Jonathon Snook

A case-control study of measles vaccination and inflammatory bowel disease

Summary Background The cause of inflammatory bowel disease (IBD) remains to be established. Evidence has linked measles infection in early childhood with the subsequent risk of developing IBD, particularly Crohns disease. A cohort study raised the possibility that immunisation with live attenuated measles vaccine, which induces active immunity to measles infection, might also predispose to the later development of IBD, provoking concerns about the safety of the vaccine. Method We report a case-control study of 140 patients with IBD (including 83 with Crohns disease) born in or after 1968, and 280 controls matched for age, sex and general practitioner (GP) area, designed to assess the influence of measles vaccination on later development of IBD. Documentary evidence of childhood vaccination history was sought from GP and community health records. Findings Crude measles vaccination rates were 56·4% in patients with IBD and 57·1% among controls. Matched odds ratios for measles vaccination were 1·08 (95% CI 0·62–1·88) in patients with Crohns disease, 0·84 (0·44–1·58) in patients with ulcerative colitis, and 0·97 (0·64–1·47) in all patients with IBD. Interpretation These findings provide no support for the hypothesis that measles vaccination in childhood predisposes to the later development of either IBD overall or Crohns disease in particular.

A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease.

Objective To clarify the relationship between childhood environment and the risk of subsequent development of Crohns disease or ulcerative colitis. Design and outcome measures A case–control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression. Setting District general hospital (secondary care institution). Participants Subjects with Crohns disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control. Results Helicobacter seroprevalence was substantially reduced in Crohns disease (OR 0.18; 95% CI, 0.06–0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38–2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01–0.51). Crohns disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23–6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21–6.91). There was no association between hepatitis A seroprevalence and either disease. Conclusion The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohns disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohns disease.

Adult endomysial antibody-negative coeliac disease and cigarette smoking.

Objective To determine the relative incidence and characteristics of endomysial antibody (EMA)-negative coeliac disease in adults. Design Retrospective analysis of prospectively collected data on adults with newly diagnosed coeliac disease, with determination of EMA status before gluten withdrawal. Setting District general hospital (secondary care institution). Participants Sixty consecutive incident cases. Main outcome measures (i) Proportion of cases who were EMA-negative; (ii) comparison of clinical and laboratory variables at diagnosis for EMA-positive and EMA-negative subjects. Results Fifteen subjects (25%, 95% CI 15–38%) were EMA negative, of whom only two were IgA deficient. There was clinical evidence in all 15 patients and histological evidence in 13 patients of a response to gluten withdrawal. No significant differences were found between EMA-positive and EMA-negative subjects with respect to histological features, age, gender, clinical manifestations, concurrent autoimmune disorders, family history of coeliac disease, or haemoglobin and albumin concentrations at diagnosis. However, EMA-negative status at diagnosis was associated strongly with current or recent cigarette smoking (OR 7.0, 95% CI 1.7–31.5, P = 0.003). Conclusions A substantial minority of patients with otherwise typical coeliac disease are EMA negative, and most of these are IgA replete. The value of EMA as a screening tool is therefore limited. EMA status in untreated coeliac disease correlates strongly with cigarette smoking history: this may be of pathogenic significance, given the previously demonstrated association between smoking and the risk of coeliac disease.

Determinants of endomysial antibody status in untreated coeliac disease.

Background Serum endomysial antibody (EMA) is a highly specific marker of untreated coeliac disease (CD). The published estimates of sensitivity however vary widely and the explanation for this remains unclear. Objective To determine the relative prevalence of EMA-negative CD and to identify clinical and histological characteristics which relate to EMA status. Method Retrospective analysis of prospectively collected data on incident cases of CD in a single hospital over a 10-year period with determination of EMA status before gluten withdrawal. Results From a total of 241 participants, 37 [15% (95% confidence interval: 11, 20%)] were EMA negative, of whom only four were IgA deficient. EMA-positive and EMA-negative patients shared a number of characteristics including female predominance and a high prevalence of HLA DQ2. EMA status was associated with age-test sensitivity and exceeded 98% below the age of 35 years, falling to around 80% in older age groups overall, and lower still in current cigarette smokers. EMA status was not influenced by sex, family history of CD, other autoimmune disease, or by potential clinical or histological markers of disease severity. Conclusion A substantial proportion of patients with true CD are EMA negative. This has implications for the pathogenesis of the disease. It also limits the value of EMA as a screening test, particularly in older adults and cigarette smokers.

The development of a nurse-led iron deficiency anaemia service in a district general hospital

Objective To improve the quality of care provided to patients with iron deficiency anaemia (IDA). Design Service development. Setting District General Hospital. Patients Adults with IDA. Main outcome measures Descriptive report of the practicalities and benefits of establishing an IDA clinic. Conclusions The IDA clinic is a novel service development which enhances the management of patients with this common condition, by facilitating prompt confirmation of the diagnosis, replacement therapy and investigation for serious underlying pathology, in particular gastrointestinal malignancy.

Clinical risk factors for underlying gastrointestinal malignancy in iron deficiency anaemia: the IDIOM study

Objective Ten percent of adults presenting with iron deficiency anaemia (IDA) have underlying cancer. This analysis – the Iron Deficiency as an Indicator Of Malignancy (IDIOM) study – was undertaken to assess whether five simple clinical parameters can usefully predict the likelihood of gastrointestinal (GI) malignancy on subsequent investigation of patients with IDA. Design Retrospective observational study, with multivariable analysis of the predictive value of sex, age, haemoglobin concentration (Hb), mean red cell volume (MCV) and iron studies for the risk of underlying GI malignancy. Setting District General Hospital IDA clinic. Patients 720 adults with confirmed IDA. Results Sex, age and Hb were strongly associated with the risk of GI malignancy—the parsimonious model including only these variables yielded ORs of 4.0 (95% CI 2.3 to 7.0) for males compared with females; 3.3 (95% CI 1.7 to 6.4) for age >70 years compared with ≤70 years; and 5.3 (95% CI 2.4 to 11.7) for a Hb of ≤91.4 g/L compared with ≥111.5 g/L. Combining these risk factors identified a subgroup (12% of the study population) at particularly low risk (<2% likelihood), and a second subgroup (16% of the study population) at especially high risk (>20% likelihood) of underlying GI malignancy. Conclusions Three simple and objective clinical parameters can be combined to provide a clinically useful cancer risk stratification model for subjects with IDA. This may assist with patient counselling and the prioritisation of investigational resources.

Aggressive Helicobacter pylori-negative peptic ulceration as the initial manifestation of Crohn's disease

Peptic ulceration is a recognised feature of Crohns disease, but the characteristics of this manifestation are rather poorly described. Furthermore, most reports in the literature relate to ulcer disease in cases of established Crohns disease. The authors report a series of four cases in which the diagnosis of Crohns disease was preceded by peptic ulceration. Potential confounding factors were as far as possible excluded, implying a true association. Characteristics of the ulcer disease included (1) a multifocal distribution, (2) Helicobacter pylori negativity and (3) an unusually aggressive clinical course despite proton pump inhibitor therapy, necessitating endoscopic or surgical intervention in three cases. Crohns-related peptic ulceration is a relatively common manifestation which may precede the diagnosis of Crohns disease itself. Recognition of the underlying diagnosis may be hampered by non-specific histology, but is important in view of the aggressive course of the ulceration, which may respond to medical therapy for Crohns disease.

Investigating for GI malignancy in iron-deficiency anaemia—the case for risk stratification

Iron deficiency anaemia (IDA) is a common clinical problem, with an incidence in excess of one case per 1000 of population per annum.1 Large case series2–4 have consistently shown that about 10% of men and postmenopausal women with IDA have underlying gastrointestinal (GI) malignancy, often in the absence of any other clinical pointer to the diagnosis. It is for this reason that IDA is recognised as an urgent indication for GI investigation.5 Tumours responsible for IDA may lie anywhere along the GI tract, though the commonest site is in the proximal colon. Bidirectional endoscopy (BDE), combines gastroscopy and colonoscopy in the same session, and is an efficient means of assessing the GI tract in IDA.4 ,5 As well as identifying cancer, it may pick up a myriad of less serious GI pathology (eg, coeliac disease, vascular malformations) in a further 20% of cases.2–4 BDE is labour-intensive, however, taking up to an hour to complete for each patient, and carries a small but significant risk of complications, particularly in the elderly and those with …

Clinical risk factors for underlying gastrointestinal malignancy in iron deficiency anaemia–prospective validation of the IDIOM score

Abstract Objective: Ten percent of adults presenting with iron deficiency anaemia (IDA) have underlying cancer. This study was undertaken to prospectively validate the observation in a previous retrospective study that three simple clinical parameters can usefully predict the likelihood of gastrointestinal (GI) malignancy on investigation of patients with IDA, and to screen for other potential clinical predictors of risk. Method: Observational study of a cohort of 643 subjects attending an IDA clinic at a District General Hospital between 2012 and 2015, with multivariable analysis of the predictive value of a series of clinical variables including sex, age and haemoglobin concentration ([Hb]) for underlying GI malignancy. Results: Analysis of the validation cohort data confirmed the original observation that sex, age, and Hb were associated with the risk of GI malignancy—the parsimonious model including only these variables yielded odds ratios of 1.9 (95% confidence interval (CI): 1.1, 3.3) for males vs. females; 1.6 (95% CI: 0.9, 2.9) for age >70 vs. ≤70 years; and 2.9 (95% CI: 1.2, 6.9) for [Hb] <90.6 g/l vs. >112 g/l. Combining data from the observation and validation cohorts (total n = 1,363) identified sub-groups with cancer risks ranging from 0% to over 20%. No other predictive clinical variables were identified. Conclusions: Three simple and objective clinical parameters can be combined to provide a clinically useful cancer risk stratification model for subjects with IDA. This may assist with patient counselling and the prioritisation of investigational resources.

PWE-167 The influence of a simple blood transfusion policy on over-transfusion in acute upper gastro-intestinal haemorrhage

Introduction Acute upper gastro-intestinal haemorrhage (AUGIH) is a common medical emergency. Whilst frequently treated with blood transfusion, RCT evidence suggests that a restrictive transfusion policy can reduce the risk of re-bleeding and death. Yet previous audits have shown a high prevalence of over-transfusion - a situation where blood is administered in excess of requirements, with the potential for deleterious effects. This study describes the impact of a simple blood transfusion policy to address over-transfusion in AUGIH. Method A cross-match policy was devised (see Table 1) to limit the number of units initially provided for patients with AUGIH according to the pre-transfusion haemoglobin concentration ([Hb]) and presence of shock and/or suspected varices. The proposed target post-transfusion [Hb] was 90–100g/l. Anonymised data was collected for all patients with suspected AUGIH during two six-month periods, before (Group 1) and after (Group 2) introduction of the policy. Over-transfusion was arbitrarily defined as a post-transfusion [Hb] exceeding 100 g/l. ResultsAbstract PWE-167 Table 1 Units for cross-match [Hb] / g/l Not shocked ANDvarices not suspected Shocked AND/ORvarices suspected 100 or more 0 0 90–99 0 2 80–89 (1) 3 70–79 2 4 60–69 3 5 Below 60 4 6 Group 1 (n = 122) and Group 2 (n = 105) were comparable in terms of age, sex, [Hb] at presentation and Rockall score. The proportion of patients over-transfused decreased from 48% in Group 1 to 28% in Group 2 (OR 0.43; 95% CI 0.19–0.98). Logistic regression analysis of combined data from the two cohorts confirmed that “initial [Hb]” and “units transfused” were the two major independent predictors of over-transfusion. The respective total blood usage figures for Groups 1 and 2 were 259 v 148 units cross-matched (a 43% reduction), and 198 v 127 units transfused in (a 36% reduction). Contributors to the latter were (1) a reduction in the proportion of patients transfused (58% v 50%; χ2=1.36, p = 0.24), and (2) a reduction in the number of units administered to each recipient (mean 2.8 v 2.4; t test 1.95, p = 0.05). Conclusion Over-transfusion in AUGIH is common and can be substantially reduced by the introduction of a simple cross-match policy. Direct benefits include a reduction in blood usage – our figures indicate a drop from 162 to 121 units per 100 patients with AUGIH. A typical DGH managing 250 cases a year could therefore potentially save £12,000 pa on blood alone – if applied across the NHS in England this equates to over £2 million pa. Further potential benefits might include reduced morbidity and mortality, and indirect cost savings from a reduction in the interventions and extended lengths of stay for rebleeding episodes. Disclosure of interest None Declared.