Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group ( P  <   0.001). The PPI response rates at 8 weeks were different ( P  =   0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.     

De novo depression and anxiety disorders and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients with hepatitis C

Background  Depression and anxiety have been associated with interferon treatment and low treatment adherence.
Aim  To study the incidence and associated risk factors of depressive and anxiety disorders during pegylated interferon plus ribavirin and treatment adherence in a prospective cohort of 176 patients with chronic hepatitis C patients.
Methods  Patients were interviewed at baseline using the Structured Clinical Interview for DSM-IV Mental Disorders and the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were completed. Both questionnaires were completed also after 4, 12 and 24 weeks of treatment.
Results  De novo depressive and/or anxiety disorders were diagnosed in 53 (36%) patients, in whom antidepressants and/or anxiolytics were administered. Higher baseline depression-subscale score (OR = 27.8, 95% CI = 2.82–333), primary education level (OR = 3.1, 95% CI = 1.40–7.03) and being an immigrant (OR = 3.2, 95% CI = 1.12–9.47) were predictors of psychiatric disorders during anti-viral therapy. The percentage of patients with good adherence was lower in those with depression and/or anxiety (79% vs. 90%, P  <   0.04). Only one patient (1%) discontinued treatment because of a major depressive episode. Depression and/or anxiety disorders had no effect on attainment of sustained virological response.
Conclusion  Early detection and treatment of depressive and anxiety disorders favours good adherence to anti-viral treatment in hepatitis C.     

The prevalence of and risk factors for erosive oesophagitis and non-erosive reflux disease: a nationwide multicentre prospective study in Korea

Background  Prospective nationwide multicentre studies that have evaluated endoscopic findings and reflux symptoms using a well-designed questionnaire are very rare.
Aim  To compare the prevalence rates of and risk factors for erosive oesophagitis and non-erosive reflux disease (NERD) in the Korean population.
Methods  A gastroscopic examination was performed on 25 536 subjects who visited 40 Healthcare Centers for a health check-up. A gastro-oesophageal reflux questionnaire and multivariate analysis were used to determine the risk factors for erosive oesophagitis and NERD.
Results  2019 (8%) and 996 subjects (4%) had erosive oesophagitis and non-erosive reflux disease, respectively; only 58% of subjects with erosive oesophagitis had reflux symptoms. Multivariate analysis showed that the risk factors for erosive oesophagitis and NERD differed, i.e. those of erosive oesophagitis were male, a Helicobacter pylori eradication history, alcohol, body mass index ≥25 and hiatal hernia. In contrast, the risk factors for NERD were female, age <40 and ≥60 vs. 40–59 years, body mass index <23 and a monthly income <$1000, glucose ≥126 mg/dL, smoking, a stooping posture at work and antibiotic usage.
Conclusions  The prevalence rates of erosive oesophagitis and NERD were 8% and 4%, respectively, in Korean health check-up subjects. The risk factors for erosive oesophagitis and NERD were found to differ, which indicates that their underlying pathogeneses are distinct.     

Treating the symptoms of gastro-oesophageal reflux disease: a double-blind comparison of omeprazole and cisapride

Background : Few studies have specifically addressed the management of the symptoms of gastro-oesophageal reflux disease, and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents.
Methods : Following endoscopy 424 patients presenting with heartburn as the predominant symptom of gastro-oesophageal reflux disease were randomized to treatment with omeprazole 20 or 10 mg once daily, or cisapride 10 mg four times daily, in a double-blind, double-dummy, parallel group, multicentre study. Symptoms and quality of life were assessed at 4 weeks. Patients still experiencing heartburn continued therapy for a further 4 weeks and the assessments were repeated.
Results : At 4 weeks, heartburn was resolved in 65% (95% CI: 57–73%), 56% (48–64%) and 41% (32%–49%) of patients treated, respectively, with omeprazole 20 mg and 10 mg once daily, and cisapride. Both omeprazole doses were significantly more effective than cisapride ( P  < 0.01). The same order of efficacy was observed regardless of the presence of erosive oesophagitis. Regurgitation and epigastric pain also improved to a greater degree with omeprazole than with cisapride. Quality of life was improved in all treatment groups, and the improvement in the reflux dimension of the Gastrointestinal Symptom Rating Scale (GSRS) score was significantly different between groups ( P  = 0.002).
Conclusions : Omeprazole 20 or 10 mg once daily is significantly more effective than cisapride in the resolution of heartburn, regardless of the presence of erosive oesophagitis, and this is accompanied by an improvement in patient quality of life.     

Epidemiological study of gastro-oesophageal reflux disease: reflux in spouse as a risk factor

Background  Gastro-oesophageal reflux disease (GERD) is a growing health-care problem with variable distribution.
Aim  To assess GERD prevalence and risk factors and their possible correlation with pathophysiology in a population-based study.
Methods  Individuals aged 18–65 years were enrolled through random cluster sampling in Tehran. Previously validated self-administered questionnaires were used.
Results  Of the 2500 questionnaires, 2057 were analysed (mean age: 34.8 ± 13.0 years, 55.1% female). Frequent GERD was seen in 18.2%. Minor symptoms increased prevalence. Female gender (OR: 1.55, 95% CI: 1.01–2.41), BMI >30 kg/m² (OR: 1.79, 95% CI: 1.03–3.12), less education (OR: 1.52, 95% CI: 1.02–2.27), smoking (OR: 1.83, 95% CI: 1.12–2.99), NSAID use (OR: 4.23, 95% CI: 1.66–10.74) and GERD in spouse (OR: 1.82, 95% CI: 1.18–2.82) were associated with frequent GERD on multivariable analysis. GERD in first-degree relatives (OR: 1.73, 95% CI: 1.23–2.43) and asthma (OR: 4.09, 95% CI: 1.27–13.15) correlated with infrequent GERD. Minor symptoms correlated with GERD history in first-degree relatives, coffee consumption and NSAID use. Prevalence in the past 3 months was similar to that in the past 12 months ( P  < 0.05).
Conclusions  Gastro-oesophageal reflux disease is common in Tehran. The association of 'infrequent symptoms' with GERD history in first-degree relatives and 'frequent symptoms' with GERD history in spouse may point to the presence of yet unknown precipitating environmental factors inducing GERD in a genetically susceptible host. Minor GERD symptoms seem to have independent contribution to GERD. Assessing GERD in the past 3 months predicts prevalence in the past year.     

Factors influencing long-term changes in mental health after interferon-alpha treatment of chronic hepatitis C

Background  Antiviral treatment with interferon-alpha (IFN-α) is associated with several acute psychiatric side effects. Little is known about long-term effects on mental health after treatment independent from viral response and the influence of pre-existing psychiatric risk-factors.
Aim  To evaluate long-term effects of antiviral treatment with interferon-alpha (IFN-α) on mental health in patients with psychiatric risk factors.
Method  We prospectively investigated long-term mental health changes in 81 hepatitis C virus-infected patients. Psychiatric outcome was measured with the Montgomery–Asberg Depression Scale (MADRS), Brief Psychiatric Rating Scale, the Global Social Functioning Scale and the Global Clinical Impression Scale 6 months after the end of antiviral treatment with IFN-α and ribavirin.
Results  Six months after antiviral therapy, 49% of the patients showed a worsening and 27.2% an improvement of depression scores. The most important predictor for a long-term improvement of depression scores was a pre-treatment MADRS score ≥5 (OR 14.21, 95% CI: 2.51–81.30). Patients with pre-existing psychiatric disorders (OR = 0.117, 95% CI: 0.024–0.558), methadone substitution (OR = 0.20, 95% CI: 0.045–0.887) or genotype 2/3 (OR = 0.341, 95% CI: 0.138–0.845) were significantly less likely to show a long-term worsening of depressive symptoms.
Conclusions  Pre-existing psychiatric risk factors increase the chance for a long-term improvement and reduce the risk for a long-term worsening of mental health after antiviral treatment of chronic hepatitis C with IFN-α.     

Predictors of serious complications due to Clostridium difficile infection

Background  Identifying individuals with severe Clostridium difficile infection (CDI) at risk for major complications has become an important objective. Presence of clinical variables that predict complications from CDI would have the potential to strongly influence management.
Aim  To determine which clinical variables predict complications from CDI.
Methods  Cross-sectional study of all individuals admitted to Temple University Hospital between 12/1/03 and 7/1/08 with the primary discharge diagnosis of CDI were eligible. Only patients experiencing their first episode of CDI were included. Abstracted data included demographic, physiological, laboratory, radiological, endoscopic, pharmacy and outcome data. Response was categorized as none, partial or complete. Complications attributed to CDI were defined as colon resection or death.
Results  Overall 32 of 200 patients (16%) experienced a complication due to CDI including death ( n  = 20) and colectomy ( n  = 12). White blood cell count above 30,000 cells/mm³ (OR = 4.06; 95% CI, 1.28–12.87) and a rise in the creatinine to over 50% above baseline (OR = 7.13; 95% CI, 3.05–16.68) predicted a complication. AROC for percent rise in serum creatinine was 0.73 (95% CI: 0.64–0.85) and 0.62 (95% CI: 0.58–0.80) for white blood cell count.
Conclusions  Severe white blood cell count elevation and a rise in the creatinine to over 50% above baseline are important independent predictors of serious adverse events due to CDI. These patients likely would benefit from more intensive care and early surgical consultation.     

Endoscopic band ligation could decrease recurrent bleeding in Mallory–Weiss syndrome as compared to haemostasis by hemoclips plus epinephrine

Background  Mallory–Weiss syndrome (MWS) with active bleeding at endoscopy may require endoscopic haemostasis the modalities of which are not well-defined.
Aim  To compare the efficacy of endoscopic band ligation vs. hemoclip plus epinephrine (adrenaline) in bleeding MWS.
Methods  From 2001 to 2008, 218 consecutive patients with a MWS at endoscopy were hospitalized in our Gastrointestinal Bleeding Unit. In 56 patients (26%), an endoscopic haemostasis was required because of active bleeding. Band ligation was performed in 29 patients (Banding group), while hemoclip application plus epinephrine injection was performed in 27 patients (H&E group). Treatment efficacy and early recurrent bleeding were retrospectively compared between the two groups.
Results  Primary endoscopic haemostasis was achieved in all patients. Recurrent bleeding occurred in 0% in Banding group vs. 18% in H&E group ( P  = 0.02). The use of hemoclips plus epinephrine (OR = 3; 95% CI = 1.15–15.8) and active bleeding at endoscopy (OR = 1.9; 95% CI = 1.04–5.2) were independent predictive factors of early recurrent bleeding.
Conclusions  Haemostasis by hemoclips plus epinephrine was an independent predictive factor of rebleeding. This result suggests that band ligation could be the first choice endoscopic treatment for bleeding MWS, but requires further prospective assessment.     

Meta-analysis: octreotide prevents post-ERCP pancreatitis, but only at sufficient doses

Background  Effects of octreotide on post-endoscopic retrograde cholangiopancreatography pancreatitis have been studied in many clinical trials. These trials have yielded inconclusive results. Results of more recent studies using larger doses, however, seem to be more optimistic.
Aim  To examine effects of octreotide at different doses on PEP.
Methods  A comprehensive search of relevant databases, including Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library and Science Citation Index yielded 18 randomized controlled trials (RCTs). Trials were divided into two groups according to the total dosage of octreotide: <0.5 mg (OCT1), ≥0.5 mg (OCT2). The rate of PEP was analysed using a fixed effect model.
Results  At doses of ≥0.5 mg, octreotide reduced the rate of PEP. In the OCT2 group, analysis revealed a statistically significant difference on PEP between the octreotide group and the controls (3.4% vs. 7.5%, pooled OR = 0.45; 95% CI: 0.28–0.73; P  = 0.001, NNT = 25). In the OCT1 group, the rate of PEP was similar between patients receiving octreotide and the controls (7.2% vs. 6.0%, pooled OR = 1.23; 95% CI: 0.80–1.91; P  = 0.35).
Conclusion  Octreotide is effective in preventing PEP, but only at sufficient doses (≥0.5 mg).     

The clinical safety of long-term lansoprazole for the maintenance of healed erosive oesophagitis

Background  The clinical safety of long-term lansoprazole therapy for the maintenance of healed erosive oesophagitis has not been extensively studied in clinical trials.
Aim  To assess the long-term clinical safety of dose-titrated lansoprazole as maintenance therapy for up to 82 months in subjects with healed erosive oesophagitis.
Methods  Clinical safety was assessed by monitoring adverse events (AEs), laboratory data including serum gastrin levels, and endoscopy.
Results  Mean duration (± s.d.) of lansoprazole treatment during the titrated open-label period was 56 ± 24 months (range <1–82 months). Overall, 189 of 195 (97%) subjects experienced a total of 2825 treatment-emergent AEs. Most AEs occurred during the first year of treatment, were mild-to-moderate in severity and resolved while on treatment. Of 155 serious AEs (in 74 subjects), only two (colitis and rectal haemorrhage in one subject) were considered treatment-related. Sixty-nine of 195 subjects (35%) experienced 187 treatment-related AEs, with diarrhoea (10%), headache (8%) and abdominal pain (6%) being the most common. Gastrin levels ≥400 pg/mL were seen in 9% of subjects; hypergastrinemia was not associated with gastro-intestinal AEs or nodules/polyps.
Conclusions  Lansoprazole maintenance therapy for up to 6 years is safe and well tolerated in subjects with healed erosive oesophagitis.     

Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis

Background  Debate exists regarding to whether thiopurine therapy is as effective in ulcerative colitis (UC) as it is in Crohn's disease.
Aim  To review systematically the efficacy of azathioprine (AZA) and mercaptopurine (MP) in UC, and to conduct a meta-analysis of randomized clinical trials evaluating the efficacy of AZA/MP for the induction or maintenance of UC clinical remission.
Methods  Selection of studies : Evaluating AZA/MP for induction and/or maintenance of clinical remission of UC. Randomized-controlled-trials comparing AZA/MP with placebo/5-aminosalicylates were included in the meta-analysis. Search strategy : Electronic and manual. Study quality : Independently assessed by two reviewers. Data synthesis : By 'intention-to-treat'.
Results  Thirty noncontrolled studies (1632 patients) were included in the systematic review. Mean efficacy of AZA/MP was 65% for induction and 76% for maintenance of the remission. Seven controlled studies were included in the meta-analysis. (i) Induction of remission: four studies (89 AZA/MP-treated patients) showed mean efficacy of 73% vs. 64% in controls (OR = 1.59; 95% CI = 0.59–4.29). (ii) Maintenance of remission: six studies (124 AZA/MP-treated patients) showed mean efficacy of 60% vs. 37% in controls (OR = 2.56; 95% CI = 1.51–4.34). When only studies comparing AZA/MP vs. placebo were considered, OR was 2.59 (95% CI = 1.26–5.3), absolute risk reduction was 23% and number-needed-to-treat (NNT) to prevent one recurrence was 5.
Conclusion  Thiopurine drugs (AZA/MP) are more effective than placebo for the prevention of relapse in UC, with an NNT of 5 and an absolute risk reduction of 23%.     

Time trends in peptic ulcer, erosive reflux oesophagitis, gastric and oesophageal cancers in a multiracial Asian population

Background  Dramatic changes in the prevalence and pattern of gastrointestinal disease has taken place in Asia in recent years.
Aim  To compare the prevalence of duodenal (DU) and gastric ulcers (GU), erosive oesophagitis (EO), gastric cancer (GCA) and oesophageal cancer (OCA) and Helicobacter pylori infection over a 10-year interval of time in a multiracial South-East Asian population.
Methods  Endoscopy records of first time gastroscopy in the University of Malaya Medical Centre, Kuala Lumpur, Malaysia were reviewed for 1989/1990 and 1999/2000.
Results  In the period of 1989–1990, 3252 records and in 1999–2000, 4615 records were analysed. Both DU (21.1–9.5%) and GU (11.9–9.4%) had decreased significantly ( P  < 0.001). EO had increased significantly from 2.0% to 8.4% ( P  < 0.001). Both GCA and OCA had declined in the 10-year interval. Helicobacter pylori prevalence had decreased from 51.7% to 30.3% ( P  < 0.001).The decrease in DU and GU was seen in all racial groups. The increase in EO was most marked in Indians and the decrease in GCA in Chinese. The proportion of H. pylori- associated DU and GU had also decreased with time.
Conclusions  Peptic ulcers and H. pylori infection had declined over a 10-year period of time and showed an opposing time trend with EO, which had increased dramatically. Both GCA and OCA had declined in prevalence.     

Evidence of allelic heterogeneity for associations between the NOD2/CARD15 gene and ulcerative colitis among North Indians

Background  Three common disease susceptibility variants in the NOD2 gene are associated with inflammatory bowel disease in Caucasians, but not in Asians.
Aim  To screen for NOD2 variants and examine susceptibility for inflammatory bowel disease in North Indians.
Methods  A case–control study was carried out in Punjab, India. Confirmed cases of ulcerative colitis and Crohn's disease and healthy controls matched for age (±10 years) and ethnicity were studied. Besides genotyping the three disease susceptibility variants (SNP8, SNP12 and SNP13), all 12 exons were resequenced to determine other potential single nucleotide polymorphisms.
Results  Two hundred and ninety-eight ulcerative colitis, 25 Crohn's disease and 262 controls were investigated. Median age (range) at diagnosis was 39 (7–78) years for ulcerative colitis and 40 (32–58) years for Crohn's disease. All three disease susceptibility variants were either monomorphic or rare in the population. Sequencing ( n  = 30) revealed two single nucleotide polymorphisms: SNP5 (268 Pro/Ser) and rs2067085 (178 Ser/Ser). The frequency of SNP5 was higher among ulcerative colitis (17% vs. 12% in controls, P  = 0.016) and Crohn's disease cases (20% vs. 12%, P  = 0.28). SNP5 carriers had elevated risks for ulcerative colitis (OR = 1.72, 95% CI = 1.17–2.52, P  = 0.005).
Conclusions  The absence of known inflammatory bowel disease susceptibility variants and potential associations between SNP5 and ulcerative colitis in North Indians suggests the presence of allelic heterogeneity for ulcerative colitis susceptibility.     

Systematic review: standard- and double-dose proton pump inhibitors for the healing of severe erosive oesophagitis – a mixed treatment comparison of randomized controlled trials

Background  No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis.
Aim  To compare the effectiveness of licensed doses of PPIs for healing severe erosive oesophagitis (i.e. esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg and 40 mg, pantoprazole 40 mg and rabeprazole 20 mg).
Methods  Systematic review of CENTRAL, EMBASE and MEDLINE for RCTs in patients with erosive oesophagitis (completed October 2008). Endoscopically verified healing rates at 4 and 8 weeks were extracted and re-calculated if not analysed by intention-to-treat. A mixed treatment comparison was used to combine direct treatment comparisons with indirect trial evidence while maintaining randomization. Odds ratios (OR) are reported compared to omeprazole 20 mg.
Results  A total of 3021 papers were identified in the literature search; 12 were of sufficient quality to be included in the analysis. Insufficient data were available to included rabeprazole. Esomeprazole 40 mg was found to provide significantly higher healing rates at 4 weeks [OR 1.84, 95% Credible Interval (95% CrI): 1.50 to 2.22] and 8 weeks (OR 1.91, 95% CrI: 1.13 to 2.88). No other PPI investigated had significantly higher healing rates than omeprazole 20 mg.
Conclusion  Esomeprazole 40 mg consistently demonstrates higher healing rates compared with licensed standard- and double-dose PPIs.     

Clinical trial: efficacy and safety of dexlansoprazole MR 60 and 90 mg in healed erosive oesophagitis – maintenance of healing and symptom relief

Background  Dexlansoprazole MR, a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, effectively heals erosive oesophagitis.
Aim  To assess dexlansoprazole MR in maintaining healed erosive oesophagitis.
Methods  Patients ( n  = 451) with erosive oesophagitis healed in either of two dexlansoprazole MR healing trials randomly received dexlansoprazole MR 60 or 90 mg or placebo once daily in this double-blind trial. The percentage of patients who maintained healing at month 6 was analysed using life table and crude rate methods. Secondary endpoints were percentages of nights and of 24-h days without heartburn based on daily diaries.
Results  Dexlansoprazole MR 60 and 90 mg were superior to placebo for maintaining healing ( P  <   0.0025). Maintenance rates were 87% and 82% for the 60 and 90 mg doses, respectively, vs. 26% for placebo (life table), and 66% and 65% vs. 14%, respectively (crude rate). Both doses were superior to placebo for the percentage of 24-h heartburn-free days (60 mg, 96%; 90 mg, 94%; placebo, 19%) and nights (98%, 97%, and 50%, respectively). Diarrhoea, flatulence, gastritis (symptoms) and abdominal pain occurred more frequently with dexlansoprazole MR than placebo, but were not dose-related.
Conclusion  Dexlansoprazole MR effectively maintained healed erosive oesophagitis and symptom relief compared with placebo, and was well tolerated.     

Biliary events and an increased risk of new onset irritable bowel syndrome: a population-based cohort study

Background  Prospective data are lacking to determine if irritable bowel syndrome (IBS) is a risk factor for cholecystectomy, or if biliary disease and cholecystectomy predisposes to the development of IBS.
Aim  To test the hypothesis that IBS and biliary tract disease are associated.
Methods  Validated symptom surveys sent to cohorts of Olmsted County, MN, (1988–1994) with follow-up in 2003. Medical histories were reviewed to determine any 'biliary events' (defined by gallstones or cholecystectomy). Analyses examined were: (i) time to a biliary event post-initial survey and separately and (ii) risk of IBS (Rome II) in those with vs. without a prior biliary event.
Results  A total of 1908 eligible subjects were mailed a follow-up survey. For analysis (i) of the 726 without IBS at initial survey, 44 (6.1%) had biliary events during follow up, in contrast to 5 of 93 (5.4%) with IBS at initial survey (HR 0.8, 95% CI 0.3–2.1). For analysis (ii) of the 59 subjects with a biliary event at initial survey, 10 (17%) reported new IBS on the follow-up survey, while in 682 without a biliary event up to 1.5 years prior to the second survey, 58 (8.5%) reported IBS on follow-up (OR = 2.2, 95% CI 1.1–4.6, P  = 0.03).
Conclusion  There is an increased risk of new IBS in community subjects who have been diagnosed as having a biliary event.     

Increased plasma ghrelin following infliximab in Crohn's disease

Background  Ghrelin, a potent orexigenic peptide produced by the stomach, may be affected by circulating inflammatory mediators.
Aim  To assess the effect of an anti-TNFα antibody on ghrelin in patients with Crohn's disease (CD).
Methods  Fifteen patients with Crohn's receiving infliximab were studied before and 1 week after infusion. Following an overnight fast, blood was sampled before a meal and then every 20 min for 2 h. Total ghrelin and CRP were measured using ELISA. Acylated ghrelin and TNFα, IFNγ, IL-1β and IL-6 were measured with bioplex. Harvey Bradshaw Activity Index was assessed.
Results  Median (95% CI) 2-h integrated plasma total ghrelin increased from 162 (99–311) before infliximab to 200 (128–387) pg/mL h, ( P  = 0.02) after. Following infliximab, 20 min postmeal, median acylated ghrelin decreased from 50.3 (24–64) to 38.6 (26–82) pg/mL, ( P  = 0.04) thus reverting to a traditional meal related ghrelin curve. Median (range) disease activity decreased from 5 (2–28) before to 3 (0–22), ( P  = 0.0001) and Median (95% CI) TNFα decreased from 2.8 (1.89–4.48) to 1.31 (0.73–2.06) pg/mL ( P  = 0.002).
Conclusions  Infliximab increases circulating total ghrelin by 25% in CD and restores the postprandial response of acylated ghrelin to food intake. Acylated and de-sacyl ghrelin remain unchanged, suggesting that an alternate isoform could be affected by infliximab.     

Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation – results from two randomized controlled studies

Background  Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole.
Aim  To assess the efficacy and safety of dexlansoprazole MR in healing erosive oesophagitis (EO).
Methods  Patients in two identical double-blind, randomized controlled trials ( n  = 4092) received dexlansoprazole MR 60 or 90 mg or lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing procedure – first for non-inferiority, then superiority, vs. lansoprazole. Secondary endpoints included week 4 healing and week 8 healing in patients with moderate-to-severe disease (Los Angeles Classification grades C and D). Life-table and crude rate analyses were performed. Symptoms and tolerability were assessed.
Results  Dexlansoprazole MR achieved non-inferiority to lansoprazole, allowing testing for superiority. Using life-table analysis, dexlansoprazole MR healed 92–95% of patients in individual studies vs. 86–92% for lansoprazole; the differences were not statistically significant ( P  >   0.025). Using crude rate analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies and 60 mg was superior in one study. Week 4 healing was >64% with all treatments in both studies. In an integrated analysis of 8-week healing in patients with moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All treatments effectively relieved symptoms and were well tolerated.
Conclusion  Dexlansoprazole MR is highly effective in healing EO and offers benefits over lansoprazole, particularly in moderate-to-severe disease.     

Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis

Background  Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis.
Aim  To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease.
Methods  Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid ( n  = 5073).
Results  A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n  = 46, mesalazine (mesalamine) n  = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P  = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6–20.6; P  = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP ( n  = 1477) (OR 5.2 95% CI: 1.8–14; P  = 0.002).
Conclusions  The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.     

The association between coeliac disease and cardiovascular disease

Background  Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear.
Aim  To investigate whether coeliac disease patients have an increased risk of cardiovascular events.
Methods  A community-based cohort study using a record-linkage database. Three hundred and sixty-seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study.
Results  The crude rates of cardiovascular events were 9.5 per 1000 person-years (95% CI: 4.4–14.6) in the coeliac cohort and 8.9 per 1000 person-years (95% CI: 7.6–10.3) in the antiendomysial antibody-negative cohort. Compared with the antiendomysial antibody-negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00–3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22–5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort ( P  = 0.05), and 34% and 26% for the antiendomysial antibody-negative cohort ( P  < 0.01).
Conclusion  Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.