bluuebunny/crossref_metadata_2025 huggingface dataset:
Change over time of bowel habit in irritable bowel syndrome: a prospective, observational, 1‐year follow‐up study (RITMO study)
Authors: GARRIGUES V. , MEARIN F. , BADÍA X. , BALBOA A. , BENAVENT J. , CABALLERO A. , DOMÍNGUEZ E. , DÍAZ‐RUBIO M. , ROSET M. , FIGUERAS M. , CUCALA M. ,   RITMO GROUP
Published: July 2010

Background

Evolution of bowel habit in irritable bowel syndrome (IBS) is not well known.

Aim

To evaluate the change over time of bowel habit in IBS patients followed‐up during 1 year.

Methods

Five hundred and seventeen patients with IBS were prospectively included in an observational study with five evaluations over a 1‐year period. Symptoms were recorded daily in diary cards during four 4‐week periods along the study. Bristol Stool Scale (BSS) was used to define bowel habit.

Results

Four‐hundred patients completed the study. Rome II showed low–moderate agreement (42%) with BSS to define bowel habit. Frequency of constipation and diarrhoea showed little changes throughout the study. Over 50% of the patients had the same bowel habit when each diary was compared with the next one. A third of patients maintained the same habit throughout the study. Most changes occurred from/to mixed or unsubtyped IBS. Only 14% of cases changed from constipation to diarrhoea or vice versa. This change was associated to female gender (OR: 2.65).

Conclusions

The frequency of constipation and diarrhoea remains relatively stable over time. Changes in IBS subtypes are common, but changes between constipation and diarrhoea are rare. Alternating IBS is more frequent in women.
Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms?
Authors: LEEDS J. S. , HOPPER A. D. , HURLSTONE D. P. , EDWARDS S. J. , MCALINDON M. E. , LOBO A. J. , DONNELLY M. T. , MORLEY S. , SANDERS D. S.
Published: July 2010

Background

Patients with coeliac disease may have diarrhoea despite being on a gluten‐free diet.

Aim

To assess whether exocrine pancreatic insufficiency causes persisting symptoms compared with controls, we determined whether pancreatic enzyme supplementation provided symptomatic benefit in coeliac patients with chronic diarrhoea.

Methods

Patients (n = 259) were subdivided into four groups: (a) new coeliac disease (n = 57), (b) coeliac disease patients on a gluten‐free diet without gastrointestinal symptoms (n = 86), (c) coeliac disease patients on a gluten‐free diet with chronic diarrhoea (n = 66) and (d) patients with chronic diarrhoea without coeliac disease (n = 50). Stool frequency and weight, before and after treatment with pancreatic enzyme supplementation were recorded.

Results

The prevalence of a low faecal elastase‐1 within the groups was: group (A) six of 57 (11%), group (B) five of 86 (6%), group (C) 20 of 66 (30%) and group (D) two of 50 (4%). Low faecal elastase‐1 was more frequent in coeliac disease patients with chronic diarrhoea vs. other subgroups of coeliac disease (P ≤ 0.0001) and controls (P ≤ 0.0003). In 18 of 20 stool frequency reduced following pancreatic enzyme supplementation from four per day to one (P ≤ 0.001). No weight increase (P = 0.3) was observed.

Conclusions

Low faecal elastase is common in patients with coeliac disease and chronic diarrhoea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.
Determining the proximal extent of ulcerative colitis: white cell scan correlates well with histological assessment
Authors: SUBRAMANIAN V. , BANERJEE A. , BEHARRY N. , FARTHING M. J. G. , POLLOK R. C. G.
Published: July 2010

Background

Assessing the extent of ulcerative colitis determines therapeutic strategies and provides prognostic information. Colonoscopy with mucosal biopsy is considered unsafe in patients with severe disease.

Aim

To assess the correlation between proximal extent of ulcerative colitis as determined by Technitium‐99‐m hexamethylpropylene amine oxime labelled leucocyte scan (white cell scan) with that determined by histological assessment.

Methods

One hundred and thirty‐five patients, with histologically‐confirmed ulcerative colitis, who had a white cell scan and histological assessment of colonic inflammation within 6 months of each other, during the years 1991–2004, were included. Overall agreement, quadratic‐weighted kappa (κ) and polychoric correlations (ρ) were calculated to estimate the inter‐rater reliability.

Results

The correlation between white cell scan and histological extent was excellent (κ = 0.7 ρ = 0.8). Macroscopic appearance on colonoscopy did not correlate as well with histological extent (κ = 0.62 and ρ = 0.67). White cell scans correlated significantly better in patients with extensive disease (P = 0.02). Colonoscopy predicted disease extent more accurately in patients with limited colitis (P = 0.002).

Conclusions

Proximal extent of ulcerative colitis determined by white cell scans correlates well with histological assessment especially in patients with more extensive disease. White cell scans offer a reasonable alternative to colonoscopy with mucosal biopsies in determining the proximal extent of colitis.
Efficacy and safety of short‐term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open‐label, multicentre trial
Authors: HINOJOSA J. , GOMOLLÓN F. , GARCÍA S. , BASTIDA G. , CABRIADA J. L. , SARO C. , CEBALLOS D. , PEÑATE M. , GASSULL M. A. ,   ON BEHALF OF GETECCU GRUPO ESPAÑOL DE TRABAJO PARA EL ESTUDIO DE E. CROHN Y COLITIS ULCEROSA (SPANISH SCIENTIFIC GROUP ON CROHN'S DISEASE AND ULCERATIVE COLITIS)
Published: July 2010

Background

The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn's disease.

Aim

To determine response and remission rates associated with the 4‐week induction phase of adalimumab treatment in patients with luminal and/or fistulizing Crohn's disease, who have lost response to or become intolerant of infliximab.

Methods

In this multicentre, prospective, open‐label, observational, 52‐week study, 50 adults received an induction dose of adalimumab (160 mg at baseline followed by 80 mg at week 2).

Results

Of the 36 patients with luminal Crohn's disease, 83% achieved clinical response [≥70‐point reduction in the Crohn's Disease Activity Index (CDAI) score] and 42% achieved clinical remission (CDAI score <150) at week 4. Of the 22 patients with fistulizing disease, five (23%) experienced fistula remission (complete closure of all fistulas that were draining at baseline), and nine (41%) experienced fistula improvement (≥50% decrease in the number of fistulas that were draining at baseline) at week 4. Of the 19 adverse events, most [13 (68%)] were mild, and no serious or infectious adverse events occurred.

Conclusions

Adalimumab may be an effective alternative in patients with luminal and/or fistulizing Crohn's disease who have lost response to or become intolerant of infliximab.
Chronic constipation: a survey of the patient perspective
Authors: JOHANSON J. F. , KRALSTEIN J.
Published: July 2010

Background  Constipation is a common, often chronic, gastrointestinal motility disorder characterized by such symptoms as straining, hard stool, and infrequent defecation. Published literature is limited regarding symptom prevalence, healthcare‐seeking behaviour, and patient satisfaction with traditional therapies for chronic constipation.

Aim  To assess the prevalence of chronic constipation among a random sample of Americans, to identify the frequency, severity and bothersomeness of their symptoms, and to assess satisfaction levels with traditional treatments.

Methods  All members (N = 37 004) of the Knowledge Networks Panel, representative of the US population, participated in a web‐based survey. Eligibility was established using a six‐question screener.

Results  Of the 24 090 panellists consenting to participate, 557 met eligibility requirements and took the 45‐question survey. The most prevalent symptom was straining (79%). Hard stool and straining were the top two severe symptoms, and bloating, straining and hard stool were the top three bothersome symptoms. Symptoms affected quality of life of more than half (52%) the respondents. Among those who worked or went to school, 12% experienced reduced productivity and a mean of 2.4 days of absence in the month before the survey. Most respondents had used (96%) or were using (72%) constipation relief therapy; however, nearly half (47%) were not completely satisfied, mainly because of efficacy (82%) and safety (16%) concerns.

Conclusions  Chronic constipation is common. Individual symptoms are often severe and bothersome, and many patients are dissatisfied with traditional treatment options, primarily because of lack of efficacy.
The role of screening and antibiotic prophylaxis in the prevention of percutaneous gastrostomy site infection caused by methicillin‐resistant Staphylococcus aureus
Authors: THOMAS S. , CANTRILL S. , WAGHORN D. J. , MCINTYRE A.
Published: July 2010

Background  Peristomal wound infections are common complications of percutaneous endoscopic gastrostomy (PEG), especially in hospitals where methicillin‐resistant Staphylococcus aureus (MRSA) is endemic. Evidence suggests that antibiotic prophylaxis at PEG insertion may reduce infection rates.

Aim  To examine rates of peristomal MRSA infection before and after introduction of a screening, decontamination and antibiotic prophylaxis protocol.

Methods  Retrospective case analysis detected new peristomal MRSA infections over a 33‐month period. Prospectively from October 2004, patients requiring PEG were screened and, if MRSA positive, received decontamination (5 days) and prophylactic teicoplanin before insertion. Peristomal wound sites were monitored after insertion.

Results  Peristomal MRSA infection was identified in 5/42 patients (12%) in 2002, 7/35 (20%) in 2003 and 7/24 (29%) in 2004 – overall infection rate 19%. Of 47 patients undergoing new PEG insertions between October 2004 and August 2006 (four known MRSA and 10 identified by screening), one (2%) developed peristomal MRSA infection 14 days postprocedure. A significant reduction in MRSA peristomal infection has been demonstrated (P < 0.01).

Conclusions  Screening for MRSA before PEG insertion identifies MRSA colonization and subsequent decontamination and antibiotic prophylaxis reduces peristomal MRSA infection rates. Where MRSA is endemic, the risk of wound site infection may remain postprocedure unless high standards of wound care are maintained.
GI Epidemiology: infection epidemiology and acute gastrointestinal infections
Authors: O’BRIEN S. J. , HALDER S. L. S.
Published: July 2010

Background

Gastrointestinal infection is a major cause of morbidity and mortality worldwide. The World Health Organisation estimated that in 2001 diarrheal disease was the third most common cause of mortality from infectious diseases worldwide, accounting for some 1.9 million deaths. Gastrointestinal infection is also linked to chronic diseases, for example Helicobacter pylori infection and gastric cancer.

Aim

To introduce the features of infection epidemiology that differentiates it from disease epidemiology in general.

Conclusion

The epidemiologic study of infection is essential for disease control. Infection epidemiology requires consideration of micro‐organisms (the infection process and transmission pathways) as well as the host (clinical presentation, behavior and immune status). Although infection epidemiologists often draw on methods used in chronic disease epidemiology there are some special features of infection epidemiology that require additional investigative approaches. We have highlighted these unique features and described some of the special methods available to track infection to its source.

Key Points

• The epidemiologic approach to the investigation of gastrointestinal infection is influenced by the interaction between micro‐organisms and the host.

• The infection epidemiologist can draw on “standard” epidemiologic techniques and on special methods.

• Collaboration with microbiologists is essential for studying infection epidemiology.

The purpose of this chapter is to introduce the features of infection epidemiology that differentiate it from disease epidemiology in general. Epidemiologic concepts covered in other chapters will not be repeated here, but readers should bear in mind that those methods are also available to use in the study of infection.
Programme of stepping down from twice daily proton pump inhibitor therapy for symptomatic gastro‐oesophageal reflux disease associated with a formulary change at a VA medical center
Authors: COTÉ G. A. , FERREIRA M. R. , ROZENBERG‐BEN‐DROR K. , HOWDEN C. W.
Published: July 2010

Background

In July 2001, our Veterans’ Affairs hospital changed its formulary proton pump inhibitor (PPI) from lansoprazole to rabeprazole. All patients previously receiving lansoprazole 30 mg twice daily were switched to rabeprazole 20 mg once daily.

Aim

To determine if patients with gastro‐oesophageal reflux disease (GERD), who were previously managed on lansoprazole 30 mg twice daily, could be maintained on rabeprazole 20 mg once daily.

Patients and methods

Four hundred and thirty‐five patients had received lansoprazole 30 mg twice daily for at least 12 months before the formulary change. Medical records were reviewed for 12 months before and after the formulary change.

Results

There were 432 men and three women with a mean age of 66.7 years (range: 38–91). Two hundred and twelve patients were excluded. Of the remaining 223, 111 (50%) were maintained successfully on rabeprazole 20 mg once daily. Twenty‐three (10%) stayed off all acid suppression during follow‐up. The number of endoscopies and clinic visits did not significantly change during the follow‐up. Fifty‐six percent who had erosive oesophagitis failed a dose taper compared with 31% of those with endoscopy‐negative GERD (P < 0.025).

Conclusions

Most patients receiving twice daily PPI therapy for GERD could be maintained on once daily PPI or no acid suppression for 12 months of follow‐up. Dose reduction was more successful in those without erosive oesophagitis.
Long‐term treatment of patients with gastro‐oesophageal reflux disease in routine care – results from the ProGERD study
Authors: NOCON M , LABENZ J , JASPERSEN D , MEYER‐SABELLEK W , STOLTE M , LIND T , MALFERTHEINER P , WILLICH S. N.
Published: July 2010

Background

Gastro‐oesophageal reflux disease (GERD) is a common condition frequently requiring long‐term pharmacological treatment.

Aim

To describe the long‐term pattern of GERD medication use in GERD patients receiving routine care.

Methods

Patients were recruited as part of the ongoing ProGERD study, a 10‐year‐cohort study including 6215 patients at baseline. GERD medication and symptoms were assessed with patient questionnaires. During follow‐up, medical treatment was prescribed by participating primary care physicians. Associations between patient characteristics and medication were analysed by logistic regression.

Results

The percentage of patients who reported using any GERD medication remained constant from year 1 to year 4 (74%, 74%, 73% and 71%). Of patients who reported using GERD medication, the majority were taking proton pump inhibitors (PPI) (79%, 84%, 85%, and 87%). Continuous PPI intake was the predominant prescription pattern (53%, 49%, 56% and 56%), followed by on‐demand treatment (26%, 35%, 29% and 29%). Continuous PPI intake was strongly associated with the presence of erosive GERD.

Conclusion

Three‐quarters of the GERD population in our study reported long‐term treatment with a PPI. Continuous PPI intake was the predominant treatment pattern, and the proportion of patients taking a PPI on a continuous basis remained constant over time.
Barrett’s oesophagus: long‐term follow‐up after complete ablation with argon plasma coagulation and the factors that determine its recurrence
Authors: FERRARIS R. , FRACCHIA M. , FOTI M. , SIDOLI L. , TARAGLIO S. , VIGANO’ L. , GIACCONE C. , REBECCHI F. , MEINERI G. , SENORE C. , PERA A. ,   GRUPPO OPERATIVO STUDIO PRECANCEROSI ESOFAGEE
Published: July 2010

Background

Argon plasma coagulation seems to be a promising technique for ablation of Barrett’s oesophagus, yet few long‐term efficacy data are available.

Aim

To report on a long‐term follow‐up and the factors that determine the recurrence of intestinal metaplasia in a cohort of patients with non dysplastic, intestinal type Barrett’s oesophagus, after complete ablation of the metaplastic mucosa with argon plasma coagulation.

Methods

Ninety‐six patients underwent endoscopic argon plasma coagulation with adequate acid suppression obtained through a continuous omeprazole therapy (50 patients) or through laparoscopic fundoplication (46 patients). Complete ablation was achieved in 94 patients who underwent follow‐up. Endoscopic and histological examinations were performed every 12 months.

Results

The median follow‐up of the patients was 36 months (range 18–98). A recurrence of intestinal metaplasia was found in 17 patients (18%), with an annual recurrence rate of 6.1%. Neither dysplasia, nor adenocarcinoma were found during the follow‐up. Through the use of logistic regression analysis, previous laparoscopic fundoplication was associated with a reduced recurrence rate of intestinal metaplasia (odds ratio 0.30, 95% confidence interval 0.10–0.93).

Conclusions

The long‐term recurrence of intestinal type Barrett’s oesophagus was low after complete ablation with argon plasma coagulation. The control of oesophageal acidity acid exposure with laparoscopic fundoplication seems to reduce the recurrence rate.
Adalimumab maintenance therapy for Crohn’s disease with intolerance or lost response to infliximab: an open‐label study
Authors: PEYRIN‐BIROULET L. , LACLOTTE C. , BIGARD M.‐A.
Published: July 2010

Background

Adalimumab is effective in inducing remission in patients with active Crohn’s disease who had secondary failure to infliximab therapy.

Aim

To evaluate the efficacy and safety of adalimumab maintenance therapy in Crohn’s disease patients who previously responded to infliximab and then lost response or became intolerant.

Methods

Twenty‐four patients with Crohn’s disease were enrolled in a 52‐week open‐label trial. The patients received a loading dose of adalimumab 80‐mg at week 0, and then 40 mg every other week starting at week 2. The primary efficacy measure was clinical remission defined as Crohn’s Disease Activity Index score < 150 at week 52.

Results

Five patients lost response to adalimumab. None of the patients experienced intolerance to adalimumab. Clinical remission rates were higher at weeks 4 (16/24, 67%) and 52 (14/24, 58%) compared with baseline (8/24, 35%) (P = 0.043 at week 52). This was accompanied by a decrease in mean C‐reactive protein concentration from 31.8 mg/mL at baseline to 9.7 mg/mL at week 52, and 3/4 (75%) patients achieved steroid‐free remission. No serious toxicities occurred in the study.

Conclusions

Adalimumab is well tolerated and appears to be effective in maintaining clinical remission in patients with Crohn’s disease and lost response or intolerance to infliximab.
Pharmacological modulation of gut mucosal and large vessel blood flow
Authors: KAMM M. A. , JORDAN C. C. , LEAKER B. R. , NICHOLSON F. B. , MURRAY C. D. R. , TAYLOR S. , MARSHALL M. , GIBBS A. , CARTER E. G. , EMMANUEL A. V.
Published: July 2010

Background

Constipation, diminished gut blood flow, ischaemic colitis and drug therapy may be associated.

Aim

To study the effect of constipating medication on, and the regulation of, gut blood flow.

Methods

24 healthy females (mean age 30) received, in a double‐blind, three‐way crossover study: (i) placebo, (ii) ipratropium 40 μg by inhalation (positive control known to reduce rectal mucosal blood flow) and (iii) oral loperamide 4 mg. Mucosal blood flow was measured at the splenic flexure and rectum using laser Doppler flowmetry. Blood flow in the superior and inferior mesenteric arteries was measured by trans‐abdominal Doppler ultrasound.

Results

Ipratropium decreased rectal mucosal blood flow by 16% (P = 0.009) and splenic flexure mucosal blood flow by 8% (P = 0.075). Loperamide caused no change in rectal (P = 0.40) or splenic flexure mucosal blood flow (P = 0.73). Neither treatment changed superior or inferior mesenteric artery blood flow. Splenic flexure mucosal blood flow showed a positive correlation with rectal mucosal blood flow (r = 0.69; P < 0.0001).

Conclusions

Vasoactive agents may reduce gut mucosal blood flow in the absence of reduced large vessel flow. Constipating drugs do not necessarily reduce gut blood flow. Rectal mucosal blood flow correlates with splenic flexure mucosal flow, and potentially may be used as a more convenient surrogate for studying splenic flexure blood flow.
High dosage rifaximin for the treatment of small intestinal bacterial overgrowth
Authors: SCARPELLINI E. , GABRIELLI M. , LAURITANO C. E. , LUPASCU A. , MERRA G. , CAMMAROTA G. , CAZZATO I. A. , GASBARRINI G. , GASBARRINI A.
Published: July 2010

Background

Rifaximin is a broad spectrum non‐absorbable antibiotic used for treatment of small intestinal bacterial overgrowth. Doses of 1200 mg/day showed a decontamination rate of 60% with low side‐effects incidence.

Aims

To assess efficacy, safety and tolerability of rifaximin 1600 mg with respect to 1200 mg/day for small intestinal bacterial overgrowth treatment.

Methods

Eighty consecutive small intestinal bacterial overgrowth patients were enrolled. Diagnosis of small intestinal bacterial overgrowth based the clinical history and positivity to H2/CH4 glucose breath test. Patients were randomized in two 7‐day treatment groups: rifaximin 1600 mg (group 1); rifaximin 1200 mg (group 2). Glucose breath test was reassessed 1 month after. Compliance and side‐effect incidence were also evaluated.

Results

One drop‐out was observed in group 1 and two in group 2. Glucose breath test normalization rate was significantly higher in group 1 with respect to group 2 both in intention‐to‐treat (80% vs. 58%; P < 0.05) and per protocol analysis (82% vs. 61%; P < 0.05). No significant differences in patient compliance and incidence of side effects were found between groups.

Conclusions

Rifaximin 1600 mg/day showed a significantly higher efficacy for small intestinal bacterial overgrowth treatment with respect to 1200 mg with similar compliance and side‐effect profile.
Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type
Authors: TAKENAKA R. , OKADA H. , KATO J. , MAKIDONO C. , HORI S. , KAWAHARA Y. , MIYOSHI M. , YUMOTO E. , IMAGAWA A. , TOYOKAWA T. , SAKAGUCHI K. , SHIRATORI Y.
Published: July 2010

Background

Although Helicobacter pylori infection is closely associated with gastric cancer development, follow‐up studies after H. pylori eradication are still scarce.

Aim

To clarify the cancer preventive effect of H. pylori eradication, with special attention to differences in effect according to histology.

Methods

Patients who underwent H. pylori eradication therapy and were followed‐up endoscopically for at least 1 year were analysed. The incidence of gastric cancer and factors associated with cancer development were investigated.

Results

A total of 1807 patients were enrolled. Six of 1519 H. pylori eradicated and five of 288 persistent subjects developed gastric cancer. Four of the eradicated subjects developed the intestinal type and two the diffuse type, while four of the persistent subjects developed the intestinal type and one the diffuse type. Kaplan–Meier analysis indicated a significantly lower incidence in eradicated patients than in persistent patients. The incidence of intestinal type was significantly lower than in eradicated patients, while the diffuse type could not be evaluated because of the low incidence.

Conclusions

Helicobacter pylori‐eradicated patients had a reduced incidence of gastric cancer compared with H. pylori‐persistent patients, particularly the intestinal type, suggesting that H. pylori is strongly associated with intestinal‐type gastric cancer.
Thiopurine metabolite monitoring in paediatric inflammatory bowel disease
Authors: OOI C. Y. , BOHANE T. D. , LEE D. , NAIDOO D , DAY A. S
Published: July 2010

Background Measurement of thiopurine metabolite levels may be useful as a clinical tool to optimize thiopurine treatment of paediatric inflammatory bowel disease (IBD).

Aim The authors evaluated correlations between 6‐thioguanine nucleotide (6‐TGN) and therapeutic response, metabolite levels and drug toxicity.

Methods Fifty‐six paediatric IBD patients treated with thiopurines had 326 metabolite level measurements and were retrospectively reviewed. Clinical status and laboratory parameters were compared with metabolite levels.

Results There was significant correlation between 6‐TGN levels and therapeutic response, with higher median 6‐TGN levels among patients with therapeutic response than those with non‐therapeutic response (194 vs. 146 pmol/8 × 108 RBC; P = 0.0004). Patients with 6‐TGN levels >235 pmol/8 × 108 RBC were more likely to achieve therapeutic response than those below the cut‐off (odds ratio, 2.5; 95% CI, 1.5–4.1). Patients who developed leukopenia tended to have higher median 6‐TGN levels than those without leukopenia (261 vs. 160 pmol/8 × 108 RBC) but the difference was not statistically significant. There was no correlation between 6‐methylmercaptopurine levels and hepatotoxicity. Two patients developed acute pancreatitis. Metabolite level measurements were helpful in identifying non‐compliance in nine patients.

Conclusions Monitoring of thiopurine metabolite levels is useful to guide and optimize dosing, as an adjunct to clinical judgement, blood count and liver biochemistry measurements to minimize the risk of drug toxicity and to confirm non‐compliance.
Double stenting of oesophagus and airways in palliative treatment of patients with oesophageal cancer is efficient but associated with a high morbidity
Authors: LECLEIRE S. , ANTONIETTI M. , DI FIORE F. , BEN‐SOUSSAN E. , BOTA S. , HELLOT M.‐F. , THIBERVILLE L. , MICHEL P. , LEREBOURS E. , DUCROTTÉ P.
Published: July 2010

Background Double stenting of oesophagus and airways may be required in palliative treatment of patients with locally advanced oesophageal cancer.

Aim To assess feasibility, efficacy and complications occurring in patients with locally advanced oesophageal cancer receiving both oesophagus and airways stenting.

Methods In one single centre between 1997 and 2005, among 180 patients with locally advanced oesophageal cancer treated by the palliative placement of a self‐expanding metal stent, patients requiring double stenting of oesophagus and airways were identified. Clinical efficacy, complications and survival were retrospectively collected.

Results Fifteen patients (8.3% of 180) required a double stenting at follow‐up. Symptomatic efficacy of oesophagus and airways stenting was 86.7% for dysphagia and 100% for dyspnoea. Median survival after the second stent insertion was 99 days. Life‐threatening early complications occurred in three patients after double stenting (20%), including two deaths following oesophageal perforation and massive haemoptysis, respectively. Procedure‐related mortality was 13.3%.

Conclusions Double stenting of oesophagus and airways is feasible in patients with locally advanced oesophageal cancer, with a relevant clinical efficacy. However, early major complications including procedure‐related death may occur in as many as 20% of patients. This treatment should be reserved to very selected patients with severe symptoms and end‐stage disease.
Does body mass index differ between patients with Barrett’s oesophagus and patients with chronic gastro‐oesophageal reflux disease?
Authors: GERSON L. B. , ULLAH N. , FASS R. , GREEN C. , SHETLER K. , SINGH G.
Published: July 2010

Background Obesity has been demonstrated to be a risk factor for the development of gastro‐oesophageal reflux disease (GERD).

Aim To perform a prospective cohort study to determine whether there was a difference in body mass index (BMI) between patients with GERD and patients with Barrett’s oesophagus (BE).

Methods We prospectively enrolled patients undergoing endoscopic evaluation for GERD and collected information regarding BMI, tobacco and/or alcohol use, and family history of GERD. Patients with non‐erosive reflux disease underwent confirmatory 24‐h pH testing.

Results Seven hundred and fifty one patients with GERD (mean ± s.d. age of 55.4 ± 14.2 years, 74% male) entered the study, and BE was present in 165 (22%, 90% male, 79% Caucasian) patients. The mean GERD symptom duration was 10.3 ± 0.4 years (range 1–62 years) with a mean body mass index of 27.8 ± 0.2 kg/m2 (range 15–55) Compared with patients having GERD alone, patients with BE were more likely to be older (P = 0.001), male (P < 0.001), current or prior tobacco users (P = 0.002), and with greater duration of GERD symptoms (P < 0.001). There was no significant difference in the BMI for patients with and without BE.

Conclusions While obesity is a risk factor for both GERD and BMI, patients with BE did not demonstrate increased BMI compared with patients having chronic GERD.
Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease
Authors: WINTER J. W. , GAFFNEY D. , SHAPIRO D , SPOONER R. J. , MARINAKI A. M. , SANDERSON J. D. , MILLS P. R.
Published: July 2010

Background Myelosuppression occurs in 2–7% of inflammatory bowel disease (IBD) patients treated with azathioprine, and can be associated with reduced activity of thiopurine methyltransferase (TPMT) in some patients. It has been proposed that pretreatment assessment of TPMT status reduces the incidence of toxicity and is cost‐effective.

Aims To determine if screening for TPMT status predicts side‐effects to azathioprine in patients with IBD and to ascertain whether screening by TPMT enzyme activity or genotype is superior.

Methods Sequential IBD patients were identified and azathioprine tolerance recorded. Blood was collected for measurement of TPMT activity and TPMT*3C, TPMT*3A and TPMT*2 genotypes.

Results Of 130 patients, 25% stopped azathioprine because of toxicity. Four patients experienced severe myelosuppression (WCC < 2). Eleven of 17 patients with reduced TPMT activity were heterozygotes, including one patient with marked TPMT deficiency who experienced severe myelosuppression. There was no association between intermediate TPMT deficiency and any side‐effect.

Conclusions Moderate reduction of TPMT activity in heterozygotes was not associated with toxicity, but very low TPMT activity caused severe myelosuppression in one patient. This would have been predicted by measuring TPMT activity but not by genotyping. Measurement of TPMT activity may therefore be superior to genotype in predicting severe myelosuppression.
Positive association between gastro‐oesophageal reflux disease and irritable bowel syndrome in a Chinese population
Authors: CHEUNG T. K. , LAM K. F. , HU W. H. C. , LAM C. L. K. , WONG W. M. , HUI W. M. , LAI K. C. , LAM S. K. , WONG B. C. Y
Published: July 2010

Background Gastro‐oesophageal reflux disease and irritable bowel syndrome are common diseases which may be related.

Aim To examine the association between gastro‐oesophageal reflux disease and irritable bowel syndrome in Chinese population in Hong Kong.

Methods Randomly selected ethnic Chinese were invited to participate in a telephone survey in 1996. Gastro‐oesophageal reflux disease was defined as subjects having heartburn and/or acid regurgitation once weekly or more. Irritable bowel syndrome was diagnosed according to the Rome I criteria. The association between gastro‐oesophageal reflux disease and irritable bowel syndrome was calculated using a statistical model which allows the odds ratio to be measured.

Results One thousand six hundred and forty‐nine subjects completed the interview (response rate 62%). The population prevalence of gastro‐oesophageal reflux disease and irritable bowel syndrome were 5% and 4%, respectively. Thirteen per cent of subjects with gastro‐oesophageal reflux disease and 11% with irritable bowel syndrome suffered from both gastro‐oesophageal reflux disease and irritable bowel syndrome. The OR of having gastro‐oesophageal reflux disease and irritable bowel syndrome together was estimated to be 3 (95% CI: 1.05, 6.27) indicating a positive association between the two diseases. This association occurred predominantly in male subjects [OR = 9.3, (95% CI: 2.3, 26.2)] but not as strong in females [OR = 1.5, (95% CI: 0.3, 4.3)]. Younger subjects were statistically more prone to the two diseases.

Conclusions There is a positive association between gastro‐oesophageal reflux disease and irritable bowel syndrome, and their association occurs predominantly in male subjects.
The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C
Authors: LO IACONO O. , VENEZIA G. , PETTA S. , MINEO C. , DE LISI S. , DI MARCO V. , RODOLICO V. , AMATO M. , FERRARO D. , GIORDANO C. , ALMASIO P.L. , CRAXÍ A.
Published: July 2010

Aims  To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti‐viral therapy on insulin resistance and serum levels of adipocytokines.

Methods  Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in ‘naïve’ patients with chronic hepatitis C, before, during and after therapy with Peg‐Interferon‐alpha 2a plus Ribavirin.

Results  Forty‐eight patients were included (M/F 28/20; mean age 50.0 ± 12.6 years; 62.5% genotype‐1). Body mass index was 26.4 ± 4.0 kg/m2, and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1–1.18), necroinflammatory activity (17.67; 1.6–194.46), and raised insulin levels (1.39; 1.1–1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54–261.11), and steatosis (6.47; 1.09–38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85–0.99), genotype non‐1 (10.61; 1.52–73.76) and absence of visceral obesity (13.78; 2.36–80.29). At the end of follow‐up, insulin and the homeostasis model assesment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment.

Conclusions  Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.
The role of genomic and antigenomic HCV‐RNA strands as predictive factors of response to pegylated interferon plus ribavirin therapy
Authors: LÓPEZ‐ALCOROCHO J. M. , RODRÍGUEZ‐IÑIGO E. , CASTILLO I. , CASTELLANOS M. E. , PARDO M. , BARTOLOMÉ J. , QUIROGA J. A. , CARREÑO V.
Published: July 2010

Background  Hepatitis C virus replicates by the synthesis of an antigenomic HCV‐RNA. As the end point of anti‐viral therapy is to decrease viral replication, the amount of antigenomic HCV‐RNA could influence the response.

Aim  To study if amounts of genomic and antigenomic HCV‐RNA in the baseline liver biopsy are predictive factors of response to anti‐viral therapy.

Methods  Eighty‐eight patients with chronic HCV infection (anti‐HIV‐negative) treated with pegyltaed‐interferon‐α2b plus ribavirin for 12 months were included. Intrahepatic genomic and antigenomic HCV‐RNA concentrations were determined by real‐time polymerase chain reaction and percentage of infected hepatocytes by in situ hybridization.

Results  Of the 88 patients, 31% were responders while 69% were not. Median of antigenomic HCV‐RNA in liver of responders and non‐responders was 120 000 copies/μg RNA (range: 10 000–775 000) vs. 150 000 copies/μg RNA (range: 100–3 200 000; P = 0.38). Median of genomic HCV‐RNA in liver of responders was 1 250 000 copies/μg RNA (range: 5000–9 000 000) and in non‐responders 3 180 000 copies/μg RNA (range: 4600–18 000 000; P = 0.0191). Predictive factors of response in the logistic regression were: intrahepatic amount of genomic HCV‐RNA, percentage of infected hepatocytes and previous therapy.

Conclusion  Response to 12 months of therapy with pegylated interferon‐α2b plus ribavirin depends on the amount of genomic HCV‐RNA in the pre‐treatment liver biopsy.
Risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in patients with unexplained chest/epigastric pain and normal upper endoscopy: a 10‐year Danish cohort study
Authors: MUNK E. M. , DREWES A. M. , GORST‐RASMUSSEN A. , GREGERSEN H. , FUNCH‐JENSEN P. , NØRGÅRD B.
Published: July 2010

Background  No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy.

Aim  To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients.

Methods  This Danish 10‐year cohort study focused on UCEP patients (n = 386), diagnosed in 1992–93. Ten age‐ and gender‐matched controls were selected per patient from Denmark’s Civil Registration System (n = 3860). Kaplan–Meier analysis and Cox’s regression analysis was used to calculate the risk of hospitalization for peptic ulcer, oesophagitis, pancreatitis or gallstone.

Results  Compared with controls, the adjusted relative risks among UCEP patients <1 and ≥1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2–18.4] and 1.7 (95% CI 0.9–3.4), for oesophagitis 8.2 (95% CI 1.2–59.2) and 1.9 (95% CI 0.7–5.0), for pancreatitis 9.2 (95% CI 2.0–41.8) and 3.9 (95% CI 1.4–10.5), and for gallstone 14.1 (95% CI 5.4–37.2) and 3.3 (95% CI 1.9–5.8).

Conclusions  UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or gallstone could be underlying early UCEP symptoms. However, the long‐term association remained strong for pancreatitis and gallstone, suggesting a genuine excess risk.
Paroxetine for prevention of depressive symptoms induced by interferon‐alpha and ribavirin for hepatitis C
Authors: RAISON C. L. , WOOLWINE B. J. , DEMETRASHVILI M. F. , BORISOV A. S. , WEINREIB R. , STAAB J. P. , ZAJECKA J. M. , BRUNO C. J. , HENDERSON M. A. , REINUS J. F. , EVANS D. L. , ASNIS G. M. , MILLER A. H.
Published: July 2010

Background Whether antidepressants prevent depression during interferon‐alpha/ribavirin treatment for hepatitis C virus infection has yet to be established.

Aim To investigate the use of paroxetine in a prospective, double‐blind, placebo‐controlled study for this indication.

Methods Sixty‐one hepatitis C virus‐infected patients were randomly assigned to the antidepressant, paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for 24 weeks during interferon‐alpha/ribavirin treatment. Primary endpoints included development of major depression and severity of depressive symptoms measured by the Montgomery Asberg Depression Rating Scale (MADRS).

Results Rates of major depression during the study were low (17%) and did not differ between groups. Nevertheless, using published MADRS cut‐off scores, the percent of subjects who met criteria for mild, moderate or severe depression during interferon‐alpha/ribavirin therapy was significantly lower in paroxetine‐ vs. placebo‐treated subjects (P = 0.02, Fisher’s exact test). Assignment to paroxetine was also associated with significantly reduced depressive symptom severity. This effect was largely accounted for by participants with depression scores above the median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal reduction in MADRS scores of 10.3 (95% CI: 2.1–18.5) compared with placebo at 20 weeks (P < 0.01). Study limitations included a small sample size and high drop‐out rate.

Conclusion This double‐blind, placebo‐controlled trial provides preliminary data in support of antidepressant pre‐treatment in hepatitis C virus patients with elevated depressive symptoms at baseline.
Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double‐blind, placebo‐controlled, dose‐ranging study to evaluate efficacy and safety
Authors: JOHANSON J. F. , UENO R.
Published: July 2010

Background

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion.

Aim

To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.

Methods

A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked.

Results

Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea.

Conclusions

Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.
Influence of genetics on irritable bowel syndrome, gastro‐oesophageal reflux and dyspepsia: a twin study
Authors: LEMBO A. , ZAMAN M. , JONES M. , TALLEY N. J.
Published: July 2010

Background

A genetic contribution has been proposed for irritable bowel syndrome (IBS) and gastro‐oesophageal reflux disease (GERD), but is controversial. No twin data exist for dyspepsia.

Aim

To determine the relative contribution of genetic factors in GERD, dyspepsia (upper abdominal pain) and IBS.

Methods

A total of 986 twin pairs (from initial mail‐out response 51%). Both members completed validated symptom and psychological questionnaires; 481 monozygotic pairs [mean (s.d.) age 53 ± 5.8 years] and 505 dizygotic pairs (mean age 54 ± 5.6 years).

Results

Prevalence of IBS, dyspepsia and GERD was 12%, 10% and 20%, respectively. Polychoric correlation for monozygotic twins for IBS (0.47) and GERD (0.44) were both substantially larger than those for dizygotic twins (0.17 and −0.37, respectively). Polychoric correlation was slightly lower in monozygotic than dizygotic twins for dyspepsia. Genetic modelling confirmed the independent additive genetic effects in GERD and IBS but not dyspepsia. Estimates of genetic variance were 22% for IBS, 13% for GERD and 0% for dyspepsia, but adjusting for anxiety and depression removed the statistical significance for IBS and GERD.

Conclusions

There is a genetic contribution to GERD and IBS but not dyspepsia; this may be mediated by the hereditability of anxiety and depression.
Distinct roles of free leptin, bound leptin and soluble leptin receptor during the metabolic‐inflammatory response in patients with liver cirrhosis
Authors: OCKENGA J. , TIETGE U. J. F. , BÖKER K. H. W. , MANNS M. P. , BRABANT G. , BAHR M. J.
Published: July 2010

Background

Alteration of the leptin system appears to play a role in the inflammatory–metabolic response in catabolic diseases such as chronic liver diseases.

Aim

To investigate the association between leptin components, inflammatory markers and hepatic energy and substrate metabolism.

Methods

We investigated in vivo hepatic substrate and leptin metabolism in 40 patients employing a combination of arterial and hepatic vein catheterization techniques and hepatic blood flow measurements. In addition to metabolic, inflammatory and neuroendocrine parameters, circulating levels of free leptin, bound leptin and soluble leptin receptor were determined.

Results

Compared with controls, bound leptin and soluble leptin receptor levels were significantly elevated in cirrhosis, while free leptin did not increase. In cirrhosis bound leptin was correlated with soluble leptin receptor (r = 0.70, P < 0.001). Free leptin was positively correlated with metabolic parameters such as energy storage (body fat mass; r = 0.36, P < 0.05), insulin and insulin resistance (r = 0.48; r = 0.46, P < 0.01) as well as with hepatic glucose and energy release (r = 0.35 and r = 0.40, P < 0.05). In contrast, bound leptin and soluble leptin receptor were linked to proinflammatory cytokines and sympathetic activity (r = 0.61 and r = 0.56, P < 0.01).

Conclusion

The components of the leptin system (free leptin, bound leptin and soluble leptin receptor) have distinct roles in metabolic and inflammatory processes in patients with liver cirrhosis. The better understanding of this metabolic and inflammatory tissue‐repair response may lead to innovative new therapeutic strategies in liver disease as well as in various other catabolic diseases.
Mesalazine downregulates c‐Myc in human colon cancer cells. A key to its chemopreventive action?
Authors: CHU E. C. , CHAI J. , AHLUWALIA A. , TARNAWSKI A. S.
Published: July 2010

Background  Dysplasia and malignant transformation of colonocytes in ulcerative colitis are associated with overexpression of c‐Myc and genes regulating cell survival. 5‐Aminosalicylates such as mesalazine may reduce the development of colorectal cancer in ulcerative colitis, but the mechanisms of its chemopreventive action are not clear.

Aims  To examine whether mesalazine affects the expression of c‐Myc in human colon cancer cell lines.

Methods  Human colon cancer cells were treated with vehicle or mesalazine (4 mm or 40 mm). We examined: (i) mRNA expression by gene array, (ii) protein expression by Western blotting and immunohistochemistry and (iii) apoptosis by Annexin V labelling.

Results  Mesalazine significantly reduced expression of c‐Myc mRNA and protein.

Conclusions  Mesalazine downregulates gene and protein expression of c‐Myc. The apoptotic and growth inhibitory effects of mesalazine are dose‐dependent. Expression of c‐Myc is significantly reduced by mesalazine 40 mm.
A clinical trial comparing pantoprazole and esomeprazole to explore the concept of achieving ‘complete remission’ in gastro‐oesophageal reflux disease
Authors: BARDHAN K. D. , ACHIM A. , RIDDERMANN T. , PFAFFENBERGER B.
Published: July 2010

Background and Aim  The outcome of gastro‐oesophageal reflux disease treatment is traditionally assessed by measuring endoscopically confirmed healing and symptom relief separately. Both terms together, indicating complete remission, are intuitively a more realistic clinical endpoint but are assessed less often.

Aim  To explore this concept, we formally compared the efficacy of the proton pump inhibitors (PPIs) pantoprazole and esomeprazole using rates of complete remission judged against rates of healing and symptom relief separately.

Methods  Five hundred and eighty‐two patients with erosive gastro‐oesophageal reflux disease were randomized to treatment for 4, 8, or 12 weeks with either pantoprazole or esomeprazole 40 mg daily. Symptom relief was assessed with the validated ReQuest™‐GI subscale.

Results  Approximately 75% of patients were free of symptoms or had no oesophageal lesions after 4 weeks’ treatment, rising to about 93% and 96%, respectively, at 12 weeks. Complete remission rates were, however, lower at these time points; approximately 60% and about 90%, respectively. Both PPIs had similar efficacy.

Conclusions  Endoscopically confirmed healing and symptom relief assessed separately over‐estimated the benefits of both drugs. In contrast, complete remission indicates that patients may be treated inadequately when given the standard 4‐ to 8‐week treatment. We suggest that complete remission is a more reliable and clinically relevant endpoint of treatment.