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What proportion of dyspepsia in the general population is attributable to Helicobacter pylori?
April 1998
H pylori+ve, p=0.32) whilst owning a dog was associated with increased risk of infection (1237/4130 (30%) vs. 1068/4176 (26%) H pylori+ve, p < 0.00001). In a logistic regression model controlling for paternal social class, number of siblings and educational status dog ownership remained a marginally significant risk factor for H pylori infection (relative risk=l.ll (95%CI 1.00-1.23), p=0.04). This association was lost when present social class was included in the model. Condusion: Dog and cat ownership, either in childhood or as an adult, are not associated with H pylori infection when controlling for markers of socio-economic status. Funded by a Northern and Yorkshire Regional Research Grant. • G0944 THE EFFECTIVENESS AND SIDE EFFECTS OF OMEPRAZOLE, CLARITHROMYCIN AND TINIDAZOLE USED IN A COMMUNITY HELICOBACTER PYLORI ERADICATION PROGRAMME. P Moayvedi, D Brannholtz*, J Nathan, IDG Richards*, AC Dowell*, S Mason**, ATR Axon on behalf of the Leeds HELP study group. Centre for Digestive Diseases, General Infirmary at Leeds, *Centre for Health Services Research and **Clinical Trials and Research Unit, University of Leeds. Leeds, UK. Introduction: It has been suggested that screening the population for Hpylori and treating those infected may reduce mortality from gastric cancer and peptic ulcer disease. The efficacy and tolerability of H pylori eradication therapies when used in the largely asymptomatic population is unknown. We have investigated this using omeprazole 20 mg bd, clarithromycin 250 mg bd and tinidazole 500 mg bd for one week (OCT). Methods: 40-49 year old subjects from 36 participating general practices were invited to attend their primary care centre. H pylori status was determined by 13C-urea breath test (13C-UBT) and those infected were randomized to receive OCT or placebo. A randomly selected subgroup of H pylori negative subjects were also given placebo. Participants were given a pre-paid envelope to return if any adverse events occurred. Subjects were interviewed at 6 months on compliance and adverse events and a further 13C-UBT was performed. Results: 903 evaluable subjects were randomized to receive OCT and 1960 to receive placebo. The overall treatment success rate for OCT was 6841903 (76%-95%CI=73-79%). 766 (85%) stated they complied with therapy and in this group the success rate was 653/766 (85%-95%CI=83-88%). 348•792 subjects taking OCT complained of adverse events compared with 197/1837 taking placebo. 28% of adverse events were therefore attributable to OCT (relative risk=2.7). Adverse events interfered with activities of daily living in 4% of the OCT and 1% of the placebo group. The commonest adverse events associated with therapy were dry mouth/bitter taste (15% attributable risk), nausea (8.4% attributable risk) and diarrhoea (6.5% attributable risk). Conclusions: OCT has a success rate of 85% in those complying with therapy as part of a community eradication programme. Adverse events attributable to treatment are common but these rarely interfere with activities of daily living. Funded by a Northern and Yorkshire Regional Research Grant.
• G0945 THE INFLUENCE OF DYSPEPSIA, HELICOBACTER PYLORI STATUS AND IRRITABLE BOWEL SYNDROME ON QUALITY OF LIFE IN THE COMMUNITY. P Moayvedi, D Braunholtz*, P Atha, AC Dowell*, S Mason**, ATR Axon on behalf of the Leeds HELP study group. Centre for Digestive Diseases, General Infirmary at Leeds, Centre for Research in Primary Care and Clinical Trials and Research Unit, University of Leeds, Leeds, UK. Introduction: Dyspepsia and IBS reduce quality of life in patients attending gastroenterology clinics. The magnitude of the effect of dyspepsia and IBS on quality of life in the community has not been investigated. We and others have shown that H pylori is associated with increased risk of dyspepsia in the community but the effect of H pylori status on quality of life is unknown. We have investigated this in a prospective cross-sectional study. Methods: Subjects between the ages of 40-49 years randomly selected from 36 general practices were invited to attend their local primary care centre. A validated IBS and dyspepsia questionnaire was administered by a research nurse and subjects completed the Psychological General Well-being Index (PGWB). H pylori status was determined by 13C-urea breath test. Results: 8,191 subjects were evaluable (25% response rate), 813 (10%) had IBS, 3,115 (38%) were dyspeptic and 2,259 (28%) were infected with H pylori. Dyspepsia (106.4 -+ 13.6 vs. 98.7 ± 15.8 p < 0.001) and IBS (104.2 +- 14.8 vs. 97.3 + 15.1 p<0.001) were associated with significantly lower PGWB scores. H pylori infection was not associated with a change in PGWB score (103.1 ± 14.8 vs. 103.1 ± 15.0 p=0.13). In a multiple regression model including social class, gender, income, work status, marital status, number of cars, type of accommodation, smoking, alcohol and coffee intake, dyspepsia (-7.0:95%CI=-7.8 to -6.5) and IBS (-4.5:95%CI=-5.8 to -3.6) remained significantly associated with a lower PGWB score. Other factors in this model that were associated with PGWB include marital status (+5.9), car ownership (+0.6) and gender (male - +2.6) Conclusion: Dyspepsia and IBS but not Hpylori are associated with a lower quality of life in the community. Funded by a Northern and Yorkshire Regional Research Grant.
Esophageal, Gastric, and Duodenal Disorders A231 • G0946 WHAT PROPORTION OF DYSPEPSIA IN THE GENERAL POPULATION IS ATTRIBUTABLE TO HELICOBACTER PYLORI? P Moavvedi, D Braunholtz*, S Duffet, S Mason**, IDG Richards*, AC Dowell*, ATR Axon on behalf of the Leeds HELP group. Centre for Digestive Diseases, General Infirmary at Leeds, *Centre for Health Services Research and **Clinical Trials and Research Unit, University of Leeds, UK. Introduction: Studies suggest 40% of the population have dyspepsia and this causes a significant drain on health service resources. Anti-secretory medication is the most expensive category in the UK drug budget and dyspepsia accounts for 5% of all general practice consultations. Helicobacter pylori is a major cause of peptic ulcer disease but the proportion of dyspepsia in the general population attributable to this infection is unknown. This has important public health implications as Helicobacter pylori screening and treatment could reduce the morbidity and costs of dyspepsia. We aimed to establish this in a prospective cross-sectional study. Methods: Subjects between the ages of 40-49 years randomly selected from 36 primary care centres were invited to attend their local practice. A nurse obtained demographic information and administered a validated dyspepsia questionnaire. H pylori status was determined by 13C-urea breath test. Results: 8,330 subjects were enrolled into the study (25% of those invited), 2,310 (28%) were H pylori positive and 3,172 (38%) had dyspepsia. Dyspepsia was reported by 44% of H pylori positive subjects compared with 36% of uninfected individuals (relative risk=1.22 p < 0.0001). Assuming the association between H pylori and dyspepsia is causal the population attributable fraction=5.7%. H pylori remained independently associated with dyspepsia in a logistic regression model controlling for gender, smoking, alcohol intake, accommodation, educational status and social class (odds ratio=l.21-95% CI=1.09-1.34). In those with dyspepsia H pylori status was not associated with a particular symptom (H pylori+ve-33% epigastric pain, 39% heartburn, 28% other, H pylori-ve-31% epigastric pain, 38% heartburn, 31% other p=0.2). Conclusion: This study suggests that H pylori infected subjects have a 22% excess risk of developing dyspepsia and that 5.7% of all dyspepsia in the community is due to this organism. Funded by a Northern and Yorkshire Regional Research Grant.
• G0947 I L l [I GENE ALLELE 2 INVOLVES THE DECREASED PRODUCTION OF GASTRIC MUCOSAL IL113 IN RESPONSE TO HELICOBACTER PYLORI OF COMMON GENETIC STRAIN IN JAPAN, AND RELATES TO THE PATHOGENESIS OF DUODENAL ULCER. T Mochizuki, K Sugimura, Y Sato, K Ishizuka, T Honma, H Enomoto, J Matsuzawa, M Kobayashi, Y Baba, A Suriki, K Suzuki, R Narisawa, H Asakura. The Third Department of Internal Medicine, Niigata University School of Medicine, Japan. Aims: Different outcomes of gastroduodenal disease associated with H. pylori infection are supposed to depend on phenotypes of infecting strains and the host's predispositions. The aim of this study was to investigate whether genetic polymorphisms of 11,1 ct, ILl ,8, ILIRA, TNFct and ICAM1 as candidates for host's factors were associated with the occurrence of peptic ulcer. Methods: After informed consent was approved, 154 patients (gastric ulcer: 39, duodenal ulcer: 43, gastroduodenal ulcer: 31, chronic gastritis: 41) infected with H. pylori were included in this study. Genomic DNA was extracted from 1-1.pylori isolates and gastric biopsy specimens. Genetic types of infecting 1t. pylori (presence of cagA, and signal sequence and midregion types of vacA) were decided by PCR using described primers (Tummuru et al; 1993, Atherton et al; 1995, 1998). Host's genetic polymorphisms of ILl a (at -889), ILl fl (at -511), TNF ct (at -308), ICAM1 (G/R241 and K/E469), and IL1RA (Intron2) were analyzed using PCR techniques as described previously. Additionally, in 71 patients, we measured ILl fl concentration in short time culture supematant of gastric biopsy specimens taken from antrum and corpus by ELISA. Results: One hundred thirty three of all isolates (86.0%) classified into both cagA-positive and sla/ml type of vacA. In subjects infected with this common strain in Japan, allele 2 frequency of 1L1 fl gene was higher in patients with duodenal ulcer than those without duodenal ulcer (47.7% vs 34.9%; p < 0.05). There were no other significant relationships between gene polymorphisms and diseases. Mucosal ILl 13production was lower in patients homozygous of allele 2 than in those homozygous of allele 1 on same condition of infecting strain as described above (antrum: median 25.8, range 5.3-150 vs 73.4, 0-400; p=0.06, corpus: 31.4, 0-80 vs 88.5, 15.8-289.5 pg/rng; p < 0.05), and in duodenal ulcer patients than in chronic gastritis patients only in corpus (44.8, 0-110.2 vs 78.5, 0-474.6; p<0.05). Conclusion: The polymorphism of ILl ,8 gene affects the level of mucosal ILl [3 production in response to H. pylori infection, and low mucosal ILl [3 production due to allele 2 in ILl ,6 gene may be one of the causes of duodenal ulcer. These results imply defensive action of ILl 13in the pathogenesis of duodenal ulcer such as inhibitory effect on gastric acid secretion.
H pylori+ve, p=0.32) whilst owning a dog was associated with increased risk of infection (1237/4130 (30%) vs. 1068/4176 (26%) H pylori+ve, p < 0.00001). In a logistic regression model controlling for paternal social class, number of siblings and educational status dog ownership remained a marginally significant risk factor for H pylori infection (relative risk=l.ll (95%CI 1.00-1.23), p=0.04). This association was lost when present social class was included in the model. Condusion: Dog and cat ownership, either in childhood or as an adult, are not associated with H pylori infection when controlling for markers of socio-economic status. Funded by a Northern and Yorkshire Regional Research Grant. • G0944 THE EFFECTIVENESS AND SIDE EFFECTS OF OMEPRAZOLE, CLARITHROMYCIN AND TINIDAZOLE USED IN A COMMUNITY HELICOBACTER PYLORI ERADICATION PROGRAMME. P Moayvedi, D Brannholtz*, J Nathan, IDG Richards*, AC Dowell*, S Mason**, ATR Axon on behalf of the Leeds HELP study group. Centre for Digestive Diseases, General Infirmary at Leeds, *Centre for Health Services Research and **Clinical Trials and Research Unit, University of Leeds. Leeds, UK. Introduction: It has been suggested that screening the population for Hpylori and treating those infected may reduce mortality from gastric cancer and peptic ulcer disease. The efficacy and tolerability of H pylori eradication therapies when used in the largely asymptomatic population is unknown. We have investigated this using omeprazole 20 mg bd, clarithromycin 250 mg bd and tinidazole 500 mg bd for one week (OCT). Methods: 40-49 year old subjects from 36 participating general practices were invited to attend their primary care centre. H pylori status was determined by 13C-urea breath test (13C-UBT) and those infected were randomized to receive OCT or placebo. A randomly selected subgroup of H pylori negative subjects were also given placebo. Participants were given a pre-paid envelope to return if any adverse events occurred. Subjects were interviewed at 6 months on compliance and adverse events and a further 13C-UBT was performed. Results: 903 evaluable subjects were randomized to receive OCT and 1960 to receive placebo. The overall treatment success rate for OCT was 6841903 (76%-95%CI=73-79%). 766 (85%) stated they complied with therapy and in this group the success rate was 653/766 (85%-95%CI=83-88%). 348•792 subjects taking OCT complained of adverse events compared with 197/1837 taking placebo. 28% of adverse events were therefore attributable to OCT (relative risk=2.7). Adverse events interfered with activities of daily living in 4% of the OCT and 1% of the placebo group. The commonest adverse events associated with therapy were dry mouth/bitter taste (15% attributable risk), nausea (8.4% attributable risk) and diarrhoea (6.5% attributable risk). Conclusions: OCT has a success rate of 85% in those complying with therapy as part of a community eradication programme. Adverse events attributable to treatment are common but these rarely interfere with activities of daily living. Funded by a Northern and Yorkshire Regional Research Grant.
• G0945 THE INFLUENCE OF DYSPEPSIA, HELICOBACTER PYLORI STATUS AND IRRITABLE BOWEL SYNDROME ON QUALITY OF LIFE IN THE COMMUNITY. P Moayvedi, D Braunholtz*, P Atha, AC Dowell*, S Mason**, ATR Axon on behalf of the Leeds HELP study group. Centre for Digestive Diseases, General Infirmary at Leeds, Centre for Research in Primary Care and Clinical Trials and Research Unit, University of Leeds, Leeds, UK. Introduction: Dyspepsia and IBS reduce quality of life in patients attending gastroenterology clinics. The magnitude of the effect of dyspepsia and IBS on quality of life in the community has not been investigated. We and others have shown that H pylori is associated with increased risk of dyspepsia in the community but the effect of H pylori status on quality of life is unknown. We have investigated this in a prospective cross-sectional study. Methods: Subjects between the ages of 40-49 years randomly selected from 36 general practices were invited to attend their local primary care centre. A validated IBS and dyspepsia questionnaire was administered by a research nurse and subjects completed the Psychological General Well-being Index (PGWB). H pylori status was determined by 13C-urea breath test. Results: 8,191 subjects were evaluable (25% response rate), 813 (10%) had IBS, 3,115 (38%) were dyspeptic and 2,259 (28%) were infected with H pylori. Dyspepsia (106.4 -+ 13.6 vs. 98.7 ± 15.8 p < 0.001) and IBS (104.2 +- 14.8 vs. 97.3 + 15.1 p<0.001) were associated with significantly lower PGWB scores. H pylori infection was not associated with a change in PGWB score (103.1 ± 14.8 vs. 103.1 ± 15.0 p=0.13). In a multiple regression model including social class, gender, income, work status, marital status, number of cars, type of accommodation, smoking, alcohol and coffee intake, dyspepsia (-7.0:95%CI=-7.8 to -6.5) and IBS (-4.5:95%CI=-5.8 to -3.6) remained significantly associated with a lower PGWB score. Other factors in this model that were associated with PGWB include marital status (+5.9), car ownership (+0.6) and gender (male - +2.6) Conclusion: Dyspepsia and IBS but not Hpylori are associated with a lower quality of life in the community. Funded by a Northern and Yorkshire Regional Research Grant.
Esophageal, Gastric, and Duodenal Disorders A231 • G0946 WHAT PROPORTION OF DYSPEPSIA IN THE GENERAL POPULATION IS ATTRIBUTABLE TO HELICOBACTER PYLORI? P Moavvedi, D Braunholtz*, S Duffet, S Mason**, IDG Richards*, AC Dowell*, ATR Axon on behalf of the Leeds HELP group. Centre for Digestive Diseases, General Infirmary at Leeds, *Centre for Health Services Research and **Clinical Trials and Research Unit, University of Leeds, UK. Introduction: Studies suggest 40% of the population have dyspepsia and this causes a significant drain on health service resources. Anti-secretory medication is the most expensive category in the UK drug budget and dyspepsia accounts for 5% of all general practice consultations. Helicobacter pylori is a major cause of peptic ulcer disease but the proportion of dyspepsia in the general population attributable to this infection is unknown. This has important public health implications as Helicobacter pylori screening and treatment could reduce the morbidity and costs of dyspepsia. We aimed to establish this in a prospective cross-sectional study. Methods: Subjects between the ages of 40-49 years randomly selected from 36 primary care centres were invited to attend their local practice. A nurse obtained demographic information and administered a validated dyspepsia questionnaire. H pylori status was determined by 13C-urea breath test. Results: 8,330 subjects were enrolled into the study (25% of those invited), 2,310 (28%) were H pylori positive and 3,172 (38%) had dyspepsia. Dyspepsia was reported by 44% of H pylori positive subjects compared with 36% of uninfected individuals (relative risk=1.22 p < 0.0001). Assuming the association between H pylori and dyspepsia is causal the population attributable fraction=5.7%. H pylori remained independently associated with dyspepsia in a logistic regression model controlling for gender, smoking, alcohol intake, accommodation, educational status and social class (odds ratio=l.21-95% CI=1.09-1.34). In those with dyspepsia H pylori status was not associated with a particular symptom (H pylori+ve-33% epigastric pain, 39% heartburn, 28% other, H pylori-ve-31% epigastric pain, 38% heartburn, 31% other p=0.2). Conclusion: This study suggests that H pylori infected subjects have a 22% excess risk of developing dyspepsia and that 5.7% of all dyspepsia in the community is due to this organism. Funded by a Northern and Yorkshire Regional Research Grant.
• G0947 I L l [I GENE ALLELE 2 INVOLVES THE DECREASED PRODUCTION OF GASTRIC MUCOSAL IL113 IN RESPONSE TO HELICOBACTER PYLORI OF COMMON GENETIC STRAIN IN JAPAN, AND RELATES TO THE PATHOGENESIS OF DUODENAL ULCER. T Mochizuki, K Sugimura, Y Sato, K Ishizuka, T Honma, H Enomoto, J Matsuzawa, M Kobayashi, Y Baba, A Suriki, K Suzuki, R Narisawa, H Asakura. The Third Department of Internal Medicine, Niigata University School of Medicine, Japan. Aims: Different outcomes of gastroduodenal disease associated with H. pylori infection are supposed to depend on phenotypes of infecting strains and the host's predispositions. The aim of this study was to investigate whether genetic polymorphisms of 11,1 ct, ILl ,8, ILIRA, TNFct and ICAM1 as candidates for host's factors were associated with the occurrence of peptic ulcer. Methods: After informed consent was approved, 154 patients (gastric ulcer: 39, duodenal ulcer: 43, gastroduodenal ulcer: 31, chronic gastritis: 41) infected with H. pylori were included in this study. Genomic DNA was extracted from 1-1.pylori isolates and gastric biopsy specimens. Genetic types of infecting 1t. pylori (presence of cagA, and signal sequence and midregion types of vacA) were decided by PCR using described primers (Tummuru et al; 1993, Atherton et al; 1995, 1998). Host's genetic polymorphisms of ILl a (at -889), ILl fl (at -511), TNF ct (at -308), ICAM1 (G/R241 and K/E469), and IL1RA (Intron2) were analyzed using PCR techniques as described previously. Additionally, in 71 patients, we measured ILl fl concentration in short time culture supematant of gastric biopsy specimens taken from antrum and corpus by ELISA. Results: One hundred thirty three of all isolates (86.0%) classified into both cagA-positive and sla/ml type of vacA. In subjects infected with this common strain in Japan, allele 2 frequency of 1L1 fl gene was higher in patients with duodenal ulcer than those without duodenal ulcer (47.7% vs 34.9%; p < 0.05). There were no other significant relationships between gene polymorphisms and diseases. Mucosal ILl 13production was lower in patients homozygous of allele 2 than in those homozygous of allele 1 on same condition of infecting strain as described above (antrum: median 25.8, range 5.3-150 vs 73.4, 0-400; p=0.06, corpus: 31.4, 0-80 vs 88.5, 15.8-289.5 pg/rng; p < 0.05), and in duodenal ulcer patients than in chronic gastritis patients only in corpus (44.8, 0-110.2 vs 78.5, 0-474.6; p<0.05). Conclusion: The polymorphism of ILl ,8 gene affects the level of mucosal ILl [3 production in response to H. pylori infection, and low mucosal ILl [3 production due to allele 2 in ILl ,6 gene may be one of the causes of duodenal ulcer. These results imply defensive action of ILl 13in the pathogenesis of duodenal ulcer such as inhibitory effect on gastric acid secretion.