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消化不良

著者: 藤田将平1) 神戸市立医療センター中央市民病院 総合内科

著者: 黒田浩一2) 神戸市立医療センター中央市民病院 感染症科

監修: 山中克郎 福島県立医科大学会津医療センター総合内科

著者校正/監修レビュー済:2022/09/28
参考ガイドライン:
  1. 2017年“American Journal of Gastroenterology”誌
  1. 2005年”Gastroenterology”誌
  1. 2020年“American Family Physician” 誌
  1. 日本消化器病学会:機能性消化管疾患診療ガイドライン2021-機能性ディスペプシア(FD)改訂第2版
患者向け説明資料

概要・推奨   

  1. 消化不良を訴える患者の診察において、警告症状を聴取することはその後の診療を進めていくにあたって有用であるがその有用性を示す確定的な根拠は示されていない。最新のガイドラインでは、60歳以上では全例に上部消化管内視鏡を推奨し、若年者では警告症状が存在する場合に症例ごとに検討すべしとしている(推奨度1)
  1. 消化不良患者に対する酸分泌抑制薬の経験的投与は、症状の軽減に有用である。プロトンポンプ阻害薬(PPI)が第1選択である(推奨度1)
  1. 内視鏡により検索されていない消化不良患者への初期治療では、ピロリ菌のtest and treat戦略(尿素呼気試験陽性者に対して除菌療法を行う、陰性者はPPIによる経験的治療を行う)は、プロトンポンプ阻害薬(PPI)の経験的投与より効果が期待できる(推奨度2)
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  1. 消化不良を訴える患者で、上部消化管内視鏡検査を施行しない場合に行うピロリ菌検査は、尿素呼気試験(UBT)または便中抗原検査(fecal antigen test: FAT)が優れている。Helicobacter pylori IgG検査は、感度・特異度で劣るため推奨されない(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
藤田将平 : 未申告[2022年]
黒田浩一 : 特に申告事項無し[2022年]
監修:山中克郎 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 2017年“American Journal of Gastroenterology”誌や2020年“American Family Physician” 誌のガイドラインに則り、上部消化管内視鏡の適応年齢を警告症状の有無を問わず60歳以上に変更した。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 消化不良は、さまざまな病態から起こり、幅広い鑑別疾患を必要とする、多くの人が訴える症状である。有病率(prevalence)は25%程度とされる[1]が、大多数の患者は医療機関を受診することはない[2]。プライマリケア医を訪れる患者の2~5%が消化不良を訴える[3]
  1. 定義がさまざまであり混乱が生じやすい。慢性的な繰り返す上腹部の痛みと不快感(逆流症状が主な症状の場合は除く)、と定義してガイドライン[4][5]は作成されている(RomeⅡの定義)。ディスペプシアとカタカナで記載されることが多い。
  1. RomeⅢ基準が2006年に発表され、食後の腹部膨満感、早期飽満感(early satiation)、心窩部と痛みまたは灼熱感、のいずれかに該当するものを「消化不良(ディスペプシア)」と定義した[6]。胸焼け症状は含んでいない。食後のもたれ感・早期飽満感を有するものを食後愁訴症候群(postprandial distress syndrome、PDS)、心窩部痛・心窩部灼熱感を有するものを心窩部痛症候群(epigastric pain syndrome、EPS)と亜分類している。さらに2016年にRome IV基準が発表され定義がわずかに改定されたが、実際の診療の影響を与えるほどの変更点はなかった[7]。これらの基準は、研究用基準のため、臨床現場になじまない。実際の臨床現場では、1カ月以上続く心窩部痛を主体とした上部消化管症状を「消化不良」とすればよい[8]
  1. 原因疾患は、機能性ディスペプシア(FD)70%、消化性潰瘍性疾患15~25%、逆流性食道炎5~15%、悪性疾患(胃癌、食道癌)2%未満、の4疾患が重要である[9]。そのほか、過敏性腸症候群、胆道系由来の痛み、胃不全麻痺などが原因となることもある。胃癌・食道癌、胃十二指腸潰瘍をいかにしてみつけるかが重要となる。
 
消化不良の鑑別診断

<図表>:消化不良の起因となる薬剤
Am Fam Physician. 2020 Jan 15;101(2):84-88.を参考に作製

出典

img1:  著者提供
 
 
 
消化不良の起因となる薬剤

消化不良の原因となる薬剤と考えられている。投与量の減量または中止により消化不良が改善する可能性があり、高額な検査を避けられるかもしれない。

出典

img1:  Evaluation and management of dyspepsia.
 
 Am Fam Physician. 1999 Oct 15;60(6):1773・・・
 
  1. “American Journal of Gastroenterology”誌、”Gastroenterology”誌、日本消化器学会各種ガイドラインを参照するとよい。
  1. 消化不良についての診療ガイドラインは、2005年に“American Journal of Gastroenterology”誌と”Gastroenterology”誌から発表された[4][5]。どちらにも意思決定のフローが掲載されている。この2つのガイドラインに大きな差はない。その後のevidenceをもとに、2017年に“American Journal of Gastroenterology”誌のガイドラインが改訂された[8]Helicobacter pylori[10]と胃食道逆流症[11]についてのガイドラインは、“American Journal of Gastroenterology”に掲載されている。Helicobacter pylori診療については欧州からも声明が発表されている[12]。日本消化器学会から、機能性ディスペプシアのガイドラインが2021年に発表された[13]。「診断と治療のフローチャート」が参考になる。日本の医療事情に沿った推奨がなされている。
 
鑑別疾患表:
  1. 機能性ディスペプシア
  1. 消化性潰瘍性疾患
  1. 逆流性食道炎
  1. 胃癌または食道癌
  1. 膵癌を中心とした腹部癌
  1. 胆管疾患
  1. 炭水化物吸収不良(乳糖、ソルビトール、果糖、マンニトール)
  1. 胃不全麻痺
  1. 肝癌
  1. 胃の浸潤性疾患(クローン病、サルコイドーシス)
  1. 腸内寄生虫(ジアルジア、ストロンギロイデス)
  1. 虚血性腸疾患
  1. 薬剤
  1. 代謝障害(高カルシウム血症、高カリウム血症)
  1. 膵炎
  1. 全身性疾患(糖尿病、甲状腺障害、副甲状腺障害、結合組織疾患)
問診・診察のポイント  
  1. 「消化不良」と判断する前に、上腹部症状が心疾患、腹壁の筋骨格系疾患、内分泌疾患由来でないか検討する。胸焼けや逆流症状が前面に出ている場合は、「消化不良」ではなくGERDと考えて、診療を進める。

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文献 

N J Talley, A R Zinsmeister, C D Schleck, L J Melton
Dyspepsia and dyspepsia subgroups: a population-based study.
Gastroenterology. 1992 Apr;102(4 Pt 1):1259-68.
Abstract/Text It has been proposed that patients with dyspepsia can be classified into symptom groupings that may represent different pathophysiological entities; however, it remains to be shown that distinct symptom subgroups exist. To estimate the prevalence of dyspepsia (defined as upper abdominal pain) and dyspepsia subgroups, an age- and sex-stratified random sample of Olmsted County, Minnesota, residents, aged 30-64 years, were mailed a valid self-report questionnaire; 82% responded (n = 835). Subgroups were as follows: those with symptoms suggestive of peptic ulceration (ulcerlike dyspepsia), those with gastric stasis (dysmotilitylike dyspepsia), those with gastroesophageal reflux (refluxlike dyspepsia), and the remainder (unspecified dyspepsia). Ulcerlike dyspepsia was the commonest subgroup (prevalence, 16.0/100; 95% confidence interval, 13.4-18.5), but 43% of subjects with dyspepsia could be classified into more than one subgroup. Nearly one third of dyspeptics also had irritable bowel symptoms, but these were not confined to any particular dyspepsia subgroup. Although dyspepsia is very common in the community and the majority have ulcerlike symptoms, there is such overlap among the dyspepsia subgroups that a classification based on symptoms alone in uninvestigated patients may not be useful.

PMID 1551533
O V Bazaldua, F D Schneider
Evaluation and management of dyspepsia.
Am Fam Physician. 1999 Oct 15;60(6):1773-84, 1787-8.
Abstract/Text Dyspepsia, often defined as chronic or recurrent discomfort centered in the upper abdomen, can be caused by a variety of conditions. Common etiologies include peptic ulcers and gastroesophageal reflux. Serious causes, such as gastric and pancreatic cancers, are rare but must also be considered. Symptoms of possible causes often overlap, which can make initial diagnosis difficult. In many patients, a definite cause is never established. The initial evaluation of patients with dyspepsia includes a thorough history and physical examination, with special attention given to elements that suggest the presence of serious disease. Endoscopy should be performed promptly in patients who have "alarm symptoms" such as melena or anorexia. Optimal management remains controversial in young patients who do not have alarm symptoms. Although management should be individualized, a cost-effective initial approach is to test for Helicobacter pylori and treat the infection if the test is positive. If the H. pylori test is negative, empiric therapy with a gastric acid suppressant or prokinetic agent is recommended. If symptoms persist or recur after six to eight weeks of empiric therapy, endoscopy should be performed.

PMID 10537391
R S Fisher, H P Parkman
Management of nonulcer dyspepsia.
N Engl J Med. 1998 Nov 5;339(19):1376-81. doi: 10.1056/NEJM199811053391907.
Abstract/Text
PMID 9801400
Nicholas J Talley, Nimish B Vakil, Paul Moayyedi
American gastroenterological association technical review on the evaluation of dyspepsia.
Gastroenterology. 2005 Nov;129(5):1756-80. doi: 10.1053/j.gastro.2005.09.020.
Abstract/Text
PMID 16285971
Nicholas J Talley, Nimish Vakil, Practice Parameters Committee of the American College of Gastroenterology
Guidelines for the management of dyspepsia.
Am J Gastroenterol. 2005 Oct;100(10):2324-37. doi: 10.1111/j.1572-0241.2005.00225.x.
Abstract/Text Dyspepsia is a chronic or recurrent pain or discomfort centered in the upper abdomen; patients with predominant or frequent (more than once a week) heartburn or acid regurgitation, should be considered to have gastroesophageal reflux disease (GERD) until proven otherwise. Dyspeptic patients over 55 yr of age, or those with alarm features should undergo prompt esophagogastroduodenoscopy (EGD). In all other patients, there are two approximately equivalent options: (i) test and treat for Helicobacter pylori (H. pylori) using a validated noninvasive test and a trial of acid suppression if eradication is successful but symptoms do not resolve or (ii) an empiric trial of acid suppression with a proton pump inhibitor (PPI) for 4-8 wk. The test-and-treat option is preferable in populations with a moderate to high prevalence of H. pylori infection (> or =10%); empirical PPI is an initial option in low prevalence situations. If initial acid suppression fails after 2-4 wk, it is reasonable to consider changing drug class or dosing. If the patient fails to respond or relapses rapidly on stopping antisecretory therapy, then the test-and-treat strategy is best applied before consideration of referral for EGD. Prokinetics are not currently recommended as first-line therapy for uninvestigated dyspepsia. EGD is not mandatory in those who remain symptomatic as the yield is low; the decision to endoscope or not must be based on clinical judgement. In patients who do respond to initial therapy, stop treatment after 4-8 wk; if symptoms recur, another course of the same treatment is justified. The management of functional dyspepsia is challenging when initial antisecretory therapy and H. pylori eradication fails. There are very limited data to support the use of low-dose tricyclic antidepressants or psychological treatments in functional dyspepsia.

PMID 16181387
Jan Tack, Nicholas J Talley, Michael Camilleri, Gerald Holtmann, Pinjin Hu, Juan-R Malagelada, Vincenzo Stanghellini
Functional gastroduodenal disorders.
Gastroenterology. 2006 Apr;130(5):1466-79. doi: 10.1053/j.gastro.2005.11.059.
Abstract/Text A numerically important group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region. Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gastroduodenal disorders is proposed. Four categories of functional gastroduodenal disorders are distinguished. The first category, functional dyspepsia, groups patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation. Based on recent evidence and clinical experience, a subgroup classification is proposed for postprandial distress syndrome (early satiation or postprandial fullness) and epigastric pain syndrome (pain or burning in the epigastrium). The second category, belching disorders, comprises aerophagia (troublesome repetitive belching with observed excessive air swallowing) and unspecified belching (no evidence of excessive air swallowing). The third category, nausea and vomiting disorders, comprises chronic idiopathic nausea (frequent bothersome nausea without vomiting), functional vomiting (recurrent vomiting in the absence of self-induced vomiting, or underlying eating disorders, metabolic disorders, drug intake, or psychiatric or central nervous system disorders), and cyclic vomiting syndrome (stereotypical episodes of vomiting with vomiting-free intervals). The rumination syndrome is a fourth category of functional gastroduodenal disorder characterized by effortless regurgitation of recently ingested food into the mouth followed by rechewing and reswallowing or expulsion. The proposed classification requires further research and careful validation but the criteria should be of value for clinical practice; for epidemiological, pathophysiological, and clinical management studies; and for drug development.

PMID 16678560
Vincenzo Stanghellini, Francis K L Chan, William L Hasler, Juan R Malagelada, Hidekazu Suzuki, Jan Tack, Nicholas J Talley
Gastroduodenal Disorders.
Gastroenterology. 2016 May;150(6):1380-92. doi: 10.1053/j.gastro.2016.02.011.
Abstract/Text Symptoms that can be attributed to the gastroduodenal region represent one of the main subgroups among functional gastrointestinal disorders. A slightly modified classification into the following 4 categories is proposed: (1) functional dyspepsia, characterized by 1 or more of the following: postprandial fullness, early satiation, epigastric pain, and epigastric burning, which are unexplained after a routine clinical evaluation; and includes 2 subcategories: postprandial distress syndrome that is characterized by meal-induced dyspeptic symptoms and epigastric pain syndrome that does not occur exclusively postprandially; the 2 subgroups can overlap; (2) belching disorders, defined as audible escapes of air from the esophagus or the stomach, are classified into 2 subcategories, depending on the origin of the refluxed gas as detected by intraluminal impedance measurement belching: gastric and supragastric belch; (3) nausea and vomiting disorders, which include 3 subcategories: chronic nausea and vomiting syndrome; cyclic vomiting syndrome; and cannabinoid hyperemesis syndrome; and (4) rumination syndrome.

Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 27147122
Paul M Moayyedi, Brian E Lacy, Christopher N Andrews, Robert A Enns, Colin W Howden, Nimish Vakil
ACG and CAG Clinical Guideline: Management of Dyspepsia.
Am J Gastroenterol. 2017 Jul;112(7):988-1013. doi: 10.1038/ajg.2017.154. Epub 2017 Jun 20.
Abstract/Text We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.

PMID 28631728
Anne Mounsey, Amir Barzin, Ashley Rietz
Functional Dyspepsia: Evaluation and Management.
Am Fam Physician. 2020 Jan 15;101(2):84-88.
Abstract/Text Functional dyspepsia is defined as at least one month of epigastric discomfort without evidence of organic disease found during an upper endoscopy, and it accounts for 70% of dyspepsia. Symptoms of functional dyspepsia include postprandial fullness, early satiety, and epigastric pain or burning. Functional dyspepsia is a diagnosis of exclusion; therefore, evaluation for a more serious disease such as an upper gastrointestinal malignancy is warranted. Individual alarm symptoms do not correlate with malignancy for patients younger than 60 years, and endoscopy is not necessarily warranted but should be considered for patients with severe or multiple alarm symptoms. For patients younger than 60 years, a test and treat strategy for Helicobacter pylori is recommended before acid suppression therapy. For patients 60 years or older, upper endoscopy should be performed. All patients should be advised to limit foods associated with increased symptoms of dyspepsia; a diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) is suggested. Eight weeks of acid suppression therapy is recommended for patients who test negative for H. pylori, or who continue to have symptoms after H. pylori eradication. If acid suppression does not alleviate symptoms, patients should be treated with tricyclic antidepressants followed by prokinetics and psychological therapy. The routine use of complementary and alternative medicine therapies has not shown evidence of effectiveness and is not recommended.

PMID 31939638
William D Chey, Benjamin C Y Wong, Practice Parameters Committee of the American College of Gastroenterology
American College of Gastroenterology guideline on the management of Helicobacter pylori infection.
Am J Gastroenterol. 2007 Aug;102(8):1808-25. doi: 10.1111/j.1572-0241.2007.01393.x. Epub 2007 Jun 29.
Abstract/Text Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70-85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7-14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple therapy for persistent H. pylori infection, though this needs to be validated in the United States.

PMID 17608775
Kenneth R DeVault, Donald O Castell, American College of Gastroenterology
Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.
Am J Gastroenterol. 2005 Jan;100(1):190-200. doi: 10.1111/j.1572-0241.2005.41217.x.
Abstract/Text Guidelines for the diagnosis and treatment of gastroesophageal reflux disease (GERD) were published in 1995 and updated in 1999. These and other guidelines undergo periodic review. Advances continue to be made in the area of GERD, leading us to review and revise previous guideline statements. GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. These guidelines were developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee, and approved by the Board of Trustees. Diagnostic guidelines address empiric therapy and the use of endoscopy, ambulatory reflux monitoring, and esophageal manometry in GERD. Treatment guidelines address the role of lifestyle changes, patient directed (OTC) therapy, acid suppression, promotility therapy, maintenance therapy, antireflux surgery, and endoscopic therapy in GERD. Finally, there is a discussion of the rare patient with refractory GERD and a list of areas in need of additional study.

PMID 15654800
P Malfertheiner, F Megraud, C O'Morain, F Bazzoli, E El-Omar, D Graham, R Hunt, T Rokkas, N Vakil, E J Kuipers
Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report.
Gut. 2007 Jun;56(6):772-81. doi: 10.1136/gut.2006.101634. Epub 2006 Dec 14.
Abstract/Text BACKGROUND: Guidelines on the management of Helicobacter pylori, which cover indications for management and treatment strategies, were produced in 2000.
AIMS: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer.
RESULTS: Eradication of H pylori infection is recommended in (a) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; (b) patients with atrophic gastritis; (c) first degree relatives of patients with gastric cancer; (d) patients with unexplained iron deficiency anaemia; and (e) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a "test and treat" strategy if other causes are excluded. Eradication of H pylori infection (a) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and (b) may prevent peptic ulcer in patients who are naïve users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility.
CONCLUSION: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.

PMID 17170018
A B R Thomson, A N Barkun, D Armstrong, N Chiba, R J White, S Daniels, S Escobedo, B Chakraborty, P Sinclair, S J O Veldhuyzen Van Zanten
The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia: the Canadian Adult Dyspepsia Empiric Treatment - Prompt Endoscopy (CADET-PE) study.
Aliment Pharmacol Ther. 2003 Jun 15;17(12):1481-91.
Abstract/Text BACKGROUND: Uninvestigated dyspepsia is common in family practice. The prevalence of clinically significant upper gastrointestinal findings (CSFs) in adult uninvestigated dyspepsia patients, and their predictability based on history, is unknown.
METHODS: Prompt endoscopy was performed within 10 days of referral, in 1040 adult patients presenting with uninvestigated dyspepsia at 49 Canadian family practitioner centres. Subsequent management strategies during a 6-month follow-up period were determined by the individual family practitioners.
RESULTS: CSFs were identified in 58% (603/1040) of patients. Erosive oesophagitis was most common (43%; N = 451); peptic ulcer was uncommon (5.3%; N = 55). Alarm symptoms were uncommon (2.8%; N = 29). Most patients had at least three dyspepsia symptoms, more than 80% had at least six, and approximately half had eight or more. Based on the dominant symptom, 463 (45%) patients had ulcer-like, 393 (38%) had reflux-like and 184 (18%) had dysmotility-like dyspepsia. The patients' dominant symptom was not predictive of endoscopic findings. Oesophagitis was more common in those with dominant reflux-like symptoms and was the most common finding in all subgroups. The prevalence of gastroduodenal findings was similar in all symptom subgroups. Helicobacter pylori (H. pylori) infection (30%; 301/1013) was associated with gastroduodenal findings.
CONCLUSIONS: Dyspepsia subclassifications, based on dominant symptom, are of limited value in predicting the presence and nature of CSFs. Oesophagitis was by far the most common diagnosis (43% of patients). CSFs were common in uninvestigated dyspepsia patients and their nature suggests patients could be initially treated effectively, without endoscopy, using empirical acid suppressive therapy.

PMID 12823150
C P Dooley, A W Larson, N H Stace, I G Renner, J E Valenzuela, J Eliasoph, P M Colletti, J M Halls, J M Weiner
Double-contrast barium meal and upper gastrointestinal endoscopy. A comparative study.
Ann Intern Med. 1984 Oct;101(4):538-45.
Abstract/Text One hundred randomly selected inpatients were examined with both double-contrast barium meal and endoscopy in a blinded prospective fashion. All studies were done by staff personnel, with equal clinical information available to both the radiologist and endoscopist. The final diagnosis was made by a review committee of participating radiologists and endoscopists. Endoscopy was more sensitive (92% versus 54%, p less than 0.001) and specific (100% versus 91%, p less than 0.05) than the double-contrast barium meal. Both procedures significantly affected the clinical outcome of the patient, the effect of endoscopy being significantly greater than that of the double-contrast barium meal. Although errors with the barium study related predominantly to an inability to show subtle lesions, poor patient cooperation and perceptual and technical failures were additional significant factors. Endoscopy is recommended for certain groups of patients.

PMID 6383166
P B Cotton, P J Shorvon
Analysis of endoscopy and radiography in the diagnosis, follow-up and treatment of peptic ulcer disease.
Clin Gastroenterol. 1984 May;13(2):383-403.
Abstract/Text
PMID 6378443
M B Wallace, V L Durkalski, J Vaughan, Y Y Palesch, E D Libby, P S Jowell, N J Nickl, S M Schutz, J W Leung, P B Cotton
Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study.
Gut. 2001 Jul;49(1):29-34.
Abstract/Text INTRODUCTION: Symptoms of dyspepsia are common but most patients do not have major upper gastrointestinal pathology. Endoscopy is recommended for dyspeptic patients over the age of 45, or those with certain "alarm" symptoms. We have evaluated the effectiveness of age and "alarm" symptoms for predicting major endoscopic findings in six practising endoscopy centres.
METHODS: Clinical variables of consecutive patients with dyspepsia symptoms undergoing upper endoscopy examinations were recorded using a common endoscopy database. Patients who had no previous upper endoscopy or barium radiography were included. Stepwise multivariate logistic regression was used to identify predictors of endoscopic findings. The accuracy of these for predicting endoscopic findings was evaluated with receiver operating characteristic analysis. The sensitivity and specificity of age thresholds from 30 to 70 years were evaluated.
RESULTS: Major pathology (tumour, ulcer, or stricture) was found at endoscopy in 787/3815 (21%) patients with dyspepsia. Age, male sex, bleeding, and anaemia were found to be significant but weak independent predictors of endoscopic findings. A multivariate prediction rule based on these factors had poor predictive accuracy (c statistic=0.62). Using a simplified prediction rule of age > or =45 years or the presence of any "alarm" symptom, sensitivity was 87% and specificity was 26%. Increasing or decreasing the age cut off did not significantly improve the predictive accuracy.
CONCLUSIONS: Age and the presence of "alarm" symptoms are not effective predictors of endoscopic findings among patients with dyspepsia. Better clinical prediction strategies are needed to identify patients with significant upper gastrointestinal pathology.

PMID 11413107
Nimish Vakil, Paul Moayyedi, M Brian Fennerty, Nicholas J Talley
Limited value of alarm features in the diagnosis of upper gastrointestinal malignancy: systematic review and meta-analysis.
Gastroenterology. 2006 Aug;131(2):390-401; quiz 659-60. doi: 10.1053/j.gastro.2006.04.029.
Abstract/Text BACKGROUND & AIMS: Alarm features such as dysphagia, weight loss, or anemia raise concern of an upper gastrointestinal malignancy in patients with dyspepsia. The aim of this study was to determine the diagnostic accuracy of alarm features in predicting malignancy by performing a metaanalysis based on the published literature.
METHODS: English-language studies were identified by searching MEDLINE, EMBASE, Cochrane Controlled Trials Register, and CINAHL. Cohort studies that measured alarm features and compared them with the endoscopic findings were included. Studies were screened for inclusion by 2 authors who independently extracted the data. Sensitivity, specificity, and likelihood ratios were calculated by comparing the alarm feature with the endoscopic diagnosis. The summary receiver operating characteristic curve method was used to summarize test characteristics across studies. Individual alarm features were also assessed when the study report permitted.
RESULTS: Eighty-three of 2600 studies met the initial screening criteria; 15 met inclusion criteria after detailed review. These 15 studies evaluated a total of 57,363 patients, of whom 458 (.8%) had cancer. The sensitivity of alarm symptoms varied from 0% to 83% with considerable heterogeneity between studies. The specificity also varied significantly from 40% to 98%. A clinical diagnosis made by a physician was very specific (range, 97%-98%) but not very sensitive (range, 11%-53%).
CONCLUSIONS: Alarm features have limited predictive value for an underlying malignancy. Their use in dyspepsia management strategies needs further refinement and study.

PMID 16890592
S Stapley, T J Peters, R D Neal, P W Rose, F M Walter, W Hamilton
The risk of oesophago-gastric cancer in symptomatic patients in primary care: a large case-control study using electronic records.
Br J Cancer. 2013 Jan 15;108(1):25-31. doi: 10.1038/bjc.2012.551. Epub 2012 Dec 20.
Abstract/Text BACKGROUND: Over 15 000 new oesophago-gastric cancers are diagnosed annually in the United Kingdom, with most being advanced disease. We identified and quantified features of this cancer in primary care.
METHODS: Case-control study using electronic primary-care records of the UK patients aged ≥40 years was performed. Cases with primary oesophago-gastric cancer were matched to controls on age, sex and practice. Putative features of cancer were identified in the year before diagnosis. Odds ratios (ORs) were calculated for these features using conditional logistic regression, and positive predictive values (PPVs) were calculated.
RESULTS: A total of 7471 cases and 32 877 controls were studied. Sixteen features were independently associated with oesophago-gastric cancer (all P<0.001): dysphagia, OR 139 (95% confidence interval 112-173); reflux, 5.7 (4.8-6.8); abdominal pain, 2.6 (2.3-3.0); epigastric pain, 8.8 (7.0-11.0); dyspepsia, 6 (5.1-7.1); nausea and/or vomiting, 4.9 (4.0-6.0); constipation, 1.5 (1.2-1.7); chest pain, 1.6 (1.4-1.9); weight loss, 8.9 (7.1-11.2); thrombocytosis, 2.4 (2.0-2.9); low haemoglobin, 2.4 (2.1-2.7); low MCV, 5.2 (4.2-6.4); high inflammatory markers, 1.7 (1.4-2.0); raised hepatic enzymes, 1.3 (1.2-1.5); high white cell count, 1.4 (1.2-1.7); and high cholesterol, 0.8 (0.7-0.8). The only PPV >5% in patients ≥55 years was for dysphagia. In patients <55 years, all PPVs were <1%.
CONCLUSION: Symptoms of oesophago-gastric cancer reported in secondary care were also important in primary care. The results should inform guidance and commissioning policy for upper GI endoscopy.

PMID 23257895
Paul Moayyedi, Nicholas J Talley, M Brian Fennerty, Nimish Vakil
Can the clinical history distinguish between organic and functional dyspepsia?
JAMA. 2006 Apr 5;295(13):1566-76. doi: 10.1001/jama.295.13.1566.
Abstract/Text CONTEXT: Upper gastrointestinal symptoms occur in 40% of the population. An accurate diagnosis would help rationalize investigation and treatment.
OBJECTIVE: To systematically review the literature of the accuracy of primary care physicians, gastroenterologists, or computer models in diagnosing organic dyspepsia.
DATA SOURCES: A search of Cochrane Controlled Trials Register (December 2003), MEDLINE (1966-December 2003), EMBASE (1988-December 2003), and CINAHL (1982-December 2003) for studies that reported on cohorts of patients attending for endoscopy that had symptoms, clinical opinion, or both recorded before investigation.
STUDY SELECTION: Studies that prospectively compared the diagnosis reached by a clinician, computer model, or both with results of upper gastrointestinal endoscopy in adult patients with upper gastrointestinal symptoms.
DATA EXTRACTION: Two authors independently assessed studies (n = 79) for eligibility and abstracted data for estimating likelihood ratios (LRs) of clinical opinion, computer models, or both in diagnosing an organic cause for dyspepsia.
DATA SYNTHESIS: Fifteen studies were identified that evaluated 11 366 patients, with 4817 patients (42%) classified as having organic dyspepsia. The computer models performed similarly to the clinician; therefore, the 2 approaches were combined. The diagnosis reached by the clinician or computer model suggesting organic dyspepsia had an LR of 1.6 (95% confidence interval [CI], 1.4-1.8), and a negative result decreased the likelihood of organic dyspepsia (LR, 0.46; 95% CI, 0.38-0.55). A diagnosis of peptic ulcer disease performed similarly with an LR of 2.2 (95% CI, 1.9-2.6), but an evaluation that suggested the absence of peptic ulcer disease had an LR of 0.45 (95% CI, 0.38-0.53). A clinical history suggesting esophagitis had an LR of 2.4 (95% CI, 1.9-3.0) vs a negative history that had an LR of 0.50 (95% CI, 0.42-0.60).
CONCLUSION: Neither clinical impression nor computer models that incorporated patient demographics, risk factors, history items, and symptoms adequately distinguished between organic and functional disease in patients referred for endoscopic evaluation of dyspepsia.

PMID 16595759
Cristino Canga, Nimish Vakil
Upper GI malignancy, uncomplicated dyspepsia, and the age threshold for early endoscopy.
Am J Gastroenterol. 2002 Mar;97(3):600-3. doi: 10.1111/j.1572-0241.2002.05536.x.
Abstract/Text OBJECTIVES: We sought to determine the frequency with which patients with upper GI malignancies present with uncomplicated dyspepsia and to determine the impact of changing the threshold for early endoscopy from 45 to 55 yr, as has recently been recommended in European studies.
METHODS: Three hundred forty-one patients with upper GI malignancies at two Milwaukee teaching hospitals were identified from electronic databases. Trained physician-investigators reviewed the charts using a specifically designed questionnaire. Staging of GI cancers was performed using the TNM classification to determine operability. Uncomplicated dyspepsia was defined as dyspepsia without alarm symptoms/signs (dysphagia, vomiting, weight loss, early satiety, GI bleeding, or anemia).
RESULTS: There were 341 patients with upper GI malignancies with a mean age of 68 yr (range = 22-94). Twenty-one patients were younger than 45 and 65 were under 55. Uncomplicated dyspepsia was the presenting symptom in five of 65 (7.7%) patients younger than 55 and one of 21 (4.8%) patients under 45 (p = 0.99). Five patients 55 or younger presented with uncomplicated dyspepsia. All had advanced, inoperable disease (stage III or higher).
CONCLUSIONS: 1) In a racially diverse United States population, upper GI malignancy presenting without alarm symptoms is uncommon. 2) Raising the threshold for immediate endoscopy in uncomplicated dyspepsia from age 45 to 55 increases the risk of missing an underlying malignancy but may not affect outcome, as incurable disease was present at diagnosis within a few weeks of the onset of symptoms.

PMID 11922553
P S Phull, C A Salmon, K G M Park, T Rapson, A M Thompson, F J Gilbert
Age threshold for endoscopy and risk of missing upper gastrointestinal malignancy--data from the Scottish audit of gastric and oesophageal cancer.
Aliment Pharmacol Ther. 2006 Jan 15;23(2):229-33. doi: 10.1111/j.1365-2036.2006.02744.x.
Abstract/Text BACKGROUND: Urgent endoscopy is indicated for suspected upper gastrointestinal malignancy. However, there is limited evidence on the age threshold for performing urgent endoscopy in uncomplicated dyspepsia (that is, without alarm features).
AIM: To quantify the risk of missing upper gastrointestinal malignancy within Scotland, if the age threshold for urgent endoscopy in uncomplicated dyspepsia was increased from 45 to 55 years.
METHODS: Analysis of data collected prospectively by the Scottish Audit of Gastric and Oesophageal Cancer. 'Alarm' features at presentation were defined as dysphagia, weight loss, gastrointestinal bleeding, anaemia, vomiting, history of gastric surgery and history of peptic ulcer disease.
RESULTS: Of the 3293 patients diagnosed with upper gastrointestinal malignancy, 290 (8.8%) patients were <55 years of age. Twenty-one of the patients aged <55 years had no alarm features (0.64% of all patients); 12 were aged 45-55 years and nine were aged <45 years. Only two patients (one aged <45 years) underwent potentially curative surgery.
CONCLUSION: Upper gastrointestinal malignancy is uncommon under 55 years of age and most of the patients present with alarm features. Raising the age threshold for endoscopy for new-onset uncomplicated dyspepsia from 45 to 55 years would not impact adversely on the diagnosis or outcome of upper gastrointestinal malignancy.

PMID 16393301
Abstract/Text BACKGROUND: The incidence of early gastric cancer has not increased despite better access to endoscopic facilities for general practitioners. Many patients receive a course of symptomatic treatment while waiting for gastroscopy.
AIMS: To ascertain the effect of antisecretory therapy on the diagnostic process and findings for patients with upper gastrointestinal cancer.
METHODS: A consecutive case study survey of the primary care records of 133 patients who had died of upper gastrointestinal cancer during 1995-97 in the South Tees health district in the north-east of England (population 300 000).
RESULTS: From the 133 patients identified, 116 had died from adenocarcinoma of the oesophagus (31) or stomach (85). Failure to reach the diagnosis of cancer at the index gastroscopy was associated with prior acid suppression therapy. Only one of 54 patients on no treatment or antacids alone was erroneously diagnosed as suffering from benign disease, whereas 22 of 62 patients treated with acid suppression were diagnosed as suffering from benign disease but at varying times later turned out to have adenocarcinoma. Twenty of 45 patients taking a proton pump inhibitor had a delayed diagnosis compared with two of 17 taking an H(2) receptor antagonist. The commonest lesion seen at index gastroscopy in those in whom the diagnosis was initially missed was gastric ulcer. Healing occurred in six patients taking a proton pump inhibitor, despite their later diagnosis of malignancy.
CONCLUSIONS: The treatment of dyspeptic symptoms with acid suppression prior to gastroscopy masks and delays the detection of gastric and oesophageal adenocarcinoma on endoscopy in one third of patients.

PMID 10716673
S J Panter, H O'Flanagan, M G Bramble, A P S Hungin
Empirical use of antisecretory drug therapy delays diagnosis of upper gastrointestinal adenocarcinoma but does not effect outcome.
Aliment Pharmacol Ther. 2004 May 1;19(9):981-8. doi: 10.1111/j.1365-2036.2004.01924.x.
Abstract/Text BACKGROUND: Upper gastrointestinal cancer carries a poor prognosis. Although the incidence of gastric adenocarcinoma is falling, oesophageal adenocarcinoma is increasing. This has been attributed to an increasing prevalence of gastro-oesophageal reflux disease, commonly treated empirically in primary care with antisecretory drugs. Treatment has been associated with delayed diagnosis but it is unclear if this influences prognosis.
AIMS: To ascertain the effect of antisecretory drugs on time to diagnosis, symptoms, tumour stage and outcome.
METHODS: A retrospective cohort study of primary care records for 747 patients diagnosed with upper gastrointestinal adenocarcinoma at South Tees NHS Trust between 1991 and 2001.
RESULTS: Mean time from the onset of symptoms to diagnosis was 30 weeks. Mean and median times at the primary care stage were longer than at the hospital stage for both oesophageal and gastric cancer (P < 0.0001). Patients with benign symptoms prescribed antisecretory drugs were referred later than those not on antisecretory drugs (P < 0.0001), as were patients with alarm symptoms (P = 0.0008). Prior use of antisecretory drugs delayed diagnosis by 17.6 weeks (mean) but had no effect on tumour stage at diagnosis or survival.
CONCLUSION: Prior antisecretory drug therapy was associated with delayed diagnosis of upper gastrointestinal adenocarcinoma irrespective of presenting symptoms. Concerns that delays might adversely affect tumour stage or long-term survival were not substantiated.

PMID 15113364
Annmarie Lassen, Jesper Hallas, Ove B Schaffalitzky de Muckadell
The risk of missed gastroesophageal cancer diagnoses in users and nonusers of antisecretory medication.
Gastroenterology. 2005 Oct;129(4):1179-86. doi: 10.1053/j.gastro.2005.07.028.
Abstract/Text BACKGROUND & AIMS: Some patients with early gastroesophageal cancer may appear to "heal" because of antisecretory medication, but the risk of a missed diagnosis is unknown. The aim of the study was to estimate the incidence of gastroesophageal cancer with or without pre-endoscopic treatment with antisecretory medication.
METHODS: We extracted data on use of endoscopies, gastroesophageal cancer diagnoses, death, migration, and use of antisecretory medication (H(2) blockers and proton pump inhibitors) from 5 population-based registries covering 1974-2002. We included all citizens in Funen County (population, 470,000) who between 1993 and 2002 were investigated by endoscopy for the first time. The patients were followed up until death, emigration, or the end of the study period.
RESULTS: Among 27,829 patients with a first endoscopy (mean age, 56 years; 48% male, 115,804 person-years of follow-up), 461 had gastroesophageal cancer diagnosed at the first endoscopy and 52 were diagnosed during a median follow-up of 2.7 years after the first endoscopy. The incidence during follow-up was similar to the background population (standardized incidence ratio, 1.24; 95% confidence interval, 0.81-1.91), increased with age, and was higher in male patients. The incidence of gastroesophageal cancer during follow-up was 46 per 100,000 person-years in users of antisecretory medication the last 180 days before the first endoscopy compared with 44 per 100,000 person-years in nonusers (age and sex standardized difference, 4 per 100,000 person-years; 95% confidence interval, -14 to 22).
CONCLUSIONS: Very few cancers are missed at endoscopy. The risk seems similar in users and nonusers of antisecretory medication before endoscopy.

PMID 16230072
D Gillen, K E McColl
Does concern about missing malignancy justify endoscopy in uncomplicated dyspepsia in patients aged less than 55?
Am J Gastroenterol. 1999 Jan;94(1):75-9. doi: 10.1111/j.1572-0241.1999.00774.x.
Abstract/Text OBJECTIVE: There is increasing interest in using noninvasive H. pylori testing rather than endoscopy in determining the management of younger patients presenting with dyspepsia. However, there is concern that this approach may result in missing potentially curable malignancy. The aim of the study was therefore to assess whether concern over occult malignancy is valid in patients aged <55 yr presenting with uncomplicated dyspepsia.
METHODS: A predetermined questionnaire was used to review the case notes of patients aged <55 yr who had presented with esophageal or gastric cancer between 1989 and 1993 within the Greater Glasgow Health Board population of 940,000.
RESULTS: A total of 169 patients aged <55 yr were diagnosed to have gastroesophageal malignancy over the 5-yr period, representing an incidence of about 1 per 28,000 total population/yr. There were only five patients who were found to have upper GI malignancy when undergoing upper GI investigation in the absence of sinister symptoms. This represents an incidence of underlying malignancy in patients of <55 yr with uncomplicated dyspepsia of 1.06 per million total population/yr. Of these five patients, all had lymph node metastases at diagnosis and four had died between 2 months and 3 yr of follow-up.
CONCLUSIONS: Upper GI malignancy is extremely rare in patients <55 yr presenting with uncomplicated dyspepsia and, when found, is usually incurable. Consequently, concern about missing underlying curable malignancy is not a valid indication for endoscoping patients <55 yr presenting with uncomplicated dyspepsia.

PMID 9934734
Nimish Vakil, Nicholas Talley, Sander Veldhuyzen van Zanten, Nigel Flook, Tore Persson, Ewa Björck, Tore Lind, Elisabeth Bolling-Sternevald, STARS I Study Group
Cost of detecting malignant lesions by endoscopy in 2741 primary care dyspeptic patients without alarm symptoms.
Clin Gastroenterol Hepatol. 2009 Jul;7(7):756-61. doi: 10.1016/j.cgh.2009.03.031. Epub 2009 Apr 10.
Abstract/Text BACKGROUND & AIMS: Current guidelines recommend empirical, noninvasive approaches to manage dyspeptic patients without alarm symptoms, but concerns about missed lesions persist; the cost savings afforded by noninvasive approaches must be weighed against treatment delays. We investigated the prevalence of malignancies and other serious abnormalities in patients with dyspepsia and the cost of detecting these by endoscopy.
METHODS: We studied 2741 primary-care outpatients, 18-70 years in age, who met Rome II criteria for dyspepsia. Patients with alarm features (dysphagia, bleeding, weight loss, etc) were excluded. All patients underwent endoscopy. The cost and diagnostic yield of an early endoscopy strategy in all patients were compared with those of endoscopy limited to age-defined cohorts. Costs were calculated for a low, intermediate, and high cost environment.
RESULTS: Endoscopies detected abnormalities in 635 patients (23%). The most common findings were reflux esophagitis with erosions (15%), gastric ulcers (2.7%), and duodenal ulcers (2.3%). The prevalence of upper gastrointestinal malignancy was 0.22%. If all dyspeptic patients 50 years or older underwent endoscopy, 1 esophageal cancer and no gastric cancers would have been missed. If the age threshold for endoscopy were set at 50 years, at a cost of $500/endoscopy, it would cost $82,900 (95% CI, $35,714-$250,000) to detect each case of cancer.
CONCLUSIONS: Primary care dyspeptic patients without alarm symptoms rarely have serious underlying conditions at endoscopy. The costs associated with diagnosing an occult malignancy are large, but an age cut-off of 50 years for early endoscopy provides the best assurance that an occult malignancy will not be missed.

PMID 19364542
Dino Vaira, Nimish Vakil, Marcello Menegatti, Ben van't Hoff, Chiara Ricci, Luigi Gatta, Giovanni Gasbarrini, Mario Quina, Jose M Pajares Garcia, Arie van Der Ende, Rene van Der Hulst, Marcello Anti, Cristina Duarte, Javier P Gisbert, Mario Miglioli, Guido Tytgat
The stool antigen test for detection of Helicobacter pylori after eradication therapy.
Ann Intern Med. 2002 Feb 19;136(4):280-7.
Abstract/Text BACKGROUND: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed.
OBJECTIVE: To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection.
DESIGN: Prospective blinded study.
SETTING: Six clinical centers in the United States and Europe.
PATIENTS: 84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms.
MEASUREMENTS: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy.
RESULTS: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%]).
CONCLUSION: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.

PMID 11848725
C T Loy, L M Irwig, P H Katelaris, N J Talley
Do commercial serological kits for Helicobacter pylori infection differ in accuracy? A meta-analysis.
Am J Gastroenterol. 1996 Jun;91(6):1138-44.
Abstract/Text OBJECTIVES: To compare the accuracy of common commercial serological kits for Helicobacter pylori and to ascertain factors affecting accuracy.
METHODS: A comprehensive MEDLINE and manual search strategy was used to identify all articles comparing two or more kits. Each article was critically appraised for sample characteristics, study design, and data handling. The data comparing accuracy of the kits was analyzed by standard statistical methods as well as summary receiver operator characteristic curves (sROCs). A sROC also was used to estimate overall test accuracy and to identify factors affecting the measurement of accuracy.
RESULTS: The 21 studies identified were of varying quality, but our analyses suggested that different commercial kits did not have significantly different accuracy. Overall, at a sensitivity of 85%, specificity was estimated to be 79%. Test accuracy measured was significantly higher in studies with smaller proportions of infected patients.
CONCLUSIONS: There is little evidence in the literature to suggest that any one of the common commercial serological kits is more accurate than any other. The overall accuracy of these kits may not be adequate for clinical decision-making in all patient groups.

PMID 8651160
D Vaira, P Malfertheiner, F Mégraud, A T Axon, M Deltenre, A M Hirschl, G Gasbarrini, C O'Morain, J M Garcia, M Quina, G N Tytgat
Diagnosis of Helicobacter pylori infection with a new non-invasive antigen-based assay. HpSA European study group.
Lancet. 1999 Jul 3;354(9172):30-3.
Abstract/Text BACKGROUND: Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H. pylori infection, we evaluated an EIA for H. pylori antigen in stool (HpSA).
METHODS: In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17-88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H. pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H. pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H. pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy.
FINDINGS: Of 272 patients with H. pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94.1% [95% CI 90.6-96.6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91.8% [87.3-95.1]).
INTERPRETATION: The stool assay was a reliable and easy-to-use tool for diagnosis of H. pylori infection. The test was accurate even shortly after treatment.

PMID 10406362
Abstract/Text BACKGROUND: Clinical guidelines support a noninvasive Helicobacter pylori "test-and-treat" strategy for individuals with uncomplicated dyspepsia. However, consensus is lacking regarding the preferred noninvasive testing method.
OBJECTIVE: To use decision analytic modeling to estimate the clinical and economic outcomes associated with noninvasive tests designed to detect either H pylori antibody or active H pylori infection.
DESIGN: Decision analytic model.
PATIENTS: A simulated patient cohort with uncomplicated dyspepsia.
INTERVENTIONS: The simulated dyspepsia cohort underwent antibody testing or testing to detect active H pylori infection (active testing). Individuals testing positive received eradication therapy.
MAIN OUTCOME MEASURES: Appropriate and inappropriate treatment prescribed, cost per patient treated, incremental cost per unnecessary treatment avoided.
RESULTS: Active testing led to a substantial reduction in unnecessary treatment for patients without active infection (antibody, 23.7; active, 1.4 per 100 patients) at an incremental cost of $37 per patient. The clinical advantage and cost-effectiveness of active testing was enhanced as the percentage of individuals with a positive antibody test result from past, but not current, infection increased.
CONCLUSIONS: Active testing for H pylori infection significantly decreases the inappropriate use of antimicrobial therapy when compared with antibody testing. The advantages of active testing should be enhanced as the widespread use of antimicrobial agents increases the proportion of patients with antibody to H pylori, but without active infection.

PMID 11570943
P Malfertheiner, F Mégraud, C O'Morain, A P S Hungin, R Jones, A Axon, D Y Graham, G Tytgat, European Helicobacter Pylori Study Group (EHPSG)
Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report.
Aliment Pharmacol Ther. 2002 Feb;16(2):167-80.
Abstract/Text Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21-22 September 2000. A "test and treat" approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test. As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients' wishes after full consultation. It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs. Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradication should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.

PMID 11860399
Abstract/Text BACKGROUND: In contrast to earlier beliefs, it is nowadays assumed that no relation exists between dyspeptic symptoms and the presence of gallstones. Although many studies indeed failed to show a relation, each has been too small to exclude it. The aim of this meta-analysis is to systematically review epidemiologic studies and to synthesize the data.
METHODS: Twenty-one controlled studies on the association between gallstones and dyspeptic symptoms were analyzed after critical appraisal with regard to selection bias, blinding, confounding, and data presentation. Most of them had reasonable validity. Inconsistencies between results of the studies could not be explained by differences in study design or validity. There was a slight indication of publication bias.
RESULTS: Upper abdominal pain was consistently associated with gallstones (pooled odds ratios, about 2.0), with no preference for the right side. The findings on biliary pain were inconsistent. The results exclude with reasonable certainty an association between gallstones and 'classical' dyspeptic symptoms such as flatulence, heartburn, and acid regurgitation, bloating, and belching. An exception was nausea and vomiting (odds ratio, 1.4). Unspecified food intolerance was related to gallstones, but fat intolerance was not.
CONCLUSIONS: We conclude that it is not sensible to call dyspeptic symptoms 'gallstone dyspepsia', since component symptoms do not show a consistent relation with gallstones, and their diagnostic meaning over and above abdominal pain has not been evaluated.

PMID 7638565
Abstract/Text Many physicians consider gallstones to be a cause of vague upper abdominal discomfort. However, both dyspepsia and gallstones are common conditions in the general population, and the relationship between the two has continued to generate controversy. In this editorial, I review the evidence for and against a relationship between gallstones and dyspepsia. The data suggest that upper abdominal discomfort, heartburn, bloating, and other vague symptoms are not related to gallstones and the routine ordering of an ultrasound in the patient with dyspepsia is not warranted.

PMID 7797821
Abstract/Text AIM: To compare lansoprazole 30 mg daily with ranitidine 150 mg b.d. in the treatment of acid-related dyspepsia in general practice.
METHODS: In a double-blind, parallel group, randomized, mutlicentre study conducted in 32 general practices in the UK, 213 patients were randomized to receive lansoprazole 30 mg daily, and 219 to receive ranitidine 150 mg b.d., for 4 weeks. All patients had experienced symptoms of reflux-like or ulcer-like dyspepsia on at least 4 of the 7 days prior to the study; 75% had experienced dyspepsia in the past, and 74 of the lansoprazole patients and 77 of the ranitidine patients had documented histories of acid-related disorders, investigating by either radiology or endoscopy.
RESULTS: After 2 weeks 55% of the lansoprazole patients and 33% of the ranitidine group were symptom-free (P = 0.001, chi 2 = 7.12) with corresponding 4-week figures of 69% and 44%, respectively (P = 0.001, chi 2 = 18.03). Similar figures were found at both 2 and 4 weeks for daytime and night-time heartburn and epigastric pain scores; in the lansoprazole group, at 4 weeks, 80% of patients were free of daytime heartburn and 81% of night-time epigastric pain, compared with 55% (P = 0.001, chi 2 = 15.44) and 65% (P = 0.01, chi 2 = 6.10) in the ranitidine group.
CONCLUSION: Superior symptom relief for patients presenting with ulcer-like and reflux-like symptoms in general practice is provided by lansoprazole 30 mg daily compared with ranitidine 150 mg twice daily.

PMID 9218080
I Mason, L J Millar, R R Sheikh, W M Evans, P L Todd, M L Turbitt, M D Taylor
The management of acid-related dyspepsia in general practice: a comparison of an omeprazole versus an antacid-alginate/ranitidine management strategy. Compete Research Group [corrected].
Aliment Pharmacol Ther. 1998 Mar;12(3):263-71.
Abstract/Text BACKGROUND: There is need for an evidence-based comparison of clinical management strategies to provide the rationale for selection of a particular therapeutic approach to treatment. Ideal dyspepsia treatment should quickly and conveniently alleviate patient symptoms whilst also minimizing the use of healthcare resources.
AIM: To examine dyspepsia symptom relief over 16 weeks and compare an omeprazole clinical management strategy with a commonly used combination of antacid-alginate followed by H2-antagonist.
METHODS: Seven hundred and twenty-five patients participated in this randomized, open, parallel group comparison over 16 weeks. Patients were randomized to receive either an omeprazole treatment strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as required, or an antacid-alginate/ranitidine treatment strategy (362) consisting of antacid-alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg q.d.s. as required.
RESULTS: A greater proportion of patients receiving the omeprazole clinical management strategy had achieved the stringent health target of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty-six per cent of omeprazole-treated patients were symptom free after the first 10 mg step compared to only 17% in the antacid-alginate treated group (P = 0.0001). Total relief of heartburn, the most common symptom at entry, was achieved by more patients in the omeprazole treatment group than the antacid-alginate/ranitidine treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks (P = 0.0001).
CONCLUSION: Treatment with the omeprazole clinical management strategy was superior to the antacid-alginate/ranitidine management strategy in providing relief of acid-related dyspepsia symptoms after 16 weeks. In addition, the omeprazole treatment strategy involved fewer GP consultations and thus minimized the use of other healthcare resources.

PMID 9570261
Kouichi Sakurai, Akihito Nagahara, Kazuhiko Inoue, Junichi Akiyama, Katsuhiro Mabe, Junichi Suzuki, Yasuki Habu, Akihiro Araki, Tsuyoshi Suzuki, Katsuaki Satoh, Haruhiko Nagami, Ryosaku Harada, Nobuo Tano, Masayasu Kusaka, Yasuhiko Fujioka, Toshikatsu Fujimura, Nobuyuki Shigeto, Tsuneyo Oumi, Jun Miwa, Hiroto Miwa, Kazuma Fujimoto, Yoshikazu Kinoshita, Ken Haruma
Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS).
BMC Gastroenterol. 2012 May 1;12:42. doi: 10.1186/1471-230X-12-42. Epub 2012 May 1.
Abstract/Text BACKGROUND: In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms.
METHODS: This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily). The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2). UMIN clinical trial registration number: UMIN000005399.
RESULTS: Of 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverse events.
CONCLUSIONS: The favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss) should receive further investigation, including prompt referral for endoscopy.
TRIAL REGISTRATION: UMIN000005399.

PMID 22548767
Gianpiero Manes, Antonella Menchise, Claudio de Nucci, Antonio Balzano
Empirical prescribing for dyspepsia: randomised controlled trial of test and treat versus omeprazole treatment.
BMJ. 2003 May 24;326(7399):1118. doi: 10.1136/bmj.326.7399.1118.
Abstract/Text OBJECTIVE: To compare the efficacy of a "Helicobacter pylori test and treat" strategy with that of an empirical trial of omeprazole in the non-endoscopic management by empirical prescribing of young patients with dyspepsia.
DESIGN: Randomised controlled trial.
SETTING: Hospital gastroenterology unit.
PARTICIPANTS: 219 patients under 45 years old presenting with dyspepsia without alarm symptoms.
INTERVENTION: Patients received treatment with omeprazole 20 mg (group A) or with a urea breath test followed by an eradication treatment in case of H pylori infection or omeprazole alone in non-infected patients (group B). Lack of improvement or recurrence of symptoms prompted endoscopy.
MAIN OUTCOME MEASURES: Improvement in symptoms assessed by a dyspepsia severity score every two months; use of medical resources (endoscopic workload and medical consultation); clinical outcome.
RESULTS: 96/109 (88%) patients in group A and 61/110 (55%) in group B (P < 0.0001) had endoscopy: in 19 patients in group A and 32 in group B (20/67 infected and 12/43 non-infected) because of no improvement; in 77 further patients in group A and 29 in group B (7 infected and 22 non-infected) because of recurrence of symptoms during follow up. Endoscopy showed peptic ulcers only in group A; oesophagitis occurred significantly more often in group B than in group A. About 80% of examinations were normal in both groups, but nine duodenal scars occurred in group A.
CONCLUSIONS: Eradication treatment allows resolution of symptoms in a large number of patients with dyspepsia and reduces the endoscopic workload. After a trial of omeprazole, symptoms recur in nearly every patient. Such treatment is also likely to mask an appreciable number of peptic ulcers and cases of oesophagitis.

PMID 12763982
Naoki Chiba, Sander J O Veldhuyzen Van Zanten, Paul Sinclair, Ralph A Ferguson, Sergio Escobedo, Eileen Grace
Treating Helicobacter pylori infection in primary care patients with uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatment-Helicobacter pylori positive (CADET-Hp) randomised controlled trial.
BMJ. 2002 Apr 27;324(7344):1012-6.
Abstract/Text OBJECTIVE: To determine whether a "test for Helicobacter pylori and treat" strategy improves symptoms in patients with uninvestigated dyspepsia in primary care.
DESIGN: Randomised placebo controlled trial.
SETTING: 36 family practices in Canada.
PARTICIPANTS: 294 patients positive for H pylori ((13)C- urea breath test) with symptoms of dyspepsia of at least moderate severity in the preceding month.
INTERVENTION: PARTICIPANTS were randomised to twice daily treatment for 7 days with omeprazole 20 mg, metronidazole 500 mg, and clarithromycin 250 mg or omeprazole 20 mg, placebo metronidazole, and placebo clarithromycin. Patients were then managed by their family physicians according to their usual care.
MAIN OUTCOME MEASURES: Treatment success defined as no symptoms or minimal symptoms of dyspepsia at the end of one year. Societal healthcare costs collected prospectively for a secondary evaluation of actual mean costs.
RESULTS: In the intention to treat population (n=294), eradication treatment was significantly more effective than placebo in achieving treatment success (50% v 36%; P=0.02; absolute risk reduction=14%; number needed to treat=7, 95% confidence interval 4 to 63). Eradication treatment cured H pylori infection in 80% of evaluable patients. Treatment success at one year was greater in patients negative for H pylori than in those positive for H pylori (54% v 39%; P=0.02). Eradication treatment reduced mean annual cost by $C53 (-86 to 180) per patient.
CONCLUSIONS: A "test for H pylori with (13)C-urea breath test and eradicate" strategy shows significant symptomatic benefit at 12 months in the management of primary care patients with uninvestigated dyspepsia.

PMID 11976244
W K Leung, S-R Lin, J Y L Ching, K-F To, E K W Ng, F K L Chan, J Y W Lau, J J Y Sung
Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication.
Gut. 2004 Sep;53(9):1244-9. doi: 10.1136/gut.2003.034629.
Abstract/Text BACKGROUND AND AIMS: Gastric intestinal metaplasia (IM) is generally considered to be a precancerous lesion in the gastric carcinogenesis cascade. This study identified the risk factors associated with progression of IM in a randomised control study.
SUBJECTS AND METHODS: A total of 587 Helicobacter pylori infected subjects were randomised to receive a one week course of anti-Helicobacter therapy (omeprazole, amoxicillin, and clarithromycin (OAC)) or placebo. Subjects underwent endoscopy with biopsy at baseline and at five years. Severity of IM was graded according to the updated Sydney classification and progression was defined as worsening of IM scores at five years in either the antrum or corpus, or development of neoplasia. Backward stepwise multiple logistic regression was used to identify independent risk factors associated with IM progression.
RESULTS: Of 435 subjects (220 in the OAC and 215 in the placebo group) available for analysis, 10 developed gastric cancer and three had dysplasia. Overall progression of IM was noted in 52.9% of subjects. Univariate analysis showed that persistent H pylori infection, age >45 years, male subjects, alcohol use, and drinking water from a well were significantly associated with IM progression. Duodenal ulcer and OAC treatment were associated with a reduced risk of histological progression. Progression of IM was more frequent in those with more extensive and more severe IM at baseline. With multiple logistic regression, duodenal ulcer (odds ratio (OR) 0.23 (95% confidence interval (CI) 0.09-0.58)) was found to be an independent protective factor against IM progression. Conversely, persistent H pylori infection (OR 2.13 (95% CI 1.41-3.24)), age >45 years (OR 1.92 (95% CI 1.18-3.11)), alcohol use (OR 1.67 (95% CI 1.07-2.62)), and drinking water from a well (OR 1.74 (95% CI 1.13-2.67)) were independent risk factors associated with IM progression.
CONCLUSION: Eradication of H pylori is protective against progression of premalignant gastric lesions.

PMID 15306578
Benjamin Chun-Yu Wong, Shiu Kum Lam, Wai Man Wong, Jian Shun Chen, Ting Ting Zheng, Rui E Feng, Kam Chuen Lai, Wayne Hsing Cheng Hu, Siu Tsan Yuen, Suet Yi Leung, Daniel Yee Tak Fong, Joanna Ho, Chi Kong Ching, Jun Shi Chen, China Gastric Cancer Study Group
Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial.
JAMA. 2004 Jan 14;291(2):187-94. doi: 10.1001/jama.291.2.187.
Abstract/Text CONTEXT: Although chronic Helicobacter pylori infection is associated with gastric cancer, the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown.
OBJECTIVE: To determine whether treatment of H pylori infection reduces the incidence of gastric cancer.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, placebo-controlled, population-based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province, China, recruited in July 1994 and followed up until January 2002. A total of 988 participants did not have precancerous lesions (gastric atrophy, intestinal metaplasia, or gastric dysplasia) on study entry.
INTERVENTION: Patients were randomly assigned to receive H pylori eradication treatment: a 2-week course of omeprazole, 20 mg, a combination product of amoxicillin and clavulanate potassium, 750 mg, and metronidazole, 400 mg, all twice daily (n = 817); or placebo (n = 813).
MAIN OUTCOME MEASURES: The primary outcome measure was incidence of gastric cancer during follow-up, compared between H pylori eradication and placebo groups. The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions, compared between the 2 groups.
RESULTS: Among the 18 new cases of gastric cancers that developed, no overall reduction was observed in participants who received H pylori eradication treatment (n = 7) compared with those who did not (n = 11) (P =.33). In a subgroup of patients with no precancerous lesions on presentation, no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo (0 vs 6; P =.02). Smoking (hazard ratio [HR], 6.2; 95% confidence interval [CI], 2.3-16.5; P<.001) and older age (HR, 1.10; 95% CI, 1.05-1.15; P<.001) were independent risk factors for the development of gastric cancer in this cohort.
CONCLUSIONS: We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China. In the subgroup of H pylori carriers without precancerous lesions, eradication of H pylori significantly decreased the development of gastric cancer. Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted.

PMID 14722144
K E L McColl, L S Murray, D Gillen, A Walker, A Wirz, J Fletcher, C Mowat, E Henry, A Kelman, A Dickson
Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia.
BMJ. 2002 Apr 27;324(7344):999-1002.
Abstract/Text OBJECTIVE: To compare the efficacy of non-invasive testing for Helicobacter pylori with that of endoscopy (plus H pylori testing) in the management of patients referred for endoscopic investigation of upper gastrointestinal symptoms.
DESIGN: Randomised controlled trial with follow up at 12 months.
SETTING: Hospital gastroenterology unit.
PARTICIPANTS: 708 patients aged under 55 referred for endoscopic investigation of dyspepsia, randomised to non-invasive breath test for H pylori or endoscopy plus H pylori testing.
MAIN OUTCOME MEASURE: Glasgow dyspepsia severity score at one year. Use of medical resources, patient oriented outcomes, and safety were also assessed.
RESULTS: In 586 patients followed up at 12 months the mean change in dyspepsia score was 4.8 in the non-invasive H pylori test group and 4.6 in the endoscopy group (95% confidence interval for difference -0.7 to 0.5, P=0.69). Only 8.2% of patients followed up who were randomised to breath test alone were referred for subsequent endoscopy. The use of non-endoscopic resources was similar in the two groups. Reassurance value, concern about missed pathology, overall patient satisfaction, and quality of life were similar in the two groups. The patients found the non-invasive breath test procedure less uncomfortable and distressing than endoscopy with or without sedation. No potentially serious pathology requiring treatment other than eradication of H pylori was missed.
CONCLUSION: In this patient group, non-invasive testing for H pylori is as effective and safe as endoscopy and less uncomfortable and distressing for the patient. Non-invasive H pylori testing should be the preferred mode of investigation.

PMID 11976239
A T Lassen, F M Pedersen, P Bytzer, O B Schaffalitzky de Muckadell
Helicobacter pylori test-and-eradicate versus prompt endoscopy for management of dyspeptic patients: a randomised trial.
Lancet. 2000 Aug 5;356(9228):455-60.
Abstract/Text BACKGROUND: Strategies based on screening for Helicobacter pylori to manage dyspeptic patients in primary care have been proposed, but the clinical consequences are unclear. We did a randomised trial to assess the efficacy and safety of a test-and-eradicate strategy compared with prompt endoscopy in the management of patients with dyspepsia.
METHODS: 500 patients presenting in primary care with dyspepsia (> or = 2 weeks of epigastric pain, no alarm symptoms) were assigned H. pylori testing plus eradication therapy or endoscopy. Symptoms, quality of life, patients' satisfaction, and use of resources were recorded during 1 year of follow-up.
FINDINGS: 250 patients were assigned test-and-eradicate, and 250 prompt endoscopy. The median age was 45 years and 28% were H. pylori infected. 1 year follow-up was completed by 447 patients. We found no differences in symptoms between the two groups (median registered days without dyspeptic symptoms=0.63 [IQR 0.27-0.81] in the test-and-eradicate group vs 0.67 [0.36-0.86] in the prompt endoscopy group; mean difference 0.04 [95% CI -0.01-0.10], p=0.12). Nor did we find any difference in quality of life or numbers of sick-leave days, visits to general practitioners, or hospital admissions. In the test-and-eradicate group, 27 (12%) of the patients were dissatisfied with management, compared with eight (4%) in the endoscopy group (p=0.013). After 1 year, the use of endoscopies in the test-and-eradicate group was 0.40 times (95% CI 0.31-0.51) the use in the endoscopy group, the use of H. pylori tests increased by a factor of 8.1 (5.7-13.1), the use of eradication treatments increased by a factor of 1.5 (0.9-2.7), and the use of proton-pump inhibitors was 0.89 (0.59-1.33) times the use in the endoscopy group. 43 (91% [80-98%]) of 47 peptic-ulcer patients would have been identified by endoscopy or treated by eradication therapy.
INTERPRETATION: A H. pylori test-and-eradicate strategy is as efficient and safe as prompt endoscopy for management of dyspeptic patients in primary care, although fewer patients are satisfied with their treatment.

PMID 10981888
Abstract/Text BACKGROUND: Management of dyspepsia remains a controversial area. Although the European Helicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do not exhibit alarm symptoms, this strategy has not been subjected to clinical trial.
AIMS: To compare a "test and treat" eradication policy against management by OGD.
PATIENTS: Consecutive subjects were prospectively recruited from open access OGD and outpatient referrals.
METHODS: H pylori status was assessed using the carbon-13 urea breath test. H pylori positive patients were randomised to either empirical eradication or OGD. Symptoms and quality of life scores were assessed at baseline and subsequent reviews over a 12 month period.
RESULTS: A total of 104 H pylori positive patients aged under 45 years were recruited. Fifty two were randomised to receive empirical eradication therapy and 52 to OGD. Results were analysed using an intention to treat policy. Dyspepsia scores significantly improved in both groups over 12 months compared with baseline; however, dyspepsia scores were significantly better in the empirical eradication group. Quality of life showed significant improvements in both groups at 12 months; however, physical role functioning was significantly improved in the empirical eradication group. Fourteen (27%) in the empirical eradication group subsequently proceeded to OGD because of no improvement in dyspepsia.
CONCLUSIONS: This randomised study strongly supports the use of empirical H pylori eradication in patients referred to secondary practice; it is estimated that 73% of OGDs in this group would have been avoided with no detriment to clinical outcome.

PMID 10403729
Nicolaas L A Arents, Jacob C Thijs, Anton A van Zwet, Marco Oudkerk Pool, Jan-Mark Gotz, Ger T van de Werf, Klaas Reenders, Wim J Sluiter, Jan H Kleibeuker
Approach to treatment of dyspepsia in primary care: a randomized trial comparing "test-and-treat" with prompt endoscopy.
Arch Intern Med. 2003 Jul 14;163(13):1606-12. doi: 10.1001/archinte.163.13.1606.
Abstract/Text BACKGROUND: The value of the "test-and-treat" strategy in the approach to dyspepsia has been evaluated only in a few secondary care studies. Most patients with dyspepsia, however, are treated by their primary care physician. This study evaluated the test-and-treat strategy in primary care.
METHODS: Patients consulting their general practitioners for dyspepsia were randomized to either direct open-access endoscopy with Helicobacter pylori testing or a test-and-treat strategy by H pylori serology. In the 12-month follow-up period, any additional treatment or referral for investigations was left at the discretion of the general practitioner. At the end of the study, data were collected concerning the number of endoscopies, changes in symptom severity and quality of life, patient satisfaction, and the use of medical resources.
RESULTS: Two hundred seventy patients were enrolled (129 who received endoscopy and 141 in the test-and-treat group). The prevalence of H pylori infection was 38.3% and 37.2% in the test-and-treat and endoscopy groups, respectively. In the test-and-treat group, 46 patients (33%) were referred for endoscopy during follow-up. Improvement in symptom severity, quality of life, and patient satisfaction was comparable in both groups. Patients in the test-and-treat group paid more dyspepsia-related visits to their general practitioner (P =.005). Patients in the endoscopy group were more often prescribed proton pump inhibitors (P =.007), whereas patients in the test-and-treat group were more often prescribed prokinetic drugs (P =.005).
CONCLUSIONS: The test-and-treat strategy proved to be as effective and safe as prompt endoscopy. Only a minority of patients were referred for endoscopy after the test-and-treat approach.

PMID 12860586
A Quadri, N Vakil
Health-related anxiety and the effect of open-access endoscopy in US patients with dyspepsia.
Aliment Pharmacol Ther. 2003 Mar 15;17(6):835-40.
Abstract/Text BACKGROUND: The role of endoscopy in dyspepsia is the subject of debate. The detection of lesions is infrequent, but patients may benefit from the knowledge that the examination is normal. We sought to determine the prevalence of health-related anxiety in dyspeptic patients referred for open-access endoscopy and to investigate the effect of endoscopy on health-related anxiety.
METHODS: Consecutive patients referred for open-access endoscopy from primary care were studied using a validated questionnaire for health-related anxiety before and after endoscopy, at 1 month and 6 months. Symptoms were assessed using a validated questionnaire at 1 and 6 months.
RESULTS: One hundred and nine patients were studied (69 women and 40 men; mean age, 49 +/- 15 years). Thirty-six of the 109 patients (33%) had high anxiety scores at baseline (mean score, 41 +/- 1), which decreased after endoscopy to 35 +/- 1 (P < 0.05). The changes persisted at 1 month (33 +/- 1) and 6 months (33 +/- 1). Endoscopic findings were as follows: normal examination, 120; erosive oesophagitis, 11 (Grade A); erosive duodenitis (all Helicobacter pylori-negative), 6. Scales for preoccupation with health and fear of illness and death showed significant improvement after endoscopy, and the effects were preserved for 6 months. Anxiety scores in our population were substantially higher than in a corresponding UK population.
CONCLUSIONS: Health-related anxiety is common in dyspeptic patients referred for endoscopy. Endoscopy decreases the preoccupation with health and fear of illness and death in patients with severe anxiety, and the effects persist for 6 months.

PMID 12641506
Abstract/Text OBJECTIVES: Patients with acid-related symptoms in general practice are often treated empirically with a standard dose of proton pump inhibitors (PPIs). The effect of higher doses is not known. The study compared the immediate symptom relieving as well as the long-term effect of standard and double dose of omeprazole in such patients.
METHODS: Consecutive patients with dyspeptic symptoms, normally treated by the general practitioner with PPIs or H2-blockers were randomized to treatment with omeprazole 40 mg, 20 mg, or placebo in the morning for 2 wk. Patients with alarm symptoms, IBS, and PPI-treated patients were excluded. Dyspeptic symptoms and Helicobacter pylori status were recorded. The study endpoint was complete relief of the dyspeptic symptoms, which initiated the consultation. Relapse rates and health-care consumption were recorded during 12-month observation.
RESULTS: Eight hundred and twenty-nine patients were randomized. Complete relief of the predominant symptom was obtained by 66%, 63%, and 35% in patients treated with omeprazole 40 mg, 20 mg, and placebo, respectively. No difference was found comparing H. pylori-positive and -negative patients. Relapse rates were high and health-care consumption during 12 months was related to the treatment outcome, but not to the omeprazole dose or the H. pylori status.
CONCLUSIONS: Compared to placebo, omeprazole 40 mg and 20 mg were equally and significantly better in relieving acid-related symptoms; the numbers needed-to-treat (NNT) were 3.2 (40 mg) and 3.7 (20 mg). Relief of the dyspeptic complaint was followed by significantly reduced health-care consumption during 12-month observation.

PMID 15180724
Linda Rabeneck, Julianne Souchek, Kimberly Wristers, Terri Menke, Eunice Ambriz, Iris Huang, Nelda Wray
A double blind, randomized, placebo-controlled trial of proton pump inhibitor therapy in patients with uninvestigated dyspepsia.
Am J Gastroenterol. 2002 Dec;97(12):3045-51. doi: 10.1111/j.1572-0241.2002.07123.x.
Abstract/Text OBJECTIVES: In patients with uninvestigated dyspepsia, a common initial management strategy in primary care is to prescribe a course of empiric antisecretory therapy and to refer those patients who do not respond for endoscopy. The objective of this research was to evaluate the effects of an empiric course of antisecretory therapy on dyspepsia-related health in patients with uninvestigated dyspepsia.
METHODS: We conducted a double blind, randomized, placebo-controlled trial in which patients with uninvestigated dyspepsia were randomized to a 6-wk course of omeprazole 20 mg p.o. b.id. versus placebo capsules p.o. bi.d. and followed over 1 yr. The patients were at least 18 yr old with at least a 1-wk history of dyspepsia without alarm features. Dyspepsia-related health was measured using the Severity of Dyspepsia Assessment (SODA), a valid, reliable, disease-specific outcome measure. The primary outcome was treatment failure, defined by a SODA Pain Intensity score > or = 29 (scores, 2-47) during follow-up. Patients who were treatment failures underwent endoscopy.
RESULTS: We enrolled 140 patients. The mean age was 51 yr, and seven (5%) were women. At 2 wk there were fewer treatment failures in the omeprazole group: 12 of 71 patients (17%) in the omeprazole group failed compared with 24 of 69 (35%) in the placebo group (p = 0.037, log rank test). Also, at 6 wk there were fewer failures in the omeprazole group: 21 of 71 patients (30%) in the omeprazole group failed compared with 31 of 69 (45%) in the placebo group in 0.067, log rank test). However, at the 1-yr follow-up, there was no significant difference in treatment failure rates in the two groups: 37 of 71 patients (52%) in the omeprazole group failed compared with 41 of 69 (59%) in the placebo group (p = 0.28, log rank test).
CONCLUSIONS: In patients with uninvestigated dyspepsia, as compared with a strategy that would entail prompt endoscopy for all patients, an initial 6-wk course of either placebo or omeprazole reduces the need for endoscopy over a 1-yr follow-up. Compared with placebo, an initial 6-wk course of omeprazole delays, but does not reduce, the need for endoscopy. For proton pump inhibitor therapy to reduce the need for endoscopy, it may need to be given continuously.

PMID 12492188
Sander J O Veldhuyzen van Zanten, Naoki Chiba, David Armstrong, Alan Barkun, Alan Thomson, Sandra Smyth, Sergio Escobedo, Joanna Lee, Paul Sinclair
A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study.
Am J Gastroenterol. 2005 Jul;100(7):1477-88. doi: 10.1111/j.1572-0241.2005.40280.x.
Abstract/Text BACKGROUND: The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies.
METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months.
RESULTS: Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p < 0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine.
CONCLUSION: Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.

PMID 15984968
L Laine, R Estrada, M Trujillo, K Knigge, M B Fennerty
Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter pylori.
Ann Intern Med. 1998 Oct 1;129(7):547-50.
Abstract/Text BACKGROUND: Proton-pump inhibitor therapy may cause false-negative results on Helicobacter pylori diagnostic testing.
OBJECTIVE: To determine the frequency and duration of conversion of urea breath test results from positive to negative in patients given a proton-pump inhibitor.
SETTING: Two urban university gastroenterology clinics.
PATIENTS: Patients infected with H. pylori who had positive results on urea breath tests.
INTERVENTION: Lansoprazole, 30 mg/d for 28 days.
MEASUREMENTS: The urea breath test was repeated at 28 days. If the results were negative, testing was repeated 3, 7, 14, and 28 days after completion of therapy until the results reverted to positive.
RESULTS: 31 (33%) of 93 patients in whom H. pylori was not eradicated had a negative breath test result while receiving lansoprazole. The proportions of patients whose breath test results were positive after completion of lansoprazole therapy were 91% (95% CI, 83% to 96%) at 3 days, 97% (CI, 90% to 99%) at 7 days, and 100% (CI, 96% to 100%) at 14 days.
CONCLUSION: Patients should not receive proton-pump inhibitors for 2 weeks before receiving the urea breath test for H. pylori infection.

PMID 9758575
Luigi Gatta, Nimish Vakil, Chiara Ricci, John F Osborn, Andrea Tampieri, Federico Perna, Mario Miglioli, Dino Vaira
Effect of proton pump inhibitors and antacid therapy on 13C urea breath tests and stool test for Helicobacter pylori infection.
Am J Gastroenterol. 2004 May;99(5):823-9. doi: 10.1111/j.1572-0241.2004.30162.x.
Abstract/Text OBJECTIVE: There is uncertainty about the best method of testing patients for Helicobacter pylori (H. pylori) infection while they are taking proton pump inhibitors. The aim of this study was to determine: (i) if the decreased sensitivity of the urea breath test during proton pump inhibitor is corrected by different techniques for breath testing and (ii) if the sensitivity of stool test is decreased with the administration of proton pump inhibitors.
METHODS: Prospective randomized single-blind study was performed in a tertiary care university hospital. Out of 72 H. pylori infected patients endoscoped for upper abdominal symptoms 48 were randomized to proton pump inhibitors (omeprazole 20 mg each day or esomeprazole 40 mg each day) and 24 to antacid (aluminum hydroxide 800 mg each day) for 14 days. Several breath tests (standard 75 mg (13)C-UBT with citric acid, with orange juice, a tablet breath test with 100 and 50 mg of (13)C), and a stool test were carried out. Baseline samples were collected before and after treatment.
RESULTS: The baseline sensitivity for all breath tests was 100% in both groups; for stool test it was 97.8% (95% CI: 88.7-96.6) and 90% (95% CI: 69.9-97.2) in the proton pump inhibitor and antacid group, respectively. After treatment, the sensitivity of tests was significantly low (UBTs range: 77.1%-85.4%; stool test: 83%; 95% CI: 63.9-91.1), while it was unchanged in the antacid group.
CONCLUSIONS: False negative breath and stool tests are equally common in patients taking proton pump inhibitors. Antacids do not impair the sensitivity of the breath tests or the stool test.

PMID 15128344
David Y Graham, Antone R Opekun, Fadi Hammoud, Yoshio Yamaoka, Rita Reddy, Michael S Osato, Hala M T El-Zimaity
Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors.
Am J Gastroenterol. 2003 May;98(5):1005-9. doi: 10.1111/j.1572-0241.2003.07426.x.
Abstract/Text OBJECTIVE: The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results.
METHOD: In the UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration.
RESULTS: Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects.
CONCLUSION: PPI-induced negative UBT results were related to the anti-H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.

PMID 12809820
W D Chey, M Woods, J M Scheiman, T T Nostrant, J DelValle
Lansoprazole and ranitidine affect the accuracy of the 14C-urea breath test by a pH-dependent mechanism.
Am J Gastroenterol. 1997 Mar;92(3):446-50.
Abstract/Text OBJECTIVES: To determine the effect of lansoprazole and high dose ranitidine on the accuracy of the 14C-urea breath test (UBT). Using intragastric pH recordings, we correlated the effect of these agents on the UBT with their potency of gastric acid suppression.
METHODS: Patients with active Helicobacter pylori infection underwent a baseline UBT before receiving 14 days of lansoprazole (30 mg/day) or ranitidine (300 mg b.i.d.). During therapy, patients were asked to undergo 24-h intragastric pH monitoring. Repeat breath testing was performed 1 day after completion of the study drugs. If the UBT was equivocal or negative (14CO2 excretion was < 200 dpm), further UBTs were completed until the 14CO2 excretion was > 200 dpm.
RESULTS: Thirteen patients received lansoprazole. Eight of thirteen patients developed a negative or equivocal UBT. All patients had 14CO2 excretion > 200 dpm 5 days after the cessation of lansoprazole. Eleven patients received ranitidine. Ranitidine led to equivocal or false negative UBTs in 2 of 11 cases. This effect resolved within 5 days of stopping ranitidine. Intragastric pH recordings revealed that the patients who experienced the most profound gastric acid suppression were those that developed equivocal or false negative UBTs.
CONCLUSIONS: Lansoprazole significantly affected the accuracy of the UBT, causing equivocal or false negative results in 61%. High dose ranitidine affected the breath test in only 18%. The ability of these drugs to suppress gastric acid secretion predicted those patients who developed equivocal or false-negative UBTs. The effect on the accuracy of the UBT resolved within 5 days of drug cessation.

PMID 9068466
V Savarino, D Tracci, P Dulbecco, M R Mele, P Zentilin, C Mansi, S Vigneri
Negative effect of ranitidine on the results of urea breath test for the diagnosis of Helicobacter pylori.
Am J Gastroenterol. 2001 Feb;96(2):348-52. doi: 10.1111/j.1572-0241.2001.03517.x.
Abstract/Text OBJECTIVES: In analogy with proton pump inhibitors, H2-antagonists may also be responsible for false-negative results on urea breath test for the detection of Helicobacter pylori. In this study we assessed the frequency and duration of false-negative urea breath tests in patients given different doses of ranitidine.
METHODS: A total of 120 consecutive dyspeptic patients infected with H. pylori on the basis of concomitant positive results of CLO-test, histology and urea breath test were recruited for this prospective, open, parallel-group study performed in an urban university gastroenterological clinic. They were randomized to receive an acute treatment with either ranitidine 300 mg once a day in the evening, ranitidine 300 mg once a day in the morning, ranitidine 150 mg b.i.d., or ranitidine 300 mg b.i.d. for 14 days. The urea breath test was performed on day 14 while patients were still taking ranitidine, and on day 21, 1 wk after completion of therapy. The test was repeated on day 28 in those patients who were still negative on day 21. Duplicate breath samples were collected after ingestion of 75 mg 13C-urea plus citric acid. A delta value >5/1000 was considered positive.
RESULTS: Of 118 patients infected with H. pylori, 15 (13%) had a negative urea breath test on day 14. The false-negative results were equally distributed among the four groups of ranitidine dosage. Nine of these patients reverted to positive at 7 days and the remaining six at 14 days after completion of therapy.
CONCLUSIONS: Our study shows that ranitidine negatively affects the results of urea breath testing, independent of the given dosage. Patients undergoing this examination for H. pylori diagnosis should discontinue use of H2-antagonists 2 wk before testing.

PMID 11232674
A F Cutler, M Elnaggar, E Brooks, K O'Mara
Effect of standard and high dose ranitidine on [13C]urea breath test results.
Am J Gastroenterol. 1998 Aug;93(8):1297-9. doi: 10.1111/j.1572-0241.1998.00412.x.
Abstract/Text OBJECTIVE: It has been suggested that standard dose H2 blockers will affect the [14-C]urea breath test. The aim of this study was to evaluate the effect of standard and high dose ranitidine on the [13C]urea breath test in a prospective cross-over study.
METHODS: Volunteers found to be positive for H. pylori by IgG serology and [13C]urea breath test were given either ranitidine 150 mg b.i.d. or 300 mg b.i.d. for 14 days. Repeat breath tests were completed on the last day of antisecretory dosing and study patients were immediately crossed over to the other ranitidine dose. The third breath test was performed at 14 days after initiation of the new dose.
RESULTS: A total of 20 volunteers were enrolled. Using the established cut-off of 2.4% for the commercial breath test, only one patient developed negative results on H2 blockers. This patient had negative breath tests on both ranitidine doses and remained test-negative off all medications 6 wk after study completion, suggesting either a false positive baseline test or an unexpected bacterial eradication. No specific trend in breath test results was observed for the group (p=NS). On ranitidine 300 mg, six of 19 patients elevated their breath results from 23% to 112% (mean 76%) above baseline.
CONCLUSION: Ranitidine at standard or high doses did not generate a reproducible decline in breath test results. Histamine 2 blockers do not need to be discontinued before urea breath testing.

PMID 9707054
Paul Moayyedi, Jon Deeks, Nicholas J Talley, Brendan Delaney, David Forman
An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews.
Am J Gastroenterol. 2003 Dec;98(12):2621-6. doi: 10.1111/j.1572-0241.2003.08724.x.
Abstract/Text OBJECTIVES: A Cochrane systematic review on the efficacy of Helicobacter pylori (H. pylori) eradication therapy in nonulcer dyspepsia concluded that this intervention had a small but statistically significant effect in curing symptoms. A systematic review in the Annals of Internal Medicine suggested that there was no statistically significant effect of H. pylori eradication therapy on nonulcer dyspepsia symptoms. We updated the Cochrane review and explored reasons for these discrepant results.
METHODS: In our update of the Cochrane review we included randomized controlled trials evaluating H. pylori eradication in nonulcer dyspepsia published up to September, 2002. A statistician and the lead author of two negative randomized controlled trials explored reasons for the differences between the Cochrane and Annals systematic reviews according to the review methodology, data analyzed, and statistical methods. Sensitivity analyses were undertaken to evaluate which differences had an impact on the review conclusions.
RESULTS: The updated review identified 12 trials evaluating H. pylori eradication versus placebo antibiotics in 2903 patients. H. pylori eradication reduced nonulcer dyspepsia (nonulcer dyspepsia relative risk = 0.91; 95% CI = 0.86-0.95). We identified five differences in methodology between the Cochrane and Annals reviews. The Annals review included all dual, triple, and quadruple H. pylori eradication therapies searched until December, 1999; did not contact authors for further information; included abstracts; and assumed that dropouts were treatment failures. The Cochrane review included only those therapies proved to be successful in eradicating H. pylori; searched until May, 2000; contacted authors for further information; included abstracts only if further information was available; and excluded dropouts from the analysis. Not including trials published in 2000 reduced the number of trials in the review and the number of patients evaluated, changing the conclusions from evidence of benefit to benefit not being proved. The method of statistical analysis did not alter conclusions when all studies were included.
CONCLUSIONS: The results of systematic reviews in a rapidly developing field depend on inclusion of all relevant studies. There is evidence for a small benefit of eradicating H. pylori in nonulcer dyspepsia, and this is confirmed by updating the Cochrane systematic review.

PMID 14687807
P Moayyedi, S Soo, J Deeks, D Forman, J Mason, M Innes, B Delaney
Systematic review and economic evaluation of Helicobacter pylori eradication treatment for non-ulcer dyspepsia. Dyspepsia Review Group.
BMJ. 2000 Sep 16;321(7262):659-64.
Abstract/Text OBJECTIVES: To evaluate efficacy and cost effectiveness of Helicobacter pylori eradication treatment in patients with non-ulcer dyspepsia infected with H pylori.
DESIGN: Systematic review of randomised controlled trials comparing H pylori eradication with placebo or another drug treatment. Results were incorporated into a Markov model comparing health service costs and benefits of H pylori eradication with antacid treatment over one year.
DATA SOURCES: Six electronic databases were searched for randomised controlled trials from January 1966 to May 2000. Experts in the field, pharmaceutical companies, and journals were contacted for information on any unpublished trials. Trial reports were reviewed according to predefined eligibility and quality criteria.
MAIN OUTCOME MEASURES: Relative risk reduction for remaining dyspeptic symptoms (the same or worse) at 3-12 months. Cost per dyspepsia-free month estimated from Markov model based on estimated relative risk reduction.
RESULTS: Twelve trials were included in the systematic review, nine of which evaluated dyspepsia at 3-12 months in 2541 patients. H pylori eradication treatment was significantly superior to placebo in treating non-ulcer dyspepsia (relative risk reduction 9% (95% confidence interval 4% to 14%)), one case of dyspepsia being cured for every 15 people treated. H pylori eradication cost pound56 per dyspepsia-free month during first year after treatment.
CONCLUSION: H pylori eradication may be cost effective treatment for non-ulcer dyspepsia in infected patients but further evidence is needed on decision makers' willingness to pay for relief of dyspepsia.

PMID 10987767
L Laine, P Schoenfeld, M B Fennerty
Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta-analysis of randomized, controlled trials.
Ann Intern Med. 2001 Mar 6;134(5):361-9.
Abstract/Text PURPOSE: To assess the effect of eradication therapy for Helicobacter pylori on symptoms of nonulcer dyspepsia.
DATA SOURCES: Duplicate searches of bibliographic databases, reviews of proceedings of annual gastroenterology and H. pylori meetings from 1995 to 1999, reviews of reference lists, and contact with primary investigators and pharmaceutical manufacturers.
STUDY SELECTION: Included studies 1) examined patients with nonulcer dyspepsia and H. pylori infection; 2) used combination therapy for H. pylori and a control therapy without efficacy against H. pylori; 3) were randomized, controlled trials; 4) lasted for at least 1 month after the end of therapy; and 5) assessed symptoms of nonulcer dyspepsia. Ten studies were included.
DATA EXTRACTION: Independent, duplicate data extraction of the methodologic quality, population, intervention, study design, duration, and outcome of the trials.
DATA SYNTHESIS: The odds ratio (OR) for treatment success in nonulcer dyspepsia with H. pylori eradication therapy compared with control therapy was 1.29 (95% CI, 0.89 to 1.89; P = 0.18). However, significant heterogeneity (P = 0.04) calls the validity of aggregating the data into question. Heterogeneity resolved with the exclusion of one study (OR, 1.07 [CI, 0.83 to 1.37]; P > 0.2). For predefined analysis of trials that used a specifically stated definition of dyspepsia (that is, upper abdominal pain or discomfort), the OR was 1.04 (CI, 0.80 to 1.35) without heterogeneity. For treatment that resulted in cure rather than persistent infection, the OR was 1.17 (CI, 0.87 to 1.59) without heterogeneity.
CONCLUSION: This meta-analysis provides little support for the use of H. pylori eradication therapy in patients with nonulcer dyspepsia.

PMID 11242496

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