bluuebunny/crossref_metadata_2025 huggingface dataset:
Original article: new surgical approaches to the Klatskin tumour
Authors: VAN GULIK T. M. , DINANT S. , BUSCH O. R. C. , RAUWS E. A. J. , OBERTOP H. , GOUMA D. J.
Published: July 2010

Background  Surgical treatment of hilar cholangiocarcinoma (Klatskin tumours) is difficult because of its central location in the liver hilum. Recent developments in surgical techniques have improved the outcome after resection.

Aim  To describe the surgical approaches currently applied in our centre and the impact of these strategies on outcome and criteria for resection.

Methods  From 1988 to 2003, 99 consecutive patients underwent resection for hilar cholangiocarcinoma. Patients were analysed for rate of R0 resections in relation with Bismuth classification. Morbidity, mortality and survival were assessed.

Results  The rate of hilar resections in combination with (extended) liver resections for type III and IV tumours increased from 24% to 95% in the last 5 years of the study period. Eight patients (8%) had Bismuth type IV tumours. Four of these patients underwent palliative local excisions of the hepatic duct confluence whereas the other four patients underwent hilar resection in combination with partial liver resection, resulting in microscopically radical resections. There was no mortality in this group. Overall postoperative morbidity and mortality were 68% and 10%, respectively.

Conclusions  An aggressive surgical approach consisting of hilar resections combined with partial liver resections including segments 1 and 4, resulted in a higher rate of R0 resections. Even Bismuth type IV tumours may be resectable depending on the biliary anatomy of the hepatic duct confluence.
Review article: the prevalence and clinical relevance of cytochrome P450 polymorphisms
Authors: WIJNEN P. A. H. M. , OP DEN BUIJSCH R. A. M. , DRENT M. , KUIPERS P. M. J. C. , NEEF C. , BAST A. , BEKERS O. , KOEK G. H.
Published: July 2010

Background Most drugs currently used in clinical practice are effective in only 25% to 60% of patients, while adverse drug reactions (ADRs) as a consequence of treatment are estimated to cost billions of US dollars and tens of thousands of deaths.

Aim To review the prevalence and clinical significance of cytochrome P450 polymorphisms.

Results The cytochrome P450 enzyme families 1–3 are responsible for 70 to 80% of all phase I dependent drug metabolisms. In 90% metabolic activity dependents on six enzymes: CYP1A2, CYP3A, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Polymorphisms in the CYP450 gene can influence metabolic activity of the subsequent enzymes. A poor metabolizer (PM) has no or very poor enzyme activity. A consequence of PM is drug toxicity if no other metabolic route is available, or when multiple drugs are metabolized by the same cytochrome. In that case dose reduction is an option to prevent toxic effects.

Conclusions In the future genotyping should be considered to identify patients who might be at risk of severe toxic responses, in order to guide appropriate individual dosage. Medical therapy should be a close cooperation between clinicians, pharmacologists and laboratory specialists, leading to reduced therapeutic errors, ADRs and health care costs.
Meta‐analysis: the use of non‐steroidal anti‐inflammatory drugs and pancreatic cancer risk for different exposure categories
Authors: CAPURSO G. , SCHÜNEMANN H. J. , TERRENATO I. , MORETTI A. , KOCH M. , MUTI P. , CAPURSO L. , DELLE FAVE G.
Published: July 2010

Background  A better understanding of predictors of risk for pancreatic ductal adenocarcinoma (PDAC) could inform preventive efforts against this lethal cancer. While aspirin (ASA) and non‐steroidal anti‐inflammatory drugs (NSAIDS) might protect against several gastrointestinal cancers, their role in the development of PDAC remains unclear.

Aim  To conduct a systematic review and meta‐analysis on the relation between ASA/NSAIDs exposure and the risk of PDAC.

Methods  We searched Pubmed, Embase, Scopus, Cochrane database of systematic reviews and reference lists of identified papers and included observational (cohort or case‐control) studies and randomized controlled trials examining exposure to ASA and/or NSAIDs and the incidence or mortality of PDAC. We defined three categories (low, intermediate, high), based on exposure duration and dose.

Results  Eight studies fulfilled our inclusion criteria (four cohort, three case controls, and one randomized controlled trial studies) enrolling 6301 patients between 1971–2004; all but one study took place in the US. The pooled OR were 0.99 (0.83–1.19), 1.11 (0.84–1.47) and 1.09 (0.67–1.75) in the low, intermediate and high exposure groups respectively, with considerable heterogeneity (I2 ranging 60–86%). Sensitivity analysis by ASA use only, study design or sex did not reveal additional important information.

Conclusions  This study did not show an association between ASA/NSAIDs and PDAC. The large baseline exposure in controls in North‐America may have obscured an association. There is need for additional studies, especially in Europe, to clarify this issue.
Review article: a pharmacoeconomic analysis of thrombocytopenia in chronic liver disease
Authors: BROWN R. S.
Published: July 2010

Background  Patients with chronic liver disease commonly experience thrombocytopenia resulting from disease or treatment. Such patients often require multiple platelet transfusions, and consequently can experience associated complications including systemic infection, iron overload, and platelet refractoriness.

Aim  To discuss the limited data available on the impact of thrombocytopenia on the medical procedures and their associated costs.

Results  Thrombocytopenia and its treatment can have a negative impact on outcomes and cost of therapy; costs associated with platelet transfusion can constitute a significant portion of the hospital budget. Inability to initiate or complete antiviral therapy for chronic hepatitis C infection due to low platelet counts can lead to dose reduction or discontinuation, lower efficacy, increased risks, and increased overall costs. Routine medical procedures can be complicated, prolonged, or precluded as a result of severe thrombocytopenia.

Conclusion  Novel therapies can safely and effectively prevent or treat thrombocytopenia in this patient population with chronic liver disease resulting in improved quality of care and significant cost savings in addition to improving treatment outcomes and quality of life (QOL) measures.
Review article: coagulation disorders in chronic liver disease
Authors: PECK‐RADOSAVLJEVIC M.
Published: July 2010

Background  The liver is the site for synthesis of the vast majority of proteins that play a central role in maintaining hemostasis, by participating in the regulation of coagulation and fibrinolysis.

Aim  To summarize the available data on the impact of coagulation disorders in patients with chronic liver disease.

Results  Hepatocellular damage in patients with severe liver disease can lead to abnormalities in the production and function of coagulation and fibrinolytic factors, disrupting the balance between coagulation and anticoagulation systems.

Conclusions  Hemostatic abnormalities (eg. impaired synthesis of clotting factors, heightened fibrinolysis, disseminated intravascular coagulation, thrombocytopenia, and platelet dysfunction) can increase the risk of bleeding in cirrhotic patients.
Review article: pharmacological approaches for the treatment of thrombocytopenia in patients with chronic liver disease and hepatitis C infection
Authors: AFDHAL N. H. , MCHUTCHISON J. G.
Published: July 2010

Background  Patients with chronic liver disease and hepatitis C virus (HCV) frequently experience thrombocytopenia that complicates the management of their disease. Traditional therapy for thrombocytopenia consists of platelet transfusion, which can be associated with significant safety and economic issues. Consequently, efforts have been directed toward developing novel approaches for the treatment of thrombocytopenia.

Aim  To summarize the available data on the limitations of traditional therapies and the effects of novel therapies currently in clinical development for the treatment of thrombocytopenia.

Results  Recent research has begun to reveal the complex mechanisms that regulate thrombopoiesis. Cytokines and growth factors, such as interleukin‐11 and thrombopoietin (TPO), play a key role in the production of platelets. A number of recent clinical studies have provided evidence that pharmacologic agents that target megakaryocyte precursors and stimulate thrombopoiesis can effectively reverse thrombocytopenia. Here, we review the regulation of thrombopoiesis, the role of TPO, and a number of novel compounds that stimulate platelet production by acting through the TPO receptor. Agents that stimulate TPO include the orally available nonpeptidic agonists eltrombopag and AKR‐501, peptidic agonists AMG‐531 and Peg‐TPOmp, and small engineered antibodies.

Conclusion  Results from clinical trials with these agents in healthy subjects confirm that activation of thrombopoiesis via the TPO pathway is an effective method of stimulating platelet production. This approach may provide safer, more effective treatment for thrombocytopenia in patients with chronic liver disease. Several of these agents are currently being tested in large scale trials.
Review article: the measurement of non‐acid gastro‐oesophageal reflux
Authors: SMOUT A. J. P. M.
Published: July 2010

Background  Oesophageal pH monitoring has been used for three decades to study gastro‐oesophageal reflux, but it does not allow detection of non‐acid reflux episodes.

Aim  To discuss the techniques by which non‐acid reflux can be measured and to evaluate the clinical relevance of such measurements.

Methods  Review of the literature on non‐acid reflux monitoring.

Results  Ambulatory oesophageal impedance monitoring (using a catheter with ring electrodes) allows one to detect all types of gastro‐oesophageal reflux, acid as well as non‐acid. Measurement of intra‐oesophageal bilirubin concentration also detects reflux irrespective of the pH, but only when there is bilirubin in the gastric juice and technical short‐comings limit the applicability of this technique. In untreated subjects, about 50% of reflux episodes are non‐acid (nadir pH > 4). In patients on acid inhibition, up to 95% of reflux episodes are non‐acid. Treatment with an acid inhibitor leads to a significant decrease in the incidence of acid reflux episodes, but not to a reduction in the total number of reflux episodes. This shift is associated with a shift in symptoms from heartburn to regurgitation. With impedance monitoring, the temporal association between symptoms that persist during inhibition of acid secretion and non‐acid reflux events can be demonstrated. In a proportion of patients with chronic cough, the coughing episodes are preceded by non‐acid reflux.

Conclusions  Intraluminal impedance monitoring of gastro‐oesophageal reflux is a feasible technique, which provides clinically important information about the relationships between symptoms and non‐acid reflux events.
Review article: the diagnosis and management of gastroparesis
Authors: HAANS J. J. L. , MASCLEE A. A. M.
Published: July 2010

Background  Gastroparesis is a disorder characterized by a delay in gastric emptying of a meal in the absence of a mechanical gastric outlet obstruction.

Aim  To provide an evidence based overview on diagnosis and management of gastroparesis.

Methods  A PubMed search was performed using search terms including gastroparesis, gastric retention, gastric emptying, accommodation, manometry, prokinetics, antiemetics, metoclopramide, domperidone, erythromycin, botulinum toxin, gastric pacing. Relevant studies were identified and original articles and reviews were collected. References in these articles were examined for relevance and included where appropriate.

Results  Diagnosis of gastroparesis is based on the presence of symptoms such as nausea, vomiting and postprandial abdominal fullness and on an objectively determined delay in gastric emptying. The true prevalence of gastroparesis is unknown. Gastric emptying can be assessed by scintigraphy and stable isotope breath tests. Management of gastroparesis consists of dietary and lifestyle measures and/or pharmacological interventions (prokinetics, antiemetics, intrapyloric botulinum toxin injection) or other interventions that focus on adequate nutrient intake either through a nasoduodenal tube, percutaneous gastrostomy or jejunostomy.

Conclusions  Accurate diagnosis of gastroparesis requires an adequate protocol to measure gastric emptying. Treatment options in gastroparesis remain limited despite the disabling nature of the disorder.
Oral pathology in untreated coelic disease
Authors: CAMPISI G. , DI LIBERTO C. , IACONO G. , COMPILATO D. , DI PRIMA L. , CALVINO F. , DI MARCO V. , LO MUZIO L. , SFERRAZZA C. , SCALICI C. , CRAXÌ A. , CARROCCIO A.
Published: July 2010

Background  Many coeliac disease patients with atypical symptoms remain undiagnosed.

Aim  To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis.

Patients and methods  One hundred and ninety‐seven coeliac disease patients and 413 controls were recruited and the oral examination was performed.

Results  Forty‐six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten‐free diet. Multi‐logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427–4.926) and soft tissue lesions (OR = 41.667, CI = 18.868–90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis.

Conclusions  The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive‐predictive value of these lesions for coeliac disease diagnosis was low.
Four‐day continuous gastric pH monitoring following anti‐acid secretory drug administration: cross‐over test to assess the early effects
Authors: SUZUKI T. , YAMAGUCHI T. , ODAKA T. , KOBAYASHI M. , SEZA A. , KOUZU T. , YOKOSUKA O.
Published: July 2010

Background There have been few reports that compare the effect of histamine H2‐receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) using continuous gastric pH monitoring for a long duration.

Aim To assess the early effects of both drugs on gastric pH using a wireless pH monitoring system.

Methods The test was conducted by a cross‐over test: 10 healthy male volunteers were administered famotidine 20 mg twice a day and lansoprazole 30 mg once a day. Monitoring of gastric pH over four consecutive days was performed using a unique method we have developed that is an elaboration of the Bravo system.

Results The time to reach a pH level of 3 or more with famotidine was significantly shorter than that for lansoprazole. The pH3 holding time ratio of famotidine during the first 4 h of administration was significantly higher than that of lansoprazole. The pH3 holding time ratio on each day from day 1 to day 3 was significantly higher following lansoprazole administration compared with famotidine administration.

Conclusions Famotidine was shown to act quickly in elevating gastric pH; however, lansoprazole was superior to famotidine in terms of its ability to elevate gastric pH for a long duration.
Infliximab dose escalation vs. initiation of adalimumab for loss of response in Crohn’s disease: a cost‐effectiveness analysis
Authors: KAPLAN G. G. , HUR C. , KORZENIK J. , SANDS B. E.
Published: July 2010

Background  Crohn’s disease patients who have lost response to 5 mg/kg of infliximab may regain response by increasing the dose of infliximab to 10 mg/kg. Alternatively, adalimumab can be used as a rescue therapy.

Aim  To determine whether dose escalation of infliximab was a cost‐effective strategy compared with adalimumab initiation after loss of response to 5 mg/kg of infliximab.

Methods  A decision‐analysis model simulated two cohorts of Crohn’s patients: (i) infliximab dose was escalated to 10 mg/kg and (ii) infliximab was discontinued and patients were started on adalimumab. The time horizon was 1 year. One‐ and two‐way sensitivity analyses were performed.

Results  The infliximab dose escalation strategy yielded more quality‐adjusted life years (0.79) compared with the adalimumab strategy (0.76). The incremental cost‐effectiveness ratio was $332 032/quality‐adjusted life year. Sensitivity analysis demonstrated that the model findings were robust. The most significant variables were the cost of infliximab and that of adalimumab, such that a reduction in the cost of infliximab by 1/3 resulted in an incremental cost‐effectiveness ratio below $80 000/quality‐adjusted life year.

Conclusion  After a Crohn’s patient has lost response to 5 mg/kg of infliximab, dose escalation will yield more quality‐adjusted life‐year compared with switching to adaliumamb; however, the cost was considerable.
Review article: the gastrointestinal tract: neuroendocrine regulation of satiety and food intake
Authors: MALJAARS J. , PETERS H. P. F. , MASCLEE A. M.
Published: July 2010

Background  The gastrointestinal tract elicits numerous signals regulating food intake and satiety, and recently many studies have been performed to elucidate the mechanisms regulating these signals.

Aim  To describe the effects of the gastrointestinal tract on satiety, satiation and food intake.

Methods  A PubMed search was performed to identify and select the relevant literature using search terms including ‘gastric satiety, intestine + satiety, satiation, cholecystokinin, ghrelin, peptide YY, glucagon‐like peptide‐1 and ileal brake’.

Results  Satiation, satiety and food intake result, among other factors, from signals originating in the stomach caused by distension and signals from the small intestine. These intestinal signals result from nutrient sensing in the gut and activate neural and humoral pathways. Activation of the distal part of the gut, the so called ileal brake, leads to reduction in hunger and food intake, and models of chronic ileal brake activation lead to massive weight loss.

Conclusion  Gastrointestinal signals are crucial for the regulation of food intake, satiety and satiation. The ileal brake deserves special attention, as both ileal intubation studies and surgical studies demonstrate that activation of the ileal brake reduces food intake. In the surgical models, weight loss occurs without adaptation to the anorectic effects of ileal brake activation.
Long‐term therapy with adefovir dipivoxil in hepatitis B e antigen‐negative patients developing resistance to lamivudine
Authors: MANOLAKOPOULOS S. , BETHANIS S. , KOUTSOUNAS S. , GOULIS J. , VLACHOGIANNAKOS J. , CHRISTIAS E. , SAVERIADIS A. , PAVLIDIS C. , TRIANTOS C. , CHRISTIDOU A. , PAPATHEODORIDIS G. , KARAMANOLIS D. , TZOURMAKLIOTIS D.
Published: July 2010

Background  The efficacy of long‐term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe‐Ag)‐negative lamivudine‐resistant chronic hepatitis B (CHB) patients is still under investigation.

Aim  To assess the safety and efficacy of the long‐term adefovir treatment alone or in combination with lamivudine in HBe‐Ag‐negative CHB patients who had developed breakthrough because of lamivudine‐resistant mutants.

Methods  Fifty‐nine patients received combination therapy, while 23 switched to adefovir alone after a 3‐month course of combination therapy.

Results  The median follow‐up after adefovir’s onset was 31 (18–40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV‐DNA <104 copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir‐resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow‐up. Re‐introduction of lamivudine in adefovir‐resistant patients achieved reduction in HBV‐DNA and biochemical remission, but re‐emergence of lamivudine mutants was observed in one patient after 7.5 months.

Conclusion  In HBe‐Ag‐negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti‐viral efficacy because of absence of viral resistance.
De novo depression and anxiety disorders and influence on adherence during peginterferon‐alpha‐2a and ribavirin treatment in patients with hepatitis C
Authors: MARTÍN‐SANTOS R. , DÍEZ‐QUEVEDO C. , CASTELLVÍ P. , NAVINÉS R. , MIQUEL M. , MASNOU H. , SOLER A. , ARDEVOL M. , GARCÍA F. , GALERAS J. A. , PLANAS R. , SOLÀ R.
Published: July 2010

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.
Tolerability and safety of mercaptopurine in azathioprine‐intolerant patients with inflammatory bowel disease
Authors: LEES C. W. , MAAN A. K. , HANSOTI B. , SATSANGI J. , ARNOTT I. D. R.
Published: July 2010

Background  Azathioprine intolerance is a common clinical problem, requiring drug withdrawal in up to 30% of patients. The successful use of mercaptopurine is described, but data to support this strategy are needed.

Aims  To assess the tolerability of mercaptopurine in inflammatory bowel disease patients previously intolerant of azathioprine, and identify predictive factors.

Methods  Sixty‐one azathioprine‐intolerant patients (31 males, median age at diagnosis 32 years, 31 with Crohn’s disease, 30 with ulcerative colitis) who had been treated with mercaptopurine were identified. Intolerances included nausea and vomiting, flu‐like illness, neutropenia, hepatotoxicity and pancreatitis.

Results  Mercaptopurine was tolerated by 59% (36 of 61) of azathioprine‐intolerant patients (median dose 1.0 mg/kg), 61% (17 of 28) in patients with azathioprine‐related nausea and vomiting, 61% (11 of 18) with flu‐like illness, 33% (three of nine) with hepatotoxicity, 100% (one of one) with neutropenia, 100% (three of three) with rash and 0% (zero of one) with pancreatitis. Mercaptopurine intolerance was frequently for a different adverse event. Those intolerant of mercaptopurine were younger (28.4 years vs. 37.0 years; P = 0.014) and more frequently female (14/30 vs. 2/29, P = 0.027). Mercaptopurine tolerability was not affected by diagnosis, location, behaviour, surgery, smoking, family history or extra‐intestinal manifestations.

Conclusion  Mercaptopurine may be tolerated in up to 60% of azathioprine‐intolerant patients, and treatment should be considered, particularly if intolerance was due to nausea, vomiting, flu‐like illness or rash.
Pre‐operative transarterial chemoembolization for resectable hepatocellular carcinoma adversely affects post‐operative patient outcome
Authors: KIM I. S. , LIM Y. S. , LEE H. C. , SUH D. J. , LEE Y. J. , LEE S. G.
Published: July 2010

Background  Long‐term outcomes after hepatic resection for hepatocellular carcinoma are not satisfactory because of high recurrence rates.

Aim  To assess whether a single session of pre‐operative transarterial chemoembolization affects post‐operative outcome.

Methods  We analysed outcomes retrospectively in 334 consecutive patients who underwent hepatic resection for hepatocellular carcinoma, initially judged resectable. Ninety‐seven of these patients had each undergone a single session of pre‐operative transarterial chemoembolization (transarterial chemoembolization + hepatic resection group), whereas 237 had not (hepatic resection group).

Results  Most clinicopathological characteristics were similar in the two groups. The overall survival rate was significantly higher in the hepatic resection than in the transarterial chemoembolization + hepatic resection group (P = 0.011), whereas their disease‐free survival rates were comparable (P = 0.67). The overall and disease‐free survival rates of the transarterial chemoembolization + hepatic resection group with incomplete tumour necrosis were significantly lower than those of the hepatic resection group (P < 0.001 and P = 0.006, respectively). Multivariate analysis showed that pre‐operative transarterial chemoembolization, serum alpha‐fetoprotein elevation (>1000 ng/mL), tumour size (>5 cm) and vascular invasion were independent risk factors for poor overall survival after hepatic resection.

Conclusions  A single session of pre‐operative transarterial chemoembolization for initially resectable hepatocellular carcinoma worsens overall survival rate. It may also increase the risk of tumour recurrence in patients who achieve incomplete tumour necrosis.
Is interleukin‐1 genotyping useful for the clinical management of patients with atrophic body gastritis?
Authors: LAHNER E. , CORLETO V. D. , D’AMBRA G. , DI GIULIO E. , DELLE FAVE G. , ANNIBALE B.
Published: July 2010

Background  Atrophic body gastritis patients are at increased risk for gastric cancer. IL‐1B/IL‐1RN polymorphisms have been associated with gastric cancer susceptibility. The relationship between these polymorphisms and the long‐term outcome of atrophic body gastritis patients is not known.

Aim  To investigate whether the genotyping of IL‐1B‐511/IL‐1RN polymorphisms is useful to characterize atrophic body gastritis patients at increased risk for gastric neoplasms.

Methods  IL‐1B‐511/IL‐1RN polymorphisms were compared between 110 atrophic body gastritis patients and 110 age‐ and gender‐matched controls, and patients were followed up (median 4.1 years) according to a cohort study design.

Results  Genotype frequencies of IL‐1B‐511/IL‐1RN were similar between patients and controls. Atrophic body gastritis patients harbouring the wild type of IL‐1B‐511/IL‐1RN polymorphisms were not different from those harbouring the proinflammatory pattern as far as regards gender, age, gastric cancer family history and metaplastic atrophy. Sixteen atrophic body gastritis patients developed a gastric neoplastic lesion at follow‐up: eight were IL‐1B‐511‐T carriers and eight were IL‐1RN‐allele‐2 carriers. Harbouring the proinflammatory genotypes was not significantly associated with developing gastric neoplastic lesions.

Conclusions  In atrophic body gastritis patients, IL‐1B‐511 and IL‐1RN polymorphisms do not appear to be associated either with specific clinical, biochemical or histological features or with the development of gastric neoplastic lesions at long‐term follow‐up.
The use of adalimumab in the management of refractory Crohn’s disease
Authors: HO G.‐T. , SMITH L. , AITKEN S. , LEE H. M. , TING T. , FENNELL J. , LEES C. W. , PALMER K. R. , PENMAN I. D. , SHAND A. G. , ARNOTT I. D. , SATSANGI J.
Published: July 2010

Background Adalimumab is a humanized monoclonal antibody targeting tumour necrosis factor‐α. Recent clinical trials have demonstrated its efficacy in Crohn’s disease; however, experience in clinical practice remains limited.

Aim To investigate the efficacy and safety of adalimumab in the clinical setting.

Methods The clinical outcomes of patients with medically refractory Crohn’s disease treated with adalimumab in the Western General Hospital Edinburgh, over a 3‐year period (2003–2006), were studied.

Results Twenty‐two (14 females; age at therapy: 32.6 years) patients were treated using an 80/40 mg induction regimen followed by fortnightly 40 mg treatment. All had proven refractory/intolerant to corticosteroids and immunosuppression. Twenty patients had had previous infliximab infusions – of these eight (36%), six (27%), three (14%) had previous infusion reactions, no response and lost response to infliximab, respectively. Over a period of 1.0 years (IQR: 0.62–2.5), Kaplan–Meier analyses showed that 68% (seven nonresponders) were in clinical remission and 67% (five surgery – discounting oral CD) avoided further surgery for active disease. 59% required dose escalation to 40 mg weekly (0.55 years; IQR: 0.22–1.4). Three (50%) primary nonresponders to infliximab achieved remission. Two patients developed serious infective complications and one patient developed lung cancer.

Conclusions Adalimumab is efficacious in refractory Crohn’s disease, with benefit observed in infliximab primary nonresponders. However, many patients require escalation of dosing regimen.
Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects
Authors: DE PRETER V. , VANHOUTTE T. , HUYS G. , SWINGS J. , RUTGEERTS P. , VERBEKE K.
Published: July 2010

Background  Dietary intervention with prebiotics can cause changes in the colonic microbiota and their metabolic activities.

Aim  To investigate whether the response to prebiotic dosing is influenced by the baseline metabolic activity of the colonic flora and bifidobacteria counts.

Methods  The 4‐week effect of lactulose (10 g bid.; n = 29) and oligofructose‐enriched inulin (10 g bid.; n = 19) was evaluated in healthy human volunteers. Lactose‐[15N, 15N]‐ureide was used to study the colonic NH3‐metabolism. Urine (48 h) and faeces (72 h) were collected and analysed for p‐cresol and 15N‐content by gas chromatography–mass spectrometry and isotope ratio mass spectrometer, respectively. Faecal bifidobacteria were quantified by real‐time polymerase chain reaction.

Results  After the 4‐week prebiotic administration period, the urinary excretion of p‐cresol and 15N was significantly decreased in both groups (P < 0.05) corresponding to a significantly higher faecal excretion of 15N (P < 0.05). The decrease in urinary 15N and p‐cresol excretion significantly correlated with baseline 15N and p‐cresol levels (P < 0.05), indicating that subjects with higher baseline levels showed a higher response to prebiotic dosing. Furthermore, a significant correlation was seen between baseline bifidobacteria counts and the effect of prebiotic intake (P < 0.05).

Conclusion  The response to prebiotic dosing, as indicated by the fate of NH3, p‐cresol and bifidobacteria, is determined by the initial colonic conditions.
The association between coeliac disease and cardiovascular disease
Authors: WEI L. , SPIERS E. , REYNOLDS N. , WALSH S. , FAHEY T. , MACDONALD T. M.
Published: July 2010

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.
The influence of co‐morbid IBS and psychological distress on outcomes and quality of life following PPI therapy in patients with gastro‐oesophageal reflux disease
Authors: NOJKOV B. , RUBENSTEIN J. H. , ADLIS S. A. , SHAW M. J. , SAAD R. , RAI J. , WEINMAN B. , CHEY W. D.
Published: July 2010

Background  A subset of patients with gastro‐oesophageal reflux disease (GERD) does not achieve complete symptom resolution with proton pump inhibitor (PPI) therapy. The factors which affect response to PPI therapy in GERD patients remain unclear.

Aims  To determine the prevalence and impact of irritable bowel syndrome (IBS) and psychological distress (PD) on GERD symptoms and disease‐specific quality of life (QoL) before and after PPI therapy and to assess the same outcomes before and after PPI therapy in non‐erosive reflux disease (NERD) and erosive oesophagitis (EO) GERD patients.

Methods  Patients undergoing oesophago‐gastroduodenoscopy (OGD) for heartburn were recruited. Participants completed validated surveys: Digestive Health Symptom Index, Reflux Disease Questionnaire, Quality of Life in Reflux and Dyspepsia and Brief Symptom Inventory (BSI). IBS was defined as >3 Manning criteria and PD as BSI score >63. At OGD, patients were classified as NERD or EO. Patients were treated with rabeprazole 20 mg/day for 8 weeks before completing follow‐up surveys.

Results  Of 132 GERD patients enrolled, 101 completed the study. The prevalence rates of IBS and PD were 36% and 41%, respectively. IBS independently predicted worse QoL before and after PPI therapy. PD independently predicted worse GERD symptoms and QoL before and after PPI therapy. There were no differences in symptoms or QoL between NERD and EO patients before or after PPI therapy.

Conclusions  IBS and PD impacted GERD symptoms and QoL before and after PPI therapy. Symptoms and QoL before and after PPI therapy were similar in NERD and EO patients.
Clinical trial: a dose–response study of fospropofol disodium for moderate sedation during colonoscopy
Authors: COHEN L. B.
Published: July 2010

Background  An effective agent is needed that provides rapid onset of sedation and quick recovery for patients undergoing colonoscopy.

Aim  To assess the efficacy and safety of fospropofol disodium in providing sedation in patients undergoing colonoscopy.

Methods  A randomized, double‐blind, multicentre trial evaluated 127 adult patients who received fospropofol (2, 5, 6.5 or 8 mg/kg) or midazolam 0.02 mg/kg following pre‐treatment with fentanyl. Supplemental doses of study medication were allowed to reach a Modified Observer’s Assessment of Alertness/Sedation scale score ≤4. Efficacy end points included sedation success, measures of clinical benefit, sedation, and recovery as well as patient‐ and doctor‐rated satisfaction.

Results  Fospropofol produced a significant dose‐dependent increase in sedation success from 24% (2 mg/kg), 35% (5 mg/kg) and 69% (6.5 mg/kg) to 96% (8 mg/kg; P < 0.001). There were also dose‐dependent trends for time to sedation, requirements for alternative sedative medication, supplemental doses of sedative and fentanyl, time to ready for discharge and doctor‐rated satisfaction scores. Fospropofol was well tolerated, with most adverse events mild‐to‐moderate in severity.

Conclusion  The 6.5 mg/kg dose of fospropofol provides the ideal balance of efficacy and safety for patients undergoing colonoscopy and has been selected for phase 3 clinical development.
Low body mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease
Authors: NOBLE C. L. , MCCULLOUGH J. , HO W. , LEES C. W. , NIMMO E. , DRUMMOND H. , BEAR S. , HANNAN J. , MILLAR C. , RALSTON S. H. , SATSANGI J.
Published: July 2010

Background  Osteoporosis is a recognized complication of inflammatory bowel disease (IBD).

Aim  To investigate the role of environmental factors and vitamin D receptor (VDR) variants on the prevalence of osteoporosis.

Methods  DEXA scans and case note review were performed on 440 IBD patients from 1997 to 2006. All the IBD patients and 240 healthy controls were genotyped for VDR variants Taq‐1 and Apa‐1 using PCR‐RFLP.

Results  Osteoporosis and osteopenia rates were 15% and 18% for IBD, 16% and 18% for Crohn’s disease (CD) and 13% and 19% for ulcerative colitis, respectively. On univariate analysis of the CD patients, low body mass index (BMI, <18.5) and smoking status (P = 0.008 and 0.005 respectively) were associated with osteoporosis and osteopenia. Low BMI was also associated with osteoporosis on multivariate analysis in CD (P = 0.021, OR 5.83, CI 1.31–25.94). No difference was observed between Taq‐1 and Apa‐1 VDR polymorphisms in IBD, CD, ulcerative colitis and healthy controls. However, CD males were more likely to carry the variant Taq‐1 polymorphism than healthy controls males (P = 0.0018, OR 1.94, CI 1.28–2.92) and female CD patients (P = 0.0061, OR 1.60, CI 1.17–2.44).

Conclusions  In this well‐phenotyped cohort of IBD patients, a relatively low prevalence of osteoporosis was observed. Low BMI was the only independent risk factor identified to be associated with osteoporosis.
Review article: improving adherence to medication in patients with inflammatory bowel disease
Authors: ROBINSON A.
Published: July 2010

Background  Adherence to medications in inflammatory bowel disease is associated with a reduced risk of both relapse and colorectal cancer development in the long term. However, many patients are non‐adherent to their prescribed treatment regimen.

Aim  To review and discuss the extent of medication non‐adherence in inflammatory bowel disease patients, the predictors of non‐adherence, and strategies for optimizing patient adherence.

Results  More than 40% of inflammatory bowel disease patients do not adhere to their medication and thus a significant number of patients are not receiving the full benefits from their treatment – that is, remission and disease maintenance. The causes of medication non‐adherence are multi‐factorial. Improving medication adherence in patients is an important challenge for physicians; understanding the different patient types, the reasons given by patients for non‐adherence and the predictors of non‐adherence will help devise suitable plans to optimize patient adherence. Approaches such as improving the physician–patient relationship, individualized therapy, providing patient information and support, self‐management programmes and practical aide memoires can be beneficial.

Conclusions  Implementation of strategies to improve medication adherence in inflammatory bowel disease patients increases the likelihood of patients achieving disease remission and maintaining remission in the long term, thereby improving symptom control and quality of life.
Systematic review: ulcer definition in NSAID ulcer prevention trials
Authors: YEOMANS N. D. , NÆSDAL J.
Published: July 2010

Background  In clinical trials of peptic ulcer prevention, the most appropriate definition of an ulcer remains challenging.

Aims  To evaluate the ulcer definitions used in clinical trials of ulcer prevention among non‐steroidal anti‐inflammatory drug users and to determine whether any specific definition is preferred.

Methods  A systematic literature search of the PubMed, Medline and EMBASE databases was conducted. Results were limited to full papers published in English from June 1987 to June 2007 that met the following criteria: randomized, controlled non‐steroidal anti‐inflammatory drug trials of ≥8 weeks’ duration, with a primary end point of ulcer upon endoscopy.

Results  Forty five publications met the inclusion criteria and were reviewed. Overall, an ulcer diameter of ≥3 mm was used in 25 publications and most included a description of ulcer depth. Of the remainder, ulcer was defined as any lesion with unequivocal/observable depth (with no lower limit for ulcer diameter; five publications) or an excavated mucosal break >3 mm (one publication), whereas nine defined a minimum ulcer size of ≥5 or >5 mm. Ulcer definition was unclear in the remaining five publications.

Conclusion  In clinical trials of ulcer prevention among non‐steroidal anti‐inflammatory drug users, a gastric or duodenal lesion ≥3 mm in diameter with significant depth is the preferred definition.
Review article: respiratory manifestations of gastro‐oesophageal reflux disease
Authors: GALMICHE J. P. , ZERBIB F. , BRULEY DES VARANNES S.
Published: July 2010

Background  Respiratory manifestations represent one of the most prevalent and difficult‐to‐manage extra‐oesophageal syndromes of gastro‐oesophageal reflux disease.

Aims  To review the epidemiology, pathophysiological mechanisms and therapeutic outcomes of reflux‐related respiratory disorders.

Methods  Search of the literature published in English using PubMed database.

Results  There is a discrepancy between the high prevalence of reflux in asthmatics and the limited efficacy of antireflux therapies. Asthma per se may cause reflux. Patients with difficult‐to‐treat asthma and/or nocturnal symptoms should be screened for reflux. Reflux can induce chronic cough through different mechanisms including micro‐aspiration and both local and central reflexes. Cough and reflux may precipitate each other. A meta‐analysis found no significant difference between placebo and proton pump inhibitors in the resolution of cough. Encouraging results have been reported, following antireflux surgery in patients selected on the basis of pH‐impedance monitoring. Attention has been drawn to obstructive sleep apnoea syndrome.

Conclusions  The role of gastro‐oesophageal reflux disease in the pathogenesis of miscellaneous respiratory disorders has been discussed for decades and established in asthma and cough. However, no major therapeutic advances have been reported recently. Future trials should concentrate on patient selection and the control of efficacy using recently developed technologies, such as pH‐impedance monitoring.
Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis
Authors: ROEDIGER W. E. W.
Published: July 2010

Background Factors initiating human ulcerative colitis (UC) are unknown. Dysbiosis of bacteria has been hypothesized to initiate UC but, to date, neither the nature of the dysbiosis nor mucosal breakdown has been explained.

Aim To assess whether a dysbiosis of anaerobic nitrate respiration could explain the microscopic, biochemical and functional changes observed in colonocytes of UC.

Methods Published results in the gastroenterological, biochemical and microbiological literature were reviewed concerning colonocytes, nitrate respiration and nitric oxide in the colon in health and UC. A best‐fit explanation of results was made regarding the pathogenesis and new treatments of UC.

Results Anaerobic nitrate respiration yields nitrite, nitric oxide (NO) and nitrous oxide. Colonic bacteria produce NO and UC in remission has a higher lumenal NO level than control cases. NO with sulphide, but not NO alone, impairs β‐oxidation, lipid and protein synthesis explaining the membrane, tight junctional and ion channel changes observed in colonocytes of UC. The observations complement therapeutic mechanisms of those probiotics, prebiotics and antibiotics useful in treating UC.

Conclusions The prolonged production of bacterial NO with sulphide can explain the initiation and barrier breakdown, which is central to the pathogenesis of UC. Therapies to alter bacterial nitrate respiration and NO production need to evolve. The production of NO by colonic bacteria and that of the mucosa need to be separated to pinpoint the sequential nature of NO damage in UC.
A randomized, placebo‐controlled, crossover, double‐blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans
Authors: MADSEN J. L. , FUGLSANG S.
Published: July 2010

Background Little is known about the role of tachykinins on human gastrointestinal motility and no data exist on the possible effect of an NK1 receptor antagonist.

Aim To examine the effect of an antiemetic dose of the selective NK1 receptor antagonist aprepitant on gastrointestinal propulsion in healthy humans.

Methods Twelve healthy volunteers participated in a crossover, double‐blind study. In random order, each volunteer had a 125‐mg capsule of aprepitant or placebo on day 1 followed by an 80‐mg capsule of aprepitant or placebo on days 2–5. Gamma camera imaging was used to measure gastric emptying, small intestinal transit and colonic transit of a radiolabelled, 1600‐kJ mixed liquid and solid meal ingested on day 2.

Results Aprepitant did not change gastric retention at 15 min, gastric half emptying time, gastric mean transit time, time to small intestinal transit of 10%, small intestinal mean transit time or colonic geometric centre after 24, 48 and 72 h.

Conclusion A 125‐mg capsule of aprepitant followed by an 80‐mg capsule of aprepitant each of the next 2–5 days did not induce major changes in the propulsive function of the gastrointestinal tract in the small number of healthy volunteers investigated.