Ethnicity in relation to incidence of oesophageal and gastric cancer in England.

BACKGROUND: This study investigated the variation in incidence of all, and six subgroups of, oesophageal and gastric cancer between ethnic groups. METHODS: Data on all oesophageal and gastric cancer patients diagnosed between 2001 and 2007 in England were analysed. Self-assigned ethnicity from the Hospital Episode Statistics dataset was used. Male and female age-standardised incidence rate ratios (IRRs) were calculated for each ethnic group, using White groups as the references. RESULTS: Ethnicity information was available for 83% of patients (76 130/92 205). White men had a higher incidence of oesophageal cancer, with IRR for the other ethnic groups ranging from 0.17 95% confidence interval (CI) (0.15-0.20) (Pakistani men) to 0.58 95% CI (0.50-0.67) (Black Caribbean men). Compared with White women, Bangladeshi women (IRR 2.02 (1.24-3.29)) had a higher incidence of oesophageal cancer. For gastric cancer, Black Caribbean men (1.39 (1.22-1.60)) and women (1.57 (1.28-1.92)) had a higher incidence compared with their White counterparts. In the subgroup analysis, White men had a higher incidence of lower oesophageal and gastric cardia cancer compared with the other ethnic groups studied. Bangladeshi women (3.10 (1.60-6.00)) had a higher incidence of upper and middle oesophageal cancer compared with White women. CONCLUSION: Substantial ethnic differences in the incidence of oesophageal and gastric cancer were found. Further research into differences in exposures to risk factors between ethnic groups could elucidate why the observed variation in incidence exists.

Do guidelines improve clinical practice? - a national survey on surveillance colonoscopies.

BACKGROUND: Colonoscopic services are increasingly being utilized in surveillance of conditions predisposing to colorectal cancers (CRC). The ACPGBI/BSG guidelines are the most commonly followed recommendations. Numerous retrospective studies have shown poor compliance with them. We conducted a national survey of colonoscopic practitioners investigating attitudes, awareness and implementation of surveillance guidelines. METHOD: A postal questionnaire was sent to a random population of 250 ACPGBI and 200 BSG members. Questions assessed practice as regards colorectal polyp surveillance, family screening and surveillance for past history of CRC. RESULTS: The ACPGBI/BSG guidelines were the most commonly followed recommendations. Only 17.2% of practitioners used the criteria that would ensure accurate implementation of guidelines for colorectal adenoma surveillance. With regards to familial surveillance for CRC, 53.5% respondents assessed familial risk accurately, while 69.3% recommended surveillance incorrectly. A total of 48.8% of ACPGBI members recommended five yearly colonoscopies following curative treatment for CRC. CONCLUSION: This study has revealed the widespread ignorance of guidelines, which will potentially translate into the gross over utilization of colonoscopic resources. Strategies to improve and audit guideline implementation must be integral to guideline formation. Methods to improve accurate guideline implementation need to be explored.

Randomised double-blind placebo-controlled trial of aloe vera for irritable bowel syndrome.

Aloe vera (AV) is suggested to be beneficial in treating irritable bowel syndrome (IBS) symptoms, but no scientific trials exist to confirm this. We aim to assess the efficacy of AV on IBS in refractory secondary care patients. Patients with IBS were randomised to receive AV or matching placebo for a month. Symptoms were assessed at baseline, 1 and 3 months. Fifty-eight patients randomised, 49 completed the protocol to 1 month and 41 to 3 months. Eleven of thirty-one (35%) AV patients, and 6 of 27 (22%) placebo patients responded at 1 month (p = 0.763). Diarrhoea predominant patients showed a trend towards a response to treatment at 1 month (10/23 V 2/14, p = 0.07). There was no evidence that AV benefits patients with IBS. However, we could not rule out the possibility that improvement occurred in patients with diarrhoea or alternating IBS whilst taking AV. Further investigations are warranted in patients with diarrhoea predominant IBS, in a less complex group of patients.

Systematic review: adipose tissue, obesity and gastrointestinal diseases.

BACKGROUND: Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. Insulin resistance is the most widely accepted link between obesity and disease, particularly colorectal cancer. The recognition that intra-abdominal fat is immunologically active sheds new light not only on the pathogenesis of obesity-related gastrointestinal conditions, but also on inflammatory conditions such as Crohn's disease. AIM: To describe the biology of adipose tissue, its impact on the immune system and explores the possible underlying mechanisms linking obesity to gastrointestinal diseases. It also looks at the role of mesenteric fat in determining severity and course of Crohn's disease. METHODS: Relevant English-language literature and abstracts cited on MEDLINE database were reviewed. RESULTS: Our recent finding of an association between obesity and subclinical bowel inflammation suggests that, apart from promoting generalized immune activation, fat also evokes local immune responses. We propose that the proinflammatory milieu promoted by obesity could underlie many of these associations and that the mechanism implicating insulin resistance may merely represent an epiphenomenon. In Crohn's disease, on the other hand, intra-abdominal fat may provide a protective mechanism. CONCLUSION: The potential of adipose tissue as a therapeutic target is vast and needs exploration.

Review article: faecal markers in the assessment of activity in inflammatory bowel disease.

The fundamental pathological process behind ulcerative colitis and Crohn's disease is intestinal inflammation. As the precise cause of this is not yet completely understood, current treatment strategies are aimed at reducing or eliminating the inflammation. Endoscopic examination and histological analysis of biopsy specimens remain the 'gold standard' methods for detecting and quantifying bowel inflammation; however, these techniques are costly, invasive, and repeated examinations are unpopular with patients. Disease activity questionnaires and laboratory 'inflammatory markers', although widely used, show an unreliable correlation with endoscopy and histology. New markers need to be developed to detect and quantify bowel inflammation. These would be of use diagnostically and also an aid to pharmacological treatment.

Antibiotics increase functional abdominal symptoms.

OBJECTIVES: Data suggest that subjects with irritable bowel syndrome are more likely to report a recent course of antibiotics. This study tests the hypothesis that a course of antibiotics is a risk factor for an increase in the number of functional bowel complaints over a 4-month period in a general population sample. METHODS: We initiated a prospective case-control study in three general practices in South London. Consecutive patients aged 16-49 attending their general practitioner with non-GI complaints and given a prescription for antibiotics were invited to participate. Comparison subjects who had not had antibiotics for 1 yr were identified from the practice records by age group, gender, and previous general practitioner visits. Fifty-eight antibiotic and 65 control patients agreed to participate. Questionnaires covering demographic, GI, and psychological data were sent at recruitment and at 4 months. Seventy-four percent of subjects completed the study. The number of symptoms at follow-up compared to that at recruitment. RESULTS: Twenty of 42 antibiotic subjects (48%) versus 11/49 control subjects (22%) demonstrated one or more additional functional bowel symptoms at 4 months (unadjusted odds ratio = 3.14 [1.27-7.75]) (chi2 = 6.4, p = 0.01). Ten of 42 antibiotic subjects (24%) versus 3/49 control subjects (6%) demonstrated two or more additional functional bowel symptoms at 4 months (unadjusted odds ratio = 4.79 [1.22-18.80]) (chi2 = 5.8, p = 0.02). CONCLUSIONS: Functional bowel symptoms come and go, but subjects who are given a course of antibiotics are more than three times as likely to report more bowel symptoms 4 months later than controls.

Ischaemic heart disease and Cag A strains of Helicobacter pylori in the Caerphilly heart disease study.

OBJECTIVE: To look for the presence of the more virulent strains of Helicobacter pylori (H pylori) in men who developed ischaemic heart disease over a 10 year period and in controls. DESIGN: The Caerphilly prospective heart disease study recruited 2512 men aged 45-59 years during 1979-83. Western blot analysis or enzyme linked immunosorbent assay (ELISA) was performed on serum taken from those who subsequently died of ischaemic heart disease, or developed non-fatal myocardial infarction, to determine H pylori and Cag A status. Similar information was available on age matched controls. RESULTS: During the first decade of the study, 312 men died of ischaemic heart disease or developed non-fatal myocardial infarction. Serum was available from 172 of these (55%). There was no evidence of an association between Cag A seropositivity and incident ischaemic heart disease or ischaemic heart disease mortality, either before or after adjustment for potential confounders (adjusted odds ratios 1.18 (95% confidence interval (CI) 0.76 to 1.85) and 1.13 (95% CI 0.61 to 2.07), respectively). Further, the odds ratios for ischaemic heart disease incidence and ischaemic heart disease mortality by H pylori seropositivity did not appear to depend on the presence or absence of Cag A strains (p = 0.76 and 0.77, respectively). CONCLUSIONS: In this cohort of middle aged men, followed over a 10 year period, there is little evidence of an association between Cag A seropositivity and either incident ischaemic heart disease or ischaemic heart disease mortality.

C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. METHODS: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.

Helicobacter pylori is an aetiological factor for ischaemic heart disease: the case in favour.

The evidence to date concerning the association between Helicobacter pylori infection and coronary heart disease is consistent with a modest increased risk. Research is currently being undertaken into factors which may modify this association. Probably, there is sufficient evidence given the ease of the proposed intervention to make it worthwhile to undertake a trial of eradication therapy.

Western blotting is useful in the salivary diagnosis of Helicobacter pylori infection.

BACKGROUND: The salivary diagnosis of Helicobacter pylori infection offers attractive possibilities for the epidemiological study of infection in children. Salivary enzyme linked immunosorbent assay (ELISA) is less reliable then serum ELISA, owing to variable transudation of immunoglobulin. In addition, children are more difficult to study because of lower specific serum antibody concentrations to H pylori. The performance of salivary western blotting in comparison with serum western blotting and serum ELISA was investigated in school children. SUBJECTS AND METHODS: Paired serum and saliva specimens were obtained from 669 [corrected] school children aged 9-11 in 10 British towns. All saliva and serum specimens were first analysed by ELISA; subsequently, western blotting of both specimens was performed on 31 and 34 specimens, respectively, to establish the criteria for positivity for western blotting. The remaining 121 specimens were then tested blindly and saliva was compared with the serum. RESULTS: The sensitivity and specificity of salivary ELISA in the 669 [corrected] specimens was 32 of 50 (64%) and 530 of 619 (86%) [corrected], respectively, when compared with serum ELISA. The western blotting validation was performed on 28 subjects with positive serum and positive salivary ELISA, 28 saliva positives with negative serum, 16 saliva negatives with positive serum, and 50 doubly negative subjects. Compared with serum western blots, the sensitivity and specificity of salivary western blots was 38 of 47 (81%) and 68 of 75 (91%), respectively. Using serum ELISA as the gold standard, the sensitivity and specificity were 32 of 44 (73%) and 72 of 78 (92%), respectively, the specificity being significantly higher than salivary ELISA (p < 0.001). CONCLUSION: Salivary western blotting for IgG is useful in the diagnosis of H pylori infection and is superior to ELISA. It also permits the identification of pathogenic strains.

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors.

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.

Chlamydia pneumoniae serology, lung function decline, and treatment for respiratory disease.

Associations have been reported between Chlamydia pneumoniae seropositivity and both acute and chronic obstructive airway diseases. Plasma specimens collected between 1979 and 1983 from 1, 773 men 45 to 59 yr of age in Caerphilly, South Wales, were tested for IgG and IgA antibodies to C. pneumoniae (TW183) by microimmunofluorescence. Subsequent mortality and medication for obstructive airway disease were ascertained at 5-yr follow-up examinations. Spirometry was performed at the first and second examinations and analyzed both cross-sectionally and longitudinally; 642 men (36%) had IgG antibodies at a titer of 1:16 or above, of whom 362 also had detectable IgA antibodies. No statistically significant associations were found between either IgG titer or IgA titer and any of the outcome measures: inhaler therapy at entry; commencement of inhalers during follow-up; death from respiratory causes; baseline FEV(1), FVC, and FEV(1)/FVC ratio; and decline in FEV(1) (p > 0.1 throughout). Men with high IgG titers (>/= 1:64) had a slower rate of decline of FEV(1) than did seronegative subjects (adjusted mean difference in 5-yr change in FEV(1): +22 ml, 95% confidence interval: -31 ml to +76 ml). Men with high IgA titers (>/= 1:16) had a slightly faster rate of decline (-12 ml, - 96 ml to +71 ml). This first prospective assessment suggests that chronic C. pneumoniae infection is not a major risk factor for progressive airflow obstruction.

Endoscopy for Helicobacter pylori sero-negative young dyspeptic patients: an economic evaluation based on a randomized trial.

BACKGROUND: A policy of withholding endoscopy in Helicobacter pylori sero-negative dyspeptic patients without sinister symptoms saves up to 36% of endoscopies. However, it is unclear whether the net cost of applying this policy outweighs that of conventional management. AIM: To determine the direct (healthcare) and indirect (productivity) costs of applying a strategy of endoscopy versus no endoscopy in H. pylori sero-negative young dyspeptics in the UK. METHOD: The direct and indirect incremental costs for both strategies were calculated amongst 154 H. pylori seronegative subjects randomized to have an endoscopy or no endoscopy before subsequent management by their general practitioners. The cost per patient of each strategy was calculated using reference values in our clinical setting and sensitivity analysis was used to test different scenarios. RESULTS: The total direct cost rose for the endoscopy group (mean Pound Sterling 103, 95% CI 78 to 127) but did not change for the non-endoscopy group (mean Pound Sterling 6, 95% CI -32 to 44). On average, direct (healthcare) costs for patients in the endoscopy group rose by Pound Sterling 96 (95% CI 51 to 142) more than those for non-endoscopy patients. Indirect (productivity) cost fell for the non-endoscopy group (mean -Pound Sterling 40, 95% CI -220 to 140) compared to a rise for the endoscopy group (mean Pound Sterling 180, 95% CI -60 to 420) (difference not significant). The total cost (including direct and indirect costs) fell for the non-endoscopy group (mean -Pound Sterling 34, 95% CI -228 to 160) but rose for the endoscopy group (mean Pound Sterling 283, 95% CI 32 to 533)--an incremental cost of Pound Sterling 317 (95% CI 0 to 634). For all assumptions in the sensitivity analysis, the mean cost in the endoscopy group was at least Pound Sterling 200 higher than in the non-endoscopy group. CONCLUSIONS: It is less expensive to manage H. pylori-negative dyspeptic patients aged under 45 without sinister symptoms by withholding endoscopy.

Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis.

BACKGROUND: Chronic Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis but whether it plays a role at an early stage in the disease is uncertain. An early estimate of atherosclerosis can be obtained by ultrasonic imaging of the carotid artery to determine intima-media thickness (IMT) and the thickness of any atheroma plaques. METHODS AND RESULTS: In 983 normal population individuals aged 30 to 70 years, we measured common carotid artery (CCA) and carotid bulb IMT, and also carotid plaque thickness and the degree of internal carotid artery (ICA) stenosis. C. pneumoniae IgA titers of >/=16 and IgG titers of >/=64 were taken as positive. There was no association between C. pneumoniae IgA or IgG seropositivity with right, left, or mean CCA or bulb IMT, or with the presence of carotid plaques. There was a significant association between IgA seropositivity and >50% mean carotid stenosis with an odds ratio of 5.24 (95% CI 1.24 to 22.21, P=0.0245) after controlling for age and sex; after controlling for other cardiovascular risk factors, this was not significant 3.96 (95% CI 0. 84 to 18.78, P=0.082). No association was found between IgA or IgG seropositivity and markers of fibrinogen, log C-reactive protein, or leukocyte count. CONCLUSIONS: We found no evidence that serological evidence of C. pneumoniae infection is associated with early atherosclerosis. It is possible that IgA seropositivity is associated with more advanced disease but this hypothesis needs to be examined in a population with a higher prevalence of advanced atherosclerosis. We found no evidence that C. pneumoniae results in a chronic systemic inflammatory state.

Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the caerphilly prospective heart disease study.

OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. DESIGN: Prospective longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors. Incidence of ischaemic heart disease was not associated with either IgG antibody titre or IgA antibody titre, but there were stronger and significant relations of IgA antibodies with all cause mortality and fatal ischaemic heart disease, which persisted after adjustment for conventional cardiovascular risk factors. The odds ratios associated with detectable IgA antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first prospective demonstration of an association between IgA antibodies to C pneumoniae, a putative marker of chronic infection, and subsequent risk of death from ischaemic heart disease. In contrast to earlier case-control studies, IgG antibodies were not associated with either prevalent or incident ischaemic heart disease.

Cytomegalovirus seropositivity and incident ischaemic heart disease in the Caerphilly prospective heart disease study.

OBJECTIVE: To assess the role of cytomegalovirus (CMV) infection in primary ischaemic heart disease. METHODS: Plasma specimens collected during 1979-83 from men in Caerphilly, south Wales, were analysed for IgG antibodies to CMV by enzyme linked immunosorbent assay and latex tests. Incident ischaemic heart disease events were ascertained after five and 10 years from death certificates, hospital records, and ECG changes; 195 incident ischaemic heart disease cases were compared with 216 controls of a similar age drawn from the rest of the cohort. RESULTS: 164 cases (84%) and 180 controls (83%) were seropositive for CMV. Optical density, an indicator of CMV antibody titre, was similar for cases and controls. Among controls, seropositivity was not associated with age, socioeconomic status currently or in childhood, smoking, height, body mass index, blood pressure, total cholesterol, fibrinogen, plasma viscosity, or leucocyte count. The unadjusted odds ratio relating CMV seropositivity to incident ischaemic heart disease was 1.06 (95% confidence interval 0.63 to 1.79) and was little changed (1.11, 0.63 to 1.97) after adjustment for age, smoking, body mass index, systolic blood pressure, total cholesterol, and socioeconomic status currently and in childhood. CONCLUSIONS: CMV infection is unlikely to be a strong risk factor for development of myocardial infarction in middle aged men.