bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummaryBackground  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

SummaryBackground  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

SummaryBackground  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

SummaryBackground  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

SummaryBackground  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

SummaryBackground 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

SummaryBackground 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

SummaryBackground 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

SummaryBackground  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

SummaryBackground  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

SummaryBackground  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

SummaryBackground  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

SummaryBackground  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.