R. F. A. Logan

Seroprevalence, correlates, and characteristics of undetected coeliac disease in England

Objective: To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK. Methods: The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45–76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants’ serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour. Results: The seroprevalence of undetected coeliac disease in this general population sample aged 45–76 was 1.2% (95% confidence interval (CI) 0.9–1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being “good or excellent” (odds ratio (OR) 1.76 (95% CI 0.90–3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14–0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected serum calcium (0.02 mmol/l; p<0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3–7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5–8.2)) compared with EMA negative participants. Conclusions: Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45–76 years, a value similar to several other countries. Those affected report “better health” but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.

Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux

Background and aims: While patients with Barrett’s oesophagus develop oesophageal adenocarcinoma more frequently than the general population, it has controversially been suggested that gastro-oesophageal reflux (GORD) itself is a more important determinant of risk. In order to assess the validity of this suggestion, we examined the risk of oesophageal cancer in patients with Barrett’s and with GORD compared with the general population in a community based cohort study. Methods: Cohorts of patients with Barrett’s (n = 1677), oesophagitis (n = 6392), and simple reflux (n = 6328), and a reference cohort (n = 13416) were selected from the General Practice Research Database. The last three cohorts were matched to the Barrett’s cohort by general practitioner practice, age, and sex. Cox’s regression analysis was used to calculate relative risks for oesophageal cancer. Standardised incidence ratio methodology was used to estimate the relative risks for oesophageal adenocarcinoma. Results: A total of 137 oesophageal cancers were identified, of which 94 prevalent cases were excluded. The hazard ratios for oesophageal cancer were 10.6 (5.1–22.0), 2.2 (0.9–5.2), and 1.7 (0.7–4.5) in the Barrett’s, oesophagitis, and reflux cohorts compared with the reference cohort, respectively. The corresponding relative risks for oesophageal adenocarcinoma were 29.8 (9.6–106), 4.5 (1.04–19.6), and 3.1 (0.6–14.2). Conclusion: Barrett’s oesophagus increases the risk of oesophageal cancer approximately 10 times and oesophageal adenocarcinoma approximately 30 times compared with the general population. There is only a modestly increased risk of oesophageal cancer in patients with reflux who have no record of Barrett’s oesophagus. Our findings therefore do not support the suggestion that gastro-oesophageal reflux disease itself predisposes to cancer.

5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study.

Background and aims: The objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for inflammatory bowel disease (IBD). Methods: The General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case control analysis, each incident CRC case with any use of a 5-ASA in the six months before the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also currently using a 5-ASA. Patients were then classified according to regularity of use. The analysis was controlled for body mass index, IBD duration, history of colorectal polyps, use of non-steroidal anti-inflammatory drugs, paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to the general practitioner for IBD symptoms in the 6–24 months before diagnosis. Results: The study population included 18 969 patients, of whom 100 had developed CRC during 5-ASA exposure. Most of these cases had a history of ulcerative colitis (76 patients). In the case control analysis, regular users, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of CRC compared with irregular users (crude odds ratio (OR) 0.7 (0.44–1.03); adjusted OR 0.60 (0.38–0.96)). Regular users of sulfasalazine with 6–12 prescriptions before had an adjusted OR of 0.95 (0.22–4.11); with 13–30 prior prescriptions this was 0.41 (0.14–1.20) and with >30 prior prescriptions this was 0.77 (0.37–1.60). For mesalazine users, these values were 1.13 (0.49–2.59), 0.30 (0.11–0.83), and 0.31 (0.11–0.84), respectively. Conclusion: These results show that regular 5-ASA use is associated with some reduction in the risk of CRC developing in ulcerative colitis.

Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971-2001.

In the last two decades, mortality from primary liver cancer has increased in the UK. We aimed to determine whether the incidence trends for these cancers were similar and in particular if the increasing occurrence of cholangiocarcinoma has continued. We calculated directly age-standardised incidence rates (using the European standard population) by subsite and histological type for all cancers of the liver, gallbladder and biliary tract in England and Wales from 1971 to 2001, using cancer registry data. The incidence of cancers of the liver, gallbladder and biliary tract increased, with the greatest rise, around 12-fold, in intrahepatic bile duct cancers. The rate of liver cell cancer increased by around 45% in males, but by <10% in females. There were marked reductions in the incidence of gallbladder and extrahepatic bile duct cancer. Cholangiocarcinoma increased around 16-fold and became the most common type of primary liver cancer in females, while hepatocellular carcinoma remained the commonest type in males. The age-specific incidence rates showed that intrahepatic bile duct cancer continued to increase throughout the 1990s in those aged 75 and over, while liver cell cancer decreased in the older age groups. In conclusion, there were increases in the incidence of primary liver cancer, which have been particularly dramatic for intrahepatic bile duct cancer, over the last three decades of the 20th century in England and Wales. There has been a halving in the incidence of gallbladder cancer and a reduction of a third in extrahepatic bile duct cancer.

Peptic ulcer bleeding in the elderly: relative roles of Helicobacter pylori and non-steroidal anti-inflammatory drugs

Background—Most ulcers are caused, one can deduce, by Helicobcter pylori or by use of non-steroidal anti-inflammatory drugs (NSAIDs). Whether both together are worse than one alone is something that is quite unknown. Aim—To study both factors in order to see whether they interact together positively. Method—A case control study of ulcer bleeding in elderly patients chosen without weeding. Results—NSAID usage increased risk substantially. So did H pylori infection (but relative risk less than three). Neither seemed to interact. Their actions were discretely intact. Conclusion—H pylori effects ulcer bleeding in an adverse manner but does not make the risk of NSAIDs worse.

Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study

Background: Inflammatory bowel disease (IBD) is known to be associated with reduced bone density but the extent to which this results in an increased risk of fracture and the contribution of corticosteroid therapy are unclear. We have conducted a large cohort study to address these issues. Methods: We selected subjects within the General Practice Research Database (GPRD) with a diagnosis of IBD and up to five matched controls for each patient. We derived dates of recorded hip fractures and also information on smoking, use of corticosteroids, and a number of other drugs. We calculated the absolute risk of fracture and the relative risk as a hazard ratio corrected for available confounders by Cox regression. Results: Seventy two hip fractures were recorded in 16 550 IBD cases and 223 in 82 917 controls. Cox modelling gave an unadjusted relative risk of hip fracture of 1.62 (95% confidence interval (CI) 1.24–2.11) for all IBD, 1.49 (1.04–2.15) for ulcerative colitis (UC) and 2.08 (1.36–3.18) for Crohn’s disease (CD). Multivariate modelling showed that both current and cumulative use of corticosteroids and use of opioid analgesics confounded this relationship. After adjusting for confounding, the relative risk was 1.41 (0.94–2.11) for UC and 1.68 (1.01–2.78) for CD. Conclusion: The risk of hip fracture is increased approximately 60% in IBD patients. Corticosteroid use is a contributor to this, both in the long term as previously recognised and also in an acute reversible manner. The majority of hip fracture risk in IBD patients however cannot be attributed to steroid use.

Antibiotic use and the development of Crohn’s disease

Background: Few environmental determinants of Crohn’s disease are well established. Some observational data exist to implicate antibiotic use as a risk factor but these are derived from studies using questionnaires to assess reported antibiotic use that were susceptible to recall bias. We have therefore explored this relationship in prospectively gathered data. Methods: We selected incident cases of Crohn’s disease from the General Practice Research Database with at least five years of data prior to diagnosis. Controls with five years of complete data were randomly selected. Data were extracted on smoking, drug prescriptions, age, sex, and a variety of symptoms and diagnoses that might be indicative of occult Crohn’s disease. Logistic regression was used to investigate the relationship between antibiotic use and Crohn’s disease. Results: A total of 587 Crohn’s disease cases and 1460 controls were available for analysis. We found that antibiotic use 2–5 years pre-diagnosis occurred in 71% of cases compared with 58% of controls (p<0.001), and the median number of courses was two in the cases and one in the controls (p<0.001). Adjusting for age, sex, smoking, and use of other drugs, antibiotic use had an odds ratio of 1.32 (1.05–1.65). We were unable to show specificity to any subgroup of antibacterials. Associations similar to that with antibiotics were also found with oral contraceptive, cardiovascular, and neurological drugs. Conclusions: We found a statistically significant association between Crohn’s disease and prior antibiotic use. This cannot be explained by recall bias, but due to lack of specificity it is unclear whether it is causal.

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.

Patient perceptions of the burden of coeliac disease and its treatment in the UK.

Background  Coeliac disease affects about 1% of the population, with the majority being undetected. As a consequence, there have been calls for the introduction of screening. Before screening is given serious consideration, it is important to assess how acceptable early diagnoses and treatment would be.

Outcomes following early red blood cell transfusion in acute upper gastrointestinal bleeding

Aliment Pharmacol Ther 2010; 32: 215–224