Recognising uncertainty: an integrated framework for palliative care in perinatal medicine.

In perinatal medicine, the number of babies with life-limiting or life-threatening conditions is increasing and the benefits of providing palliative care with a holistic, interdisciplinary approach are well documented. It can be particularly challenging, however, to integrate palliative care into routine care where there exists uncertainty about a baby's diagnosis or potential outcome.This framework, developed collaboratively by the British Association of Perinatal Medicine (BAPM) and the Association of Paediatric Palliative Medicine (APPM), offers supportive guidance for all healthcare professionals working in perinatal medicine across antenatal and neonatal services.

Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning.

The ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which likely affects models' generalizability across subtypes.

UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

Incidence of diabetes mellitus following hospitalisation for COVID-19 in the United Kingdom: A prospective observational study.

Background: People hospitalised for coronavirus disease 2019 (COVID-19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness.

Methods: We analysed a multicentre prospective cohort study (PHOSP-COVID) of people ≥18 years discharged from NHS hospitals across the United Kingdom following COVID-19.

Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency.

The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease.

Thromboelastography for rapid diagnosis of heparin-like anticoagulant release during anaphylaxis-induced coagulopathy in systemic mastocytosis: a case report.

Anaphylaxis can induce life-threatening coagulopathy by releasing various mediators from activated mast cells. These mediators directly affect coagulation and fibrinolytic pathways, increasing the bleeding risk. Diagnosis and management of anaphylaxis-induced coagulopathy remain challenging.

Barriers to Effective Prehospital and Hyperacute Stroke Care in India: A Physician Perspective.

Introduction: The incidence of stroke is increasing in India. Prehospital stroke care is crucial for reducing stroke morbidity and mortality, but its implementation in India faces several challenges. Limited original research exists on prehospital stroke care in India, making it essential to identify the problems in implementing effective prehospital stroke care.

Intensive Lifestyle Intervention, Cardiac Biomarkers, and Cardiovascular Outcomes in Diabetes: Look AHEAD Cardiac Biomarker Ancillary Study.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular outcomes and are recommended for measurement in type 2 diabetes (T2D). However, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers and the prognostic association of changes in these biomarkers with risk of adverse cardiovascular outcomes in T2D are not well-established.

Objectives: This study sought to evaluate the effects of an ILI on cardiac biomarkers and the association of changes in cardiac biomarkers with risk of cardiovascular outcomes in T2D.

Oxidized Phospholipids and Calcific Aortic Valvular Disease.

Background: Oxidized phospholipids (OxPLs) are carried by apolipoprotein B-100-containing lipoproteins (OxPL-apoB) including lipoprotein(a) (Lp[a]). Both OxPL-apoB and Lp(a) have been associated with calcific aortic valve disease (CAVD).

Objectives: This study aimed to evaluate the associations between OxPL-apoB, Lp(a) and the prevalence, incidence, and progression of CAVD.

Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis.

Background: Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage.

Objective: To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6 g of fibrinogen) of cryoprecipitate on 28-day mortality.

Wish to die trying to live: unwise or incapacitous? The case of University Hospitals Birmingham NHS Foundation Trust versus 'ST'.

The recent legal dispute about medical treatment for a 19-year-old patient, Sudiksha Thirumalesh, (known initially by the Court of Protection as 'ST') in A NHS Trust versus ST & Ors (2023) raised several challenging ethical issues. While Sudiksha's case bears similarities to other high-profile cases in England and Wales, there are key differences. Crucially, Sudiksha herself was part of the disagreement.

Effectiveness of a digital health and financial incentive intervention to promote physical activity in patients with type 2 diabetes: study protocol for a randomised controlled trial with a nested qualitative study-ACTIVATE trial.

Background: The prevention of type 2 diabetes (T2DM) is recognised as a health care priority in the UK. In people living with T2DM, lifestyle changes (e.g.

Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance.

The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs.

A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking.

Integrating proteomic and transcriptomic data with genetic architectures of problematic alcohol use and alcohol consumption behaviours can advance our understanding and help identify therapeutic targets. We conducted systematic screens using genome-wise association study data from ~3,500 cortical proteins (N = 722) and ~6,100 genes in 8 canonical brain cell types (N = 192) with 4 alcohol-related outcomes (N ≤ 537,349), identifying 217 cortical proteins and 255 cell-type genes associated with these behaviours, with 36 proteins and 37 cell-type genes being new. Although there was limited overlap between proteome and transcriptome targets, downstream neuroimaging revealed shared neurophysiological pathways.

Effect of the National Enhanced Service for weight management on the content of annual review consultations for patients living with obesity and hypertension and/or diabetes.

Guidelines specify that clinicians should support patients living with obesity by referring to weight management programmes (WMPs), but clinicians do so infrequently. To provide additional support to patients living with obesity and weight-related conditions, the UK government instated the National Enhanced Service (NES) for weight management in England, including a reimbursement to general practices for referring eligible patients to WMPs. To assess the impact of the NES on conversations regarding weight and relevant behavioural risk factors in primary care consultations we recruited 11 medical practices in England where the NES was operating and six comparator practices from Scotland and Wales where the NES was not implemented.