North Bristol NHS Trust

About: North Bristol NHS Trust is a healthcare organization based out in Bristol, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 2204 authors who have published 2811 publications receiving 61110 citations.

De novo mutations in GRIN1 cause extensive bilateral polymicrogyria.

Abstract: Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-d-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-d-aspartate receptor signalling in the pathogenesis of polymicrogyria.

Vancomycin therapeutic drug monitoring: is there a consensus view? The results of a UK National External Quality Assessment Scheme (UK NEQAS) for Antibiotic Assays questionnaire

Abstract: This study investigated vancomycin therapeutic drug monitoring (TDM) and issues related to patient management. Questionnaires were distributed to 310 participants in the UK National External Quality Assessment Scheme (NEQAS) for Antibiotic Assays. The response rate was 57.4%. The majority (76%) had an 'in-house' assay service based, almost exclusively, in the microbiology department, and a fluorescence polarization immunoassay (FPIA) was used by 97%. Almost half (48.7%) had an assay service available for 24 h/day, 7 days/week and 92.7% expected same-day results. The majority (80%) had issued guidelines for vancomycin use. A 12 hourly initial dosing regimen was used by 89%. Trough assay samples were taken or=10 mg/L as 'toxic' but 13 concentrations were quoted as toxic post-dose measurements. In conclusion, there was a wide variability and poor consensus with regard to post-dose vancomycin assay sampling times, target ranges and what constituted a toxic level.

Orthoplastic surgical collaboration is required to optimise the treatment of severe limb injuries: A multi-centre, prospective cohort study

Abstract: Open fractures are severe, complex, limb-threatening and high-energy injuries, often involving lesions of both bone and soft tissues. Traditionally, treatment has been piecemeal by orthopaedic and plastic surgeons. This study aimed to prospectively investigate whether combining orthopaedic and plastic surgery in treating these injuries is more effective than the conventional orthopaedic care. A prospective multi-centre cohort study was conducted. Differences in the type of approach to severe limb trauma allowed a comparison between combined orthoplastic and traditional exclusively orthopaedic treatment. Time for fracture and soft tissue healing and the recovery of limb function were the main outcome measures studied. All patients suffering from a severe open tibial fracture were prospectively included between January 2012 and December 2013 and followed until December 2014. Recruiting units were as follows: (1) an established orthoplastic centre, (2) a unit without experience in the orthoplastic approach and (3) a unit where the orthoplastic approach has been recently introduced in a developing country (Pakistan). A total of 160 patients were included in the study. Of these, 70% were treated with an orthoplastic approach, whereas 30% were treated by an orthopaedic team. All outcome measures were statistically improved by the orthoplastic approach. A coordinated, combined pathway to both the bony and the soft tissue components of open tibial fractures through orthoplastic surgery can be successfully delivered with attention to important timelines to achieve better patient outcomes in different socio-economic settings.

Use of infliximab in juvenile onset rheumatological disease-associated refractory uveitis: efficacy in joint and ocular disease

Abstract: There is an identified disparity between the efficacy of tumour necrosis factor (TNF) inhibition in the treatment of uveitis in paediatric onset inflammatory arthritis and that of joint disease.1–5 We retrospectively reviewed the case notes of six patients with aggressive, refractory joint and ocular paediatric-onset disease treated with infliximab in a multidisciplinary clinic. Our report uses the Standardised Uveitis Nomenclature (SUN) grading system6 for uveitis and steroid dose as an outcome measure. All patients received weekly infliximab infusions at 0, 2, 6 and 8 weeks. Patients were maintained on low dose immunosuppression with methotrexate while receiving treatment. Five of six patients had previously been treated with another anti-TNF agent (three …