A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

Background: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.

Methods: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037).

Kinetic chain revisited: consensus expert opinion on terminology, clinical reasoning, examination, and treatment in people with shoulder pain.

Background: The purpose of this study was to reach consensus on the most appropriate terminology and issues related to clinical reasoning, examination, and treatment of the kinetic chain (KC) in people with shoulder pain among an international panel of experts.

Methods: A 3-round Delphi study that involved an international panel of experts with extensive clinical, teaching, and research experience in the study topic was conducted. A search equation of terms related to the KC in Web of Science and a manual search were used to find the experts.

Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health.

Congenital erosive and vesicular dermatosis with reticulated scarring in twins, associated with oesophageal atresia.

This is a case of twins who had a rarely seen diagnosis of congenital erosive and vesicular dermatosis. This report includes a description of the case and discussion around the topic. Click https://www.

Human leukocyte antigen B*0702 is protective against ocular Stevens-Johnson syndrome/toxic epidermal necrolysis in the UK population.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are part of a disease continuum of vesiculobullous mucocutaneous reactions affecting the skin and mucous membranes including the ocular surface. Manifestations of disease range from mild dry eye to progressive conjunctival cicatrisation, limbal epithelial stem cell failure and corneal blindness. In Far Eastern and South East Asian populations where SJS/TEN is prevalent, numerous human leukocyte antigen (HLA) gene variants at the A, B and C loci have been identified as risk factors for developing SJS/TEN with severe ocular complications (SOC).

Protocol for a multi-site pilot and feasibility randomised controlled trial: Surgery versus PhysiothErapist-leD exercise for traumatic tears of the rotator cuff (the SPeEDy study).

Background: Clinically, a distinction is made between types of rotator cuff tear, traumatic and non-traumatic, and this sub-classification currently informs the treatment pathway. It is currently recommended that patients with traumatic rotator cuff tears are fast tracked for surgical opinion. However, there is uncertainty about the most clinically and cost-effective intervention for patients with traumatic rotator cuff tears and further research is required.

Development of a physiotherapist-led exercise programme for traumatic tears of the rotator cuff for the SPeEDy study.

Objectives: The SPeEDy study (Surgery vs. physiotherapist-led exercise for traumatic tears of the rotator cuff) is a two-arm, parallel group, pilot and feasibility randomised controlled trial aiming to evaluate the feasibility of a future main trial. In this paper, the development process and the resultant physiotherapist-led exercise programme used in the SPeEDy study is described.

Integrin alpha-2 and beta-1 expression increases through multiple generations of the EDW01 patient-derived xenograft model of breast cancer-insight into their role in epithelial mesenchymal transition in vivo gained from an in vitro model system.

Background: Breast cancers acquire aggressive capabilities via epithelial to mesenchymal transition (EMT), in which various integrins/integrin-linked kinase signalling are upregulated.

Methods: We investigated this in two patient-derived xenografts (PDXs) developed from breast-to-bone metastases, and its functional significance in a breast cancer cell line system. ED03 and EDW01 PDXs were grown subcutaneously in immunocompromised SCID mice through 11 passages and 7 passages, respectively.

Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial.

Background: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less.

An evaluation of 1 year of advice calls to a tropical and infectious disease referral Centre.

Objectives: Many secondary care departments receive external advice calls. However, systematic advice-call documentation is uncommon and evidence on call nature and burden infrequent. The Liverpool tropical and infectious disease unit (TIDU) provides specialist advice locally, regionally and nationally.

People with obsessive-compulsive disorder often remain symptomatic following psychological treatment: A clinical significance analysis of manualised psychological interventions.

Background: Previous meta-analyses conclude that efficacious psychological treatments for obsessive-compulsive disorder (OCD) exist. However, determining the efficacy of psychological treatments requires multiple forms of assessment. We conducted an individual patient data meta-analysis of randomised controlled trials (RCTs) of manualised psychological therapy for adults with OCD.

Rapid cognitive decline in a patient with chronic lymphocytic leukaemia: a case report.

Background: The use of monoclonal antibodies in various settings has been linked to the development of progressive multifocal leukoencephalopathy (PML). Whilst this association is well-described with agents such as rituximab and natalizumab, the literature describing the occurrence of PML with ofatumumab therapy (especially in a haematology setting) is sparse. This case aims to draw attention to the above association with a particular focus on the mechanisms by which B-cell-depleting therapy can precipitate PML during the treatment of haematological malignancy.

Genetic associations with clozapine-induced myocarditis in patients with schizophrenia.

Clozapine is the most effective antipsychotic drug for schizophrenia, yet it can cause life-threatening adverse drug reactions, including myocarditis. The aim of this study was to determine whether schizophrenia patients with clozapine-induced myocarditis have a genetic predisposition compared with clozapine-tolerant controls. We measured different types of genetic variation, including genome-wide single-nucleotide polymorphisms (SNPs), coding variants that alter protein expression, and variable forms of human leucocyte antigen (HLA) genes, alongside traditional clinical risk factors in 42 cases and 67 controls.

Performance Evaluation of a New Point of Care Viscoelastic Coagulation Monitoring System in Major Abdominal, Orthopaedic and Vascular Surgery.

Viscoelastic Coagulation Testing (VCT), or Thromboelastography has the potential to improve the cost and clinical effectiveness of surgical and medical care by preventing unnecessary treatment and by improving treatment for bleeding, via targeted transfusion strategies. Recently a new viscoelastic coagulation monitoring system, the VCM System, has been developed, which has several advantages over existing systems. The VCM system is a small, portable device, that is designed to be simple to operate and can be used to reliably perform viscoelastic testing at the patient's bedside.

Validity of the International Prostate Symptoms Score in predicting urinary retention after joint replacement.

Postoperative urinary retention necessitating catheterization after major lower limb arthroplasty surgery adds to the patients' postoperative discomfort and increases the risk of urinary tract infection with potential risk of transient bacteraemia and seeding of infection to prosthetic joints. Preoperative evaluation of patients with lower urinary tract symptoms may help to identify at-risk patients and the International Prostate Symptoms Score (IPSS) has been used as a screening tool to quantify the severity of symptoms in males. A prospective cohort of 303 patients undergoing total hip or knee arthroplasty was evaluated using the IPSS.

Prevalence of unmet needs for spasticity management in care home residents in the East Midlands, United Kingdom: a cross-sectional observational study.

Objective: To establish the prevalence of unmet need for spasticity management in care home residents in two counties of the United Kingdom.

Design: Cross-sectional observational study with a six-month follow-up arm for participants with identified unmet needs.

Setting: 22 care homes in Derbyshire and Nottinghamshire.

Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts.

Blood samples, bone marrow, tumours and metastases where possible were collected from SCID mice bearing orthotopic xenografts of the triple-negative MDA-MB-468 cell line or a transplantable ER-positive patient derived xenograft (ED-03), and assessed using human-specific, tandem-nested RT-qPCR for markers relating to detection of circulating (CTCs) and disseminated tumour cells (DTCs), breast cancer clinicopathology, the 'cancer stem cell' phenotype, metabolism, hypoxia and epithelial-mesenchymal plasticity (EMP). Increased levels of SNAI1, ILK, NOTCH1, CK20, and PGR, and a decrease/loss of EPCAM in CTCs/DTCs were observed relative to the primary xenograft across both models. Decreased CD24 and EGFR was restricted to the MDA-MB-468 model, while increased TFF1 was seen in the ED-03 model.

Qualitative Evaluation of Cancer Survivors' Experiences of Metacognitive Therapy: A New Perspective on Psychotherapy in Cancer Care.

Background: Preliminary evidence suggests that metacognitive therapy (MCT), a brief, process-focused psychological intervention, alleviates distress in cancer survivors. In a longitudinal qualitative study nested in an open trial of MCT for cancer survivors, we explored how patients understood, experienced and applied MCT.

Methods: Patients received six MCT sessions.

Do hospital pressures change following rotavirus vaccine introduction? A retrospective database analysis in a large paediatric hospital in the UK.

Objective: Hospitals in the UK are under increasing clinical and financial pressures. Following introduction of childhood rotavirus vaccination in the UK in 2013, rotavirus gastroenteritis (RVGE) hospitalisations reduced significantly. We evaluated changes in 'hospital pressures' (demand on healthcare resources and staff) following rotavirus vaccine introduction in a paediatric setting in the UK.

Implementation of genotype-guided dosing of warfarin with point-of-care genetic testing in three UK clinics: a matched cohort study.

Background: Warfarin is a widely used oral anticoagulant. Determining the correct dose required to maintain the international normalised ratio (INR) within a therapeutic range can be challenging. In a previous trial, we showed that a dosing algorithm incorporating point-of-care genotyping information ('POCT-GGD' approach) led to improved anticoagulation control.

Metacognitive therapy home-based self-help for cardiac rehabilitation patients experiencing anxiety and depressive symptoms: study protocol for a feasibility randomised controlled trial (PATHWAY Home-MCT).

Background: Anxiety and depression are common among patients attending cardiac rehabilitation services. Currently available pharmacological and psychological interventions have limited effectiveness in this population. There are presently no psychological interventions for anxiety and depression integrated into cardiac rehabilitation services despite emphasis in key UK National Health Service policy.