Prediction of chronic severe intestinal failure-associated liver disease by current criteria in adults: A descriptive cohort study.

Introduction: Intestinal failure-associated liver disease covers a spectrum of conditions from mild to end-stage disease. Currently, there are 9 diagnostic criteria divided to four categories: cholestasis, steatosis, fibrosis, and unclassified. Our aim was to evaluate the application of these criteria to patients with chronic severe liver disease in patients with intestinal failure.

Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog.

The emerging field of senolytics is centered on eliminating senescent cells to block their contribution to the progression of age-related diseases, including cancer, and to facilitate healthy aging. Enhancing the selectivity of senolytic treatments toward senescent cells stands to reduce the adverse effects associated with existing senolytic interventions. Taking advantage of lipofuscin accumulation in senescent cells, we describe here the development of a highly efficient senolytic platform consisting of a lipofuscin-binding domain scaffold, which can be conjugated with a senolytic drug via an ester bond.

CD24 Positive Nucleus Pulposus Cells in Adult Human Intervertebral Discs Maintain a More Notochordal Phenotype Than GD2 Positive Cells.

Background: Notochordal cells (NCs) present in the nucleus pulposus (NP) of the developing human intervertebral disc (IVD) disappear during the first decade of life. This loss coincides with the onset of IVD degeneration, therefore these cells are hypothesized to be important in NP homeostasis. Putative NC-derived (CD24) and progenitor (TIE2/GD2) cell sub-populations have previously been identified in the adult human NP, but their characteristics have yet to be compared.

The Impact of Age and Sex on Fasting Plasma Glucose and Glycated Haemoglobin (HbA1c) in the Non-diabetes Population.

Introduction: We previously reported sex differences in the distribution of glycated haemoglobin (HbA1c) for men/women aged < 50 years vs older individuals, with implications for delayed diabetes diagnosis. Here, we explored whether this pattern was also seen in matched fasting plasma glucose (FPG) levels.

Methods: We extracted data on same-day, paired HbA1c and FPG levels from clinical biochemistry laboratory databases from Mersey and West Lancashire Teaching Hospitals NHS Trust (n = 10,153) and Cambridge University Hospitals NHS Foundation Trust (n = 10,022) between Jan 2019 and Dec 2023.

How Does Thyroid Hormone Profile Differ on and Off Replacement Treatment?

Introduction: There continues to be much discussion around optimisation of thyroid hormone status in hypothyroid individuals. We here looked the way that free T4(FT4) and thyroid-stimulating hormone (TSH) related to each other in a large laboratory sample of people who underwent a thyroid function test (TFT), split between those on levothyroxine replacement (monitoring test) and those who underwent a test to check for thyroid hormone imbalance (diagnostic test; not on levothyroxine).

Methods: TFT test (FT4/TSH) results were extracted from the Salford Royal Hospital Laboratory Information Management System during 2009-2012.

Involving People With Lived Experience in Electronic Health Record Database Studies Reflections and Learning From the CHOOSE Study.

Background: Patient and public involvement and engagement (PPIE) is integral to health research. Reporting of PPIE methods and impact is becoming increasingly common in health research. However, reporting on PPIE in studies using large, routinely collected electronic health record data sets is less common.

Physiotherapists' Experiences and Perceived Acceptability of Delivering a Knee Bracing Intervention for People With Symptomatic Knee Osteoarthritis in a Randomised Trial (PROP OA): A Qualitative Study.

Objectives: To explore physiotherapists' experiences and perceived acceptability of delivering a bracing intervention for knee osteoarthritis (OA) in the 'PROvision of braces for Patients with knee OA' (PROP OA) randomised controlled trial.

Method: Semi-structured telephone interviews with consenting physiotherapists who received the PROP OA training programme and delivered the knee bracing intervention (advice, information and exercise instruction plus knee brace matched to patients' clinical and radiographic presentation and with adherence support). Interviews were recorded and transcribed verbatim.

A qualitative study exploring the digital therapeutic alliance with fully automated smartphone apps.

Background: Digital mental health interventions are increasingly used to scale up access to mental health support, yet very few mental health apps are empirically supported, with high attrition rates. The therapeutic alliance between therapists and clients is a key factor in predicting psychological therapy retention and outcomes. Understanding how this concept translates to the digital context, the so-called digital therapeutic alliance (DTA), may help enhance retention and outcomes in digital mental health.

Association of urinary eosinophilic protein X at age 3 years and subsequent persistence of wheezing and asthma diagnosis in adolescence.

Background: Wheezing is common in early life, but most children stop wheezing by school age. However, the prediction of course of wheezing through childhood is difficult.

Objective: To investigate whether urinary EPX (a marker of eosinophil activation) in children at age 3 years may be useful for the prediction of wheeze persistence and future asthma diagnosis.

The PAUL Glaucoma Implant in the management of uveitic glaucoma-3-year follow-up.

Background/objectives: Evaluate the mid-term outcomes of the PAUL Glaucoma Implant (PGI) in the management of uveitic glaucoma.

Subjects/methods: This was a single-centre, multi-surgeon, retrospective analysis of 50 consecutive cases of PGI for uveitic glaucoma performed between April 2019 and August 2021. Primary outcomes include: complete and qualified success (IOP ≥5 mmHg to ≤21 mmHg with ≥20% IOP reduction) or failure (IOP exceeding the success criteria, additional glaucoma procedures, no perception of light vision).

Assessing the Value of New Antimicrobials: Evaluations of Cefiderocol and Ceftazidime-Avibactam to Inform Delinked Payments by the NHS in England.

Objectives: The UK has recently established subscription-payment agreements for two antimicrobials: cefiderocol and ceftazidime-avibactam. This article summarises the novel value assessments that informed this process and lessons learned for future pricing and funding decisions.

Methods: The evaluations used decision modelling to predict population incremental net health effects (INHEs), informed by systematic reviews, evidence syntheses, national surveillance data and structured expert elicitation.

Decoding T cell senescence in cancer: Is revisiting required?

Senescence is an inherent cellular mechanism triggered as a response to stressful insults. It associates with several aspects of cancer progression and therapy. Senescent cells constitute a highly heterogeneous cellular population and their identification can be very challenging.

Small volume fluid resuscitation and supplementation with 20% albumin versus buffered crystalloids in adults with septic shock: A protocol for a randomised feasibility trial.

Background: Fluid therapy is universally administered in the management of patients with sepsis, however excessive cumulative fluid balance has been shown to result in worse outcomes. Hyperoncotic albumin results in both lower fluid volumes and early cumulative fluid balance, and may reduce short-term mortality in patients with septic shock.

Methods: In this single centre, open label, feasibility trial; patients with early septic shock will be randomly allocated either 20% albumin for resuscitation and daily supplementation, versus buffered crystalloids alone for all fluid therapy.

Centre-level fluid management practices in the BISTRO trial and their lack of association with participant fluid status and blood pressure in non-anuric haemodialysis patients.

Introduction: Fluid assessment and management is a key aspect of good dialysis care and is affected by patient-level characteristics and potentially centre-level practices. In this secondary analysis of the BISTRO trial we wished to establish whether centre-level practices with the potential to affect fluid status were stable over the course of the trial and explore if they had any residual associations with participant's fluid status.

Methods: Two surveys (S) of fluid management practices were conducted in 32 participating centres during the trial, (S1: 2017-18 and S2: 2021-22).

Digital AVATAR therapy for distressing voices in psychosis: the phase 2/3 AVATAR2 trial.

Distressing voices are a core symptom of psychosis, for which existing treatments are currently suboptimal; as such, new effective treatments for distressing voices are needed. AVATAR therapy involves voice-hearers engaging in a series of facilitated dialogues with a digital embodiment of the distressing voice. This randomized phase 2/3 trial assesses the efficacy of two forms of AVATAR therapy, AVATAR-Brief (AV-BRF) and AVATAR-Extended (AV-EXT), both combined with treatment as usual (TAU) compared to TAU alone, and conducted an intention-to-treat analysis.

Virtual screening-led design of inhibitor scaffolds for the NLRP3 inflammasome.

The NLRP3 inflammasome is a key target for drug discovery due to its implication in a range of inflammation-related diseases. In this work, we identify new inhibitors of the NLRP3 inflammasome via a hierarchical virtual screening strategy using molecular similarity, docking and MD simulation. The most potent inhibitors identified from a subsequent biological assay (IC of 1 - 4 μM) feature a sulfonamide group, a motif known to favour NLRP3 inhibition, in conjunction with an indole, benzofuran or tricyclic 6,7-dihydro-5H-indeno[5,6-b]furan ring, yielding novel scaffolds.

The CO-produced Psychosocial INtervention delivered by GPs to young people after self-harm (COPING): protocol for a feasibility study.

Background: Self-harm in young people is a growing concern and reducing rates a global priority. Rates of self-harm documented in general practice have been increasing for young people in the UK in the last two decades, especially in 13-16-year-olds. General practitioners (GPs) can intervene early after self-harm but there are no effective treatments presently available.