Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1

Abstract: Background We recently observed mutations in ADAR1 to cause a phenotype of bilateral striatal necrosis (BSN) in a child with the type I interferonopathy Aicardi-Goutieres syndrome (AGS). We therefore decided to screen patients with apparently non-syndromic BSN for ADAR1 mutations, and for an upregulation of interferon-stimulated genes (ISGs). Methods We performed Sanger sequencing of ADAR1 in a series of patients with BSN presenting to us during our routine clinical practice. We then undertook detailed clinical and neuroradiological phenotyping in nine mutation-positive children. We also measured the expression of ISGs in peripheral blood from these patients, and in children with BSN who did not have ADAR1 mutations. Results Nine ADAR1 mutation-positive patients from seven families demonstrated an acute (five cases) or subacute (four cases) onset of refractory, four-limb dystonia starting between 8 months and 5 years of age. Eight patients were developmentally normal at initial presentation. In seven cases, the disease was inherited as an autosomal recessive trait, while two related patients were found to have a heterozygous (dominant) ADAR1 mutation. All seven mutation-positive patients assayed showed an upregulation of ISGs (median: 12.50, IQR: 6.43–36.36) compared to controls (median: 0.93, IQR: 0.57–1.30), a so-called interferon signature, present many years after disease onset. No interferon signature was present in four children with BSN negative for mutations in ADAR1 (median: 0.63, IQR: 0.47–1.10). Conclusions ADAR1 -related disease should be considered in the differential diagnosis of apparently non-syndromic BSN with severe dystonia of varying evolution. The finding of an interferon signature provides a useful screening test for the presence of ADAR1 mutations in this context, and may suggest novel treatment approaches.

Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment

Abstract: AIMS: In September 2012 the UK's Commission on Human Medicines (CHM) recommended changes in management of paracetamol poisoning: use of a single '100mg/L' nomogram treatment line; ceasing risk assessment; treating all staggered/uncertain ingestions; increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions, and costs of paracetamol poisoning. METHODS: Prospectively collected data from adult patients presenting to 3 large UK hospitals from 3 Sept 2011 to 3 Sept 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90,000 patients/annum with paracetamol overdose. RESULTS: There were increases in the numbers:- presenting to hospital (before 1703, after 1854; increase 8.9%[95%CI 1.9-16.2] p=0.011); admitted (1060/1703 [62.2%] vs 1285/1854 [69.3%]; increase: 7.1% [4.0-10.2], pCONCLUSIONS: The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in assessment of poisoning. Language: en

Alexithymia in Adolescents with Autism Spectrum Disorder: Its Relationship to Internalising Difficulties, Sensory Modulation and Social Cognition

Abstract: Alexithymia is a personality trait frequently found in adults with autism spectrum disorder (ASD), and has been linked to impairments in emotion recognition and empathy. The presentation of alexithymia within ASD at younger ages remains unexplored, and was examined in the present study. Alexithymia rates were significantly elevated in ASD (55 %; 31/56 scoring above cut-off) versus non-ASD adolescents (16 %; 5/32 scoring above cut-off). Within individuals with ASD, alexithymia was associated with increased self-reported anxiety, parent-reported emotional difficulties, self-reported sensory processing atypicalities, and poorer emotion recognition, but was not associated with theory of mind ability. Overall, our results suggest that alexithymia is highly prevalent, and has selective cognitive correlates in young people with ASD.

Apixaban versus Dalteparin for the Treatment of Acute Venous Thromboembolism in Patients with Cancer: The Caravaggio Study

Abstract: International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years (β = 80%; α one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.