Impact of general practice endorsement on the social gradient in uptake in bowel cancer screening

This is a summary of independent research funded by the National Institute for Health. Research (NIHR)’s Programme Grants for Applied Research Programme (RP-PG-0609–10106

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 (Pinteraction=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

Patterns of clinical presentation of adult coeliac disease in a rural setting

BACKGROUND: In recent years there has been increasing recognition that the pattern of presentation of coeliac disease may be changing. The classic sprue syndrome with diarrhoea and weight loss may be less common than the more subtle presentations of coeliac disease such as an isolated iron deficiency anaemia. As a result, the diagnosis of this treatable condition is often delayed or missed. Recent serologic screening tests allow non-invasive screening to identify most patients with the disease and can be applied in patients with even subtle symptoms indicative of coeliac disease. Both benign and malignant complications of coeliac disease can be avoided by early diagnosis and a strict compliance with a gluten free diet. AIM: The aim of this study is to evaluate the trends in clinical presentation of patients diagnosed with adult coeliac disease. In addition, we studied the biochemical and serological features and the prevalence of associated conditions in patients with adult coeliac disease. METHODS: This is an observational, retrospective, cross-sectional review of the medical notes of 32 adult patients attending the specialist coeliac clinic in a district general hospital. RESULTS: Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia. There were no malignant complications observed during the follow up of our patients. CONCLUSION: Most adults with coeliac disease have a sub clinical form of the disease and iron deficiency anaemia may be its sole presenting symptom. Only a minority of adult coeliac disease patients present with classical mal-absorption symptoms of diarrhoea and weight loss. Patients with atypical form of disease often present initially to hospital specialists other than a gastro-enterologist. An awareness of the broad spectrum of presentations of adult coeliac disease, among doctors both in primary care and by the various hospital specialists in secondary care, is necessary to avoid delays in diagnosis. It is important to include serological screening tests for coeliac disease systematically in the evaluation of adult patients with unexplained iron deficiency anaemia or unexplained gastro-intestinal symptoms and in those who are considered to be at increased risk for coeliac disease

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