Psyllium is superior to docusate sodium for treatment of chronic constipation

Background:

Stool softening is a physician’s first step in the management of chronic constipation.

Aim:

To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium.

Methods:

The multi-site, randomized, double-blind, parallel-design study of 170 subjects with chronic idiopathic constipation involved a 2-week baseline (placebo) phase followed by 2 weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Stools were collected and assessed.

Results:

Compared to baseline, psyllium increased stool water content vs. docusate (psyllium 2.33% vs. docusate 0.01%, P = 0.007). Psyllium also increased stool water weight (psyllium 84.0 g/BM; docusate 71.4 g/BM; P = 0.04), total stool output (psyllium 359.9 g/week; docusate 271.9 g/week; P = 0.005), and O’Brien rank-type score combining objective measures of constipation (psyllium 475.1; docusate 403.9; P = 0.002). Bowel movement (BM) frequency was significantly greater for psyllium (3.5 BM/week) vs. docusate (2.9 BM/week) in treatment week 2 (P = 0.02), with no significant difference (P > 0.05) between treatment groups in treatment week 1 (3.3 vs. 3.1 BM/week).

Conclusion:

Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation.

     

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety

Summary

Background

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion.

Aim

To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.

Methods

A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked.

Results

Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea.

Conclusions

Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

     

Alternating bowel pattern: what do people mean?

Summary

Background

With the introduction of new therapies, the subgrouping of patients based on bowel pattern has become important. However, the appropriate definition of an alternating bowel pattern remains unclear.

Aim

To determine if specific symptoms are reported by people with an alternating bowel pattern.

Methods

Using the Rochester Epidemiology Project, a series of population‐based surveys were undertaken in which valid self‐report gastrointestinal symptom questionnaires were mailed to 4029 randomly selected members of the community. One question asked was ‘How would you describe your usual bowel pattern in the last year'?

Results

3022 subjects (74%) provided questionnaire data and 2718 were eligible for this analysis, the mean age was 57 years, with a range of 20–98 years (median = 61). Of these, 9.2%, 2.5% and 7.6% reported their usual bowel pattern as being constipated, diarrhoea, or alternating respectively. At least 50% of those reporting alternating bowel pattern reported incomplete evacuation (63%), urgency (57%), straining (55%) and loose stool (50%). The proportion of alternators reporting each individual symptom was between that of diarrhoea and constipation except for mucus and incomplete evacuation; however, no symptom was unique to alternators.

Conclusion

People who self‐report an alternating bowel pattern appear to represent a blend of constipation and diarrhoea symptoms, rather than a distinct subgroup.

     

Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial

Summary

Background

Enteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment.

Aim

To evaluate nitazoxanide, a thiazolide anti‐infective agent, in treating viral gastroenteritis in adults and adolescents.

Methods

50 out‐patients at least 12 years of age (mean 33.5 years) presenting with diarrhoea and stool‐positive by enzyme‐linked immunosorbent assay for norovirus, rotavirus or adenovirus were enrolled in a double‐blind, placebo‐controlled clinical trial. Patients were randomly assigned either nitazoxanide 500 mg or placebo twice daily for 3 days. The primary end point was time from first dose to resolution of symptoms. Analysis was modified intent‐to‐treat for 45 patients, excluding five patients with other identified enteropathogens at baseline.

Results

The median time from first dose to resolution of symptoms was 1.5 days (IQR: 0.5–2.5) for nitazoxanide‐treated patients and 2.5 days (IQR: 1.5–4.5) for the placebo group. Significant reductions in time to resolution of symptoms were observed for all patients analysed (P < 0.0001) and for subsets of patients with rotavirus (P = 0.0052) and norovirus (P = 0.0295). The number of patients with adenovirus (n = 5) was too small to draw any conclusion. No significant adverse events were reported.

Conclusions

Nitazoxanide may play an important role in managing viral gastroenteritis in adults.

     

Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine

Background:

Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (⁷⁵Selenium HomotauroCholic Acid Test) can accurately diagnose this condition.

Aim:

To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine.

Method:

Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed.

Results:

Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3–12.6). Their median daily faecal weight was 285 g (range 85–676) and median faecal fat output was 17 mmol/24 h (range 8.3–38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea.

Conclusions:

Idiopathic bile acid malabsorption, once suspected, especially by documenting true ‘large volume’ watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.

     

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions

Summary

Background

Zollinger–Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long‐term maintenance.

Aims

The safety and efficacy data for short‐term (6‐month) treatment of Zollinger–Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years.

Methods

The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid‐reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h.

Results

Twenty‐four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90–100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported.

Conclusions

Maintenance oral pantoprazole therapy up to 3 years at dosages of 40–120 mg b.d. was effective and well tolerated in patients with Zollinger–Ellison syndrome and other hypersecretory conditions.

     

Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro-oesophageal reflux disease in Western patients with non-ulcer dyspepsia

Summary

Background

The effect of Helicobacter pylori eradication on the development of gastro‐oesophageal reflux disease is controversial.

Aim

To determine the incidence of symptoms of reflux disease and of erosive oesophagitis, and the relationship to changes in histological gastritis, in patients with non‐ulcer dyspepsia over 12 months.

Methods

Six hundred and ninety‐three patients in two similar randomized placebo controlled trials of H. pylori eradication in non‐ulcer dyspepsia were studied. Symptoms were assessed using the validated Gastrointestinal Symptom Rating Scale during a 1‐week run‐in period, at 6 months and 12 months. Endoscopy was performed at baseline to exclude patients with pathology and at 3 months and 12 months to determine if oesophagitis was present. Gastric biopsies were scored using the modified Sydney Classification.

Results

Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin) treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was 82% in the active treatment group. Antrum‐predominant gastritis (55%) was more frequently found than corpus‐predominant gastritis (6%). In patients with antrum‐predominant gastritis, heartburn and regurgitation scores improved significantly 12 months after eradication. Erosive oesophagitis developed in 15/232 patients in the eradication group (7%) compared with 2/227 (2%) in the control group, but there was no significant difference when adjusted for oesophagitis present at baseline.

Conclusions

Antrum‐predominant gastritis is the most common pattern of gastritis seen in non‐ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non‐ulcer dyspepsia; the development of oesophagitis is uncommon.

     

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia

Background

: The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established.

Aim

: To determine whether eradication of H. pylori might be of benefit in non‐ulcer dyspepsia patients.

Methods

: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro‐oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical‐appearing placebos.

Results

: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active‐treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active‐treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo‐treated patients (31%, P=0.048). Within the active‐treatment group, therapeutic success was significantly more frequent in the non‐infected patients (84% vs. 64%, P=0.04).

Conclusions

: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non‐ulcer dyspepsia, a small proportion of H. pylori‐infected patients may benefit from eradication treatment.

     

Allopurinol in addition to 5-aminosalicylic acid based drugs for the maintenance treatment of ulcerative colitis

Background:

To investigate the value of combined treatment with allopurinol and 5‐aminosalicylic (5‐ASA) based drugs as maintenance treatment for ulcerative colitis (UC).

Methods:

199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5‐ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months.

Results:

Intention‐to‐treat analysis after 6 and 12 months showed similar results in both groups. A log‐rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar.

Conclusions:

It appears possible that allopurinol in combination with 5‐ASA is better than 5‐ASA alone for a 6‐month, but not a 12‐month period. This has to be verified in further dose‐ranging studies.

     

Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study

Background

Germinated barley foodstuff (GBF) has been shown to attenuate intestinal injury in animal models, largely by increasing luminal short-chain fatty acid production.

Aim

To investigate the safety and efficacy of GBF in the treatment of ulcerative colitis (UC).

Methods

Ten patients with active UC received 30 g of GBF daily for 4 weeks in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Pre- and post-treatment stool concentrations of short-chain fatty acids were measured by gas-liquid chromatography.

Results

Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 6.9 ± 1.4 to 2.8 ± 1.5 (mean ± S.E.M., P < 0.05). The endoscopic index score fell from 6.1 ± 2.3 to 3.8 ± 2.3 (P < 0.0001). Patients showed an increase in stool butyrate concentrations after GBF treatment (P < 0.05). No side-effects were observed.

Conclusions

Oral GBF therapy may have a place in management of ulcerative colitis, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

     

Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders

Aim:

To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea.

Source:

Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these.

Results:

In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT₃ antagonists.

Conclusion:

Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.

     

Effect of potassium-magnesium citrate on upper gastrointestinal mucosa

Background:

Potassium supplements may cause mucosal damage of the gastrointestinal tract.

Aim:

To evaluate the effect of a new potassium supplement, potassium-magnesium citrate (K-Mag), on upper gastrointestinal mucosa and to compare it with an older potassium supplement, potassium citrate (Urocit-K).

Methods:

A randomized and double-blind study was conducted utilizing 36 healthy adults. Subjects were randomized into three groups: K-Mag (70 mmol/day K, 35 mmol/day citrate and 17.6 mmol/day Mg); Urocit-K (70 mmol/day K and 23.4 mmol/day citrate), and placebo. All subjects took 5 tablets b.d. of the allocated drug and 2 mg t.d.s. of glycopyrrolate for 7 days. On day 8, stool was examined for occult blood, a symptom score was calculated and an oesophagogastroduo-denoscopy was performed. Mucosal lesions were scored at five anatomic sites.

Results:

Demographic characteristics and symptom score were similar in the three groups (< 10% with more than mild symptoms). There were no significant differences in the endoscopic scores at any site examined nor in the total scores among the three groups. Erosion or ulcers were found in 18% of K-Mag, 23% of Urocit-K and 17% of the placebo group.

Conclusion:

Short-term use of K-Mag does not appear to induce lesions in the upper gastrointestinal mucosa and its oral tolerance is similar to Urocit-K or placebo.

     

Delta-9-tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study

Background:

Delta-9-tetrahydrocannabinol (THC), the active constituent of marijuana, is an effective agent in the prevention of chemotherapy-induced nausea and vomiting.

Aim:

To determine the effect of THC on gastric emptying of a radiolabelled solid food in humans.

Methods:

Thirteen healthy volunteers underwent gastric emptying studies after receiving THC and placebo in a randomized double-blind fashion on 2 separate days. THC, at a dose of 10 mg/m² of body surface area, or placebo were administered.

Results:

Gastric emptying after THC was slower than placebo in all subjects. Mean percentage of isotope remaining in the stomach was significantly greater than after placebo from 30 min (85.5 ± 4.3% vs. 94.2 ± 1.4% placebo and THC, respectively, P < 0.05) to 120 min (45.6 ± 7.2% vs. 73.9 ± 7.1% placebo and THC, respectively, P < 0.001) after the test meal. No correlation was found between plasma THC levels and the delay in gastric emptying.

Conclusions:

THC at a dose used for preventing chemotherapy-induced nausea and vomiting significantly delays gastric emptying of solid food in humans. Therefore, the anti-emetic property of THC may be mediated through the central nervous system.

     

An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis

Summary

Background

Fatigue is a debilitating symptom which frequently impairs the quality of life of patients with primary biliary cirrhosis (PBC). Although the mechanisms underpinning fatigue in PBC remain unclear, there is an emerging consensus that CNS mechanisms play a key role. It has recently been shown that there is a strong association between abnormalities in sleep regulation, in particular excessive daytime somnolence, and fatigue severity in PBC. The CNS‐acting drug modafinil has an established role in the treatment of excessive daytime somnolence in non‐liver disease states.

Aim

To explore, in an open label study, the responses of PBC patients suffering from significant daytime somnolence and associated fatigue to modafinil therapy.

Methods

All patients in the series (n = 21) underwent daytime somnolence assessment using the Epworth Sleepiness Scale and PBC symptom assessment using the PBC‐40, a multi‐domain, disease specific, psychometrically robust quality of life measure. Modafinil was started at a dose of 100 mg/day and was titrated according to tolerability and response. Patients underwent repeat Epworth Sleepiness Scale and PBC‐40 assessment after 2 months of treatment.

Results

Significant improvement was seen in Epworth Sleepiness Scale scores with modafinil therapy [15 ± 3 vs. 8 ± 6, P < 0.0005 (intention‐to‐treat analysis)]. An equally significant improvement in fatigue severity was also seen [PBC‐40 fatigue domain score (46 ± 6 vs. 34 ± 12, P < 0.0001) (intention‐to‐treat analysis)].

Conclusions

Open label modafinil therapy was associated, where tolerated by patients, with improvement in excessive daytime somnolence and associated fatigue in PBC. Further study in placebo‐controlled trials is warranted.

     

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C

Summary

Background

The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC).

Aim

To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC.

Methods

Ninety‐eight consecutive treatment‐naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM‐IV, at baseline and both during and after treatment.

Results

Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti‐viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one).

Conclusion

Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

     

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Summary

Background

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes.

Aim

To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro‐oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms.

Methods

Thirty‐two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24‐h pH‐metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full‐dosage PPI therapy (esomeprazole 40 mg/day) was prescribed.

Results

In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus–heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01).

Conclusions

This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

     

Comparison of simple tests for the non-invasive diagnosis of clinically silent cirrhosis in chronic hepatitis C

Summary

Background

Biopsy is the gold standard for assessing cirrhosis in patients with chronic hepatitis C virus infection, but it is expensive and at risk of complications. Alternative non‐invasive methods have been developed but their usefulness remains uncertain.

Aim

To compare the accuracy of five non‐invasive scores in detecting cirrhosis.

Methods

We reviewed the charts and liver biopsies of 228 consecutive, treatment‐naïve, hepatitis C virus‐positive patients, 13.2% of whom with histological diagnosis of cirrhosis. The five alternative scores were age‐platelet index, cirrhosis discriminant score, aspartate transaminases to platelet ratio index, Pohl's index, and aspartate transaminases/alanine transaminases ratio.

Results

The specificities of the scores were good (87–100%), but not so their sensitivities (17–67%). Accordingly positive likelihood ratios were generally good but negative likelihood ratios were suboptimal. Combinations of the scores independently related to cirrhosis only slightly change this diagnostic accuracy. Using double cut‐offs to exclude/diagnoses cirrhosis, cirrhosis discriminant score classified 21% of patients without misdiagnoses and aspartate transaminases to platelet ratio index classified 85% of case with 9% of misdiagnoses.

Conclusions

The five scores showed variable sensitivities and specificities in detecting liver cirrhosis, both individually and in combination. The use of double cut‐off points may make the cirrhosis discriminant score and aspartate transaminases to platelet ratio index useful to reduce the number of patients submitted to liver biopsy.

     

Continuous treatment with omeprazole 20 mg daily for up to 6 years in Barrett's oesophagus

Background:

Because of the malignant potential of Barrett’s oesophagus, an aim of treatment is to cause the columnar epithelium to regress. A logical approach is to decrease acid reflux which is an important aetiological factor in Barrett’s oesophagus. Treatment with omeprazole 20–80 mg over 1–3 years has yielded conflicting but largely disappointing results.

Aim:

To determine if treatment of Barrett’s oesophagus with omeprazole 20 mg daily for up to 6 years can cause regression of the Barrett’s epithelium.

Patients and Methods:

Forty-seven patients with Barrett’s oesophagus were treated in an open prospective study. Nine patients were treated for 2 years, 12 for 3 years, 10 for 4 years, eight for 5 years and eight for 6 years. Patients were endoscoped at 1–2-year intervals and endoscoped at the end of the treatment period.

Results:

No significant shortening of the length of the Barrett’s segment was seen during any treatment period, although omeprazole controlled reflux symptoms and was well tolerated. Macroscopic squamous islands appeared in 55% of patients, mostly in the first 2–3 years although in five patients they appeared later in treatment.

Conclusion:

Treatment of Barrett’s oesophagus with omeprazole 20 mg daily for periods of up to 6 years did not cause regression in the length of the Barrett’s segment, but it did lead in over half of the patients to partial re-epithelialization in the form of squamous islands.

     

Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study

Aim:

To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria.

Methods:

Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored.

Results:

The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0% vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups, but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators’ global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01).

Conclusions:

Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/discomfort) more than placebo does.

     

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients

Summary

Background

Proximal acid reflux is common in gastro‐oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton‐pump inhibitors.

Aim

To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux.

Methods

Thirty seven consecutive gastro‐oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24‐h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis.

Results

At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non‐hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Δ + 2.5 min (95% confidence interval: 0.4–4.5); P < 0.02].

Conclusions

The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro‐oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.