Proton pump inhibitor co-therapy with nonsteroidal anti-inflammatory drugs--nice or necessary?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory, analgesic, and anti-pyretic effects, whereas low-dose aspirin (also an NSAID) is used for cardiovascular prophylaxis. The main concern limiting use of these drugs is their gastrointestinal (GI) toxicity. GI side effects include ulcers (found at endoscopy in 15%-30% of patients using NSAIDs regularly), complications such as upper GI bleeding (annual incidence of 1.0%-1.5%), and development of upper GI symptoms such as dyspepsia (occurring in up to 60% of patients taking NSAIDs). Histamine-2 receptor antagonists are not effective at preventing NSAID-induced gastric ulcers when used at standard doses, although they can decrease upper GI symptoms. Misoprostol effectively decreases NSAID-induced ulcers and GI complications but is used infrequently in the United States-perhaps because of issues of compliance (multiple daily doses) and side effects (eg, diarrhea, dyspepsia). Once-daily proton pump inhibitor (PPI) therapy also decreases the development of NSAID-associated ulcers and recurrent NSAID-related ulcer complications; it also decreases upper GI symptoms in NSAID users. In patients using aspirin, the addition of a cyclooxygenase-2-specific inhibitor appears to significantly increase GI risk to the level of a nonselective NSAID; aspirin plus a nonselective NSAID appears to increase GI risk still higher. Patients taking low-dose aspirin who have risk factors for GI complications (including concomitant nonselective NSAID therapy) should receive medical co-therapy, such as a PPI.     

Proton pump inhibitor versus prokinetic therapy in patients with functional dyspepsia: is therapeutic response predicted by Rome III subgroups?

Background  

The comparative effectiveness of proton pump inhibitor versus prokinetic therapy in relieving the symptoms of patients with functional dyspepsia remains unknown. Whether the Rome III subgroups predict therapeutic response has not been investigated.     

Helicobacter pylori “test-and-treat” strategy is not suitable for the management of patients with uninvestigated dyspepsia in Shanghai

Objective. The safety of Helicobacter pylori “test-and-treat” and “test-and-endoscopy” strategies for the management of young patients with uninvestigated dyspepsia has not been evaluated in Shanghai. Material and methods. A total of 14,101 consecutive patients with dyspepsia receiving endoscopy in our hospital from October 2002 to December 2003 were retrospectively studied. The detection rates of esophageal or gastroduodenal malignancies and alarm symptoms were investigated, and H. pylori status was assessed. Results. A total of 202 (1.4%) gastrointestinal (GI) malignancies were found, including 162 cases (1.15%) of gastric cancer, 4 of gastric lymphoma, 35 (0.25%) of esophageal cancer and 1 case of duodenal cancer. Among those patients with GI malignancies, 99 (49.0%) were infected with H. pylori and 108 (53.5%) presented with alarm symptoms. Eighteen patients (0.46%, 18/3952) under 45 years of age were diagnosed as having gastric cancer. Of these patients, 5 (27.8%) presented with alarm symptoms and 13 (72.2%) were infected with H. pylori. If the H. pylori “test-and-treat” strategy were used in dyspeptic patients under the age of 45 years without alarm symptoms in the Shanghai region, then 13 cases (72.2%) of gastric cancer would be missed. If the H. pylori “test-and-endoscopy” strategy were applied, then 3 cases (16.7%) of gastric cancer would be missed. Conclusions.H. pylori “test-and-treat” and “test-and-endoscopy” strategies are both not suitable for the management of patients with uninvestigated dyspepsia in Shanghai. For most Shanghai dyspeptic patients, prompt endoscopy should be recommended as the first-line initial management option.     

Halitosis in patients with Helicobacter pylori-positive non-ulcer dyspepsia: an indication for eradication therapy?

BACKGROUND: The aims of this study were to investigate the frequency of halitosis before and after eradication therapy and to determine whether halitosis is a valid indication for eradication therapy in patients with Helicobacter pylori (H. pylori)-positive non-ulcer dyspepsia. METHODS: Dyspepsia, related symptoms, and halitosis were investigated by way of a questionnaire. Only H. pylori-positive patients who showed no organic lesions on endoscopic examination and no atrophy histopathologically were included. A total of 148 patients fulfilled the above criteria and completed the study. Four weeks after the end of eradication treatment, the symptoms were re-evaluated and repeat endoscopy was done to check for H. pylori in the gastric mucosa. Results: H. pylori eradication was successful in 109 patients (73.6%). Prior to treatment, bloating was the most frequent symptom (74.3%), followed by diurnal pain (62.2%) and halitosis (61.5%). The most successfully resolved symptoms in the group as a whole, regardless of eradication status, were halitosis, diurnal pain, and hunger-like pain, respectively. In the patients with confirmed H. pylori eradication, the most successfully resolved symptoms were halitosis and hunger-like pain, respectively. CONCLUSION: Halitosis is a frequent, but treatable, symptom of H. pylori-positive non-ulcer dyspepsia and may be a valid indication for eradication therapy.     

Comparison between empirical prokinetics, Helicobacter test-and-treat and empirical endoscopy in primary-care patients presenting with dyspepsia： A one-year study

AIM: To investigate the optimal strategy to treat dyspeptic patients in primary care. METHODS: Dyspeptic patients presenting to primary care outpatient clinics were randomly assigned to: (1) empirical endoscopy, (2) H pylori test-and-treat, and (3) empirical prokinetic treatment with cisapride. Early endoscopy was arranged if patients remained symptomatic after 2 wk. Symptom severity, quality-of-life (SF-36) as well as patient preference and satisfaction were assessed. All patients underwent endoscopy by wk 6. Patients were followed up for one year. RESULTS: Two hundred and thirty four patients were recruited (163 female, mean age 49). 46% were H pylori positive. 26% of H pylori tested and 25% of empirical prokinetic patients showed no improvement at wk 2 follow-up and needed early endoscopy. 15% of patients receiving empirical cisapride responded well to treatment but peptic ulcer was the final diagnosis. Symptom resolution and quality-of-life were similar among the groups. Costs for the three strategies were HK$4343, $1771 and $1750 per patient. 66% of the patients preferred to have early endoscopy. CONCLUSION: The three strategies are equally effective. Empirical prokinetic treatment was the least expensive but peptic ulcers may be missed with this treatment. The H pylori test-and-treat was the most cost-effective option.     

Should the presence of polymorphisms of CYP2C19 enzymes influence the choice of the proton pump inhibitor for treatment of Helicobacter pylori infection?

There are variations in the CYP2C19 genotypes, that are important for the metabolism of PPIs. Patients who are heterozygotes for the mutation, but especially homozygotes, have a much slower metabolism, which will result in more profound acid suppression. Studies have been published, that suggest that the success rate of anti-Helicobacter therapy is in part related to the CYP2C19 genotype of the patient. However, it is important to keep in mind that most studies that have evaluated this have been carried out in Asia, in particular in Japan, where the prevalence of poor metabolizers (PM) is much higher than, for example, in Caucasians. The systematic review published in this issue suggests that particularly for omeprazole in combination with amoxicillin or amoxicillin and clarithromycin the success rate is much lower when compared to other proton pump inhibitors (PPIs). However, there was marked heterogeneity when the results were pooled in formal meta-analysis. Study quality was suboptimal and other factors such as resistance to antibiotics may explain the observed differences in success rates. More clinical trial data are needed before we can accept the conclusions of this meta-analysis.     

Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough： A comparison between two different daily doses of lansoprazole

AIM:To compare two different daily doses oflansoprazole given for 12 weeks and to assess the roleof gastrointestinal (GI) investigations as criteria forselecting patients.METHODS:Out of 45 patients referred for unexplainedchronic persistent cough,36 had at least one of theGI investigations (endoscopy,24-h esophageal pH-metry and a 4-week trial of proton pump inhibitor (PPI)therapy) positive and were randomly assigned to receiveeither 30 mg lansoprazole o.d.or 30 mg lansoprazoleb.i.d,for 12 weeks.Symptoms were evaluated atbaseline (visit 1) after the PPI test (visit 2) and after the12-week lansoprazole treatment period (visit 3).RESULTS:Thirty-five patients completed the studyprotocol.Twenty-one patients (60.0%) reportedcomplete relief from their cough with no differencebetween the two treatment groups (58.8% and 61.1%had no cough in 30 mg lansoprazole and 60 mglansoprazole groups,respectively).More than 80% ofthe patients who had complete relief from their cough atthe end of the treatment showed a positive response tothe PPI test.CONCLUSION:Twelve weeks of lansoprazole treatmenteven at a standard daily dose,is effective in patientswith chronic persistent cough.A positive response to aninitial PPI test seems to be the best criterion for selectingpatients who respond to therapy.