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.

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.

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.

The long-term risk of malignancy following a diagnosis of coeliac disease or dermatitis herpetiformis: a cohort study.

BACKGROUND: People with coeliac disease are known to be at increased risk of malignancy; however, long-term risks of malignancy beyond 10-15 years are largely unstudied. AIM: To estimate how long an increased risk of malignancy among coeliac disease patients persists following diagnosis and treatment, using data from a cohort with an average follow-up of 25 years. METHODS: People with coeliac disease diagnosed in the Lothian region of Scotland, United Kingdom, were followed up from January 1970 or the date of coeliac disease diagnosis (whichever was later) until the first occurrence of death, emigration, cancer diagnosis or the end of 2004. Standardised incidence ratios were calculated to compare the cancer incidence rates among this group with those from the population of Scotland. RESULTS: Overall, the risk of any malignancy in coeliac disease patients compared with the general population was increased 40% [standardised incidence ratio (SIR) = 1.41; 95% CI 1.09-1.78]. An increased risk for cancer overall persisted for up to 15 years, beyond which no overall increase in malignancy risk was observed, although the risk of non-Hodgkin's lymphoma remained raised beyond 15 years (SIR = 5.15; 95% CI 1.40-13.2). In total, there were 14 non-Hodgkin's lymphomas in the cohort, providing an overall incidence of 1.3 per 1000 person-years. CONCLUSIONS: The overall risk of malignancy in coeliac patients declines with time after diagnosis and is not significantly increased after 15 years. Most of the increased risk can be attributed to the development of haematological malignancies, despite their very low absolute rate of occurrence.

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.

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

BACKGROUND: Acute upper gastrointestinal bleeding (AUGIB) accounts for 14% of RBC units transfused in the UK. In exsanguinating AUGIB the value of RBC transfusion is self evident, but in less severe bleeding its value is less obvious. AIM: To examine the relationship between early RBC transfusion, re-bleeding and mortality following AUGIB, which is one of the most common indications for red blood cell (RBC) transfusion. METHOD: Data were collected on 4441 AUGIB patients presenting to UK hospitals. The relationship between early RBC transfusion, re-bleeding and death was examined using logistic regression. RESULTS: 44% were transfused RBCs within 12 hours of admission. In patients transfused with an initial haemoglobin of <8 g/dl, re-bleeding occurred in 23% and mortality was 13% compared with a re-bleeding rate of 15%, and mortality of 13% in those not transfused. In patients transfused with haemoglobin >8 g/dl, re-bleeding occurred in 24% and mortality was 11% compared with a re-bleeding rate of 6.7%, and mortality of 4.3% in those not transfused. After adjusting for Rockall score and initial haemoglobin, early transfusion was associated with a two-fold increased risk of re-bleeding (Odds ratio 2.26, 95% CI 1.76-2.90) and a 28% increase in mortality (Odds ratio 1.28, 95% CI 0.94-1.74). CONCLUSIONS: Early RBC transfusion in AUGIB was associated with a two-fold increased risk of re-bleeding and an increase in mortality, although the latter was not statistically significant. Although these findings could be due to residual confounding, they indicate that a randomized comparison of restrictive and liberal transfusion policies in AUGIB is urgently required.

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. AIM: To assess patients' views as to the diagnosis and treatment of disease. METHODS: Coeliac disease patients who had taken a gluten-free diet for at least 12 months (mean 60 months) were mailed a questionnaire. Coeliac patients presenting with typical classical symptoms were compared with those diagnosed without such symptoms. RESULTS: Overall, 83% (147/177) of coeliac patients returned the questionnaires. Two-thirds (68%, 101/147) reported that their dietary restrictions reduced their enjoyment of food; 46% (68/147) believed their food cost them more and estimated this to be an extra 10 pounds sterling (16 euros) per week. Of those reporting greater cost, 31 (21%) said this was a problem for them. Half (54%, 80/147) reported doing things they enjoyed less often because of their diet, with the most common activity sacrificed being dining out (n = 65). In spite of these findings, 81% (119/147) reported being pleased that they were diagnosed, with 66% (59/89) of cases with classical symptoms wishing they had been diagnosed earlier compared with 45% (23/51) of those without such symptoms (chi(2) = 6.0, P < .05). In contrast, 27% (14/51) of coeliacs diagnosed without classical symptoms regretted being diagnosed with their condition compared with 10% (9/89) of those with classical symptoms (chi(2) = 7.1, P < .01). CONCLUSIONS: Even after several years of a gluten-free diet, many patients with coeliac disease regard it as a substantial burden, with a quarter of screen detected patients reporting regret at being diagnosed. Our findings question how acceptable screening for coeliac disease would be in people with minimal or no symptoms.

Clinical trial: a randomized trial of early endoscopy, Helicobacter pylori testing and empirical therapy for the management of dyspepsia in primary care.

BACKGROUND: Early endoscopy, Helicobacter pylori eradication and empirical acid suppression are commonly used dyspepsia management strategies in primary care but have not been directly compared in a single trial. AIM: To compare endoscopy, H. pylori test and refer, H. pylori test and treat and empirical acid suppression for dyspepsia in primary care. METHODS: Patients presenting to their general practitioner with dyspepsia were randomized to endoscopy, H. pylori'test and treat', H. pylori test and endoscope positives, or empirical therapy with symptoms, patient satisfaction, healthcare costs and cost effectiveness at 12 months being the outcomes. RESULTS: At 2 months, the proportion of patients reporting no or minimal dyspeptic symptoms ranged from 74% for those having early endoscopy to 55% for those on empirical therapy (P = 0.009), but at 1 year, there was little difference among the four strategies. Early endoscopy was associated with fewer subsequent consultations for dyspepsia (P = 0.003). 'Test and treat' resulted in fewer endoscopies overall and was most cost-effective over a range of cost assumptions. Empirical therapy resulted in the lowest initial costs, but the highest rate of subsequent endoscopy. Gastro-oesophageal cancers were found in four patients randomized to the H. pylori testing strategies. CONCLUSIONS: While early endoscopy offered some advantages 'Test and treat' was the most cost-effective strategy. In older patients, early endoscopy may be an appropriate strategy in view of the greater risk of malignant disease.

Meta-analysis: Helicobacter pylori'test and treat' compared with empirical acid suppression for managing dyspepsia.

BACKGROUND: Which of Helicobacter pylori'test and treat' or empirical acid suppression should be preferred for the initial management of uncomplicated dyspepsia is controversial. Aim To conduct an individual patient data meta-analysis of randomized controlled trials (RCTs) of 'test and treat' vs. empirical acid suppression in adults with uncomplicated dyspepsia in primary care. METHODS: Investigators provided original data sets for analysis. Effect of management strategy on symptom status and dyspepsia-related resource use at 12-month follow-up was examined by pooling symptom and cost data to obtain relative risk (RR) of remaining symptomatic at 12 months and weighted mean difference (WMD) in costs between the two strategies with 95% confidence intervals (CI). RESULTS: We identified three eligible RCTs containing 1547 patients, 791 (51%) of whom were assigned to 'test and treat'. There was no difference detected in symptom-cure at 12 months (RR = 0.99; 95% CI: 0.95-1.03). There was a nonsignificant trend towards cost-savings with 'test and treat' (WMD in costs = - 28.91 pound; 95% CI: - 68.48 pound to 10.65 pound). CONCLUSIONS: There was little difference in symptom-resolution or costs between the two strategies. A combination of patient and physician preference should determine the initial approach to the management of uncomplicated dyspepsia.

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study.

BACKGROUND: Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality. AIMS: To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population. METHODS: Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios. RESULTS: Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77-1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73-1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67-3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44-6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03-1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70-1.23). CONCLUSIONS: Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.

Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma.

The effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene-gene and gene-nutrient interactions. We investigated the combined effects of three polymorphisms in the TS gene region, TSER, TS 3R G>C, and TS 1494del6, dietary intakes of folate and other B vitamins, and genotype for other folate metabolism variants, in a colorectal adenoma (CRA) case-control study. Individuals homozygous for TS 1494del6 del/del were at significantly reduced CRA risk compared to those with either ins/del or ins/ins genotypes (odds ratio 0.52; 95% confidence interval: 0.31-0.85, P=0.009). We also observed evidence of interactions between TS 1494del6 genotype and intake of folate, and vitamins B6 and B12, and MTHFR C677T genotype, with the reduction in risk in del/del homozygotes being largely confined to individuals with high nutrient intakes and MTHFR 677CC genotype (P interaction=0.01, 0.006, 0.03, and 0.07, respectively). TSER genotype, when considered either alone or in combination with TS 3R G>C genotype, did not significantly influence CRA risk. These findings support a role for TS in colorectal carcinogenesis, and provide further evidence that functional polymorphisms in folate metabolism genes act as low-risk alleles for colorectal neoplasia and participate in complex gene-gene and gene-nutrient interactions.

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.

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.

Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study.

BACKGROUND & AIMS: Previous studies have raised concern about reduced fertility and increased adverse pregnancy-related events in women with celiac disease, but none has estimated overall fertility compared with the general female population. METHODS: We compared computerized primary care data for 1521 women with celiac disease with data for 7732 age- and practice-matched women without celiac disease. We estimated population-based rates of fertility and adverse pregnancy outcomes. RESULTS: Crude fertility rates were 48.2 and 47.7 live births per 1000 person-years for women with and without celiac disease, respectively (rate ratio, 1.01; 95% confidence interval, 0.90-1.14). Age-specific fertility rates showed that women with celiac disease had lower fertility when younger but higher fertility when older compared with women without celiac disease. This increase in relative fertility with increasing age held whether women had treated or untreated celiac disease. Risks of cesarean section (odds ratio, 1.33; 95% confidence interval, 1.03-1.70) and miscarriage (rate ratio, 1.31; 95% confidence interval, 1.06-1.61) were moderately higher in women with celiac disease, but risks of assisted birth, breech birth, preeclampsia, postpartum hemorrhage, ectopic pregnancy, stillbirth, and termination were similar. CONCLUSIONS: Overall, women with celiac disease have fertility similar to that of the general female population, but they have their babies at an older age. Although our findings may reflect a disease effect, the age shift in fertility rates and the increase in cesarean section risk is consistent with socioeconomic or educational advantages of women with celiac disease.

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.

Risk of extra-oesophageal malignancies and colorectal cancer in Barrett's oesophagus and gastro-oesophageal reflux.

BACKGROUND: The relationship between Barrett's oesophagus and colorectal cancer and other extra-oesophageal malignancies (EOM) has been a matter of controversy. These relationships have therefore been examined in a prospective study design in the General Practice Research Database. METHODS: Cohorts of patients having Barrett's oesophagus (n=1677), oesophagitis (n=6392), and simple reflux (n=6328), and a standard reference cohort representing the general population in the UK (n=13,416) were selected. The last three cohorts were matched to the Barrett's cohort by general practice, age and sex. Incident outcomes occurring beyond the first year of the follow-up were used for analyses. Hazard ratios and 95% confidence intervals were calculated using Cox's proportional hazards regression. The associations with cataract and oesophageal cancer were explored for comparison. RESULTS: Incident cases of 567 EOM (including 74 colorectal cancers), 448 cataract and 43 oesophageal cancers were used in the final analysis. The relative risks for colorectal cancer compared to the standard reference cohort were 1.16 (0.42-3.21) in the Barrett's cohort, 1.39 (0.76-2.54) in the oesophagitis cohort, and 0.93 (0.45-1.90) in the simple reflux cohort. The corresponding relative risks in the Barrett's cohort were 1.29 (0.90-1.85), 1.60 (1.10-2.32), and 10.56 (5.07-21.99) for EOM, cataract and oesophageal cancer, respectively. CONCLUSIONS: The risk of colorectal cancer was not higher in any of the Barrett's oesophagus, oesophagitis, or reflux cohorts compared to the general population. The explanations for the modest increase in the risk of EOM and cataract in the above cohorts are unclear but they may be mediated by ascertainment bias or shared risk factors.

Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls.

AIM: Patients with primary biliary cirrhosis may be at increased risk of osteoporosis but to what extent this is reflected in an increased fracture risk is unknown. We have enquired about the fracture experience of female primary biliary cirrhosis patients compared with sex- and age-matched controls. METHODS: Patients aged 30-75 with primary biliary cirrhosis and age-matched controls were sent a postal questionnaire asking about their fracture history and details of risk factors for osteoporosis. RESULTS: 85 eligible patients with primary biliary cirrhosis and 116 controls responded. Forty-one per cent of patients with primary biliary cirrhosis and 30% of controls reported ever having had a fracture odds ratio 1.5 (95% confidence interval: 0.80-2.89). Twenty-eight per cent of primary biliary cirrhosis patients and 23.3% of controls reported a fracture after the age of 30, odds ratio 1.2 (95% confidence interval: 0.57-2.56), and 14.1% of primary biliary cirrhosis patients and 12.1% of controls reported a low impact fracture of the long bones or of the vertebrae odds ratio 1.0 (95% confidence interval: 0.31-2.68). CONCLUSIONS: No overall increased fracture risk in patients with primary biliary cirrhosis was observed. As a group, unselected patients with primary biliary cirrhosis do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified. Further work investigating subgroups of patients with primary biliary cirrhosis at potentially high risk of osteoporosis, such as those with advanced disease or severe cholestasis is required.

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.

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.