Dyspepsia Research: 2002-2006
     
Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001960.
Pharmacological interventions for non-ulcer dyspepsia.
Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D.
McMaster University, Department of Medicine, Gastroenterology Division, HSC-3N51d, 1200 Main Street West, Hamilton, Ontario, Canada. moayyep@mcmaster.ca

BACKGROUND: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that pound450 million is spent on dyspepsia drugs in the UK each year. OBJECTIVES: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H(2) antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to January 2006), EMBASE (1988 to January 2006), CINAHL (1982 to January 2006), SIGLE, and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, trial quality and extracted data. MAIN RESULTS: We included 73 trials: prokinetics (19 trials with dichotomous outcomes evaluating 3178 participants; relative risk reduction (RRR) 33%; 95% confidence intervals (CI) 18% to 45%), H(2)RAs (12 trials evaluating 2,183 participants; RRR 23%; 95% CI 8% to 35%) and PPIs (10 trials evaluating 3,347 participants; RRR 13%; 95% CI 4% to 20%) were significantly more effective than placebo. Bismuth salts (six trials evaluating 311 participants; RRR 40%; 95% CI -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial evaluating 109 participants; RRR -2%; 95% CI -36% to 24%) and sucralfate (two trials evaluating 246 participants; RRR 29%; 95% CI -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic results could be due to publication bias or other small study effects. AUTHORS' CONCLUSIONS: There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.

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Phytomedicine. 2006 Sep 13; [Epub ahead of print]
Phytotherapy for functional dyspepsia: A review of the clinical evidence for the herbal preparation STW 5.
Rosch W, Liebregts T, Gundermann KJ, Vinson B, Holtmann G.
Medical Department, North West Hospital, Frankfurt, Germany.

Functional gastrointestinal disorders such as functional (or non-ulcer) dyspepsia are characterized by a broad spectrum of symptoms referred to the upper abdomen without a detectable cause utilizing routine diagnostic measures. It is now believed that disordered gut function (including abnormalities like disturbances of motility such as postprandial fundic relaxation, gastric emptying and disturbed visceral sensory function) play a key role for the manifestation of these disorders. The underlying pathophysiology is not yet fully understood. However, the available data suggest that a number of factors may contribute to the manifestation of symptoms. These factors include environmental factors such as acute infections as trigger event, psychological stressors that may precede acute exacerbations and a genetic predisposition. Considering the large number of mechanisms, a treatment targeting a single mechanism is unlikely to be effective in all patients. Indeed, chemically defined treatments usually gain a 10-15% superiority over placebo. In recent years placebo-controlled studies have demonstrated superiority of a commercial multicomponent herbal preparation, STW 5, with the trade name Iberogast((R)) for the treatment of patients with functional dyspepsia and irritable bowel syndrome. This phytopharmacon is a combination of nine plant extracts each with a number of different active constituents. Pharmacological studies have shown different effects of the single plant extracts on the (molecular) mechanisms which are discussed as underlying the manifestation of symptoms. Various well-controlled clinical trials have independently confirmed clinical efficacy and safety. The clinically efficacy of this multicomponent herbal preparation questions the current trend of highly targeted drug molecules that usually target one single receptor population while it has not been shown that a single receptor group plays a pivotal role for the control of symptoms. Herbal medicines are obtained from various plants and contain complex extracts with a large number of different active substances. While there are only limited head-to-head comparisons with conventional chemically defined medications, the combination of extracts with various gastrointestinal active ingredients appears to be advantageous for a heterogenous condition such as functional dyspepsia.

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Minerva Gastroenterol Dietol. 2006 Sep;52(3):249-59.
NSAIDs-induced gastrointestinal damage. Review.
Arroyo M, Lanas A.
Service of Gastroenterology, University Hospital of Zaragoza, Zaragoza, Spain.

Non-steroidal anti-inflammatory drugs (NSAIDs), along with analgesics, are the most widely prescribed medication in the world. However, NSAIDs cause numerous side effects, being the gastrointestinal (GI) events the most common ones with an increase of risk of serious GI complications between 2.5- and 5-fold, as compared with individuals not taking NSAIDs. Factors that increase the risk for serious events in NSAID-using patients include a history of ulcer or ulcer complications, advanced age (=/>65 years), the use of high-dose NSAIDs, more than one NSAID, anticoagulants or corticosteroid therapy. If NSAID therapy is required, we must balance GI and cardiovascular risk and the therapy should be prescribed at the lowest possible dose and for the shortest period of time. The use of NSAID without gastroprotective co-therapy is considered appropriate in patients <65 years, not taking aspirin and having no GI history. In patients with GI risk factors, but no cardiovascular risk, coxibs or NSAIDs plus proton pump inhibitor (PPI) or misoprostol are valid options. Patients with a history of ulcer bleeding should receive coxib plus PPI therapy and should be tested and treated for Helicobacter pylori infection. Coxib therapy has better GI tolerance than traditional NSAIDs and PPI therapy is effective both in treatment and prevention of NSAID-induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.

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Am J Gastroenterol. 2006 Sep;101(9):2096-106. Epub 2006 Jun 30.
Erratum in: Am J Gastroenterol. 2006 Sep;101(9):2171.
Esomeprazole 40 mg once a day in patients with functional dyspepsia: the randomized, placebo-controlled "ENTER" trial.
van Zanten SV, Armstrong D, Chiba N, Flook N, White RJ, Chakraborty B, Gasco A.
Division of Gastroenterology, Dalhousie University, Halifax, Canada.

OBJECTIVE: The etiologies of functional dyspepsia (FD) are unclear, but in some studies, treatment with a proton pump inhibitor has been beneficial. The objective of this study was to evaluate the efficacy of esomeprazole 40 mg once a day compared to placebo in achieving symptom relief in primary care patients with FD. METHODS: This was a randomized, placebo-controlled trial in adult FD patients, who had at least moderate severity of symptoms, defined as a score of > or =4 on a 7-point Global Overall Symptom (GOS) scale. Patients were excluded if they had predominant symptoms of heartburn or regurgitation; after a normal baseline endoscopy, patients were randomized to esomeprazole 40 mg once daily or placebo for 8 wk. The primary outcome measure was symptom relief (GOS < or =2) at 8 wk. RESULTS: Of the 502 enrolled patients, 224 were randomized. The main reasons for exclusion were abnormal endoscopic findings, especially esophagitis. A significantly greater proportion of patients in the esomeprazole group achieved symptom relief at 4 but not at 8 wk compared to placebo: 4 wk esomeprazole 50.5% versus placebo 32.2%, p= 0.009; 8 wk esomeprazole 55.1% versus placebo 46.1%, p= 0.16. A similar relationship at 4 and 8 wk was seen for symptom resolution (GOS = 1) and improvement (DeltaGOS > or =2). CONCLUSION: For the primary outcome measure of symptom relief at 8 wk, there was no statistically significant difference between esomeprazole 40 mg once a day and placebo. However, at 4 wk, esomeprazole was significantly more effective than placebo for symptom relief. The difference in therapeutic gain between 4 and 8 wk was largely due to a higher placebo response rate at 8 wk.

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Aliment Pharmacol Ther. 2006 Aug 1;24(3):475-92.
Review article: current and emerging therapies for functional dyspepsia.
Saad RJ, Chey WD.
University of Michigan Medical Center, Ann Arbor, MI 48109, USA.

Functional dyspepsia represents a heterogeneous group of gastrointestinal disorders marked by the presence of upper abdominal pain or discomfort. Although its precise definition has evolved over the last several decades, this disorder remains shrouded in controversy. The symptoms of functional dyspepsia may overlap with those of other functional bowel disorders including irritable bowel syndrome and non-erosive reflux disease. There may be coexistent psychological distress or disease complicating its presentation and response to therapy. Given the prevalence and chronicity of functional dyspepsia, it remains a great burden to society. Suspected physiological mechanisms underlying functional dyspepsia include altered motility, altered visceral sensation, inflammation, nervous system dysregulation and psychological distress. Yet the exact pathophysiological mechanisms that cause symptoms in an individual patient remain difficult to delineate. Numerous treatment modalities have been employed including dietary modifications, pharmacological agents directed at various targets within the gastrointestinal tract and central nervous system, psychological therapies and more recently, complementary and alternative treatments. Unfortunately, to date, all of these therapies have yielded only marginal results. A variety of emerging therapies are being developed for functional dyspepsia. Most of these therapies are intended to normalize pain perception and gastrointestinal motor and reflex function in this group of patients.

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Chin J Dig Dis. 2006;7(3):127-33.
NSAID-induced gastrointestinal damage: current clinical management and recommendations for prevention.
Lanas A, Ferrandez A.
Service of Gastroenterology, University Hospital of Zaragoza, Spain. alanas@unizar.es

Gastrointestinal toxicity is a common adverse effect of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and patients at risk should receive prevention therapies. Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) are safer to the gastrointestinal tract than traditional NSAIDs. Current prevention strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as coxibs and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone. However, patients with a previous bleeding ulcer should receive the combination of a coxib plus a PPI, and Helicobacter pylori should be tested for and treated if present. Coxib and NSAID therapy should be prescribed with caution in patients with increased cardiovascular risk and should be prescribed at the lowest possible dose and for the shortest period of time. These patients will probably be treated with low-dose aspirin or other antiplatelet agents, which puts them at increased risk of upper gastrointestinal complications. The risk of gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower than that with traditional NSAIDs plus aspirin, but all these patients may benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern, coxib instead of NSAID therapy should be considered. Coxib therapy has better gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective both in the treatment and prevention of NSAID-induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.

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Phytomedicine. 2006 Jul 18; [Epub ahead of print]
Functional dyspepsia - A multicausal disease and its therapy.
Allescher HD.
Center for Internal Medicine, Gastroenterology, Hepatology and Metabolism, Klinikum Garmisch-Partenkirchen, Academic Teaching Hospital of the Ludwig-Maximilians-University Munich, Auenstr. 6, 82467 Garmisch-Partenkirchen, Germany.

Functional dyspepsia is a common chronic disorder with non-specific upper abdominal symptoms which can not be explained by organic or biochemical abnormalities. The dyspeptic symptoms are very compromising and bothersome and result in a substantial reduction of quality of life. The substantial direct and indirect medical and economical costs induce a high socioeconomic interest in the pathogenesis and the treatment options of this disease. Over the past 30 years several theories about the etiology of the symptoms in functional dyspepsia patients have been put forward. These include disorders of gastrointestinal motility, acid secretion, visceral hypersensitivity, adaptation and accommodation, Hp-infection, mucosal inflammation and finally genetic predisposition. There is increasing evidence that functional dyspepsia is a multi-causal disorder, which leads to altered processing of afferent information from the gastrointestinal tract to the CNS. Autonomic hypersensitivity and altered central processing could be a common phenomenon whereas motility changes, inflammation or altered secretion could increase neural afferent inputs. Treatment of this complex disorder could and should involve these different levels of symptom generation. Thus different approaches with anti-secretory, spasmolytic, prokinetic and anti-inflammatory effects and most preferably reduction of visceral hypersensitivity seem logical. This could explain the variety of drugs which show a positive symptomatic response. Whether a combination of these effects could be clinically superior remains to be shown, but would offer a logical approach for the use of substances with a multi-target action.

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Internist (Berl). 2006 Jun;47(6):568-77.
[Functional dyspepsia - diagnosis of desperation?]
[Article in German]
Liebregts T, Adam B, Holtmann G.
Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, University of Adelaide, North Terrace, SA 5000 , Adelaide, Australia, gholtman@mail.rah.sa.gov.au.

Dyspepsia comprises a broad spectrum of predominantly upper abdominal symptoms, such as pain, indigestion, nausea, early satiety and bloating. While these symptoms are highly prevalent, in less than 50% of patients presenting with dyspepsia, structural lesions or biochemical abnormalities are found that explain the symptoms when routine clinical tests are used. In patients without structural lesions the diagnosis of functional dyspepsia is justified. Exclusion of life-threatening disorders as the cause of symptoms and reassurance of the patient as well as proper explanation of the diagnosis and its underlying disease mechanisms (i.e. symptoms are due to a sensitive gut) is crucial and can be considered as an essential element of treatment. Since there is a remarkable comorbidity of anxiety and depression, psychosomatic interventions might be necessary in selected patients. Based on controlled clinical trials few drugs, such as proton pump inhibitors, prokinetics, tricyclic antidepressants, simethicone and selected herbal preparations have been found to be effective for treatment of functional dyspepsia. Effects of H. pylori eradication, even though strongly advocated, are most likely due to undiagnosed peptic ulcer disease in a very small group of patients. While there is currently no therapy that cures functional dyspepsia, the therapeutic target is to control symptoms.

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J Gastroenterol. 2006 May;41(5):408-17.
Acupuncture for functional gastrointestinal disorders.
Takahashi T.
Department of Surgery, Duke University Medical Center, Durham, NC 27705, USA.

Functional gastrointestinal (GI) symptoms are common in the general population. Especially, motor dysfunction of the GI tract and visceral hypersensitivity are important. Acupuncture has been used to treat GI symptoms in China for thousands of years. It is conceivable that acupuncture may be effective in patients with functional GI disorders because it has been shown to alter acid secretion, GI motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes muscle contractions via the somatoparasympathetic pathway, while at the upper abdomen (CV-12) it causes muscle relaxation via the somatosympathetic pathway. In some patients with gastroesophageal reflux disease (GERD) and functional dyspepsia (FD), peristalsis and gastric motility are impaired. The stimulatory effects of acupuncture at ST-36 on GI motility may be beneficial to patients with GERD or FD, as well as to those with constipation-predominant irritable bowel syndrome (IBS), who show delayed colonic transit. In contrast, the inhibitory effects of acupuncture at CV-12 on GI motility may be beneficial to patients with diarrhea-predominant IBS, because enhanced colonic motility and accelerated colonic transit are reported in such patients. Acupuncture at CV-12 may inhibit gastric acid secretion via the somatosympathetic pathway. Thus, acupuncture may be beneficial to GERD patients. The antiemetic effects of acupuncture at PC-6 (wrist) may be beneficial to patients with FD, whereas the antinociceptive effects of acupuncture at PC-6 and ST-36 may be beneficial to patients with visceral hypersensitivity. In the future, it is expected that acupuncture will be used in the treatment of patients with functional GI disorders.

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World J Gastroenterol. 2006 May 7;12(17):2694-700.
Drug treatment of functional dyspepsia.
Monkemuller K, Malfertheiner P.
Divison of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke Medical School, University of Magdeburg, Magdeburg, Leipziger Strabe 44, 39120 Magdeburg, Germany.

Symptomatic improvement of patients with functional dyspepsia after drug therapy is often incomplete and obtained in not more than 60% of patients. This is likely because functional dyspepsia is a heterogeneous disease. Although great advance has been achieved with the consensus definitions of the Rome I and II criteria, there are still some aspects about the definition of functional dyspepsia that require clarification. The Rome criteria explicitly recognise that epigastric pain or discomfort must be the predominant complaint in patients labelled as suffering from functional dyspepsia. However, this strict definition can create problems in the daily primary care clinical practice, where the patient with functional dyspepsia presents with multiple symptoms. Before starting drug therapy it is recommended to provide the patient with an explanation of the disease process and reassurance. A thorough physical examination and judicious use of laboratory data and endoscopy are also indicated. In general, the approach to treat patients with functional dyspepsia based on their main symptom is practical and effective. Generally, patients should be treated with acid suppressive therapy using proton-pump inhibitors if the predominant symptoms are epigastric pain or gastroesophageal reflux symptoms. Although the role of Helicobacter pylori (H pylori) in functional dyspepsia continues to be a matter of debate, recent data indicate that there is modest but clear benefit of eradication of H pylori in patients with functional dyspepsia. In addition, H pylori is a gastric carcinogen and if found it should be eliminated. Although there are no specific diets for patients with FD, it may be helpful to guide the patients on healthy exercise and eating habits.

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World J Gastroenterol. 2006 May 7;12(17):2701-7.
Functional dyspepsia: are psychosocial factors of relevance?
Barry S, Dinan TG.
Department of Psychiatry, Alimentary Pharmacobiotic Centre, University College Cork, Cork, Ireland.

The pathogenesis of Functional Dyspepsia (FD) remains unclear, appears diverse and is thus inadequately understood. Akin to other functional gastrointestinal disorders, research has demonstrated an association between this common diagnosis and psychosocial factors and psychiatric morbidity. Conceptualising the relevance of these factors within the syndrome of FD requires application of the biopsychosocial model of disease. Using this paradigm, dysregulation of the reciprocal communication between the brain and the gut is central to symptom generation, interpretation and exacerbation. Appreciation and understanding of the neurobiological correlates of various psychological states is also relevant. The view that psychosocial factors exert their influence in FD predominantly through motivation of health care seeking also persists. This appears too one-dimensional an assertion in light of the evidence available supporting a more intrinsic aetiological link. Evolving understanding of pathogenic mechanisms and the heterogeneous nature of the syndrome will facilitate effective management. Co-morbid psychiatric illness warrants treatment with conventional therapies. Acknowledging the relevance of psychosocial variables in FD, the degree of which is subject to variation, has implications for assessment and management. Available evidence suggests psychological therapies may benefit FD patients particularly those with chronic symptoms. The rationale for use of psychotropic medications in FD is apparent but the evidence base to support the use of antidepressant pharmacotherapy is to date limited.

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World J Gastroenterol. 2006 May 7;12(17):2656-9.
Reassessment of functional dyspepsia: a topic review.
Chua AS.
Ipoh Gastro Centre, 31 Lebuhraya Taman Ipoh, Ipoh Garden South, 31400, Ipoh, Perak, Malaysia. andrewchua@myjaring.net

Dyspepsia itself is not a diagnosis but stands for a constellation of symptoms referable to the upper gastrointestinal tract. It consists of a variable combination of symptoms including abdominal pain or discomfort, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation. Patients with heartburn and acid regurgitation invariably have gastroesophageal reflux disease and should be distinguished from those with dyspepsia. There is a substantial group of patients who do not have a definite structural or biochemical cause for their symptoms and are considered to be suffering from functional dyspepsia (FD). Gastrointestinal motor abnormalities, altered visceral sensation, dysfunctional central nervous system-enteral nervous system (CNS-ENS) integration and psychosocial factors have all being identified as important pathophysiological correlates. It can be considered as a biopsychosocial disorder with dysregulation of the brain-gut axis being central in origin of disease. FD can be categorized into different subgroups based on the predominant single symptom identified by the patient. This subgroup classification can assist us in deciding the appropriate symptomatic treatment for the patient.

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J Gastroenterol Hepatol. 2006 Apr;21(4):767-71.
Efficacy of camostat mesilate compared with famotidine for treatment of functional dyspepsia: is camostat mesilate effective?
Ashizawa N, Hashimoto T, Miyake T, Shizuku T, Imaoka T, Kinoshita Y.
Department of Gastroenterology, Tamatsukuri Kousei-nenkin Hospital, Yatsuka, Japan. ashizawa.n@smn.enjoy.ne.jp

BACKGROUND: Differentiation between functional dyspepsia and early chronic pancreatitis is difficult because these diseases do not produce specific abnormalities in laboratory testing. The aim of this study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against functional dyspepsia and to characterize patients with favorable responses. METHODS: Dyspeptic patients who exhibited no abnormalities on laboratory blood and urine testing, abdominal ultrasonography and upper gastrointestinal endoscopy were randomized to receive camostat mesilate 200 mg three times daily or famotidine 20 mg twice daily for 4 weeks. Symptoms severity was recorded before and at 2 and 4 weeks after starting treatment using a visual analog scale. RESULTS: Epigastralgia was significantly improved after 2 and 4 weeks of treatment in both groups (P < 0.01); this improvement tended to be more marked in the camostat mesilate group (P < 0.05 at 2 weeks). The beneficial effect of camostat mesilate on epigastralgia was more prominent in chronic alcohol drinkers at 2 weeks (P < 0.05) and 4 weeks (P < 0.01). CONCLUSIONS: Camostat mesilate is superior to famotidine for relieving epigastralgia in patients with functional dyspepsia. Its pain-relieving effect is greater in patients who habitually drink alcohol.

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Curr Treat Options Gastroenterol. 2006 Apr;9(2):147-56.
Prevention and Treatment of NSAID-Induced Gastroduodenal Injury.
Lanas A.
Service of Gastroenterology, University Hospital, Zaragoza, Spain, 50009 alanas@unizar.es.

NSAIDs increase the risk of gastrointestinal (GI) complications. Those at risk should be considered for alternatives to NSAID therapy, modifications of risk factors, and prevention strategies with co-therapy with gastroprotective agents (proton-pump inhibitors or misoprostol) or COX-2 selective inhibitors (coxibs). Since coxibs, and probably other nonselective NSAIDs, may increase the risk of cardiovascular events, prevention strategies must take into account both GI and cardiovascular risk factors. All NSAIDs and coxibs should be prescribed at the lowest possible dose and for the shortest period of time. In patients with GI risk factors but no cardiovascular risk, coxibs or NSAIDs plus PPI or misoprostol are valid options. Patients with a history of ulcer bleeding should receive coxib plus PPI therapy and should be tested and treated for Helicobacter pylori infection. Most patients with increased cardiovascular risk will be treated with antiplatelet agents. It is not known whether co-therapy with low-dose aspirin will reduce the incidence of cardiovascular events, but it will further increase GI risk. It is currently unclear whether the risk of developing upper GI events with coxib plus aspirin is lower than it is with NSAIDs plus aspirin. However, all these patients should benefit from PPI co-therapy. Helicobacter pylori eradication should be considered as an additional therapeutic option when we want to further reduce the GI risk in specific patients. When the lower GI tract is of concern, coxib rather than NSAID therapy should be considered as the first option. Coxib therapy has better GI tolerance than NSAIDs, but patients with peptic ulcers or dyspepsia during NSAID/coxib treatment need PPI co-therapy.

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Am J Med. 2006 Mar;119(3):217-24.
Smoking increases the treatment failure for Helicobacter pylori eradication.
Suzuki T, Matsuo K, Ito H, Sawaki A, Hirose K, Wakai K, Sato S, Nakamura T, Yamao K, Ueda R, Tajima K.
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.

PURPOSE: Treatment failure for Helicobacter pylori (H. pylori) eradication is encountered in approximately 10-20% of patients, and many studies have pointed to a link with smoking. To investigate the effects of smoking on eradication outcome, we performed a meta-analysis. METHODS: A PubMed search was performed to retrieve articles published up to August 2005. Pooled odds ratio (OR) and differences rate for H. pylori eradication failure in smokers compared with nonsmokers were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: Twenty-two published studies (5538 patients), which provided information on eradication failure according to smoking status, were included in the analysis. The summary OR for eradication failure among smokers relative to nonsmokers was 1.95 (95% confidence interval [CI]: 1.55-2.45; P <.01). It corresponds with the differences in eradication rates between smokers and nonsmokers (8.4% [95% CI: 3.3-13.5%, P <.01]). Meta-regression analysis demonstrated that a high proportion of nonulcer dyspepsia patients in studies revealed a higher failure rate among smokers, compared with a low proportion of nonulcer dyspepsia. CONCLUSIONS: Our meta-analysis demonstrated that smoking increases the treatment failure rate for H. pylori eradication.

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Can J Gastroenterol. 2006 Feb;20(2):113-7.
Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen.
Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A.
Digestive Endoscopy, Umberto I Hospital, Altamura, Bari.

BACKGROUND: Helicobacter pylori eradication rates achieved by standard seven-day triple therapies are decreasing in several countries, while a novel 10-day sequential regimen has achieved a very high success rate. A longer 10-day triple therapy, similar to the sequential regimen, was tested to see whether it could achieve a better infection cure rate. METHODS: Patients with nonulcer dyspepsia and H pylori infection were randomly assigned to one of the following three therapies: esomeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g for seven days or 10 days, or a 10-day sequential regimen including esomeprazole 20 mg plus amoxycillin 1 g for five days and esomeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg for the remaining five days. All drugs were given twice daily. H pylori eradication was checked four to six weeks after treatment by using a 13C-urea breath test. RESULTS: Overall, 213 patients were enrolled. H pylori eradication was achieved in 75.7% and 77.9%, in 81.7% and 84.1%, and in 94.4% and 97.1% of patients following seven-day or 10-day triple therapy and the 10-day sequential regimen, at intention-to-treat and per protocol analyses, respectively. The eradication rate following the sequential regimen was higher than either seven-day (P=0.002) or 10-day triple therapy (P=0.02), while no significant difference emerged between the latter two regimens (P=0.6). CONCLUSIONS: The 10-day sequential regimen was significantly more effective than both triple regimens, while 10-day triple therapy failed to significantly increase the H pylori eradication rate achieved by the standard seven-day regimen.

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N Engl J Med. 2006 Feb 23;354(8):832-40.
A placebo-controlled trial of itopride in functional dyspepsia.
Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C.
Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital and University of Adelaide, Adelaide, SA, Australia. gholtman@mail.rah.sa.gov.au

BACKGROUND: The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with acetylcholinesterase effects, in patients with functional dyspepsia. METHODS: Patients with functional dyspepsia were randomly assigned to receive either itopride (50, 100, or 200 mg three times daily) or placebo. After eight weeks of treatment, three primary efficacy end points were analyzed: the change from baseline in the severity of symptoms of functional dyspepsia (as assessed by the Leeds Dyspepsia Questionnaire), patients' global assessment of efficacy (the proportion of patients without symptoms or with marked improvement), and the severity of pain or fullness as rated on a five-grade scale. RESULTS: We randomly assigned 554 patients; 523 had outcome data and could be included in the analyses. After eight weeks, 41 percent of the patients receiving placebo were symptom-free or had marked improvement, as compared with 57 percent, 59 percent, and 64 percent receiving itopride at a dose of 50, 100, or 200 mg three times daily, respectively (P<0.05 for all comparisons between placebo and itopride). Although the symptom score improved significantly in all four groups, an overall analysis revealed that itopride was significantly superior to placebo, with the greatest symptom-score improvement in the 100- and 200-mg groups (-6.24 and -6.27, vs. -4.50 in the placebo group; P=0.05). Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo (73 percent vs. 63 percent, P=0.04). CONCLUSIONS: Itopride significantly improves symptoms in patients with functional dyspepsia. (ClinicalTrials.gov number, NCT00272103.). Copyright 2006 Massachusetts Medical Society.

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S Afr Med J. 2006 Jan;96(1):57-61.
Evaluation of the buffering capacity of powdered cow's, goat's and soy milk and non-prescription antacids in the treatment of non-ulcer dyspepsia.
Lutchman D, Pillay S, Naidoo R, Shangase N, Nayak R, Rughoobeer A.
School of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, South Africa. lutchmand@ukzn.ac.za

BACKGROUND: Non-ulcer dyspepsia (NUD) is the term most commonly used to describe a heterogeneous and often ill-defined group of dyspepsia patients whose symptoms of upper abdominal pain, discomfort or nausea persist in the absence of identifiable cause. Treatment choice commonly includes over the counter medicines and home remedies, e.g. milk. OBJECTIVE: To determine the relative buffering capacity of goat's, cow's and soy milk, non-prescription antacid drugs and combinations thereof. METHODS: The buffering capacities of 25 ml aliquots of each of the powdered milk products, the antacids alone and the combination of antacid and milk were determined. Statistical analysis was used to determine any significant differences in buffering capacity. RESULTS: When the antacids were examined alone, significant differences in buffering capacity were observed. When powdered milk products were examined alone, cow's milk had a significantly higher buffering capacity than either goat's or soy milk. There was no significant difference between goat's and soy milk. In the combination of cow's milk with each of the antacids, brand A and B had a similar buffering capacity, significantly higher than that observed with brand C. CONCLUSIONS: The combination with best observed buffering capacity was brand A with cow's milk, and the weakest buffering capacity was observed with brand C with soy milk. The results obtained can be attributed to the chemical constituents of the antacids and the milk products.

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Dig Dis Sci. 2006 Jan;51(1):89-98.
Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in a population with a high prevalence of infection: results of a 12-month randomized, double blind, placebo-controlled study.
Mazzoleni LE, Sander GB, Ott EA, Barros SG, Francesconi CF, Polanczyk CA, Wortmann AC, Theil AL, Fritscher LG, Rivero LF, Cartell A, Edelweiss MI, Uchoa DM, Prolla JC.
Departments of Gastroenterology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. lemazzoleni@yahoo.com.br

Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were randomized to receive either lansoprazole, amoxicillin, and clarithromycin or lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed at baseline and at 3 and 12 months. There was an overall trend, although not statistically significant, for a benefit of H. pylori eradication. Of the patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement, versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis, it was found that of the patients without endoscopic gastric erosions, 15 of 34 (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic improvement (P = 0.015). Helicobacter pylori eradication did not prove to be clinically beneficial, although a tendency to symptomatic benefit was detected. Further studies are necessary to confirm the implications of endoscopic gastric erosions in these patients.

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BMJ. 2006 Jan 28;332(7535):199-204. Epub 2006 Jan 20. Comment in: BMJ. 2006 Jan 28;332(7535):187-8.
Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial.
Lane JA, Murray LJ, Noble S, Egger M, Harvey IM, Donovan JL, Nair P, Harvey RF.
Department of Social Medicine, University of Bristol, Bristol BS8 2PR. Athene.lane@bristol.ac.uk

OBJECTIVE: To determine the impact of a community based Helicobacter pylori screening and eradication programme on the incidence of dyspepsia, resource use, and quality of life, including a cost consequences analysis. DESIGN: H pylori screening programme followed by randomised placebo controlled trial of eradication. SETTING: Seven general practices in southwest England. PARTICIPANTS: 10,537 unselected people aged 20-59 years were screened for H pylori infection (13C urea breath test); 1558 of the 1636 participants who tested positive were randomised to H pylori eradication treatment or placebo, and 1539 (99%) were followed up for two years. INTERVENTION: Ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily for two weeks or placebo. MAIN OUTCOME MEASURES: Primary care consultation rates for dyspepsia (defined as epigastric pain) two years after randomisation, with secondary outcomes of dyspepsia symptoms, resource use, NHS costs, and quality of life. RESULTS: In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS costs were 84.70 pounds sterling (74.90 pounds sterling to 93.91 pounds sterling) greater per participant in the eradication group over two years, of which 83.40 pounds sterling (146 dollars; 121 euro) was the cost of eradication treatment. No difference in quality of life existed between the two groups. CONCLUSIONS: Community screening and eradication of H pylori is feasible in the general population and led to significant reductions in the number of people who consulted for dyspepsia and had symptoms two years after treatment. These benefits have to be balanced against the costs of eradication treatment, so a targeted eradication strategy in dyspeptic patients may be preferable.

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Phytomedicine. 2006 Jan;13(1-2):11-5. Epub 2005 Aug 15.
Efficacy and tolerability of potato juice in dyspeptic patients: a pilot study.
Chrubasik S, Chrubasik C, Torda T, Madisch A.
Department of Forensic Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, Germany. sigrun.chrubasik@klinikum.uni-freiburg.de

In Europe, use of potatoes (Solani tuberosi tuberecens) is a traditional remedy for stomach complaints. We performed a pilot study on the effectiveness and tolerability of freshly squeezed potato juice in patients suffering from dyspeptic symptoms. After informed written consent, 44 patients with various dyspeptic symptoms were enrolled, to drink for 1 week twice daily 100ml or more of potato juice (Biotta, if complaints persisted, a further 100ml was recommended. Validated outcome measures included the gastrointestinal symptom (GIS) profile, a disease-specific health assessment questionnaire (QOLRAD) and self-rated treatment success (efficacy, a 5-point Likert Scale). The study was completed by 42 patients. The GIS and QOLRAD scores improved significantly by 41.9+/-40.8% (p=0.001) and 50.7+/-36.1% (p<0.001), respectively (ITT); the absolute values changed from 11.5+/-5.1 to 6.3+/-5.3 (GIS) and 62.0+/-25.7 to 32.0+/-28.8 (QORAD). Sixteen, 18 and 26 patients, respectively, rated the effectiveness of the treatment as very good or good on the GIS, QOLRAD (improvements >60%) and on efficacy, respectively. Poor treatment success was achieved in 13 (GIS), 11 (QOLRAD) and 10 (Efficacy), not necessarily by the same patients. Since about two-thirds of the patients benefited to some extent from the treatment, potato juice in its present formulation may be useful for self-treatment. However, placebo-controlled studies with a longer treatment period are needed to confirm this.

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Dig Dis Sci. 2005 Dec;50(12):2286-95.
Natural course of functional dyspepsia after Helicobacter pylori eradication: a seven-year survey.
di Mario F, Stefani N, Bo ND, Rugge M, Pilotto A, Cavestro GM, Cavallaro LG, Franze A, Leandro G.
University of Parma, Parma, Italy. francesco.dimario@unipr.it

The role of Helicobacter pylori(Hp) in functional dyspepsia (FD) is controversial and previously published data do not help to clarify whether Hp eradication affects the natural course of FD. The aim of this study was to assess the clinical course of FD during a long follow-up period of 7 years in a homogeneous sample of Hp-eradicated patients. Among patients referred between 1991 and 1996, patients with FD and infected with Hp were enrolled. Patients were administered a structured symptom questionnaire and evaluated after Hp eradication at each 12-month time points. Patients were divided into three FD subgroups: predominantly ulcer-like, dismotility-like, and reflux-like symptom clusters. A composite symptom score ranging from 0 (no symptom) to 3 (severe symptoms) was assigned to each FD cluster. Of the 1685 screened patients, 405 had FD and 211 of them (52.1%) were also Hp-positive. During the follow-up, the amount of missing information varied from 10% to 17.5% within the first 6 years and was 30.8% at 7 years. The rates of improved patients ranged from 33% (reflux-like) to 34.9% (dismotility-like) to 47.3% (ulcer-like). However, only a proportion of 10%-50% of them was symptom-free after eradication and also at each 12-month evaluation, whereas the other patients became symptomatic at different times. FD symptoms slightly improve after Hp eradication over a long period of time but a large percentage of these improved patients may experience FD symptoms again, even after some years of well-being after Hp eradication.

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Am J Gastroenterol. 2005 Dec;100(12):2743-8.
Diet and functional gastrointestinal disorders: a population-based case-control study.
Saito YA, Locke GR 3rd, Weaver AL, Zinsmeister AR, Talley NJ.
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

BACKGROUND: Diet has been implicated to play a role in functional gastrointestinal disorders (FGID) in clinic-based studies. No population-based data comparing food and nutrient consumption between individuals with FGID and without gastrointestinal symptoms are available. OBJECTIVES: The purpose of this study was to compare the dietary consumption of specific food items and nutrients between individuals with FGID and without symptoms in a population-based sample. METHODS: A validated self-report Bowel Disease Questionnaire was mailed to an age- and gender-stratified random sample of participants aged 20-50 yr from Olmsted County, Minnesota. All patients who reported either FGID symptoms (irritable bowel or dyspepsia) or no gastrointestinal symptoms were invited to undergo a blinded physician interview and physical exam and to complete a validated Harvard Food Frequency Questionnaire. Wilcoxon rank sum tests and logistic regression were used for statistical analysis. RESULTS: In total, 222 of the 260 eligible (85%) subjects participated and 218 provided diet data: 99 were FGID cases and 119 were healthy controls. Cases and controls consumed similar number of servings per week of wheat-containing foods, lactose-containing foods, caffeinated drinks, and fructose-sweetened beverages. Cases were slightly more likely to consume >or=7 servings per week of norepinephrine- and epinephrine-containing foods (57%vs 45%, p= 0.10), but not serotonin- or tryptophan-containing foods. No differences were observed for amount of intake of calories, fiber, protein, iron, calcium, niacin, and vitamins C, D, E, niacin, B(1), B(2), B(6), and B(12). Cases reported consuming more fat (median, 33%vs 31%) and less carbohydrates (median, 49%vs 52%) than controls. CONCLUSIONS: No differences were seen in the consumption of frequently suspected "culprit" foods between community residents with and without FGID symptoms. While symptoms may be due to food sensitivity rather than altered diet composition, the role of fat and perhaps norepinephrine and epinephrine in foods in gut symptoms needs to be studied further.

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World J Gastroenterol. 2005 Nov 14;11(42):6577-81.
Management of functional dyspepsia: Unsolved problems and new perspectives.
Madisch A, Miehlke S, Labenz J.
Medical Department I, Technical University Hospital, Fetscherstrasse 74, D-01307 Dresden, Germany. ahmed.madisch@uniklinikum-dresden.de

The common characteristic criteria of all functional gastrointestinal (GI) disorders are the persistence and recurrence of variable gastrointestinal symptoms that cannot be explained by any structural or biochemical abnormalities. Functional dyspepsia (FD) represents one of the important GI disorders in Western countries because of its remarkably high prevalence in general population and its impact on quality of life. Due to its dependence on both subjective determinants and diverse country-specific circumstances, the definition and management strategies of FD are still variably stated. Clinical trials with several drug classes (e.g., proton pump inhibitors, H2-blockers, prokinetic drugs) have been performed frequently without validated disease-specific test instruments for the outcome measurements. Therefore, the interpretation of such trials remains difficult and controversial with respect to comparability and evaluation of drug efficacy, and definite conclusions can be drawn neither for diagnostic management nor for efficacious drug therapy so far. In view of these unsolved problems, guidelines both on the clinical management of FD and on the performance of clinical trials are needed. In recent years, increasing research work has been done in this area. Clinical trials conducted in adequately diagnosed patients that provided validated outcome measurements may result in better insights leading to more effective treatment strategies. Encouraging perspectives have been recently performed by methodologically well-designed treatment studies with herbal drug preparations. Herbal drugs, given their proven efficacy in clinical trials, offer a safe therapeutic alternative in the treatment of FD which is often favored by both patients and physicians. A fixed combination of peppermint oil and caraway oil in patients suffering from FD could be proven effective by well-designed clinical trials.

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Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001961.
Initial management strategies for dyspepsia.
Delaney B, Ford A, Forman D, Moayyedi P, Qume M, Delaney B.

BACKGROUND: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn. OBJECTIVES: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) Initial pharmacological therapy (including endoscopy for treatment failures).(b) Early endoscopy.(c) Testing for Helicobacter pylori (H. pylori )and endoscope only those positive.(d) H. pylori eradication therapy with or without prior testing. SEARCH STRATEGY: Trials were located through electronic searches and extensive contact with trialists. SELECTION CRITERIA: All randomised controlled trials of dyspeptic patients presenting in primary care. DATA COLLECTION AND ANALYSIS: Data were collected on dyspeptic symptoms, quality of life and use of resources. An individual patient data meta-analysis of health economic data was conducted MAIN RESULTS: Twenty-five papers reporting 27 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (three trials) and histamine H2-receptor antagonists (H2RAs) (three trials), early endoscopy with initial acid suppression (five trials), H. pylori test and endoscope versus usual management (three trials), H. pylori test and treat versus endoscopy (six trials), and test and treat versus acid suppression alone in H. pylori positive patients (four trials), were pooled. PPIs were significantly more effective than both H2RAs and antacids. Relative risks (RR) and 95% confidence intervals (CI) were; for PPI compared with antacid 0.72 (95% CI 0.64 to 0.80), PPI compared with H2RA 0.63 (95% CI 0.47 to 0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with H. pylori test and treat (OR 0.75, 95% CI 0.58 to 0.96), but was not cost effective (mean additional cost of endoscopy US$401 (95% CI $328 to 474). Test and treat may be more effective than acid suppression alone (RR 0.59 95% CI 0.42 to 0.83). AUTHORS' CONCLUSIONS: Proton pump inhibitor drugs (PPIs) are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease (GORD). The relative efficacy of histamine H2-receptor antagonists (H2RAs) and PPIs is uncertain. Early investigation by endoscopy or H. pylori testing may benefit some patients with dyspepsia but is not cost effective as part of an overall management strategy.

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J Pediatr Surg. 2005 Oct;40(10):1547-50.
Nonulcer dyspepsia and Helicobacter pylori eradication in children.
Farrell S, Milliken I, Murphy JL, Wootton SA, McCallion WA.
Department of Child Health, Institute of Clinical Science, Queen's University, Belfast BT12 6BJ, Northern Ireland. s.farrell@qub.ac.uk

BACKGROUND: Controversy exists over Helicobacter pylori eradication therapy in the treatment of patients with nonulcer dyspepsia. The lack of pediatric studies has made it difficult to draw conclusions about the use of eradication in dyspeptic children. The aim of this study was to examine long-term symptom severity in pediatric patients with nonulcer dyspepsia and H pylori gastritis after H pylori eradication. METHODS: Thirty-nine children (mean age, 9.0 years) with dyspepsia and H pylori gastritis were prospectively recruited. Severity of symptoms was graded before H pylori eradication. Each patient was followed up at 6, 12, and on average, 61.6 months after eradication, with reassessment of symptoms and H pylori status. RESULTS: There was a significant reduction in the severity of symptoms at 6 and 12 months, and at long-term follow-up compared with the preeradication scores (all P < . 001). At long-term follow-up, reinfection with H pylori was associated with more severe symptoms than if the patients remained free of infection (P = .045). CONCLUSIONS: This study has demonstrated a significant long-term improvement in nonulcer dyspepsia in children after eradication of H pylori. This provides further evidence for the consideration of H pylori eradication in pediatric patients presenting with nonulcer dyspepsia.

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Am J Gastroenterol. 2005 Oct;100(10):2324-37.
Guidelines for the management of dyspepsia.
Talley NJ, Vakil N; Practice Parameters Committee of the American College of Gastroenterology.
Division of Gastroenterology and Hepatology, Mayo Clinic, Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, Rochester, Minnesota 55905, USA.

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.

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Int J Clin Pract. 2005 Oct;59(10):1210-7.
Appropriate choice of proton pump inhibitor therapy in the prevention and management of NSAID-related gastrointestinal damage.
Singh G, Triadafilopoulos G.
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94062, USA. gsingh@stanford.edu

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal adverse effects, ranging from dyspepsia and peptic ulcer disease to more serious complications such as haemorrhage or perforation. NSAID-induced gastrointestinal toxicity is a significant medical problem worldwide. Misoprostol is effective in reducing NSAID-induced mucosal damage, but patient compliance is limited by poor tolerance. Histamine receptor antagonists are relatively effective against duodenal ulcers but offer no significant protection against gastric ulcers. Proton pump inhibitors (PPIs), such as pantoprazole, omeprazole and lansoprazole, have been shown to be effective in preventing the development of gastric and duodenal ulcers in high-risk patients taking NSAIDs. PPI therapy is also beneficial in healing NSAID-induced ulcers and preventing their recurrence in patients requiring ongoing NSAID therapy. PPIs have an excellent safety profile, and pantoprazole--with its low potential for drug-drug interactions--is particularly suitable for administration to elderly patients who often require concomitant treatment with other medications.

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Am J Gastroenterol. 2005 Aug;100(8):1696-701.
Seven versus ten days of rabeprazole triple therapy for Helicobacter pylori eradication: a multicenter randomized trial.
Calvet X, Ducons J, Bujanda L, Bory F, Montserrat A, Gisbert JP; Hp Study Group of the Asociacion Espanola de Gastroenterologia.
Digestive Diseases Unit, Hospital de Sabadell, Barcelona, Spain.

BACKGROUND: Ten-day triple therapy is somewhat more effective than 7-day treatment for curing Helicobacter pylori infection. Recent studies have suggested that rabeprazole-a proton pump inhibitor with fast onset of acid inhibition-could raise the efficacy of 7-day therapies to the levels obtained with 10-day treatment. OBJECTIVE: To compare the efficacy of 7- and 10-day rabeprazole-based triple therapy for H. pylori eradication. PATIENTS AND METHODS: Four hundred and fifty-eight patients were randomized to 7 or 10 days of triple therapy, including rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1 g, all twice a day. Cure rates were evaluated by urea breath test. RESULTS: Two hundred and thirty-seven patients received 7-day and 221 received 10-day therapy. Groups were comparable in terms of demographic variables. Intention to treat cure rates were 73.8% (95% CI: 67-79%) for 7-day and 79.6% (95%: CI:74-85%) for 10-day therapy (p= 0.09). Per-protocol cure rates were 81.8% (95% CI:76-86%) and 89.3% (95% CI: 84-93%), p= 0.02, respectively. Cure rates were similar in peptic ulcer patients but in subjects without ulcer they were clearly lower for 7-day therapy: 66%versus 77% by intention to treat (p= 0.08) and 73%versus 91% in the per-protocol analysis (p= 0.004). Side effects and compliance in the two groups were comparable. CONCLUSIONS: Seven- and 10-day triple therapies seem equally efficient in peptic ulcer patients. In contrast, 7-day therapy is significantly less effective in nonulcer dyspepsia patients. Ten-day therapy, therefore, seems preferable when treating nonulcer patients.

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Fundam Clin Pharmacol. 2005 Aug;19(4):421-7.
Eradication of Helicobacter pylori: recent advances in treatment.
McLoughlin RM, O'Morain CA, O'Connor HJ.
Department of Gastroenterology, Adelaide and Meath Hospital, Tallaght, Dublin 24 and Faculty of Health Sciences, Trinity College, Dublin, Ireland.

Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.

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Curr Gastroenterol Rep. 2005 Aug;7(4):289-96.
Frontiers in functional dyspepsia.
Fajardo NR, Cremonini F, Talley NJ.
Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, Plummer 6-56, 200 First Street SW, Rochester, MN 55905, USA. Talley.Nicholas@mayo.edu.

Functional dyspepsia (FD) refers to unexplained pain or discomfort in the upper abdomen and is commonly seen in gastroenterology practice. The underlying pathophysiologic mechanisms associated with FD are unclear, although traditionally, delayed gastric emptying, visceral hypersensitivity to acid or mechanical distention, and impaired gastric accommodation have been implicated as putative physiologic disturbances. It also remains uncertain whether FD and irritable bowel syndrome are different presentations of the same disorder. Recent data on pathophysiologic mechanisms of FD have focused on postprandial motor disturbances (accelerated gastric emptying, antral-fundic incoordination, and abnormal phasic contractions), alterations of neurohormonal mechanisms in response to a meal, and previous acute infection. Pharmacologic therapies for FD may be guided by these novel mechanisms, as current available therapeutic options are limited. Novel prokinetics and gastric accommodation modulators, visceral analgesics, and agents targeting the neurohormonal response to food ingestion are the next therapeutic frontiers in FD. This review summarizes traditional knowledge and more recent advances in the pathophysiology of FD and potential therapeutic opportunities.

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Curr Treat Options Gastroenterol. 2005 Aug;8(4):325-36.
Treatment of functional dyspepsia.
Halder SL, Talley NJ.
Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA. Talley.Nicholas@mayo.edu.

Functional dyspepsia (FD) is a common reason a patient presents with upper gastrointestinal symptoms for medical care. Although treatment of FD remains expensive, the agents are rarely used in a systematic manner; the majority of treatments are empirical and the results short lived once therapy is ceased. This is partly due to the lack of consistent pathophysiologic markers in FD, so therapy is symptom driven. This review appraises the best evidence on available interventions. A structured scheme for deciding on appropriate therapies is to consider the possible putative pathophysiologic mechanisms. Eradicating Helicobacter pylori, if present, is a first-line strategy. In patients who have symptoms suggesting excessive gastric acid secretion, particularly epigastric pain, antisecretory agents are recommended. Prokinetics may confer benefits on symptoms suggestive of upper gastrointestinal dysmotility, like fullness or early satiety. However, their use is limited due to availability issues. The expanding field of psychologic therapies provides a promising avenue of treatment. Complementary medicines are now widely use and their benefits have been suggested in recent controlled trials. Emerging treatments include cholecystokinin 1 blockers, opioid receptor agonists, and serotonergic agents, although their application in FD is in the preliminary stages.

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Am J Gastroenterol. 2005 Jul;100(7):1477-88.
A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study.
Veldhuyzen van Zanten SJ, Chiba N, Armstrong D, Barkun A, Thomson A, Smyth S, Escobedo S, Lee J, Sinclair P.
Division of Gastroenterology, Dalhousie University, Halifax, Nova Scotia, Canada.

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.

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Dig Liver Dis. 2005 Jul;37(7):496-500. Epub 2005 Apr 1.
Quadruple therapy with lactoferrin for Helicobacter pylori eradication: a randomised, multicentre study.
Zullo A, De Francesco V, Scaccianoce G, Hassan C, Panarese A, Piglionica D, Panella C, Morini S, Ierardi E.
Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy. zullo66@yahoo.it

BACKGROUND: Helicobacter pylori eradication rate with standard triple therapies is decreasing. Recently, lactoferrin administration has been shown to significantly increase the cure rate of 7-day rabeprazole, clarithromycin and tinidazole triple therapy. We assessed whether lactoferrin also increases the eradication rate of 7-day esomeprazole, clarithromycin and amoxycillin triple therapy as first-line treatment. METHODS: Overall, 133 consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomised to receive either a standard 7-day triple therapy with esomeprazole 20mg b.i.d., clarithromycin 500 mg b.i.d. and amoxycillin 1g b.i.d. (68 patients) or a quadruple therapy comprising of the same regimen plus lactoferrin 200mg b.i.d. (65 patients). H. pylori at entry was assessed by endoscopy, while bacterial eradication was checked by (13)C urea breath test 4-6 weeks after treatment. RESULTS: H. pylori eradication following standard triple therapy was achieved in 53/68 (77.9%; 95% CI = 68-88) and in 53/66 (80.3%; 95% CI = 71-89) patients at ITT and PP analyses, respectively. Following the quadruple regimen, the infection was cured in 50/65 (76.9%; 95% CI = 67-87) and 50/64 (78.1%; 95% CI = 68-88) patients at ITT and PP analyses, respectively. No statistically significant difference emerged between the two therapeutic regimens, both at ITT (p = 0.9) and PP analyses (p = 0.9). Side effects were complained by seven (10.3%) patients and six (9.2%) patients following the triple and quadruple regimens, respectively (p = 0.9), with only one patient in the quadruple group interrupting the treatment due to side effects. CONCLUSIONS: Quadruple therapy with lactoferrin did not significantly increase the H. pylori cure rate of standard 7-day clarithromycin-amoxycillin based triple therapy in non-ulcer dyspepsia patients.

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Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1386-92.
[Guideline "Dyspepsia"]
[Article in Dutch]
de Wit NJ, van Barneveld TA, Festen HP, Loffeld RJ, van Pinxteren B, Numans ME; NHG-CBO-werkgroep 'Maagklachten'.
Universitair Medisch Centrum Utrecht, Julius Centrum voor Gezondheidswetenschappen en Eerstelijns Geneeskunde, Postbus 85.060, Utrecht. n.j.dewit@umcutrecht.nl

For the management of patients with dyspepsia a multidisciplinary working party has made recommendations, i.e. about indications for prompt endoscopy, the management of dyspeptic complaints of recent onset, the application of diagnostic tests and treatment of recurrent dyspepsia and the indications for long term use of acid suppressants. Endoscopy is indicated in every patient with alarm symptoms, i.e. blood loss, dysphagia, weight loss or anemia in combination with dyspepsia. Age alone is not a decisive factor in this. Given the good prognosis of recent onset dyspepsia, the application of diagnostic tests is generally not required. Treatment should be restricted to antacids or H2 receptor antagonists. Only in case of persistent or recurring complaints, diagnostic tests or another treatment (Helitobacter pylori diagnostic tests, empirical treatment or endoscopy) should be considered. Testing for H. pylori is especially effective in patients at risk for peptic ulcer disease: those with recurrent complaints, and those with a history of peptic ulcer, without typical reflux symptoms or those with a history ofpeptic ulcer. Short term empirical treatment with a proton pump inhibitor is especially effective in patients with typical reflux symptoms. Endoscopy is the only way to rule out malignancy, and should be used to solve serious diagnostic uncertainty in patient or physician. The only indication for continuous proton pump inhibitor treatment is severe oesophagitis. All other patients with less severe reflux disease should preferably be treated on either on demand or intermittent basis. Long term proton pump inhibitor treatment is not indicated for patients with peptic ulcer disease or functional dyspepsia.

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Am J Chin Med. 2005;33(2):249-57.
Clinical and psychological assessment on xinwei decoction for treating functional dyspepsia accompanied with depression and anxiety.
Zhao L, Gan AP.
Graduate Department, Hubei College of Traditional Chinese Medicine, Wuhan, 430061, China. chinesemd@hotmail.com

The purpose of this study is to explore the psychological efficacy of Xinwei Decoction, a traditional Chinese herbal medicine, to treat functional dyspepsia (FD) accompanied with depression and anxiety. Seventy-three subjects, divided into three groups, had been given herbal medicine (Xinwei Decoction), prokinetic agent (Domperidone) and placebo, respectively for 8 weeks. Before and after treatment, all subjects were examined with FD symptom scale, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). As a result, the total scores of the three groups in FD symptom scale, HAMD and HAMA after treatment decreased in different levels, with the decrease in the herbal group more significant than the other two groups (p < 0.01), indicating the efficacy of the herbal medicine. The total effective rates of the herbal, Domperidone and placebo groups were 90%, 67% and 31%, respectively, which indicated significant effect differences between Xinwei Decoction and Domperidone (p < 0.05) and between Xinwei Decoction and placebo (p < 0.01), showing that the efficacy of herbal therapy was superior to that of the other two therapies. Furthermore, there was no one in the Domperidone and placebo groups being cured of depression and anxiety, while the curing rate in the herbal group was about 70%, indicating the efficacy of herbal medicine in comparison to that of Domperidone and placebo for anti-depression and anti-anxiety. The result demonstrated that Xinwei Decoction could not only alleviate FD symptoms but also relieve depression and anxiety.

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Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6.
New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline.
Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S.
Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.

Summary Background : In functional gastrointestinal (GI) disorders including functional dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent of contributions of psychosomatic factors. As a therapy for IBS patients, the effectiveness of antidepressants has been reported. Aim : In this study, we evaluated the efficacy of H(2)-receptor antagonist (famotidine) and 5-HT(4) receptor agonist (mosapride citrate). In addition, the effect of antidepressants was assessed as the second-step therapy. Methods : Patients complaining upper GI symptoms were diagnosed as FD excluding organic diseases. Randomized patients received 20 mg/day of famotidine or 15 mg/day of mosapride citrate for 4 weeks and the efficacy was compared between the two groups based on a 10-point visual analogue scale. When symptoms were not relieved (score improvement 0-2 points), patients received amitriptyline (30 mg/day) or no medication for 4 weeks randomly. Patients who had depression in psychological test (SDS) were omitted. Results : As the first-step therapy, both famotidine and mosapride showed beneficial effects regardless of FD subtypes, age and gender. The efficacy of these two drugs in relieving FD symptoms was not significantly different. In patients who failed in the first-step therapy, amitriptyline showed beneficial effects. Conclusions : These findings might be clinically important in view of the efficient relief of symptoms in FD patients.

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Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:37-41.
Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsia.
Kinoshita Y, Hashimoto T, Kawamura A, Yuki M, Amano K, Sato H, Adachi K, Sato S, Oshima N, Takashima T, Kitajima N, Abe K, Suetsugu H.
Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Japan.

Summary Background : An effective therapeutic strategy for functional dyspepsia (FD) has not been well-established. Aim : We investigated and compared the therapeutic effects of famotidine, mosapride and tandospirone for the control of dyspeptic symptoms. Methods : Fully examined FD patients of outpatient clinics at seven different medical centres were enrolled in the study. They were randomly assigned to three groups based on the type of drug administered: famotidine, mosapride and tandospirone. The effects of treatment over 4 weeks were assessed by visual analogue scales. Results : All of the drugs showed beneficial effects, although famotidine was the most effective for symptom relief, which was significantly greater than tandospirone, while the effect of mosapride was similar to that of famotidine. No subtype of FD showed a better response to a particular type of drug. Conclusions : For the treatment of FD, famotidine demonstrated the best therapeutic effect, followed by mosapride, while that of tandospirone was significantly lower.

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Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:32-6.
Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and
antianxiety therapies.
Seno H, Nakase H, Chiba T.
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Summary Background : The treatment of functional dyspepsia is controversial. Aim : The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. Patients and methods : Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. Results : Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 +/-0.14 to 1.57 +/- 0.20; in the famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride- and famotidine-treated patients (P <0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary, visual analogue scale score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and at 2 weeks, respectively, without any significant improvement. Conclusions : A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients.

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Can J Gastroenterol. 2005 May;19(5):285-303.
Evidence-based recommendations for short- and long-term management of uninvestigated dyspepsia in primary care: An update of the Canadian Dyspepsia Working Group (CanDys) clinical management tool.
VAN Zanten SJ, Bradette M, Chiba N, Armstrong D, Barkun A, Flook N, Thomson A, Bursey F.
Dalhousie University, Halifax, Canada.

The present paper is an update to and extension of the previous systematic review on the primary care management of patients with uninvestigated dyspepsia (UD). The original publication of the clinical management tool focused on the initial four- to eight-week assessment of UD. This update is based on new data from systematic reviews and clinical trials relevant to UD. There is now direct clinical evidence supporting a test-and-treat approach in patients with nondominant heartburn dyspepsia symptoms, and head-to-head comparisons show that use of a proton pump inhibitor is superior to the use of H2-receptor antagonists (H2RAs) in the initial treatment of Helicobacter pylori-negative dyspepsia patients. Cisapride is no longer available as a treatment option and evidence for other prokinetic agents is lacking. In patients with long-standing heartburn-dominant (ie, gastroesophageal reflux disease) and nonheartburn-dominant dyspepsia, a once-in-a-lifetime endoscopy is recommended. Endoscopy should also be considered in patients with new-onset dyspepsia that develops after the age of 50 years. Conventional nonsteroidal anti-inflammatory drugs, acetylsalicylic acid and cyclooxygenase-2-selective inhibitors can all cause dyspepsia. If their use cannot be discontinued, cotherapy with either a proton pump inhibitor, misoprostol or high-dose H2RAs is recommended, although the evidence is based on ulcer data and not dyspepsia data. In patients with nonheartburn-dominant dyspepsia, noninvasive testing for H pylori should be performed and treatment given if positive. When starting nonsteroidal anti-inflammatory drugs for a prolonged course, testing and treatment with H2RAs are advised if patients have a history of previous ulcers or ulcer bleeding.

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Aliment Pharmacol Ther. 2005 May 15;21(10):1231-9.
Helicobacter pylori eradication does not cause reflux oesophagitis in functional dyspeptic patients: a randomized, investigator-blinded, placebo-controlled trial.
Ott EA, Mazzoleni LE, Edelweiss MI, Sander GB, Wortmann AC, Theil AL, Somm G, Cartell A, Rivero LF, Uchoa DM, Francesconi CF, Prolla JC.
Hospital de Clinicas de Porto Alegre, Gastroenterology Service, Porto Alegre, Rio Grande do Sul, Brazil. eduott@terra.com.br

BACKGROUND: The protective role of Helicobacter pylori in gastro-oesophageal reflux disease has been widely discussed. AIM: To assess the risk of reflux oesophagitis in patients with functional dyspepsia after treatment for H. pylori infection. METHODS: A randomized, placebo-controlled, investigator-blinded trial was carried out on 157 functional dyspeptic patients. Patients were randomized to receive lansoprazole, amoxicillin and clarithromycin (antibiotic group) or lansoprazole and identical antibiotic placebos (control group). Upper gastrointestinal endoscopy was performed at baseline, 3 and 12 months after randomization. The primary aim was to detect the presence of reflux oesophagitis. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 147 patients (94%) and 133 (85%) completed 3 months and 12 months follow-up, respectively. The eradication rate of H. pylori was 90% in the antibiotic group (74 of 82) and 1% (one of 75) in the control group. At 3 months, reflux oesophagitis was diagnosed in 3.7% (three of 82) in the antibiotic group and 4% (three of 75) in the control group (P > 0.2). At 12 months, diagnosis was established in five new cases within the first group and in four within the second (P > 0.2). No difference was found in heartburn symptoms. CONCLUSIONS: H. pylori eradication does not cause reflux oesophagitis in this western population of functional dyspeptic patients.

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Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002301.
Psychological interventions for non-ulcer dyspepsia.
Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D.

BACKGROUND: Studies have also shown that non-ulcer dyspepsia (NUD) patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain. OBJECTIVES: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores in patients with NUD. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 3-1999), MEDLINE (1966-99), EMBASE (1988-99), PsycLIT (1987-1999) and CINAHL (1982-99). Bibliographies of retrieved articles were also searched and experts in the field were contacted. Searches were updated on 10 December 2002 and 21 January 2004. The searches were re-run on 24 January 2005 and no new trials were found SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified. DATA COLLECTION AND ANALYSIS: Data collected included both individual and global dyspepsia symptom scores and quality of life (QoL) scores. MAIN RESULTS: We identified only four trials each using different psychological interventions; three presented results in a manner that did not allow synthesis of the data to form a meta-analysis. All trials suggested that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials used statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size was too small. Unadjusted data was not statistically significant. The other problems of psychological intervention included low recruitment and high drop out rate, which has been shown to be greater in patients receiving group therapy. AUTHORS' CONCLUSIONS: There is insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD.

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Curr Treat Options Gastroenterol. 2005 Apr;8(2):175-183.
Idiopathic Dyspepsia.
Stanghellini V, Poluzzi E, De Ponti F, De Giorgio R, Barbara G, Corinaldesi R.
Department of Internal Medicine and Gastroenterology, University of Bologna, Policlinico S. Orsola-Malpighi Via Massarenti 9, Bologna, I-40138, Italy. v.stanghellini@unibo.it.

Idiopathic dyspepsia refers to pain and/or discomfort perceived in the epigastrium that is not secondary to organic, systemic, or metabolic diseases. Symptoms may overlap with those of gastroesophageal reflux disease and irritable bowel syndrome. Gastrointestinal motor disorders, hypersensitivity to mechanical or chemical stimuli, and psychosocial factors can act individually or in concert to induce the symptoms of dyspepsia. Accordingly, there is no single therapy, and treatment must be individualized. Eradication of Helicobacter pylori infection rarely achieves symptom improvement. Treatment of idiopathic dyspepsia should begin by reassuring the patient about the benign nature of the syndrome and educating them on the knowledge that has been achieved in recent years regarding potential causes of the syndrome. Both prokinetic and antisecretory drugs have been reported to improve dyspeptic symptoms, but results are not completely convincing. Although well-designed studies demonstrate superiority of proton pump inhibitors over placebo, it should be noted that patients with nonerosive gastroesophageal reflux disease were invariably included; when these patients are excluded, the benefit of antisecretory medications is questionable. We suggest that patients with idiopathic dyspepsia be initially treated according to the predominant symptom. Those with epigastric pain/burning should receive a trial with standard doses of proton pump inhibitors for 4 to 8 weeks, whereas prokinetic patients should be prescribed at recommended doses for similar periods of time to patients with nonpainful dyspeptic symptoms such as posprandial fullness, early satiety, nausea, or vomiting. Nonresponders may benefit from combination therapies or short trials with higher doses of drugs. Visceral analgesics and antidepressants can also be prescribed alone or in combinations with other therapeutic strategies. Recent studies demonstrate utility for psychologic therapy and hypnotherapy, although truly controlled studies are difficult in this area. Herbal medicines deserve further evaluation.

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Med Clin (Barc). 2005 Mar 26;124(11):401-5.
[Effect of the Helicobacter pylori eradication in patients with functional dyspepsia: randomised placebo-controlled trial]
[Article in Spanish]
Ruiz Garcia A, Gordillo Lopez FJ, Hermosa Hernan JC, Arranz Martinez E, Villares Rodriguez JE.
Area 10 Atencion Primaria, IMSALUD, Getafe, Madrid, Spain. aruiz.gapm10@salud.madrid.org

BACKGROUND AND OBJECTIVE: The Helicobacter pylori eradication in patients with functional dyspepsia has been the subject of controversy because trials come to contradictory conclusions. The objective of this trial was to evaluate the effect, compared with placebo, of the eradication treatment in patients with functional dyspepsia. PATIENTS AND METHOD: Randomized double blind placebo controlled trial. We included 158 patients attended by family physicians (Area 10 Primary Care, Health Institute of Madrid) with functional dyspepsia and Helicobacter pylori infection detected by the ureasa test in endoscopy. An OCA (ameprazole clarithromycin and amoxicillin group (n = 79) and a placebo group (n = 79) were randomized. During 7 days, patients at the OCA group received omeprazole (20 mg bid), clarithromycin (500 mg bid) and amoxicillin (1000 mg bid) daily, and patients at the control group received the placebo agent twice daily. Dyspepsia improvement according to a Likert scale (5 steps), and eradication of H. pylori by 13C-urea breath test were evaluated during one year. RESULTS: Both groups were homogeneous in relation to age, sex and dyspepsia degree. The average age (standard deviation) of studied patients was 41.99 (13.93) years. At one year of follow up, H. pylori was eradicated in 81.01% (64/79) of the OCA group and 5.06% (4/79) of the placebo group. The difference of dyspepsia improvement (22.78%; 95% confidence interval [CI], 7.62-37.79) between the OCA group (41.77%; 95% CI, 30.77-53.41), and the placebo group (18.99%; 95% CI 11.03-29.38) was significant (p = 0.0018). CONCLUSION: Eradication of Helicobacter pylori in patients with functional dyspepsia is more effective improving symptoms than placebo.

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Aliment Pharmacol Ther. 2005 Jan 1;21(1):91-6.
Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients.
Qasim A, Sebastian S, Thornton O, Dobson M, McLoughlin R, Buckley M, O'Connor H, O'Morain C.
Gastroenterology Department, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland.

BACKGROUND: Optimal management approach is not well defined for subjects who fail initial first- and second-line Helicobacter pylori eradication attempts and are dealt on a case-by-case basis by the specialists. AIM: To evaluate the efficacy and safety of standard and 'rescue' eradication therapies at primary and secondary care levels. METHODS: H. pylori infected dyspepsia patients referred to our C13 urea breath testing laboratory between January 1999 to February 2002 were included. Eradication failure at secondary care level was treated using strategies including antibiotic sensitivity testing and the use of rifabutin- and furazolidone-based therapies. RESULTS: 3280 patients received standard first-line eradication therapy, which was successful in 2530 (77%) patients. Second-line therapy (bismuth-based 'quadruple') or triple therapy (altering constituent antibiotics) was successful in 56% of 270 treated patients. Subsequent eradication attempts using rifabutin-based (n = 34) and furazolidone-based (n = 10) regimens were successful in 38% and 60% patients respectively. H. pylori eradication rates were significantly different for guidelines compliant (94.8%) and non-compliant (82%) groups (P = 0.0001). H. pylori eradication rates for non-ulcer dyspepsia (40%) and peptic ulcer disease (36%) were not significantly different. CONCLUSIONS: Available H. pylori eradication therapies remain very effective and compliance to guidelines achieves high success rates. Furazolidone-based 'rescue' regimen achieved high eradication rates after failure of the standard first-line, second-line and rifabutin-based therapies.

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Cochrane Database Syst Rev. 2005 Jan 25;(1):CD002096.
Eradication of Helicobacter pylori for non-ulcer dyspepsia.
Moayyedi P, Soo S, Deeks J, Delaney B, Harris A, Innes M, Oakes R, Wilson S, Roalfe A, Bennett C, Forman D.
Department of Medicine, Gastroenterology Division, McMaster University, 1200 Main Street West, Hamilton, Ontario, CANADA, L8N 3Z5.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. These searches were updated in October 2004. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Seventeen randomised controlled trials were included in the systematic review. Fourteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Thirteen of these trials gave results as dichotomous outcomes evaluating 3186 patients and there was no significant heterogeneity between the studies. There was a 8% relative risk reduction in the H pylori eradication group (95% CI = 3% to 12%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 18 (95% CI = 12 to 48). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

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Aliment Pharmacol Ther. 2004 Dec;20(11-12):1279-87.
Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast).
Melzer J, Rosch W, Reichling J, Brignoli R, Saller R.
Department of Internal Medicine, Complementary Medicine, University Hospital Zurich, Zurich, Switzerland. joerg.melzer@usz.ch

BACKGROUND: Despite a long-standing use of herbal drugs with dyspeptic symptoms, little attention has been paid to their clinical evaluation. AIM: To assess efficacy and safety of the herbal drug preparation STW 5 (containing, e.g. Iberis, peppermint, chamomile) in the treatment of functional dyspepsia. METHODS: Research in electronic databases, consultation of experts and of the producer identified STW 5 (Iberogast) as descriptor in six randomized-controlled trials. The raw data of three placebo-controlled studies which met the selection criteria, were reanalysed and pooled for meta-analysis; one reference-controlled study supported the safety analysis (STW 5: n = 199, control: n = 198). RESULTS: Pooled data showed verum (n = 138) to be more effective than placebo (n = 135) with regard to the severity of the most bothersome gastrointestinal symptom (P-value: 0.001, odds ratio: 0.22, 95% CI: 0.11-0.47). A fourth randomized-controlled trial showed no significant difference between STW 5 and cisapride. As to safety, adverse events were similar with verum and placebo; no serious adverse events occurred. DISCUSSIONS: From the point of view of efficacy and safety, the herbal medicinal product STW 5 appears to be a valid therapeutic option for patients seeking phytotherapy for their symptoms of functional dyspepsia.

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Ned Tijdschr Geneeskd. 2004 Nov 27;148(48):2390-6.
[The effect of Helicobacter pylori eradication on chronic use of acid-suppressant medication by patients in general practice; a randomised, double-blind study]
[Article in Dutch]
Hurenkamp GJ, Grundmeijer HG, van der Ende A, Tytgat GN, Assendelft WJ, van der Hulst RW.
Academisch Medisch Centrum/Universiteit van Amsterdam, Meibergdreef 9, 11 05 AZ, Amsterdam. g.j.hurenkamp@amc.uva.nl

OBJECTIVE: To study the feasibility of tapering long-term acid-suppressant drugs (ASD) use in chronic dyspeptic patients in relation to Helicobacter pylori eradication. DESIGN: Prospective randomised double-blind study. METHOD: Patients from 54 general-practitioner practices in the Amsterdam area were studied in the period 1 April 1997 - 30 September 1999 after selection on the basis of their use of acid suppressants for a period of at least 8 weeks. After gastroscopy the patients with a peptic ulcer (PUD) and H. pylori were treated with eradication therapy and patients without an ulcer but with H. pylori were randomised for eradication or placebo treatment. After a gradual reduction of acid suppressants over a 3-week period following the intervention, the patients kept a diary for 24 weeks of the quantities of acid suppressants and antacids they used. RESULTS: Of the 1083 patients approached, 434 were prepared to undergo the gastroscopy. Data for the follow-up period were available for 186 of the 227 H. pylori-positive patients. Of them 61% stopped ASD use during follow-up. The mean daily ASD dosage per patient decreased by 85% from 1.85 to 0.27 units (p < 0.05), with minimal antacids use. Of the 75 patients with peptic-ulcer disease 86% stopped ASD use. In patients with functional dyspepsia no difference in ASD use was observed after successful H. pylori eradication or placebo. Patients with mild reflux disease (GERD) used more ASD after H. pylori eradication than after placebo (p < 0.05). CONCLUSION. After H. pylori eradication many patients with PUD stopped ADS use, while GERD patients used more ASD than after placebo. A gradual withdrawal of long-term ASD use, supported by antacids and on-demand use of low-dosage ASD, facilitated reduction of ASD use during 6 months.

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Wien Med Wochenschr. 2004 Nov;154(21-22):528-34.
[Evidence-based medicine and phytotherapy for functional dyspepsia and irritable bowel syndrome: a systematic analysis of evidence for the herbal preparation Iberogast]
[Article in German]
Holtmann G, Adam B, Vinson B.
Departament of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australien. gholtman@mail.rah.sa.gov.au

Functional gastrointestinal disorders like functional dyspepsia and irritable bowel syndrome are characterized by more or less specific symptoms and the absence of structural lesions to explain symptoms. Other studies suggest that abnormalities of specific gut function are linked to manifestation of symptoms. These abnormalities include disturbances of motility such as postprandial fundic relaxation, gastric emptying and disturbed visceral sensory function. The underlying pathophysiology is not fully understood. However, various studies point towards hereditary (or molecular) factors modified by environmental factors. Considering this broad spectrum of factors it is conceivable that treatments targeting a single mechanism are most likely to improve symptoms only in patients with a disturbance linked to this mechanism. Thus overall efficacy in the whole patient population is limited. Indeed, superiority of chemically defined treatments targeting a single receptor yield a benefit over placebo of between 10 and 15%. In recent years well-controlled studies have demonstrated superiority of specific herbal preparations. This in particular held true for combinations of various plant extracts or herbal extracts with a number of different active ingredients. However, efficacy of herbal treatment for functional GI disorders cannot be taken for granted and these drugs need to be rigorously tested for efficacy and safety. In this context, same standards apply as for conventional chemically defined medications.

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Curr Opin Gastroenterol. 2004 Nov;20(6):546-50.
Functional dyspepsia.
Kleibeuker JH, Thijs JC.
Department of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands.

PURPOSE OF REVIEW: Functional dyspepsia is a common disorder, most of the time of unknown etiology and with variable pathophysiology. Therapy has been and still is largely empirical. Data from recent studies provide new clues for targeted therapy based on knowledge of etiology and pathophysiologic mechanisms. RECENT FINDINGS: The role of Helicobacter pylori gastritis in the pathogenesis of functional dyspepsia has been defined: It is causative in a small minority of patients. Associations between (groups of) symptoms and pathophysiologic mechanisms have been established, but there is much overlap and interaction, and their relevance for the individual patient is uncertain, especially because of the variability of symptoms over time. Little progress has been made in pharmacotherapy of functional dyspepsia, but exploratory studies show interesting new options. Hypnotherapy seems a promising alternative. SUMMARY: For the time being, diagnostic strategies for patients with suspected functional dyspepsia continue to be directed at excluding other disorders, in particular peptic ulcer disease and gastroesophageal reflux disease. In the presence of reflux symptoms, acid inhibitory therapy, preferably with a proton pump inhibitor, is a rational choice; otherwise, therapy is still empirical. Hypnotherapy is an option that could be seriously considered.

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Vnitr Lek. 2004 Nov;50(11):858-66.
[The role of anti-ulcerative drugs in treatment and prevention of gastropathies induced by nonsteroidal anti-inflammatory drugs]
[Article in Czech]
Fialova P, Vlcek J.
Katedra socialni a klinicke farmacie Farmaceuticke fakulty UK, Hradec Kralove.

Nonsteroidal anti-inflammatory drugs (NSAIDs) as effective agents for the relief of pain and inflammation are among the most widely prescribed drugs. Unfortunately, their benefits especially for patients with osteoarthritis and other chronic musculoskeletal conditions, are accompanied by well established toxicity. A significant percentage of NSAIDs users experience some type of gastrointestinal adverse events, ranging from manageable dyspepsia to clinically important complications (gastrointestinal bleeding, ulcer perforation, obstruction). In an attempt to reduce the incidence of NSAID-induced gastropathy, the following approaches have been proposed: avoidance of NSAIDs or minimising their dosage, selecting NSAID known to cause less damage and coprescription of various agents. Patients who require NSAIDs therapy should be assessed for factors that increase risk of gastrointestinal damage. In high risk patients, use of misoprostol, which reduces even serious gastrointestinal complications, or proton pump inhibitors, whose efficacy in preventing gastroduodenal ulcers due to NSAIDs exposure has been demonstrated in large clinical trials, is possible to use. The first step in the treatment of NSAID-associated ulcers lies in discontinuation of NSAIDs therapy. If NSAIDs cannot be withdrawn, an antisecretory therapy should be initiated. Proton pump inhibitors appear to be the most effective at healing NSAID-related ulcers among whose with continuous NSAIDs therapy. Another therapeutic option in the management of NSAID-gastropathy is to use specific cyclooxygenase-2 inhibitors. However, the clinical experience with these agents is still limited and further surveillance to resolve this issue as well as e.g. the role of Helicobacter pylori infection in NSAID-induced gastrointestinal injury are needed.

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Gut. 2004 Dec;53(12):1758-63.
Helicobacter pylori test and eradicate versus prompt endoscopy for management of dyspeptic patients: 6.7 year follow up of a randomised trial.
Lassen AT, Hallas J, Schaffalitzky de Muckadell OB.
Department of Medical Gastroenterology, Odense University Hospital, 5000 Odense C, Denmark. Annmarie.lassen@ouh.fyns-amt.dk

BACKGROUND: Dyspepsia is a chronic disease with significant impact on the use of health care resources. A management strategy based on Helicobacter pylori testing has been recommended but the long term effect is unknown. AIM: To investigate the long term effect of a test and treat strategy compared with prompt endoscopy for management of dyspeptic patients in primary care. PATIENTS: A total of 500 patients presenting in primary care with dyspepsia were randomised to management by H pylori testing plus eradication therapy (n = 250) or by endoscopy (n = 250). Results of 12 month follow up have previously been presented. METHODS: Symptoms, quality of life, and patient satisfaction were recorded during a three month period, a median 6.7 years after randomisation (range 6.1-7.3 years). Number of endoscopies, antisecretory medication, H pylori treatments, and hospital visits were recorded from health care databases for the entire follow up period. RESULTS: Median age was 45 years; 28% were H pylori infected. Use of resources was registered in all 500 patients (3084 person years) of whom 312 completed diaries. We found no difference in symptoms between the two groups. Median proportion of days without symptoms was 0.52 (interquartile range 0.10-0.88) in the test and eradicate group versus 0.64 (0.14-0.90) in the prompt endoscopy group (p = 0.27) (mean difference 0.05 (95% confidence interval (CI) -0.03 to 0.14)). Compared with the prompt endoscopy group, the test and eradicate group underwent fewer endoscopies (mean difference 0.62 endoscopies/person (95% CI 0.38-0.86)) and used less antisecretory medication (mean difference 102 defined daily doses/person (95% CI -1 to 205)). CONCLUSION: On a long term basis, a H pylori test and eradicate strategy is as efficient as prompt endoscopy for management of dyspeptic patients in primary care and reduces the use of endoscopy and antisecretory medication.

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Hepatogastroenterology. 2004 Nov-Dec;51(60):1856-9.
Effects of mineral-water supplementation on gastric emptying of solids in patients with functional dyspepsia assessed with the 13C-octanoic-acid breath test.
Anti M, Lippi ME, Santarelli L, Gabrielli M, Gasbarrini A, Gasbarrini G.
Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy.

BACKGROUND/AIMS: Functional dyspepsia is a major problem in terms of prevalence and drug-therapy expenditures. In dyspeptic patients the symptoms are frequently caused by delayed gastric emptying. Conventional treatment is often inefficient. Mineral-water supplementation is prescribed for the treatment of this condition, but there is no concrete proof of its actual efficacy. The aim of this study was to evaluate the effect of supplementation with mineral waters with high mineral salt contents (Acqua Tettuccio, Acqua Regina, Montecatini Terme) on gastric emptying of solids and symptoms in patients with functional dyspepsia. METHODOLOGY: Eight patients with functional dyspepsia and two healthy (non-dyspeptic) controls were placed on high-mineral-content water supplementation (500 cc/day) for eight days. Before and after completion of the supplementation treatment, patient symptoms were scored and the 13C-octanoic-acid breath test was administered to assess gastric emptying. RESULTS: After the treatment, the dyspeptic subjects presented clear decreases in parameters of gastric emptying (half time and lag time) as well as an improvement in symptom scores. CONCLUSIONS: Health spa treatments based on consumption of waters with a high content of mineral salts seem to be capable of improving gastric emptying of solids in dyspeptics. Longer and longitudinal studies are needed to verify the persistence of this effect.

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Aliment Pharmacol Ther. 2004 Nov 15;20(10):1171-9.
Classification of dyspepsia and response to treatment with proton-pump inhibitors.
Meineche-Schmidt V.
General Practice, Klampenborg, Denmark.

Summary Background : Lacking an objective 'gold standard' for diagnosing dyspepsia, several symptom-based classifications have been suggested. Aim : To assess if response to proton-pump inhibitor treatment could provide useful information for current or future dyspepsia classification. Methods : Post hoc analyses of 829 patients treated with omeprazole or placebo in a randomized-controlled trial. The 'true' response to omeprazole (trial response minus placebo response) was assessed according to different classifications of dyspepsia and different symptoms. Results : Symptoms described with the words 'burning' or 'sour' and patients with reflux-like dyspepsia demonstrated high response to omeprazole treatment, whereas patients with abdominal pain or ulcer-like dyspepsia responded unpredictably to omeprazole. The response to omeprazole in patients with epigastic pain was related to the pattern of other dyspeptic symptoms. Patients with heartburn or regurgitation overlapped extensively with patients with epigastric pain. Conclusion : The study demonstrated significant problems in the current classification of dyspepsia: 'the most bothersome symptom' was not independently related to the omeprazole effect and, in patients with abdominal pain, the response to omeprazole was dependent on the presence or absence of other dyspeptic symptoms. The overlap of symptoms indicates that heartburn and regurgitation should be recognized as symptoms of dyspepsia in primary care.

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Nurs Stand. 2004 Nov 3-9;19(8):33-8.
Test and treat Helicobacter pylori before endoscopy.
Livett H.
University Hospitals Coventry and Warwickshire NHS Trust, Coventry. helen.livett@uhcw.nhs.uk

BACKGROUND: Helicobacter pylori may have major implications for patients' wellbeing and future health. If a patient is found to be H. pylori positive it is important that the infection is eradicated because of the risk of associated peptic ulcers and gastric cancers. There are, however, great demands on NHS gastroenterology and endoscopy services and following the introduction of recent guidelines for dyspepsia some of these issues may be addressed. The literature suggests that a strategy of test and treat before endoscopy referral will benefit patients and be cost-effective. CONCLUSION: There is evidence that, over a period of time, it is more prudent to test and treat H. pylori first and then review the patient's condition before endoscopy is performed (if no other symptoms are identified.

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Clin Gastroenterol Hepatol. 2004 Nov;2(11):957-67.
Complementary and alternative medicine in gastroenterology: The good, the bad, and the ugly.
Koretz RL, Rotblatt M.

A large proportion of the American population avails itself of a variety of complementary and alternative medicine (CAM) interventions. Allopathic practitioners often dismiss CAM because of distrust or a belief that there is no sound scientific evidence that has established its utility. However, although not widely appreciated, there are thousands of randomized controlled trials (RCTs) that have addressed the efficacy of CAM. We reviewed the RCTs of herbal and other natural products, acupuncture, and homeopathy as examples of typical CAM modalities, focusing on conditions of interest to gastroenterologists. Peppermint (alone or in combination) has supportive evidence for use in patients with dyspepsia, irritable bowel syndrome, and as an intraluminal spasmolytic agent during barium enemas or endoscopy. Ginger appeared to be effective in relieving nausea and vomiting due to motion sickness or pregnancy. Probiotics were useful in childhood diarrhea or in diarrhea due to antibiotics; one particular formulation (VSL#3) prevented pouchitis. Acupuncture appeared to ameliorate postoperative nausea and vomiting and might be useful elsewhere. There is even a suggestion that homeopathy has efficacy in treatment of gastrointestinal problems or symptoms. The major problem in interpreting these CAM data is the generally low quality of the RCTs, although that quality might not be different compared to RCTs in the general medical literature. Gastroenterologists should become familiar with these techniques; it is likely that their patients already are.

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Gastroenterology. 2004 Nov;127(5):1329-37.
The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis.
Moayyedi P, Delaney BC, Vakil N, Forman D, Talley NJ.
Gastroenterology Division, McMaster University, Hamilton, Ontario, Canada. moayyep@mcmaster.ca

BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.

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Orv Hetil. 2004 Oct 17;145(42):2141-5.
[The effect of Heliobacter pylori eradication on prokinetic treatment on the quality of life in functional dyspepsia]
[Article in Hungarian]
Buzas GM.
Ferencvarosi Egeszsegugyi Szolgalat, Gasztroenterologia, Budapest. drgybuzas@hotmail.com

INTRODUCTION: The quality life is impaired in functional dyspepsia. Little is known, however, about the impact of different therapies on the quality of life in this condition. AIM OF STUDY: The scope of this study is to detect the change-over time of the quality of life under two different treatments in functional dyspepsia. METHODS: One-hundred-one Helicobacter pylori positive and 98 Helicobacter pylori negative functional dyspepsia patients have been enrolled in a prospective, controlled study. Organic digestive diseases were excluded by endoscopy and abdominal ultrasound. The quality of life was assessed by a disease-specific questionnaire developed by the MAPI Research Institute, Lyon, France, translated and validated in Hungarian. Helicobacter pylori positive patients received one week triple regimen consisting in 2 x 40 mg pantoprazole + 2 x 1000 mg amoxicillin + 2 x 500 mg clarithromycin followed by on-demand ranitidine (1-2 x 150 mg) during 1 year of follow-up. Control 13C-urea breath test was performed 6 weeks after eradication. Helicobacter pylori negative patients received 3 x 10 mg cisapride for 6 weeks followed by on-demand prokinetic for 1 year. The questionnaire was self-administred at baseline, after 6 weeks and 1 year. RESULTS: The eradication rate of Helicobacter pylori was of 76.4% on an 'intention-to treat' and 82.6% on 'per protocol' analysis. In patients with successful eradication, the standardized and transformed quality of life score increased after 6-8 weeks from 56.2 + 9.8 (95% confidence interval: 53.9-58.4) to 70.8 + 10.7 (68.3-73.5) (p = 0.0001) and to 75.3 + 9.3 (73.2-77.5) at 1 year (p = 0.005). In the patients with failed eradication, the quality of life has not been changed significantly (p = 0.76). The quality of life scores increased in Helicobacter pylori negative cases from 60.0 + 9.8 (58.0-62.0) to 73.3 + 9.6 (71.3 + 75.4) after 6 weeks (p = 0.0001) and to 76.5 + 8.5 (74.5 - 78.4) at 1 year (p = 0.56). The effect size was large in both groups and there were no differences between the treatment arms either at 6-8 weeks (p = 0.11) or after 1 year (p = 0.43). CONCLUSIONS: Eradication of Helicobacter pylori infection and prokinetic treatment lead to significant improvement of the quality of life in functional dyspepsia. The disease-specific questionnaire was sensitive enough to capture the changes over time induced by the given therapies.

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Am J Gastroenterol. 2004 Sep;99(9):1817-22.
A systematic review of psychological therapies for nonulcer dyspepsia.
Soo S, Forman D, Delaney BC, Moayyedi P.
South Tyneside District Hospital, South Shields, Tyne & Wear, U.K.

OBJECTIVES: We conducted a systematic review to determine the effectiveness of psychological interventions including psychodrama, cognitive behavioral therapy, relaxation therapy, guided imagery, or hypnosis in the improvement of dyspepsia symptoms in patients with nonulcer dyspepsia (NUD). DESIGN: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL, and PsycLIT, using appropriate subject headings and text words and searching bibliographies of retrieved articles. All randomized controlled trials (RCTs) or quasi-randomized studies were eligible. RESULTS: The four eligible trials all used different psychological interventions including applied relaxation therapy, psychodynamic psychotherapy, cognitive therapy, and hypnotherapy. Trials did not present data in a form that could be synthesized. All reported an improvement in the dyspepsia symptom scores at the end of treatment and at 1 yr in the intervention arm compared with controls. All studies only achieved statistically significant results through adjusting for baseline differences between groups. This reflects the small sample sizes of the trials. There were also problems with assumptions made in the statistical analyses used to achieve statistical significance. The studies highlighted problems with recruitment and compliance. CONCLUSIONS: There was insufficient evidence on the efficacy of psychological therapies in NUD. This emphasizes the need for appropriately powered well-designed trials in this area. (Am J Gastroenterol 2004;99:1817-1822)

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Cochrane Database Syst Rev. 2004;(3):CD002301.
Psychological interventions for non-ulcer dyspepsia.
Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D.

BACKGROUND: Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain. OBJECTIVES: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores patients with NUD. SEARCH STRATEGY: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using very broad subject headings and text words. Bibliographies of retrieved articles were also searched and experts in the field were contacted. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified. DATA COLLECTION AND ANALYSIS: Data collected included individual, global dyspepsia symptom scores and quality of life (QoL) scores. MAIN RESULTS: We identified only four trials, each using different psychological interventions and three presenting results in a manner, that did not allow synthesis of the data to form a meta-analysis. All trials suggest that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials use statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size of these papers was too small. Unadjusted data was not statistically significant. The other problem of psychological intervention include low recruitment and high drop out rate which has been shown to be greater in patients receiving group therapy. REVIEWERS' CONCLUSIONS: There is currently insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD. There is also no evidence on the combined effects of pharmacological and psychological therapy. Nevertheless, if there are any benefits of psychological therapies, they are likely to persist long-term and NUD is a chronic relapsing and remitting disorder. Psychological therapies may therefore be offered to patients with severe symptoms that have not responded to pharmacological therapies.

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Best Pract Res Clin Gastroenterol. 2004 Aug;18(4):717-33.
Functional dyspepsia: drugs for new (and old) therapeutic targets.
Cremonini F, Delgado-Aros S, Talley NJ.
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic College of Medicine, Charlton 8-138, 200 First Street SW, Rochester MN 55905, USA.

The therapeutic management of functional dyspepsia remains a major challenge for the gastroenterologist. Current therapies available are based on putative underlying pathophysiologic mechanisms, including gastric acid sensitivity, slow gastric emptying and Helicobacter pylori infection, but only a small proportion of patients achieve symptomatic benefit from these therapeutic approaches. Relatively novel mechanistic concepts under testing include impaired gastric accomodation, visceral hypersensitivity, and central nervous system dysfunction. Serotonergic modulators (e.g. the 5-HT4 agonist tegaserod, the 5-HT3 antagonist alosetron and the 5-HT1P agonist sumatriptan), CCK-1 antagonists (e.g. dexloxiglumide), opioid agonists (e.g. asimadoline), N-methyl-d-aspartate (NMDA) receptor antagonists (e.g dextromethorphan), neurokinin antagonists (e.g. talnetant), capsaicin-like agents and antidepressants are among the agents currently under investigation. It seems unlikely, however, that targeting a single mechanism with an individual drug will result in complete symptom remission in most cases.

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Aliment Pharmacol Ther. 2004 Aug 15;20(4):423-30.
Identifying response to acid suppressive therapy in functional dyspepsia using a random starting day trial--is gastro-oesophageal reflux important?
Madsen LG, Wallin L, Bytzer P.
Department of Medical Gastroenterology, Glostrup University Hospital, Glostrup, Denmark.

BACKGROUND: Single subject trials offer an alternative approach to identify and characterize responders to a specific treatment. AIM: To test a new single subject trials design, called random starting day trial, to identify acid-related symptoms in dyspepsia. METHODS: A total of 119 patients with functional dyspepsia entered a 12-day, double-blind random starting day trial. All patients started on placebo and switched to omeprazole 80 mg/day at a randomized and blinded day between day 5 and day 9, with active treatment continuing for the rest of the trial. Based on changes of a daily symptom score, response was defined as a sustained > or =50% reduction of symptoms within 3 days of active treatment. RESULTS: Thirteen of 119 patients (11%) were classified as spontaneous responders because of complete symptom relief before switching to omeprazole. Of the remaining 106 patients, 15 (15.6%) were classified as responders. Five of six (83%) responders compared with 28 of 53 (53%) non-responders had pathological reflux. Multivariate testing identified symptoms suggestive of gastro-oesophageal reflux predictive of response. CONCLUSIONS: The random starting day trial design could identify a subset of dyspeptic patients with a uniform symptomatic response to acid-suppressive therapy. Response seems to be associated with gastro-oesophageal reflux. The random starting day trial needs to be further validated to be considered as a reliable instrument in clinical research.

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Am Fam Physician. 2004 Jul 1;70(1):107-14.
Evaluation and management of nonulcer dyspepsia.
Dickerson LM, King DE.
Department of Family Medicine, Medical University of South Carolina, Charleston, South Carolina 29406, USA. macfarll@musc.edu

When no organic cause for dyspepsia is found, the condition generally is considered to be functional, or idiopathic. Nonulcer dyspepsia can cause a variety of symptoms, including abdominal pain, bloating, nausea, and vomiting. Many patients with nonulcer dyspepsia have multiple somatic complaints, as well as symptoms of anxiety and depression. Extensive diagnostic testing is not recommended, except in patients with serious risk factors such as dysphagia, protracted vomiting, anorexia, melena, anemia, or a palpable mass. In these patients, endoscopy should be considered to exclude gastroesophageal reflux disease, peptic or duodenal ulcer, and gastric cancer. In patients without risk factors, consideration should be given to empiric therapy with a prokinetic agent (e.g., metoclopramide), an acid suppressant (histamine-H2 receptor antagonist), or an antimicrobial agent with activity against Helicobacter pylori. Treatment of patients with H. pylori infection and nonulcer dyspepsia (rather than peptic ulcer) is controversial and should be undertaken only when the pathogen has been identified. Psychotropic agents should be used in patients with comorbid anxiety or depression. Treatment of nonulcer dyspepsia can be challenging because of the need to balance medical management strategies with treatments for psychologic or functional disease.

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Am J Gastroenterol. 2004 Jun;99(6):1050-8.
Empiric treatment with high and standard dose of omeprazole in general practice: two-week randomized placebo-controlled trial and 12-month follow-up of health-care consumption.
Meineche-Schmidt V.

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.

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Am J Med. 2004 Jun 1;116(11):740-8.
Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials.
Peura DA, Kovacs TO, Metz DC, Siepman N, Pilmer BL, Talley NJ.
University of Virginia, Charlottesville, Virginia, USA. DAP8V@hscmail.mcc.virginia.edu

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

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Ann Ital Med Int. 2004 Apr-Jun;19(2):84-9.
[Functional dyspepsia: definition, classification, clinical and therapeutic management]
[Article in Italian]
Montalto M, Santoro L, Vastola M, Curigliano V, Cammarota G, Manna R, Gasbarrini G.
Istituto di Medicina Interna e Geriatria, Universita Cattolica del Sacro Cuore di Roma, Policlinico A Gemelli. mmontalto@rm.unicatt.it

Dyspepsia is a very common syndrome characterized by pain and/or discomfort of the upper abdomen. Sometimes, an organic disease causes this syndrome (organic dyspepsia); more frequently, there are no known diseases (functional dyspepsia). These latter conditions are identified by exclusion. The pathogenesis of this syndrome is yet to be clarified. Currently, functional dyspepsia is classified in ulcer-like dyspepsia, dysmotility-like dyspepsia and nonspecific dyspepsia, in which symptoms do not clearly fit into any of the above categories. The current guidelines for the management of "uninvestigated dyspepsia" suggest testing for Helicobacter pylori infection and relative treatment if positive. A gastroscopy should be performed in case of persistence of symptoms to discriminate between the organic and functional forms. In the latter, to optimize patient management, it is necessary to find the exact subgroup. Antacids, H2-receptor antagonists and proton pump inhibitors have been demonstrated to be useful in ulcer-like dyspepsia. Prokinetic agents are more effective in the dysmotility-like dyspepsia. Further studies will be necessary to confirm the efficacy of emerging therapeutic strategies.

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Clin Gastroenterol Hepatol. 2004 Apr;2(4):301-8.
Levosulpiride and cisapride in the treatment of dysmotility-like functional dyspepsia: a randomized, double-masked trial.
Mearin F, Rodrigo L, Perez-Mota A, Balboa A, Jimenez I, Sebastian JJ, Paton C.
Institute of Functional and Motor Digestive Disorders, Centro Medico Teknon, Barcelona, Spain. fmearinm@meditex.es

BACKGROUND & AIMS: Levosulpiride is a benzamide derivate D(2) dopamine antagonist with prokinetic activity that can accelerate gastric emptying and reduce discomfort in response to gastric distention. The aim of the study is to compare the clinical efficacy of levosulpiride and cisapride in patients with dysmotility-like functional dyspepsia. METHODS: In a exploratory pilot study performed as a multicenter, randomized, double-masked trial, the effects of 8 weeks of treatment with either levosulpiride, 25 mg, 3 times daily (n = 69) or cisapride, 10 mg, 3 times daily (n = 71) were compared. Individual symptoms (pain/discomfort, fullness, bloating, early satiety, and nausea/vomiting), global symptom score, effect on health-related quality of life (HRQoL), and anxiety-state and anxiety-trait were evaluated. Adverse events also were recorded. RESULTS: Both levosulpiride and cisapride improved dyspeptic symptoms and decreased total symptom score (79.9% and 71.3%, respectively); no significant statistical difference between treatments was found (P = 0.07 for total symptom score). HRQoL improved similarly after both treatments, whereas no change was observed in anxiety. Medication-related adverse effects were present in 13 of 69 patients (18.8%) in the levosulpiride group and 8 of 71 patients (11.3%) in the cisapride group. Significantly more (P = 0.03) patients treated with cisapride had to abandon the trial because of side effects. CONCLUSIONS: Levosulpiride is at least as effective as cisapride in the treatment of dysmotility-like functional dyspepsia.

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Korean J Gastroenterol. 2004 Mar;43(3):160-7.
[The effect of mosapride on quality of life in functional dyspepsia]
[Article in Korean]
Cho YK, Choi MG, Kim SH, Lee IS, Kim SW, Chung IS, Lee SY, Choi SC, Seol SY.
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seocho-gu, Seoul, Korea.

BACKGROUND/AIMS: It is unknown whether the prokinetics improve the quality of life in patients with functional dyspepsia. Thus, we evaluate the effect of the mosapride, selective 5-HT4 agonist, on the symptom and life quality of patients with functional dyspepsia using the Nepean dyspepsia index-Korean version (NDI-K), a reliable and validated disease-specific quality of life questionnaire. METHODS: A single, open trial was performed in 129 patients with functional dyspepsia. Patients were received mosapride 5 mg t.i.d before each meal for 4 weeks. The symptoms and quality of life were measured with the NDI-K at baseline and 4 weeks. The responsiveness of the NDI-K was evaluated by correlation with symptom scores. RESULTS: All the 15 symptom scores and the dyspepsia score decreased after treatment (p<0.05). The total symptom score decreased from 60.9 +/- 25.8 to 24.7 +/- 20.4 (p=0.001). Correlations were observed between the total symptom score and the NDI-K score (r=0.47, p=0.001), and between the total symptom score and each score in 5 subscales (r=0.25-0.44, p=0.001). The NDI-K score was significantly increased in the effective group whose dyspepsia score decreased more than 50% of the score at baseline, compared with that of ineffective group. Any significant adverse effect and prolongation of QT interval were not occurred in all patients. CONCLUSIONS: A prokinetic drug, mosapride improves the symptoms and the quality of life in patients with functional dyspepsia.

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Dtsch Med Wochenschr. 2004 Mar 26;129(13):671-5.
[Long-term course of reflux symptoms following Helicobacter pylori eradication]
[Article in German]
Peitz U, Raps S, Plein K, Leodolter A, Hotz Dagger J, Malfertheiner P.
Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universitat Magdeburg, Germany. ulrich.peitz@medizin.uni-magdeburg.de

BACKGROUND AND OBJECTIVE: Conflicting data regarding new onset or deterioration of gastroesophageal reflux disease (GORD) following eradication of Helicobacter pylori infection have been reported. Successful eradication therapy may influence gastric acid output. The study aimed to to investigate whether patients with pre-existing GORD or peptic ulcer disease may experience deterioration of GORD. PATIENTS AND METHODS: 75 consecutive patients of a prospective longitudinal study (median age 66 years, n = 45 males) had received successful H. pylori eradication therapy because of the following main diagnosis: peptic ulcer (n = 37), GORD (n = 16), functional dyspepsia (n = 22). Two to three years later, they had an interview regarding the course of their dyspeptic and reflux symptoms. Negative H. pylori status at present was confirmed by (13)C-urea breath test in all patients. Ten patients were excluded because of proton pump inhibitor treatment. RESULTS: Patients with deterioration of GORD (new onset or increasing reflux symptoms) were found significantly more frequently in the group with functional dyspepsia (36 %) compared to pre-existing GORD (16 %) or peptic ulcer disease (5 %). Improvement of pre-existing reflux complaints were reported mostly by patients with peptic ulcer disease. There was no significant impact of initial reflux manifestations like reflux symptoms or reflux oesophagitis on the course. CONCLUSIONS: During long-term follow-up after H. pylori eradication, patients experience improvement as frequently as deterioration of reflux symptoms. There is a tendency towards improvement of reflux symptoms if peptic ulcer disease had been the indication for eradication, but towards deterioration in patients with initial functional dyspepsia. A clinical relevant prediction, however, is not feasible.

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Curr Treat Options Gastroenterol. 2004 Apr;7(2):121-131.
Treatment of Functional Dyspepsia.
Delgado-Aros S, Cremonini F, Talley NJ.
Clinical Enteric Neuroscience Translational & Epidemiological Research Program, Mayo Clinic, Charlton 8-138, 200 First Street SW, Rochester, MN 55905, USA. talley.nicholas@mayo.edu

Functional dyspepsia is a common chronic condition. It can have a major impact on quality of life and remains a large burden on healthcare resources. Its underlying mechanisms are not fully understood and therapies are mainly empirical. In this review, we summarize the best evidence on available therapeutic interventions in functional dyspepsia. Helicobacter pylori eradication, for those infected, is likely a safe and cost-effective strategy but benefits only a minority. Antisecretory agents such as proton-pump inhibitors and histamine-2 receptor antagonists have shown some benefit and are recommended as the first-line option in the absence of H. pylori infection. There is a lack of strong evidence of benefit from prokinetic agents, and cisapride, the most studied agent, is largely unavailable. Antidepressants need to be adequately tested in functional dyspepsia, but both psychotherapy and hypnotherapy interventions have shown promising results. Herbal therapies need further study in these patients. 5-Hydroxytryptamine3 (5-HT(3)) and 5-HT(4) receptor antagonists, and cholecystokinin type A and neurokinin receptor antagonists remain promising emerging therapies.

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Cochrane Database Syst Rev. 2004;(1):CD002301.
Psychological interventions for non-ulcer dyspepsia.
Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D.

BACKGROUND: Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain. OBJECTIVES: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores patients with NUD. SEARCH STRATEGY: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using very broad subject headings and text words. Bibliographies of retrieved articles were also searched and experts in the field were contacted. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified. DATA COLLECTION AND ANALYSIS: Data collected included individual, global dyspepsia symptom scores and quality of life (QoL) scores. MAIN RESULTS: We identified only four trials, each using different psychological interventions and three presenting results in a manner, that did not allow synthesis of the data to form a meta-analysis. All trials suggest that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials use statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size of these papers was too small. Unadjusted data was not statistically significant. The other problem of psychological intervention include low recruitment and high drop out rate which has been shown to be greater in patients receiving group therapy. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD. There is also no evidence on the combined effects of pharmacological and psychological therapy. Nevertheless, if there are any benefits of psychological therapies, they are likely to persist long-term and NUD is a chronic relapsing and remitting disorder. Psychological therapies may therefore be offered to patients with severe symptoms that have not responded to pharmacological therapies.

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Aliment Pharmacol Ther. 2004 Feb;19 Suppl 1:1-8.
Review article: uninvestigated dyspepsia and non-ulcer dyspepsia-the use of endoscopy and the roles of Helicobacter pylori eradication and antisecretory therapy.
Chey WD, Moayyedi P.
Department of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA. wchey@umich.edu

Due to its prevalence, impact on quality-of-life and the associated significant health resource utilization, dyspepsia is a major healthcare concern. The available management strategies for uninvestigated dyspepsia include prompt endoscopy, the 'test-and-treat' strategy for Helicobacter pylori, and empiric antisecretory therapy. There is consensus that endoscopy should be reserved for patients with alarm features (e.g. symptom onset after 45 years of age, recurrent vomiting, weight loss, dysphagia, evidence of bleeding, anaemia), H. pylori-positive individuals who fail test-and-treat, and those with an inadequate response to empiric antisecretory therapy. Factors influencing the decision between test-and-treat and empiric antisecretory therapy in uninvestigated dyspepsia include the local prevalence of H. pylori and peptic ulcer disease and the proportion of ulcers attributable to H. pylori. For uninvestigated dyspepsia in patients without alarm features, test-and-treat is the preferred initial management method in Europe based on the relatively high prevalence of H. pylori/peptic ulcer disease whereas empiric antisecretory therapy is preferred in many parts of the United States, where the prevalence of H. pylori/peptic ulcer disease is relatively low. In patients with non-ulcer dyspepsia, H. pylori eradication and empiric antisecretory therapy result in comparable and small, but statistically significant, improvements in dyspepsia. Empiric antisecretory therapy is the preferred initial method of managing non-ulcer dyspepsia in Europe and the US. The test-and-treat approach would receive increased enthusiasm if H. pylori cure is shown to prevent development of gastric cancer in non-ulcer dyspepsia patients in a large Western trial.

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Hepatogastroenterology. 2004 Jan-Feb;51(55):303-8.
Lack of benefit of treating Helicobacter pylori infection in patients with functional dyspepsia. Randomized one-year follow-up study.
Gisbert JP, Cruzado AI, Garcia-Gravalos R, Pajares JM.
Department of Gastroenterology, University Hospital of La Princesa, Madrid, Spain. gisbert@meditex.es

BACKGROUND/AIMS: To assess whether H. pylori therapy is significantly better than control therapy in patients with functional dyspepsia, and to assess whether curing the infection relieves symptoms of dyspepsia. METHODOLOGY: We prospectively included consecutive H. pylori-positive patients in whom a gastroscopy was carried out and who were diagnosed of functional dyspepsia. At endoscopy, biopsies were obtained (histology and rapid urease test), and a 13C-urea breath test was carried out. Patients were randomly assigned to 10 days of treatment with either eradication therapy (omeprazole, amoxicillin and clarithromycin) or with ranitidine. No antisecretory therapy was prescribed thereafter. Breath test was repeated four weeks after completing eradication treatment. A validated five-point Likert scale was used to measure severity of symptoms, both at the beginning of the study and 6 and 12 months after treatment. RESULTS: Fifty patients were included in the study. Sixteen patients were randomized to ranitidine and 34 to eradication treatment. The two groups were well balanced for base-line characteristics. One patient in each treatment arm was lost to follow-up at 12 months. Differences between ranitidine and eradication groups were not demonstrated in any of the symptom comparisons, either initially or at 12 months. The rates of treatment success for each symptom were similar in both groups. H. pylori was eradicated in 76% of the patients receiving antibiotics. Differences between groups of patients with eradication success and failure were not demonstrated in any of the symptom comparisons, either initially or at 12 months. Among the groups given eradication regimen, the rates of treatment success for each symptom were similar in the group with H. pylori eradication success and failure. CONCLUSIONS: H. pylori eradication is not likely to play a major role in the treatment of symptoms in patients with functional dyspepsia.

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Dig Liver Dis. 2004 Jan;36(1):7-12.
Empirical Helicobacter pylori "rescue" therapy after failure of two eradication treatments.
Gisbert JP, Gisbert JL, Marcos S, Pajares JM.
Department of Gastroenterology, La Princesa University Hospital, Madrid, Spain. gisbert@meditex.es

AIM: Even with the current most effective Helicobacter pylori treatment regimens, approximately 20% of patients do not eradicate the infection. Several "rescue" therapies have been recommended, but they still fail to eradicate H. pylori in approximately 20-30% of the cases. Our aim was to evaluate the efficacy of different rescue therapies prescribed to patients in whom two consecutive H. pylori eradication regimens had failed. METHODS: Design. Prospective single-centre study. Patients. Consecutive patients in whom two eradication regimens had failed to eradicate H. pylori. Intervention. Third eradication regimens included: (1) omeprazole-amoxicillin-clarithromycin for 7 days; (2) quadruple therapy with omeprazole-bismuth-tetracycline-metronidazole for 7 days; (3) omeprazole-amoxicillin-clarithromycin-bismuth for 14 days; and (4) omeprazole-amoxicillin-rifabutin for 14 days. H. pylori antibiotic susceptibility was unknown and, therefore, rescue regimens were chosen empirically. In no case, was the same regimen repeated. Outcome. H. pylori eradication was defined as a negative in 13C-urea breath test 8 weeks after completing the therapy. RESULTS: Forty-eight patients were included (mean age 45 years, 44% males, 82% with peptic ulcer and 18% with functional dyspepsia). No patient was lost from follow-up. Adverse effects were described in 21% of the patients. One patient receiving omeprazole, amoxicillin and rifabutin was removed from medication due to adverse effects (vomiting). Overall, mean H. pylori eradication with third therapy after failure of two eradication treatments was 34/48 (71%; 95% confidence interval 57-82%) by intention-to-treat and 34/47 (72%; 95% confidence interval 58-83%) by per-protocol. CONCLUSION: It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximise H. pylori eradication, based on the different possibilities of empirical treatment.

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Digestion. 2004;69(1):45-52. Epub 2004 Jan 30.
Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial.
Madisch A, Holtmann G, Mayr G, Vinson B, Hotz J.
Medical Department I, Technical University Hospital Dresden, Dresden, Germany.

BACKGROUND: We aimed to assess the efficacy and safety of a herbal preparation STW 5-II containing extracts from bitter candy tuft, matricaria flower, peppermint leaves, caraway, licorice root and lemon balm for the treatment of patients with functional dyspepsia. METHODS: 120 patients with functional dyspepsia were randomly assigned to 1 of 4 treatment groups. Each patient received the treatment for three consecutive 4-week treatment blocks. The first two treatment blocks were fixed. For the third treatment period, medication was based upon the investigator's judgement of symptom improvement during the preceding treatment period. In patients without adequate control of symptoms, the treatment was switched, or if symptoms were controlled, the treatment was continued. The primary outcome measure was the improvement of a standardized gastrointestinal symptom score (GIS). FINDINGS: During the first 4 weeks, the GIS significantly decreased in subjects on active treatment compared to the placebo (p < 0.001). During the second 4-week period, symptoms further improved in subjects who continued on active treatment or who switched to the active treatment (p < 0.001), while symptoms deteriorated in subjects who switched to placebo. After 8 weeks 43.3% on active treatment and 3.3% on placebo reported complete relief of symptoms. (p < 0.001 vs. placebo). CONCLUSION: In patients with functional dyspepsia, the herbal preparation tested improved dyspeptic symptoms significantly better than placebo. Copyright 2004 S. Karger AG, Basel

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Med Clin (Barc). 2004 Jan 31;122(3):87-91.
[Efficacy of Helicobacter pylori eradication in nonulcer dyspepsia]
[Article in Spanish]
Gonzalez Carro P, Legaz Huidobro ML, Perez Roldan F, Esteban Lopez Jamar JM, Valenzuela Gamez JC, Ponte Tellechea A, Ruiz Carrillo F, Pedraza Martin C, Diaz De Rojas F, Saez Bravo JM.
Hospital General Mancha-Centro. Alcazar de San Juan. Ciudad Real. Espana.

Background and objective: The relationship between Helicobacter pylori infection and functional dyspepsia (FD) is disputed. Although there is a greater prevalence of infection by H. pylori in subjects with non-ulcer dyspepsia than in healthy subjects, results regarding the eradication of infection have been inconclusive so far in terms of disease improvement. In this study, we administered eradicating treatment to a group of patients with both FD and infection by H. pylori to determine the possible beneficial effect of such a treatment. Thus, our objective was to study the effectiveness of eradication therapy for H. pylori in the clinical course of FD.Patients and method: This was a randomized, double-blind study in 93 consecutive patients diagnosed with FD and infection by H. pylori who received eradicating treatment with omeprazol, amoxicillin and clarythromicin for 7 days (group A, n = 47) vs. placebo, amoxicillin and clarythromicin for 7 days (group B, n = 46). We analyzed the clinical evolution of the disease within the following 9 months.Results: Both groups of treatment were comparable concerning all the variables studied except for the consumption of alcohol, with a greater prevalence in group A, yet no patient consumed more than 40 g per day. The average age of patients was 42 (18-65). Eradication of H. pylori occurred in 65.9% of patients in group A and 4.3% of patients in group B. 40% of all patients included in the study had improved symptoms. In 60.6% of patients whose infection was eradicated, their symptoms improved, as opposed to 25% of patients whose infection was not eradicated (p = 0.001). Among patients whose symptoms improved following eradication, 70% had had an FD duration of less than 3 years and in 30% FD had lasted for more than 3 years (p < 0.05).Conclusions: The eradication of H. pylori in patients with short-lasting FD may lead to a significant clinical benefit, especially in those whose duration of symptoms is below 3 years.

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J Intern Med. 2004 Jan;255(1):125-9.
Beta-lactamase inhibitor enhances Helicobacter pylori eradication rate.
Ojetti V, Migneco A, Zocco MA, Nista EC, Gasbarrini G, Gasbarrini A.
Departments of Internal Medicine and Gastroenterology, Gemelli Teaching Hospital, Catholic University of Rome, Rome, Italy.

OBJECTIVES: One-week triple therapy, a combination of acid suppression with two antibiotics, is the gold standard for anti-Helicobacter pylori treatment. There is increasing evidence of H. pylori resistance to classical triple therapy. Recently, it was reported that the amoxicillin-clavulanate combination had a slightly higher activity than amoxicillin alone against H. pylori, and that beta-lactamase inhibitors had 'in-vitro' antibacterial activity against H. pylori. SETTING: To evaluate the efficacy of 1 week triple therapy omeprazole, clarithromycin and amoxicillin plus clavulanate compared with omeprazole, clarithromycin and amoxicillin for H. pylori eradication. The study was open randomized. SUBJECTS: Sixty dyspeptic patients (36 male, 24 female; mean age 53 +/- 9 years) with Helicobacter pylori infection never treated before, were enrolled and randomly assigned to two different 7-day triple therapies: (i) (n = 30) amoxicillin 875 mg plus clavulanic acid 125 mg b.i.d., clarithromycin 500 mg b.i.d., omeprazole 20 mg b.i.d. (ACCO); (ii) (n = 30) amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d., omeprazole 20 mg b.i.d. (ACO). Bacterial eradication was assessed by 13C-urea breath test 4-6 weeks after therapy. Information on gastrointestinal symptoms and antibiotic-related side-effects were recorded using a questionnaire. RESULTS: All patients completed the study. A significantly higher H. pylori eradication rate with ACCO compared with ACO: (26/30) 86.6 vs. (20/30) 66.6%, respectively (P < 0.05) were observed. No major side-effects were reported, whilst 8% patients complained of mild side-effects; no significant differences were noted between the two groups. CONCLUSIONS: Our results suggest that amoxicillin and clavulanate in combination achieve a higher H. pylori eradication rate than amoxicillin alone, without any increase in side-effects. The combination of amoxicillin and clavulanate may represent an alternative therapeutic scheme for the treatment of H. pylori infection.

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Aliment Pharmacol Ther. 2004 Jan 15;19(2):219-31.
Dyspeptic symptoms associated with Helicobacter pylori infection are influenced by strain and host specific factors.
Treiber G, Schwabe M, Ammon S, Walker S, Klotz U, Malfertheiner P.
Department of Gastroenterology/Hepatology, University Hospital, Magdeburg, Germany. gerhard.treiber@medizin.uni-magdeburg.de

BACKGROUND: Dyspepsia can be associated with H. pylori infection. AIM: To assess dyspeptic symptoms and potentially influencing factors before and up to 6 months following successful H. pylori eradication therapy. METHODS: Prospective cohort study involving H. pylori positive subjects from ambulatory or hospitalized care. Main outcome measures were symptoms during baseline and follow-up, the proportion of symptom-free patients, and symptom scores. RESULTS: After successful eradication, the summary score of all dyspeptic symptoms decreased and during follow-up, the proportion of symptom-free patients was higher in the group with peptic ulcers (69.4% vs. 40.9%, P < 0.0001) than with functional dyspepsia (FD). Regardless of diagnosis, virulent strains of H. pylori were associated with a higher prevalence of epigastric pain before treatment: absolute risk-difference (ARD) with Oip-A: 18.2%, Odds Ratio (OR) 2.35 [1.3-4.2, 95%-CI], P = 0.01; with Cag-A: 24.6%, OR 2.81 [1.6-5], P = 0.01. Low-dose aspirin in part was a major risk factor in FD for previous weight loss bdfore study entry. Post-treatment, non-ulcer patients were more likely to suffer from distention/bloating. Likewise, alcohol induced persistence of nausea and vomiting in this population. CONCLUSIONS: Dyspeptic symptoms in H. pylori infected patients are more common with virulent strains. Symptoms are more likely to persist despite successful eradication if patients initially harboured virulent strains or concomitant aspirin or alcohol intake are present. In one-third of peptic ulcer patients, symptoms will not be cured 3 months after therapy.

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Intern Med J. 2003 Dec;33(12):604-9.
Management of dyspepsia at the beginning of the twenty-first century.
Duggan A.
Department of Gastroenterology, John Hunter Hospital, New South Wales, Australia.

Abstract Dyspepsia remains a frequent intercurrent management problem for the non-gastroenterologist. However, the causes for dyspepsia have changed markedly in recent decades. In contrast to gastro-oesophageal reflux -disease, both gastro-oesophageal malignancy and peptic ulcer disease have become uncommon causes for -dyspepsia. Concurrent with these changes, management strategies for dyspepsia have changed. Once aware of these changes the non-gastroenterologist can effectively manage the majority of patients with dyspepsia. The present paper reviews these key changes in dyspepsia management. (Intern Med J 2003; 33: 604-609)

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Aliment Pharmacol Ther. 2003 Dec;18(11-12):1099-105.
Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial.
Holtmann G, Adam B, Haag S, Collet W, Grunewald E, Windeck T.
Division of Internal Medicine, Department of Gastroenterology, University of Essen, Germany Winicker Norimed GmbH, Nuremberg, Germany Lichtwer Pharma AG, Berlin, Germany.

BACKGROUND: : This study aimed to assess the efficacy of artichoke leaf extract (ALE) in the treatment of patients with functional dyspepsia (FD). METHODS: : In a double-blind, randomized controlled trial (RCT), 247 patients with functional dyspepsia were recruited and treated with either a commercial ALE preparation (2 x 320 mg plant extract t.d.s.) or a placebo. The primary efficacy variable was the sum score of the patient's weekly rating of the overall change in dyspeptic symptoms (four-point scale). Secondary variables were the scores of each dyspeptic symptom and the quality of life (QOL) as assessed by the Nepean Dyspepsia Index (NDI). RESULTS: : Two hundred and forty-seven patients were enrolled, and data from 244 patients (129 active treatment, 115 placebo) were suitable for inclusion in the statistical analysis (intention-to-treat). The overall symptom improvement over the 6 weeks of treatment was significantly greater with ALE than with the placebo (8.3 +/- 4.6, vs. 6.7 +/- 4.8, P < 0.01). Similarly, patients treated with ALE showed significantly greater improvement in the global quality-of-life scores (NDI) compared with the placebo-treated patients (- 41.1 +/- 47.6 vs. - 24.8 +/- 35.6, P < 0.01). CONCLUSION: : The ALE preparation tested was significantly better than the placebo in alleviating symptoms and improving the disease-specific quality of life in patients with functional dyspepsia.

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Antimicrob Agents Chemother. 2003 Dec;47(12):3780-3.
Nitazoxanide in treatment of Helicobacter pylori: a clinical and in vitro study.
Guttner Y, Windsor HM, Viiala CH, Dusci L, Marshall BJ.
Department of Gastroenterology, Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia.

Nitazoxanide (NTZ) is an antibiotic with microbiological characteristics similar to those of metronidazole but without an apparent problem of resistance. The aim of this study was the prospective evaluation of NTZ given as a single agent in the treatment of Helicobacter pylori infection. Twenty culture-positive patients with dyspepsia who had previously failed at least one course of H. pylori eradication therapy were enrolled. Subjects received 1 g of NTZ twice daily for 10 days. The safety and tolerability of the drug were assessed by physical examination, monitoring of adverse events, and clinical laboratory evaluation. Urea breath tests (UBTs) were performed 6 weeks posttreatment. H. pylori was isolated from UBT-positive patients by the string test or endoscopy with biopsy, and the MICs for these isolates were compared to those for isolates obtained pretherapy. The levels of tizoxanide, the active deacylated derivative of NTZ, were measured in blood, saliva, and tissue from two patients during treatment. The UBT results were positive for all 20 patients after completion of NTZ therapy. The MIC results demonstrated that the NTZ susceptibilities of none of the strains isolated from the patients posttherapy had changed significantly. No major adverse reactions were observed, but frequent minor side effects were observed. In conclusion, NTZ did not eradicate H. pylori when it was given as a single agent.

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Rev Gastroenterol Disord. 2003;3 Suppl 4:S30-9.
The Role of Proton Pump Inhibitors in NSAID-Associated Gastropathy and Upper Gastrointestinal Symptoms.
Laine L.
Gastrointestinal Division, Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found with an endoscopy in 15%-30% of patients who are using NSAIDs regularly, and the annual incidence of upper gastrointestinal (GI) clinical events is 2.5%-4.5% among those who use NSAIDs regularly. Upper GI symptoms, such as dyspepsia, also occur in up to 60% of patients taking NSAIDs. H2-receptor antagonists when used at standard doses are not effective at preventing gastric ulcers resulting from the use of NSAIDs. Misoprostol effectively decreases NSAID-induced ulcers and GI complications, but issues of compliance (multiple daily doses) and side effects (eg, diarrhea and dyspepsia) may limit its use. Once-daily therapy with proton pump inhibitors has been documented to significantly decrease the development of NSAID-associated ulcers in endoscopic studies, reduce the rate of NSAID-related ulcer complications, and reduce upper GI symptoms in NSAID users.

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Anticancer Res. 2003 Sep-Oct;23(5A):3699-702.
Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of
Helicobacter pylori.
Mahady GB, Pendland SL, Yun GS, Lu ZZ, Stoia A.
Department of Pharmacy Practice, UIC/NIH Center for Botanical Dietary Supplements Research, PAHO/WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, 833 S. Wood St, MC 877, Chicago, IL 60612, USA. mahady@uic.edu

BACKGROUND: Ginger root (Zingiber officinale) has been used traditionally for the treatment of gastrointestinal ailments such as motion sickness, dyspepsia and hyperemesis gravidarum, and is also reported to have chemopreventative activity in animal models. The gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since Helicobacter pylori (HP) is the primary etiological agent associated with dyspepsia, peptic ulcer disease and the development of gastric and colon cancer, the anti-HP effects of ginger and its constituents were tested in vitro. MATERIALS AND METHODS: A methanol extract of the dried powdered ginger rhizome, fractions of the extract and the isolated constituents, 6-,8-,10-gingerol and 6-shogoal, were tested against 19 strains of HP, including 5 CagA+ strains. RESULTS: The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a minimum inhibitory concentration range of 6.25-50 micrograms/ml. One fraction of the crude extract, containing the gingerols, was active and inhibited the growth of all HP strains with an MIC range of 0.78 to 12.5 micrograms/ml and with significant activity against the CagA+ strains. CONCLUSION: These data demonstrate that ginger root extracts containing the gingerols inhibit the growth of H. pylori CagA+ strains in vitro and this activity may contribute to its chemopreventative effects.

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Am J Gastroenterol. 2003 Sep;98(9):1963-9.
Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia.
Veldhuyzen van Zanten S, Fedorak RN, Lambert J, Cohen L, Vanjaka A.
Division of Gastroenterology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

OBJECTIVES: The aim of this study was to compare the effect of a combination of lansoprazole, clarithromycin, and amoxicillin (LCA) versus placebo on the severity of symptoms in functional dyspepsia patients who were positive for Helicobacter pylori (H. pylori). METHODS: This was a double-blind, randomized, controlled clinical trial in adult patients with functional dyspepsia who were H. pylori positive. Patients were randomized to 7-day treatment with LCA or identical looking placebo. H. pylori status was confirmed by the urea breath test performed at baseline, at 6 wk, and at 6 and 12 months. The severity of eight upper GI symptoms was measured on a five-point Likert scale. The main outcomes were the change in average severity of the dyspepsia summary score of the eight symptoms and the proportion of patients who improved >/=4 points on the dyspepsia summary score. RESULTS: A total of 157 patients were included in the intention-to-treat analysis. LCA achieved cure of H. pylori infection in 82% of patients compared to 6% in the placebo group. The severity of dyspepsia symptoms improved over the 12-month study period, but for none of the outcome measures was there a significant difference between LCA and placebo. CONCLUSIONS: There was no difference in sustained improvement of dyspepsia symptoms when LCA was compared with placebo. An 82% cure rate of H. pylori infection was observed with LAC.

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Aliment Pharmacol Ther. 2003 Sep 15;18(6):615-25.
Helicobacter pylori eradication is beneficial in the treatment of functional dyspepsia.
Malfertheiner P, MOssner J, Fischbach W, Layer P, Leodolter A, Stolte M, Demleitner K, Fuchs W.
Otto-von-Guericke-Universitat, Zentrum fur Innere Medizin, Magdeburg, Germany. peter.malfertheiner@medizin.uni-magdeburg.de

AIM: To assess whether the eradication of Helicobacter pylori leads to long-term relief of symptoms in functional dyspepsia. METHODS: Eight hundred patients with functional dyspepsia were randomized to receive double-blind treatment with twice-daily 30 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L30AC), twice-daily 15 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L15AC), or once-daily 15 mg lansoprazole for 14 days (LP). Dyspepsia and reflux symptoms were monitored for 12 months. RESULTS: In intention-to-treat analysis, the non-ulcer dyspepsia sum score showed a statistically significant benefit in terms of symptom relief in the L30AC group (P = 0.0068) compared with the LP group, but there was no significant difference between the L15AC and LP groups (P = 0.2). When all patients in the two eradication therapy arms were considered together, successful eradication had a significant benefit with regard to the complete absence of symptoms (P < 0.04). H. pylori eradication did not lead to an increase in reflux symptoms. CONCLUSION: This study suggests that H. pylori infection causes dyspeptic symptoms in a subset of patients with functional dyspepsia, and that these patients may obtain long-term symptomatic benefit following H. pylori eradication.

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Am J Gastroenterol. 2003 Sep;98(9):1952-62.
The effect of a Helicobacter pylori treatment strategy on health care expenditures in patients with peptic ulcer disease and dyspepsia.
Kearney DJ, Liu CF, Crump C, Brousal A.
Primary and Specialty Medical Care Service, VA Puget Sound Health Care System, Seattle, Washington, USA.

OBJECTIVE: The aim of this study was to determine whether treatment for Helicobacter pylori (H. pylori) for patients with dyspepsia or a history of peptic ulcer decreases hospital expenditures. METHODS: Patients receiving acid suppressive medications were interviewed. Those with a documented ulcer, a self-reported ulcer, or dyspepsia were tested for H. pylori and treated with antibiotics if seropositive. Acid suppressive medications were stopped on completion of H. pylori therapy unless there was a history of gastroesophageal reflux disease (GERD) or Barrett's esophagus, and were started again at the discretion of primary care providers. Total hospital costs and GI medication costs in the 12 months before H. pylori treatment were compared to costs 12 months after H. pylori treatment. RESULTS: A total of 432 consecutive patients were treated for H. pylori. Of the patients, 125 (29%) had dyspepsia, 45 (10%) documented peptic ulcer, and 262 (61%) self-reported peptic ulcer. Total costs (mean 327 US dollars +/- 349 vs 291 USA dollars +/- 362, p = 0.06) and medication costs (mean 207 US dollars +/- 237 vs 224 US dollars +/- 277, p = 0.38) were not significantly different after treatment versus before treatment. A significant decrease in expenditures was limited to patients chronically on acid suppressive medications who had documented peptic ulcers and no history of GERD or Barrett's esophagus (mean 482 US dollars +/- 274 vs 282 US dollars +/- 218, p = 0.03). CONCLUSIONS: Treatment of H. pylori for patients with chronic dyspepsia or self-reported peptic ulcer does not reduce expenditures over 1 yr of follow up. H. pylori treatment for patients chronically receiving acid suppressive treatment with a prior documented ulcer significantly reduces expenditures if GERD and Barrett's esophagus are absent.

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Helicobacter. 2003 Aug;8(4):307-9.
Salvage therapy after two or more prior Helicobacter pylori treatment failures: the super salvage regimen.
Dore MP, Marras L, Maragkoudakis E, Nieddu S, Manca A, Graham DY, Realdi G.
Institute of Internal Medicine, University of Medicine, Sassari, Italy.

BACKGROUND: Although effective therapies are available for curing Helicobacter pylori infection, the problem persists about what to do for patients who fail two or more treatment courses despite a good compliance. AIM: To test a twice a day midday quadruple therapy as salvage therapy. METHODS: Dyspeptic H. pylori-infected patients who failed two or more courses of anti-H. pylori therapy received omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg twice a day (with the midday and evening meals) for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology 4-6 weeks after therapy. Eradication was defined as no positive test. RESULTS: Seventy-one patients were enrolled and 68 completed the full 14 days of therapy (mean age 46 years; 28 men). Thirty-three patients had failed prior treatment twice, 19 had failed three times, and 16 had failed four or more times. The cure rates were: intention to treat=93% (66/71); (95% CI=84% to 98%), per protocol=97% (66/68); (95% CI=89%- 100%). Success was excellent irrespective of diagnosis, age, prior treatment protocols, or smoking status. Moderate side-effects were experienced by only two patients. CONCLUSION: Midday bismuth subcitrate based twice a day quadruple therapy was an excellent salvage therapy. BID midday quadruple regimen should be considered as the therapy of choice.

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Aliment Pharmacol Ther. 2003 Jul 15;18(2):223-9.
What is the long-term outcome of the different subgroups of functional dyspepsia?
Heikkinen M, Farkkila M.
Department of Medicine, Unit of Gastroenterology, Kuopio University Hospital, Finland. markku.heikkinen@kuh.fi

BACKGROUND: Functional dyspepsia is often a long-lasting disorder that accounts for substantial healthcare costs. It has been classified into subgroups assuming that it can guide management of dyspepsia. AIM: To evaluate the clinical significance of subgrouping functional dyspepsia in a long-term perspective study. METHODS: Consecutive patients with dyspepsia identified by general practitioners were investigated. Those patients with functional dyspepsia (n=201) were enrolled in this study. Initially, patients were divided into five subgroups (ulcer-like, dysmotility-like, reflux-like, unspecified, and irritable bowel syndrome-like). Patients' medical histories were reviewed after 6-7 years, and the number and outcome of repeated investigations were analysed. At the end of follow-up, patients filled in a questionnaire similar to that at baseline, and were invited for gastroscopy. RESULTS: Only 2% of patients developed peptic ulcer during follow-up, none of them were in the ulcer-like subgroup. When referrals to hospital and examinations during follow-up were registered, no statistically significant differences existed between subgroups. Patients with reflux-like dyspepsia made fewer revisits than others (P=0.02), but had used antidyspepsia drugs during the previous year more often (P=0.036). Stability of the subgroups over time was poor. CONCLUSIONS: Functional dyspepsia is a long-lasting disorder with a very good prognosis. Subgroups of functional dyspepsia play only a minor role in prediction of the long-term outcome, and their usefulness in clinical practice is also hampered by subgroup instability over time.

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Helicobacter. 2003;8 Suppl 1:36-43.
Helicobacter pylori and nonmalignant diseases.
Isakov V, Malfertheiner P.
Department of Gastroenterology, Moscow Regional Research Clinical Institute (MONIKI), Moscow, Russia. Vassili.Isakov@rambler.ru

Eradication of Helicobacter pylori has lead to a significant decrease in the prevalence of peptic ulcer disease world-wide. Despite the fact that H. pylori eradication is the only way to cure peptic ulcer disease, a substantial number of patients still need antisecretory agents to be symptoms-free after eradication. During the past year several randomized controlled trials on H. pylori eradication in patients taking NSAIDs have been published but contradictory results have been obtained. In certain parts of the world, NSAIDs are becoming the main cause of peptic ulcer disease complications such as bleeding or perforation. Some patients with nonulcer dyspepsia do benefit from eradication of H. pylori as was shown in several studies. Long-term trials with cost/efficacy analysis are still needed to demonstrate the benefit of H. pylori eradication over acid inhibition in this group of patients. H. pylori prevalence is lower in patients with gastro-esophageal reflux disease, but according to recent systematic reviews it varies geographically. There are more data now to show that eradication of H. pylori in duodenal ulcer patients does not increase the incidence of GERD. The 'test and treat' strategy for patients with uninvestigated dyspepsia was strongly supported by both meta-analysis and the results of recent randomized controlled trials. Even in developed countries where the prevalence of H. pylori decreases, this strategy allows resolution of symptoms in a larger number of patients with dyspepsia compared to empirical treatment with proton pump inhibitors and reduces the endoscopic workload.

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Aliment Pharmacol Ther. 2003 Jul 1;18(1):117-24.
Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?
Bolling-Sternevald E, Lauritsen K, Talley NJ, Junghard O, Glise H.
Department of Biomedicine and Surgery, Linkoping, Sweden. elisabeth.bolling-sternevald@astrazeneca.com

BACKGROUND: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown. METHODS: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo-controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self-administered questionnaires for the assessment of symptoms and health-related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis. RESULTS: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome. CONCLUSIONS: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.

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Gastrointest Endosc. 2003 Jul;58(1):9-13.
Low yield of endoscopy in patients with persistent dyspepsia taking proton pump inhibitors.
Smith T, Verzola E, Mertz H.
Vanderbilt University, Department of Medicine, Division of Gastroenterology, Nashville, Tennessee 37232, USA.

BACKGROUND: Options for the evaluation of dyspepsia include a Helicobacter pylori test-and-treat strategy, empiric acid suppression, and initial endoscopy. The aim of this study was to determine the yield of endoscopy in patients in whom empiric therapy is unsuccessful compared with patients who received no empiric therapy and to identify factors associated with endoscopic findings. METHODS: A total of 100 patients with dyspepsia referred for endoscopy completed a questionnaire that included a query concerning response to therapy. EGD findings were compared in patients taking an H2-receptor antagonist, patients taking a proton pump inhibitor, and those not receiving empiric therapy. RESULTS: There were fewer endoscopic findings in patients being treated with a proton pump inhibitor compared with those taking an H2-receptor antagonist or those not receiving therapy (p < 0.01). Fewer proton pump inhibitor recipients had esophagitis or ulcer compared with patients in the no therapy group. Lack of symptom relief (<20%) by acid suppression was highly associated with a normal endoscopy (17/17). CONCLUSIONS: Patients with persistent dyspepsia being treated with a proton pump inhibitor have fewer endoscopic abnormalities compared with patients with dyspepsia taking an H2-receptor antagonist and those receiving no therapy. For patients with partial symptom relief, proton pump inhibitor therapy may mask endoscopic findings, particularly esophagitis. Interruption of proton pump inhibitors before endoscopy may increase diagnostic yield. Endoscopy is unlikely to yield a positive finding in patients who experience no symptom relief while taking a proton pump inhibitor or H2-receptor antagonist.

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Arch Intern Med. 2003 Jul 14;163(13):1606-12.
Approach to treatment of dyspepsia in primary care: a randomized trial comparing "test-and-treat" with prompt endoscopy.
Arents NL, Thijs JC, van Zwet AA, Oudkerk Pool M, Gotz JM, van de Werf GT, Reenders K, Sluiter WJ, Kleibeuker JH.
Regional Public Health Laboratory, Groningen/Drenthe, The Netherlands.

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.

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Gastroenterol Clin North Am. 2003 Jun;32(2):577-99.
Functional dyspepsia: evaluation and treatment.
Simren M, Tack J.
Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Herestraat 49, B-3000, Leuven, Belgium.

Functional dyspepsia is one of the most common disorders seen in general practice and by gastroenterologists. New concepts regarding the pathophysiology and its role for the symptom pattern have emerged during the last few years. This is of importance for development of new treatment alternatives in the near future. At the moment, however, empirical treatment with acid-suppressive agents and prokinetics is the recommended therapeutic approach in the management of these patients, despite limited efficacy. Identification and treatment of H pylori infection has been recommended for uninvestigated dyspepsia, because it may cure underlying peptic ulcer disease, but is unlikely to provide symptomatic benefit to patients with functional dyspepsia. Refractory patients may respond to antidepressants or to psychologic treatments, but proof of efficacy is limited. New and more effective approaches are badly needed for functional dyspepsia.

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J Indian Med Assoc. 2003 Jun;101(6):387-8.
Efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia.
Shenoy KT, Veenasree, Leena KB.
Department of Gastroenterology, Medical College, Thiruvananthapuram.

To document the clinical efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia an open-label, non-comparative study, was undertaken at the Medical College, Thiruvananthapuram, among patients with endoscopically confirmed diagnosis of non-ulcer dyspepsia or chronic gastritis. Itopride hydrochloride 50 mg (1 tablet) thrice a day for 2 weeks was administered among them. Relief of symptoms at the end of two weeks treatment, assessed as marked/complete, moderate, slight, none or worse; QT interval on ECG; adverse events; haemogram; serum chemistry for hepatic and renal functions. None had QT prolongation on ECG. At the end of 2 weeks' treatment, moderate to complete relief of symptoms was reported by 22 patients (73%), whereas 5 (17%) reproted slight improvement, and 3 (10%) reported no improvement. Clinical tolerability was excellent in 28 patients (93%) and good in 2 (7%). None of the patients had any prolongation of QT on ECG, nor did any patient show any abnormality in haemogram or serum chemistry during the treatment.

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Clin Neuropharmacol. 2003 May-Jun;26(3):112-4.
Effectiveness of Gorei-san (TJ-17) for treatment of SSRI-induced nausea and dyspepsia: preliminary observations.
Yamada K, Yagi G, Kanba S.
Departments of Neuropsychiatry and Clinical Ethics, University of Yamanashi, Faculty of Medicine, Yamanashi, Japan. yamadak@yamanashi.ac.jp

Selective serotonin reuptake inhibitors (SSRIs) are apt to cause gastrointestinal adverse events such as nausea and dyspepsia. Gorei-san (TJ-17), which is composed of five herbs (Alismatis rhizoma, Atractylodis lanceae rhizoma, Polyporus, Hoelen, and Cinnamomi cortex), is a Japanese herbal medicine that has been used to treat nausea, dry mouth, edema, headache, and dizziness. The authors investigated the efficacy of TJ-17 for patients who experienced nausea or dyspepsia induced by SSRIs. Twenty outpatients who experienced nausea or dyspepsia induced by SSRIs were recruited for the study. Seventeen patients were female, three were male, and patient age ranged from 21 to 74 years (49.8 +/- 17.0 years). TJ-17 was added to the previous regimen. Nausea and dyspepsia disappeared completely in nine patients, decreased in four patients, decreased slightly in two patients, and did not change in five patients. No adverse events were associated with the addition of TJ-17 in any patient.

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BMJ. 2003 May 24;326(7399):1118.
Empirical prescribing for dyspepsia: randomised controlled trial of test and treat versus
omeprazole treatment.
Manes G, Menchise A, de Nucci C, Balzano A.
Department of Gastroenterology, Cardarelli Hospital, Via Solimena 101, 80129 Naples, Italy. gimanes@tin.it

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.

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Hepatogastroenterology. 2003 Jan-Feb;50(49):278-83.
Effect of fluoxetine on symptoms and gastric dysrhythmia in patients with functional dyspepsia.
Wu CY, Chou LT, Chen HP, Chang CS, Wong PG, Chen GH.
Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, 160 Section 3, Taichung-Kang Road, Taichung, 407, Taiwan. chun@vghtc.vghtc.gov.tw

BACKGROUND/AIMS: Although antidepressants have been used for decades in treating patients with functional abdominal syndromes, how they influence gastrointestinal motility remains unclear. We aimed to assess the role of depression in functional dyspepsia, and the effect of antidepressants on the functional dyspepsia patients' symptoms and gastric myoelectrical activity. METHODOLOGY: We conducted an open clinical trial with 40 functional dyspepsia patients. Zung self-rating depression scale was used in evaluating the patients' depression. Cutaneous electrogastrography and evaluation of upper gastrointestinal symptoms were performed before and after administration of a one-month course of fluoxetine. RESULTS: In the baseline study, the depressed functional dyspepsia patients had higher symptom scores than non-depressed patients (P < 0.05). The depressed functional dyspepsia patients had higher percentages of tachygastria than healthy controls (P < 0.05), but the electrogastrography parameters of depressed and non-depressed functional dyspepsia patients were not different. After one-month fluoxetine treatment, the symptom scores improved significantly in the depressed functional dyspepsia patients (P < 0.05), but not in the non-depressed patients. Electrogastrography did not improve in either group. CONCLUSIONS: Depressive functional dyspepsia patients had higher symptom scores and responded well to fluoxetine treatment. However, electrogastrography did not improve after the treatment. These findings suggest that depression is significant in the presentation of functional dyspepsia symptoms, but not correlated with gastric myoelectrical activity.

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Adv Ther. 2003 Jan-Feb;20(1):43-9.
Efficacy of a herbal preparation in patients with functional dyspepsia: a meta-analysis of double-blind, randomized, clinical trials.
Gundermann KJ, Godehardt E, Ulbrich M.
Department of Pharmacology and Toxicology, Pomeranian Medical Academy, Szczecin, Poland.

A meta-analysis was performed of double-blind, randomized clinical studies that evaluated the efficacy of the herbal preparation Iberogast in patients with functional dyspepsia. All studies had the same duration and used the same dosage of active treatment and the same primary outcome measure, a dyspepsia-specific gastrointestinal symptom score. Of the 592 trial participants, 196 were treated with Iberogast and 192 with placebo or cisapride (positive control). The individual studies all showed a substantial improvement of symptoms with Iberogast but varying results regarding its statistically significant superiority to placebo. The meta-analysis of all studies, however, demonstrated a clear, highly significant overall therapeutic effect of Iberogast in the treatment of functional dyspepsia. Tolerability of the preparation was excellent.

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Rev Gastroenterol Disord. 2003 Winter;3(1):25-30.
Update on the role of drug therapy in non-ulcer dyspepsia.
Talley NJ.
Department of Medicine, University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia.

Non-ulcer dyspepsia is common and is often confused with other diagnoses. It remains a condition identified by exclusion, and continues to be a challenge to manage. Currently, only a limited number of pharmacological options are available. Antacids are no more effective than placebo in treating nonulcer dyspepsia. H2-receptor antagonists appear to be superior to placebo in efficacy, but many of the studies suggesting this finding have had a suboptimal study design. Proton pump inhibitors have been shown to be superior to placebo, although questions remain as to whether the only subgroup that responds is comprised of patients with unrecognized gastroesophageal reflux disease. Studies have found that prokinetic agents are superior to placebo, but currently only a very limited number of agents within this class can be prescribed in the United States. Sparse data support the role of metoclopramide and its side effects limit its use even further. The eradication of Helicobacter pylori has a small but positive therapeutic benefit in non-ulcer dyspepsia, and can be considered in those confirmed to be infected. Sucralfate is unlikely to be effective, and misoprostol is ineffective. Bismuth alone is probably not efficacious. Tricyclic antidepressants may have a therapeutic role, but this is not firmly established and this class of medication should be reserved for resistant cases. Emerging therapies include drugs that relax the gastric fundus, such as buspirone or sumatriptan, and the new prokinetic tegaserod. Psychological therapies may play a role but studies of these therapies are limited. Therapy for non-ulcer dyspepsia remains challenging and is usually empiric; it will remain so until the mechanisms that induce symptoms of dyspepsia are better understood.

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Aliment Pharmacol Ther. 2003 May 15;17(10):1215-27.
Systematic review: Antacids, H2-receptor antagonists, prokinetics, bismuth and sucralfate therapy
for non-ulcer dyspepsia.
Moayyedi P, Soo S, Deeks J, Forman D, Harris A, Innes M, Delaney B.
Gastroenterology Unit, City Hospital NHS Trust, Birmingham, UK. p.moayyedi@bham.ac.uk

BACKGROUND: Evidence for the effectiveness of antacids, histamine-2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non-ulcer dyspepsia is conflicting. AIM: To conduct a systematic review evaluating these therapies in non-ulcer dyspepsia. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse. RESULTS: Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27-63%] and histamine-2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7-35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, - 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine-2 receptor antagonist results could be due to publication bias. CONCLUSIONS: The meta-analyses suggest that histamine-2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity-related issues.

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Gastroenterol Clin Biol. 2003 Mar;27(3 Pt 2):432-9.
[Should we take into account Helicobacter pylori infection in a patient with dyspeptic symptoms?]
[Article in French]
Jian R, Coffin B.
Service d'Hepato-Gastroenterologie, Hopital Europeen Georges-Pompidou, 75015 Paris. raymond.jian@egp.ap-hop-paris.fr

Dyspepsia is a common disorder that presents many clinical dilemmas in patient management despite progress accomplished in the treatment of acid related diseases with proton pomp inhibitors (PPI) and of ulcer disease with eradication of Helicobacter pylori (Hp) infection. Traditionally, uninvestigated patients presenting with dyspeptic symptoms are subjected to prompt endoscopy. This policy is still required in patients older than 45 years or with risk factors of esophageal and gastric cancer. The present review of the literature suggests that in younger patients with no alarming features, a strategy taking into account Hp infection is safe and cost-effective. The best policy consists in an Hp breath test followed by eradication in Hp+ patients. In Hp- patients, empirical treatment with PPI seems the most efficient strategy. In both cases, endoscopy is required when symptoms persist or rapidly recur. In France, where endoscopy is cheap and its accessibly optimal, prompt endoscopy could still be preferable. In absence of well-conducted controlled studies in our country, it is thus not possible to formally recommend the test-and-treat strategy in the management of uninvestigated dyspepsia. In patients with functional dyspepsia (no lesions detected by endoscopy), review of the literature suggests that the therapeutic benefit of eradicating Hp is, if it exists, of little value. Should we eradicate Hp systematically or only in patients mostly concerned by such benefit (ulcer-like and refractory dyspepsia)? The answer will come from the place of eradication of Hp in the general population for prevention of some gastric cancers.

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Gut. 2003 Jan;52(1):40-6.
Treatment of Helicobacter pylori in functional dyspepsia resistant to conventional management: a double blind randomised trial with a six month follow up.
Koelz HR, Arnold R, Stolte M, Fischer M, Blum AL; FROSCH Study Group.
Division of Gastroenterology, Department of Medicine, Triemli Hospital, Zurich, Switzerland. hrkoelz@hin.ch

BACKGROUND: Previous studies on the treatment of Helicobacter pylori infection in functional dyspepsia have shown little, if any, effect on dyspeptic symptoms. However, whether such treatment might be of benefit in patients resistant to acid inhibitors has not been formally tested. AIM: The present study investigated the effect of H pylori treatment in patients with functional dyspepsia resistant to conventional treatment. PATIENTS: A total of 181 H pylori positive patients with chronic functional dyspepsia who had not responded to a one week antacid run-in and two week double blind antisecretory or placebo treatment were included. METHODS: Patients were randomised to two weeks of treatment with omeprazole 40 mg twice daily combined with amoxicillin 1 g twice daily or omeprazole 20 mg once daily alone. The primary outcome variable ("response") was defined as no need for further therapy or investigations for dyspeptic symptoms 4-6 months after treatment. RESULTS: H pylori infection was healed in 10% of patients after omeprazole and in 52% after omeprazole plus amoxicillin. The respective "response" rates were 66% and 62% (NS). H pylori treatment and cure of H pylori infection had no effect on complete resolution of all dyspeptic symptoms, individual symptoms, or various aspects of quality of life. CONCLUSION: In functional dyspepsia, H pylori treatment and cure of H pylori are no more effective for symptoms over six months than short term acid inhibition. These results do not support treatment of H pylori in functional dyspepsia.

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Cochrane Database Syst Rev. 2003;(2):CD001961.
Initial management strategies for dyspepsia (Cochrane Review).
Delaney BC, Moayyedi P, Forman D.
Department of Primary Care and General Practice, Primary Care and Clinical Sciences Building, The University of Birmingham, Edgbaston, Birmingham, West Midlands, UK, B15 2TT. b.c.delaney@bham.ac.uk

BACKGROUND: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn. OBJECTIVES: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) initial pharmacological therapy (including endoscopy for treatment failures) (b) early endoscopy (c) testing for Helicobacter pylori and endoscope only those positive (d) H.pylori eradication therapy with or without prior testing. SEARCH STRATEGY: Trials were located through electronic searches and extensive contact with trialists. SELECTION CRITERIA: All randomised controlled trials of dyspeptic patients presenting in primary care. DATA COLLECTION AND ANALYSIS: Data was collected on dyspeptic symptoms, quality of life and use of resources. MAIN RESULTS: Twenty papers reporting 23 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (two trials) and H2 receptor antagonists (three trials), early endoscopy with initial acid suppression (five trials), H.pylori 'test and scope' v usual management (three trials), H.pylori test and treat v. endoscopy (four trials), and test and treat v. acid suppression alone in H.pylori positive patients (two trials), were pooled. PPIs were significantly more effective than both H2RAs and antacids. Relative risks (RR) and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with initial prescribing (RR 0.89 (0.77-1.02). H.pylori test and endoscopy increases costs in primary care, but does not improve symptoms. H.pylori test and eradicate may be as effective as endoscopy- based management and reduces costs, by decreasing the proportion of patients that are endoscoped. 'Test and treat' may be more effective than acid suppression alone, RR 0.59 (0.42-0.83). REVIEWER'S CONCLUSIONS: PPIs are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is uncertain. Early investigation by endoscopy or H.pylori testing may benefit some patients with dyspepsia. The review will be updated in 2004 with an individual patient data meta-analysis of the economic data, and a subgroup analysis by age and predominant dyspeptic symptom.

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Aliment Pharmacol Ther. 2003 Jun 1;17(11):1381-7.
One-week triple therapy with esomeprazole, clarithromycin and metronidazole provides effective eradication of Helicobacter pylori infection.
Veldhuyzen Van Zanten S, Machado S, Lee J.
Division of Gastroenterology, Department of Medicine, Dalhousie University, Halifax, Canada; AstraZeneca Canada Inc., Mississauga, Ontario, Canada.

AIM: To compare the eradication rates of treatment with esomeprazole, metronidazole and clarithromycin (EMC) vs. omeprazole, metronidazole and clarithromycin (OMC), given for 7 days. OMC treatment was followed by 3 weeks of treatment with 20 mg omeprazole alone; the EMC group received placebo. METHODS: A randomized, double-blind, controlled study was conducted in 36 Canadian centres. Patients had a minimum 3-month history of dyspepsia, with or without a previous history of peptic ulcer disease, and were Helicobacter pylori positive by urea breath test. The eradication of H. pylori was determined by two negative breath tests performed at least 4 and 8 weeks following the completion of treatment. RESULTS: The intention-to-treat and per protocol populations consisted of 379 and 339 patients, respectively. The success rates of EMC/placebo were 76% (144/190) by intention-to-treat and 80% (138/172) by per protocol analysis; for OMC/omeprazole, the rates were 72% (137/189) and 75% (125/167), respectively. The difference between the two treatment groups was not significant. Treatment was well tolerated. CONCLUSIONS: A 7-day regimen of esomeprazole, metronidazole and clarithromycin is effective and well tolerated for the eradication of H. pylori infection.

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Dig Liver Dis. 2003 Mar;35(3):157-64.
Dyspepsia and Helicobacter pylori infection: a prospective multicentre observational study.
Perri F, Festa V, Grossi E, Garbagna N, Leandro G, Andriulli A; "NUD-LOOK" Study Group.
Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, I.R.C.C.S., San Giovanni Rotondo 71013, Italy. perrisgr@tin.it

OBJECTIVES: Dyspepsia still represents an unsolved clinical enigma. AIM: The aims of this study were to determine whether symptoms and Helicobacter pylori infection are predictors of organic disease in uninvestigated dyspepsia, and if H. pylori eradication improves symptoms in functional dyspepsia. METHODS: An observational study was performed on outpatients with uninvestigated dyspepsia. Symptoms were scored and H. pylori status determined. Patients with functional dyspepsia and H. pylori infection were randomly given either a standard eradicating treatment or a 1-month course of empirical treatment. The latter was also given to functional dyspeptic patients without infection. Symptoms were re-assessed in functional dyspeptic patients at 2- and 6-month follow-up visits. Patients receiving eradicating treatment were re-tested for H. pylori at the 2 month visit. RESULTS: A total of 860 patients were studied and 605 (70.3%) were affected by functional dyspepsia. H. pylori infection was diagnosed in 71.8% of patients with organic dyspepsia and in 65.0% with functional dyspepsia (p=0.053). Male sex, anaemia, smoking habit, age over 45 years, and severe epigastric pain, but not H. pylori infection, were independent predictors of organic disease. Symptoms significantly improved in most functional dyspeptic patients regardless of their H. pylori status and type of treatment. CONCLUSION: H. pylori infection is not a strong predictor of organic disease in uninvestigated dyspepsia. H. pylori eradication is not essential to improve symptoms in functional dyspepsia.

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Drugs. 2003;63(9):869-92.
New developments in the treatment of functional dyspepsia.
Stanghellini V, De Ponti F, De Giorgio R, Barbara G, Tosetti C, Corinaldesi R.
Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy.

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria.The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia.Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT(4) receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT(4) receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT(3) receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK(1)/NK(2)) and cholecystokinin (CCK)(1) receptors.

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Scand J Gastroenterol. 2002 Dec;37(12):1395-402.
Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial.
Bolling-Sternevald E, Lauritsen K, Aalykke C, Havelund T, Knudsen T, Unge P, Ekstrom P, Jaup B, Norrby A, Stubberod A, Melen K, Carlsson R, Jerndal P, Junghard O, Glise H.
Dept. of Biomedicine, Linkoping, Sweden. elisabeth.bolling-sternevald@astrazeneca.com

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.

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Am J Gastroenterol. 2002 Dec;97(12):3045-51.
A double blind, randomized, placebo-controlled trial of proton pump inhibitor therapy in patients with uninvestigated dyspepsia.
Rabeneck L, Souchek J, Wristers K, Menke T, Ambriz E, Huang I, Wray N.
Department of Veterans Affairs Health Services Research and Development Center of Excellence and the Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

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.

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Pharmacol Res. 2002 Dec;46(6):525-31.
Effects of a bicarbonate-alkaline mineral water on gastric functions and functional dyspepsia: a preclinical and clinical study.
Bertoni M, Olivieri F, manghetti M, Boccolini E, Bellomini MG, Blandizzi C, Bonino F, Del Tacca M.
Gastroenterology Unit, University Hospital of Pisa, Pisa, Italy.

The present study was performed in order to evaluate: (1) the influence of a bicarbonate-alkaline mineral water (Uliveto) on digestive symptoms in patients with functional dyspepsia; (2) the effects of Uliveto on preclinical models of gastric functions. Selected patients complained of dyspeptic symptoms in the absence of digestive lesions or Helicobacter pylori infection within the previous 3 months. They were treated with Uliveto water (1.5 l day(-1)) for 30 days. Frequency and severity of symptoms were assessed at baseline and day 30 by a score system. Preclinical experiments were carried out on rats, allowed to drink Uliveto or oligomineral water for 30 days. Animals then underwent pylorus ligation to evaluate gastric secretion of acid, pepsinogen, and mucus. In separate experiments, gastric emptying was assessed. Crenotherapy was associated with a relief of epigastric pain, retrosternal pyrosis, postprandial fullness and gastric distention. At preclinical level, Uliveto water increased acid and pepsinogen secretions as well as gastric emptying, without changes in bound mucus. The enhancing actions of Uliveto on gastric secretions and emptying were prevented by L-365,260, an antagonist of gastrin/CCK-2 receptors. These findings indicate that a regular intake of Uliveto favors an improvement of dyspeptic symptoms. The preclinical study suggests that the clinical actions of Uliveto water depend mainly on its ability to enhance gastric motor and secretory functions.

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Dig Dis Sci. 2002 Nov;47(11):2591-5.
5-HT1-receptor agonist sumatriptan modifies gastric size after 500 ml of water in dyspeptic patients and normal subjects.
Malatesta MG, Fascetti E, Ciccaglione AF, Cappello G, Grossi L, Ferri A, Marzio L.
School of Gastroenterology, G. d'Annunzio University, Pescara, Italy.

Sumatriptan, a 5-HT1-receptor agonist has been shown to delay gastric emptying of liquids and solids in humans. However, no data are available of the effect of sumatriptan on gastric adaptation after distension with liquids and on symptoms induced by gastric distension. In 23 normal subjects and 30 dyspeptic patients with normal upper gastrointestinal endoscopy and real-time ultrasonography, the transverse gastric proximal and distal area and sagittal axis of the proximal stomach were determined by real-time ultrasonography and computed tomography after 500 ml of water. The area was determined by real-time ultrasonography and computed tomography twice at times 48 hr apart. Thirty minutes before real-time ultrasonography, placebo or sumatriptam were give subcutaneously in a double-blind fashion. Epigastric pain, bloating, heartburn, and nausea were also monitored through an intensity score from zero to 10 performed during the test. In six dyspeptic patients, the gastric distension was performed also with real-time ultrasonography and computed tomography after placebo and hyoscine butyl-bromide, a quaternary anticholinergic agent. Real-time ultrasonography and computed tomography demonstrated that after sumatriptan there is a reduction in proximal and distal transverse area and an increase in the sagittal axis of the proximal stomach. Hyoscine butyl-bromide increased all gastric measurements. Among the symptoms evaluated, only nausea was significantly reduced by sumatriptan (P < 0.01). Sumatriptan modifies gastric size, with a reduction in the transverse section and an increase of the sagittal axis of the proximal stomach and improves the nausea induced by gastric distension in dyspeptic patients.

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Curr Gastroenterol Rep. 2002 Dec;4(6):455-8.
Nonulcer dyspepsia.
Vakil N.
Division of Gastroenterology, Department of Medicine, University of Wisconsin Medical School, Aurora Sinai Medical Center, Milwaukee, WI 53233, USA. nvakil@wisc.edu

Nonulcer dyspepsia is a common condition in clinical practice. It is a heterogeneous disorder, and no single therapeutic agent is effective in all patients. The treatment of nonulcer dyspepsia is still dissatisfactory. Eradication of Helicobacter pylori organisms has a limited role and little effect. Antisecretory therapy has a modest effect in alleviating symptoms. Prokinetic agents may be effective, but selection bias in the trials performed to date may exaggerate their benefit. Partial 5-HT(4) agonists stimulate gastric emptying and may also affect gastric accommodation. They are promising but need further study. Data are limited on 5-HT(3) antagonists and hypnotherapy. New treatment approaches are necessary for this common and often chronic condition.

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Digestion. 2002;66(2):92-8.
Effect of Helicobacter pylori eradication or of ranitidine plus metoclopramide on Helicobacter pylori-positive functional dyspepsia. A randomized, controlled follow-up study.
Alizadeh-Naeeni M, Saberi-Firoozi M, Pourkhajeh A, Taheri H, Malekzadeh R, Derakhshan MH, Massarrat S; Iranian Functional Dyspepsia Study Group.
Department of Internal Medicine, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

BACKGROUND: A definitive treatment for functional dyspepsia (FD), and the role of Helicobacter pylori eradication on the course of this disease are controversial. AIM: To investigate the effect of a combination of acid-suppressing and prokinetic drugs or eradication therapy on the course of H. pylori-positive FD. METHOD: A total of 157 patients with endoscopically-proven H. pylori-positive FD and no response to 4 weeks of antacid therapy were randomly divided into 2 groups. 84 were placed on bismuth subnitrate plus metronidazole and amoxicillin (group A) and 73 received ranitidine and metoclopramide for 4 weeks (group B). The severity of symptoms (7 items) were assessed on a 6-point categorical scale. Group B patients who failed to respond to their medication underwent eradication therapy after 3 months. All patients were followed and assessed for 9 months after the end of therapy by the same clinicians who initiated the therapy. RESULTS: At the end of the medication period, symptom's score decreased significantly, and to the same extent. At 3-month follow-up moderate or complete response was achieved in 27.4% (group A) and 19.2% (group B) by intention-to-treat analysis. 34 patients of group B, not responding to treatment, underwent eradication therapy and followed as group A. Eradication of H. pylori was successful in 60 of 110 controlled patients (54%). After 9-month follow-up, complete or moderate response was observed in only 30% of 60 patients in whom H. pylori had been eradicated (intention-to-treat analysis), compared to 38% in 50 noneradicated cases (p > 0.05, 95% CI: 19-43 vs. 24-52). CONCLUSION: Eradication therapy with bismuth compound is effective as ranitidine plus metoclopramide in a subgroup of patients with FD not responding to antacid therapy. There is no difference in improvement between patients cured or not cured from H. pylori infection. This suggests that bismuth compounds were effective in FD when used in the eradication regimen. Combination therapy with acid-suppressing drugs plus prokinetic and bismuth seems to hold promise for FD. Copyright 2002 S. Karger AG, Basel

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Forsch Komplementarmed Klass Naturheilkd. 2002 Oct;9(5):277-82.
[Efficacy of tea blends in the treatment of dyspeptic disorders--an application observation]
[Article in German]
Iten F, Meier B, Saller R.
Abteilung fur Naturheilkunde, Universitatsspital Zurich, Switzerland.

BACKGROUND: Medicinal teas present one of the oldest galenic preparations of herbal remedies. Their use is primarily determined by tradition and empirics. One of their traditional domains are gastrointestinal disorders, which belong to the most frequent wellness disorders. While the effectiveness and compatibility of essential oils, modern drug extracts, and alcoholic extracts from bitters and etheric-oil drugs in the treatment of dyspeptic disorders have been documented in placebo-controlled clinical trials, little attention has so far been given to aqueous extracts from bitters and etheric-oil drugs, which are equivalent to the standard method of preparing herbal teas. PURPOSE: The presented application observation in clinical practice tried to give evidence for effectiveness and tolerability of medicinal teas in the treatment of dyspeptic disorders and to quantify their extent. MATERIAL AND METHODS: We collected information about effectiveness, compatibility, and side effects of herbal teas from 89 patients (w = 56; m = 33) suffering from dyspeptic disorders. The data were reported with a questionnaire that was sent to physicians and pharmacists experienced in phytotherapy. RESULTS: It could be shown that complaints in patients with primary dyspeptic symptoms (n = 79) decreased by an average of 74%. Final overall assessment revealed that the physicians as well as the patients estimated an effectiveness of 2.9 points as good (3 = good). Compatibility was considered as good to very good (4 = very good), with an average rating of 3.3 points. Two patients stopped therapy because of an extreme aversion to the bitter taste of the teas. No other serious side effects were reported. CONCLUSION: The herbal teas can be considered effective, very well tolerable and to a large extent free from serious side effects. However, due to the limited observation time, no final conclusion could be given concerning long-term compatibility. Copyright 2002 S. Karger GmbH, Freiburg

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Can J Gastroenterol. 2002 Sep;16(9):635-41.
Etiology of dyspepsia: implications for empirical therapy.
Hunt RH, Fallone C, Veldhuyzen Van Zanten S, Sherman P, Flook N, Smaill F, Thomson AB; Canadian Helicobacter pylori Study Group.
Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Canada.

Dyspepsia describes a symptom complex thought to arise in the upper gastrointestinal tract and includes, in addition to epigastric pain or discomfort, symptoms such as heartburn, acid regurgitation, excessive burping or belching, a feeling of slow digestion, early satiety, nausea and bloating. Based on the evidence that heartburn cannot be reliably distinguished from other dyspeptic symptoms, the Rome definition appears to be too narrow and restrictive. It is particularly ill suited to the management of uninvestigated dyspepsia at the level of primary care. In patients presenting with uninvestigated dyspepsia, a symptom benefit is associated with a 'test and treat' approach for Helicobacter pylori infection. A substantial proportion of those who do not benefit prove to have esophagitis on endoscopy. In those with functional dyspepsia, the benefits of H pylori eradication, if any, appear to be modest. Hence, a 'symptom and treat' acid-suppression trial with proton pump inhibitors, and a 'test and treat' strategy for H pylori are two acceptable empirical therapies for patients with univestigated dyspepsia.

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Eur J Gastroenterol Hepatol. 2002 Sep;14(9):991-9.
Effects of carbonated water on functional dyspepsia and constipation.
Cuomo R, Grasso R, Sarnelli G, Capuano G, Nicolai E, Nardone G, Pomponi D, Budillon G, Ierardi E.
Epatogastroenterologia, Dipartimento di Medicina Clinica e Sperimentale, Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131 Naples, Italy. r.cuomo@unina.it

OBJECTIVE: The effects of carbonated beverages on the gastrointestinal tract have been poorly investigated. Therefore, this study aims to assess the effect of carbonated water intake in patients with functional dyspepsia and constipation. METHODS: Twenty-one patients with dyspepsia and secondary constipation were randomized into two groups in a double-blind fashion. One group (10 subjects) drank carbonated water and the other (11 subjects) tap water for almost 15 days. Patients were evaluated for dyspepsia and constipation scores, and underwent a satiety test by a liquid meal, radionuclide gastric emptying, sonographic gallbladder emptying and colonic transit time, using radio-opaque markers. RESULTS: The dyspepsia score was significantly reduced with carbonated water (before = 7.9 +/- 2.8 after = 5.4 +/- 1.7; 0.05) and remained unmodified after tap water (9.7 +/- 5.3 9.9 +/- 4.0). The constipation score also decreased significantly ( 0.05) after carbonated water (16.0 +/- 3.9 12.1 +/- 4.4; 0.05) and was not significantly different with tap water (14.7 +/- 5.1 13.7 +/- 4.7). Satiety was significantly reduced with carbonated water (before = 447 +/- 146 kcal after = 590 +/- 245; 0.01). Gallbladder emptying (delta percent contraction) was significantly improved only with carbonated water (39.9 +/- 16.1% 53.6 +/- 16.7%; 0.01). CONCLUSION: In patients complaining of functional dyspepsia and constipation, carbonated water decreases satiety and improves dyspepsia, constipation and gallbladder emptying.

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Aliment Pharmacol Ther. 2002 Oct;16(10):1689-99.
Systematic review: herbal medicinal products for non-ulcer dyspepsia.
Thompson Coon J, Ernst E.
Department of Complementary Medicine, School of Sport and Health Sciences, University of Exeter, UK. J.Thompson-Coon@exeter.ac.uk

BACKGROUND: Non-ulcer dyspepsia is predominantly a self-managed condition, although it accounts for a significant number of general practitioner consultations and hospital referrals. Herbal medicinal products are often used for the relief of dyspeptic symptoms. AIMS: : To critically assess the evidence for and against herbal medicinal products for the treatment of non-ulcer dyspepsia. METHODS: Systematic searches were performed in six electronic databases and the reference lists located were checked for further relevant publications. No language restrictions were imposed. Experts in the field and manufacturers of identified herbal extracts were also contacted. All randomized clinical trials of herbal medicinal products administered as supplements to human subjects were included. RESULTS: Seventeen randomized clinical trials were identified, nine of which involved peppermint and caraway as constituents of combination preparations. Symptoms were reduced by all treatments (60-95% of patients reported improvements in symptoms). The mechanism of any anti-dyspeptic action is difficult to define, as the causes of non-ulcer dyspepsia are unclear. There appear to be few adverse effects associated with these remedies, although, in many cases, comprehensive safety data were not available. CONCLUSIONS: There are several herbal medicinal products with anti-dyspeptic activity and encouraging safety profiles. Further research is warranted to establish their therapeutic value in the treatment of non-ulcer dyspepsia.

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Aliment Pharmacol Ther. 2002 Sep;16(9):1641-8.
A randomized placebo-controlled trial of simethicone and cisapride for the treatment of patients with functional dyspepsia.
Holtmann G, Gschossmann J, Mayr P, Talley NJ.
Division of Gastroenterology and Hepatology, University of Essen, Germany. g.holtmann@uni-essen.de

AIM: To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia. METHODS: One hundred and eighty-five patients with functional dyspepsia were randomized and treated in a double-dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of the patients' rating of 10 upper gastrointestinal symptoms (graded as absent = 0, moderate = 1, severe = 2 or very severe = 3). Outcome measures were assessed at baseline and after 2, 4 and 8 weeks of treatment (intention-to-treat). RESULTS: At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded significantly (all P values < 0.0001) better improvement of symptoms compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P = 0.0007), but the differences were not statistically significant after 4 and 8 weeks. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases, compared to 15% and 16% receiving cisapride and placebo, respectively. CONCLUSIONS: Simethicone and cisapride were significantly better than placebo for symptom control in patients with functional dyspepsia after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the prokinetic cisapride in the first 2 weeks of treatment

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Forsch Komplementarmed Klass Naturheilkd. 2002 Dec;9 Suppl 1:1-20.
[Iberogast: a modern phytotherapeutic combined herbal drug for the treatment of functional disorders of the gastrointestinal tract (dyspepsia, irritable bowel syndrome)--from phytomedicine to "evidence based phytotherapy." A systematic review]
[Article in German]
Saller R, Pfister-Hotz G, Iten F, Melzer J, Reichling J.
Abteilung Naturheilkunde, Departement Innere Medizin, Universitatsspital Zurich, Switzerland. reinhard.saller@dim.usz.ch

Iberogast is a complex herbal preparation. As a fixed drug combination (9 constituents) it is composed of a fresh plant extract of Iberis amara and of extracts of 8 other dried herbal drugs ( Chelidonii herba, Cardui mariae fructus, Melissae folium, Carvi fructus, Liquiritiae radix, Angelicae radix, Matricariae flos, Menthae piperitae folium). The pharmacological effects as well as the therapeutic effectiveness, tolerability, and toxicity of Iberogast were experimentally and clinically recorded and documented using modern investigation tools. Both the experimental as well as the clinical studies indicated a regulatory influence of Iberogast on the whole gastrointestinal tract by a special dual action. While the included extracts of the dried herbal drugs have mainly spasmolytic properties, the fresh plant extract of Iberis amara has a tonic effect on the gastrointestinal tract. Depending on the predistension of the gastric or intestinal wall, the tonic or the spasmolytic effects of Iberogast prevail. Both the fresh plant extract of Iberis amara and the combined preparation of Iberogast were found to be toxicologically safe in therapeutically effective doses. For the estimation of the clinical effectiveness a systematic review was performed (data research: January 1970 to September 2002). As shown in controlled (according GCP standard) as well as supportive and uncontrolled clinical studies, the symptoms of functional dyspepsia and of irritable bowel syndrome (one controlled study and one observational study) could be significantly reduced by these herbal preparation in comparison to placebo. Two trials comparing Iberogast with the prokinetics metoclopramide and cisapride demonstrated a comparable therapeutic effectiveness of the herbal preparation and the prokinetics in the treatment of dyspepsia. Adverse events were rare and, with respect to frequency and spectrum, partly the same as found with placebo. Another advantage of Iberogast is that it targets only the gastrointestinal tract and the enteral nervous system, but not the central nervous system. Because of its special dual action, its clinically proven effectiveness, and its good tolerability, Iberogast may be a drug of first choice in the treatment of functional gastrointestinal diseases and their corresponding symptoms.

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Phytomedicine. 2002 Dec;9(8):694-9.
Artichoke leaf extract reduces mild dyspepsia in an open study.
Marakis G, Walker AF, Middleton RW, Booth JC, Wright J, Pike DJ.
Hugh Sinclair Unit of Human Nutrition, The University of Reading, UK.

A recent post-marketing study indicated that high doses of standardised artichoke leaf extract (ALE) may reduce symptoms of dyspepsia. To substantial these findings, this study investigated the efficacy of a low-dose ALE on amelioration of dyspeptic symptoms and improvement of quality of life. The study was an open, dose-ranging postal study. Healthy patients with self-reported dyspepsia were recruited through the media. The Nepean Dyspepsia Index and the State-Trait Anxiety Inventory were completed at baseline and after 2 months of treatment with ALE, which was randomly allocated to volunteers as 320 or 640 mg daily. Of the 516 participants, 454 completed the study. In both dosage groups, compared with baseline, there was a significant reduction of all dyspeptic symptoms, with an average reduction of 40% in global dyspepsia score. However, there were no differences in the primary outcome measures between the two groups, although relief of state anxiety, a secondary outcome, was greater with the higher dosage (P = 0.03). Health-related quality of life was significantly improved in both groups compared with baseline. We conclude that ALE shows promise to ameliorate upper gastro-intestinal symptoms and improve quality of life in otherwise healthy subjects suffering from dyspepsia.

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Aliment Pharmacol Ther. 2002 Jul;16 Suppl 4:95-104.
Review article: dyspepsia: how to manage and how to treat?
Talley NJ.
Nepean Hospital, Penrith, NSW, Australia. ntalley@med.usyd.au

Recent guidelines for dyspepsia, defined as pain or discomfort centred in the upper abdomen, emphasize that in younger patients with no alarm features and not taking nonsteroidal anti-inflammatory drugs, testing for Helicobacter pylori and treatment of the infection if present is a standard of care. If H. pylori is not present, empirical management (e.g. acid suppression) is often prescribed. It is further recommended that if patients relapse or fail to respond to treatment then upper endoscopy be undertaken. However, these guidelines have become controversial for a number of reasons. Firstly, the prevalence of H. pylori infection is falling as is the incidence of peptic ulcer disease due to the infection. Idiopathic peptic ulcer disease is also being increasingly recognized. Furthermore, the cost-effectiveness of endoscoping treatment failures has been questioned, as the yield is low and patient management is usually not altered. Finally, it remains controversial whether the treatment of H. pylori infection in functional dyspepsia is of value, and two recent high quality meta-analyses have reached diametrically opposite conclusions. Alternative strategies, such as initially treating with acid suppression and then considering H. pylori infection in those who fail have been suggested, as has in low H. pylori prevalent regions the abandonment of a test-and-treat strategy. However, appropriate management trials of these alternative strategies in primary care are lacking. The management of patients with functional dyspepsia who fail initial antisecretory therapy is now difficult; prokinetics have fallen into some disrepute. Tricyclic antidepressants (at a low dose) may be useful in a subset, but adequate trials are lacking.

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Eksp Klin Gastroenterol. 2002;(2):35-6, 101.
[Inhibitors of proton pump in the treatment of non-ulcer functional dyspepsia of the reflux-like type]
[Article in Russian]
Ivanova NG.
Central Research Institute of Gastroenterology, Moscow.

The results of two treatment types of the patients with chronic gastritis and with non-ulcerative functional dyspepsia (NFD) at reflux-similar variant are represented. The patients received Omeprasol (Losec) or Rabeprasol (Pariet) accordingly 20 mg once per day in the morning, 30-60 minutes before the breakfast. The treatment course was 7 days. The investigations have shown the following: the level of acidity has decreased in all the patients treated by Rabeprasol, normal acidity is detected in the all 15 patients, the level of gastric acidity has decreased in the patients, treated by Omeprasol. However the hyperacidity was preserved in 10 from 12 patients.

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J Am Pharm Assoc (Wash). 2002 May-Jun;42(3):460-8.
Dyspepsia: initial evaluation and treatment.
Erstad BL.
Department of Pharmacy Practice & Science, College of Pharmacy, University of Arizona, Tucson 85721-0207, USA. erstad@pharmacy.arizona.edu

OBJECTIVE: To provide recommendations for the initial evaluation and management of dyspepsia. DATA SOURCES: Articles identified through a MEDLINE search for human studies published in English between 1966 and June 2001, using the primary search term dyspepsia and the secondary search terms diagnosis, complications, and treatment; textbooks with information on the diagnosis and management of gastrointestinal (GI) disorders; and bibliographies of retrieved publications and textbooks. STUDY SELECTION: Articles that focused on dyspepsia as well as factors suggestive of more complicated GI disorders that would require pharmacists to refer patients to a physician. DATA EXTRACTION: Performed by the author manually. DATA SYNTHESIS: Functional dyspepsia (i.e., upset stomach or indigestion with no identifiable lesion) is a common complaint that may be relieved by medications, including antacids, histamine2-receptor antagonists, proton pump inhibitors, and promotility agents. However, therapy should not mask important warning signs and symptoms of more complicated diseases, as that could delay both diagnosis and more definitive treatment. Peptic ulcer disease and gastroesophageal reflux disease each account for about 20% of patients presenting with dyspepsia. Gastric cancer is an important disease to consider in the differential diagnosis of dyspepsia in patients older than 45 years, especially elderly patients (65 years and older). CONCLUSION: Nonprescription medications can relieve functional dyspepsia, but pharmacists must be aware of common features of diseases that require patient referral to a physician for further evaluation.

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Gut. 2002 May;50 Suppl 4:iv63-6.
Use of antisecretory agents as a trial of therapy.
Fennerty MB.
Division of Gastroenterology, OHSU, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201-2098, USA. fennerty@OHSU.edu

Dyspepsia is a common clinical condition, and its diagnostic evaluation and treatment result in the expenditure of enormous healthcare resources each year. Studies indicate that the omeprazole test is the most sensitive and cost effective test for diagnosing gastro-oesophageal reflux disease (GORD) in patients with extra-oesophageal or more "classic" symptoms suggestive of GORD. Studies also indicate that a therapeutic trial of omeprazole in patients with dyspepsia results in greater symptom improvement and lower costs than treatment with less potent acid suppression.

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Int J Clin Pract. 2002 Mar;56(2):132-9.
An overview of the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole.
Bown RL.
Department of Medicine, Frimley Park Hospital NHS Trust, Camberley, Surrey, UK.

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion in a dose-dependent manner via inhibition of H+/K+-adenosine triphosphatase in gastric parietal cells. It also exhibits antibacterial activity against Helicobacter pylori in vitro. During almost 10 years of clinical use, lansoprazole has proved effective and well tolerated in a wide range of acid-related disorders, including gastro-oesophageal reflux disease (GORD), duodenal ulcers, gastric ulcers, non-steroidal anti-inflammatory drug-related ulcers, as well as non-ulcer dyspepsia and acid hypersecretion. It is also used, in combination with antibiotics, for H. pylori eradication. In the above indications, lansoprazole has generally proved to be superior to the histamine H2-receptor antagonists, and is at least as effective as the other currently available proton pump inhibitors. This review aims to evaluate the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole in acid-related disorders, with particular emphasis on its use in GORD and H. pylori eradication regimens.

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