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Aliment Pharmacol Ther 2010; 32: 119–130 Background Immunosuppression is a risk factor for carcinogenesis. Thiopurines specifically contribute to this. As thiopurines are used more aggressively in the treatment of IBD, it is likely that we will see more thiopurine-related malignancy. Aim To review the literature, exploring how immunosuppression , thiopurines specifically, might cause cancer and which malignancies occur in practice, placing specific emphasis on IBD cohorts. Methods Search terms included ‘malignancy’‘cancer’‘azathioprine’‘mercaptopurine’‘tioguanine (thioguanine)’‘thiopurine’ and ‘inflammatory bowel disease’‘Crohn’s disease’‘ulcerative colitis’. We also searched for specific cancers (lymphoma, colorectal cancer, skin cancer, cervical cancer) and reviewed the reference lists of the articles detected. Results Immunosuppression is associated with an increased risk of cancer. Thiopurines are associated with specific additional risks. In IBD cohorts, very few thiopurine-related malignancies have been reported. However, studies suggest a relative risk of 4–5 for lymphoma. This still translates into a low actual risk, (one extra lymphoma in every 300–1400 years of thiopurine treatment). Conclusions Whilst we must be aware of this risk and counsel our patients appropriately, thiopurines remain a mainstay of IBD therapy. We present practical advice aimed at minimizing our patients’ risk of developing malignancy, whilst optimizing the benefits that thiopurines can provide. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 1155–1164 Background Travellers’ diarrhoea, a common problem worldwide with significant medical impact, is generally treated with anti-diarrhoeal agents and fluid replacement. Systemic antibiotics are also used in selected cases, but these may be associated with adverse effects, bacterial resistance and drug–drug interactions. Aim To review the clinical evidence supporting the efficacy and safety of the minimally absorbed oral antibiotic rifaximin in travellers' diarrhoea. Methods PubMed and the Cochrane Register of Controlled Clinical Trials (to January 2010) and International Society of Travel Medicine congress abstracts (2003–2009) were searched to identify relevant publications. Results A total of 10 publications were included in the analysis. When administered three times daily for 3 days, rifaximin is superior to placebo or loperamide; it is at least as effective as ciprofloxacin in reducing duration of illness and restoring wellbeing in patients with travellers' diarrhoea, both with and without identification of a pathogen, as well as in diarrhoea caused by Escherichia coli infection. Rifaximin demonstrates only minimal potential for development of bacterial resistance and for cytochrome P450-mediated drug–drug interactions, and its tolerability profile is similar to that of placebo. Conclusion When antibiotic therapy is warranted in uncomplicated travellers' diarrhoea, rifaximin may be considered as a first-line treatment option because of its favourable efficacy, tolerability and safety profiles. [ABSTRACT FROM AUTHOR]

Presents a response by R. K. Sterling & M. L. Shiffman to a letter to the editor about the article "Mycophenolate mofetil for the treatment of primary sclerosing cholangitis," that was previously published in the journal "Alimentary Pharmacology & Therapeutics."

Background Non-adherence to 5-aminosalicylic acid (5-ASA) medication can limit the established benefits of this therapy in ulcerative colitis (UC). Aim To determine rates and predictors of non-adherence to 5-ASA therapy in UC patients. Methods Medication adherence was assessed using self-report data and urinary drug excretion measurements. Participants completed a study-specific questionnaire and two validated questionnaires: Beliefs about Medicine Questionnaire (BMQ)-Specific and Satisfaction with Information about Medicines Scale. Results A total of 169 participants provided self-report adherence data; 151 also provided urine samples. Adherence rates were 111/151 (68%) according to self-report and 90/151 (60%) according to urine analysis, but the two measures were not correlated (χ2 = 0.12, P = 0.725). Logistic regression identified a significant association between self-reported non-adherence and younger age [odds ratio (OR) for increased age 0.954, 95% confidence interval (CI) 0.932–0.976] and also doubts about personal need for medication (OR for BMQ – Specific Necessity scores 0.578, 95% CI 0.366–0.913). For non-adherence based on urine analysis, only South Asian ethnicity was independently associated with non-adherence (OR 2.940, 95% CI 1.303–6.638). Conclusions Our observations confirm the difficulty of accurately assessing medication adherence. Nonmodifiable (younger age, South Asian ethnicity) and potentially modifiable (medication beliefs) predictors of non-adherence were identified. [ABSTRACT FROM AUTHOR]

Background Ileus occurs after abdominal surgery and may be severe. Inhibition of prostaglandin release reduces post-operative ileus in a rat model. Aim To determine whether prostaglandin inhibition by cyclooxygenase inhibitors, celecoxib or diclofenac, could enhance gastrointestinal recovery and reduce post-operative ileus in humans. Methods Two hundred and ten patients undergoing elective major abdominal surgery were randomized to receive twice daily placebo ( n = 67), celecoxib (100 mg, n = 74) or diclofenac (50 mg, n = 69), preoperatively and continuing for up to 7 days. Primary outcomes were hallmarks of gut recovery. Secondary outcomes were paralytic ileus, pain and complications. Results There was no clinically significant difference between the groups for restoration of bowel function. There was a significant reduction in paralytic ileus in the celecoxib-treated group ( n = 1, 1%) compared with diclofenac ( n = 7, 10%) and placebo ( n = 9, 13%); P = 0.025, RR 0.20, CI 0.01–0.77. Pain scores, analgesia, transfusion requirements and adverse event rates were similar between study groups. Conclusions Perioperative low dose celecoxib, but not diclofenac, markedly reduced the development of paralytic ileus following major abdominal surgery, but did not accelerate early recovery of bowel function. This was independent of narcotic use and had no increase in post-operative complications. [ABSTRACT FROM AUTHOR]

Background Cyclooxygenase-2 (COX-2) is involved in oesophageal carcinogenesis, but the clinical and prognostic significance of COX-2 expression in oesophageal squamous cell carcinoma (ESCC) remains controversial. Aim To evaluate the clinicopathological and prognostic role of COX-2 expression in ESCC. Methods Studies assessing clinical or prognostic significance of COX-2 expression in ESCC published until December 2008 were selected. A meta-analysis was performed to clarify the impact of COX-2 expression on clinicopathological parameters or overall survival (OS) in ESCC. Results A total of 19 studies met the inclusion criteria, among which 17 studies were about the clinicopathological significance of COX-2 expression in ESCC, 12 studies were dealing with prognostic role of COX-2 expression in ESCC and 10 studies evaluated both of them. Overexpression of COX-2 was significantly correlated with not only the depth of invasion and TNM stage, with a combined odds ratio (OR) of 0.55 (95%CI: 0.34–0.90, Z = 2.41, P = 0.02) and 0.55 (95%CI: 0.32–0.95, Z = 2.13, P = 0.03) respectively but also the reduced OS with relative risk (RR) 1.42, 95% CI: 1.07–1.90, Z = 2.43, P = 0.02). Conclusions COX-2 might play an important role in the progress of ESCC, overexpression of COX-2 correlates with not only the depth of invasion and TNM stage but also the reduced OS. COX-2 might be a potential therapy target for ESCC and work as a prognostic factor for ESCC patients, yet the clinicopathological and prognostic role of COX-2 in ESCC still needs further confirmation by well-designed prospective studies. [ABSTRACT FROM AUTHOR]

Background Interferon (IFN-α)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results. Aim To investigate the natural course of IFNα-based -treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study. Methods We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFNα-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively. Results During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit. Conclusions IFNα-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR. [ABSTRACT FROM AUTHOR]

Background No consensus is available on the optimal initial treatment in Wilson disease. Aim To assess systematically the available literature of treatment in newly presenting patients with a presymptomatic, hepatic or neurological presentation of Wilson disease. Methods A systematic literature search of the MEDLINE, EMBASE and COCHRANE databases was performed. Original studies on clinical efficacy ofd-penicillamine, trientine, tetrathiomolybdate or zinc monotherapy as initial treatment in Wilson disease were included. A descriptive analysis of the relevant published data was performed. Results One randomized trial and 12 observational studies met the inclusion criteria. These studies were quite heterogeneous and generally of low validity. Nevertheless, according to currently available data, patients with hepatic presentation of Wilson disease are probably most effectively treated byd-penicillamine. Zinc seems to be preferred aboved-penicillamine for treatment of presymptomatic and neurological patients, as in these subgroups, the tolerance profile is in favour of zinc, while no obvious differences in clinical efficacy could be observed. Conclusions There is lack of high-quality evidence to estimate the relative treatment effects of the available drugs in Wilson disease. Therefore, multicentre prospective randomized controlled comparative trials are necessary. [ABSTRACT FROM AUTHOR]

Background Several randomized-controlled trials (RCTs) have sought to determine the efficacy of bovine lactoferrin in Helicobacter pylori eradication with equivocal results. Aim To evaluate the effect of bovine lactoferrin supplementation in H. pylori eradication. Methods Electronic databases, reviews, bibliographies, abstracts and conference proceedings were searched. Included trials had to be randomized or quasi-randomized and controlled, using bovine lactoferrin in the intervention group, treating Helicobacter-infected subjects and evaluating eradication of H. pylori as an outcome. Results The search identified five eligible RCTs (of 169). Data were available for 682 subjects (bovine lactoferrin group- n = 316; control group- n = 366). The pooled odds ratio (five studies) for eradication by intention-to-treat analysis was 2.22 (95% CI 1.44–3.44; P = 0.0003) using the fixed effects model (FEM) and 2.24 (95% CI 1.15–4.35; P = 0.0003) using the random effects model (REM) (Cochran’s Q = 6.83; P = 0.145). The pooled risk difference was 0.11 (95% CI 0.05–0.16; P = 0.0001) by FEM (Cochran’s Q = 6.67; P = 0.154) and 0.10 (95% CI 0.04–0.17; P = 0.0023) by REM. There was no significant difference in incidence of adverse effects. Conclusion Bovine lactoferrin potentially improves H. pylori eradication rates without any impact on adverse effects, but available evidence is limited and further research is necessary to confirm the findings. [ABSTRACT FROM AUTHOR]

Background Dexlansoprazole MR heals all grades of erosive oesophagitis (EO). Aim To assess efficacy and safety of dexlansoprazole MR in maintaining healed EO and heartburn relief. Methods In this randomized, double-blind trial, 445 patients with healed EO received dexlansoprazole MR 30 mg or 60 mg or placebo once daily for 6 months. This trial assessed maintenance of endoscopic healing (primary endpoint) and continued symptom relief based on daily diaries (secondary endpoints). Results Dexlansoprazole MR 30 mg and 60 mg were superior to placebo for maintaining healed EO ( P < 0.0025; Hochberg’s). By life-table analysis, maintenance rates were 75%, 83% and 27% for dexlansoprazole MR 30 mg, 60 mg and placebo respectively. Crude maintenance rates were 66% for both dexlansoprazole MR doses and 14% for placebo. Dexlansoprazole MR controlled heartburn (medians of 91–96% for 24-h heartburn-free days, 96–99% for heartburn-free nights). The only more common adverse event occurring at a significantly higher rate in dexlansoprazole MR groups than placebo when analysed per patient-months of exposure was upper respiratory tract infection. Conclusions Dexlansoprazole MR effectively maintained EO healing and symptom relief; most patients were heartburn-free for >90% of days. Both doses were well tolerated. [ABSTRACT FROM AUTHOR]

Background Ulcerative colitis (UC) has a major impact on the quality of life (QoL) of affected patients. Patient-reported outcomes have not been thoroughly evaluated in patients with UC receiving oral mesalazine (mesalamine). Aim To examine the effect of mesalazine on QoL of patients with mildly and moderately active UC and assess the time course of change, baseline disease severity, mesalazine dose and responder status on QoL parameters. Methods Inflammatory Bowel Disease Questionnaire (IBDQ) data were combined from two double-blind, randomized, multicentre, active-controlled trials assessing 2.4 and 4.8 g/day oral delayed-release mesalazine in 687 patients. Mean score changes from baseline were compared at 3 and 6 weeks and effects of baseline severity, mesalazine dose and response to therapy were examined. Results Mesalazine significantly improved IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively; P < 0.0001 for both). Improvement was greater for patients with moderate disease. Greater week 6 changes occurred in clinical responders than nonresponders (50.1 vs. 23.6 points, respectively; P < 0.0001). Conclusions Delayed-release oral mesalazine produces significant clinical and statistical improvements in QoL of patients with UC by 3 weeks, with further improvement at 6 weeks. [ABSTRACT FROM AUTHOR]

Background There are few studies examining the stability of gastrointestinal symptoms during prolonged periods of follow-up. Aim To examine this issue in individuals previously recruited into a community screening programme for Helicobacter pylori providing symptom data at study entry. Methods All traceable participants were sent dyspepsia and IBS questionnaires by post at 10 years. Symptom subgroups were assigned at baseline and 10-year follow-up. Individuals symptomatic at both time points who changed subgroup were compared with those symptomatic and remaining in the same subgroup. Results Three-thousand eight hundred and nineteen individuals provided data. At baseline, 2417 (63%) were asymptomatic or did not meet diagnostic criteria for a subgroup. Of these, 1648 (68%) remained asymptomatic at 10 years, whilst 769 (32%) reported symptoms. Of the 1402 individuals symptomatic at baseline, 404 (29%) remained in the same subgroup at 10 years, 603 (43%) changed subgroup and symptoms resolved or did not meet criteria for a subgroup in 395 (28%). Symptom stability was more likely in males [odds ratio (OR): 1.50; 99% confidence interval (CI): 0.97–2.31] and older subjects (OR per year: 1.09; 99% CI: 1.01–1.17). Conclusion Of those subjects symptomatic at baseline, almost three-quarters remained symptomatic at 10 years, but over 40% changed symptom subgroup. [ABSTRACT FROM AUTHOR]

Background Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. Aim To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Methods Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. Results 5-Aminosalicylic acids (5-ASA) remain the standard first-line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once-daily dosing, micropellet formulations, and high-dose tablets offer enhanced efficacy and improved compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ) and it has a role as a chemo-preventive agent in long-standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti-inflammatory targeted therapies include an anti-CD3 antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-γ agonists. Conclusion The evolution of novel oral 5-ASA formulations and dosage regimens, and recent development of new molecules have expanded the therapeutic armamentarium of UC. [ABSTRACT FROM AUTHOR]

Background While numerous studies report prevalence of constipation, use of laxatives is poorly understood. Aim To conduct a survey in seven countries evaluating prevalence of constipation and laxative use in its treatment. Methods Thirteen thousand eight hundred seventy-nine adults [approximately 2000 each from US, UK, Germany (GE), France (FR), Italy (IT), Brazil (BR) and South Korea (SK)] completed questionnaires assessing occurrence, frequency, duration and laxative use for treating constipation. Results Overall, 12.3% of adults had constipation [range: 5% (GE) to 18% (US)] in the prior year. A greater percent of women from all countries and elderly from all except SK and BR reported constipation; odds ratios for constipation among women and elderly were 2.43 (95% CI: 2.18–2.71) and 1.5 (95% CI: 1.25–1.73) vs. men and young subjects. Among those with constipation, 16% (SK) to 40% (US) used laxatives. Laxative use was generally associated with increasing age, symptom frequency and lower income and education. A similar percentage of men and women with constipation reported using laxatives; a greater percentage of women used laxatives for a longer time. Conclusions Prevalence of self-defined constipation and laxative use varies among countries. Prevalence is generally related to gender and age, whereas laxative use is related to age, but not to gender. [ABSTRACT FROM AUTHOR]

Background The evidence on whether high-dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed. Aim To evaluate the evidence on the usefulness of high-dose PPI in standard triple therapy by performing a systematic review and a meta-analysis. Methods A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high-dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager. Results Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention-to-treat cure rate of 82% was achieved with high-dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01–1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg. Conclusion High-dose PPI seems more effective than standard-dose for curing H. pylori infection in 7-day triple therapy. [ABSTRACT FROM AUTHOR]

Background Remission and response are the main outcomes to evaluate the efficacy of new treatments for Crohn’s disease (CD). Aim To explain variation of remission and response rates in active luminal CD. Methods We studied control patients from trials of biological therapies through articles retrieved by MEDLINE search (from 1997 to 2007) and by bibliography review. Thousand nine hundred and thirteen control patients from 28 trials were identified; data were extracted by three independent observers and pooled by DerSimonian and Laird random effect model; factors influencing remission and clinical response were explored by metaregression for aggregated data. Results The pooled control rates of remission and response were 17% and 33%, respectively, both with significant heterogeneity among studies ( P < 0.0001). At metaregression, the time of primary outcome evaluation was associated with remission, whereas the trial’s criteria for defining response and publication year were predictors of response. CDAI score, CRP levels or other clinical variables related with disease activity or concomitant medications were not significant factors. Conclusions Populations used as ‘add-on’ treatment comparator in trials of biological therapies for active luminal CD are poorly characterized and outcomes are heterogeneous. Planning of future trials will require better description of patients and concomitant therapies, blinding of outcome assessors and homogeneous criteria of outcome definition. [ABSTRACT FROM AUTHOR]

Background The efficacy of treatment against hepatitis C virus has improved, but it is still far from ideal. Thus, new antihepatitis C virus therapies are required. Aim To evaluate the data on antihepatitis C virus approaches beyond the current standard combination of pegylated interferon-alpha and ribavirin. Method We reviewed the available literature regarding novel antihepatitis C virus options, given alone or in combination with existing agents. Results New interferons and ribavirin alternatives have been tried aiming to improve the efficacy and the safety/tolerability profile of standard agents. The hepatitis C virus polymerase and NS3/4A protease have been rather popular targets for new antihepatitis C virus agents. The combination of such inhibitors with pegylated interferon-alpha and ribavirin seems to act synergistically and to prevent viral resistance, compared to monotherapies. Several novel immunomodulators are currently evaluated and may be useful in combination therapies. Alternative strategies (inhibition of hepatitis C virus protein translation, assembly/release or binding) or agents with different modes of action (statins, S-adenosylmethionine and herbs) need further evaluation. Conclusions Many novel promising antihepatitis C virus agents are being developed, offering hope for future therapies that may target multiple points of the viral life cycle and/or host immune response. Newer approaches should ideally provide safe, effective and more tolerable therapy to all chronic hepatitis C virus patients. [ABSTRACT FROM AUTHOR]

Background A new technique of gene regulation, termed RNA interference, has emerged recently. RNA interference utilizes short double-stranded RNA to inhibit selectively gene expression of complementary RNA nucleotide sequences after transcription, but prior to translation. Gastrointestinal and hepatic disorders may be particularly amenable to therapeutic RNA interference intervention because of the relative ease of delivery of drugs to the gastrointestinal tract and liver. Aim To examine the published literature for potential clinical uses of RNA interference in gastroenterology and speculate on future therapies for luminal disease. Methods Reports were identified using PubMed and the search term ‘RNA interference’, focusing on therapeutic uses related to gastrointestinal and liver disease. Results Cellular and animal models demonstrate the potential application of short-interfering RNA-based therapies for viral hepatitis and inflammatory bowel disease. With validation of specific targets and better in vivo delivery of short-interfering RNA, RNA interference may represent a new frontier for molecular-targeted therapy in gastroenterology and hepatology. Conclusions Short-interfering RNA provides a novel and specific means to inhibit gene expression. Translation to the clinical arena will require further definition of side-effects, off-target effects and delivery systems. Ultimately, mucosally applied or endoscopically delivered short-interfering RNA could be one of the earliest clinical uses of short-interfering RNA therapy. [ABSTRACT FROM AUTHOR]

Background More than two-thirds of ulcerative colitis patients experience at least one relapse over a period of 10 years. Treatments that reduce the likelihood of relapses also reduce the risk of long-term complications. Aim To review three topics: the current standard of treatment for ulcerative colitis, evolving concepts in treatment, and disease modification as a treatment goal of the future. Results Currently, 5-aminosalicylates are the standard treatment for the induction and maintenance of remission in mild-to-moderate ulcerative colitis patients. Evidence suggests that patients who take oral 5-aminosalicylates regularly are nearly six times more likely to experience regression in disease severity than those who do not. Additional treatment options such as corticosteroids, immunomodulators, biological therapies and ciclosporin are available for moderate-to-severe ulcerative colitis patients, or those who do not respond to 5-aminosalicylate. Surgery becomes pertinent for more than one-third of ulcerative colitis patients during the course of their disease. With the availability of a variety of therapies, advances in surgery and improved management strategies, a better understanding of patient treatment expectations can help improve the quality of care for ulcerative colitis patients. Conclusions Disease modification is increasingly becoming a treatment goal in the management of ulcerative colitis. However, long-term studies are needed to examine further the disease modifying role of 5-aminosalicylates. [ABSTRACT FROM AUTHOR]

Background At least 25% of individuals diagnosed with Crohn’s disease (CD) have onset of disease in childhood. Almost all children with CD have nutritional impairments, such as weight loss or stunting, at diagnosis or subsequently. Nutritional therapy (exclusive enteral nutrition) is established as a valid and effective treatment in paediatric CD. The advantages of this approach are induction of remission and control of inflammatory changes, mucosal healing, positive benefits to growth and overall nutritional status, and avoidance of other medical therapies. Aim To provide a comprehensive up-to-date review of the roles of nutritional therapy in CD and of the data supporting this therapy. Methods A search of PubMed was performed with search terms ‘enteral nutrition’, ‘nutritional therapy’, ‘Crohn disease’ and ‘children’. Relevant articles were selected from this search. In addition, the reference lists of available articles were reviewed for further relevant articles. Results Nutritional therapy offers numerous benefits in the management of CD. Recent work has begun to elucidate the likely mechanisms of this therapy. These include direct mucosal anti-inflammatory effects and alteration of intestinal microflora. Conclusion Further studies are required to define longer-term effects of nutritional therapy in patients with CD. [ABSTRACT FROM AUTHOR]

Background Patient acceptance of bowel preparation can affect colon cancer screening compliance. Aim To compare patient acceptance, preference and tolerability of 32-sodium phosphate tablets vs. 2L polyethylene glycol solution plus 4 bisacodyl tablets for bowel preparation. Methods A prospective, randomized, investigator-blinded, multicentre trial was performed. Results were based on responses to a patient questionnaire. Results 411 patients (205 sodium phosphate; 206 polyethylene glycol plus bisacodyl) completed the study preparation and patient questionnaire prior to colonoscopy. More patients receiving sodium phosphate vs. polyethylene glycol plus bisacodyl found it easy to take (77% vs. 42%), reported it to be without taste (47% vs. 6%), found it easy to take with respect to volume of liquid prescribed (72% vs. 27%) and indicated they would take the same preparation again in the future (96% vs. 74%, P < 0.0001 for all). Fewer patients receiving sodium phosphate vs. polyethylene glycol plus bisacodyl had to take time off work or change ordinary activities to take the study preparation (18% vs. 52%, P < 0.0001). Nausea, vomiting, bloating and abdominal pain were reported less frequently with sodium phosphate ( P < 0.0013). Conclusion The 32-tablet sodium phosphate dosing regimen was easier to take and better tolerated, when compared to 2L polyethylene glycol plus bisacodyl tablets for bowel preparation. [ABSTRACT FROM AUTHOR]

Background Racecadotril (acetorphan) is an antisecretory drug that exerts its antidiarrhoeal effects by inhibiting intestinal enkephalinase. Aim To summarize studies testing the efficacy and safety of racecadotril for treating children with acute gastroenteritis. Methods Reports were gathered by searching electronic databases MEDLINE, EMBASE, the Cochrane Library (all up to April 2007), relevant journals, and bibliographies of reviewed articles. Only randomized-controlled trials were included. Results Three randomized-controlled trials (471 participants) met the inclusion criteria. Two trials reported stool output, and data suggested less stool output in the racecadotril group than in the control group. The duration of diarrhoea was significantly reduced in the three trials reporting this outcome. Achievement of a cure by day 5 was similar in both groups. Adverse effects were similar in both groups. Conclusions The small number of included trials provided some evidence in favour of the use of racecadotril over placebo or no intervention, to reduce the stool output and duration of diarrhoea in children with acute gastroenteritis. However, more data in out-patients are needed. The safety as well as the cost-effectiveness of the therapy should be explored, before routine therapy with racecadotril is recommended. [ABSTRACT FROM AUTHOR]

Aim To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn’s disease remission. Methods A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn’s disease activity index >150, or an increase in baseline by at least 60–100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated. Results Treatment with pH 7-dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12–0.65; P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17–0.85; P = 0.0113). However, treatment with controlled-release mesalazine and pH 6-dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6-dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and 4.4%, respectively, for pH 6-dependent mesalazine. Conclusion Further trials of pH 7-dependent mesalazine formulations are warranted in the maintenance of remission in Crohn’s disease. [ABSTRACT FROM AUTHOR]

Aim To review evidence for the effectiveness of Lactobacillus GG (LGG) in treating acute infectious diarrhoea in children. Methods The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and LGG: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials (RCTs) were included. Results Eight RCTs (988 participants) met the inclusion criteria. Compared with controls, LGG had no effect on the total stool volume (two RCTs, n = 303). However, LGG was associated with a significant reduction in diarrhoea duration (seven RCTs, 876 infants, weighted mean difference, WMD −1.1 days (95% confidence interval, CI −1.9 to −0.3), particularly of rotavirus etiology (WMD −2.1 days, 95% CI −3.6 to −0.6), risk of diarrhoea >7 days (one RCT, n = 287, relative risk 0.25, 95% CI 0.09–0.75) and duration of hospitalization (three RCTs, n = 535, WMD −0.58, 95% CI −0.8 to −0.4; significance was lost in the random effect model). There was no reduction in the number of stools at any time interval. Conclusions The use of LGG is associated with moderate clinical benefits in the treatment of acute diarrhoea in children. These findings should be interpreted with caution due to the important methodological limitations and heterogeneity of most of the studies. [ABSTRACT FROM AUTHOR]

Aim To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis. Methods In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0–3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation ( r). Results 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively ( P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores ( r = −0.029, −0.029 and −0.021; P = 0.003, 0.003 and 0.032, respectively). Conclusion A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated. [ABSTRACT FROM AUTHOR]

Background Constipation is a common, often chronic, gastrointestinal motility disorder characterized by such symptoms as straining, hard stool, and infrequent defecation. Published literature is limited regarding symptom prevalence, healthcare-seeking behaviour, and patient satisfaction with traditional therapies for chronic constipation. Aim To assess the prevalence of chronic constipation among a random sample of Americans, to identify the frequency, severity and bothersomeness of their symptoms, and to assess satisfaction levels with traditional treatments. Methods All members ( N = 37 004) of the Knowledge Networks Panel, representative of the US population, participated in a web-based survey. Eligibility was established using a six-question screener. Results Of the 24 090 panellists consenting to participate, 557 met eligibility requirements and took the 45-question survey. The most prevalent symptom was straining (79%). Hard stool and straining were the top two severe symptoms, and bloating, straining and hard stool were the top three bothersome symptoms. Symptoms affected quality of life of more than half (52%) the respondents. Among those who worked or went to school, 12% experienced reduced productivity and a mean of 2.4 days of absence in the month before the survey. Most respondents had used (96%) or were using (72%) constipation relief therapy; however, nearly half (47%) were not completely satisfied, mainly because of efficacy (82%) and safety (16%) concerns. Conclusions Chronic constipation is common. Individual symptoms are often severe and bothersome, and many patients are dissatisfied with traditional treatment options, primarily because of lack of efficacy. [ABSTRACT FROM AUTHOR]

Background Over-the-counter histamine-2 receptor antagonists, antacids and alginate/antacids are commonly used for gastro-oesophageal reflux disease. Aim To conduct a systematic review and meta-analysis of related treatment trials. Methods We performed a systematic search and abstraction of randomized, placebo-controlled trials conducted during 1972–2005. Study quality was measured by the Jadad score (0–5). Results were pooled using random effects model. Results Ten trials ( n = 3442, placebo = 2940; Jadad score 3.5) showed a higher response with histamine-2 receptor antagonists in regard to complete relief of heartburn, symptomatic improvement, and episodes requiring rescue antacids. The absolute benefit increase was 10–12% and relative benefit increase was 19–41%. Four trials ( n = 578, placebo = 577; Jadad score 3.5) showed a trend in favour of antacids in symptomatic improvement (absolute benefit increase 8%, 95% CI: 0–16%; relative benefit increase 0.11) and requirement of rescue antacids (OR 0.70, 95% CI: 0.59–0.84). Four trials ( n = 146, placebo = 138; Jadad score 3.8) found alginate/antacid combination superior to placebo in symptomatic improvement (absolute benefit increase 26%, 95% CI: 12%–41%, relative benefit increase 0.60). Conclusions Over-the-counter medications are effective in treating symptomatic gastro-oesophageal reflux disease. Compared with the placebo response, which ranged between 37% and 64%, the relative benefit increase was up to 41% with histamine-2 receptor antagonists, 60% with alginate/antacid combinations, and 11% with antacids. [ABSTRACT FROM AUTHOR]

Background Functional abdominal pain disorders (FAPD) are common in school-aged children; however, there is no reliable treatment. Aim To determine the efficacy of Lactobacillus rhamnosus GG (LGG) for treating FAPD in children. Methods A total of 104 children who fulfilled the Rome II criteria for functional dyspepsia (FD), or irritable bowel syndrome (IBS), or functional abdominal pain (FAP) were enrolled in a double-blind, randomized controlled trial in which they received LGG ( n = 52), or placebo ( n = 52) for 4 weeks. Results For the overall study population, those in the LGG group were more likely to have treatment success (no pain) than those in the placebo group (25% vs. 9.6%, relative benefit (RB) 2.6, 95% confidence interval (CI): 1.05–6.6, number needed to treat (NNT) 7, 95% CI: 4–123). For children with IBS ( n = 37), those in the LGG group were more likely to have treatment success than those in the placebo group (33% vs. 5%, RB 6.3, 95% CI: 1.2–38, NNT 4, 95% CI: 2–36) and reduced frequency of pain ( P = 0.02), but not pain severity ( P = 0.10). For the FD group ( n = 20) and FAP group ( n = 47), no differences were found. Conclusion The LGG appears to moderately increase treatment success, particularly among children with IBS. [ABSTRACT FROM AUTHOR]

Background In November 2002, alosetron HCl (Lotronex, GlaxoSmithKline Research Triangle Park, NC, USA) was re-introduced to the US marketplace for women with severe diarrhoea-predominant irritable bowel syndrome. In support of the re-introduction, a risk management programme was implemented, which included a patient follow-up study in which all users of alosetron could participate. Aim We report on the methods used and the effectiveness of key elements of the risk management programme. Methods Patients voluntarily enroled in the study and completed questionnaires at baseline, after 5 and 10 weeks, and quarterly thereafter. Questions focussed on patient eligibility, knowledge of risks and benefits, and adherence to the recommended programme elements for education, prescribing and dispensing. Results Between December 2002 and 2004, 4803 patients enrolled in the study, and <3% were lost to follow-up. The average follow-up time was approximately 6 months, and the response rate for each assessment was >95%. A total of 90% of patients at baseline met the full clinical criteria recommended for the treatment. Patient adherence to the risk management programme was >87%. Conclusions Using the Lotronex risk management programme, patients met clinical criteria, were knowledgeable about treatment risks and benefits, and were adherent to the process elements of the programme. These patients seemed to engage in active dialogue with their physicians about symptoms and use of alosetron. [ABSTRACT FROM AUTHOR]

Background Hepatitis B virus-associated glomerulonephritis is an infrequent complication of chronic hepatitis B virus (HBV) with significant morbidity. A causal association between hepatitis B virus infection and the development of glomerulonephritis remains controversial. Also, the optimal therapy is undefined although several approaches have been made. Aim To evaluate the efficacy and safety of anti-viral therapy (interferon or lamivudine) in HBV-associated glomerulonephritis by a systematic review and meta-analysis of clinical trials. Methods The primary outcome was clinical response (as a measure of efficacy); the secondary outcomes were drop-out rate (as a measure of tolerability), and virological response. We used the random effects model of DerSimonian and Laird, with heterogeneity, sensitivity and meta-regression analyses. Results We identified six clinical trials (84 unique patients); three had controlled design. The overall estimate for proteinuria remission was 65.2% (95% confidence intervals: 52.7-75.9%), Q-test for heterogeneity = 7.731, P = 0.172, I2 = 35.327. The overall estimate for hepatitis B e antigen clearance was 62.0% (95% confidence intervals: 50.5-72.2%). The overall estimate for drop-out rate was 12.7% (95% confidence intervals: 6.4-23.6%). Meta-regression analysis showed a significant link between hepatitis B e antigen clearance and logit rate of proteinuria remission after interferon therapy [coefficient -2.585 (S.E. 1.089), P = 0.017]. Conclusion Remission of the nephrotic syndrome is accompanied by clearance of HBV replication, supporting the role of the virus in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. Aim To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. Methods Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. Results Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment. Conclusions Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption. [ABSTRACT FROM AUTHOR]

Background Though functional gastrointestinal complaints are recognised as being common throughout the world, there have been few comparative studies of prevalence. Aim To compare the prevalence and management of abdominal cramping/pain in nine countries. Methods In a two-stage community survey, approximately 1000 subjects were interviewed in each of nine countries to establish the demographics of individuals with abdominal cramping/pain (stage 1) followed by market research-driven interviews with ≥200 sufferers per country (stage 2). Results 9042 subjects were interviewed in stage 1. Mexico (46%) and Brazil (43%) had the highest prevalence of abdominal cramping/pain; Japan the lowest (10%). Abdominal cramping/pain was more common in women (12–55%) than in men (7–38%). About 1717 subjects participated in stage 2; 65% were women and the average age at symptom onset was 29 years. The frequency of episodes differed between countries, being highest in the US (61% suffered at least once in a week). Sufferers in the US and Latin America reported a higher usage of medications (around 90%) than those in Europe (around 72%). In most countries over-the-counter drugs were principally used. Antispasmodic drugs were most popular in Latin America and Italy, antacids in Germany and the UK. Drug therapy decreased the duration of episodes (by up to 81% in Brazil). Conclusions The community prevalence, severity, healthcare seeking and medication usage related to abdominal cramping/pain are high overall, but vary considerably between countries. [ABSTRACT FROM AUTHOR]

Acid suppression therapy with proton pump inhibitors is associated with well-established benefits in the management of gastro-oesophageal reflux (GERD) and other acid-related disorders. However, a number of issues still remain unsettled. Despite their clinical efficacy, when given once daily, currently available proton pump inhibitors may not adequately control intragastric acidity during the night in a significant proportion of both healthy subjects and GERD patients, in whom symptom relief remains suboptimal. Although some novel proton pump inhibitors have been synthesized, only few reached clinical testing. Amongst them, tenatoprazole represents a true advance displaying a long half-life (five to seven times longer than that of currently available drugs) and extended acid suppression covering both day and night. All the available clinical studies suggest both pharmacokinetic and pharmacodynamic advantages of tenatoprazole over esomeprazole. As this last compound provides – amongst the members of the class – the most effective control of intragastric pH whatever the parameter considered, it is conceivable that tenatoprazole could similarly be better than the other existing proton pump inhibitors. Tenatoprazole appears to be a promising proton pump inhibitor for the treatment of acid-related diseases, where it has the potential to address unmet clinical needs. [ABSTRACT FROM AUTHOR]

Several important pathophysiological mechanisms have been identified in functional dyspepsia, however a complete understanding of these mechanisms and beneficial therapeutic strategies are still lacking. Based on the currently available literature we aimed at providing a critical view on one of these pathophysiological mechanisms, impaired accommodation. Although impaired gastric accommodation is identified as a major pathophysiological mechanism, the clinical evidence supporting its role as an important therapeutic target is currently still lacking. Treatment with fundic relaxant drugs has shown conflicting results and has been rather disappointing in general. These negative findings could be explained by the fact that impaired fundic accommodation is part of a more complex disorder involving other regions of the proximal gut or by the increasing insight that central mechanisms may play an important role. Future studies of impaired accommodation should take these considerations into account. [ABSTRACT FROM AUTHOR]

Background Mesalazine is among the medications most commonly prescribed by gastroenterologists, having to a large extent superseded sulfasalazine (sulphasalazine). However, there are still a number of aspects regarding its use which provoke debate and controversy. Aim To provide a systematic assessment of the evidence for the use of mesalazine in ulcerative colitis and Crohn's disease. Methods References were identified using PubMed database. Additional references were identified with related article searches. Results Mesalazine has a clear role in the maintenance of remission in ulcerative colitis and management of mild to moderately active disease, although the efficacy of topical preparations or combined topical and oral is clearly superior to oral alone. Evidence that increasing the dose of oral mesalazine improves efficacy is not clear-cut. The benefits of mesalazine in the management of acute Crohn's disease and the maintenance of remission are questionable and alternative treatments are usually more appropriate. Emerging evidence suggests that maintenance mesalazine reduces the risk of neoplastic progression in chronic ulcerative colitis. Compliance with therapy is thus important, as is an understanding of individuals most likely to default on this. Conclusion Evidence for a beneficial effect of mesalazine is largely confined to the management of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background Acid pockets at the gastro-oesophageal junction escape buffering from meals in the stomach. Combining high-dose antacid with alginate may therefore be of benefit in gastro-oesophageal reflux disease. Aim To characterize the antacid and raft-forming properties of Rennie alginate suspension (containing high-dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands). Methods The in vitro acid-neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH-recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double-blind, placebo-controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers. Results Compared with Gaviscon, Rennie alginate had a higher acid-neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long-lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min. Conclusions The dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro-oesophageal reflux disease particularly considering recent findings regarding ‘acid pockets’. [ABSTRACT FROM AUTHOR]

Background Diagnosis of Whipple's disease, a rare systemic infection affecting predominantly the small bowel, is based on the identification of the bacterium Tropheryma whipplei. Aims To make explicit diagnostic uncertainties in Whipple's disease through a decision analysis, considering two different clinical scenarios at presentation. Methods Using appropriate software, a decision tree estimated the consequences after testing different strategies for diagnosis of Whipple's disease. Probabilities and outcomes to determine the optimum expected value were based on MEDLINE search. Results In patients with clinically-predominant intestinal involvement, diagnostic strategies considering intestinal biopsy for histology (including appropriate staining) and the polymerase chain reaction testing for bacterial DNA were similarly effective. In case of failure of one procedure, the best sequential choice was a polymerase chain reaction analysis after a negative histology. Of the five strategies tested for cases with predominant focal neurological involvement, the stereotaxis cerebral biopsy evidenced the highest expected value. However, using quality-adjusted life-years considering the morbidity of methods, intestinal biopsy for PCR determination was the best choice. Conclusions In patients with Whipple's disease having predominant digestive involvement, intestinal biopsies for histology should be indicated first and, if negative, a bacterial polymerase chain reaction determination should be the next option. Although the molecular polymerase chain reaction assessment of cerebral biopsies has the highest diagnostic yield in neurological Whipple's disease, its associated morbidity means that analyses of intestinal samples are more appropriate. [ABSTRACT FROM AUTHOR]

When patients with the typical reflux symptoms of heartburn, regurgitation, or both, undergo endoscopy, up to 75% will not have endoscopic oesophagitis or evidence of Barrett's oesophagus. These patients have been described as having endoscopic negative or, more commonly, non-erosive reflux disease (NERD). Patients without oesophagitis, but with a positive pH test, can be diagnosed with gastro-oesophageal reflux disease (GERD). Some experts also consider a response to proton pump inhibitor therapy as proof of GERD in a patient with the correct symptoms and a negative endoscopy. Patients with normal acid exposure, but who report symptoms with a majority of their reflux episodes documented during an ambulatory pH study, have also been considered to have NERD, although others have labelled them as having ‘functional heartburn’. Finally, there are some patients who have reflux symptoms and respond to reflux therapy, but have no demonstrable reflux by either endoscopy or ambulatory reflux testing. Whether these patients are part of the GERD spectrum or have another diagnosis is not clear. It seems that the most widely used definition of functional disease (the Rome II criteria) would include these patients as having functional heartburn, as it was defined as ‘greater than or equal to 12 weeks of either continuous or intermittent symptoms of burning retrosternal discomfort or pain without pathologic GERD, achalasia, or other motility disorders with a recognized pathologic basis’. This article reviews potential differences in pathophysiology between erosive oesophagitis and NERD; explores whether symptoms can help distinguish NERD patients from erosive oesophagitis patients; and explores the evaluation and therapy of these patients. [ABSTRACT FROM AUTHOR]

Background Pegylated interferon alfa-2a (40 KD) plus ribavirin therapy induces sustained virological response rates up to 63% in randomized-controlled trials. Aim To conduct a prospective open-label programme to examine the efficacy and safety of this therapy in routine clinical practice. Methods Treatment-naive patients with chronic hepatitis C received, at the discretion of the investigator, pegylated interferon alfa-2a 180 μg/week + ribavirin 800 mg/day for 24 or 48 weeks. In total, 508 patients were enrolled [334 non-cirrhotic; 174 cirrhotic (defined as stage F3 and F4)]. Results In genotype 1 patients treated for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and 34% in cirrhotics. Sustained virological response rates in genotype 2 or 3 non-cirrhotics were 79% (24 weeks) and 72% (48 weeks). Corresponding values for cirrhotic genotype 2/3 were 66% and 44%. The negative predictive value of an early virological response at week 12 was 94%. Predictive factors for sustained virological response on multivariate analysis were genotype (2/3 vs. 1), low viral load and degree of fibrosis. Rates of serious adverse events (≤5%) and adverse events inducing withdrawal (≤8%) were comparable with the phase III trials. Conclusion Efficacy and safety of pegylated interferon alfa-2a + ribavirin in clinical practice is comparable with results of randomized-controlled trials. [ABSTRACT FROM AUTHOR]

Although proton-pump inhibitors are highly effective for the treatment of gastro-oesophageal reflux disease, there are issues with long-term maintenance therapy: not all patients require full daily dose for maintenance treatment, some patients are reluctant to take long-term daily medication, and long-term PPI therapy is inadequate for some patients. This article aims to review alternatives to daily proton-pump inhibitor therapy for the long-term management of gastro-oesophageal reflux disease, including intermittent or on-demand proton-pump inhibitor use, as well as endoscopic and surgical options. On-demand proton-pump inhibitor therapy has demonstrated efficacy in achieving acceptable symptom control, healing and maintenance of quality of life for a proportion of patients with gastro-oesophageal reflux disease. Endoscopic antireflux procedures can reduce the need for proton-pump inhibitor therapy, but safety and durability of these procedures require more study. Surgical treatment of gastro-oesophageal reflux disease in properly selected patients has demonstrated efficacy in reducing symptoms and the need for proton-pump inhibitor therapy; however, long-term follow-up suggests that it is not a permanent solution for many patients. While daily proton-pump inhibitor therapy remains the main treatment regimen option for most patients with gastro-oesophageal reflux disease, on-demand therapy may prove effective for many patients. Endoscopic anti-reflux therapies and surgery are options for patients who prefer nonpharmacological treatment, but experience is limited at this point in time for the former. [ABSTRACT FROM AUTHOR]

Background : Studies have shown that past alcohol consumption reduces response rates in patients with chronic hepatitis C treated with interferon monotherapy. Aim : To clarify the importance of alcohol consumption on response rates in patients undergoing treatment with pegylated interferon and ribavirin. Methods : In a single centre, prospective study, median daily alcohol consumption (determined by previously validated method) and quartiles of alcohol consumption were calculated. Univariate and binary logistic regression analyses were performed using treatment response status as the dependent variable. Results : Overall, in an intention-to-treat analysis, 34 of 115 patients (30%) responded to treatment. In univariate analysis, black patients, especially those with hepatitis C virus genotype 1, high viral load and low alanine aminotransferase were significantly less likely to respond. Predictors of response by regression analysis included alcohol <30 g/day (OR = 3.02, 95% CI: 1.02–8.93; P = 0.04), non-genotype 1 status (OR = 1.98, 95% CI: 1.03–3.80; P = 0.04) and non-black race (OR = 2.79, 95% CI: 1.33–5.85; P = 0.006). Conclusions : Median daily alcohol use >30 g/day is associated with failure to respond to pegylated interferon and ribavirin for treatment of hepatitis C. Past alcohol use should be evaluated when considering treatment for hepatitis C. [ABSTRACT FROM AUTHOR]

Bifidobacteria, naturally present in the dominant colonic microbiota, represent up to 25% of the cultivable faecal bacteria in adults and 80% in infants. As probiotic agents, bifidobacteria have been studied for their efficacy in the prevention and treatment of a broad spectrum of animal and/or human gastrointestinal disorders, such as colonic transit disorders, intestinal infections, and colonic adenomas and cancer. The aim of this review is to focus on the gastrointestinal effects of bifidobacteria as probiotic agents in animal models and man. The traditional use of bifidobacteria in fermented dairy products and the GRAS (‘Generally Recognised As Safe’) status of certain strains attest to their safety. Some strains, especially Bifidobacterium animalis strain DN-173 010 which has long been used in fermented dairy products, show high gastrointestinal survival capacity and exhibit probiotic properties in the colon. Bifidobacteria are able to prevent or alleviate infectious diarrhoea through their effects on the immune system and resistance to colonization by pathogens. There is some experimental evidence that certain bifidobacteria may actually protect the host from carcinogenic activity of intestinal flora. Bifidobacteria may exert protective intestinal actions through various mechanisms, and represent promising advances in the fields of prophylaxis and therapy. [ABSTRACT FROM AUTHOR]

Acid suppression plus two antibiotics is currently considered the gold standard anti- Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively ( P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level ( P < 0.01) and area under the curve ( P < 0.02). Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens. [ABSTRACT FROM AUTHOR]

Although recent studies suggest that gastro-oesophageal reflux disease may frequently contribute to ear, nose and throat and respiratory diseases, the cause-and-effect relationship is far from proven. The review will address this controversial topic emphasizing recent literature raising concerns about the credibility of this association and our tests to make this diagnosis. The author believes these extraoesophageal symptoms suspected to be secondary to gastro-oesophageal reflux disease are an unresolved issue, but selective use of aggressive proton-pump inhibitor therapeutic trials may help to resolve this problem in our individual patients. [ABSTRACT FROM AUTHOR]

The management of primary sclerosing cholangitis (PSC) is hindered by incomplete understanding of the pathogenesis of the disease and the lack of good prognostic models. Few large randomized controlled trials of drug therapy have been published. Best practice in the management of PSC is currently based therefore on careful interpretation of the available evidence, close observation of individual patients and clinical experience of the disease. Drug therapy is useful for alleviating symptoms. Ursodeoxycholic acid may slow progression of the disease and reduce the frequency of complications. Consensus is emerging on the issues of screening for the malignant complications of PSC and the indications for liver transplantation are becoming broader and encompassing the earliest stages of cholangiocarcinoma. In view of the rarity of the disease in the general population, large international collaborations to study PSC are necessary to provide clearer answers in areas of uncertainty, and these are now beginning to emerge. [ABSTRACT FROM AUTHOR]

To determine the efficacy of threeHelicobacter pylorieradication regimens and factors affecting the eradication results in Finland.A total of 342H. pylori-positive adult patients from primary health care referred for gastroscopy at 23 centres in different parts of Finland were randomized to receive either (i) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d.s. (LAM), (ii) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC), or (iii) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s. (RMT). A13C-urea breath test was performed 4 weeks after therapy.The eradication result could be assessed in 329 cases. Intention-to-treat cure rates of LAM, LAC, and RMT were 78, 91 and 81%. The difference was significant between LAM and LAC (P = 0.01) and between LAC and RMT (P = 0.04). The eradication rates in cases with metronidazole-susceptible vs. -resistant isolates were for LAM 93% vs. 53% (P = 0.00001), for LAC 95% vs. 84%, and for RMT 91% vs. 67% (P = 0.002). Previous antibiotic use, smoking, and coffee drinking reduced the efficacy of therapy.In unselected patients in primary health care, LAC was the most effective first-line eradication. [ABSTRACT FROM AUTHOR]

Oral ulceration is a common problem, and is sometimes a marker of gastroenterological disease. Patients with signs or symptoms of oral ulcers are sometimes referred to gastroenterology clinics, however, in most instances the ulcers does not reflect gastrointestinal disease. Indeed, a spectrum of disorders other than those of the gut can give rise to oral mucosal ulcers ranging from minor local trauma to significant local disease such as malignancy or systemic illness. This present article reviews aspects of the aetiology, diagnosis and management of common ulcerative disorders of the oral mucosa. [ABSTRACT FROM AUTHOR]

: The treatment effects of primary prophylactic endoscopic variceal ligation are unclear.: To compare the treatment effects of endoscopic variceal ligation andβ-blockers for primary prophylaxis of oesophageal variceal bleeding. In addition, a subgroup analysis was done with the purpose to delineate differences in the effects of intervention that were biologically based.: We performed a literature search for randomized controlled trials, which compared the treatment effects of endoscopic variceal ligation withβ-blockers for primary prophylaxis of oesophageal variceal bleeding. Of the 955 articles screened, eight randomized-controlled trials including 596 subjects (285 with endoscopic variceal ligation and 311 withβ-blockers) were analysed. Outcomes measures evaluated were first gastrointestinal bleed, first variceal bleed, all-cause deaths, bleed-related deaths and severe adverse events. The measure of association employed was relative risk; with heterogeneity and sensitivity analyses.: Variceal obliteration was obtained in 261 (91.6%) patients and targetβ-blockers therapy was achieved in 294 (94.5%) patients (P = 0.19). Endoscopic variceal ligation compared withβ-blockers significantly reduced rates of first gastrointestinal bleed by 31% (RR, 0.69; 95% CI: 0.49–0.96;P = 0.03; NNTB = 15) and first variceal bleed by 43% (RR, 0.57; 95% CI: 0.38–0.85;P = 0.0067; NNTB = 11). All-cause deaths and bleed-related deaths were unaffected (RR, 1.03; 95% CI: 0.79–1.36;P = 0.81 and RR, 0.84; 95% CI: 0.44–1.61;P = 0.60 respectively). Severe adverse events were significantly less in endoscopic variceal ligation compared withβ-blockers (RR, 0.34; 95% CI: 0.17–0.69;P = 0.0024; NNTB = 28). Sensitivity analysis of five trials published in peer review journals and four trials with high quality showed results similar to those seen in the primary analysis of all the eight trials, confirming stability of conclusions. Following variceal obliteration with endoscopic variceal ligation, oesophageal varices recurred in 83 (29.1%) patients. Seven (28.1%) patients bled with one fatal outcome. In subgroup analyses, endoscopic variceal ligation had significant advantage compared wtihβ-blockers in trials including≤30% patients with alcoholic cirrhosis,>30% patients with Child Class C cirrhosis and>50% patients with large varices.: In patients with cirrhosis with moderate to large varices and who have not bled, endoscopic varices ligation compared withβ-blockers significantly reduced bleeding episodes and severe adverse events, but had no effect on mortality. [ABSTRACT FROM AUTHOR]

: To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re-exposed to gluten after only a few years and now on a gluten-containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten-free diet after childhood diagnosis.: A total of 195 adults with a biopsy suggestive of coeliac disease in childhood, who either had adhered to a gluten-free diet for at least 1 year after diagnosis and now are either on gluten-free diet (n = 110) or on gluten-containing diet (n = 85), and adults with newly diagnosed coeliac disease (n = 165) underwent a medical check-up.: Body mass index and main laboratory indices were statistically different among groups (lowest in never on gluten-free diet, highest in gluten-free diet). The lowest average levels of bone mineral density were found among never on gluten-free diet patients. Prevalence of autoimmune disorders was increased in never on gluten-free diet when compared with the transient gluten-free diet and gluten-free diet groups. Histology revealed villous subatrophy in all patients of never on gluten-free diet group, in 39 of 110 patients of gluten-free diet and in 84 of 85 of transient gluten-free diet groups. Herpetiform dermatitis was found in three patients of gluten-free diet, three of transient gluten-free diet and three of never on gluten-free diet. Dental enamel defects were found in 15 patients of transient gluten-free diet, 43 of never on gluten-free diet and in zero of the gluten-free diet group. Pregnancy outcome was not significantly different between the two groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten-free diet group. Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten-free diet group when compared with the other two groups.: Gluten withdrawal in childhood partly protects coeliac adults from clinical and behavioural effects of gluten sensitivity. [ABSTRACT FROM AUTHOR]

: Symptoms of irritable bowel syndrome are often cyclical and thus may require repeated rather than continuous therapy. Tegaserod is effective and well-tolerated for irritable bowel syndrome with constipation but data on retreatment are lacking.: To assess whether tegaserod retreatment is as efficacious and well-tolerated as initial treatment in a primary care setting.: This open-label trial was designed to evaluate the effectiveness of tegaserod under real-life conditions. Irritable bowel syndrome with constipation patients received tegaserod 6 mg b.d. for 12 weeks; response was assessed at weeks 4 and 12. Responders (those achieving satisfactory relief for at least 2 of the previous 4 weeks) at weeks 4 and/or 12 entered an 8-week withdrawal period where symptom recurrence was assessed. Patients experiencing recurrence could receive tegaserod 6 mg b.d. for another 4 weeks (retreatment phase) and on completion, could choose to continue tegaserod in a 6-month extension study.: A total of 513 patients received initial treatment with tegaserod; 85.0% (436 of 513) responded. 403 responders entered the withdrawal period; symptoms recurred in 83.9% (338 of 403) after a mean of 38 days. Of the 307 patients who subsequently entered retreatment 89.3% (274 of 307) responded. Among patients entering the retreatment period, 269 (87.6%) had responded within the first 4 weeks of initial treatment. Of these, 243 (90.3%) responded to tegaserod retreatment. Adverse events were infrequent and similar during 4 weeks of the initial treatment period (11.1%) and on retreatment (10.4%). The extension study, completed by 188 of 232 (81.0%) patients, demonstrated good long-term tolerability of tegaserod.: Irritable bowel syndrome with constipation patients can be successfully treated, and retreated, with tegaserod 6 mg b.d. Tegaserod was well-tolerated during initial and retreatment periods. [ABSTRACT FROM AUTHOR]