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Aims and ObjectivesBenzodiazepine overdose causes significant morbidity and mortality amongst the UK population. Flumazenil is an effective antidote but concerns regarding side effects have limited its use in the UK. This project aims to review flumazenil use within NHS Lothian.Method and DesignA search was conducted on the electronic note system for ‘flumazenil’ over the last 2 years. These notes were reviewed by two toxicologists who stated yes/no/insufficient information as to whether flumazenil was indicated. Additionally, the two toxicologists reviewed intubations within the ED caused by toxins/overdose. Each case was given a yes/no/unsure for whether flumazenil was indicated.Results and ConclusionWith duplicates removed there were 39 mentions of ‘flumazenil’. It was considered but not given in 14 cases and it was given in the remaining 25. Of the cases where flumazenil was given both reviewers agreed with its administration in 9 cases and both disagreed with its administration in 3 cases. The two reviewers directly disagreed on 3 occasions with the remaining 10 at least one reviewer ‘unsure/insufficient information’.Of the 14 where it was considered but not given the reviewers agreed that it was not indicated in 10 of the cases. They both agreed in two of the cases that it was indicated and the remaining two at least one reviewer was ‘unsure/insufficient information’.Of the 15 intubations, in 4 cases both reviewers thought flumazenil was indicated, 4 cases at least one reviewer thought it was indicated and the other was ‘unsure/insufficient information’.From reviewing flumazenil use it is obvious that there is significant variation in its use as well as disagreement amongst expert reviewers as to when it is indicated/contraindicated. We have also identified at least 4 occasions where flumazenil could have potentially avoided an ICU admission. This project demonstrates a need for a comprehensive guideline for flumazenil use in the ED.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO , the strongest association signal (rs17782313, P = 2.9 × 10 −6 ) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z -score units; P = 2.8 × 10 −15 ) and 5,988 children aged 7–11 (0.13 Z -score units; P = 1.5 × 10 −8 ). In case-control analyses ( n = 10,583), the odds for severe childhood obesity reached 1.30 ( P = 8.0 × 10 −11 ). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families ( P (pedigree disequilibrium test average; PDT-avg) = 2.4 × 10 −4 ). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.