Table 1

Table 2

References
 

Table 1 Characteristics of association studies (n=23)
 

Ref No	Definition of dyspepsia symptoms	Exclusion criteria	Case selection	Control selection	Determination of Helicobacter pylori infection	Control of confounders	Quality score compared with median
w1	Abdominal symptoms (pain, discomfort, fullness after meal or other upper abdominal symptoms) lasting >6 months	Patients with "evidence of organic disease"	Consecutive patients to unknown-type of clinic. Germany (n=16)	Age and sex matched, recruited by advertisement (n=16)	Serology	Age and sex	Above
w2	Epigastric or periumbilical pain and/or nausea and vomiting or regurgitation >1 month	Recent non-steroidal anti-inflammatory drugs, antibiotics, H2 blockers, bismuth salts	Children referred for evaluation of dyspepsia. Turkey (n=56)	Children seen in outpatient clinic for non-gastrointestinal complaints. None had abdominal pain or vomiting (n=48)	Serology	Age groups	Below
w3	Defined dyspepsia as patients having consulted GP or received a 2 month treatment with H2 blocker or omeprazole in preceding 6 months	Gastro-oesophageal reflux disease, peptic ulcer disease, patients previously given eradication therapy	Six urban general practices. Patients identified from computer search and "opportunistically" recruited. All aged >50. UK (n=89)	Computer search identified patients routinely attending practice with problems unrelated to dyspepsia (n=147)	Helisal near patient test with whole blood	No	Below
w4	Recurrent epigastric pain, worse after meals, temporarily relieved by antacids and lasting "several months"	Biliary diseases, increased liver function tests, diabetes, excess alcohol consumption, cirrhosis, or lower abdominal complaints	Patients from Addis Ababa and 13 provinces in Ethiopia (n=136)	Volunteers: nurses and patients admitted for non-abdominal complaints and awaiting discharge (n=71)	Biopsy obtained by upper gastrointestinal endoscopy	No	Above
w5	Persistent upper abdominal discomfort >3 months (epigastric pain, postprandial fullness, early satiety, nausea and vomiting, anorexia, acid regurgitation)	Gastrointestinal surgery, recent non-steroidal anti-inflammatory drugs, antibiotics, bismuth drugs, lesions found on upper gastrointestinal endoscopy, abnormal ultrasonogram, gastro-oesophageal reflux disease	Patients referred to outpt gastroenterology clinic. Kaohsiung, Taiwan (n=28)	Patients "admitted" for routine physical check up (n=10)	Biopsy obtained by upper endoscopy	No	Below
w6	Defined as upper abdominal pain and/or combination of at least 3 symptoms including and pain, nausea and vomiting, anorexia, heartburn, acid regurgitation, postprandial fullness, belching, and abdominal distension lasting >3 months. Non-ulcer dyspepsia included above symptoms in absence of ulcer history. Separated out in analysis irritable bowel syndrome	Recent non-steroidal anti-inflammatory drugs, gastro-oesophageal reflux disease	Employees who underwent periodic medical examination, aged >35, and responded positively to symptom questionnaire. Japan (n=30)	Employees undergoing periodic medical examination with no history of dyspeptic symptoms or abdominal complaints (n=145)	Serology	Age	Above
w7	Defined criteria of generalised abdominal symptoms and pain modalities. Gastro-oesophageal reflux disease included only if abdominal pain or discomfort present. Ulcer-like dyspepsia quantified	Irritable bowel syndrome	Randomised population sample responding to questionnaire. Sweden (n=50)	Matched for age, sex, and education level. Obtained from random population sample (n=50)	Serology	Age, sex, and education level	Above
w8	Non-ulcer dyspepsia not defined	Peptic ulcer disease, history of cancer, and portal hypertension	Consecutive patients who had had upper gastrointestinal endoscopy as part of a clinical investigation. India (n=119)	Healthy asymptomatic volunteers from the rural population (n=30)	Biopsy obtained by upper endoscopy	No	Below
w9	Patients with "dyspepsia and erosive pyloric changes grades 2 and 3" referred to gastrointestinal clinic, lasting >1 month. Upper gastrointestinal endoscopy excluded peptic ulcer disease, oesophagitis, history of cancer	Recent non-steroidal anti-inflammatory drugs, excess alcohol consumption, aged <16 and >65	Patients from a randomised controlled trial examining psychotherapy on dyspeptic symptoms. Norway (n=87)	Recruited from national register in Norway (n=77)	14C-urea breath testing	No	Above
w10	Dyspepsia undefined	Gastrointestinal carcinoma	Patients undergoing upper gastrointestinal endoscopy. Malaysia (n=214)	Male blood donors and patients attending health screening clinics (n=1417)	Biopsy obtained by upper endoscopy	No	Below
w11	Upper abdominal pain related to meals in absence of jaundice	H2 blockers, antibiotics, bismuth compounds in preceding 4 weeks. Also excluded portal gastropathy or gastric varices	Consecutive patients attending outpt clinic. India (n=526)	Patients with no upper gastrointestinal symptoms in the preceding 4 weeks who were admitted to hospital for investigations (n=82)	Biopsy obtained by upper endoscopy	Age and sex	Below
w12	Symptoms of epigastric pain or burning, postprandial fullness, nausea, vomiting scored 0-3 and lasting >6 months	Gastrointestinal surgery, peptic ulcer disease, excess alcohol consumption,gastro-oesophageal reflux disease, irritable bowel syndrome, recent non-steroidal anti-inflammatory drugs, antibiotics	Selective from consecutive outpatients referred for chronic dyspepsia and normal upper gastrointestinal endoscopy. Italy (n=45)	Individuals from different socioeconomic and educational classes, some hospital employees and medical students. No other information provided (n=15)	Biopsy obtained by upper endoscopy	Age and sex	Above
w13	Upper abdominal pain with daily heartburn or acid regurgitation during past 2 weeks	Peptic ulcer disease, renal stones, gallstones, and coronary heart disease	All inhabitants aged 20 to 69 with positive dyspeptic responses to health questionnaire. Sorreisa, Norway (n=309)	Random sample of non-dyspeptic respondents to population survey (n=310)	Biopsy obtained by upper endoscopy	Age and sex	Above
w14	Non-ulcer disease defined by "Collin-Jones criteria"	Peptic ulcer disease, gastro-oesophageal reflux disease, abnormal ultrasonogram or abnormal results of blood tests	Consecutive patients with non-ulcer disease. India (n=50)	Healthy asymptomatic volunteers (n=10)	Biopsy obtained by upper endoscopy	Age and sex	Above
w15	Non-ulcer disease defined as chronic epigastric pain >3 months plus 2 of the following: exacerbation or relief by meals, exacerbation by hunger, night waking, heartburn, relief of pain by antacids or milk, epigastric tenderness	Patients with nausea and vomiting, prominently "gaseous symptoms" or gastro-oesophageal reflux disease, antibiotics, anti-ulcer drugs, illness, gastrointestinal surgery, irritable bowel syndrome, gallbladder disease, pancreatitis	138 patients referred for assessment of dyspepsia; sub-sample used in study. Nigeria (n=40)	Healthy asymptomatic volunteers recruited from hospital staff, medical students, and acquaintances. Excluded if upper gastrointestinal pain or symptoms preceding 2 years (n=40)	Biopsy obtained by upper endoscopy	Age, sex, religion, ethnic group, and education level	Above
w16	Chronic or recurrent upper abdominal pain or nausea >3 months	Recent antibiotics, bismuths, gastrointestinal surgery, pregnancy, duodenal ulcer and gastric ulcer groups	Patients referred for upper gastrointestinal endoscopy. Boston, USA (N=37)	Patients undergoing endoscopic retrograde cholangiopancreatography for presumed pancreatic or biliary disease on the basis of increased liver function tests (n=24	Biopsy obtained by upper endoscopy	No	Below
w17	Upper gastrointestinal dyspeptic symptoms such as epigastric pain, nausea, vomiting, heartburn, halitosis, burping, postprandial bloating, and flatulence for >6 months	Recent non-steroidal anti-inflammatory drugs	Consecutive patients referred for upper gastrointestinal endoscopy. Normal ultrasonogram and endoscopy results. London, UK (n=55)	Patients undergoing upper gastrointestinal endoscopy for anaemia, with no dyspeptic symptoms and normal endoscopic results (n=15)	Biopsy obtained by upper endoscopy	Age, sex, smoking, and alcohol	Above
w18	Epigastric discomfort after meals, fullness, eructation and belching, bloating or abdominal distension, and normal physical examination	Emergent referrals for upper gastrointestinal endoscopy, gastrointestinal surgery, cancer, steroids, recent non-steroidal anti-inflammatory drugs, antibiotics, anticoagulants, investigational drugs in past 4 weeks	Patients referred for upper gastrointestinal endoscopy. Normal ultrasonogram and endoscopy result. The Netherlands (n=240)	Healthy asymptomatic volunteers: students, hospital staff, and patients with haemorrhoids (n=34)	Biopsy obtained by upper endoscopy	No	Below
w19	Undefined symptoms. Included patients taking non-steroidal anti-inflammatory drugs	Abnormal endoscopic diagnoses	Patients referred for upper gastrointestinal endoscopy. Los Angeles, USA (n=31)	Asymptomatic volunteers participating in another study protocol (n=15)	Biopsy obtained by upper endoscopy	No	Below
w20	Undefined symptoms	Gastrointestinal bleed, acetylsalicylic acid, recent non-steroidal anti-inflammatory drugs, H2 antagonist or cytoprotective, surgery, peptic ulcer disease, cancer, abnormal endoscopic results	Patients referred for upper gastrointestinal endoscopy. Ireland (n=20)	Healthy asymptomatic controls (n=9)	Biopsy obtained by upper endoscopy	No	Below
w21	Structured symptom questionnaire with dyspepsia defined as intermittent or persistent upper gastrointestinal pain, nausea, or discomfort within 6 months	Illness, jaundice, or gastrointestinal bleed, peptic ulcer disease found at endoscopy	Random sample of male monks aged >21 with symptoms of dyspepsia. Tibet (n=111)	Random population of Tibetan monks without dyspeptic symptoms (n=60)	Biopsy obtained by upper endoscopy	No	Above
w22	Pain centred in upper abdomen occurring over previous year. Standardised assessment of ulcer-like, reflux-like, and dysmotility-like symptoms		Consecutive healthy blood donor volunteers recruited over 6 week period with symptoms of dyspepsia. Germany (n=44)	Consecutive healthy blood donor volunteers with dyspeptic symptoms (n=115)	Serology	No	Above
w23	Frequent or occasional abdominal pain, heartburn, acid regurgitation, nausea and vomiting occurring in the year before study	Patients of "foreign extraction"	Random sample of adults with dyspeptic symptoms within the year preceding study entry. Denmark (n=431)	Random sample of adults without dyspeptic symptoms (n=3158)	Serology	Age, sex, gastrointestinal history, recent non-steroidal anti-inflammatory drugs, weight, and sociodemographic indicators	Below

 

Table 2 Characteristics of eradication trials (n=5)
 

Ref No	Study population (patients positive for Helicobacter pylori)	Eradication treatment	Symptom assessment	Definition and assessment of dyspepsia	Quality score
w24	Referred patients. Italy (n=80)	Colloidal bismuth subcitrate 240 mg twice daily for 4 weeks	Baseline and 8 weeks after end of treatment	Dyspepsia undefined. Symptoms of abdominal pain, nausea, burping, meterosim assessed	34
w25	Referred patients. UK (n=50)	Colloidal bismuth subcitrate 30 ml four times daily for 3 weeks or erythromycin ethylsuccinate 10 ml four times daily for 2 weeks	Baseline and after treatment	Dyspepsia undefined. Symptoms of nausea, vomiting, heartburn, indigestion, and belching assessed. Total score range -4 to +4	42
w26	Referred patients. Belgium (n=45)	Amoxycillin suspension 1 g twice daily for 8 days	Before and after treatment	Upper gastrointestinal symptoms of nausea and vomiting, heartburn, epigastric pain defined dyspepsia. Symptoms graded from 0-3 and added to give score between 0 and 18	35
w27	Multicentred trial for referred patients (n=328). Excluded patients with peptic ulcer disease and gastro-oesophageal reflux disease	Omeprazole 20 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily for 7 days	Before, 6, and 12 months after treatment	Pain or discomfort centred in upper abdomen >6 months. Pain or discomfort rated on 7 point Likert scale. Gastrointestinal symptom rating scale. Psychological general wellbeing index	62
w28	Multicentred trial with 89% subjects from referred population and 11% from primary care. Excluded patients with peptic ulcer disease and gastro-oesophageal reflux disease (n=275)	Omeprazole 20 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily for 7 days	1, 3, 6, 9, and 12 months after treatment	Pain or discomfort in the upper abdomen using published criteria. Pain or discomfort rated on 7 point Likert scale. Gastrointestinal symptom rating scale. Psychological general wellbeing index	69

1. Holtmann G, Talley NJ, Goebell H. Association between H. pylori, duodenal mechanosensory thresholds, and small intestinal motility in chronic unexplained dyspepsia. Dig Dis Sci 1996;41:1285-91.
2. Gurakan F, Kocak N, Yuce A. Helicobacter pylori serology in childhood. Turk J Ped 1996;38:329-34.
3. Hobbs FDR, Delaney BC, Rowsby M, Kenkre JE. Effect of Helicobacter pylori eradication therapy on dyspeptic symptoms in primary care. Fam Pract 1996;13:225-8.
4. Tsega E, Gebre W, Manley P, Asfaw T. Helicobacter pylori, gastritis and non-ulcer dyspepsia in Ethiopian patients. Ethiop Med J 1996;34:65-71.
5. Su YC, Jan CM, Wang WM, Chen LT, Wu DC, Liu CS, et al. Does Helicobacter pylori infection play a role in the pathogenesis of non-ulcer dyspepsiaC a study of gastric emptying time. Kaohsiung J Med 1995;11:8-14.
6. Schlemper RJ, Van Der Werf S, Biemond I, Lamers C. Dyspepsia and Helicobacter pylori in Japanese employees with and without ulcer history. J Gastroenterol Hepatol 1995;10:633-8.
7. Agreus L, Engstrand L, Svardsudd K, Nyren O, Tibblin G. Helicobacter pylori seropositivity among Swedish adults with and without abdominal symptoms. A population-based epidemiologic study. Scand J Gastroenterol 1995;30:752-7.
8. Prasad S, Mathan M, Chandy G, Rajan DP, Venkateswaran S, Ramakrishna BS, et al. Prevalence of Helicobacter pylori in southern Indian controls and patients with gastroduodenal disease. J Gastroenterol Hepatol 1994;9:501-6.
9. Wilhelmsen I, Haug TT, Sipponen P, Berstad A. Helicobacter pylori in functional dyspepsia and normal controls. Scand J Gastroenterol 1994;29:522-7.
10. Uyub AM, Raj SM, Visvanathan R, Nazim M, Aiyar S, Annar AK, et al. Helicobacter pylori infection in north-eastern peninsular Malaysia. Evidence for an unusually low prevalence. Scand J Gastroenterol 1994;29:209-13.
11. Gill HH, Desai HG, Majmudar P, Mehta PR, Prabhu SR. Epidemiology of Helicobacter pylori: the Indian scenario. Indian J Gastroenterol 1993;12:9-11.
12. Tucci A, Corinaldesi R, Stanghellini V, Tosetti C, Di Febo G, Paparo GF, et al. Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia. Gastroenterology 1992;103:768-74.
13. Bernersen B, Johnsen R, Bostad L, Straume B, Sommer A-I, Burhol PG. Is Helicobacter pylori the cause of dyspepsia? BMJ 1992;304:1276-9.
14. Mukhopadhyay DK, Tandon RK, Dasarathy S, Mathur M, Wali JP. A study of Helicobacter pylori in north Indian subjects with non-ulcer dyspepsia. Indian J Gastroenterol 1992;11:76-9.
15. Holcombe C, Kaluba J, Lucas SB. Non-ulcer dyspepsia in Nigeria: a case-control study. Trans Royal Soc Trop Med Hygiene 1991;85:553-5.
16. Strauss RM, Wang TC, Kelsey PB, Compton CC, Ferraro MJ, Perez-Perez G, et al. Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy. Am J Med 1990;89:464-9.
17. Rokkas T, Pursey C, Uzoechina E, Dorrington L, Simmons NA, Filipe MI, et al. Campylobacter pylori and non-ulcer dyspepsia. Am J Gastroenterol 1987;82:1149-52.
18. Rauws EA, Langenberg W, Houthoff HJ, Zanen HC, Tytgat GNJ. Campylobacter pyloridis-associated chronic active antral gastritis. A prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterology 1988;94:33-40.
19. Pettross CW, Appleman MD, Cohen H, Valenzuela JE, Chandrasoma P, Laine LA. Prevalence of Campylobacter pylori and association with antral mucosal histology in subjects with and without upper gastrointestinal symptoms. Dig Dis Sci 1988;33:649-53.
20. Collins JSA, Hamilton PW, Watt PCH, Sloan JM, Love AHG. Superficial gastritis and Campylobacter pylori in dyspeptic patientsC a quantitative study using computer-linked image analysis. J Path 1989;158:303-10.
21. Katelaris PH, Tippett GHK, Norbu P, Lowe DG, Brennan R, Farthing MJG. Dyspepsia, Helicobacter pylori, and peptic ulcer in a randomly selected population in India. Gut 1992;33:1462-6.
22. Holtmann G, Goebell H, Holtmann M, Talley NJ. Dyspepsia in healthy blood donors. Pattern of symptoms and association with Helicobacter pylori. Dig Dis Sci 1994;39:1090-8.
23. Rosenstock S, Kay L, Rosenstock C, Andersen LP, Bonnevie O, Jorgensen T. Relation between Helicobacter pylori infection and gastrointestinal symptoms and syndromes. Gut 1997;41:169-76.
24. Vaira D, Holton J, Ainley C, Falzon m, Osborn J, D'Anna L, et al. Double blind trial of colloidal bismuth subcitrate versus placebo in Helicobacter pylori positive patients with non-ulcer dyspepsia. Ital J Gastroenterol 1992;24:400-4.
25. McNulty CA, Gearty JC, Crump B, Davis M, Donovan IA, Melikian V, et al. Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsuccinate. BMJ 1986;293:645-9.
26. Glupczynski Y, Burette A, Labbe M, Deprez C, De Reuck M, Deltenre M. Campylobacter pylori-associated gastritis: a double-blind placebo-controlled trial with amoxycillin. Am J Gastroenterol 1988;83:365-72.
27. Blum AL, Talley NJ, O’Morain C, Veldhuyzen van Zanten S, Labenz J, Stolte M, et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1875-81.
28. Talley NJ, Janssens J, Lauritsen K, Racz I, Bolling-Sternevald E. Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months’ of follow-up. BMJ 1999;318:833-7.

Online poll

Find out more>>