Richard F. Logan

Risk assessment after acute upper gastrointestinal haemorrhage.

The aim of this study was to establish the relative importance of risk factors for mortality after acute upper gastrointestinal haemorrhage, and to formulate a simple numerical scoring system that categorizes patients by risk. A prospective, unselected, multicentre, population based study was undertaken using standardised questionnaires in two phases one year apart. A total of 4185 cases of acute upper gastrointestinal haemorrhage over the age of 16 identified over a four month period in 1993 and 1625 cases identified subsequently over a three month period in 1994 were included in the study. It was found that age, shock, comorbidity, diagnosis, major stigmata of recent haemorrhage, and rebleeding are all independent predictors of mortality when assessed using multiple logistic regression. A numerical score using these parameters has been developed that closely follows the predictions generated by logistical regression equations. Haemoglobin, sex, presentation (other than shock), and drug therapy (non-steroidal anti-inflammatory drugs and anticoagulants) are not represented in the final model. When tested for general applicability in a second population, the scoring system was found to reproducibly predict mortality in each risk category. In conclusion, a simple numerical score can be used to categorize patients presenting with acute upper gastrointestinal haemorrhage by risk of death. This score can be used to determine case mix when comparing outcomes in audit and research and to calculate risk standardised mortality. In addition, this risk score can identify 15% of all cases with acute upper gastrointestinal haemorrhage at the time of presentation and 26% of cases after endoscopy who are at low risk of rebleeding and negligible risk of death and who might therefore be considered for early discharge or outpatient treatment with consequent resource savings.

Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of peptic ulcer complications, but it is not clear whether some drugs are more likely than others to cause such complications. We compared previous use of NSAIDs in 1144 patients aged 60 and older admitted to hospitals in five large cities with peptic ulcer bleeding and in 1126 hospital controls and 989 community controls matched for age and sex. Peptic ulcer bleeding was strongly associated with use of non-aspirin NSAIDs of any type during the 3 months before admission (411 cases, 351 controls; odds ratio 4.5 [95% CI 3.6 to 5.6]). The odds ratios for peptic ulcer bleeding were lowest for ibuprofen (2.0 [1.4-2.8]) and diclofenac (4.2 [2.6-6.8]), and intermediate for indomethacin, naproxen, and piroxicam (11.3 [6.3-20.3], 9.1 [5.5-15.1], and 13.7 [7.1-26.3]). Azapropazone and ketoprofen carried the highest risks (31.5 [10.3-96.9] and 23.7 [7.6-74.2]). Risks also increased with drug dose (low dose 2.5 [1.7-3.8], intermediate 4.5 [3.3-6.0], and high 8.6 [5.8-12.6]) for all drugs combined. Appropriate clinical strategies could prevent many episodes of peptic ulcer bleeding: NSAIDs should be used only in patients who do not respond to other analgesics; the lowest possible doses should be used; and the least toxic NSAIDs should be selected.

A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21.

Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 × 10−7, allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 × 10−14 (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16–1.39) and 1.47 (95% c.i.: 1.34–1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10–1.34; P = 6.89 × 10−5). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.

Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom

Abstract Objective: To describe the current epidemiology of acute upper gastrointestinal haemorrhage. Design: Population based, unselected, multicentre, prospective survey. Setting: 74 hospitals receiving emergency admissions in four health regions in the United Kingdom. Subjects: 4185 cases of acute upper gastrointestinal haemorrhage in which patients were aged over 16 years identified over four months. Outcome measures: Incidence and mortality. Results: The overall incidence of acute upper gastrointestinal haemorrhage in the United Kingdom is 103/100000 adults per year. The incidence rises from 23 in those aged under 30 to 485 in those aged over 75. At all ages incidence in men was more than double that in women except in elderly patients. 14% of the haemorrhages occurred in inpatients already in hospital for some other reason. In 27% of cases (37% female, 19% male) patients were aged over 80. Overall mortality was 14% (11% in emergency admissions and 33% in haemorrhage in inpatients). In the emergency admissions, 65% of deaths in those aged under 80 were associated with malignancy or organ failure at presentation. Mortality for patients under 60 in the absence of malignancy or organ failure at presentation was 0.8%. Conclusions: The incidence of acute upper gastrointestinal haemorrhage is twice that previously reported in England and similar to that reported in Scotland. The incidence increases appreciably with age. Although the proportion of elderly patients continues to rise and mortality increases steeply with age, age standardised mortality is lower than in earlier studies. Deaths occurred almost exclusively in very old patients or those with severe comorbidity.

Prophylactic aspirin and risk of peptic ulcer bleeding

Abstract Objective: To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. Design: A case-control study with hospital and community controls. Setting: Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. Subjects: 1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. Results: 144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. Conclusion: No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications. Key messages Key messages This finding applies to doses in common use of 75, 150, and 300 mg daily Despite these results, overall benefits of treatment are likely considerably to outweigh possible risks

Aspirin for the Chemoprevention of Colorectal Adenomas: Meta-analysis of the Randomized Trials

BACKGROUND Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups. METHODS We combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas >or=1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided. RESULTS We identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied. CONCLUSION Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.

Prospective survey of childhood inflammatory bowel disease in the British Isles

The incidence of inflammatory bowel disease in children in western countries may be rising. Since there is no prospective national data on the incidence of inflammatory bowel disease in the UK and Republic of Ireland (ROI), we undertook a prospective survey to determine this incidence. The incidence during 1998 and 1999 was 5.2/100,000 per year in children aged younger than 16 years. Those from an Asian background were over-represented and more likely to have ulcerative colitis.

Malignancy and mortality in people with coeliac disease: population based cohort study

Abstract Objective To quantify the risks of malignancy and mortality in people with coeliac disease compared with the general population. Design Population based cohort study. Setting General practice research database. Participants 4732 people with coeliac disease and 23 620 matched controls. Main outcome measures Hazard ratios for malignancy and mortality. Results Of the 4732 people with coeliac disease, 134 (2.8%) had at least one malignancy and 237 (5.0%) died. The overall hazard ratios were: for any malignancy 1.29 (95% confidence interval 1.06 to 1.55), for mortality 1.31 (1.13 to 1.51), for gastrointestinal cancer 1.85 (1.22 to 2.81), for breast cancer 0.35 (0.17 to 0.72), for lung cancer 0.34 (0.13 to 0.95), and for lymphoproliferative disease 4.80 (2.71 to 8.50). The increased risk was primarily in the first year after diagnosis, with the risk for only lymphoproliferative disease remaining significantly raised thereafter. After excluding events in the year after diagnosis, the hazard ratio for malignancy was 1.10 (0.87 to 1.39) and for mortality was 1.17 (0.98 to 1.38), giving absolute excess rates of 6 and 17 per 10 000 person years, respectively. Conclusions People with coeliac disease have modest increases in overall risks of malignancy and mortality. Most of this excess risk occurs in the year of follow up after diagnosis. People with coeliac disease also have a noticeably reduced risk of breast cancer. The mechanism of this merits further attention as it may provide insights into the cause of this common malignancy.

Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit

Objective To describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with acute upper gastrointestinal bleeding (AUGIB) in the 2007 UK Audit. Design Multi-centre survey. Setting All UK hospitals admitting patients with AUGIB. Participants All adults (>16 years) presenting in or to UK hospitals with AUGIB between 1 May and 30 June 2007. Results Data on 6750 patients (median age 68 years) was collected from 208 participating hospitals. New admissions (n=5550) were younger (median age 65 years) than inpatients (n=1107, median age 71 years), with less co-morbidity (any co-morbidity 46% vs 71%, respectively). At presentation 9% (599/6750) had known cirrhosis, 26% a history of alcohol excess, 11% were taking non-steroidal anti-inflammatory drugs and 28% aspirin. Peptic ulcer disease accounted for 36% of AUGIB and bleeding varices 11%. In 13% there was evidence of further bleeding after the first endoscopy. 1.9% underwent surgery and 1.2% interventional radiology for AUGIB. Median length of stay was 5 days. Overall mortality in hospital was 10% (675/6750, 95% CI 9.3 to 10.7), 7% in new admissions and 26% among inpatients. Mortality was highest in those with variceal bleeding (15%) and with malignancy (17%). Conclusions AUGIB continues to result in substantial mortality although it appears to be lower than in 1993. Mortality is particularly high among inpatients and those bleeding from varices or upper gastrointestinal malignancy. Surgical or radiological interventions are little used currently.

Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests

Introduction The Bowel Cancer Screening Programme in England began operating in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. The programme aims to reduce mortality from colorectal cancer by 16% in those invited for screening. Methods All subjects eligible for screening in the National Health Service in England are included on one database, which is populated from National Health Service registration data covering about 98% of the population of England. This analysis is only of subjects invited to participate in the first (prevalent) round of screening. Results By October 2008 almost 2.1 million had been invited to participate, with tests being returned by 49.6% of men and 54.4% of women invited. Uptake ranged between 55–60% across the four provincial hubs which administer the programme but was lower in the London hub (40%). Of the 1.08 million returning tests 2.5% of men and 1.5% of women had an abnormal test. 17 518 (10 608 M, 6910 F) underwent investigation, with 98% having a colonoscopy as their first investigation. Cancer (n=1772) and higher risk adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of women investigated, respectively. 71% of cancers were ‘early’ (10% polyp cancer, 32% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with only 14% being right-sided compared with expected figures of 67% and 24% for left and right side from UK cancer registration. Conclusion In this first round of screening in England uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials. Although there was the expected improvement in cancer stage at diagnosis, the proportion with left-sided cancers was higher than expected.