A postal questionnaire inquiring about routine sedation and premedication practice for upper gastrointestinal endoscopy was sent to 1048 doctors. Of 665 appropriate returns, 81% were from consultant physicians and surgeons. Most endoscopists (90%) reported using an intravenous benzodiazepine for at least three quarters of endoscopies and 54% of physicians and 69% of surgeons always did so. Midazolam was the intravenous sedative used by a third of ali respondents and 13% also used an additional intravenous agent, usualiy pethidine. Over the previous two years a total of 119 respiratory arrests, 37 cardiac arrests, and 52 deaths were identified. Adverse outcomes were reported more frequently by consultant physicians, by those who 'titrated' the intravenous sedative, and by those who used an additional intravenous agent, but were reported equaliy frequently by endoscopists using midazolam and endoscopists using diazepam. There is an urgent need for a prospective study to identify the circumstances and risk factors associated with adverse outcomes related to endoscopy.

AIMS:The aim of this study was to investigate MlF expression and activity in human sporadic colorectal adenomas and in intestinal adenomas from the Apc mouse model of familial adenomatous polyposis. METHODS: lmmunohistochemistry was performed on archival formalin-fixed, paraffin-embedded human sporadic colorectal adenomas (n=56), and on small and large intestine of Apc mice and wild type littermates. Human MLF protein levels were analysed in fresh paired colorectal adenoma and normal mucosa samples by ELSA (n=16) and by Western blot analysis (n=8). A phydroxyphenylpyruvate (HPP) tautomerase assay was used to measure specific MIF activity in paired fresh tissue (n=20). RESULTS: In human colorectal tissue, immunohistochemistry and Western blot analysis both demonstrated increased MIF protein levels in adenomas compared with paired normal colorectal mucosa. MIF was localised to both epithelial (particularly the apical membrane) and stromal cells in adenomas. The ELISA demonstrated a mean 1.9-fold increase (95% CI 1.1-2.7) in immunoreactive MlF in adenomas compared with paired normal mucosa. The HPP tautomerase assay revealed a mean 1.5-fold increase (95% CI 1.2-1.7) in MIF activity in adenomas. Inmunohistochemical analysis in the Apc mouse intestine revealed a similar pattern of protein localisation in adenomas and histologically normal mucosa, with MIF localisation in dysplastic epithelial cells being prominent. CONCLUSIONS: MIF protein levels are increased in human sporadic colorectal adenomas and in intestinal adenomas from the Apc mouse. The precise role of MIF in epithelial and stromal cell compartments of adenomas during the early stages of intestinal tumorigenesis is currently being investigated.

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In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory depression and even death. There have been at least ten studies comparing diazepam with midazolam for upper gastrointestinal endoscopy but many have involved relatively small numbers and none have adequately addressed the question of dosage in the elderly. We have carefully recorded the dose of intravenous midazolam used to produce adequate sedation prior to upper gastrointestinal endoscopy in 800 consecutive patients. The dose of midazolam decreased markedly with age in both male and female patients. There was a highly significant correlation in both sexes between age and the dose of midazolam (rho -0.787, P < 0.001 for males and rho -0.768, P < 0.001 for females). There was only a small difference in dose in men and women, an average of 1 mg; and no difference in dose over the age of 70 years. In patients over 70 years of age the dose of midazolam necessary for endoscopy is often so small that overdosage is all too easy.

ObjectivesData on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB.SettingSix UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery.Participants936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds.Primary and secondary outcome measuresHealthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level.ResultsMean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million.ConclusionsAUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB.Trial registration numberISRCTN85757829 and NCT02105532.

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