Poor outcomes in hospitalized patients with gastrointestinal bleeding: impact of baseline risk, bleeding severity, and process of care.

OBJECTIVES: Previous studies have found higher mortality rates among inpatients (IPs) compared with new admissions (outpatients, OPs) with acute upper gastrointestinal bleeding (AUGIB), but no studies have investigated the cause for this. The objective of this study was to determine whether the difference in outcomes between IPs and OPs with AUGIB can be explained by differences in baseline characteristics, bleeding severity, or processes of care. METHODS: Data were collected from 6,657 presentations with all-cause AUGIB from 212 UK hospitals as part of a nationwide audit. RESULTS: IPs were older (77 vs. 65 years, P<0.001), had greater comorbidity, and presented with more severe bleeding. There was no difference in median time to endoscopy (24 vs. 24 h, P=0.67) or receipt of endotherapy (19% vs. 17%, P=0.29). IPs had an odds of mortality 4.8 times that of OPs (26% vs. 7%; odds ratio (OR) 4.8, 95% confidence interval (CI) 3.9-5.8); after adjusting for baseline characteristics, this fell by 24% to 3.3 (95% CI 3.2-4.9) and after adjusting for bleeding severity alone to 4.0 (95% CI 3.2-4.9); adjusting for care processes had minimal effect. IPs had more than a twofold increased odds of rebleeding (20% vs. 12%; OR 2.1, 95% CI 1.7-2.5); adjusting for both baseline characteristics and severity of bleeding reduced this by 50% (OR 1.4, 95% CI 1.3-2.4), but process of care had no additional impact. CONCLUSIONS: IPs present with both higher baseline risks and more severe bleeding. These differences in baseline characteristics explain some but not all of the greater mortality of IPs with AUGIB.

Socioeconomic variation in uptake of colonoscopy following a positive faecal occult blood test result: a retrospective analysis of the NHS Bowel Cancer Screening Programme.

BACKGROUND: Bowel cancer is a serious health burden and its early diagnosis improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals with a positive test result. Socioeconomic inequalities have been demonstrated for FOBt uptake, but it is not known whether they persist at the next stage of the screening pathway. The aim of this study was to assess the association between colonoscopy uptake and area socioeconomic deprivation, controlling for individual age and sex, and area ethnic diversity, population density, poor self-assessed health, and region. METHODS: Logistic regression analysis of colonoscopy uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged between 60 and 69 years. RESULTS: Overall colonoscopy uptake was 88.4%. Statistically significant variation in uptake is found between quintiles of area deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9-89.1%), quintiles of poor self-assessed health (87.5-89.5%), non-white ethnicity (84.6-90.6%) and population density (87.9-89.3%), and geographical regions (86.4-90%). CONCLUSION: Colonoscopy uptake is high. The variation in uptake by socioeconomic deprivation is small, as is variation by subgroups of age and sex, poor self-assessed health, ethnic diversity, population density, and region.

National audit of the use of surgery and radiological embolization after failed endoscopic haemostasis for non-variceal upper gastrointestinal bleeding.

BACKGROUND: Following non-variceal upper gastrointestinal bleeding (NVUGIB), 10-15 per cent of patients experience further bleeding. Although surgery has been the traditional salvage therapy, there is renewed interest in transcatheter arterial embolization (TAE). This study examined the use, clinical characteristics and outcomes of patients receiving salvage surgery or TAE after failed endoscopic haemostasis for NVUGIB. METHODS: A UK national audit of upper gastrointestinal bleeding was undertaken in May and June 2007. A logistic regression model was used to identify clinical predictors of endoscopic failure. RESULTS: Data were analysed from 4478 patients involving 212 UK centres. Some 533 (11·9 per cent) experienced further bleeding, of whom 163 (30·6 per cent) proceeded to salvage therapy with surgery (97), TAE (60) or both (6). Among surgical patients (mean age 71 years), 66·0 per cent (68 of 103) had a Rockall score of at least 3 and emergency surgery was carried out between midnight and 08.00 hours in 21 per cent, with a consultant surgeon present in 89 per cent of operations. Some 9 per cent of patients had further bleeding after TAE, resulting in later surgery. The mortality rate was 29 per cent after surgery, 10 per cent after TAE and 23·2 per cent among those with further bleeding after the index endoscopy that was managed by endoscopy alone. The strongest predictors of endoscopic failure were coagulopathy (odds ratio 3·27, 95 per cent confidence interval 2·37 to 4·53) and a haemoglobin level of 10 g/dl or less (odds ratio 2·22, 1·71 to 2·87, for haemoglobin 8-10 g/dl). CONCLUSION: Salvage surgery and embolization are required in fewer than 4 per cent of patients with NVUGIB. The high postoperative mortality rate, reflecting age, co-morbidity and severity of bleeding, warrants a prospective study to establish the effectiveness and safety of TAE as an alternative to surgery in the management of bleeding after failure of endoscopic therapy.

What predicts failed cannulation and therapy at ERCP? Results of a large-scale multicenter analysis.

UNLABELLED: STUDY BACKGROUND AND AIMS: Predicting outcome at endoscopic retrograde cholangiopancreatography (ERCP) remains difficult. Our aim was to identify the risk factors for failed ERCP. PATIENTS AND METHODS: A prospective multicenter study of ERCP was performed in 66 hospitals across England. Data on 4561 patients were collected using a structured questionnaire completed at the time of ERCP. RESULTS: In total 3209 patients had not had an ERCP prior to the study period. Considering their first ever ERCP, 2683 (84 %) were successfully cannulated, 2241(70 %) had all intended therapy completed, 360 (11 %) had some intended therapy completed, and 608 (19 %) were considered to have had a failed procedure. For first ever ERCP, factors associated with incomplete procedure (odds ratio and 95 % confidence interval) were: Billroth surgery (9.2, 3.2 - 26.7), precutting (2.0, 1.6 - 2.7), common bile duct (CBD) stone size and number (3.2, 2.1 - 4.8 for multiple, large stones), interventions in the pancreatic duct (3.4, 1.6 - 7.0), and CBD stenting (2.8, 2.2 - 3.5). Analysis of the 1352 patients who had undergone an ERCP prior to the study period indicated previous failed ERCP was also predictive of incomplete therapy (1.5, 1.1 - 2.1). The modified Schutz score correlated with ERCP completion, as did the Morriston score, even when modified to include only variables measurable before the procedure. CONCLUSION: This study confirms that patient- and procedure-based variables are key predictors of technical success and validates current methods of rating ERCP difficulty. Of note, a correlation between outcome and institutional factors, such as unit and endoscopist caseload, was not demonstrated.

Outcomes following acute nonvariceal upper gastrointestinal bleeding in relation to time to endoscopy: results from a nationwide study.

BACKGROUND AND STUDY AIMS: Despite the established efficacy of therapeutic endoscopy, the optimum timeframe for performing endoscopy in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) remains unclear. The aim of the current audit study was to examine the relationship between time to endoscopy and clinical outcomes in patients presenting with NVUGIB. PATIENTS AND METHODS: This study was a prospective national audit performed in 212 UK hospitals. Regression models examined the relationship between time to endoscopy and mortality, rebleeding, need for surgery, and length of hospital stay. RESULTS: In 4478 patients, earlier endoscopy ( < 12 hours) was not associated with a lower mortality or need for surgery compared with later ( > 24 hours) endoscopy (odds ratio [OR] for mortality 0.98, 95 % confidence interval [CI] 0.88 - 1.09 for endoscopy > 24 hours vs. < 12 hours; P = 0.70). In patients receiving therapeutic endoscopy, there was a nonsignificant trend towards an increase in rebleeding associated with later endoscopy (OR 1.13, 95 %CI 0.97 - 1.32 for endoscopy > 24 hours vs. < 12 hours), with the converse seen in patients not requiring therapeutic endoscopy (OR 0.83, 95 %CI 0.73 - 0.95 for endoscopy > 24 hours vs. < 12 hours; interaction P = 0.003). Later endoscopy ( > 24 hours) was associated with an increase in risk-adjusted length of hospital stay (1.7 days longer, 95 %CI 1.39 - 1.99 vs. < 12 hours; P < 0.001). CONCLUSIONS: Earlier endoscopy was not associated with a reduction in mortality or need for surgery. However, it was associated with an increased efficiency of care and potentially improved control of hemorrhage in higher risk patients, supporting the routine use of early endoscopy unless specific contraindications exist. These results may help inform the debate about emergency endoscopy service provision.

Mortality from acute upper gastrointestinal bleeding in the United kingdom: does it display a "weekend effect"?

OBJECTIVES: An increased mortality in patients presenting to hospital at weekends has been observed for several medical conditions. The aim of this study is to examine the relationship between weekend presentation to hospital following acute upper gastrointestinal bleeding and mortality. METHODS: Data were collected on 6,749 patients presenting to 212 UK hospitals. A logistic regression model was used to examine the relationship between weekend presentation to hospital and mortality. RESULTS: Patients presenting at the weekend were more likely to present with shock (39% vs. 36%), hematemesis (41% vs. 38%), and receive red cell transfusion (42% vs. 39%). Only 38% of those presenting at weekends underwent endoscopy within 24 h compared with 55% admitted on weekdays (adjusted odds ratio (OR)=0.47, 95% confidence interval (CI)=0.41-0.54), although the proportion of all patients receiving endoscopic therapy was identical at weekends compared with weekdays (24%). After adjustment for confounders, there was no evidence of a difference between weekend and weekday mortality (OR=0.93; 95% CI=0.75-1.16). Similar results were seen when restricting the analysis to those patients who underwent endoscopy (n=5,004) (OR=0.87, 95% CI=0.65-1.16). There was no difference in the OR for mortality for weekend compared with weekday presentation between patients presenting to hospitals with an out-of-hours (OOH) endoscopy rota compared with those presenting to hospitals without such a facility. CONCLUSIONS: In this large prospective study of acute upper gastrointestinal bleeding in the United Kingdom, there was no increase in mortality for weekend vs. weekday presentation despite patients being more critically ill and having greater delays to endoscopy at weekends. Provision of an OOH endoscopy service at weekends in the remaining UK hospitals may not lead to further reductions in case fatality, although a reduction in OOH endoscopy provision from current levels could lead to an increase in mortality at weekends.

Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis.

AIM: Antioxidants, such as vitamin A, C and E, selenium and ß-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population. METHOD: A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed. RESULTS: Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus ß-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos. CONCLUSION: The review demonstrates that antioxidants (vitamin A, C and E, selenium and ß-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.

Service evaluation of faecal immunochemical testing and anaemia for risk stratification in the 2-week-wait pathway for colorectal cancer.

Background: New national guidance on urgent referral for investigation of colorectal cancer included faecal occult blood testing in 2015. A service evaluation of faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC was undertaken. Methods: Postal FIT was incorporated into the colorectal cancer 2-week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal, and outcomes of investigations were recorded prospectively. Anaemia was defined as a haemoglobin level below 120 g/l in women and 130 g/l in men. Results: FIT kits were sent to 1106 patients, with an 80·9 per cent return rate; 810 patients completed investigations and 40 colorectal cancers were diagnosed (4·9 per cent). FIT results were significantly higher in patients with anaemia (median (i.q.r.) 4·8 (0·8-34·1) versus 1·2 (0-6·4) µg Hb/g faeces in those without anaemia; P < 0·001). Some 60·4 per cent of patients (538 of 891) had a result lower than 4 µg haemoglobin (Hb) per g faeces (limit of detectability), and 69·7 per cent (621 of 891) had less than 10 µg Hb/g faeces. Some 60 per cent of patients with colorectal cancer had a FIT reading of 150 µg Hb/g faeces or more. For five colorectal cancers diagnosed in patients with a FIT value below 10 µg Hb/g faeces, there was either a palpable rectal mass or the patient was anaemic. A FIT result of more than 4 µg Hb/g faeces had 97·5 per cent sensitivity and 64·5 per cent specificity for a diagnosis of colorectal cancer. A FIT result above 4 µg Hb/g faeces and/or anaemia had a 100 per cent sensitivity and 45·3 per cent specificity for colorectal cancer diagnosis. Conclusion: FIT is most useful at the extremes of detectability; strongly positive readings predict high rates of colorectal cancer and other significant pathology, whereas very low readings in the absence of anaemia or a palpable rectal mass identify a group with very low risk. High return rates for FIT within this 2WW pathway indicate its acceptability.

Could stool collection devices help increase uptake in bowel cancer screening programmes?

OBJECTIVE: To understand the usage and acceptability of a faecal collection device amongst participants in the National Health Service Bowel Cancer Screening Programme, with the aim of influencing future uptake. SETTING: Participants completing faecal occult blood test retests as part of the routine Bowel Cancer Screening Programme in Eastern England. METHODS: A faecal collection device and questionnaire were sent to all potential retest participants during a one-month period to collect information on prior stool collection methods and ease of use and usefulness of the enclosed faecal collection device. RESULTS: Out of 1087 participants invited, 679 (62.5%) returned their questionnaire. Of these, 429 (63.2%) trialled the faecal collection device at least once, 163 (38.4%) found the device made collecting their sample easier than previously, 189 (44.6%) found it made collection more difficult and 72 (17.0%) said it made no difference. Similar numbers reported finding that the faecal collection device made collecting the sample more pleasant (130, 31.5%), less pleasant (103, 25.0%) and no different (179, 43.4%) compared with previous collection without a faecal collection device. CONCLUSION: Although a small proportion of participants found the faecal collection device helpful, a considerable majority did not or did not use it at all. Offering faecal collection devices is unlikely to produce a substantial increase in bowel cancer screening uptake.

Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study.

BACKGROUND AND STUDY AIMS: Analyses of endoscopic retrograde cholangiopancreatography (ERCP) complication are often constrained by the number of endpoints observed. This large-scale study aimed to identify the principal risk factors for ERCP complication. PATIENTS AND METHODS: This was a prospective multicenter study of ERCP complications, based in five English regions. An exploratory univariable analysis of patients' first recorded procedures identified potentially important patient- and procedure-related factors. For overall complications and pancreatitis, variables significant in univariable analysis were included in multiple regression. RESULTS: A total of 66 centers collected data on 5264 ERCPs, performed on 4561 patients. A therapeutic intervention was attempted in 3447/4561 (76%) of patients as part of their first recorded ERCP. Following first recorded ERCP, 230 patients (5.0%) suffered > or = 1 complication: pancreatitis in 74 (1.6%), cholangitis in 48 (1.0 %), hemorrhage in 40 (0.9%), perforation in 20 (0.4%), and miscellaneous in 54 (1.2%). Significant factors from multiple regression were included in a multi-level analysis, which incorporated variables measured at the level of the endoscopist and hospital. For overall complication, risk factors ( P value, odds ratio [OR], 95% confidence interval [CI]) were: cannulation attempts > 1 ( P = 0.094, OR 1.32, 95% CI 0.95-1.83), precut ( P = 0.033, OR 1.55, 95 % CI 1.04-2.32), and suspected sphincter of Oddi dysfunction ( P = 0.121, OR 1.97, 95 % CI 0.84-4.64). For pancreatitis, risk factors ( Pvalue, OR, and 95 % CI) were: cannulation attempts > 1 ( P = 0.0001, OR 3.14, 95% CI 1.74-5.67), female sex ( P < 0.001, OR 2.22, 95% CI 1.43-3.45), age ( P < 0.002, OR 1.09 per 5 year decrease, 95% CI 1.03-1.15), and performance in a district (as opposed to university) hospital ( P = 0.034, OR 2.41, 95% CI 1.08-5.41). CONCLUSION: Careful patient selection combined with skilled cannulation minimizes complications. Higher-risk procedures should be performed in specialist centers.

Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn's disease: a general population-based study.

BACKGROUND: Recently, interest has been revived in whether people with coeliac disease, in contrast to other inflammatory gastrointestinal diseases, have an increased risk of schizophrenia. AIM: To compare the risk of schizophrenia in people diagnosed with coeliac disease, ulcerative colitis and Crohn's disease with the general population. METHODS: We used data from the UK General Practice Research Database. People with coeliac disease, Crohn's disease and ulcerative colitis were matched individually with five age-, sex- and general practice-matched controls. The prevalence of schizophrenia was calculated and compared between disease groups and their respective controls. We calculated odds ratios for schizophrenia using conditional logistic regression adjusting for smoking status. RESULTS: In people with coeliac disease, Crohn's disease and ulcerative colitis the prevalence of schizophrenia was 0.25%, 0.27% and 0.24%, respectively, compared with a general population prevalence of 0.37%. The adjusted odds ratios showed no association between schizophrenia and gastrointestinal disease (coeliac disease vs. controls 0.76, 95% CI: 0.41-1.4; Crohn's disease vs. controls 0.74, 95% CI: 0.44-1.3; ulcerative colitis 0.71, 95% CI: 0.44-1.1). CONCLUSIONS: Contrary to recent findings we found no evidence of an increased risk of schizophrenia in people with coeliac disease compared with the general population.

Is an internal comparison better than using national data when estimating mortality in longitudinal studies?

BACKGROUND: Discrepancies between the results of different studies looking at mortality in similar disease cohorts led us to consider the impact of methodology upon outcome. METHODS: Cohort studies were carried out using age, sex, practice, and calendar time matched control groups in the general practice research database. Data were used on all subjects with inflammatory bowel disease, coeliac disease, or Barrett's oesophagus. Mortality data for the population of England and Wales were obtained from the UK Office for National Statistics. The study compared hazard ratios (HR) for mortality using the matched controls to those found when an indirect standardisation to the mortality experience of England and Wales was carried out. RESULTS: For all three conditions the mortality risk was slightly lower when the national population data were used compared with the internal comparison group (coeliac disease HR 1.33 v standardised mortality ratios (SMR) 1.25, Barrett's oesophagus HR 1.32 v SMR 1.32, inflammatory bowel disease HR 1.50 v SMR 1.34). CONCLUSIONS: A bias was found towards underestimating mortality risk when cohort studies use national population death rates as a comparator. Estimates obtained when an internal comparison group has been used are probably more appropriate.

Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association.

BACKGROUND: Population data supporting an association between the autoimmune cholestatic liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis and coeliac disease, is limited and at times contradictory. AIM: To explore the relationship between coeliac disease and both primary biliary cirrhosis and primary sclerosing cholangitis within the General Practice Research Database, a UK-based longitudinal primary care database. METHODS: We identified 4732 people with diagnosed coeliac disease and 23 620 age- and sex-matched controls within the General Practice Research Database. We calculated the prevalence of primary biliary cirrhosis and primary sclerosing cholangitis for both the coeliac disease and control group. RESULTS: There was a higher prevalence of primary biliary cirrhosis in adults with coeliac disease, compared with controls [0.17% vs. 0.05%, odds ratio 3.63 (95% confidence interval: 1.46-9.04)]. Primary sclerosing cholangitis was also more common in the coeliac disease group [0.04% vs. 0%, fishers exact test (P = 0.03)]. CONCLUSIONS: There was a threefold or greater increase in risk of both primary biliary cirrhosis and primary sclerosing cholangitis in people with coeliac disease compared with the general population. The association with primary biliary cirrhosis was weaker than in some reports and it is difficult on the basis of this study to justify screening patients with coeliac disease for either primary biliary cirrhosis or primary sclerosing cholangitis.

Experience of 5-aminosalicylate nephrotoxicity in the United Kingdom.

AIM: To study 5-aminosalicylate nephrotoxicity in patients with inflammatory bowel disease in the UK. METHODS: A detailed postal questionnaire was sent to all 1298 names in the British Society of Gastroenterology database and 290 consultant members of the Renal Association. The British Society of Gastroenterology reported new cases monthly, the Renal Association 6 monthly. Results were expressed as estimated glomerular filtration rate. RESULTS: Retrospective study: cases--British Society of Gastroenterology:Renal Association 202:87, aged 15-76 years. Median peak (range) creatinine (British Society of Gastroenterology:Renal Association) - 300:301 (78-1200) micromol/L. Prospective study - 59 cases, median age 52 years (M:F ratio: 47:12). Median pre-treatment estimated glomerular filtration rate: 76.9 (123.9-39), at diagnosis 28.4 (80.5-3.6, creatinine range: 92-1361 micromol/L), recovery 46.8 [111.2-end stage renal failure] mL/min/1.73 m2. Recovery of renal function was significantly improved for patients treated for < 12 months [n = 10, median recovery estimated glomerular filtration rate 70.5 (92-26.9) vs. > 12 months 38.4 (111.2-end stage renal failure) mL/min/1.73 m2, P = 0.028]. CONCLUSIONS: Regular monitoring of renal function may allow earlier detection of nephrotoxicity, particularly during the first year of therapy. Based on an inflammatory bowel disease prevalence in the United Kingdom of 412 x 10(5) with about 50% on treatment, we estimate that the incidence of clinical nephrotoxicity in patients taking 5-aminosalicylate therapy is approximately one in 4000 patients/year.

Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial.

OBJECTIVES: Data 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. SETTING: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery. PARTICIPANTS: 936 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 MEASURES: Healthcare 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. RESULTS: Mean 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. CONCLUSIONS: AUGIB 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 NUMBER: ISRCTN85757829 and NCT02105532.

Inflammatory bowel disease: is there any relation between smoking status and disease presentation? European Collaborative IBD Study Group.

Smoking is associated with Crohn's disease and nonsmoking with ulcerative colitis. The aim of this study was to compare the clinical features at diagnosis and during the first year of follow-up in smokers and nonsmokers with inflammatory bowel disease (IBD). In 19 centers across Europe, a prospective study was performed of 457 newly diagnosed patients with Crohn's disease and 930 with ulcerative colitis. The characteristics of the disease were recorded by the treating physician by using a standard protocol at the time of diagnosis. Treatment characteristics were assessed after 1 year of follow-up. Weight loss occurred significantly more often in smoking patients with Crohn's disease, as well as in smokers with ulcerative colitis (p < 0.02), and diarrhea was more frequent in smoking patients with Crohn's disease compared with non-smoking individuals (p < 0.01). Patients with Crohn's disease who smoke were less likely to have colonic involvement (p < 0.01) and were more often prescribed immunosuppressive medication (p < 0.02). The study suggests that (a) smoking protects the colon from inflammation and (b) is associated with more active disease in Crohn's disease. The association between weight loss and smoking in both diseases is probably due to a general effect of smoking. The reported relation between smoking and the course of Crohn's disease is a strong argument for encouraging patients to give up smoking.

Immunosuppressive therapy for ulcerative colitis: results of a nation-wide survey among consultant physician members of the British Society of Gastroenterology.

BACKGROUND: The role of immunosuppressive therapy in ulcerative colitis remains controversial. There is little information available on how frequently immunosuppressives are used, the circumstances, dose and duration of use and perceived benefit. METHODS: A postal survey was sent to consultant gastroenterologist members of the British Society of Gastroenterology. RESULTS: Questionnaires were returned by 81% of the 496 UK consultants approached. Azathioprine use was frequent, with 93% reporting previous use and 86% use within the past year. Although 95% usually prescribed a < or =2 mg/kg dose, only 39% were prepared to prescribe higher doses. There was marked variation in duration of use, with 46% using azathioprine for <2 years and 17% continuing it for 4 years or longer. Consultants with more experience of azathioprine in ulcerative colitis used it at higher maintenance doses for longer periods, and in patients with less extensive disease. Cyclosporin use was reported by 47% of those caring for ulcerative colitis patients, with 36% having used it at least once in the past year. However, 65% of users estimated that fewer than 50% of patients subsequently avoided colectomy. On stopping cyclosporin only 21% always introduced an alternative immunosuppressive, while 23% never did so. Potentially serious side-effects attributable to azathioprine and cyclosporin were reported by 36% and 45% of users of each drug, respectively. CONCLUSIONS: This survey reveals considerable variation in the amount and pattern of immunosuppressive use in ulcerative colitis, with serious side-effects commonly seen. There is a pressing need for further randomized controlled trials to provide reliable evidence as to how immunosuppressive therapy should be used in ulcerative colitis.

Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding.

AIM: To investigate the role of Helicobacter pylori, expressing the virulence marker CAGA (cytotoxin associated gene product A) in ulcer complications and its interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) and other risk factors. DESIGN: Case control study using conditional logistic regression analysis. SETTING: University and City Hospitals, Nottingham. SUBJECTS: 203 consecutive patients with ulcer bleeding and 203 age- and sex-matched controls. RESULTS: Ulcer bleeding was more likely with positive H. pylori serology (odds ratio = 3.3, 95% CI: 1.7--6.6 for CagA positive, but only OR = 1.6, 95% CI: 0.7-3.7 for CagA negative serology), current smoking (OR 2.2, 95% CI: 1.04-4.7), aspirin < or = 300 mg daily (OR 7.7, 95% CI: 2.8-20.6), all other nonsteroidal anti-inflammatory drugs (NSAIDs: OR 10.6, 95% CI: 3.1-35.7 for < or = 1 defined daily dose lower and OR 22.6, 95% CI: 6.2-82.0 for higher doses) and past ulcer history (OR 5.6, 95% CI: 2.3-14.1). Aspirin < or = 300 mg daily was used by 25.1% of patients vs. 7.4% of controls. Smoking only enhanced risk in the presence of H. pylori, with a synergistic interaction (interaction odds ratio = 4.9, 2.4-9.9, P=0.002). Conversely, risks with non-aspirin NSAIDs were reduced in the presence of H. pylori, particularly if CagA-positive (interaction odds ratio=0.21, 0.05-0.9, P=0.03). CONCLUSIONS: CagA positive H. pylori infection is associated with an increased risk of ulcer bleeding. The risk from non-aspirin NSAIDs is even higher, but is less in H. pylori infected people. Low-dose aspirin is now commonly associated with ulcer bleeding.

Risk of vascular disease in adults with diagnosed coeliac disease: a population-based study.

BACKGROUND: It has been suggested that vascular disease mortality may be reduced in coeliac disease because of lower levels of blood pressure, cholesterol and body mass. AIM: To examine whether people with coeliac disease are at reduced risk of various vascular diseases. METHODS: We identified 3,790 adults with diagnosed coeliac disease and 17,925 age- and sex-matched controls in the General Practice Research Database. We estimated odds ratios for diagnosed hypertension, hypercholesterolaemia and atrial fibrillation and hazard ratios for myocardial infarction and stroke. RESULTS: Adults with coeliac disease, compared with controls, were less likely to have had a diagnosis of hypertension [11% vs. 15%, odds ratio 0.68 (95% confidence interval: 0.60-0.76)] or hypercholesterolaemia [3.0% vs. 4.8%, odds ration 0.58 (95% confidence interval: 0.47-0.72)] but slightly more likely to have had atrial fibrillation [2.1% vs. 1.7%, odds ratio 1.26 (95% confidence interval: 0.97-1.64)]. The hazard ratio for myocardial infarction was 0.85 (95% confidence interval: 0.63-1.13), while the hazard ratio for stroke was 1.29 (95% confidence interval: 0.98-1.70). CONCLUSIONS: Although rates of myocardial infarction and stroke were not substantially different, adults with coeliac disease do have a lower prevalence of hypertension and hypercholesterolaemia compared with the general population. The effect of a gluten-free diet on cardiovascular risk factors should be determined before any screening programmes for coeliac disease are instituted.

Prescribing of nonsteroidal anti-inflammatory drugs in general practice: determinants and consequences.

AIM: To use Prescribing Analysis and Costs data to investigate factors associated with differences in rates of nonsteroidal anti-inflammatory drug prescribing in Nottingham general practices. RESULTS: Poisson regression analysis revealed that the Age. Sex and Temporary Resident Prescribing Unit Index was the largest identifiable influence; larger practice size and a higher index of deprivation were also significantly associated with lower prescribing, whilst the number of partners was associated with higher levels of prescribing. However, even after correcting for the influence of age, sex and temporary residents, there was an 5.9-fold variation in rates of prescribing. A similar Poisson regression analysis to identify factors associated with admission to hospital with ulcer bleeding in the elderly over the preceding 57 months identified the rate of nonsteroidal anti-inflammatory drug (NSAID) prescribing as the only significant influence. CONCLUSION: The data are compatible with 1 hospital admission per 2823 NSAID prescriptions (95% confidence intervals 2098-8110) and they emphasize the need for strategies to reduce levels of NSAID prescribing.