bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of treatment of Helicobacter pylori on the prevention of gastroduodenal ulcers in patients receiving long‐term NSAIDs: a double‐blind, placebo‐controlled trial
Authors: Lai K. C. , Lau C. S. , Ip W. Y. , Wong B. C. Y. , Hui W. M. , Hu W. H. C. , Wong R. W. M. , Lam S. K.
Published: December 2004

Background : There is controversy as to whether Helicobacter pylori and non‐steroidal anti‐inflammatory drugs interact to cause peptic ulcers.

Aim : To study whether the eradication of H. pylori in patients on long‐term non‐steroidal anti‐inflammatory drug therapy prevents the development of ulcers.

Methods : Patients infected with H. pylori whilst receiving long‐term non‐steroidal anti‐inflammatory drug therapy, but with no ulcers at baseline endoscopy, were randomized to receive either triple antibiotic therapy (metronidazole 300 mg, clarithromycin 250 mg and amoxicillin 500 mg, given four times daily; n = 70) or placebo (n = 70) for 2 weeks. Non‐steroidal anti‐inflammatory drugs were continued throughout the study period. Endoscopy was repeated 12 weeks after the end of treatment. The development of ulcers was compared between the two groups.

Results : Endoscopy at 12 weeks revealed peptic ulcer development in five [7%; 95% confidence interval (CI), 2–16] of the patients who received triple therapy and in six (9%; 95% CI, 3–18) of those who received placebo (P = 1.00). No significant difference in the development of ulcers was found between patients with persistent H. pylori infection (7/80; 9%; 95% CI, 4–17) and those with the eradication of H. pylori (4/52; 8%; 95% CI, 2–19) (P = 1.00).

Conclusions : The eradication of H. pylori in patients receiving long‐term treatment with non‐steroidal anti‐inflammatory drugs did not prevent ulcer development. However, because the rate of ulcer development was low, a study with a larger sample size is required to confirm this finding.
Bile composition in inflammatory bowel disease: ileal disease and colectomy, but not colitis, induce lithogenic bile
Authors: Pereira S. P. , Bain I. M. , Kumar D. , Dowling R. H.
Published: December 2004

Background : Inflammatory bowel disease is a risk factor for gall‐bladder stones, but there is controversy about the composition of these stones and whether such patients develop lithogenic bile.

Methods : In 54 gallstone‐free inflammatory bowel disease patients and 13 non‐inflammatory bowel disease patients with cholesterol‐rich gallstones, we measured the biliary cholesterol saturation indices, nucleation times and bilirubin concentrations, and determined the bile acid composition and molecular species of phosphatidylcholine, in gall‐bladder bile.

Results : Patients with Crohn's colitis or ulcerative colitis had less saturated bile (mean cholesterol saturation index, 0.9) and longer nucleation times (median, 21 days) than those with ileal Crohn's disease (1.5; 14 days) or those who had undergone colectomy (1.6; 5 days). In patients with ileal Crohn's disease, the mean biliary bilirubin concentration was two‐ to three‐fold higher than that in the other groups, and was associated with a decrease in the percentage of biliary deoxycholate and an increase in the percentage of ursodeoxycholate, compared with disease controls, but phosphatidylcholine species were similar.

Conclusions : Patients with small bowel Crohn's disease, or who have undergone colonic resection, have supersaturated bile and an increased risk of cholesterol gallstone formation. In patients with ileal disease, the presence of high biliary bilirubin concentrations and low percentage of deoxycholic acid may also favour the formation of mixed, pigment‐rich, gallstones.
Antibiotic‐associated diarrhoea and Clostridium difficile> in the community
Authors: Beaugerie L. , Flahault A. , Barbut F. , Atlan P. , Lalande V. , Cousin P. , Cadilhac M. , Petit J.‐C. ,   FOR THE STUDY GROUP
Published: December 2004

Background : Clostridium difficile is the main cause of nosocomial infectious diarrhoea and the causative agent of antibiotic‐associated colitis. The involvement of C. difficile infection in antibiotic‐associated diarrhoea in the community is poorly documented.

Methods : We studied prospectively 266 adult out‐patients in the Paris (France) area who were prescribed a 5–10‐day course of antimicrobial chemotherapy. Stools were screened for C. difficile before and 14 days after the start of treatment by standard culture, toxigenic culture and testing for the cytopathic effect of toxin B. Patients were requested to note daily stool frequency and consistency. Diarrhoea was defined as the passage of at least three loose stools per day.

Results : Forty‐six (17.5%) of the 262 assessable patients had diarrhoea during the study period. Diarrhoea was mild and self‐limited in all patients, and lasted for only 1 day in 65.6% of cases. C. difficile was isolated before and after treatment from one patient, who did not develop diarrhoea. C. difficile was detected only on day 14 in 10 patients (3.8%). The isolate was toxin producing in seven patients. Four of these seven patients had mild self‐limited diarrhoea. Toxin‐producing C. difficile was isolated significantly more frequently from patients who had diarrhoea than from those who were diarrhoea free (8.7% vs. 1.4%, P = 0.02).

Conclusion : The acquisition of toxin‐producing C. difficile appears to be frequent during antimicrobial chemotherapy in the community [estimated rate of 2700 (1150–5400) cases per 100 000 exposures to antibiotics]. However, C. difficile is not the main agent of mild antibiotic‐associated diarrhoea in out‐patients.
Determination of the reduction in gastric acidity necessary to prevent pathological oesophageal reflux in patients with gastro‐oesophageal reflux disease treated with a proton pump inhibitor
Authors: Gardner J. D. , Sloan S. , Miner P. B. , Robinson M.
Published: December 2004

Background : In subjects with gastro‐oesophageal reflux disease treated with a gastric antisecretory agent, the extent to which gastric acidity needs to be reduced to prevent pathological oesophageal acid exposure is not known.

Methods : Gastric and oesophageal pH were measured in 26 healthy subjects and in 59 subjects with gastro‐oesophageal reflux disease. In 27 of the subjects with gastro‐oesophageal reflux disease, pH was also recorded on days 1, 2 and 8 of treatment with 20 mg omeprazole and 20 mg rabeprazole in a randomized, two‐way, cross‐over fashion.

Results : Receiver operating characteristic analysis was used to determine values for the integrated oesophageal acidity and time oesophageal pH≤4 that gave optimal cut‐off points for distinguishing between normal and pathological oesophageal reflux. Using these cut‐off points, we found that the probability of no pathological oesophageal reflux (Y) could be best fitted by an exponential equation, Y = a(e–bX) + c, where a, b and c are constants and X is the value of the integrated gastric acidity. There was close agreement between the predicted and observed percentages of subjects with pathological oesophageal reflux during different days of treatment.

Conclusions : In subjects with gastro‐oesophageal reflux disease treated with a proton pump inhibitor, the value of the integrated gastric acidity can predict the likelihood of pathological oesophageal reflux.
The 4G/4G genotype of the 4G/5G polymorphism of the type‐1 plasminogen activator inhibitor (PAI‐1) gene is a determinant of penetrating behaviour in patients with Crohn's disease
Authors: Sans M. , Tàssies D. , PellisÉ M. , Espinosa G. , Quintó L. , Piqué J. M. , Reverter J. C. , Panés J.
Published: December 2004

Background : Crohn's disease is a heterogeneous disorder with polygenic inheritance.

Aim : To assess the effect of the 4G/5G polymorphism of the type‐1 plasminogen activator inhibitor (PAI‐1) gene, the major inhibitor of fibrinolysis, on Crohn's disease susceptibility and phenotype.

Methods : One hundred and fifty‐seven patients with Crohn's disease and 350 controls were included prospectively. Medical records were reviewed to determine changes in the Crohn's disease phenotype. The 4G/5G polymorphism was assessed by polymerase chain reaction techniques.

Results : The frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes were similar in patients with Crohn's disease and controls. The 4G/4G genotype (P < 0.0001; odds ratio, 4.84) and male sex (P = 0.009; odds ratio, 2.63) were independent risk factors for penetrating behaviour in Crohn's disease. Most Crohn's disease patients had a non‐penetrating phenotype at diagnosis. The probability of development of a penetrating phenotype within 5 years of diagnosis was higher in patients with the 4G/4G genotype (72% vs. 19%, P < 0.0001).

Conclusions : The 4G/4G genotype of the PAI‐1 gene does not influence Crohn's disease susceptibility, but increases by five‐fold the probability of penetrating behaviour. Most patients with the 4G/4G genotype have a non‐penetrating phenotype at diagnosis, but develop a penetrating behaviour within 5 years. Genotyping the 4G/5G polymorphism may be useful for the identification of a sub‐group of patients with aggressive Crohn's disease, who might benefit from specific therapy.
Longevity of silicone and polyurethane catheters in long‐term enteral feeding via percutaneous endoscopic gastrostomy
Authors: Sartori S. , Trevisani L. , Nielsen I. , Tassinari D. , Ceccotti P. , Abbasciano V.
Published: December 2004

Background : As percutaneous endoscopic gastrostomy (PEG) is often used for many months or years, the longevity of the feeding tubes plays an important role in the global outcome and costs of PEG.

Aim : A retrospective study to evaluate the longevity of silicone and polyurethane PEG catheters.

Methods : The records of 297 patients who were fed via PEG for over 90 days were evaluated. The material of the PEG catheter, duration of follow‐up, local complications, need to remove PEG because of tube deterioration or local complications and time from PEG placement to PEG removal were recorded and compared.

Results : Two hundred and twenty‐eight patients had polyurethane and 69 had silicone PEG catheters. The follow‐up ranged from 116 to 3207 days for the polyurethane group and from 98 to 1861 days for the silicone group. No differences were observed in either local complications or PEG removal because of local complications. Tube deterioration causing PEG removal occurred in 36 of the 228 polyurethane PEG catheters and in 25 of the 69 silicone PEG catheters (P = 0.0005). Tube deterioration occurred significantly earlier in the 25 silicone catheters than in the 36 polyurethane catheters. The mean time from PEG placement to PEG removal was 287 days (95% confidence interval, 239–335) for silicone tubes and 573.9 days (95% confidence interval, 425–723) for polyurethane tubes (P = 0.0024).

Conclusion : Polyurethane PEG catheters seem to be more resistant to deterioration than silicone PEG catheters, and at present they should be preferred for long‐term enteral feeding via PEG.
High‐dose azathioprine in children with inflammatory bowel disease
Authors: Fuentes D. , Torrente F. , Keady S. , Thirrupathy K. , Thomson M. A. , Walker‐Smith J. A. , Murch S. H. , Heuschkel R. B.
Published: December 2004

Background:  Azathioprine is widely used as maintenance therapy in children with moderate to severe inflammatory bowel disease (IBD). There is no data on safety at higher doses and its impact on growth and surgical morbidity in children.

Methods:  This retrospective cohort study included all children treated with azathioprine and diagnosed with IBD between 1996–2001. Outcome measures included indications for azathioprine use, adverse‐effects and reasons for treatment discontinuation. Height and weight at diagnosis, treatment onset and current follow‐up was recorded, and Z scores for height standardised for time.

Results:  107 children received azathioprine at 3 mg/kg. 61% had Crohn's disease and 83% started azathioprine within 2 years of diagnosis. Only 2/107 children had to stop azathioprine because of persistent adverse effects and 16/107 required surgery. There was a trend toward better growth in a group of children with Crohn's disease following treatment with high dose azathioprine therapy (P = 0.08).

Conclusions: Azathioprine is a safe and well‐tolerated maintenance therapy at 3 mg/kg for children with IBD. The prevalence of surgery and growth failure in a cohort of children with moderate to severe IBD appears less than previously reported. In children with Crohn's disease, growth velocity may be maximised by an emphasis on nutritional therapy and the use of high dose azathioprine.
The impact of gastrointestinal symptoms on health status in patients with cardiovascular disease
Authors: Laheij R. J. F. , Van Rossum L. G. M. , Krabbe P. F. M. , Jansen J. B. M. J. , Verheugt F. W. A.
Published: December 2004

Background : Drugs for the management of cardiovascular disease may provoke gastrointestinal discomfort and complications.

Aim : To evaluate whether upper gastrointestinal symptoms affect the health status of patients with cardiovascular disease.

Methods : Two weeks after discharge, 958 consecutive patients, who had been admitted to the Coronary Care Unit of the University Hospital Nijmegen between January and September 2001, were sent a questionnaire for the evaluation of gastrointestinal symptoms and health status.

Results : The questionnaire was returned by 632 patients (66%), with 334 patients (53%) reporting gastrointestinal symptoms. The self‐rated health status (mean and 95% confidence interval), evaluated by visual analogue scale, was 70 (68–72) for patients without and 61 (59–63) for patients with gastrointestinal symptoms (P = 0.001). Patients with gastrointestinal symptoms reported significantly higher rates of problems with mobility (50% vs. 37%), self‐care (19% vs. 10%), usual activities (70% vs. 52%), pain/discomfort (96% vs. 38%) and anxiety/depression (41% vs. 20%) when compared with those without gastrointestinal symptoms.

Conclusion : Upper gastrointestinal symptoms strongly impaired the health status of patients with cardiovascular disease.
Induction interferon and ribavirin for re‐treatment of chronic hepatitis C patients unresponsive to interferon alone
Authors: Sievert W. , Batey R. , Mollison L. , Pianko S. , Mcdonald J. , Marinos G. , Reed W. , Warner S. , Bowden S. , De Solom R. , Bhathal P. ,   FOR THE AUSHEP INVESTIGATORS
Published: December 2004

Background : The optimal treatment for hepatitis C patients unresponsive to interferon is unclear. High‐dose induction interferon may enhance early viral clearance, whilst ribavirin reduces relapse; in combination, they may improve sustained virological response rates.

Aim : To compare the efficacy and safety of re‐treatment with interferon induction, with or without ribavirin, in interferon non‐responders.

Methods : We randomized 218 biochemical interferon non‐responders to 10 MU interferon α2b daily for 4 weeks, followed by 5 MU thrice weekly for 48 weeks plus ribavirin (II + R), or to the same interferon regimen plus placebo (II + P). All patients were viraemic at entry.

Results : The sustained virological response in the II + R group was 39%[95% confidence interval (CI), 30–48%], compared with 16% (95% CI, 9–23%) in the II + P group (P < 0.002). The study drug was discontinued for intolerable symptoms during induction in 9% of the II + R group and in 5% of the II + P group. By logistic regression, a sustained virological response was more likely following II + R treatment (odds ratio, 4.4; 95% CI, 2.1–9.7) and less likely in patients with genotype 1 or 4 (odds ratio, 0.16; 95% CI, 0.07–0.36).

Conclusion : High‐dose induction interferon plus ribavirin is well tolerated and effective for patients unresponsive to interferon alone.
Impact of moderate alcohol consumption on histological activity and fibrosis in patients with chronic hepatitis C, and specific influence of steatosis: a prospective study
Authors: HÉzode C. , Lonjon I. , Roudot‐Thoraval F. , Pawlotsky J.‐M. , Zafrani E.‐S. , Dhumeaux D.
Published: December 2004

Aim : To evaluate the effects of minimal to moderate alcohol consumption on the severity of histological lesions in patients with chronic hepatitis C.

Methods : Daily alcohol intake (none, 1–20, 21–30, 31–50 g/day) and histological activity and fibrosis were recorded in 260 patients with chronic hepatitis C.

Results : The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 53.8% in abstinent patients to 86.5% for an intake between 31 and 50 g/day (P = 0.003). In multivariate analysis, age > 40 years, alcohol intake between 31 and 50 g/day and moderate or severe steatosis were independently related to histological activity. The proportion of patients with moderate (F2) or marked (F3) fibrosis or cirrhosis (F4) gradually increased from 29.0% in abstinent patients to 67.6% for an intake between 31 and 50 g/day (P < 0.001). Multivariate analysis also showed that alcohol intake between 31 and 50 g/day, moderate or severe steatosis and histological activity were independently related to fibrosis. The deleterious effect of alcohol intake on histological lesions differed according to gender.

Conclusions : This study demonstrates that both activity and fibrosis gradually increase according to the amount of alcohol ingested, and that even moderate alcohol consumption, as low as 31–50 g/day in men and 21–50 g/day in women, may aggravate histological lesions in patients with chronic hepatitis C.
Reflux symptoms in general practice: diagnostic evaluation of the Carlsson–Dent gastro‐oesophageal reflux disease questionnaire
Authors: Numans M. E. , De Wit N. J.
Published: December 2004

Background : Amongst primary care patients with dyspeptic symptoms, those with reflux‐like symptoms or gastro‐oesophageal reflux disease are expected to benefit most from empirical proton pump inhibitor therapy. Recognition of this patient group, however, is difficult. The Carlsson–Dent gastro‐oesophageal reflux disease questionnaire was developed to justify the selection of primary care patients for empirical proton pump inhibitor treatment.

Aim : To evaluate the diagnostic test characteristics of the Carlsson–Dent questionnaire in a primary care population.

Methods : A prospective, open‐label, multi‐centre diagnostic prevalence study was conducted amongst primary care adults with reflux symptoms. All patients completed the questionnaire and underwent gastroscopy. If no abnormalities were found, the patients were prescribed 2 weeks of treatment with omeprazole (20 mg daily). Receiver operating characteristic curve analysis was used to determine the overall discriminative value of the questionnaire. Diagnostic test characteristics of both the cut‐off score (total diagnostic score) in the questionnaire and the physician's provisional classification were measured using oesophagitis and omeprazole treatment success as the reference tests.

Results : Of the 536 patients included, 515 underwent endoscopy. No abnormalities were found in 286 (55%). Omeprazole treatment success occurred more frequently in patients with a total diagnostic score of > 7 and oesophagitis II–IV in patients with a total diagnostic score of > 9. The diagnostic test characteristics of the questionnaire were comparable with those of the physician's provisional classification. The area under the receiver operating characteristic curve did not exceed 0.65. Kappa values for observer agreement with the gold standard were far below 0.4.

Conclusion : The diagnostic performance of this version of the Carlsson–Dent questionnaire was poor. It equalled the physician's clinical judgement and therefore its value for clinical use is limited.
A summary of Food and Drug Administration‐reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole and pantoprazole
Authors: Labenz J. , Petersen K. U. , Rösch W. , Koelz H. R.
Published: December 2004

Background : Pantoprazole is claimed to have a lower potential for drug interaction than other proton pump inhibitors.

Aim : To estimate the frequency of adverse events and drug interactions reported to the Food and Drug Administration in patients receiving omeprazole, lansoprazole or pantoprazole.

Methods : The study involved a search of the Food and Drug Administration's database for adverse events and drug interactions with omeprazole, lansoprazole or pantoprazole as primary or secondary suspect drug. An estimate of the amount of drug dispensed during the adverse event collection period (from US drug launch) was obtained from the International Medical Statistics health database.

Results : Of the suspected drug interactions recorded, vitamin K antagonist interactions, although rare, were the most common. The frequency of vitamin K antagonist interactions was 0.09 per million packages for omeprazole and 0.11 per million packages for lansoprazole and pantoprazole. Interactions with benzodiazepines or phenytoin were even rarer, being reported in less than 10 patients on each proton pump inhibitor.

Conclusion  The frequency of reported drug interactions was low for omeprazole, lansoprazole and pantoprazole and vitamin K antagonist interactions were by far the most common. These potentially important drug interactions, although rare, were no less frequent on pantoprazole than on omeprazole or lansoprazole, suggesting a class effect.
Diagnostic investigation rates and use of prescription and non‐prescription medications amongst dyspeptics: a population‐based study of 2300 Australians
Authors: Westbrook J. I. , Talley N. J.
Published: December 2004

Background : There is limited knowledge of the diagnostic investigation rates and use of prescription and non‐prescription drugs amongst dyspeptics.

Aim : To assess the investigation rates and use of prescription and non‐prescription anti‐ulcer medications amongst dyspeptics in the population.

Methods : A cross‐sectional survey was performed of 2300 Australians.

Results : Of 748 dyspeptics, 422 (56%) had consulted a doctor regarding dyspepsia at some time in their life. Of the consulters, 64% had undergone investigations at some time: 37% an endoscopy, 54% a barium meal and 27% both. A diagnosis of peptic ulcer was reported by 31% of those investigated. The symptom profile of gastroscopy patients differed significantly from that of uninvestigated dyspeptics. Of the consulters, 36% had taken anti‐ulcer prescription drugs in the last 3 months: Histamine‐2 receptor antagonists (73% of prescriptions), proton pump inhibitors (17%), cytoprotectants (5%) and prokinetic drugs (5%). Antacids were taken by 30% of non‐consulting dyspeptics, 44% of consulters not on prescription drugs and 58% of dyspeptics taking prescription drugs. Advancing age, but not gender, was associated with diagnostic investigation and prescription and non‐prescription drug usage.

Conclusions : There are high rates of diagnostic investigation amongst dyspeptics who consult doctors. Many individuals with dyspepsia decide to self‐medicate with antacids regardless of consulting or prescriptions, suggesting that current management is suboptimal.
The advent of capsule endoscopy — a not‐so‐futuristic approach to obscure gastrointestinal bleeding
Authors: Lewis B. , Goldfarb N.
Published: December 2004

Capsule endoscopy is a new, wireless, endoscopic examination of the small intestine. To date, two small clinical trials have been reported utilizing capsule endoscopy in patients with obscure gastrointestinal bleeding, and have shown its superiority to push enteroscopy in diagnosing the cause of blood loss. No outcome studies have been reported.

This paper proposes a change in practice guidelines for obscure bleeding. It is our opinion that, in the future, with the advent of wireless capsule endoscopy, the evaluation of patients with obscure gastrointestinal bleeding will be very different from the practice of medicine today. We believe that capsule endoscopy will become the first‐line method for the evaluation of patients with obscure bleeding, once upper endoscopy and colonoscopy have been shown to be negative.

In patients with active bleeding, capsule endoscopy will confirm the small bowel as the site of bleeding, providing a location, or, if the study is negative for the small intestine, may indicate that the bleeding is either colonic or gastric in origin. In a patient with active bleeding within the small intestine, the capsule will guide further evaluation and therapy. A patient with a small bowel tumour detected by capsule endoscopy will proceed directly to laparoscopic surgery. If the site of bleeding is identified in the proximal small bowel and there is no mass, push enteroscopy will be used to re‐identify the site and cauterize it. A distal small bowel site will require surgical intervention, coupled with intra‐operative enteroscopy. Should the patient be too sick to undergo surgery, medical therapy utilizing hormonal agents will be considered. A colonic site will be evaluated by colonoscopy. In patients with a more occult or intermittent type of bleeding and in those whose upper endoscopies and colonoscopies are negative, capsule endoscopy will be used similarly to identify a bleeding lesion and thereby direct subsequent testing or treatment.
Famotidine for infant gastro‐oesophageal reflux: a multi‐centre, randomized, placebo‐controlled, withdrawal trial
Authors: Orenstein S. R. , Shalaby T. M. , Devandry S. N. , Liacouras C. A. , Czinn S. J. , Dice J. E. , Simon T. J. , Ahrens S. P. , Stauffer L. A.
Published: December 2004

Background :  Gastro‐oesophageal reflux afflicts up to 7% of all infants. Histamine‐2 receptor antagonists are the most commonly prescribed medications for this disorder, but few controlled studies support this practice.

Aim : To evaluate the safety and efficacy of famotidine for infant gastro‐oesophageal reflux disease.

Methods : Thirty‐five infants, 1.3–10.5 months of age, entered an 8‐week, multi‐centre, randomized, placebo‐controlled, two‐phase trial: first 4 weeks, observer‐blind comparison of famotidine 0.5 mg/kg and famotidine 1.0 mg/kg; second 4 weeks, double‐blind withdrawal comparison (safety and efficacy) of each dose with placebo.

Results : No serious adverse events were reported. Eleven patients had 16 non‐serious, possibly drug‐related adverse experiences: 6 patients with agitation or irritability (manifested as head‐rubbing in two), 3 patients with somnolence, 2 patients with anorexia, 2 with headache, 1 patient with vomiting, 1 patient with hiccups, and 1 patient with candidiasis. Of the 35 infants, 27 completed Part I. There were significant score improvements for famotidine 0.5 mg/kg in regurgitation frequency (P = 0.04), and for famotidine 1.0 mg/kg in crying time (P = 0.027) and regurgitation frequency (P = 0.004) and volume (P = 0.01). Eight infants completed Part II on double‐blind treatment, which was insufficient for meaningful comparisons.

Conclusions : Histamine‐2 receptor antagonists may cause agitation and headache in infants. A possibly efficacious famotidine dose for infants is 0.5 mg/kg (frequency adjusted for age). As 1.0 mg/kg may be more efficacious in some, the dosage may require individualization based on response. Further sizeable placebo‐controlled evaluations of histamine‐2 receptor antagonists in infants with gastro‐oesophageal reflux disease are warranted.
Helicobacter pylori eradication and gastric ulcer healing — comparison of three pantoprazole‐based triple therapies
Authors: Malfertheiner P. , Kirchner T. , Kist M. , Leodolter A. , Peitz U. , Strobel S. , Bohuschke M. , Gatz G. ,   THE BYK ADVANCED GASTRIC ULCER STUDY (BAGUS) GROUP
Published: December 2004

Aim : To study the efficacy of three pantoprazole‐based triple therapy regimens for the eradication of Helicobacter pylori infection and gastric ulcer healing.

Methods : In an open, multi‐centre, randomized study, 519 H. pylori‐positive patients with active gastric ulcer were randomized to receive pantoprazole (40 mg) (P) and two of three antibiotics: clarithromycin (500 mg) (C), metronidazole (500 mg) (M) or amoxicillin (1000 mg) (A). Triple therapy (PAC, PCM, PAM) was administered twice daily for 7 days, followed by pantoprazole until the ulcer had healed. Antrum and corpus biopsies were taken to determine the pattern of gastritis, to assess the H. pylori status and to determine the strain susceptibility to antibiotics, and from the ulcer margins and base to exclude malignancy. Scores based on the Sydney system were used to categorize the gastritis phenotypically.

Results : The H. pylori eradication rates for the per protocol (intention‐to‐treat) analysis were 89% (67%) for PAC, 83% (68%) for PCM and 76% (60%) for PAM, with a significant difference between PAC and PAM. Healing rates after 4 weeks were 91% for PAM, 90% for PCM and 88% for PAC (per protocol analysis). The eradication rates were lower in patients in whom strains resistant to any antibiotic used in the triple therapies were detected. Successful eradication [odds ratio, 5.2 (3.3; 8.3)] and the ulcer size (< 15 mm) were significant predictors for healing after 4 weeks. The regimens showed a comparable safety profile and compliance.

Conclusions : Pantoprazole‐based triple therapies are effective in the eradication of H. pylori infection in gastric ulcer patients, as reported in previous similar sized studies in duodenal ulcer patients. Successful eradication and an ulcer size of < 15 mm are the best predictors of gastric ulcer healing after 4 weeks.
Gastrointestinal transit and release of 5‐aminosalicylic acid from 153Sm‐labelled mesalazine pellets vs. tablets in male healthy volunteers
Authors: Brunner M. , Greinwald R. , Kletter K. , Kvaternik H. , Corrado M. E. , Eichler H. G. , Müller M.
Published: December 2004

Background : Mesalazine (5‐aminosalicylic acid)‐containing formulations, designed to optimize drug delivery to the ileo‐caecal region, represent a cornerstone in the treatment of inflammatory bowel diseases.

Aim : To test, by means of pharmaco‐scintigraphy, whether novel mesalazine‐containing pellets release 5‐aminosalicylic acid in the same target region as mesalazine tablets (Salofalk).

Methods : Fourteen healthy male volunteers received a single dose of either pellets or tablets containing 500 mg of mesalazine and 2 mg of 152Sm2O3 with a 1‐week washout period. The gastrointestinal transit of 153Sm, incorporated into the formulations, was followed by gamma‐scintigraphy. Mesalazine release was verified by assessing 5‐aminosalicylic acid plasma pharmacokinetics.

Results : The formulations reached the ileo‐caecal target region almost at the same time (3.3 ± 1 and 3.8 ± 1 h for pellets and tablets, respectively). Plasma 5‐aminosalicylic acid tmax values were comparable and corresponded to the time during which the formulations were located in the target region. Plasma AUC values were significantly lower for pellets, which might be explained by a more prolonged release of 5‐aminosalicylic acid.

Conclusions : Novel mesalazine pellets and Salofalk tablets release active 5‐aminosalicylic acid in the same target region and pass through the gastrointestinal tract under fasting conditions in healthy volunteers in a comparable time. From a comparison of in vitro dissolution and plasma concentration data, a slower and more prolonged release of 5‐aminosalicylic acid from pellets is suggested.
Rabeprazole is superior to omeprazole for the inhibition of peptone meal‐stimulated gastric acid secretion in Helicobacter pylori‐negative subjects
Authors: Ohning G. V. , Walsh J. H. , Pisegna J. R. , Murthy A. , Barth J. , Kovacs T. O. G.
Published: December 2004

Background: Peptone meal‐stimulated gastric acid output is considered to be a reliable means to evaluate drug‐mediated inhibition of stimulated gastric acid output, an important measure of the efficacy of the agents — such as proton pump inhibitors — used to treat acid‐related disorders.

Aim: To compare the initial and overall inhibitory effects on peptone meal‐stimulated gastric acid secretion of rabeprazole and omeprazole, 20 mg, in Helicobacter pylori‐negative subjects on the first and eighth days of treatment.

Methods: Healthy volunteers (n = 27) were randomized in a single‐centre, double‐blind, double‐dummy, 2 × 2 cross‐over study. Subjects received an oral dose of rabeprazole or omeprazole, 20 mg once daily, for 8 days. After a 2–4‐week washout period, subjects were crossed over to receive the other medication for 8 days. Peptone meal‐stimulated gastric acid secretion was measured at hours 11 and 23 at baseline and on days 1 and 8 of treatment.

Results: On days 1 and 8, rabeprazole demonstrated a significantly greater inhibition of peptone meal‐stimulated gastric acid secretion compared with omeprazole at all time points (P < 0.03). Median values of steady‐state inhibition on day 1 were statistically significant at hour 23 (rabeprazole 100% vs. omeprazole 74%, P < 0.02).

Conclusions: Rabeprazole, 20 mg, demonstrated superior control of peptone meal‐stimulated gastric acid secretion compared with omeprazole, 20 mg, after the first dose and after the eighth daily dose. Rabeprazole achieved a more rapid onset of acid inhibition and a greater steady‐state reduction in peptone meal‐stimulated gastric acid secretion.
Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six‐week placebo‐controlled, double‐blind, multicentre trial
Authors: Holtmann G. , Adam B. , Haag S. , Collet W. , Grünewald E. , Windeck T.
Published: December 2004

Background : This study aimed to assess the efficacy of artichoke leaf extract (ALE) in the treatment of patients with functional dyspepsia (FD).

Methods : In a double‐blind, randomized controlled trial (RCT), 247 patients with functional dyspepsia were recruited and treated with either a commercial ALE preparation (2 × 320 mg plant extract t.d.s.) or a placebo. The primary efficacy variable was the sum score of the patient's weekly rating of the overall change in dyspeptic symptoms (four‐point scale). Secondary variables were the scores of each dyspeptic symptom and the quality of life (QOL) as assessed by the Nepean Dyspepsia Index (NDI).

Results : Two hundred and forty‐seven patients were enrolled, and data from 244 patients (129 active treatment, 115 placebo) were suitable for inclusion in the statistical analysis (intention‐to‐treat). The overall symptom improvement over the 6 weeks of treatment was significantly greater with ALE than with the placebo (8.3 ± 4.6, vs. 6.7 ± 4.8, P < 0.01). Similarly, patients treated with ALE showed significantly greater improvement in the global quality‐of‐life scores (NDI) compared with the placebo‐treated patients (− 41.1 ± 47.6 vs. − 24.8 ± 35.6, P < 0.01).

Conclusion : The ALE preparation tested was significantly better than the placebo in alleviating symptoms and improving the disease‐specific quality of life in patients with functional dyspepsia.
Adherence to proton pump inhibitors or H2‐receptor antagonists during the use of non‐steroidal anti‐inflammatory drugs
Authors: Sturkenboom M. C. J. M. , Burke T. A. , Tangelder M. J. D. , Dieleman J. P. , Walton S. , Goldstein J. L.
Published: December 2004

Background : The efficacy of proton pump inhibitors (PPIs) or histamine‐2 receptor antagonists (H2RAs) prescribed as prophylaxis for NSAID‐related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence.

Aim : To describe patient adherence to prophylactically prescribed PPIs and H2RAs in the clinical setting.

Methods : We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non‐specific NSAID users prescribed a PPI or H2RA specifically as prophylaxis for NSAID‐related UGI toxicity. Patients were classified as non‐adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription.

Results : The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs, and 5 with both PPI and H2RA. Eighty‐five percent of H2RA users and 7% of PPI users were prescribed these drugs at doses below the minimum recommended/effective dose for NSAID‐associated gastroduodenal ulcer prophylaxis. Thirty‐seven percent of patients were non‐adherent. The lowest rate of non‐adherence was associated with the first NSAID prescription (9%), increasing to 61% for patients with 3 prescriptions. In a cohort of subjects who stopped their NSAID and were followed for up to 2 years (n = 711), there was significant persistent use of acid suppressive agents; 40% of patients had at least one additional prescription for the acid suppressive agent after stopping NSAIDs, and> 30% received enough drug to cover a period longer than 2 months after stopping their NSAID.

Conclusions : The pattern of PPI and H2RA prescriptions, when prescribed as prophylactic strategy, does not correspond with the pattern of NSAID use. Physicians should consider the medical impact of non‐adherence with dual therapies and the impact of prolonged use of GPAs on treatment cost.
A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis
Authors: Austin A. S. , Mahida Y. R. , Clarke D. , Ryder S. D. , Freeman J. G.
Published: December 2004

Background : Tumour necrosis factor‐α is thought to be important in the pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and thalidomide inhibit endotoxin‐induced tumour necrosis factor‐α production in vitro.

Aims : To assess the toxicity of oxpentifylline (pentoxifylline) and thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient and tumour necrosis factor‐α production.

Methods : In an open‐label pilot study, 20 abstinent patients with stable alcoholic cirrhosis and oesophageal varices were recruited; 12 patients completed haemodynamic measurements before and after treatment with oxpentifylline (pentoxifylline) 1800 mg (n = 6) or thalidomide 200 mg (n = 6) daily for 2 weeks. Tumour necrosis factor‐α production was assessed in ex vivo monocyte cultures stimulated with endotoxin.

Results : Thalidomide reduced the hepatic venous pressure gradient from 19.7 mmHg (9.3–23.5 mmHg) to 12.2 mmHg (4.7–19.5 mmHg) (P = 0.03) without reducing the hepatic blood flow or altering systemic haemodynamic parameters. Thalidomide reduced ex vivo tumour necrosis factor‐α production by approximately 50%. Oxpentifylline (pentoxifylline) had no significant effect on any of the parameters measured. Side‐effects led to dose reduction or treatment withdrawal in 40% of patients.

Conclusion : Thalidomide, but not oxpentifylline (pentoxifylline), reduces the hepatic venous pressure gradient in stable alcoholic cirrhotics, an effect that may be mediated by the inhibition of tumour necrosis factor‐α production. The role of tumour necrosis factor‐α inhibitory drugs in the therapy of portal hypertension should be investigated in a randomized controlled trial.
Current management of chronic hepatitis B
Authors: Papatheodoridis G. V. , Hadziyannis S. J.
Published: December 2004

Chronic hepatitis B can be diagnosed in patients with increased aminotransferases, hepatitis B virus viraemia and necroinflammation with fibrosis on liver biopsy. Although, ideally, all patients with chronic hepatitis B should be treated, therapeutic intervention is currently recommended for cases with a relatively satisfactory likelihood of response and/or advanced disease. A realistic therapeutic approach aims to sustain hepatitis B e antigen (HBeAg) loss and hepatitis B e antibody (anti‐HBe) seroconversion in HBeAg‐positive chronic hepatitis B and to sustain biochemical and virological remission in HBeAg‐negative chronic hepatitis B. Currently, three drugs are licensed for chronic hepatitis B: interferon‐alpha, lamivudine and adefovir dipivoxil. In patients with HBeAg‐positive chronic hepatitis B, all of these drugs achieve HBeAg loss (24–33%) and anti‐HBe seroconversion (12–30%) rates significantly superior to those observed in untreated placebo controls. In patients with HBeAg‐negative chronic hepatitis B, the sustained off‐therapy response rate is 20–25% after a ≥ 12‐month course of interferon‐alpha and minimal (< 10%), if any, after a 12‐month course of lamivudine or adefovir. Long‐term lamivudine induces an initial response in 70–90% of patients, but only 30–40% of patients remain in remission after the third year due to progressively increasing viral resistance. Long‐term adefovir achieves a response in approximately 70% of patients at 12 months, which is maintained at 24 months with rare (< 2%) drug resistance. Adefovir is also effective against lamivudine‐resistant strains. Many other anti‐viral agents, immunomodulatory approaches and combination therapies are currently being evaluated in chronic hepatitis B.
Atrophic gastritis as a cause of hyperhomocysteinaemia
Authors: Santarelli L. , Gabrielli M. , Cremonini F. , Santoliquido A. , Candelli M. , Nista E. C. , Pola P. , Gasbarrini G. , Gasbarrini A.
Published: December 2004

Background : Hyperhomocysteinaemia is an independent risk factor for atherosclerosis. It is often related to low levels of vitamin B12 and/or folate, enzymatic co‐factors of methionine metabolism. Atrophic gastritis, often caused by Helicobacter pylori infection, may impair vitamin absorption.

Aim : To assess whether the presence of atrophic gastritis is associated with hyperhomocysteinaemia via deficiency of its vitamin co‐factors.

Methods : Thirty‐one patients with atrophic gastritis were recruited. The control group consisted of 28 patients with non‐atrophic gastritis, matched with patients for sex, age and body mass index. The presence and degree of gastric atrophy were assessed by histology. H. pylori infection was assessed by histology/serology. Blood samples were collected for the measurement of homocysteine, vitamin B12 and folates.

Results : Multiple logistic regression analysis showed that atrophic gastritis (odds ratio, 5.3; 95% confidence interval, 1.23–25.26; χ2 = 5.2; P = 0.01) and low vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03–22.08; χ2 = 3.6; P < 0.05) were both predictors of hyperhomocysteinaemia. None of the other variables considered in the analysis, including H. pylori status, showed a significant association with hyperhomocysteinaemia.

Conclusions : The present study suggests that atrophic gastritis, rather than H. pylori infection per se, may be a contributing factor to hyperhomocysteinaemia, possibly via vitamin B12 malabsorption.
Lipase inhibition by orlistat: effects on gall‐bladder kinetics and cholecystokinin release in obesity
Authors: Mathus‐Vliegen E. M. H. , Van Ierland‐Van Leeuwen M. L. , Terpstra A.
Published: December 2004

Background : Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction.

Aim : To study whether orlistat, by lipase inhibition, impairs gall‐bladder emptying, thus further predisposing weight‐losing obese subjects to gallstone formation.

Methods : Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 × 60 mg orlistat or 3 × 120 mg orlistat, underwent gall‐bladder emptying studies measured by ultrasound. Meal‐induced cholecystokinin release and gall‐bladder emptying were investigated at the start, at randomization and after 1 and 12 months.

Results : One month of dieting did not change gall‐bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall‐bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall‐bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat.

Conclusions : One month of lipase inhibition by orlistat significantly impaired gall‐bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.
Do we need a new gastro‐oesophageal reflux disease questionnaire?
Authors: Stanghellini V. , Armstrong D. , Mönnikes H. , Bardhan K. D.
Published: December 2004

Background : Gastro‐oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self‐assessed symptom questionnaires are now key instruments in clinicaltrials.

Aim : To evaluate the validity of available GERD measurement tools.

Methods : An ideal GERD symptom assessment instrument, suitable as a primary end‐point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self‐assessed; (vii) use ‘word pictures’ which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use.

Results : A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria.

Conclusion : There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.
The pharmacokinetics and effects on blood pressure of multiple doses of the novel anti‐migraine drug zolmitriptan (311C90) in healthy volunteers
Authors: Dixon* Ruth , Gillotin Catherine , Gibbens Michael , Posner John , Peck Richard W.
Published: December 2004

Aims Zolmitriptan (311C90), a novel, selective, centrally and peripherally acting 5‐HT1D‐receptor agonist is under development as an acute treatment for migraine. The tolerability, pharmacokinetics and effects on blood pressure and heart rate of multiple doses of 5 or 10 mg (5 doses administered over 24 h) were compared, in healthy adult volunteers, with those after placebo and single doses of zolmitriptan.

Methods Twelve subjects participated in a randomized, balanced, crossover comparison. Plasma and urine concentrations of zolmitriptan and its metabolites, pulse rate and blood pressure were measured at intervals after drug. Ten volunteers completed the study.

Results Zolmitriptan was well tolerated after single and multiple doses throughout the study. There was no evidence of significant changes in the pharmacokinetic parameters of zomitriptan or its metabolites after the last dose compared to the first, except for an expected rise in peak concentrations and a small, apparent increase in the amount of drug excreted in urine and hence in CLR. After the last 10 mg dose, mean dosing interval zolmitriptan AUC was 80.3 ng ml−1 h compared with 86.5 ng ml−1 h after the single 10 mg dose (95% CI for ratio 0.76–1.13). There was no evidence of changes in the pharmacokinetic parameters of zolmitriptan and its metabolites after 10 mg compared with 5 mg, except a small increase in zolmitriptan CLR. There were no statistically significant increases in peak systolic or diastolic blood pressure after the last doses of zolmitriptan compared to placebo or in peak blood pressure after the last dose compared to the first. There were no significant differences between blood pressure immediately before the first and last doses of each multiple dose regimen. Peak erect systolic blood pressure after the last 10 mg dose (137 mmHg) was significantly lower than that after placebo (147 mmHg, 95% CI for difference −18, −2) and that after the last 5 mg dose (148 mmHg, 95% CI −19, −3).

Conclusions Repeated doses of 5 or 10 mg zolmitriptan are well tolerated despite higher plasma concentrations than expected from single doses.