Appropriateness of colonoscopy in Europe (EPAGE II). Screening for colorectal cancer.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for screening for colorectal cancer (CRC) in asymptomatic individuals without personal history of CRC or polyps, and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews, and primary studies regarding colonoscopy for screening for colorectal cancer was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy in these circumstances. RESULTS: Available evidence for CRC screening comes from small case-controlled studies, with heterogeneous results, and from indirect evidence from randomized controlled trials (RCTs) on fecal occult blood test (FOBT) screening and studies on flexible sigmoidoscopy screening. Most guidelines recommend screening colonoscopy every 10 years starting at age 50 in average-risk individuals. In individuals with a higher risk of CRC due to family history, there is a consensus that it is appropriate to offer screening colonoscopy at < 50 years. EPAGE II considered screening colonoscopy appropriate above 50 years in average-risk individuals. Panelists deemed screening colonoscopy appropriate for younger patients, with shorter surveillance intervals, where family or personal risk of colorectal cancer is higher. A positive FOBT or the discovery of adenomas at sigmoidoscopy are considered appropriate indications. CONCLUSIONS: Despite the lack of evidence based on randomized controlled trials (RCTs), colonoscopy is recommended by most published guidelines and EPAGE II criteria available online (http://www.epage.ch), as a screening option for CRC in individuals at average risk of CRC, and undisputedly as the main screening tool for CRC in individuals at moderate and high risk of CRC.

The validity of a symptom diary in ratings of dyspepsia measured against a detailed interview: do patients and clinicians agree in their assessment of symptoms?

BACKGROUND: Patients' self-assessment of symptoms is central in drug treatment trials of functional dyspepsia. The validity of such ratings is important. AIM: To validate a diary for monitoring severity and duration of dyspepsia. METHOD: We compared the diary-cards with two clinicians' ratings of the patient's open-ended responses to the same questions administered by interview. Agreements were evaluated by estimation of the overall agreement and weighted kappa values (Kw). RESULTS: Forty-six patients were evaluated. The Kw between the two clinicians rating severity and duration of symptoms were 0.59 and 0.86, respectively. Overall agreement between patients' diary rating and clinicians' consensus rating of severity were 52%, and a moderate agreement with Kw of 0.49 was found. For duration of symptoms the overall agreement and Kw were 67% and 0.59, respectively. Qualitative data revealed useful insight in the possible causes of suboptimal agreement between patients and clinicians. CONCLUSIONS: We found a moderate to good agreement between patient and observer ratings, indicating that patients to a reasonable extent interpret severity and duration of dyspeptic symptoms in the same way as do investigators. A ceiling effect of the duration scale indicates suboptimal response categories, which should be adjusted before further use.

Impact of an information video before colonoscopy on patient satisfaction and anxiety - a randomized trial.

BACKGROUND AND STUDY AIMS: Anxiety before colonoscopy may have adverse consequences and increase requirements for sedation and analgesics. We aimed to examine the effects of adding an information video to our usual preprocedural information. PATIENTS AND METHODS: 162 colonoscopy patients were randomly assigned to video (72) or no video (90) groups. Patients in the video group watched a video on colonoscopy procedures and cleansing. The patients' situational anxiety was measured using the State-Trait Anxiety Inventory (STAI) questionnaire. Patients rated pain and overall satisfaction related to the procedure. The colonoscopist and the endoscopy nurse, who were blinded to the patient's allocation, completed questionnaires on use of medication, procedure outcome, and their assessments of patient pain and toleration of the procedure. RESULTS: There were no differences between the two groups concerning situational anxiety (mean STAI-State score 45.0 +/- 13.3 vs. 45.9 +/- 12.9, P = 0.7), rating of pain, tolerability of the procedure, or the willingness to undergo a future colonoscopy. The staff rated the outcomes equally in the two groups. There was no difference in use of midazolam, but patients, who had seen the video used higher doses of fentanyl ( P < 0.02). Situational anxiety ratings were significantly higher in women, and they found the procedure significantly more painful ( P = 0.001) and were less satisfied ( P < 0.05). CONCLUSIONS: An information video shown to patients preparing for colonoscopy had no impact on tolerability or anxiety. Colonoscopy is less tolerable and more painful for women and this is probably related to a higher degree of anxiety. Endoscopy personnel should be aware of these gender differences and adjust information and medication accordingly.

Systematic review: quality of trials on the symptomatic effects of the low FODMAP diet for irritable bowel syndrome.

BACKGROUND: The low Fermentable Oligo-, Di- Monosaccharides, and Polyoles (FODMAP) diet is a new treatment option for irritable bowel syndrome (IBS). Experts refer to the diet as supported by high level of evidence, but an evaluation of the quality of trials is lacking. AIM: To provide a systematic review of the quality of trials on the symptomatic effects of the low FODMAP diet for IBS. METHODS: Pubmed and EMBASE were searched for randomised controlled trials (RCTs) reporting effect of the low FODMAP diet on IBS symptoms. The quality of trials was evaluated by estimating risk of bias and assessing trial methodology. RESULTS: Nine RCTs were eligible, including 542 patients. The intervention period was from 2 days to 6 weeks and one trial included a 6-month follow-up. Three trials intervened by providing meals, controlling with a diet high in FODMAP content. In six trials, the intervention was instruction by a dietician and a variety of control interventions were used, all with limited established efficacy. Domains with a high risk of bias were identified for all the trials. High risk of bias dominated domains regarding blinding, with only one trial double-blinded. CONCLUSIONS: The RCTs on the low FODMAP diet are characterized by high risk of bias. The diet has not been studied in a randomised, controlled setting for more than 6 weeks and trials examining the effect of the important reintroduction period are lacking. There is a risk that the symptomatic effects reported in the trials are driven primarily by a placebo response.

The epidemiology of irritable bowel syndrome: Symptom development over a 3-year period in Denmark. A prospective, population-based cohort study.

BACKGROUND: We aimed to explore the natural history of irritable bowel syndrome (IBS) in Denmark over 3 years by studying development of IBS symptoms and associated factors. METHODS: A cohort study was carried out using a web panel representative of the Danish general population 18-50 years. The survey, including a questionnaire based on the Rome III criteria for IBS, was conducted in January 2010, January 2011, and March 2013. KEY RESULTS: The prevalence of IBS was 15.4% (920/5986). The incidence was 10.3%, and was three times higher for persons with unspecific gastrointestinal (GI) symptoms compared to asymptomatic persons. Of respondents with IBS symptoms in both 2010 and 2011, 69% (131/191) also reported symptoms of IBS in 2013, which was significantly more compared to respondents with IBS symptoms in 2010 reporting to be asymptomatic or having unspecific GI symptoms in 2011 (20% and 39%, respectively, P<.001). Being diagnosed with IBS predicted fulfilling the criteria for IBS 3 years later (OR: 2.59, 95% CI: 1.11-6.10). Fulfilling criteria for IBS after 1 year also led to a high risk of IBS symptoms 3 years later in asymptomatic persons and persons with unspecific symptoms at baseline. CONCLUSIONS & INFERENCES: The vast majority of persons fulfilling criteria for IBS report GI symptoms after one and 3 years. Fulfilling IBS criteria after 1 year led to a high risk of reporting IBS symptoms after 3 years. In the general population having an IBS diagnosis predicts persistently fulfilling the Rome III criteria for IBS 3 years later.

Randomised clinical trial: addition of alginate-antacid (Gaviscon Double Action) to proton pump inhibitor therapy in patients with breakthrough symptoms.

BACKGROUND: Symptomatic breakthrough in proton pump inhibitor (PPI)-treated gastro-oesophageal reflux disease (GERD) patients is a common problem with a range of underlying causes. The nonsystemic, raft-forming action of alginates may help resolve symptoms. AIM: To assess alginate-antacid (Gaviscon Double Action, RB, Slough, UK) as add-on therapy to once-daily PPI for suppression of breakthrough reflux symptoms. METHODS: In two randomised, double-blind studies (exploratory, n=52; confirmatory, n=262), patients taking standard-dose PPI who had breakthrough symptoms, assessed by Heartburn Reflux Dyspepsia Questionnaire (HRDQ), were randomised to add-on Gaviscon or placebo (20 mL after meals and bedtime). The exploratory study endpoint was change in HRDQ score during treatment vs run-in. The confirmatory study endpoint was "response" defined as ≥3 days reduction in the number of "bad" days (HRDQ [heartburn/regurgitation] >0.70) during treatment vs run-in. RESULTS: In the exploratory study, significantly greater reductions in HRDQ scores (heartburn/regurgitation) were observed in the Gaviscon vs placebo (least squares mean difference [95% CI] -2.10 [-3.71 to -0.48]; P=.012). Post hoc "responder" analysis of the exploratory study also revealed significantly more Gaviscon patients (75%) achieved ≥3 days reduction in "bad" days vs placebo patients (36%), P=.005. In the confirmatory study, symptomatic improvement was observed with add-on Gaviscon (51%) but there was no significant difference in response vs placebo (48%) (OR (95% CI) 1.15 (0.69-1.91), P=.5939). CONCLUSIONS: Adding Gaviscon to PPI reduced breakthrough GERD symptoms but a nearly equal response was observed for placebo. Response to intervention may vary according to whether symptoms are functional in origin.

Prescribing of acid suppressive therapy: interactions between hospital and primary care.

BACKGROUND: Overuse of acid suppressive therapy in the hospital setting and in primary care is well documented. AIM: To describe interactions between prescriptions of acid suppressive therapy in hospital and in primary care. METHODS: All patients admitted to hospital over a 24-month period were identified. Details about prescription of acid suppressive therapy were retrieved. All prescriptions of acid suppressive therapy redeemed by these patients 12 months before and after discharge were retrieved from a prescription database. RESULTS: A total of 549 of 4477 patients (12.3%) were treated with acid suppressive therapy while in hospital, but acid suppressive therapy was prescribed de novo in only 192 (35%) of these cases. Information about indication for acid suppressive therapy and planned duration of therapy were given in the discharge letter in only 25% and 17% of the cases, respectively. Among patients treated with acid suppressive therapy during admission, prescriptions on acid suppressive therapy were redeemed by 67% in the year before admission and by 74% in the year after discharge. Among patients who had the acid suppressive therapy discontinued during admission (n = 67), 48% resumed acid suppressive therapy within the following 12 months. Of all subjects treated with acid suppressive therapy in the hospital catchment area, 7.8% were seen in our department. CONCLUSIONS: Decisions about acid suppressive therapy prescribing in hospital has little influence on prescribing in primary care.

Irritable bowel syndrome: the burden and unmet needs in Europe.

Irritable bowel syndrome affects approximately 10-15% of the European population, although prevalence rates vary depending on the classification used and the country surveyed. This may be due to differences in patterns of medical care and diagnosis of the condition. Up to 70% of individuals with irritable bowel syndrome may not have been formally diagnosed. The disorder affects 1.5-3 times as many women as men and poses a significant economic burden in Europe, estimated at euro 700-euro 1600 per person per year. It also reduces quality of life and is associated with psychological distress, disturbed work and sleep, and sexual dysfunction. It is a chronic disorder, which affects many individuals for more than 10 years. Most patients are managed in primary care, although some are referred to gastroenterologists and other specialists. Patients with irritable bowel syndrome undergo more abdomino-pelvic surgery than the general population. We propose that a positive diagnosis of the condition may avoid the delay in diagnosis many patients experience. We conclude that, in Europe, there are significant unmet needs including lack of familiarity with irritable bowel syndrome, difficulties in diagnosis and lack of effective treatments for the multiple symptoms of the disorder. The development of pan-European guidelines for irritable bowel syndrome will benefit patients with this condition in Europe.

Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

BACKGROUND: Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. AIM: To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. METHODS: This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. RESULTS: One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. CONCLUSION: In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21).

Abnormal hepatic vein Doppler waveform in patients without liver disease.

In patients with liver cirrhosis Doppler ultrasound often detects absence of the retrograde (hepatopetal) flow phase in the hepatic vein, suggestive of an increased stiffness of the liver parenchyma around the vein. This is rarely or never reported in healthy control persons. We examined the frequency of absent retrograde flow in a consecutive series of 139 patients referred for abdominal ultrasound. We used state-of-the-art ultrasound scanners, and placed the Doppler gate so that in non-forced end-expiration it would sample the right hepatic vein 4-6 cm from the vena cava. There was no association between the hepatic vein flow pattern and age, sex or body mass index. 43 of 139 studied patients showed absent retrograde flow. Review of the case records revealed liver disease in 26 patients and no sign of liver disease in 17 patients. We suggest that absent retrograde flow in the hepatic veins may be seen not only in patients with overt liver disease but also in apparently liver-healthy patients.

Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults.

BACKGROUND: Gastrointestinal symptoms are reportedly common in diabetes, but a causal link is controversial and adequate population control data are lacking. OBJECTIVE: To determine whether gastrointestinal symptoms are more frequent in persons with diabetes, particularly in those with poor glycemic control. METHODS: Fifteen thousand adults were mailed a questionnaire (response rate, 60.0%) containing validated questions on the frequency of troublesome gastrointestinal symptoms within the past 3 months, diabetic status, and self-reported glycemic control. The prevalence of 16 symptoms and 5 symptom complexes, reported to occur often or very often, was compared using logistic regression analysis, adjusting for age and sex. RESULTS: Overall, 8657 eligible subjects responded; 423 (4.9%) reported having diabetes. Most (94.8%) had type 2 diabetes mellitus. Adjusting for age and sex, all 16 symptoms and the 5 symptom complexes were significantly more frequent in subjects with diabetes compared with controls. An increased prevalence rate of symptoms was significantly associated with poorer levels of glycemic control but not with duration of diabetes or type of diabetic treatment. CONCLUSIONS: Diabetes mellitus is associated with an increased prevalence of upper and lower gastrointestinal symptoms. This effect may be linked to poor glycemic control but not to duration of diabetes or type of treatment.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark.

BACKGROUND: Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. AIM: To determine the use of proton pump inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. METHODS: A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients, the Danish National Prescription Register, and the Danish Person Register. RESULTS: The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before. The probability for inadequate dosing 1 year before surgery (<180 DDD) was significantly increased for younger patients, patients operated in the period 2000-2003, patients who had not undergone pre-surgical manometry, pH- or impedance monitoring, and patients who had not redeemed prescriptions on NSAID or anti-platelet drugs. CONCLUSION: Compliance with medical therapy should be evaluated thoroughly before planning anti-reflux surgery, as a high proportion of patients receive inadequate dosing of acid-suppressive therapy prior to the operation.

Drug-induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions.

BACKGROUND: A large variety of drugs have been implicated in causing dyspepsia. Due to the high background incidence of dyspepsia it is impossible to distinguish between spontaneous and truly drug-related symptoms. Most patients with dyspeptic symptoms are treated empirically. Drug-induced dyspepsia might therefore be reflected in the sequencing of prokinetics relative to other medications. AIM: To screen a large prescription database for signs of drug-induced functional dyspepsia, applying a symmetry principle. METHODS: Prescription data on all incident users of cisapride and metoclopramide were used to identify individuals who had started their first therapies with a prokinetic drug and an index drug within a 100-day span. A dyspepsia-provoking effect of the index drug would manifest as an excess of persons with the prokinetic drug prescribed last in this selected population. Relative to conventional analyses based on case-control or cohort design, this principle is robust to confounders that are stable over time. RESULTS: In the cisapride analysis (1825 persons) no single drug had adjusted rate ratios significantly above unity. An inverse signal for antidepressants (rate ratio 0.57; 95% CI: 0.39-0.84) suggests that these drugs may have a therapeutic effect against functional dyspepsia. In the metoclopramide analysis (6126 persons) positive signals were found for 14 drugs, all well-known for causing nausea as a side-effect, with the exception of insulin (rate ratio 2.91, 95% CI: 1.40-8.11). CONCLUSIONS: Drug-induced symptoms of functional dyspepsia are rare and do not contribute to the use of cisapride. The start of insulin treatment may induce nausea.

Review article: acid suppression in the management of gastro-oesophageal reflux disease--an appraisal of treatment options in primary care.

Gastro-oesophageal reflux disease (GERD) is one of the most common conditions presenting to the primary care physician. Despite progress in understanding and treatment of the disease, strategies for capitalizing on these advances are less well developed. In many practices, H2-receptor antagonists still remain the most widely prescribed treatment for GERD, despite the availability of the more effective acid-suppressant proton pump inhibitors. This review examines the relative efficacies of acid-suppressant drugs in minimizing oesophageal acid exposure and outlines the evidence for the superiority of proton pump inhibitors over standard-dose H(2)-antagonists in symptom relief, erosion healing and prevention of relapse in GERD. Current prescribing patterns and considerations for the general practitioner are also examined. The availability and impact of over-the-counter H(2)-antagonists on the treatment of GERD and their relative cost-effectiveness vs. proton pump inhibitors are also addressed. A hierarchy of drug efficacy (full-dose proton pump inhibitor > half-dose proton pump inhibitor > high-dose H(2)-antagonist > standard-dose H(2)-antagonist or prokinetic) applies in principle to all GERD patients, (with or without oesophagitis). The most effective initial therapy for GERD is also likely to be the most cost-effective one, if treatment failure leads to higher utilization of medical resources. The application of these recommendations to the management of non-endoscoped GERD, endoscopy-negative GERD and low-grade oesophagitis as well as higher grade oesophagitis is also reviewed.

Personal view: rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease and non-erosive reflux disease are chronic, highly prevalent conditions requiring long-term treatment that is both effective and practical. On-demand therapy with a proton pump inhibitor may meet that need. It is becoming a mainstay of long-term treatment because it reduces the risk of over- and under-treatment, is cost-effective and user friendly. Epidemiological and clinical observations speak also in its favour. However, for the anticipated benefits of on-demand therapy to accrue in clinical practice, on-demand treatment algorithms are required. These algorithms must specify the initial evaluation and treatment of candidates, and follow-up protocols for an on-demand strategy. Our group has developed such algorithms, which are presented here.

Reproducibility of a symptom response to omeprazole therapy in functional dyspepsia evaluated by a random-starting-day trial design.

BACKGROUND: Satisfactory treatment options for functional dyspepsia are lacking. Single subject trial designs may identify subgroups of patients with a uniform response to therapy. AIM: To test reproducibility of response in a new random-starting-day trial design developed to identify acid-related symptoms in functional dyspepsia. METHODS: One hundred and nineteen patients with functional dyspepsia completed a 12-day, double-blind random-starting-day trial with an initial placebo run-in followed by switch to omeprazole on a randomized and blinded day (between days 5 and 9) with active treatment continuing for the rest of the trial. Response was defined as a sustained > or =50% reduction of a daily symptom-score within 3 days of active treatment. Fifty-nine patients repeated the random-starting-day trial at relapse of symptoms. RESULTS: After exclusion of placebo responders, 14% (15 of 106) were classified as responders in the first and 20% (10 of 50) in the subsequent random-starting-day trial series. Sixty-eight per cent (40 of 59) of the patients reproduced their initial response with a chance-corrected agreement of 0.29. Comparing response patterns using different symptom rating-scales showed good correlation (kappa 0.60). CONCLUSION: Reproducibility of response in a random-starting-day trial was imperfect, mainly because of the low response rates and strict response criteria. Lack of symptom stability impairs the value of the random-starting-day trial and only patients with frequent and stable symptoms should be evaluated in this design.

Identifying response to acid suppressive therapy in functional dyspepsia using a random starting day trial--is gastro-oesophageal reflux important?

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.

A randomized, double-blind, comparative study of standard-dose rabeprazole and high-dose omeprazole in gastro-oesophageal reflux disease.

BACKGROUND: Rabeprazole has a faster onset of antisecretory action than omeprazole, and it is of interest to determine whether this translates into faster symptom relief in patients with gastro-oesophageal reflux disease. AIMS: To assess the relief from heartburn after 3 days of treatment with standard-dose rabeprazole or high-dose omeprazole (primary end-point). Secondary end-points included the decrease in score for other symptoms of gastro-oesophageal reflux disease, healing rates and quantification of antacid use. METHODS: Patients with endoscopically confirmed erosive oesophagitis were randomized to receive 4 weeks of double-blind treatment with rabeprazole (20 mg) or omeprazole (40 mg). Patients who were not healed after 4 weeks received a further 4 weeks of treatment. RESULTS: Two hundred and seventy-four patients were screened, 251 patients were randomized and 230 patients completed the trial. The numbers of patients with relief from heartburn on day 4 were similar in the two groups (84% for rabeprazole; 95% confidence interval, 76-90%; 83% for omeprazole; 95% confidence interval, 75-89%). There were no significant differences between the treatments in the relief from other gastro-oesophageal reflux disease symptoms or in healing rates. The number of reports of severe heartburn during the first 3 days was higher in the omeprazole group (daytime heartburn: 4.7% for rabeprazole vs. 10.3% for omeprazole, P=0.005; night-time heartburn: 4.7% for rabeprazole vs. 9.8% for omeprazole, P=0.01; statistical comparisons defined post hoc). CONCLUSIONS: Standard-dose rabeprazole was as effective as high-dose omeprazole in relieving symptoms by day 4 of treatment and in healing oesophageal lesions, but had a faster onset of action in patients with severe heartburn. This suggests that the improved pharmacological properties of rabeprazole translate into a clinically relevant advantage.

Six-month trial of on-demand rabeprazole 10 mg maintains symptom relief in patients with non-erosive reflux disease.

BACKGROUND: Compliance studies have shown that patients with reflux symptoms generally take their medication only when experiencing these symptoms. AIM: To evaluate the efficacy of on-demand rabeprazole maintenance therapy in patients with non-erosive reflux disease. METHODS: This multicentre, randomized, double-blind, placebo-controlled, withdrawal study compared 6 months of on-demand treatment with rabeprazole 10 mg vs. placebo. Adults with a history of reflux symptoms, a negative endoscopy, and > or = 3 days of moderate to very severe heartburn in the 7 days before enrollment (N = 535) entered 4 weeks of open-label, acute treatment with rabeprazole 10 mg once daily. Patients with complete symptom relief then entered the on-demand phase. The primary end-point was discontinuation due to lack of heartburn control during the on-demand phase. RESULTS: Eighty-three percent (432 of 523) of patients reported complete symptom relief at the end of the acute phase. During on-demand treatment, rates of discontinuation because of inadequate heartburn control were 20% (28 of 139) for placebo vs. 6% (16 of 279) for rabeprazole (P < 0.00001). Antacid use was twofold higher in the placebo group vs. the rabeprazole group (P = 0.0009). CONCLUSIONS: Rabeprazole 10 mg once daily is highly effective in acute symptom relief and as on-demand long-term maintenance therapy in non-erosive reflux disease patients.

Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus.

BACKGROUND: Gastrointestinal symptoms are commonly reported as side-effects of oral hypoglycaemic drugs. It may be very difficult to distinguish between spontaneous and truly drug-related symptoms due to the high background incidence of gastrointestinal symptoms. Gastrointestinal symptoms in diabetic patients have also been linked to factors associated with long-standing disease and suboptimal control. AIM: To explore the association between gastrointestinal symptoms and treatment with oral hypoglycaemic drugs in a large cohort of subjects with type 2 diabetes. PATIENTS AND METHODS: 956 subjects with type 2 diabetes participated in the study. All subjects completed a validated, self-administered questionnaire on gastrointestinal symptoms, diabetes, drug use and various potential risk factors for gastrointestinal symptoms. The association between oral hypoglycaemics and nine gastrointestinal symptom groups was assessed based on logistic regression. RESULTS: 405 of the 956 patients used oral hypoglycaemic drugs. Metformin use was independently associated with chronic diarrhoea (odds ratio 3.08, 95% CI: 1.29-7.36, P < 0.02) and with faecal incontinence (odds ratio 1.95, 95% CI: 1.10-3.47, P < 0.05). Use of sulphonylureas was associated with less abdominal pain, but not with any other gastrointestinal symptom. CONCLUSIONS: Troublesome gastrointestinal symptoms do not appear to be caused by oral hypoglycaemics, except for diarrhoea and faecal incontinence, which are strongly and independently associated with metformin use.