bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of hepatic venous pressure gradient for in‐hospital mortality of patients with severe acute alcoholic hepatitis
Authors: RINCON D. , LO IACONO O , RIPOLL C , GOMEZ‐CAMARERO J , SALCEDO M , CATALINA M. V , HERNANDO A , CLEMENTE G , MATILLA A , NUÑEZ O , BAÑARES R
Published: July 2010

Background

Hepatic venous pressure gradient (HVPG) has prognostic value in complications and survival of patients with liver cirrhosis. However, the relationship between HVPG and the outcome of acute alcoholic hepatitis (AAH), as well as the specific features of portal hypertension syndrome in this setting, have not been defined.

Aims

To evaluate the prognostic value of HVPG and to analyse the degree of portal hypertension and hyperdynamic circulation in patients with severe AAH.

Methods

Early measurements of HVPG were performed in 60 patients with severe AAH, and compared with the haemodynamic findings of 37 and 29 liver transplantation candidates with alcoholic or viral end‐stage cirrhosis respectively.

Results

Twenty‐three patients (38%) died during hospitalization. Portal hypertension and hyperdynamic circulation were more severe in AAH patients. HVPG was greater in non‐survivors [26.9 (7.4) vs. 19.4 (5.2) mmHg,P < 0.001]. Only 4/31 (13%) patients with HVPG ≤ 22 mmHg died from the episode of AAH, vs. 19/29 (66%) patients with HVPG > 22 (P < 0.001). Encephalopathy (OR 9.4; CI 1.4–64.8), Model for End‐Stage Liver Disease (MELD) score > 25 (OR 7.4; CI 1.4–39.9) and HVPG > 22 mmHg (OR 6.7; CI 1.1–39.9) were independently associated to in‐hospital mortality.

Conclusions

Early measurement of HVPG provides important prognostic information on the short‐term outcome of patients with severe AAH. In addition, MELD score also seems to be a strong prognostic factor in these patients.
Perceptions and practices on the management of gastro‐oesophageal reflux disease: results of a national survey comparing primary care physicians and gastroenterologists
Authors: BRETAGNE J.‐F. , HONNORAT C. , RICHARD‐MOLARD B. , SOUFFLET C. , BARTHÉLEMY P.
Published: July 2010

Background

Literature comparing generalist and specialist care is accumulating in many disease areas, but very few studies focussed on gastrointestinal diseases and little is known about gastro‐oesophageal reflux disease.

Aim

To compare the management of gastro‐oesophageal reflux disease (GERD) by French primary care physicians and gastroenterologists.

Methods

A postal survey was conducted in a representative sample of French physicians who were asked to complete a questionnaire that consisted of 44 questions relating to their usual medical practice for the diagnostic and therapeutic management of frequent GERD.

Results

136 primary care physicians and 91 gastroenterologists participated in the survey (54%). Alarm symptoms were identified more frequently by primary care physicians than gastroenterologists, but the appraisal of their seriousness was less acute by primary care physicians than gastroenterologists. Upper endoscopy was prescribed more frequently by gastroenterologists (64% vs. 38%, P < 0.01). Physicians in both groups mainly recommended lifestyle modification. For GERD treatment, most respondents declared using a ‘step‐down’ strategy with proton pump inhibitors, and only slight differences in drug prescription were identified between primary care physicians and gastroenterologists. Both groups of physicians also have similar perception of symptom persistence after treatment, but satisfaction with treatments was slightly higher for gastroenterologists than primary care physicians (7.6 vs. 7.1 on a scale from 0 to 10, P < 0.01).

Conclusions

Overall patterns of GERD diagnosis and management are comparable between primary care physicians and gastroenterologists. Both groups perceive that GERD therapy can still be improved.
Treatment of chronic he1patitis C genotype 1 with peginterferon‐ α2a (40 kDa) plus ribavirin under routine clinical practice in Spain: early prediction of sustained virological response rate
Authors: DIAGO M. , OLVEIRA A. , SOLÁ R. , ROMERO‐GÓMEZ M. , MORENO‐OTERO R. , PÉREZ R. , SALMERÓN J. , ENRÍQUEZ J. , PLANAS R. , GAVILÁN J. C. , DEL OLMO J. , URIBARRENA R. , SILLERO C. , BENÍTEZ A. , SÁNCHEZ‐GALDÓN S. , DALMAU B. , ERAÑA L. , MONTORO M. , PORTU J. , GARIJO J. M. , BARNIOL R. , DOMÍNGUEZ A. , ROTA R. , OLCOZ J. L. , ANTÓN M. , PAMPLONA X. , CASANOVAS T. , JIMÉNEZ E. , HUARTE M. , DÍAZ F. , SÁNCHEZ‐RUANO J. , ORIVE M. , MUÑOZ‐SÁNCHEZ M. , ROSET M.
Published: July 2010

Background Sustained virological response rates of up to 52% have been obtained with peginterferon α2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized‐controlled trials.

Aim To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain.

Methods Treatment‐naïve patients received pegylated interferon α2a (40 kDa) 180 µg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population.

Results The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%.

Conclusion If sustained virological response is the goal, a treatment‐decision based on a 12‐week evaluation during routine clinical practice is feasible.
Symptom overlap in patients with upper gastrointestinal complaints in the Canadian confirmatory acid suppression test (CAST) study: further psychometric validation of the reflux disease questionnaire
Authors: VAN ZANTEN S. V. , ARMSTRONG D. , BARKUN A. , JUNGHARD O. , WHITE R. J. , WIKLUND I. K.
Published: July 2010

Background The reflux disease questionnaire (RDQ) is a short, patient‐completed instrument.

Aims To investigate the psychometric characteristics of the RDQ in patients with heartburn‐predominant (HB) and non‐heartburn predominant (NHB) dyspepsia.

Methods HB (n = 388) and NHB (n = 733) patients were randomized to esomeprazole 40 mg daily or twice daily for 1 week, followed by 3 weeks of esomeprazole 40 mg daily.

Results High factor loadings (0.78–0.86) supported the ‘regurgitation’ dimension of the RDQ. Overlapping factor loadings in the ‘heartburn’ and ‘dyspepsia’ dimensions suggested symptom overlap. All dimensions demonstrated high internal consistency (Cronbach’s alpha: 0.79–0.90). Intra‐class correlation coefficients over 4 weeks were good (0.66–0.85). The RDQ showed good responsiveness over 4 weeks of treatment, with high effect sizes (≥0.80). Moderate or large symptom improvements were reported by 90% and 77% of HB and NHB patients, respectively, following treatment. Patients who responded to acid suppression also experienced symptom benefits in all RDQ dimensions.

Conclusions The RDQ is reliable, valid and responsive to change in HB and NHB patients. The symptom overlap is important but need not play a major role in determining treatment strategy as both patient groups benefited from proton pump inhibitor treatment.
Cyclooxygenase‐2 selectivity of non‐steroidal anti‐inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident
Authors: ABRAHAM N. S. , EL‐SERAG H. B. , HARTMAN C. , RICHARDSON P. , DESWAL A.
Published: July 2010

AimTo assess degree of cyclooxygenase‐2 (COX‐2) selectivity of a non‐steroidal anti‐inflammatory drug (NSAID) and risk of myocardial infarction (MI) or cerebrovascular accident (CVA).

MethodsPrescription fill data were linked to medical records of a merged VA‐Medicare dataset. NSAIDs were categorized by Cox‐2 selectivity. Incidence of CVA and MI within 180 days of index prescription was assessed using Cox‐proportional hazards models adjusted for gender, race, cardiovascular and pharmacological risk factors and propensity for prescription of highly COX‐2 selective NSAIDs.

ResultsOf 384 322 patients (97.5% men and 85.4% white), 79.4% were prescribed a poorly selective, 16.4% a moderately selective and 4.2% a highly selective NSAID. There were 985 incident cases of MI and 586 cases of CVA in >145 870 person‐years. Highly selective agents had the highest rate of MI (12.3 per 1000 person‐years; [95% CI: 12.2–12.3]) and CVA (8.1 per 1000 person‐years; [95% CI: 8.0–8.2]). Periods without NSAID exposure were associated with lowest risk. In adjusted models, highly selective COX‐2 selective NSAIDs were associated with a 61% increase in CVA and a 47% increase in MI, when compared with poorly selective NSAIDs.

ConclusionsThe risk of MI and CVA increases with any NSAID. Highly COX‐2 selective NSAIDs confer the greatest risk.
Cochrane systematic review: pegylated interferon plus ribavirin vs. interferon plus ribavirin for chronic hepatitis C
Authors: SIMIN M. , BROK J. , STIMAC D. , GLUUD C. , GLUUD L. L.
Published: July 2010

Background About 170 million patients worldwide have chronic hepatitis C. Pegylated interferon plus ribavirin is currently the recommended therapy.

Aim To evaluate the beneficial and harmful effects of pegylated interferon plus ribavirin vs. interferon plus ribavirin for chronic hepatitis C infection.

Methods We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, Science Citation Index Expanded and contacted pharmaceutical companies and authors of trials (to March 2005).

Results We included 18 randomized clinical trials with 4811 patients. Eleven trials (61%) had allocation bias risks and all had assessment bias risk because of lack of blinding. Compared with interferon plus ribavirin, pegylated interferon plus ribavirin had significant beneficial effects on sustained virological response [risk ratio (RR): 0.80; 95% CI: 0.74–0.88]. Data were insufficient to determine impact on long‐term outcomes. Pegylated interferon plus ribavirin significantly increased dose reductions (RR: 1.44; 95% CI: 1.14–1.82) and adverse events including neutropenia (RR: 2.25; 95% CI: 1.58–3.21), thrombocytopenia (RR: 2.28; 95% CI: 1.14–4.54), arthralgia (RR: 1.19; 95% CI: 1.05–1.35), and injection‐site reaction (RR: 2.56; 95% CI: 1.06–6.22).

Conclusions Pegylated interferon plus ribavirin compared with interferon plus ribavirin increased the proportion of patients with sustained virological response, but at the cost of more adverse events.
Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol – a randomized, double‐blind, placebo‐controlled study
Authors: CHASSANY O. , BONAZ B. , BRULEY DES VARANNES S. , BUENO L. , CARGILL G. , COFFIN B. , DUCROTTÉ P. , GRANGÉ V.
Published: July 2010

Background Abdominal pain is the predominant symptom in irritable bowel syndrome patients. Phloroglucinol and its methylated derivative are antispasmodic agents acting on smooth muscle.

Aim To evaluate the efficacy of phloroglucinol/trimethylphloroglucinol on pain intensity during an acute exacerbation of pain of irritable bowel syndrome over a 1‐week period treatment.

Methods Irritable bowel syndrome Rome II patients seeking medical advice for an acute exacerbation of abdominal pain were randomized to phloroglucinol/trimethylphloroglucinol (62.2 mg P + 80 mg TMP) two pills three times daily or placebo for 7 days. Patients were included if they had a pain with a minimal intensity of 40 on a 100‐mm visual analogue scale, and if pain occurred at least 2 days during the week previous inclusion.

Results Three hundred and seven patients were included by 78 general practitioners. The intent‐to‐treat population included 300 patients, aged of 46.9 ± 14.8 years (73% female). The relative decrease of pain intensity at day 7 was 57.8 ± 31.7% vs. 46.3 ± 34.7% (Δ = 11.5 ± 3.8%, [CI95%: 4.0 ; 19.1], P = 0.0029) and the percentage of patients with at least a 50% decrease of pain intensity was 62% vs. 47% (Δ = 15.3 ± 5.7%, [CI95%: 4.1 ; 26.5], P = 0.0078) in phloroglucinol/trimethylphloroglucinol and placebo groups, respectively.

Conclusions A 1‐week phloroglucinol/trimethylphloroglucinol treatment significantly reduces pain intensity in irritable bowel syndrome patients consulting their general practitioners for pain exacerbation.
Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features
Authors: MATHURIN P. , BEUZIN F. , LOUVET A. , CARRIÉ‐GANNE N. , BALIAN A. , TRINCHET J. C. , DALSOGLIO D. , PREVOT S. , NAVEAU S.
Published: July 2010

Background Studies using consecutive liver biopsies constitute an attractive approach to gaining insight into the pathogenesis of alcoholic liver disease.

Aim To analyse histological factors at baseline, which are predictive of fibrosis progression and recurrence of alcoholic hepatitis.

Results A total of 193 drinkers underwent consecutive biopsies at an interval of 4 years. At baseline, 20 had normal livers, 135 steatosis, five fibrosis and 33 alcoholic hepatitis. The fibrosis score increased from 1.07 ± 0.07 to 1.7 ± 0.94 (P < 0.001). In multivariate analysis, only steatosis (P = 0.04), alcoholic hepatitis (P = 0.0004) and stage of fibrosis (P < 0.0001) were independent predictive factors of the fibrosis score at the second biopsy. Cirrhosis developed more frequently in patients with steatosis (11%) and alcoholic hepatitis (39%) than in others (0%, P < 0.0001). Alcoholic hepatitis recurred more frequently in patients with alcoholic hepatitis at baseline: 58% vs. 15%, P < 0.0001. In multivariate analysis, alcoholic hepatitis at the first biopsy was the only predictive factor of its recurrence (P < 0.0001).

Conclusions In a large cohort of drinkers with consecutive biopsies, steatosis, fibrosis stage and alcoholic hepatitis at baseline were independent predictive factors of fibrosis progression. In terms of mechanisms, we propose a novel concept of multiple hits of alcoholic hepatitis occurring in the same patient.
Temporal trends in new and recurrent oesophageal strictures in a Medicare population
Authors: EL‐SERAG H. B. , LAU M.
Published: July 2010

Background  The widespread use of proton pump inhibitors for gastro‐oesophageal reflux disease could result in a decline in new as well as recurrent gastro‐oesophageal reflux disease‐related oesophageal strictures. The temporal trends of strictures have not been examined in population‐based studies.

Methods  To examine the temporal trends in strictures, we calculated the age‐adjusted incidence rates of new oesophageal strictures with or without oesophageal dilation in a sample of Medicare beneficiaries between 1992 and 2000. We also examined recurrent dilations recorded at least 3 months after a new stricture or the preceding recurrent stricture.

Results  The age‐adjusted rates for strictures accompanied with dilation declined by approximately 11% from 215 per million to 192 per million. New oesophageal strictures with dilation declined as a proportion of all upper endoscopies procedures (from 2.6% to 1.9%). Recurrent dilation within 1 year declined dramatically from 16% (9.5% CI: 12.5–20.3) in 1992 to 8% (95% CI: 4.43–10.62) in 2000. In multivariable proportional hazards model, there was a 30% risk reduction of recurrent oesophageal strictures.

Conclusions  This population‐based study indicates that the incidence of new as well as recurrent oesophageal strictures has been declining. In the face of rising incidence of other gastro‐oesophageal reflux disease‐related complications, it is important to understand the explanation of the present observations.
Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy
Authors: GOLDSTEIN J. L. , EISEN G. M. , LEWIS B. , GRALNEK I. M. , AISENBERG J. , BHADRA P. , BERGER M. F.
Published: July 2010

Background  Small bowel mucosal injury associated with non‐selective non‐steroidal anti‐inflammatory drugs is being increasingly recognized.

Aim  To evaluate the incidence of small bowel injury in healthy subjects receiving celecoxib or ibuprofen plus omeprazole using video capsule endoscopy (VCE).

Methods  Subjects with normal baseline VCE were randomly assigned to receive celecoxib 200 mg b.d., ibuprofen 800 mg t.d.s. plus omeprazole 20 mg o.d. or placebo for 2 weeks. The primary end point was mean number of small bowel mucosal breaks per subject. Secondary end points included correlation of faecal calprotectin levels with the primary outcome.

Results  After treatment, the mean number of small bowel mucosal breaks per subject and the percentage of subjects with mucosal breaks were 0.7/25.9% for ibuprofen/omeprazole compared with 0.2/6.4% for celecoxib and 0.1/7.1% placebo (both comparisons P < 0.001). There were no significant differences between celecoxib and placebo in any measure. Mean increases in faecal calprotectin levels were higher in subjects receiving ibuprofen/omeprazole compared with celecoxib (P < 0.001), but no correlation was determined between these levels and small bowel mucosal breaks.

Conclusions  Among healthy subjects with no baseline endoscopic lesions, celecoxib was associated with significantly fewer small bowel mucosal breaks than ibuprofen/omeprazole as assessed by VCE.
Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels
Authors: HUI C.‐K. , ZHANG H.‐Y. , SHEK T. , YAO H. , YUENG Y.‐H. , LEUNG K.‐W. , LAI S.‐T. , LAI J.‐Y. , LEUNG N. , LAU G. K. ,   FOR THE HONG KONG LIVER FIBROSIS STUDY GROUP
Published: July 2010

Background

Although chronic hepatitis C virus‐infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression.

Aim

To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time.

Methods

Eighty‐two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow‐up was 8.1 years. Forty‐seven of the 82 patients (57.3%) had a second liver biopsy.

Results

At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03–2.5, P = 0.02).

Conclusion

Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.
Systematic review: the potential influence of mesalazine formulation on maintenance of remission in Crohn’s disease
Authors: STEINHART A. H. , FORBES A. , MILLS E. C. , RODGERS‐GRAY B. S. , TRAVIS S. P. L.
Published: July 2010

Aim To evaluate the effectiveness of pH 6‐/pH 7‐dependent and controlled‐release mesalazines in maintaining medically and surgically induced Crohn’s disease remission.

Methods A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn’s disease activity index >150, or an increase in baseline by at least 60–100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated.

Results Treatment with pH 7‐dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12–0.65;P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17–0.85;P = 0.0113). However, treatment with controlled‐release mesalazine and pH 6‐dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7‐dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled‐release mesalazine and NNT = 11 and 23 for pH 6‐dependent mesalazine). Therapeutic benefit was highest for pH 7‐dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled‐release mesalazine, and 9.8% and 4.4%, respectively, for pH 6‐dependent mesalazine.

Conclusion Further trials of pH 7‐dependent mesalazine formulations are warranted in the maintenance of remission in Crohn’s disease.
Irritable bowel syndrome: patients’ attitudes, concerns and level of knowledge
Authors: LACY B. E. , WEISER K. , NODDIN L. , ROBERTSON D. J. , CROWELL M. D. , PARRATT‐ENGSTROM C. , GRAU M. V.
Published: July 2010

Background

Irritable bowel syndrome (IBS) is a common, chronic disorder that reduces patients’ quality‐of‐life. Although highly prevalent, little is known about patients’ understanding of this disorder.

Aim

To evaluate the knowledge, fears and concerns of IBS patients.

Methods

Seven hundred thirty‐six IBS patients (Rome II criteria) were eligible for inclusion in this prospective study. Each patient received a validated questionnaire to evaluate knowledge, attitudes and fears regarding IBS.

Results

A total of 261 of 664 potential respondents completed the questionnaire (39.3%). 83% of respondents were women, with a mean age of 53.7 years, and mean duration of symptoms of 14.2 years. Patients frequently believed that IBS develops because of anxiety (80.5%), dietary factors (75.1%) and depression (63.2%). Few respondents (28.7%) recognized that abdominal pain is the cardinal symptom of IBS, and 40.6% stated that colonoscopy can diagnose IBS. One in seven patients stated that IBS turns into cancer, and 29.9% noted that IBS increases the risk of inflammatory bowel disease.

Conclusions

Many IBS patients have significant misconceptions regarding the nature of their disease and its prognosis. An overwhelming majority of IBS patients believe that anxiety, dietary factors and depression cause IBS. These findings are discordant with physicians’ views and practices and highlight the need for patient‐oriented educational programs.
Primary antibiotic resistance in Helicobacter pylori strains isolated in northern and central Italy
Authors: ZULLO A. , PERNA F. , HASSAN C. , RICCI C. , SARACINO I. , MORINI S. , VAIRA D.
Published: July 2010

Background  Helicobacter pylori resistance to antibiotics is increasing worldwide, and it reduces the efficacy of therapy.

Aim  To assess current primary antibiotic resistance in H. pylori strains isolated in Italy.

Methods  Between June 2004 and June 2006, H. pylori strains were isolated consecutively in the two participating centres (Bologna, northern Italy; Rome, central Italy) from patients never previously treated for the infection. Isolated strains were tested for primary clarithromycin, metronidazole and levofloxacin resistance using as break point the minimal inhibitory concentration ≥1, ≥8 and ≥1 mg/L for the three antibiotics, respectively.

Results  Overall, 255 H. pylori strains were evaluated. The resistance rate was 16.9% for clarithromycin, 29.4% for metronidazole and 19.1% for levofloxacin. Clarithromycin resistance was significantly higher in non‐ulcer dyspepsia than in peptic ulcer patients (19.1% vs. 0%, P = 0.02), metronidazole resistance was higher in foreign than Italian patients (50% vs. 22.9%, P = 0.0004) and levofloxacin resistance was higher in old than younger patients (28.4% vs. 14.4%, P = 0.048). Levofloxacin resistance was also more frequent in those strains with either clarithromycin or metronidazole resistance.

Conclusion  A very high rate of primary resistance towards the tested antibiotics was detected in our study.
Review article: the role of surgery in gastro‐oesophageal reflux disease
Authors: VAKIL N.
Published: July 2010

Background  Rates for laparoscopic fundoplication are declining in the United States and there is no consensus on the indications for referral to surgery in gastro‐oesophageal reflux disease.

Aim  To highlight recent studies on the outcomes of laparoscopic fundoplication in adults that cast doubt on the traditional indications for surgery in reflux disease.

Results  Patients who are well maintained on medical therapy have more to lose with surgical intervention than to gain, and should not be offered surgery. Likewise, the notion that surgery prevents oesophageal cancer is a hypothesis that is not supported by current evidence, therefore surgical intervention should not be offered to these patients.

The only clear‐cut candidates for surgery include: patients with anatomic abnormalities such as a large hiatus hernia, or those with persistent regurgitation that causes troublesome symptoms despite medical therapy; and carefully selected patients with extra‐oesophageal disorders who have symptoms of reflux disease such as heartburn and regurgitation, an incomplete response to medical therapy and persistent plus demonstrable reflux on pH or impedance testing that is associated with their symptoms.

Patients should be aware of the high likelihood of needing continued acid inhibitory therapy following surgery and the possibility of side‐effects.

Conclusion  Only a few carefully selected patients should undergo fundoplication for reflux disease.
Risk of acute liver injury associated with the use of drugs: a multicentre population survey
Authors: SABATÉ M. , IBÁÑEZ L. , PÉREZ E. , VIDAL X. , BUTI M. , XIOL X. , MAS A. , GUARNER C. , FORNÉ M. , SOLÀ R. , CASTELLOTE J. , RIGAU J. , LAPORTE J.‐R.
Published: July 2010

Background Acute liver injury of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce.

Aim To estimate the risk of acute liver injury associated with the use of drugs.

Methods In a population survey study, 126 cases of acute liver injury were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each drug as the ratio between the incidence of acute liver injury among the exposed population to the drug and the incidence of acute liver injury among those not exposed to it. Drug consumption data were used to estimate the exposed population.

Results Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point relative risk > 25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low‐dose acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk < 5).

Conclusions This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth specific studies.
Decreasing prevalence combined with increasing eradication of Helicobacter pylori infection in the United States has not resulted in fewer hospital admissions for peptic ulcer disease‐related complications
Authors: MANUEL D. , CUTLER A. , GOLDSTEIN J. , FENNERTY M. B. , BROWN K.
Published: July 2010

Background  Helicobacter pylori infection is a major cause of peptic ulcer disease, but the prevalence of this infection has been decreasing steadily. Additionally, eradication of H. pylori decreases ulcer recurrence and prevents ulcer complications such as bleeding.

Aim  To examine whether the decreased prevalence of H. pylori and increased use of eradication regimens have affected the prevalence of peptic ulcer disease‐related hospitalizations.

Methods  We chose to study a period between 1996 and 2005. The number of gastric and duodenal ulcers as primary or secondary hospital discharge diagnoses per year for the 10‐year span was collected from five large US hospitals. Collected data were analysed using Spearman correlation.

Results  No statistically significant trend was observed in the number of gastric or duodenal ulcers listed as primary or secondary discharge diagnoses at any of the five healthcare centres.

Conclusions  Despite a decreasing prevalence of H. pylori and the increasing use of successful H. pylori eradication regimens, the prevalence of peptic ulcer disease and its complications has not changed. In the US other aetiologies, including non‐steroidal anti‐inflammatory drugs, may be playing a larger role than once thought.
Environmental risk factors in the development of adenocarcinoma of the oesophagus or gastric cardia: a cross‐sectional study in a Dutch cohort
Authors: DE JONGE P. J. F. , WOLTERS L. M. M. , STEYERBERG E. W. , VAN DEKKEN H. , KUSTERS J. G. , KUIPERS E. J. , SIERSEMA P. D.
Published: July 2010

Background  Risk factors for adenocarcinoma of the oesophagus (OAC) and gastric cardia (GCA) are not yet established.

Aim  To compare environmental risk factors between patients with OAC and GCA.

Methods  One‐hundred and twenty‐six patients with OAC, 43 with GCA and 57 with squamous cell carcinoma filled out a questionnaire with information on demographic and lifestyle characteristics, physical activity levels, family history, gastro‐oesophageal reflux disease symptoms and medication use.

Results  OAC and GCA patients were similar with regard to male predominance and age, alcohol intake and smoking, use of fruits and vegetables, body posture and occupational activities (P > 0.05). GCA patients less often had heartburn compared with OAC patients [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.2–0.96] and had these symptoms less frequently and for a shorter period (OR 0.3, CI 0.1–1.0 and OR 0.1, CI 0.03–0.6, respectively). Former and current aspirin use was lower among GCA patients than OAC patients (OR 0.2, CI 0.05–0.7 and OR 0.4, CI 0.1–0.9, respectively), whereas no difference in non‐steroidal anti‐inflammatory drug use was detected.

Conclusion  Although OAC and GCA share several environmental risk factors, OAC is more frequently associated with a history of gastro‐oesophageal reflux disease, suggesting a more important role for gastro‐oesophageal reflux in OAC compared with GCA.
Efficacy of mitemcinal, a motilin agonist, on gastrointestinal symptoms in patients with symptoms suggesting diabetic gastropathy: a randomized, multi‐center, placebo‐controlled trial
Authors: MCCALLUM R. W. , CYNSHI O. ,   US INVESTIGATIVE TEAM
Published: July 2010

Background Mitemcinal, an oral motilin agonist, accelerates gastric emptying.

Aim To investigate if mitemcinal was superior to placebo in relief of symptoms attributed to gastroparesis.

Methods In a randomized, double‐blind design, 392 insulin‐requiring diabetics with symptoms attributable to gastroparesis were treated for 3 months with placebo, mitemcinal 5 or 10 mg bid. On a weekly basis, patients assessed whether there was adequate relief of their gastroparesis symptoms. Patients were classified as Complete Responders (CR) if there were three consecutive positive monthly responses, which required at least 50% of their weekly responses in a month being positive. An Overall Responder (OR) had at least 75% positive weekly responses for the whole treatment period.

Results Mitemcinal 10 mg produced a significantly better response rate than placebo with a 10.6% increase in the OR (P < 0.05 vs. placebo). Mitemcinal 10 mg also produced statistically significant increases in the CR and OR in the subgroup identified by baseline body mass index (<35 kg/m2) and haemoglobin A1c (<10%) (P < 0.01 vs. placebo). Adverse events did not differ from placebo frequency levels.

Conclusions Mitemcinal can induce a statistically significant response to treatment in a subset of diabetic gastroparesis where future prokinetic clinical trials should be focused.
Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro‐oesophageal reflux disease groups
Authors: DICKMAN R. , PARTHASARATHY S. , MALAGON I. B. , JONES P. , HAN B. , POWERS J. , FASS R.
Published: July 2010

Background Nocturnal gastro‐oesophageal reflux diseases (GERD) can lead to oesophageal mucosal injury and extra‐oesophageal complications.

Aim To compare distribution of oesophageal acid exposure during sleep time among patients with non‐erosive reflux disease and abnormal pH test (NERD‐positive), erosive oesophagitis (EO) and Barrett’s oesophagus (BO).

Methods Patients underwent endoscopy followed by 24‐h oesophageal pH testing. Oesophageal acid exposure was assessed every 2 h of the sleep period (0–2, 2–4, 4–6 and 6–8 h). Each period of 2 h was evaluated for acid reflux parameters. All groups were matched by age, time from last meal and duration of sleep time.

Results Thirty‐eight patients were enrolled (NERD‐positive, 16; EO, 1.4; and BO, 8). All GERD groups demonstrated higher oesophageal acid exposure in the first vs. second half of the sleep period as determined by percent time pH <4 (BO: 34.7 vs.11.6, EO: 13.5 vs. 6.9, NERD‐positive: 8.8 vs. 2.5, allP < 0.01). In general, patients with BO had a significantly higher distribution of oesophageal acid exposure than those with NERD‐positive and EO.

Conclusions Oesophageal acid exposure generally declines throughout the sleep period regardless of GERD group, but BO patients demonstrated the greatest decline during the sleep period.
Determinants of the short‐term gastric damage caused by NSAIDs in man
Authors: BJARNASON I. , SCARPIGNATO C. , TAKEUCHI K. , RAINSFORD K. D.
Published: July 2010

BackgroundThe short‐term gastric damage seen with non‐steroidal anti‐inflammatory drugs (NSAIDs) in man may involve inhibition of cyclooxygenase (COX‐1) and COX‐2 as well as the topical irritancy, which is dependant on the acidity (pKa) and/or lipophilicity (logP7.4).

AimTo study the quantitative relationship between NSAID‐induced short‐term gastric damage, their physicochemical properties and contrasting roles of COX‐1 and COX‐2 inhibition.

MethodsWe identified studies that allowed a qualitative comparison of the gastric injury (Lanza scores) induced by NSAIDs with their pKa and logP7.4. Damage was correlated with gastric COX inhibition and potency to inhibit COX‐1 and 2 and their COX‐2/COX‐1 selectivity ratio.

ResultsThe gastric damage correlates significantly with pKa (r = −0.69;P < 0.01), logP(r = −0.58,P < 0.05) and potency of the NSAIDs to inhibit COX‐1 (r = −0.61,P < 0.02), but not with COX‐2 inhibition or COX‐2/COX‐1 selectivity.

ConclusionAgainst a background of COX‐1 and COX‐2 inhibition, the physicochemical properties of NSAID appear to play an important role in short‐term gastric damage.
Meta‐analysis: the efficacy of rectal beclomethasone dipropionate vs. 5‐aminosalicylic acid in mild to moderate distal ulcerative colitis
Authors: MANGUSO F. , BALZANO A.
Published: July 2010

Background  Beclomethasone dipropionate (BDP) is a second‐generation steroid with topical effects and minimal systemic activity for patients with ulcerative colitis (UC).

Aim  To review all available literature to assess the efficacy of enema/foam BDP compared with enema/foam 5‐aminosalicylic acid (5‐ASA) in the control of left‐sided mild–moderate UC.

Methods  We selected randomized controlled trials of enema/foam BDP compared with enema/foam 5‐ASA treatment in patients with UC. Two reviewers assessed trial quality and extracted data independently.

Results  Four trials involving 428 UC patients, 209 treated with 5‐ASA (1–4 g o.d.) and 219 with BDP (3 mg o.d.), were included. Intention‐to‐treat analysis showed that 5‐ASA induced improvement/remission of UC in 146 (69.9%) patients, while BDP in 143 (65.3%). The test for heterogeneity (Cochran Q) was not significant and Mantel–Haenszel pooled estimate of odds ratio was 1.23 (95% CI = 0.82–1.85). The results did not change when analysis was performed on a per‐protocol basis.

Conclusion  The randomized controlled trials identified in this review showed that rectal BDP has equal effect as 5‐ASA to control symptoms in UC.
Systematic review: the adverse effects of sodium phosphate enema
Authors: MENDOZA J. , LEGIDO J. , RUBIO S. , GISBERT J. P.
Published: July 2010

BackgroundSodium‐phosphate enemas are widely used to treat constipation, and are rarely associated with side effects.

AimA systematic review of the literature was conducted to identify the most common adverse effects of sodium‐phosphate enemas and associated risk factors.

MethodsA systematic search was conducted in Internet (MEDLINE), and the Cochrane Library, from January 1957 to March 2007.

ResultsA total of 761 references were identified initially, and 39 relevant papers were finally selected. The most common therapeutic indications included constipation (63%). Sixty‐eight per cent of the patients having adverse effects had associated conditions, the most common being gastrointestinal motility disorders, cardiological diseases and renal failure. Virtually, all side effects were due to water and electrolyte disturbances. Most patients were under 18 years of age (66%) or older than 65 years (25%). A total of 12 deaths were found.

ConclusionThe main side effects caused by sodium phosphate enemas are water and electrolyte disturbances. The main risk factors are extreme age and associated comorbidity.
Novel endoscopic observation in Barrett’s oesophagus using high resolution magnification endoscopy and narrow band imaging
Authors: ANAGNOSTOPOULOS G. K. , YAO K. , KAYE P. , HAWKEY C. J. , RAGUNATH K.
Published: July 2010

Background High resolution magnification endoscopy with narrow band imaging (NBI) may improve the detection of specialised intestinal metaplasia (SIM) and dysplasia in Barrett’s oesophagus.

Aims To describe the magnified endoscopic features with the use of NBI in Barrett’s oesophagus.

Methods Three hundred and forty‐four areas from 50 patients with Barrett’s oesophagus were studied using high resolution magnification endoscopy (HRME) with NBI and targeted biopsies were obtained. The sensitivity, specificity, predictive values of the various patterns for the prediction of SIM and dysplasia were calculated.

Results The magnified endoscopic features of Barrett’s oesophagus with the use of NBI consist of microstructural/microvascular patterns. The yield of SIM according to the patterns was: (i) Regular microstructural pattern with tubular/linear/villous pattern 90.6% and with circular pattern 0%; and (ii) Absent microstructural pattern 98.9%. The sensitivity, specificity, positive and negative predictive values of the combination of regular microstructural pattern (tubular/villous/linear) and absent microstructural pattern to detect SIM were 100%, 78.8%, 93.5% and 100%, respectively. The sensitivity, specificity, positive and negative predictive values of the irregular microvascular/microstructural pattern for the prediction of high grade dysplasia were 90%, 100%, 99.2% and 100%, respectively.

Conclusion High resolution magnification endoscopy with NBI allows clear visualisation of microstructural and microvascular patterns within Barrett’s oesophagus, and allows targeted biopsy with a high yield of SIM and high grade dysplasia.
Relationship between the Fibrotest and portal hypertension in patients with liver disease
Authors: THABUT D. , IMBERT‐BISMUT F. , CAZALS‐HATEM D. , MESSOUS D. , MUNTENAU M. , VALLA D. C. , MOREAU R. , POYNARD T. , LEBREC D.
Published: July 2010

Background  The best technique to estimate portal hypertension (PHT) is to measure the hepatic venous pressure gradient (HVPG), which is an invasive method.

Aim  To assess the relationship between the Fibrotest (Biopredictive, Paris, France) and the presence and degree of PHT in patients with liver disease, and to determine if the Fibrotest can diagnose severe PHT, defined by HVPG ≥ 12 mmHg, in cirrhotic patients.

Methods  Patients who underwent a transjugular liver biopsy were prospectively included. HVPG was measured, and classification of histological lesions assessed. The same day, blood samples for Fibrotest were performed.

Results  A total of 130 patients were included (no or minimal fibrosis: 12%, moderate fibrosis 17%, cirrhosis 71%). There was a significant correlation between Fibrotest and HVPG (Pearson correlation coefficient = 0.58, P < 0.0001), also weaker in cirrhotic patients (Pearson correlation coefficient = 0.24, P = 0.02). In cirrhotic patients, Fibrotest was significantly higher when there was a severe PHT (0.87 ± 0.15 vs. 0.73 ± 0.14, respectively, P = 0.02). The areas under the receiver operating characteristic curves for the diagnosis of severe PHT was 0.79 ± 0.07, not different from that of platelets and Child‐Pugh score.

Conclusion  In patients with liver disease or cirrhosis, Fibrotest is correlated with the presence and degree of PHT. Other studies are needed to confirm these results, especially in non‐decompensated cirrhotic patients.
Aspirin chemoprevention in patients with increased risk for colorectal cancer: a cost‐effectiveness analysis
Authors: DUPONT A. W. , ARGUEDAS M. R. , WILCOX C. M.
Published: July 2010

Background  Aspirin chemoprevention combined with colonoscopy screening is not cost‐effective for the general population. However, the cost‐effectiveness of aspirin in individuals with prior adenoma resection has not been evaluated.

Aim  To evaluate the cost‐effectiveness of aspirin chemoprevention alone and in combination with colonoscopy surveillance in patients with prior adenoma resection.

Methods  A model of the natural history of individuals with a history of endoscopic polypectomy was constructed. Four strategies were compared: (i) no intervention, (ii) routine colonoscopy surveillance, (iii) aspirin chemoprevention alone, and (iv) aspirin therapy combined with colonoscopy.

Results  Compared with no intervention, all other strategies were more costly but were associated with gains in years of life saved. Aspirin chemoprevention alone was associated with a gain of 0.0092 years, whereas routine colonoscopic surveillance and combination strategy were associated with further gains in years of life saved (0.0124 and 0.0138 years, respectively). Compared with no intervention, the incremental cost‐effectiveness ratio of routine colonoscopy surveillance was $78 226 per year of life saved, and the incremental cost‐effectiveness ratio of combination aspirin and colonoscopy was $60 942 per year of life saved.

Conclusion  Aspirin chemoprevention combined with colonoscopic surveillance in post‐polypectomy patients may be considered a cost‐effective strategy.
A randomized, double‐blind, placebo‐controlled trial of lenalidomide in the treatment of moderately severe active Crohn’s disease
Authors: MANSFIELD J. C. , PARKES M. , HAWTHORNE A. B. , FORBES A. , PROBERT C. S. J. , PEROWNE R.C. , COOPER A. , ZELDIS J. B. , MANNING D. C. , HAWKEY C. J.
Published: July 2010

Background  Therapy targeted at tumour necrosis factor‐α has an established role in Crohn’s disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful antitumour necrosis factor‐α properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn’s disease.

Aim  To evaluate the efficacy and safety of lenalidomide in subjects with moderately severe active Crohn’s disease.

Methods  In a multicentre, double‐blind, placebo‐controlled parallel group study 89 subjects were randomized to lenalidomide 25 mg daily, 5 mg daily or placebo. Subjects were treated for 12 weeks. The primary end point was a 70‐point reduction in Crohn’s Disease Activity Index.

Results  The overall clinical response rate was not significantly different between the three groups: lenalidomide 25 mg 26%, lenalidomide 5 mg 48% and placebo 39%. Lenalidomide was generally well tolerated with only one serious adverse event, a deep vein thrombosis, being attributed to treatment.

Conclusion  Lenalidomide, an oral agent with antitumour necrosis factor‐α properties, was not effective in active Crohn’s disease in contrast to reports of benefit from thalidomide. The reasons for this lack of efficacy are speculative, other physiological activities may offset its action on inflammatory cytokines, or its antitumour necrosis factor‐α action without apoptosis may be insufficient for activity in Crohn’s disease.
Effects of multispecies probiotic supplementation on intestinal microbiota in irritable bowel syndrome
Authors: KAJANDER K. , KROGIUS‐KURIKKA L. , RINTTILÄ T. , KARJALAINEN H. , PALVA A. , KORPELA R.
Published: July 2010

Background  A multispecies probiotic has shown beneficial effects in irritable bowel syndrome. In addition, certain other probiotics have demonstrated advantageous effects, but the mechanisms behind this are poorly understood.

Aim  To investigate the mode of action of a multispecies probiotic consisting of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 by monitoring its effects on intestinal microbiota and markers of microbial activity.

Methods  A total of 55 irritable bowel syndrome patients participated in this placebo‐controlled double‐blind trial. Subjects received either multispecies probiotic or placebo supplementation daily during a 6‐month period. The composition of intestinal microbiota was analysed with real‐time polymerase chain reaction, short‐chain fatty acids with gas chromatography and enzymes with spectrophotometer.

Results  Each supplemented probiotic strain was detected in faecal samples. Intestinal microbiota remained stable during the trial, except for Bifidobacterium spp., which increased in the placebo group and decreased in the probiotic group (P = 0.028). No changes in short‐chain fatty acids occurred. A decrease in ß‐glucuronidase activity was detected in 67% of the subjects in the probiotic group vs. 38% in the placebo group (P = 0.06).

Conclusions  Factors other than the microbial groups and metabolites studied herein seem responsible for the alleviation of irritable bowel syndrome symptoms by the multispecies probiotic.
Pharmacodynamics of peginterferon alfa‐2a and peginterferon alfa‐2b in interferon‐naïve patients with chronic hepatitis C: a randomized, controlled study
Authors: BRUNO R. , SACCHI P. , SCAGNOLARI C. , TORRIANI F. , MAIOCCHI L. , PATRUNO S. , BELLOMI F. , FILICE G. , ANTONELLI G.
Published: July 2010

Background  Peginterferon alfa‐2a and alfa‐2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus.

Aim  To compare the pharmacodynamics of peginterferon alfa‐2a and peginterferon alfa‐2b in interferon‐naive patients with chronic hepatitis C.

Methods  Patients were randomized to receive peginterferon alfa‐2a, 180 μg (n = 10) or peginterferon alfa‐2b 1.0 μg/kg (n = 12) once weekly. The enzymatic activity of 2′5′‐oligoadenylate synthetase and levels of neopterin and β2‐microglobulin were measured at baseline and at 24, 48, 120 and 168 h.

Results  Oligoadenylate synthetase activity and serum neopterin and β2‐microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration‐time curve of either peginterferon and the area under the concentration‐time curve for 2′,5′‐oligoadenylate synthetase, neopterin and β2‐microglobulin. The area under the concentration‐time curves calculated for these three markers did not correlate with body mass index stratified at <25 and ≥25 kg/m2 for either peginterferon.

Conclusions  Despite pharmacokinetic differences between peginterferon alfa‐2a and peginterferon alfa‐2b, the pharmacodynamic profiles of the two formulations appear to be comparable.