Day: 12/19/2011

Review article: the treatment of functional abdominal bloating and distension

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Abdominal bloating and distension are common symptoms in patients with functional gastrointestinal disorders (FGIDs), however, relatively little is known about their treatment.

Aim  To review the treatment trials for abdominal bloating and distension.

Methods  A literature review in Medline for English-language publications through February 2010 of randomised, controlled treatment trials in adults. Study quality was assessed according to Jadad’s score.

Results  Of the 89 studies reviewed, 18% evaluated patients with functional dyspepsia, 61% with irritable bowel syndrome (IBS), 10% with chronic constipation and 10% with other FGIDs. No studies were conducted in patients diagnosed with functional abdominal bloating. The majority of trials investigated the efficacy of prokinetics or probiotics, although studies are heterogeneous with respect to diagnostic criteria and outcome measures. In general, bloating and/or distension were evaluated as secondary endpoints or as individual symptoms as part of a composite score rather than as primary endpoints. A greater proportion of IBS patients with constipation reported improvement in bloating with tegaserod vs. placebo (51% vs. 40%, P < 0.0001) and lubiprostone (P < 0.001). A greater proportion of nonconstipating IBS patients reported adequate relief of bloating with rifaximin vs. placebo (40% vs. 30%, P < 0.001). Bloating was significantly reduced with the probiotics, Bifidobacterium infantis 35624 (1 × 108 dose vs. placebo: −0.71 vs. −0.44, P < 0.05) and B. animalis (live vs. heat-killed: −0.56 ± 1.01 vs. −0.31 ± 0.87, P = 0.03).

Conclusions  Prokinetics, lubiprostone, antibiotics and probiotics demonstrate efficacy for the treatment of bloating and/or distension in certain FGIDs, but other agents have either not been studied adequately or have shown conflicting results.

Source: Alimentary Pharmacology & Therapeutics

 

 

 

 

 

The incidence, predictors and management of anaemia and its association with virological response in HCV / HIV coinfected persons treated with long-term pegylated interferon alfa 2a and ribavirin

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The association of anaemia with outcomes in the HCV/HIV coinfected persons undergoing HCV treatment remains unclear.

Aims  To study the incidence, predictors and management of anaemia, and its association with outcomes among persons treated with pegylated interferon and weight-based ribavirin.

Methods  Retrospective analysis of a prospective controlled treatment trial of HCV/HIV coinfection.

Results  Among 329 subjects enrolled, 40% developed anaemia during the first 12–18 weeks of treatment (median haemoglobin decrease at week 4: 2.2 g/dL). Among 169 subjects who achieved early virological response and received therapy for 72 weeks, 55% eventually developed anaemia. However, median haemoglobin levels stayed stable after 12–18 weeks of initial therapy. Among these 169 subjects, 45% were prescribed an erythropoiesis stimulating agent (ESA), with 17% receiving it prior to a drop in haemoglobin meeting protocol definition of anaemia. Only 27% completed the study without any ribavirin dose modification. Age >40 years, lower BMI, zidovudine use and lower entry haemoglobin were significant predictors of anaemia in the multi-covariate model. Among all 329, sustained virological response (SVR) rate was similar in those with or without anaemia (23% vs. 30%; P = 0.17) with no evidence of association between anaemia or ESA use and treatment response.

Conclusions  Anaemia is common in HCV/HIV coinfected persons undergoing HCV treatment, and only a minority of them are able to maintain ribavirin dose. Persons with age >40 years, lower baseline haemoglobin and lower baseline BMI should be monitored carefully. Prescription of erythropoiesis stimulating agent is common, but anaemia or erythropoiesis stimulating agent use is not associated with SVR.

Source: Alimentary Pharmacology & Therapeutics

 

 

 

 

Systematic review: management options for primary sclerosing cholangitis and its variant forms – IgG4-associated cholangitis and overlap with autoimmune hepatitis

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Primary sclerosing cholangitis (PSC) remains a challenging disease to manage. The main goals are prevention of disease progression and reduction of the increased cancer risk.

Aims  To review the management strategies for PSC and its variant forms based on published studies.

Methods  Publications were identified using Pubmed, Medline and Ovid search engines.

Results  Distinguishing PSC from variants, such as IgG4-associated cholangitis, and overlap with autoimmune hepatitis is essential to guide treatment decisions. There is no proven efficacious medical treatment for PSC. Ursodeoxycholic acid has been disappointing in low and moderate doses, and potentially dangerous in higher doses, although its role and optimal dose in chemoprevention requires investigation. The novel bile acid, 24-norursodeoxycholic acid, has shown promise in mouse models; human trials are in progress. Dominant strictures are optimally managed by dilatation and stenting to relieve obstructive complications, although exclusion of biliary malignancy is essential. Liver transplantation is the only proven therapy for those with advanced disease. Cholangiocarcinoma remains the most unpredictable and feared complication. In highly selected groups, neo-adjuvant chemoradiation with liver transplantation seems promising, but requires further validation. Screening for inflammatory bowel disease and surveillance for colorectal carcinoma should not be overlooked.

Conclusions  The effective management of PSC and its variants is hindered by uncertainties regarding pathogenesis of disease and factors responsible for its progression. Genome studies may help to identify further targets for drug therapy and factors leading to malignant transformation.

Source: Alimentary Pharmacology & Therapeutics

 

 

 

Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life –– a double-blind, placebo-controlled study

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Recent research suggests that an imbalance of the intestinal microbiota and a dysfunctional intestinal barrier might trigger irritable bowel syndrome (IBS). As probiotics have been reported to restore the intestinal microbiota and the gut barrier, the therapeutic potential of probiotics within IBS became of strong interest.

Aim  To assess the efficacy of Bifidobacterium bifidum MIMBb75 in IBS.

Methods  A total of 122 patients were randomised to receive either placebo (N = 62) or MIMBb75 (N = 60) once a day for 4 weeks. The severity of IBS symptoms was recorded daily on a 7-point Likert scale.

Results  MIMBb75 significantly reduced the global assessment of IBS symptoms by −0.88 points (95% CI: −1.07; −0.69) when compared with only −0.16 (95% CI: −0.32; 0.00) points in the placebo group (P < 0.0001). MIMBb75 also significantly improved the IBS symptoms pain/discomfort, distension/bloating, urgency and digestive disorder. The evaluation of the SF12 sum scores showed a significant gain in quality of life within the bifidobacteria group. Furthermore, adequate relief was reported by 47% of the patients in the bifidobacteria and only by 11% of the patients in the placebo group (P < 0.0001). Overall responder rates were 57% in the bifidobacteria group but only 21% in the placebo group (P = 0.0001). MIMBb75 was well tolerated and adverse events were not different from placebo.

Conclusions Bifidobacterium bifidum MIMBb75 effectively alleviates global IBS and improves IBS symptoms simultaneously with an improvement of quality of life. Considering the high efficacy of MIMBb75 in IBS along with the good side-effect profile, MIMBb75 is a promising candidate for IBS therapy.

Source: Alimentary Pharmacology & Therapeutics.

 

 

 

Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett’s oesophagus for 1 year

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Barrett’s oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett’s oesophagus.

Aim  To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett’s oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared.

Methods  Seventy-seven nondysplastic Barrett’s oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett’s oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL.

Results  In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05).

Conclusions  Treatment of Barrett’s oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole.

Source: Alimentary Pharmacology & Therapeutics.

 

 

 

Review article: delivery and efficacy of topical 5-aminosalicylic acid (mesalazine) therapy in the treatment of ulcerative colitis

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The use of topical therapy in the treatment of ulcerative colitis has declined in recent years despite evidence of good efficacy.

Aims  To review US prescription trends for 5-aminosalicylic acid (5-ASA) since the US approval of Asacol extended-release oral mesalazine (mesalamine) in 1992; to estimate the optimal level of 5-ASA exposure in the distal colon; to determine factors influencing distal colonic exposures; and to compare the effectiveness of different 5-ASA formulations (oral, topical suspension, foam, suppositories) in clinical trials.

Methods  Review of clinical trials, physiologic studies and prescription trends of various mesalazine formulations for treatment of distal ulcerative colitis.

Results  Between 1992 and 2009, prescriptions for oral mesalazine increased sixfold, whereas topical suspensions declined by 10%. In clinical trials, topical therapy resulted in higher remission and clinical response rates than oral therapy, with trends to earlier improvement. The mucosal concentrations of 5-ASA achieved by topical agents in the distal colon were up to 200-fold higher than those achieved by oral administration alone. Despite active colitis, over 40% of a topically administered 4 g 5-ASA suspension (equal to 1.6 g) reached the sigmoid colon. This likely represents a therapeutic exposure of 5-ASA. Although topical therapies are less convenient than oral medications, treatment algorithms have failed to take into account quality of life improvements resulting from more rapid and complete treatment response.

Conclusions  Topical mesalazine therapy is superior to oral therapy in distal ulcerative colitis for both therapeutic response and drug delivery. Practice patterns should be re-evaluated in light of this information.

Source: Alimentary Pharmacology & Therapeutics.

 

Review article: loss of response to anti-TNF treatments in Crohn’s disease

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Loss of response to anti-TNF agents in Crohn’s disease is an emerging clinical problem.

Aim  To review the causes, incidence and management approach of loss of response.

Methods  A search of medical database (PubMed) and of meetings’ proceedings for definitions, causes and incidence of loss of response was carried out. Personal correspondence with principal investigators was conducted to retrieve missing data.

Results  Various definitions of loss of response abound, hampering the ability to assess accurately the magnitude and management of this clinical problem. We propose to distinguish between a clinical worsening on anti-TNF treatment and a true loss of response to anti-TNFs. Accordingly, loss of response to anti-TNFs at 12 months of therapy occurs in 23–46% of patients when judged by dose intensification, or 5–13% when gauged by drug discontinuation rates. The management of loss of response should allow for a period of watchful waiting as quite often the patients’ symptoms may resolve without alteration of therapy. If they do not, then identifying the correct mechanism responsible for clinical deterioration is prudent. Once symptoms are ascertained to arise from inflammatory IBD activity, drug level and antidrug antibody measurement can then help distinguish between non-adherence to therapy, immunogenicity and non-immune clearance of anti-TNF, or an un-chequered inflammation despite adequate anti-TNF levels. The latter finding may be best addressed by a switch to another class of immunomodulators, whereas a low drug level should probably be managed by dose intensification or a switch to another anti-TNF.

Conclusion  Studies defining how best to translate drug-level monitoring and other mechanistic considerations into clinical decisions are urgently needed.

Source: Alimentary Pharmacology & Therapeutics

 

Review article: reflux and its consequences – the laryngeal, pulmonary and oesophageal manifestations

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Gastro-oesophageal reflux disease (GERD) is one of the commonest diseases of Western populations, affecting 20 to 30% of adults. GERD is multifaceted and the classical oesophageal symptoms such as heartburn and regurgitation often overlap with atypical symptoms that impact upon the respiratory system and airways. This is referred to as extra-oesophageal reflux disease (EERD), or laryngopharyngeal reflux (LPR), which manifests as chronic cough, laryngitis, hoarseness, voice disorders and asthma.

Aim  The ‘Reflux and its consequences’ conference was held in Hull in 2010 and brought together a multidisciplinary group of experts all with a common interest in the many manifestations of reflux disease to present recent research and clinical progress in GERD and EERD. In particular new techniques for diagnosing reflux were showcased at the conference.

Methods  Both clinical and non-clinical key opinion leaders were invited to write a review on key areas presented at the `Reflux and its consequences’ conference for inclusion in this supplement.

Results and conclusion  Eleven chapters contained in this supplement reflected the sessions of the conference and included discussion of the nature of the refluxate (acid, pepsin, bile acids and non-acid reflux); mechanisms of tissue damage and protection in the oesophagus, laryngopharynx and airways. Clinical conditions with a reflux aetiology including asthma, chronic cough, airway disease, LPR, and paediatric EERD were reviewed. In addition methods for diagnosis of reflux disease and treatment strategies, especially with reference to non-acid reflux, were considered.

Source: Alimentary Pharmacology & Therapeutics.

 

 

 

 

 

 

 

Review article: in vivo imaging by endocytoscopy

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Endocytoscopy (EC) enables in vivo microscopic imaging at 1400-fold magnification, thereby allowing the analysis of mucosal structures at the cellular level. In contrast to fluorescence imaging with confocal laser endomicroscopy which allows analysis of mucosal structures up to 250 μm in depth, EC is based on the principle of contact light microscopy and only allows visualisation of the very superficial mucosal layer.

Aim  To systematically review the feasibility and diagnostic yield of EC for in vivo diagnosis of diseases.

Methods  A systematic search of the literature on diagnostic interventions in the gastrointestinal tract using EC was performed by searches in MEDLINE, Current Contents, PubMed, cross-references and references from relevant articles using the search terms ‘endocytoscopy’, ‘endocytoscope’, ‘magnification endoscopy’, ‘endocytoscopic imaging’, ‘virtual histology’ and ‘optical biopsy’. Only full manuscripts and case reports published in English were included.

Results  Overall twenty-nine relevant reports were identified. EC was feasible to detect oesophageal squamous cell cancer with sensitivity, specificity and accuracy of 95%, 84% and 82%, respectively. Moreover, EC reached excellent sensitivity and specificity for in vivo diagnosis of colon polyps (91% and 100%, respectively). Other diagnostic applications of EC included diagnosis of Barrett’s oesophagus, Helicobacter pylori, coeliac disease and small cell lung cancer. No serious complications of EC have yet been reported.

Conclusions  Endocytoscopy is a safe and effective new endoscopic imaging technique to obtain in vivo histology and guided biopsies with high diagnostic accuracy. Therefore, endocytoscopy has the potential to facilitate both diagnosis and patient management.

Source: Alimentary Pharmacology & Therapeutics.

 

 

Clinical predictors of poor outcomes among patients with nonvariceal upper gastrointestinal bleeding in Europe.

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Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a common medical emergency associated with substantial morbidity and mortality. Despite advances in endoscopic and pharmacological treatment during the past two decades, the incidence of mortality associated with NVUGIB has remained relatively constant.

Aim  To report outcomes and predictive factors for bleeding continuation/re-bleeding and mortality of NVUGIB in clinical practice in different European countries.

Methods  This observational, retrospective cohort study (NCT00797641; ENERGIB) was conducted in Belgium, Greece, Italy, Norway, Portugal, Spain and Turkey. Eligible patients were hospitalised (new admissions or inpatients), presenting with overt NVUGIB with endoscopy from 1 October to 30 November, 2008. Patients were managed according to routine care, and data regarding bleeding continuation/re-bleeding, pharmacological treatment, surgery and mortality during 30-days after the initial bleed were collected. A multivariate analysis of clinical factors predictive of poor outcomes was conducted.

Results  Overall, 2660 patients (64.7% men; mean age 67.7 years) were evaluable. Significant differences across countries in bleeding continuation/re-bleeding (range: 9–15.8%) or death (2.5–8%) at 30 days were explained by clinical factors (number of comorbidities, age > 65 years, history of bleeding ulcers, in-hospital bleeding, type of lesion or type of concomitant medication). Other factors (country, size of hospital, profile of team managing the event, or endoscopic/pharmacological therapy received) did not affect these outcomes. Similar predictors were observed in patients with high-risk stigmata.

Conclusion  Differences in the outcomes of nonvariceal upper gastrointestinal bleeding in clinical practice across some European countries are explained mainly by patient-related factors, and not by management factors.

Source: Alimentary Pharmacology & Therapeutics.