds are a limited resource, yet research indicates that recommendations for postoperative critical care admission based on patient-level risk stratification are not followed. It is unclear how prioritisation decisions are made in real-world settings and the effect of this prioritisation on outcomes.

Methods: This was a prespecified analysis of an observational cohort study of adult patients undergoing inpatient surgery, conducted in 274 hospitals across the UK and Australasia during 2017.

Adult inflammatory leukoencephalopathies.

Inflammatory white matter disorders may commonly mimic genetic leukoencephalopathies. These include atypical presentations of common conditions, such as multiple sclerosis, together with rare inflammatory disorders. A structured approach to such cases is essential, together with judicious use of the many available diagnostic biomarkers.

Associations between Aircraft Noise, Sleep, and Sleep-Wake Cycle: Actimetric Data from the UK Biobank Cohort near Four Major Airports.

Background: Nighttime aircraft noise may affect people's sleep, yet large-scale evidence using objective and subjective measures remains limited.

Objective: Our aim was to investigate associations between nighttime aircraft noise exposure and objectively measured sleep disturbance using a large UK cohort.

Methods: We used data from 105,770 UK Biobank cohort participants exposed and unexposed to aircraft noise who lived in 44 local authority districts near 4 international airports in England.

Impact of donor transaminases on liver transplant utilisation and unnecessary organ discard: national registry cohort study.

Background: Donor liver transaminases (ALT and AST) have been used to decline livers for transplant, despite evidence that they do not influence transplant outcomes. This study assesses the effect that raised donor transaminases have on the unnecessary decline of livers.

Methods: This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019).

Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19.

We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes.

Cognitive activity significantly affects the dynamic cerebral autoregulation, but not the dynamic vasoreactivity, in healthy adults.

Introduction: Neurovascular coupling (NVC) is an important mechanism for the regulation of cerebral perfusion during intensive cognitive activity. Thus, it should be examined in terms of its effects on the regulation dynamics of cerebral perfusion and its possible alterations during cognitive impairment. The dynamic dependence of continuous changes in cerebral blood velocity (CBv), which can be measured noninvasively using transcranial Doppler upon fluctuations in arterial blood pressure (ABP) and CO tension, using end-tidal CO (EtCO) as a proxy, can be quantified via data-based dynamic modeling to yield insights into two key regulatory mechanisms: the dynamic cerebral autoregulation (dCA) and dynamic vasomotor reactivity (DVR), respectively.

Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.

Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion. In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D), which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D.

Nurse understaffing associated with adverse outcomes for surgical admissions.

Background: Nurses play a crucial role in maintaining the safety of surgical patients. Few nurse staffing studies have looked specifically at surgical patients to examine the impact of exposure to low staffing on patient outcomes.

Methods: A longitudinal patient analysis was conducted in four organizations in England using routine data from 213 910 admissions to all surgical specialties.

An immunology model for accelerated coronary atherosclerosis and unexplained sudden death in the COVID-19 era.

The immunological basis for cardiac deaths remote from potential triggering viral infection, including SARS-CoV-2 infection, remains enigmatic. Cardiac surface inflammation, including the pericardium, epicardium and superficial myocardium with associated coronary artery vasculitis in infant Kawasaki Disease (KD) and multisystem inflammatory syndrome in children (MIS-C) is well recognised. In this perspective, we review the evidence pointing towards prominent post-viral infection related epicardial inflammation in older subjects, resulting in atherosclerotic plaque destabilisation with seemingly unrelated myocardial infarction that may be temporally distant from the actual infectious triggers.

Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling.

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naive pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumor sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor.

Geographical Inequality in Access to Aortic Valve Intervention in England: A Report from the UK Transcatheter Aortic Valve Implantation Registry and National Adult Cardiac Surgery Audit.

Background: For patients with severe aortic stenosis, transcatheter aortic valve implantation (TAVI) is a less invasive but equally effective treatment option compared with surgical aortic valve replacement (SAVR). In 2019, we reported low rates of TAVI in the UK compared with other countries in western Europe and highlighted profound geographical variation in TAVI care. Here, we provide contemporary data on access to aortic valve replacement by either TAVI or SAVR across clinical commissioning groups in England.

Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial.

Background: Motor neuron disease represents a group of progressive and incurable diseases that are characterised by selective loss of motor neurons, resulting in an urgent need for rapid identification of effective disease-modifying therapies. The MND SMART trial aims to test the safety and efficacy of promising interventions efficiently and definitively against a single contemporaneous placebo control group. We now report results of the stage two interim analysis for memantine and trazodone.

Carriage of Streptococcus pneumoniae in adults hospitalised with community-acquired pneumonia.

Objectives: We aimed to determine the prevalence of and risk factors for nasopharyngeal and oral pneumococcal carriage in adults with community-acquired pneumonia (CAP), and the relationship between carried and disease-causing serotypes.

Methods: Between 2016 and 2018, nasopharyngeal swabs, oral-fluid, and urine were collected from hospitalised adults recruited into a prospective cohort study of CAP. Pneumococcal carriage was detected by semi-quantitative real-time PCR of direct and culture-enriched nasopharyngeal swabs and culture-enriched oral-fluid.

Dietary pattern trajectories in early childhood and their associations with patterns of maternal feeding practices in a multi-ethnic Asian cohort.

Background: Maternal feeding practices play a major role in children's dietary intakes. However, there is limited data on the associations between trajectories of dietary patterns (DPs) and patterns of maternal feeding practices during early childhood.

Methods: Using data from a multi-ethnic Asian cohort study, namely the Growing Up in Singapore Towards healthy Outcomes (GUSTO), dietary intakes were measured using Food Frequency Questionnaires in children at 18 months, 5 and 7 years of age.

Differential diagnosis of suspected multiple sclerosis: considerations in people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia.

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis.

Epithelial Interleukin-1 Receptor-Like-1 Activation Is Contingent on Interleukin-33 Isoforms and Asthma-Related Receptor Variation.

Introduction: The interleukin-33/interleukin-1 receptor-like-1 (IL-33/IL1RL1) signalling pathway is implicated in asthma pathogenesis, with IL1RL1 nonsynonymous genetic polymorphisms associated with disease risk. We aimed to determine these variants' effect on IL1RL1 signalling induced by different IL33 isoforms thought to be elevated in the asthmatic airway.

Method: In a project funded by GSK plc, which has developed an IL-33 receptor inhibitor for asthma treatment, human embryonic kidney 293 (HEK293) cells expressing secreted embryonic alkaline phosphatase (SEAP) driven by a nuclear factor kappa-beta (NF-κB) promoter, were transiently transfected with IL1RL1, containing one of four extracellular and Toll/interleukin 1 receptor (TIR) domain haplotypes.