Showing papers in "Alimentary Pharmacology & Therapeutics in 2006"

Review article: prebiotics in the gastrointestinal tract

Abstract: ummary Background Prebiotics are short-chain carbohydrates that alter the composition, or metabolism, of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, whilst at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. Aim To review published evidence for prebiotic effects on gut function and human health. Methods We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhoea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focussing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clinical study or meta-analysis on this topic. Results Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clinical context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. Conclusions It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.

Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease.

Abstract: Summary Background Crohn's disease is associated with small bowel cancer whilst risk of colorectal cancer is less clear Aim To ascertain the combined estimates of relative risk of these cancers in Crohn's disease Methods MEDLINE was searched to identify relevant papers Exploding references identified additional publications When two papers reviewed the same cohort, the later study was used Results Meta-analysis showed overall colorectal cancer relative risk in Crohn's disease as 25 (13–47), 45 (13–149) for patients with colonic disease and 11 (08–15) in ileal disease Meta-regression showed reduction in relative risk over the past 30 years Subgroup analysis showed Scandinavia had significantly lower colorectal cancer relative risk than the UK and North America Cumulative risk analysis showed 10 years following diagnosis of Crohn's disease relative risk of colorectal cancer is 29% (15%–53%) Meta-analysis showed small bowel cancer relative risk in Crohn's disease is 332 (159–609) Small bowel cancer relative risk has not significantly reduced over the last 30 years Conclusion Relative risk of colorectal and small bowel cancers are significantly raised in Crohn's disease Cumulative risk of colorectal cancer of 29% at 10 years suggests a potential benefit from routine screening However, the value of screening requires rigorous appraisal

Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.

Abstract: Summary Background Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. Aim To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. Patients and methods 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 × 109 viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. Results Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). Conclusions Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.

Prolonged n‐3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non‐alcoholic fatty liver disease: a pilot study

Abstract: SUMMARY Background Recent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-a ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking. Aim

The effect of bolus viscosity on swallowing function in neurogenic dysphagia.

Abstract: ummary Aim To assess the pathophysiology and treatment of neurogenic dysphagia. Methods 46 patients with brain damage, 46 with neurodegenerative diseases and eight healthy volunteers were studied by videofluoroscopy while swallowing 3–20 mL liquid (20.4 mPa s), nectar (274.4 mPa s) and pudding (3931.2 mPa s) boluses. Results Volunteers presented a safe and efficacious swallow, short swallow response (≤740 ms), fast laryngeal closure (≤160 ms) and strong bolus propulsion (≥0.33 mJ). Brain damage patients presented: (i) 21.6% aspiration of liquids, reduced by nectar (10.5%) and pudding (5.3%) viscosity (P < 0.05) and (ii) 39.5% oropharyngeal residue. Neurodegenerative patients presented: (i) 16.2% aspiration of liquids, reduced by nectar (8.3%) and pudding (2.9%) viscosity (P < 0.05) and (ii) 44.4% oropharyngeal residue. Both group of patients presented prolonged swallow response (≥806 ms) with a delay in laryngeal closure (≥245 ms), and weak bolus propulsion forces (≤0.20 mJ). Increasing viscosity did not affect timing of swallow response or bolus kinetic energy. Conclusions Patients with neurogenic dysphagia presented high prevalence of videofluoroscopic signs of impaired safety and efficacy of swallow, and were at high risk of respiratory and nutritional complications. Impaired safety is associated with slow oropharyngeal reconfiguration and impaired efficacy with low bolus propulsion. Increasing bolus viscosity greatly improves swallowing function in neurological patients.

Systematic review: evidence‐based management of hepatocellular carcinoma – an updated analysis of randomized controlled trials

Abstract: The treatment strategy of hepatocellular carcinoma applied following scientific guidelines is only supported by 77 randomized controlled trials published so far, a figure that clearly pinpoints hepatocellular carcinoma as an 'orphan' cancer in terms of clinical research when compared with other high-prevalent cancers worldwide. A systematic review analysing 61 randomized controlled trials (1978-2002) showed a modest survival benefit from chemoembolization in patients with intermediate tumours, and the lack of an effective first-line treatment option for patients with advanced disease. These conclusions have been endorsed by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. The present updated evidence-based approach includes 16 randomized controlled trials published from 2002 to 2005 assessing percutaneous ablation (seven), other loco-regional therapies (three) and systemic therapies (six). Eight showed high-quality methodological profiles. Four randomized controlled trials demonstrated a better local hepatocellular carcinoma control in tumours larger than 2 cm treated by radiofrequency ablation compared with ethanol injection. No survival advantages were obtained from systemic treatments in patients with advanced hepatocellular carcinoma, an area that is an unmet need. Therefore, there is an urgent request to conduct well-designed phase III investigations in hepatocellular carcinoma patients.

Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure.

Abstract: Summary Background A quadruple therapy has been generally recommended as rescue regimen for Helicobacter pylori eradication failures. Aims To systematically review the efficacy and tolerance of levofloxacin-based rescue regimens, and to conduct a meta-analysis of studies comparing these regimens with quadruple therapy for H. pylori eradication failures. Methods Selection of studies – levofloxacin-based rescue regimens. For the meta-analysis, randomized-controlled trials comparing levofloxacin-based and quadruple regimens. Search strategy – electronic and manual. Assessment of study quality – independently by two reviewers. Data synthesis –‘intention-to-treat’ eradication rate. Results Mean eradication rate with levofloxacin-based regimens was 80%. Ten-day regimens were more effective than 7-day combinations (81% vs. 73%; P < 0.01). The meta-analysis showed better results with levofloxacin than with the quadruple combination (81% vs. 70%; OR = 1.80; 95% CI = 0.94–3.46). This difference reached statistical significance and heterogeneity markedly decreased when a single outlier study was excluded or when only high-quality studies were considered. Meta-analysis showed less adverse effects with levofloxacin than with quadruple regimen, both overall (19% vs. 44%; OR = 0.27; 95% CI = 0.16–0.46) and regarding severe adverse effects (0.8% vs. 8.4%; OR = 0.20; 95% CI =0.06–0.67). Conclusions After H. pylori eradication failure, levofloxacin-based rescue regimen is more effective and better tolerated than the generally recommended quadruple therapy. A 10-day combination of levofloxacin–amoxicillin–proton pump inhibitor constitutes an encouraging second-line alternative.

Review article: the clinical pharmacology of proton pump inhibitors.

Abstract: Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night.

Systematic review: managing anaemia in Crohn's disease

Abstract: Summary Background Anaemia is a serious complication of Crohn's disease that triggers hospitalization and, if not interfered with, may lead to death. Aims To systematically summarize and compare the literature on anaemia in Crohn's disease. Methods For this systematic review the literature was searched for English-language articles using anaemia, Crohn* and IBD as key words. 144 articles were identified and sorted according to the following topics: prevalence, aetiology, diagnostic tests and therapy. Results The reported prevalence of anaemia varied between 6.2% and 73.7%, with higher reported frequencies in older studies and in in-patients. Iron deficiency is the most common underlying condition. Vitamin B12 deficiency is related to the extent of ileal resection but has rarely impact on anaemia. Diagnostic criteria are not established and treatment guidelines are missing. Oral iron supplementation seems effective for short periods but intolerance leads to discontinuation in up to 21%. Eleven of 11 studies show that oral iron enhances intestinal inflammation and colon carcinogenesis in animal models of colitis. Intravenous iron supplementation with iron sucrose has been tested in over 250 Crohn's disease patients, is safe, effective and does not carry such hazards. Conclusions As disease activity is determining the degree of anaemia in Crohn's disease, implementation of more effective therapy for Crohn's disease will lower its incidence. However, further studies regarding the safety and effectiveness of iron supplementation are needed.

Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy.

Abstract: Summary Background Recent evidence found probiotics could inhibit Helicobacter pylori colonization from both in vitro and in vivo studies. Aim To systematically evaluate whether adding probiotics to anti-H. pylori regimens could improve eradication rates and reduce side effects during anti-H. pylori treatment. Methods Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing probiotics supplementation to placebo or no treatment during anti-H. pylori regimens. Statistical analysis was performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also performed. Results We identified 14 randomized trials (n = 1671). Pooled H. pylori eradication rates were 83.6% (95% CI = 80.5–86.7%) and 74.8% (95% CI = 71.1–78.5%) for patients with or without probiotics by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34–2.54); the occurrence of total side effects were 24.7% (95% CI = 20.0–29.4%) and 38.5% (95% CI = 33.0–44.1%) for groups with or without probiotics, especially for diarrhoea, the summary OR was 0.44 (95% CI = 0.30–0.66). Conclusions Our review suggests that supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy-related side effects.

Effectiveness of an 'half elemental diet' as maintenance therapy for Crohn's disease: A randomized-controlled trial.

Abstract: SUMMARY Background Although thiopurines have a proven role in maintenance therapy for Crohn’s disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines. Aim To evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as ‘half elemental diet’. Methods Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n ! 26) or a free diet group (n ! 25). The primary outcome measure of this study was the occurrence of relapse over the 2-year period. Results The relapse rate in the half elemental diet group was significantly lower [34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16‐0.98)] than that in the free diet group after a mean follow-up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study.

Systematic review: oral bowel preparation for colonoscopy

Abstract: Summary Background There are many published trials of colon cleansing regimens for colonoscopy but no clear consensus regarding relative performance. Aim To identify high quality controlled trials comparing two or more bowel preparation regimens and to compare efficacy and tolerability. Methods A comprehensive systematic review was carried out to identify candidate studies. Quality appraisal was carried out on all identified studies. Results were meta-analysed where possible and qualitatively compared if not. Results Eighty-two studies qualified for analysis. Polyethylene glycol and sodium phosphate were the most frequently investigated preparations. There was no significant efficacy difference between the two, but sodium phosphate was better tolerated. Sodium picosulphate/magnesium citrate, a commonly prescribed preparation, was investigated in four studies, with no clear benefit over other regimens demonstrated. Safety was not recognized as a problem in the randomized controlled trials. Published case series demonstrate that sodium phosphate is associated with the highest risk of clinically significant electrolyte disturbances. Conclusion Shortcomings in study design limit the value of many of the studies. Based on these results, no single bowel preparation emerges as consistently superior. New preparations are required that combine better efficacy and tolerability, in addition to rigorous new validated study designs, allowing unequivocal comparisons to be made.

Systematic review: adherence issues in the treatment of ulcerative colitis

Abstract: Ulcerative colitis is a chronic inflammatory and debilitating disease requiring lifelong treatment. First-line therapy for ulcerative colitis is 5-aminosalicylic acid, which suffers from poor patient adherence outside the clinical trial setting. Formulations to deliver 5-aminosalicylic acid to the disease activity site, both orally and topically, are often inconvenient and require multiple daily dosing. Such regimens can interfere with normal life and reduce the overall quality of life, negatively impacting on treatment adherence and leading to poorer long-term outcomes. These include increased morbidity with an elevated risk of symptomatic relapse, possible greater risk of colorectal cancer and higher overall costs of care. Ulcerative colitis patients cite treatment regimen complexity, tablet quantity and dose frequency as key negative influencers of adherence. Solutions to these issues include addressing patient concerns, simplifying daily regimens and utilizing new formulations such as micropellet and multimatrix oral formulations, rectal gel and once-daily suppository formulations. This review examines the prevalence and impact of non-adherence to 5-aminosalicylic acid therapy among patients with ulcerative colitis, as well as drug delivery strategies that may enhance dosing regimens to improve patient acceptability, adherence and long-term clinical outcomes. It is a combination of understanding patient behaviour, recognizing signs of non-adherent behaviour and utilizing management strategies to change behaviour that will improve patient outcomes.

Systematic review: are probiotics useful in controlling gastric colonization by Helicobacter pylori?

Abstract: Helicobacter pylori is a highly prevalent pathogen considered as an aetiological factor for gastroduodenal ulcers, and a risk factor for gastric adenocarcinoma and lymphoma in humans. Most subjects colonized by this micro-organism are asymptomatic and remain untreated. In symptomatic patients, the antibiotic treatment has a high cost and is not 100% effective because of resistance to antibiotics and to moderate patient compliance. This review discusses the role of probiotics as alternative solutions to assist in the control of H. pylori colonization in at-risk populations. The evidence that some strains of Lactobacillus and Bifidobacterium are able to inhibit H. pylori growth through the release of bacteriocins or organic acids, and may also decrease its adhesion to epithelial cells, is reviewed. In addition, probiotics have a possible role in the stabilization of the gastric barrier function and the decrease of mucosal inflammation. Other aspects that are considered are the contribution of probiotics to the healing of the gastric mucosa linked to their antioxidant and anti-inflammatory properties. Clinical trials in colonized adults and children are reviewed, and suggest that probiotics do not eradicate H. pylori but maintain lower levels of this pathogen in the stomach; in combination with antibiotics, probiotics may increase eradication rate and/or decrease adverse effects. Papers suggesting similar effects on H. pylori by foodstuffs such as berry juice and some milk proteins are quoted. Regular intake of these and other dietary products might constitute a low-cost, large-scale alternative solution applicable for populations at-risk for H. pylori colonization.

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit.

Abstract: Summary Background Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients. Aims To evaluate 6-week mortality in cirrhotic patients admitted to an ICU, and to compare general and liver-specific prognostic scores. Methods A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child–Pugh, Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves. Results Major indication for admission was respiratory failure (35.6%). Median (range) Child–Pugh, APACHE II, MELD and SOFA scores were 11 (5–15), 18 (0–44), 24 (6–40) and 11 (0–21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, ≥3 = 90%), higher FiO2, lactate, urea and bilirubin; resulting in good discrimination [area under receiver operating characteristic curve (AUC) = 0.83], similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child–Pugh (AUC = 0.78 and 0.72, respectively). Conclusions Cirrhotics admitted to ICU with ≥3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child–Pugh scores.

A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children.

Abstract: Summary 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.

Review article: fructose malabsorption and the bigger picture

Abstract: Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine. The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short-chain poorly absorbed carbohydrates such as sorbitol. The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking. It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.

Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy.

Abstract: SUMMARYBackgroundIt is controversial whether proton pump inhibitor use leads to fundicgland polyp development.AimTo determine whether fundic gland polyp development is due to protonpump inhibitor use and to investigate mechanisms involved.MethodsProton pump inhibitor use and the presence of fundic gland polypswere assessed in consecutive patients undergoing oesophagogastroduo-denoscopy. Biopsies from fundic gland polyps and gastric mucosa weretaken. Dysplasia was graded as negative, low or high grade. Prevalenceof parietal cell hyperplasia and parietal cell protrusions and the propor-tional cystic area were assessed.Results599 patients participated, 322 used proton pump inhibitors, 107 hadfundic gland polyps. Long-term proton pump inhibitor use was associ-ated with an increased risk of fundic gland polyps (1–4.9 years use: OR2.2, 95% CI: 1.3–3.8; ‡5 years: OR 3.8, 95% CI: 2.2–6.7) while short-term therapy (<1 year) was not (OR 1.0, 95% CI: 0.5–1.8). Low-gradedysplasia was found in one fundic gland polyp. Fundic gland polypsassociated with long-term proton pump inhibitor use had a larger pro-portional cystic area and higher frequency of parietal cell hyperplasiaand parietal cell protrusion.ConclusionsLong-term proton pump inhibitor use is associated with an up to four-fold increase in the risk of fundic gland polyps. Risk of dysplasia isnegligible. Aetiologically, these polyps seem to arise because of parietalcell hyperplasia and parietal cell protrusions resulting from acid sup-pression.

Review article: Infliximab therapy for inflammatory bowel disease--seven years on.

Abstract: Infliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and extra-intestinal manifestations of inflammatory bowel disease. Recently, the active ulcerative colitis trials (ACT) studies have shown that infliximab is also efficacious to treat ulcerative colitis resistant to standard therapy. Induction with 5 mg/kg infliximab at weeks 0, 2 and 6 is advocated. The response to infliximab is improved when concomitant immunosuppressive therapy is given. As the majority of patients will relapse if not retreated, a long-term strategy is necessary. Although episodic therapy can be used, the optimal strategy is systematic maintenance treatment with 5 mg/kg intravenous (i.v.) every 8 weeks. Long-term maintenance therapy with infliximab results in a reduction of the rate of complications, hospitalizations and surgeries associated with Crohn's disease. Safety problems with the monoclonal antibody infliximab treatment mainly concern the formation of antibodies to infliximab, which may lead to infusion reactions, loss of response and serum sickness-like delayed infusion reactions. Latent tuberculosis needs to be screened for. The rate of other opportunistic infections is slightly increased mainly in patients treated concomitantly with immunosuppression. There is no evidence that malignancy rates in patients treated with antitumour necrosis factor strategies are increased.

Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease

Abstract: For both wheat allergy and coeliac disease the dietary avoidance of wheat and other gluten-containing cereals is the only effective treatment. Estimation of the maximum tolerated amount of gluten for susceptible individuals would support effective management of their disease. Literature was reviewed to evaluate whether an upper limit for gluten content in food, which would be safe for sufferers from both diseases, could be identified. When setting gluten limits for coeliac disease sufferers, the overall potential daily intake should be considered, while for wheat allergy limits should be based on single servings. For coeliac disease sufferers this limit should lie between 10 and 100 mg daily intake. For wheat allergy, lowest eliciting doses for children lie in the lower milligram range, while for adults they are most significantly higher. Gliadins (part of the gluten proteins) not only trigger coeliac disease, but are also major allergens in wheat allergy. Therefore, measurement of gliadins with validated enzyme-linked immunosorbent assay methods provides an appropriate marker for assessing gluten and/or wheat protein contents in food. Available data suggest that a maximum gluten content for 'gluten-free' foods could be set, which protects both wheat allergy sufferers and coeliac patients.

Review article: proton pump inhibitors and bacterial overgrowth.

Abstract: Summary Proton pump inhibitors are potent drugs producing profound suppression of gastric acid secretion. Consequently, they are highly effective at treating acid-related disorders. There have been concerns that the suppression of gastric acid will alter the bacterial flora of the upper gastrointestinal tract and lead to complications such as cancer, enteric or other infections and malabsorption. Studies have confirmed that proton pump inhibitors do alter the bacterial population but present evidence indicates that this only rarely leads to clinical disease. As with all drugs, proton pump inhibitors should only be used for disorders shown clearly to benefit from the therapy and where the benefits will outweigh the small risks associated with them. Further research to more fully quantify the risk associated with PPI therapy is required.

Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without cavernous transformation.

Abstract: Summary Background Treatment options for patients with portal vein thrombosis are limited. Aim To evaluate the feasibility and efficacy of transjugular intrahepatic portosystemic shunt for portal vein thrombosis with/without cavernomatous transformation. Methods A survey of such patients, referred for transjugular intrahepatic portosystemic shunt between 1994 and 2005, was performed. Success rates, complications, transjugular intrahepatic portosystemic shunt patency and clinical progression were examined. Results Transjugular intrahepatic portosystemic shunt was attempted in 28 patients (13 cirrhotics). Indications were: presurgery/transplantation (2), worsening of ascites (2), variceal bleeding (15 – 8 elective), refractory ascites (3), portal biliopathy (3) and portal vein thrombosis complicating Budd–Chiari syndrome (2). Transjugular intrahepatic portosystemic shunt was placed successfully in 19 of 28 (73%); 23 of 28 had complete portal vein thrombosis and 9 of 23 had cavernous transformation and transjugular intrahepatic portosystemic shunt was successfully placed in six of these. In the 19 patients with transjugular intrahepatic portosystemic shunt, the mean follow-up was 18.1 months (range 5–70): six patients had stent revisions; three had liver transplantation, one died of bleeding. Most cirrhotic patients had an improvement in the Child-Pugh score. In the failed transjugular intrahepatic portosystemic shunt group, two of nine died, and three had further bleeding. Conclusions Transjugular intrahepatic portosystemic shunt should be considered for selected patients with symptomatic complete portal vein thrombosis with/without cavernous transformation, as clinical improvement and less rebleeding occur when transjugular intrahepatic portosystemic shunt placement is successful.

Impact of Endoscopist Withdrawal Speed On Polyp Yield: Implications for Optimal Colonoscopy Withdrawal Time

Abstract: ummary Background In 2002, a U.S. Multi-Society Task Force on Colorectal Cancer recommended that the withdrawal phase for colonoscopy should average at least 6–10 min. This was based on 10 consecutive colonoscopies by two endoscopists with different adenoma miss rates. Aims To characterize the relationship between endoscopist withdrawal time and polyp detection at colonoscopy, and to determine the withdrawal time that corresponds to the median polyp detection rate. Design Procedural data from out-patient colonoscopies performed at the Mayo Clinic, Rochester during 2003 were reviewed. Endoscopists were characterized by their mean withdrawal time for a negative procedure and individual polyp detection rate. Results A total of 10 955 colonoscopies performed by 43 endoscopists were analysed. Median withdrawal time was 6.3 min (range: 4.2–11.9); polyp detection rate was 44.0% (all polyps), 29.8% (≤5 mm), 5.9% (6–9 mm), 6.7% (10–19 mm), 2.1% (≥20 mm). Longer withdrawal time was associated with higher polyp detection rate (r = 0.76; P < 0.0001); this relationship weakened for larger polyps (r = 0.19 for polyps 6–9 mm, r = 0.28 for polyps 10–19 mm, r = 0.02 for polyps ≥20 mm). Overall median polyp detection rate corresponded to a withdrawal time of 6.7 min. Conclusion Our findings support a colonoscopy withdrawal time of at least 7 min, which correlates with higher colon polyp detection rates.

Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children

Abstract: ummary Background Saccharomyces boulardii is a non-pathogenic probiotic yeast considered useful against enteropathogens. Aim To assess the effectiveness of S. boulardii 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 S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. Results Five randomized-controlled trials (619 participants) met the inclusion criteria. Combined data from four randomized-controlled trials showed that S. boulardii significantly reduced the duration of diarrhoea compared with control. The pooled weighted mean difference was −1.1 days (95% CI: −1.3 to −0.8) with a fixed model and remained significant in a random effect model. Saccharomyces boulardii significantly reduced the risk of diarrhoea on days 3, 6 and 7. Also the risk of diarrhoea lasting >7 days was significantly reduced in the S. boulardii group vs. control group (1 RCT, n = 88, RR 0.25, 95% CI: 0.08–0.83; NNT 5, 95% CI: 3–20). Conclusions There exists a moderate clinical benefit of S. boulardii therapy in otherwise healthy infants and children with acute gastroenteritis, mainly a shorter duration of diarrhoea. However, these results should be interpreted with caution due to methodological limitations of the included studies.

The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5‐year UK inception cohort

Abstract: Summary Background Corticosteroids remain the mainstay of first-line therapy in active inflammatory bowel disease Aims To determine the clinical outcome after the first corticosteroid-therapy and to identify factors which predict response/failure Methods 216 (136 ulcerative colitis and 80 Crohn's disease) patients were identified in this 5-year inception cohort The outcomes of early (30 days) and late (1 year) responses were used Multivariate analyses were performed to identify factors associated with outcome Results 86 (63%) and 60 (75%) ulcerative colitis and Crohn's disease required corticosteroid therapy, respectively In ulcerative colitis, at 30 days, 69 (51%), 42 (31%) and 25 (18%) patients demonstrated complete response, partial response and no response, respectively For Crohn's disease, these outcomes were observed in 32 (40%), 28 (35%) and 20 (25%) After 1 year, 75 (55%), 23 (17%) and 29 (21%) patients with ulcerative colitis demonstrated prolonged response, corticosteroid-dependence or required surgery, respectively For Crohn's disease, these outcomes were observed in 30 (38%), 19 (24%) and 27 (35%) patients Extensive ulcerative colitis was a predictor of surgery (P = 0001, OR: 152) In Crohn's disease, inflammatory disease behaviour was negatively associated with surgery (P = 002, OR: 013) Conclusion Although corticosteroids are effective, dependence/resistance remains common Patients with extensive ulcerative colitis and fistulizing/stricturing Crohn's are most at risk of failing corticosteroid therapy

Lifestyle factors and symptoms of gastro-oesophageal reflux – a population-based study

Abstract: Summary Background Although the symptoms of gastro-oesophageal reflux disease are common in the general adult population, the aetiology of gastro-oesophageal reflux disease is still largely unknown. Lifestyle factors such as diet, body mass index, and smoking have been frequently suggested as possible risk factors. Aim In the present study, we investigated the relationship between various lifestyle factors and gastro-oesophageal reflux disease symptoms. Methods A total of 7124 subjects were interviewed as part of the German National Health Interview and Examination Survey, a representative sample of the general adult population. We examined a variety of possible risk factors, including age, gender, body mass index, smoking, alcohol consumption, sports and different foods. To investigate the association between lifestyle and symptoms, we used a multiple logistic regression model, including various gastro-oesophageal reflux disease patient characteristics. Results We found an association among those with reflux symptoms who were overweight and obese (odds ratio: 1.8, 95% confidence interval: 1.5–2.2; odds ratio: 2.6, 95% confidence interval: 2.2–3.2), respectively. Further risk factors included smoking and the frequent consumption of spirits, sweets, or white bread. Physical activity and the consumption of fruits seemed to have some protective effect. Conclusions Lifestyle factors – in particular overweight, obesity and smoking – were associated with increased reflux symptoms.

Review article: intestinal serotonin signalling in irritable bowel syndrome

Abstract: Alterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between enterochromaffin cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized. Elements of serotonin signalling that are altered in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin-selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin-selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin-selective reuptake transporter downregulation. While a psychiatric co-morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.

Review article: bacterial translocation in the critically ill--evidence and methods of prevention.

Abstract: Summary Background Delayed sepsis, systemic inflammatory response syndrome (SIRS) and multiorgan failure remain major causes of morbidity and mortality on intensive care units One factor thought to be important in the aetiology of SIRS is failure of the intestinal barrier resulting in bacterial translocation and subsequent sepsis Aim This review summarizes the current knowledge about bacterial translocation and methods to prevent it Methods Relevant studies during 1966–2006 were identified from a literature search Factors, which detrimentally affect intestinal barrier function, are discussed, as are methods that may attenuate bacterial translocation in the critically ill patient Results Methodological problems in confirming bacterial translocation have restricted investigations to patients undergoing laparotomy There are only limited data available relating to specific interventions that might preserve intestinal barrier function or limit bacterial translocation in the intensive care setting These can be categorized broadly into pre-epithelial, epithelial and post-epithelial interventions Conclusions A better understanding of factors that influence translocation could result in the implementation of interventions which contribute to improved patient outcomes Glutamine supplementation, targeted nutritional intervention, maintaining splanchnic flow, the judicious use of antibiotics and directed selective gut decontamination regimens hold some promise of limiting bacterial translocation Further research is required

Review article: Altering the natural history of Crohn's disease--evidence for and against current therapies.

Abstract: Summary Background The natural course of Crohn's disease is characterized by flare-ups altered with periods of remission. The majority of Crohn's disease patients need surgery within 10 years of diagnosis. Major advances in treatment options over the past years have made our treatment goals more ambitious and modification of the natural course has become the ultimate endpoint. Aim To review the evidence of existing therapies for Crohn's disease for changing the natural history. Methods A Medline search was undertaken by using ‘natural history’, ‘Crohn's disease’, ‘therapy’ (corticosteroids, azathioprine, methotrexate, infliximab and enteral feeding), ‘surgery’, ‘hospitalizations’ and ‘mucosal healing’. Results Corticosteroids do not alter the disease course and maintenance therapy with corticosteroids should be avoided given their side effects. The immunomodulators azathioprine and methotrexate heal the mucosa but their onset of action is slow. Infliximab therapy introduces rapid mucosal healing and is associated with decreased hospitalizations and surgical interventions. Despite the fact that immunomodulators and infliximab are effective in maintaining clinical and endoscopic remission, there is little hard evidence at present that these therapies alter the natural history of the disease. The main reason being the fact that these therapies have so far been used only in refractory patients and that early initiation in the right patient is crucial in order to change the disease course. Conclusion Prospective studies should validate predictors of complicated disease and randomized studies in high-risk groups should be performed to answer if early introduction of immunomodulators or biological therapies slows down disease progression and alters natural history.

Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma)

Abstract: Gastrointestinal dysmotility in systemic sclerosis (scleroderma) is prevalent in 90% of patients, increasing morbidity and in some cases mortality. The resultant gastrointestinal complications are usually extensive, involving many regions of the gut from the oesophagus to the anus. Collagen replacement of vascular and enteric smooth muscle results in hypomotility, lumen dilatation, tensile rigidity and eventual loss of organ functions. The aim of this paper is to provide an overview of systemic sclerosis-related gastrointestinal dysmotility and available/potential therapeutic options. We evaluated published data on the pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis patients using the MEDLINE database for English and non-English articles from 1966 to July 2005. Based on this systematic review, lifestyle and medical therapy approaches are preferred as they often improve and/or ameliorate symptoms. Surgery is only recommended with serious, rare complications such as bowel perforation or ischaemia. Alternative therapies such as acupuncture-based therapies are well tolerated, with clinical improvement and may be of potential therapeutic benefit for systemic sclerosis gastrointestinal dysmotility. Further elucidation of initiating and persistent mechanisms of systemic sclerosis-related gastrointestinal dysmotility will optimize the development of a multidisciplinary and more directed treatment regimen.