Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group ( P  <   0.001). The PPI response rates at 8 weeks were different ( P  =   0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.     

Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly

Background:

Small bowel bacterial overgrowth secondary to drug-induced hypochlorhydria may be of particular importance in the elderly, in whom anti-ulcer drugs are commonly prescribed and the consequences of malabsorption may be severe.

Methods:

Duodenal aspirates were obtained from elderly individuals before (n=24) and during a 2-month treatment course with either omeprazole (20 mg daily; n=8) or ranitidine (300 mg b.d.; n=6), and from six patients with small bowel bacterial overgrowth who had diarrhoea and malabsorption.

Results:

Before treatment, duodenal bacterial counts were normal (< 10⁴ colony forming units/mL) in 23 elderly subjects (96%). However, six of 14 patients (43%) treated with omeprazole (5 of 8) or ranitidine (1 of 6) developed bacterial counts> 10⁵ cfu/mL. All remained asymptomatic and had normal lactulose breath H₂ profiles during treatment.

Conclusion:

Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly but, in the short term, this bacterial overgrowth is not associated with malabsorption.

     

Prognostic Factors Related to Recovery from Diarrhea among U.S. Students with Diarrhea in Mexico

Background: Medical charts of subjects treated with placebo from five double-blinded placebo-controlled clinical trials were reviewed to determine pre-enrollment prognostic factors related to later recovery from diarrhea.
Method: Recovery or time from initiation of a placebo until passage of the last unformed stool after being declared well was calculated for each subject.
Results: A longer duration of diarrhea was associated with presence of fever (rate ratio = 0.34; 95% CI = 0.2–0.9), presence of an invasive pathogen in the stool (rate ratio = 0.35; 95% CI = 0.2–0.7) or a noninvasive pathogen in stool (rate ratio = 0.7; 95% CI = 0.6–1.0), severe abdominal pain or cramps (rate ratio = 0.5; 95% CI = 0.3–0.9), passage of more than five watery stools per 24 hours (rate ratio = 0.58; 95% CI = 0.4–0.8). Severe vomiting predicted a shorter duration of post-enrollment diarrhea (rate ratio = 2.43; 95% CI = 1.1–5.6).
Conclusion: A number of clinical and microbiologic factors found in travelers with diarrhea in the present study predicted duration of untreated diarrhea. The authors suggest the use of antimicrobial therapy in travelers with predictors of a long duration of diarrhea. Data developed in the present study may be used to create a historical control for clinical trials of antidiarrheal compounds using the same study criteria.     

Meta-analysis: yield of diagnostic tests for coeliac disease in dyspepsia

Background  The prevalence of coeliac disease (CD) may be increased in individuals with dyspepsia, but evidence is conflicting.
Aims  To conduct a systematic review and meta-analysis of studies reporting prevalence of CD in dyspepsia.
Methods  MEDLINE, EMBASE, and CINAHL were searched up to February 2009. Case series and case-control studies applying serological tests and/or distal duodenal biopsy for CD to unselected adults with dyspepsia were eligible. Prevalence of positive coeliac serology and biopsy-proven CD were pooled for all studies and compared between cases and controls using an odds ratio (OR) and 95% confidence interval (CI).
Results  Fifteen studies were identified. Prevalence of positive coeliac serology was higher in cases with dyspepsia (7.9%) compared with controls (3.9%), but not significantly so (OR for positive endomysial antibodies or tissue transglutaminase 1.89; 95% CI 0.90–3.99). Prevalence of biopsy-proven CD following positive serology was also higher (3.2% in cases vs. 1.3% in controls), but again this was not statistically significant (OR 2.85; 95% CI 0.60–13.38). Prevalence of biopsy-proven CD was 1% in ten studies performing duodenal biopsy first-line.
Conclusion  Prevalence of biopsy-proven CD in subjects with dyspepsia was 1% and was higher than in controls, although this difference was not statistically significant.     

Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome

BACKGROUND: Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non-irritable bowel syndrome subjects. AIM: To assess the prevalence of small intestinal bacterial overgrowth by glucose breath test in patients with irritable bowel syndrome symptoms with respect to a consistent control group. METHODS: Consecutive patients with irritable bowel syndrome according to Rome II criteria were enrolled. The control population consisted of 102 sex- and age-matched healthy subjects without irritable bowel syndrome symptoms. All subjects underwent glucose breath test. A peak of H2 values >10 p.p.m above the basal value after 50 g of glucose ingestion was considered suggestive of small intestinal bacterial overgrowth. RESULTS: A total of 65 irritable bowel syndrome patients and 102 healthy controls were enrolled. Positivity to glucose breath test was found in 31% of irritable bowel syndrome patients with respect to 4% in the control group, the difference between groups resulting statistically significant (OR: 2.65; 95% CI: 3.5-33.7, P < 0.00001). CONCLUSIONS: The present case-control study showed an epidemiological association between irritable bowel syndrome and small intestinal bacterial overgrowth. Placebo-controlled small intestinal bacterial overgrowth-eradication studies are necessary to clarify the real impact of small intestinal bacterial overgrowth on irritable bowel syndrome symptoms.     

Meta-analysis: zinc supplementation for acute gastroenteritis in children

Background  Uncertainty exists regarding the use of zinc in the treatment of acute gastroenteritis in children living in Europe, where zinc deficiency is rare.
Aim  To review evidence for the effectiveness of zinc in treating acute gastroenteritis in children, with special emphasis on data from developed countries.
Methods  MEDLINE, EMBASE, and the Cochrane Library were searched through November 2007 for randomized controlled trials (RCTs) relevant to acute gastroenteritis in children younger than 5 years of age and zinc; additional references were obtained from the reviewed articles.
Results  Eighteen RCTs (11 180 participants, mainly from developing countries) met the inclusion criteria. Use of zinc was associated with a significant reduction in diarrhoea duration (13 RCTs, 5643 infants, weighted mean difference −0.69 day, 95% CI −0.97 to −0.40) and the risk of diarrhoea lasting longer than 7 days [eight RCTs, n  = 5769, relative risk (RR) 0.71, 95% CI 0.53–0.96]. No significant reduction in stool volume was observed for those receiving zinc compared with placebo (three RCTs, n  = 606, standardized mean difference, −0.38, 95% CI −1.04 to 0.27). Combined data from five RCTs ( n  = 3156) showed that zinc significantly increased the chance of vomiting compared to the control agent (RR 1.2, 95% CI 1.05–1.4).
Conclusions  These data confirm that zinc supplementation can be useful for treating acute gastroenteritis in children, particularly those from developing countries. However, the role of zinc supplements in treating children with acute gastroenteritis in developed countries needs further evaluation.     

Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation

Background  A sensation of abdominal swelling (bloating) and actual increase in girth (distension) are troublesome features of irritable bowel syndrome (IBS), which is more common in patients with constipation, especially those with delayed transit.
Aim  To establish whether a fermented dairy product containing Bifidobacterium lactis DN-173 010 reduces distension in association with acceleration of gastrointestinal transit and improvement of symptoms in IBS with constipation.
Methods  A single centre, randomized, double-blind, controlled, parallel group study in which patients consumed the test product or control product for 4 weeks. Distension, orocaecal and colonic transit and IBS symptoms were assessed on an intention-to-treat population of 34 patients.
Results  Compared with control product, the test product resulted in a significant reduction in the percentage change in maximal distension [median difference – 39%, 95% CI (−78, −5); P  = 0.02] and a trend towards reduced mean distension during the day [−1.52 cm (−3.33, 0.39); P  = 0.096]. An acceleration of orocaecal [−1.2 h (−2.3,0); P  = 0.049] as well as colonic [−12.2 h (−22.8, −1.6); P  = 0.026] transit was observed and overall symptom severity [−0.5 (−1.0, −0.05); P  = 0.032] also improved.
Conclusions  This probiotic resulted in improvements in objectively measured abdominal girth and gastrointestinal transit, as well as reduced symptomatology. These data support the concept that accelerating transit is a useful strategy for treating distension.     

Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease

Background  Small-intestinal bacterial overgrowth (SIBO) is known to be present in patients with cirrhosis, predisposing to various complications.
Aim  To determine the frequency of SIBO in cirrhotics and correlate with severity of cirrhosis.
Methods  Small-intestinal bacterial overgrowth was determined by glucose–hydrogen breath test (GHBT). A basal breath-hydrogen >20 ppm or a rise by ≥12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis.
Results  Of the 53 cirrhotics, 26 (49%) had SIBO, compared to one (8%) control ( P  = 0.010). The prevalence of SIBO increased with severity of cirrhosis (Child–Pugh A 20%, B 52% and C 73%; P  = 0.013). On multivariate analysis, SIBO was independently associated with serum bilirubin and ascites. The best cut-off of serum bilirubin was ≥2 mg/dL [AUROC 0.77 (95% CI 0.64–0.90)] predicting SIBO with sensitivity 65%, specificity 81%, positive predictive value 77%, negative predictive value 71% and accuracy 74%. Patients having combination of ascites and serum bilirubin ≥2 mg/dL had 82% chance, while patients having neither had only 10% chance of having SIBO.
Conclusions  Small-intestinal bacterial overgrowth was prevalent in about half of cirrhotics. Its frequency increased with increase in severity of cirrhosis. Ascites and raised serum bilirubin reliably predicted presence of SIBO.     

One-week low-dose triple therapy for Helicobacter pylori is sufficient for relief from symptoms and healing of duodenal ulcers

Aim : To test the hypothesis that 1-week low-dose triple therapy for H. pylori is sufficient for relief from dyspeptic symptoms and healing of duodenal ulcers.
Methods : Fifty-nine out-patients with duodenal ulcers and positive rapid urease test participated in this randomized, double-blind, two-centre study. All patients were treated for 1 week with omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. In a double-blind fashion, patients were then randomly treated for another 3 weeks with either omeprazole 20 mg once daily or an identical-looking placebo. Patients were investigated endoscopically before treatment for H. pylori , after 2 weeks and after 4 weeks. H. pylori infection was assessed by a ¹³C-urea breath test at the time of enrolment and 4 weeks after cessation of any study medication.
Results : Fifty-two patients were included in the 'all patients treated' analysis of efficacy. The overall H. pylori cure rate was 96% (95% CI=87–100%), with no difference between the treatment groups. After 2 weeks duodenal ulcer healing was confirmed in 91% (95% CI=80–100%) of patients treated with omeprazole and in 76% (95% CI=60–91%) in the placebo group ( P =0.14). After 4 weeks all ulcers had healed. Relief from dyspeptic symptoms and adverse events (13.8 and 16.7%) did not differ between the treatment groups.
Conclusions : One-week low-dose triple therapy consisting of omeprazole, clarithromycin and metronidazole is a highly effective and well-tolerated approach to the cure of H. pylori infection in patients with a duodenal ulcer. Our data suggest that continuation of antisecretory drug therapy beyond anti- H. pylori therapy is actually excessive regarding relief from dyspeptic symptoms and healing of duodenal ulcers.     

Efficacy of an intravenous proton pump inhibitor after endoscopic therapy with epinephrine injection for peptic ulcer bleeding in patients with uraemia: a case-control study

Background  Patients with peptic ulcer bleeding and uraemia are prone to re-bleeding.
Aim  To compare the efficacy of an intravenous proton pump inhibitor in treating peptic ulcer bleeding in patients with uraemia and those without uraemia.
Methods  High-risk peptic ulcer bleeding patients received endoscopic therapy with epinephrine (adrenaline) injection plus intravenous omeprazole (40 mg bolus followed by 40 mg infusion every 12 h) for 3 days. Re-bleeding, volume of blood transfusion, hospital stay, need for surgery, and mortality were analysed.
Results  The uraemic group had similar 7-day re-bleeding rate (6/42, 14.29% vs. 6/46, 13.04%, P  =   0.865) to that of non-uraemic patients, but more re-bleeding episodes beyond 7 days (4/42, 9.52% vs. 0/46, 0%, P  =   0.032, OR [95% CI] = 1.105 [1.002–1.219]) and all-cause mortality (4/42 vs. 0/46 P  =   0.032, OR [95% CI] = 1.105 [1.002–1.219]). The uraemic group also had more units of blood transfusion after endoscopic therapy (mean ± s.d. 4.33 ± 3.35 units vs. 2.15 ± 1.65 units, P  <   0.001), longer hospital stay (mean ± s.d. 8.55 ± 8.12 days vs. 4.11 ± 1.60 days, P  <   0.001) and complications during hospitalization (9/42 vs. 0/46, P  =   0.001, OR [95% CI] = 1.273 [1.087–1.490]).
Conclusion  Endoscopic therapy with epinephrine injection plus an intravenous proton pump inhibitor can offer protection against early re-bleeding in uraemic patients with peptic ulcer bleeding, but has a limited role beyond 7 days.     

The benefit of pancreatic enzyme substitution after total gastrectomy

The aim of the present study was to evaluate the effect of the pancreatic enzyme preparation Kreon on abdominal symptoms, bowel habits, faecal fat excretion and oro-caecal transit time in patients after total gastrectomy for carcinoma of the stomach with Roux-en-Y anastomosis. A hydrogen breath test was carried out in each patient to detect bacterial overgrowth. In a double-blind crossover trial, 15 patients were treated with either Kreon or placebo (3.6 g/day) in two test-periods each of seven days. During treatment with the active substance, the stool consistency became more solid (P less than 0.05). The number of bowel movements and the abdominal symptoms, however, remained statistically unchanged. Treatment with Kreon did not influence the oro-caecal transit time. Faecal fat excretion did not significantly decrease in the whole group of patients. However, in those patients with massive steatorrhoea (free and esterified fatty acids greater than 350 mmol/72 h; upper reference limit 60 mmol/72 h) a significant (P less than 0.05) reduction from a median excretion of 643 mmol/72 h to 501 mmol/72 h was seen. Such a decrease in faecal fat excretion did not occur in patients with steatorrhoea below this limit. Bacterial overgrowth or rapid upper intestinal transit were not over-represented in patients with a high-degree of steatorrhoea. We conclude that after total gastrectomy pancreatic enzyme substitution reduces massive steatorrhoea and improves stool consistency.     

Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers

Background  The mechanism of action of bisacodyl in the unprepared human colon remains unclear.
Aim  To evaluate the effect of oral bisacodyl on the overall and regional colonic transit in humans.
Methods  In a double-blind, randomized, placebo-controlled study of 25 healthy participants, effects of oral bisacodyl (5 mg p.o. per day) and placebo on colonic transit were compared. A validated scintigraphy method was used to measure colonic transit. The primary transit endpoints, ascending colon emptying t _1/2 and geometric centre of colon isotope at 24 h (overall transit), were compared (Wilcoxon rank sum test).
Results  There were significant treatment effects on ascending colon t _1/2, with the bisacodyl group demonstrating accelerated emptying [median 6.5 h, interquartile range 5.0–8.0 h] relative to the placebo group [11.0 h (7.0–17.1); P  = 0.03]. Numerical differences in colonic geometric centre 24 h [bisacodyl median 3.0 (2.2–3.8), placebo 4.0 (3.1–4.6)] were not significant ( P  = 0.19). There were no significant differences observed in geometric centre 4 h.
Conclusion  Oral 5 mg bisacodyl accelerates ascending colon in the unprepared colon in healthy adults; this action may contribute to the drug's efficacy in constipation.     

High-dose proton pump inhibitor plus amoxycillin for the treatment or retreatment of Helicobacter pylori infection

Background : The combination of 120 mg of omeprazole (40 mg t.d.s.) and amoxycillin has been reported to be effective for treating H. pylori infections.
Methods : Normal volunteers with H. pylori infection received high-dose omeprazole (40 mg t.d.s.) or lansoprazole (60 mg t.d.s.) plus amoxycillin 750 mg t.d.s. for 14 days. The studies were open label and not randomized as those receiving omeprazole plus amoxycillin had previously failed lower dose omeprazole (20 mg b.d.) plus amoxycillin therapy more than 6 months previously. Those receiving lansoprazole plus amoxycillin had not been previously treated. Four to 6 weeks after ending antimicrobial therapy, H. pylori status was determined by Genta stain of gastric mucosal biopsies.
Results : Forty-three volunteers entered the study and 41 completed it. The overall success with high-dose proton pump inhibitor plus amoxycillin was 34.9%. For the individual regimens the per-protocol results were 48% (95% CI=28–69%) with lansoprazole and 12.5% (95% CI=2–38%) with omeprazole. Compliance was >95% for both regimens. Side-effects were experienced by four lansoprazole and three omeprazole subjects, and caused two omeprazole subjects to withdraw. Cure rates were similar among different races and ethnic groups, between men and women, and between smokers and non-smokers. The level of the pre-treatment urea breath test also did not predict outcome.
Conclusion : High-dose proton pump inhibitor plus amoxycillin combinations for treatment of H. pylori infection yielded unacceptable results, as the 95% confidence intervals did not include an 80% cure rate. These combinations do not yield consistent results worldwide and cannot be recommended as primary therapy.     

High effectiveness and safety of one-week antibiotic regimen in Helicobacter pylori eradication

Background: Helicobacter pylori is strongly associated with peptic ulcer: H. pylori eradication markedly decreases the recurrence rate of duodenal and gastric ulcer, but the optimum length of antibiotic therapy in the eradication of H. pylori is still unclear.
Aim: To verify the effectiveness and side-effect profile of an eradicating regimen consisting of omeprazole 20 mg daily for 4 weeks and, during the first week, combination antimicrobial treatment with tinidazole 500 mg b.d. plus clarithromycin 250 mg b.d. in patients with active duodenal and gastric ulcer.
Methods: One hundred and ninety-six duodenal ulcer patients and 27 gastric ulcer patients with H. pylori infection were admitted into an open prospective study. Compliance was assessed by an accurate interview.
Results: Overall, H. pylori was successfully eradicated in 201 of 223 patients (intention-to-treat 90.1%; 95% CI=85–94%): 176 of 196 duodenal ulcer patients became H. pylori- negative (89.8%; CI=85–94%) as well as 25 of 27 gastric ulcer patients (92.6%; CI=76–99%). Compliance was excellent in 221 of 223 (99.1%) patients evaluated as having taken all the medication as prescribed. Sixteen patients (7.2%) developed mild side effects during treatment.
Conclusion: This combination treatment had excellent results with almost absolute compliance and a very low rate of minor side effects.     

Systematic review: secondary prevention with band ligation, pharmacotherapy or combination therapy after bleeding from oesophageal varices

Background  Variable methods are available for secondary prevention after oesophageal variceal bleeding (EVB).
Aim  To compare band ligation (BL), pharmacotherapy (PT) and BL+PT for EVB secondary prevention.
Methods  A systematic search of databases, references and meeting abstracts was conducted for randomized trials of BL, PT or BL+PT. The outcomes were mortality, rebleeding and adverse events. A random-effects model was used for meta-analyses.
Results  Twelve trials were included (6 BL vs. PT, 4 BL+PT vs. BL, 2 BL+PT vs. PT). All trials used beta-blockers ± isosorbide mononitrate (ISMN) as PT. Mortality was not significantly different among trials. Rebleeding was not significantly different for BL vs. PT (RR 1.00, 95% CI 0.73–1.37). BL reduced rebleeding compared with PT for trials with mean beta-blocker dose <80 mg/day (RR 0.67, 95% CI 0.49–0.91). There were nonsignificant differences in rebleeding for BL+PT vs. BL (RR 0.57, 95% CI 0.31–1.08) and BL+PT vs. PT (RR 0.76, 95% CI 0.56–1.03). There was no difference in adverse events between BL vs. PT, but was higher with BL+PT vs. BL.
Conclusion  Band ligation and PT alone are comparable for secondary prevention of rebleeding after EVB. Further trials with adequate PT dosing are required to determine the efficacy of combination BL+PT therapy.     

Epidemiological study of gastro-oesophageal reflux disease: reflux in spouse as a risk factor

Background  Gastro-oesophageal reflux disease (GERD) is a growing health-care problem with variable distribution.
Aim  To assess GERD prevalence and risk factors and their possible correlation with pathophysiology in a population-based study.
Methods  Individuals aged 18–65 years were enrolled through random cluster sampling in Tehran. Previously validated self-administered questionnaires were used.
Results  Of the 2500 questionnaires, 2057 were analysed (mean age: 34.8 ± 13.0 years, 55.1% female). Frequent GERD was seen in 18.2%. Minor symptoms increased prevalence. Female gender (OR: 1.55, 95% CI: 1.01–2.41), BMI >30 kg/m² (OR: 1.79, 95% CI: 1.03–3.12), less education (OR: 1.52, 95% CI: 1.02–2.27), smoking (OR: 1.83, 95% CI: 1.12–2.99), NSAID use (OR: 4.23, 95% CI: 1.66–10.74) and GERD in spouse (OR: 1.82, 95% CI: 1.18–2.82) were associated with frequent GERD on multivariable analysis. GERD in first-degree relatives (OR: 1.73, 95% CI: 1.23–2.43) and asthma (OR: 4.09, 95% CI: 1.27–13.15) correlated with infrequent GERD. Minor symptoms correlated with GERD history in first-degree relatives, coffee consumption and NSAID use. Prevalence in the past 3 months was similar to that in the past 12 months ( P  < 0.05).
Conclusions  Gastro-oesophageal reflux disease is common in Tehran. The association of 'infrequent symptoms' with GERD history in first-degree relatives and 'frequent symptoms' with GERD history in spouse may point to the presence of yet unknown precipitating environmental factors inducing GERD in a genetically susceptible host. Minor GERD symptoms seem to have independent contribution to GERD. Assessing GERD in the past 3 months predicts prevalence in the past year.