bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐dose or standard‐dose proton pump inhibitors for maintenance therapy of gastro‐oesophageal reflux disease: a cost‐effectiveness analysis
Authors: You J. H. S. , Lee A. C. M. , Wong S. C. Y. , Chan F. K. L.
Published: December 2004

Background : Studies on the use of low‐dose proton pump inhibitor for the maintenance therapy of gastro‐oesophageal reflux disease have shown that it might be comparable with standard‐dose proton pump inhibitor treatment and superior to standard‐dose histamine‐2 receptor antagonist therapy.

Aim : To compare the impact of standard‐dose histamine‐2 receptor antagonist, low‐dose proton pump inhibitor and standard‐dose proton pump inhibitor treatment for the maintenance therapy of gastro‐oesophageal reflux disease on symptom control and health care resource utilization from the perspective of a public health organization in Hong Kong.

Methods : A Markov model was designed to simulate, over 12 months, the economic and clinical outcomes of gastro‐oesophageal reflux disease patients treated with standard‐dose histamine‐2 receptor antagonist, low‐dose proton pump inhibitor and standard‐dose proton pump inhibitor. The transition probabilities were derived from the literature. Resource utilization was retrieved from a group of gastro‐oesophageal reflux disease patients in Hong Kong. Sensitivity analysis was conducted to examine the robustness of the model.

Results : The standard‐dose proton pump inhibitor strategy was associated with the highest numbers of symptom‐free patient‐years (0.954 years) and quality‐adjusted life‐years gained (0.999 years), followed by low‐dose proton pump inhibitor and standard‐dose histamine‐2 receptor antagonist. The direct medical cost per patient in the standard‐dose proton pump inhibitor group (US$904) was lower than those of the low‐dose proton pump inhibitor and standard‐dose histamine‐2 receptor antagonist groups.

Conclusions : The standard‐dose proton pump inhibitor strategy appears to be the most effective and least costly for the maintenance management of patients with gastro‐oesophageal reflux disease in Hong Kong.
Impact of carbohydrate and fat intake on weight‐reducing efficacy of orlistat
Authors: Ullrich A. , Erdmann J. , Margraf J. , Schusdziarra V.
Published: December 2004

Background : Orlistat treatment of obesity results in a poor long‐term weight loss (< 5%) in about 30% of patients.

Aim : Total energy and macronutrient intake were examined to assess the effect of a change in eating habits on weight loss.

Methods : Sixty‐two patients consumed a hypocaloric diet, together with orlistat (3 × 120 mg/day), for 72 weeks, with a maximal fat allowance of 30% of the energy intake. At regular intervals, food diaries were recorded.

Results : Fifty‐six patients completed the study and lost 8.5 ± 0.88 kg (P < 0.001). Energy intake was ≈ 1500 kcal/day during the entire study period. In three sub‐groups established according to weight loss (1, < 5%; 2, > 5% and < 10%; 3, > 10%), fat intake was within the recommended range in all groups during the first 6 months, but thereafter only in group 3. All groups increased their carbohydrate consumption, with the greatest increase in group 1, which could account for the rapid regain of initially lost body weight in this group.

Conclusion : At the beginning of a weight management programme in conjunction with orlistat, a low fat intake is advised for an efficient reduction in body weight. Subsequently, in patients with poor long‐term weight loss, dietary recommendations must also consider carbohydrate restriction to ensure an adequate hypocaloric diet.
The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism
Authors: Kawamura M. , Ohara S. , Koike T. , Iijima K. , Suzuki J. , Kayaba S. , Noguchi K. , Hamada S. , Noguchi M. , Shimosegawa T.
Published: December 2004

Background : The acid suppressive effect of lansoprazole is influenced by the P450 2C19 (CYP2C19) polymorphism.

Aim : To investigate whether the CYP2C19 genotype is related to the healing of erosive reflux oesophagitis during treatment with lansoprazole.

Methods : Eighty‐eight Japanese patients with erosive reflux oesophagitis were treated with a daily oral dose of 30 mg lansoprazole for 8 weeks. The CYP2C19 genotype, Helicobacter pylori infection status and serum pepsinogen I/II ratio were assessed before treatment. At 4 and 8 weeks, the healing of erosive reflux oesophagitis was evaluated endoscopically.

Results : The healing rates were 57.1%, 69.2% and 72.7% at 4 weeks and 77.4%, 95.0% and 100% at 8 weeks in homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers, respectively. At 8 weeks, the healing rate of erosive reflux oesophagitis was significantly lower in homozygous extensive metabolizers than in the other two groups (P < 0.05). The H. pylori status and serum pepsinogen I/II ratio had less influence than CYP2C19 polymorphism on the healing rate of erosive reflux oesophagitis.

Conclusions : The therapeutic effect of lansoprazole on erosive reflux oesophagitis is influenced by the CYP2C19 genotype status. Therefore, a test of CYP2C19 genotype may be useful for the medical treatment of reflux oesophagitis with lansoprazole.
Safety, efficacy and costs of pharmacotherapy for functional gastrointestinal disorders: the case of alosetron and its implications
Authors: Ladabaum U.
Published: December 2004

Background: Functional gastrointestinal disorders cause substantial morbidity, but not mortality. Alosetron may achieve ‘adequate relief ’ in diarrhoea‐predominant irritable bowel syndrome, but may cause major complications, including death.

Aim: To appraise, quantitatively, the trade‐off between possible symptomatic improvement and serious complications in the treatment of functional gastrointestinal disorders.

Methods: A decision analytical model was used to examine alosetron or standard treatment for 6 months in 45‐year‐old women with diarrhoea‐predominant irritable bowel syndrome using the health care system's perspective.

Results: Assuming a 14% higher ‘adequate relief’ rate with alosetron compared to standard care, and a complication rate of four per 1000 persons in 6 months, alosetron gained 0.00081 quality‐adjusted life‐years (QALYs) per patient at a cost of $358 700 per QALY gained. Alosetron gained QALYs if ‘adequate relief’ increased the patients' utility by more than 0.01 in the base case. In probabilistic analysis, alosetron gained QALYs in 98.2% of iterations at a median cost of $212 600 per QALY (interquartile range, $138 000–338 900 per QALY). Results were highly sensitive to the utility gain with ‘adequate relief’ and alosetron's response and complication rates.

Conclusions: Alosetron's benefit‐to‐risk profile appears to be favourable, but its cost per QALY gained may be substantial. Decision analyses on treatments for functional gastrointestinal disorders are likely to be highly sensitive to the utility estimates used. There is a pressing need for direct utility measurements in functional gastrointestinal disorders.
Helicobacter pylori infection is not involved in the pathogenesis of either erosive or non‐erosive gastro‐oesophageal reflux disease
Authors: Zentilin P. , Iiritano E. , Vignale C. , Bilardi C. , Mele M. R. , Spaggiari P. , Gambaro C. , Dulbecco P. , Tessieri L. , Reglioni S. , Mansi C. , Mastracci L. , Vigneri S. , Fiocca R. , Savarino V.
Published: December 2004

Background : The majority of reflux patients have non‐erosive reflux disease.

Aim : To evaluate the influence of Helicobacter pylori on oesophageal acid exposure in patients with both non‐erosive and erosive reflux disease and in a group of controls. The pattern and distribution of chronic gastritis were also assessed.

Methods : One hundred and twelve consecutive patients with symptoms of gastro‐oesophageal reflux disease agreed to undergo both upper gastrointestinal endoscopy and 24‐h oesophageal pH‐metry. Patients were grouped as H. pylori‐positive or H. pylori‐negative on the basis of both CLO‐test and histology, and as cases with or without oesophagitis on the basis of endoscopy. The controls consisted of 19 subjects without reflux symptoms and with normal endoscopy and oesophageal pH‐metry.

Results : H. pylori was positive in 35 patients (31%) and in six controls (31%); oesophagitis was found in 44 patients (39%) and non‐erosive reflux disease in 68 (61%). The prevalence of chronic gastritis in the antrum and corpus was higher in H. pylori‐positive than in H. pylori‐negative patients (P < 0.001), but was more frequently mild (P < 0.001) than moderate or severe. The percentage total time the oesophageal pH < 4.0 was higher in patients than in controls (P < 0.008–0.001), but there was no difference between H. pylori‐positive and H. pylori‐negative patients (12.3% vs. 12%, P = 0.43) or H. pylori‐positive and H. pylori‐negative controls (1.07% vs. 1.47%, P = 0.19).

Conclusions : H. pylori infection had the same prevalence in reflux patients and in controls. It did not affect oesophageal acid exposure, as there was no difference between H. pylori‐positive and H. pylori‐negative individuals. The high prevalence of mild body gastritis in H. pylori‐positive patients suggests that H. pylori eradication is unlikely to lead to gastric functional recovery, which might precipitate or worsen symptoms and lesions in patients with gastro‐oesophageal reflux disease.
Antigen stool test for assessment of Helicobacter pylori infection in patients with upper gastrointestinal bleeding
Authors: Peitz U. , Leodolter A. , Kahl S. , Agha‐Amiri K. , Wex T. , Wolle K. , Günther T. , Steinbrink B. , Malfertheiner P.
Published: December 2004

Background : Re‐bleeding of Helicobacter pylori‐associated peptic ulcer disease is reduced by H. pylori eradication.

Aim : To validate a non‐invasive test, the Premium Platinum HpSA™ stool test, in patients with upper gastrointestinal bleeding.

Methods : Stool samples of consecutive patients with relevant bleeding from gastric or duodenal ulcers or erosions were collected at initial endoscopy and during the following week. Samples were assessed using the HpSA™ test. H. pylori status was defined by three biopsy‐based reference methods: culture, rapid urease test and histology. It was positive if culture was positive or if rapid urease test and histology were positive.

Results : One hundred and fourteen patients (mean age, 66 years) were included. In accordance with the definition, 56 (49%) were H. pylori positive. The sensitivity and specificity of the first stool sample were 84% and 90%, respectively. The respective values for two samples from consecutive days were 91% and 86%. In comparison with a serum immunoglobulin G antibody enzyme‐linked immunoabsorbent assay, the HpSA™ test showed superior specificity.

Conclusions : The diagnostic accuracy, in particular the sensitivity, of the HpSA™ stool test is reduced by upper gastrointestinal bleeding. The positive predictive value of 89%, however, justifies the initiation of eradication therapy on the basis of a positive stool test. A negative test result should be confirmed by a further diagnostic method.
Diverticular disease of the colon — on the rise: a study of hospital admissions in England between 1989/1990 and 1999/2000
Authors: Kang J. Y. , Hoare J. , Tinto A. , Subramanian S. , Ellis C. , Majeed A. , Melville D. , Maxwell J. D.
Published: December 2004

Background:  Diverticular disease emerged as a common problem in Western countries over the course of the 20th century.

Aims:  To determine the time trends in diverticular disease for hospital admissions in England between 1989/1990 and 1999/2000 and population mortality rates from 1979 to 1999.

Methods:  Hospital Episode Statistics were obtained from the Department of Health and mortality data from the Office for National Statistics.

Results:  Between 1989/1990 and 1999/2000, annual age‐standardized hospital admission rates for diverticular disease increased by 16% for males (from 20.1 to 23.2 per 100 000) and 12% for females (from 28.6 to 31.9 per 100 000). Female rates were significantly higher than male rates throughout the study period. The proportions of admissions with an operation increased by 16% for males (from 22.9% to 24.1%) and 14% for females (from 19.7% to 22.3%). Older patients were less likely to undergo operation than younger patients. In‐patient case fatality rates and population mortality rates remained unchanged.

Conclusions: Admission rates for diverticular disease increased over the study period. The proportion of patients who underwent operation increased, but in‐patient and population mortality rates remained unchanged. With an ageing population, diverticular disease will become an increasingly important clinical problem in England.
Non‐cardiac chest pain: prevalence, risk factors, impact and consulting — a population‐based study
Authors: Eslick G. D. , Jones M. P. , Talley N. J.
Published: December 2004

Background : Little is known about the prevalence and importance of non‐cardiac chest pain in the general population.

Aim : To evaluate the magnitude and impact of this condition.

Methods : A validated self‐report questionnaire was mailed to a sample of 1000 residents of Penrith, selected randomly from the electoral rolls. Symptoms, risk factors, psychological distress, quality of life and demographics were measured.

Results : The response rate was 73% (n = 672; mean age, 46 years; 52% female). Chest pain ever was reported by 39% of the population; 7% reported a history of myocardial infarction and 8% a history of angina. Two hundred and nineteen (33%) cases were classified as non‐cardiac chest pain; only 23% had consulted a physician about chest pain in the previous year. The only independent risk factor for non‐cardiac chest pain was the frequency of heartburn (odds ratio, 1.74; 95% confidence interval, 1.08–2.79; P = 0.02). None of the gastrointestinal (heartburn, dysphagia, acid regurgitation) or psychological (anxiety, depression, neuroticism) risk factors were significantly associated with consulting for non‐cardiac chest pain.

Conclusions : Non‐cardiac chest pain is remarkably common in the general population and negatively impacts on the quality of life. Gastro‐oesophageal reflux disease is a key risk factor for non‐cardiac chest pain in the community. Health care seeking for non‐cardiac chest pain remains unexplained.
The clinical course of fistulating Crohn's disease
Authors: Bell S. J. , Williams A. B. , Wiesel P. , Wilkinson K. , Cohen R. C. G. , Kamm M. A.
Published: December 2004

Aim : To determine the clinical characteristics, management and outcome of Crohn's fistulas from the time of first presentation.

Methods : Patients treated for fistulas 6 years previously were assessed for disease demographics, fistula characteristics and treatment from first presentation to final follow‐up.

Results : Eighty‐seven patients with active Crohn's fistulas were evaluated. The median age was 35 years and the median duration of Crohn's disease was 8 years at study entry. Disease was ileo‐colonic or colonic in 85%, and 65% had rectal involvement. A single fistula was present in one‐third and multiple fistulas in two‐thirds; 65% of fistulas were perianal; 80% of fistulas were complex. After a median follow‐up from the last treatment of 5.9 years, 68% of patients showed healing of all fistulas, 18% showed healing of some fistulas and 14% showed no healing of fistulas. The fistula site did not influence healing. Perianal and recto‐vaginal fistulas took a median of 2.6 years to heal. Half of the complex fistulas required a stoma, resection or proctectomy.

Conclusions : Healing is usually achieved. However, morbidity is great and healing is slow. Proctectomy is required in one‐fifth of patients, and perineal healing is often slow. Defining the perianal fistula anatomy as complex or simple determines the likelihood of healing and the type of surgical approach required.
Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta‐analysis
Authors: Gené E. , Calvet X. , Azagra R. , Gisbert J. P.
Published: December 2004

Background: Triple therapy (proton pump inhibitor, clarithromycin and amoxicillin or an imidazole) is the first‐line treatment for Helicobacter pylori infection. However, the effectiveness of triple therapy is decreasing due to the increase in antibiotic resistance. Quadruple therapy (proton pump inhibitor, tetracycline, metronidazole and a bismuth salt) is a very effective regimen even in areas of high prevalence of antibiotic resistance, and may be an alternative first‐line treatment.

Aim: To compare triple vs. quadruple therapy for the first‐line treatment of H. pylori infection.

Methods: An extensive literature search was performed to identify randomized trials comparing triple vs. quadruple therapy. Selected trials were included in a meta‐analysis using Review Manager 4.1.

Results: Four studies met the inclusion criteria. Eradication rates with quadruple therapy were slightly higher in both the intention‐to‐treat (81% vs. 78%; odds ratio, 0.83; 95% confidence interval, 0.61–1.14) and per protocol (88% vs. 85%; odds ratio, 0.81; 95% confidence interval, 0.55–1.20) analysis, although the differences were not statistically significant. Nor were there significant differences in compliance or adverse effects between the therapies.

Conclusion: Triple and quadruple therapies seem to be roughly equivalent in terms of effectiveness, compliance and side‐effects profile when administered as first‐line treatment for H. pylori infection.
Effect of propranolol and depot lanreotide SR on postprandial and circadian portal haemodynamics in cirrhosis
Authors: Schiedermaier P. , Koch L. , Stoffel‐Wagner B. , Layer G. , Sauerbruch T.
Published: December 2004

Background : Long‐acting somatostatin analogues have been suggested as an alternative to propranolol for the prevention of variceal rebleeding.

Aim : To compare the effectiveness of lanreotide SR, a new depot formulation injected once‐weekly, and propranolol in reducing circadian portal blood flow (PVF) and meal‐stimulated hepatic venous pressure gradient (HVPG) in patients with liver cirrhosis.

Methods : Patients were randomized to receive either lanreotide SR intramuscularly (30 mg once weekly, n = 12) or propranolol (n = 12) orally. Hemodynamic measurements were performed on day 0 and on day 21 after a 3‐week period of drug administration, while patients received three standard oral liquid test meals. On each study day 27 PVF measurements were performed over 24 h and eight measurements of HVPG during the first postprandial period.

Results : Propranolol was more effective than lanreotide SR in reducing baseline HVPG (−21.9 vs. −13.6%, P = 0.04) and meal‐stimulated HVPG (−16.6 vs. −3.8%, P = 0.04). Propranolol reduced circadian PVF significantly by 9.3% (P = 0.03) but not lanreotide SR.

Conclusions : Long‐term treatment with propranolol reduced baseline and postprandial HVPG and circadian PVF, while lanreotide SR did not. The results of our study do not encourage clinical testing of lanreotide SR 30 mg for the prevention of variceal haemorrhage.
Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire on a Chinese population
Authors: Lu C.‐L. , Chen C.‐Y. , Lang H.‐C. , Luo J.‐C. , Wang S.‐S. , Chang F.‐Y. , Lee S.‐D.
Published: December 2004

Background : Irritable bowel syndrome is a common condition seen in Western countries. In Asia, however, it is less known and even less studied.

Aim : To determine the prevalence and social impact of irritable bowel syndrome as well as the health‐seeking behaviour of irritable bowel syndrome patients in Taiwan

Methods : Using the modified Rome II questionnaire, a survey was carried out in a population receiving physical check‐up (n = 2865).

Results : The prevalence of irritable bowel syndrome in Taiwan was 22.1% and 17.5% (κ = 0.73) according to the Rome II and I criteria, respectively. No gender difference was found between subjects with and without irritable bowel syndrome symptoms. Irritable bowel syndrome subjects were likely to undertake an excessive number of physician‐visits (P < 0.01). Such subjects were often absent from work/school, with more days of absenteeism than irritable bowel syndrome‐free subjects (P < 0.01). They also suffered obvious sleep disturbance (P < 0.01). Nearly half of the irritable bowel syndrome subjects were ‘consulters’, and they were more likely to have frequent physician‐visits, suffer from work/school absenteeism, and endure sleep disturbance and bowel symptoms than irritable bowel syndrome nonconsulters (P < 0.05).

Conclusions : Irritable bowel syndrome is common in a Chinese population of Taiwan. Similar to irritable bowel syndrome in the West, it also involves significant social and medical burdens. However, in the irritable bowel syndrome subjects of Taiwan there is no gender difference, and more irritable bowel syndrome subjects will seek physician consultations, which may be due to Taiwan's easily accessible and affordable heath care facilities.
Gastric acid‐suppressive therapy and community‐acquired respiratory infections
Authors: Laheij R. J. F. , Van Ijzendoorn M. C. , Janssen M. J. R. , Jansen J. B. M. J.
Published: December 2004

Background : Bacteria and viruses have been detected in the stomach of patients during acid‐suppressive therapy.

Aim : To investigate whether subjects using acid‐suppressive drugs more often develop community‐acquired respiratory infections when compared to those who do not use acid‐suppressive drugs.

Methods : 700 study subjects were recruited during a single week in December 2002. Information on the prevalence of clinical manifestations of infections and complications in the preceding month was assessed by questionnaire. Furthermore, subjects were asked to report antibiotic therapy and physician visits related to possible infection.

Results : Questionnaires were returned by 405 subjects (58%). Consumption of acid‐suppressive drugs was reported by 91 individuals, of whom 79 used proton‐pump inhibitors (20%) and 12 H2‐receptor antagonists (3%). Overall, 101 (25%) responders reported clinical manifestations of respiratory infection in the preceding month. Subjects using acid‐suppressive drugs were 2.34 times [95% confidence interval (CI) 1.4–4.1] more likely to have clinical manifestations of infection than individuals not using acid‐suppressive drugs. Subjects using acid‐suppressive drugs visited a physician 3.72 times more often (95% CI 2.1–6.8) for an infection and received antibiotic therapy 4.19 times more often (95% CI 2.2–8.1) in comparison to individuals not using acid‐suppressive drugs.

Conclusions : Subjects using acid‐suppressive drugs more often reported community‐acquired respiratory infections in comparison to those who did not use acid‐suppressive drugs.
13C‐methacetin breath test for monitoring hepatic function in cirrhotic patients before and after liver transplantation
Authors: Petrolati A. , Festi D. , De Berardinis G. , Colaiocco‐Ferrante L. , Di Paolo D. , Tisone G. , Angelico M.
Published: December 2004

Background : In patients with chronic liver disease, the measurement of liver function is critical for monitoring disease progression, predicting the prognosis and choosing therapeutic strategies. The 13C‐methacetin breath test is a simple, non‐invasive diagnostic tool based on an inexpensive, non‐toxic substance, which allows the accurate measurement of liver functional reserve.

Aim : To investigate the 13C‐methacetin breath test as a tool to monitor hepatic function in liver transplant candidates and recipients.

Methods : Twenty‐eight cirrhotic patients listed for orthotopic liver transplantation and 10 healthy controls were studied. The 13C‐methacetin breath test (75 mg per os) was performed at baseline and at 12‐week intervals. Intra‐operative measurements were obtained during the liver transplantation procedure in nine patients. Results were expressed as the 13C‐methacetin cumulative oxidation percentage 45 min after substrate ingestion.

Results : The mean 13C‐methacetin cumulative oxidation at 45 min was 16.4 ± 3.5% in healthy controls and 5.4 ± 4.2% in cirrhotic patients at the time of listing. In 11 patients who underwent successful liver transplantation, mean oxidation increased from 3.3 ± 1.6% before transplantation to 17.0 ± 5.2% at 6 months of follow‐up. Variations in methacetine oxidation were closely related to the recovery of liver function. The mean intra‐operative 13C‐methacetin cumulative oxidation increased from 0.1% during the anhepatic phase to 3.7 ± 2.0% 2 h after reperfusion.

Conclusions : The 13C‐methacetin breath test is a simple and potentially useful tool for monitoring hepatic function in cirrhotic patients listed for liver transplantation, and during the intra‐operative and post‐operative phases.
Randomized study of different ‘second‐line’ therapies for Helicobacter pylori infection after failure of the standard ‘Maastricht triple therapy’
Authors: Perri F. , Festa V. , Merla A. , Barberani F. , Pilotto A. , Andriulli A.
Published: December 2004

Background : Triple therapy with proton pump inhibitor, clarithromycin and amoxicillin and, in the event of eradication failure, quadruple therapy with proton pump inhibitor, bismuth, tetracycline and metronidazole have been proposed in Maastricht as the optimal sequential treatment of Helicobacter pylori infection.

Aim : To compare two second‐line regimens with quadruple therapy.

Methods : One hundred and eighty patients with a previous failed course of standard therapy were randomly given one of the following 7‐day treatments: ranitidine bismuth citrate 400 mg b.d. plus amoxicillin 1 g b.d. and tinidazole 500 mg b.d. (RBCAT), pantoprazole 40 mg b.d. plus amoxicillin 1 g b.d. and levofloxacin 500 mg/day (PAL) and pantoprazole 40 mg b.d., bismuth citrate 240 mg b.d., tetracycline 500 mg q.d.s. and metronidazole 500 mg b.d. (PBTM). The eradication rate was assessed by 13C‐urea breath test. Side‐effects and compliance were evaluated by a standardized questionnaire and by counting returned medication.

Results : The RBCAT, PAL and PBTM groups achieved mean intention‐to‐treat eradication rates of 85%, 63% and 83%, respectively (P < 0.05 for PAL vs. either RBCAT or PBTM). Compliance was optimal in all patients, although side‐effects were more commonly observed in the PBTM group than in the other two patient groups (P < 0.0001).

Conclusions : Both RBCAT and PBTM can be used as second‐line therapies. Conversely, PAL did not achieve satisfactory eradication rates.
Role of antibiotic sensitivity testing before first‐line Helicobacter pylori eradication treatments
Authors: Neri M. , Milano A. , Laterza F. , Di Bonaventura G. , Piccolomini R. , Caldarella M. P. , Balatsinou C. , Lapenna D. , Cuccurullo F.
Published: December 2004

Background : The resistance of Helicobacter pylori to antibiotics has been advocated as a major cause of treatment failure, and antimicrobial sensitivity testing has been proposed to improve efficacy; however, its role before first‐line therapy has not been investigated in detail.

Aim : To assess whether antimicrobial sensitivity testing improves the eradication rate of first‐line anti‐Helicobacter treatments and to compare the effectiveness of ranitidine bismuth citrate and omeprazole in the presence of H. pylori resistance to antibiotics.

Methods : Two hundred and forty‐two patients were assigned to either empirical or antimicrobial sensitivity testing‐based treatment; within each group, subjects were further randomized to receive ranitidine bismuth citrate, 400 mg b.d., tinidazole, 500 mg b.d., and clarithromycin, 500 mg b.d., or omeprazole, 20 mg b.d., clarithromycin, 500 mg b.d., and amoxicillin, 1 g b.d., for 1 week, with substitution of the resistant antibiotic in the antimicrobial sensitivity testing‐based treatment group.

Results : Eradication rates were 67% [confidence interval (CI), 55–79%] in the empirical treatment group and 76% (CI, 65–87%) in the antimicrobial sensitivity testing‐based group (P = N.S.). The overall success rate was 60% (CI, 51–69%) with omeprazole and 82% (CI, 73–91%) with ranitidine bismuth citrate (P < 0.03); the latter overcame antibiotic resistance in 12 of 15 strains vs. zero of eight strains by omeprazole.

Conclusions : Antimicrobial sensitivity testing before first‐line treatment does not improve the eradication rate, which is greater when ranitidine bismuth citrate is included in the treatment.
Lansoprazole reduces ulcer relapse after eradication of Helicobacter pylori in nonsteroidal anti‐inflammatory drug users – a randomized trial
Authors: Lai K. C. , Lam S. K. , Chu K. M. , Hui W. M. , Kwok K. F. , Wong B. C. Y. , Hu H. C. , Wong W. M. , Chan O. O. , Chan C. K.
Published: December 2004

Aim : To study whether prophylaxis with lansoprazole could prevent relapse of ulcers after eradication of Helicobacter pylori in patients with NSAID‐related peptic ulcers.

Methods : Patients who presented with peptic ulcers and were found to be infected with H. pylori while receiving NSAIDs were recruited into the study. They received, twice daily, lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg for 1 week, followed by lansoprazole 30 mg daily for 4 weeks. Patients with healed ulcers and H. pylori eradicated were given naproxen 750 mg daily, and randomly assigned to receive lansoprazole 30 mg daily or no treatment for 8 weeks. The primary endpoint was the cumulative recurrence of symptomatic and complicated ulcers.

Results : At the end of the 8‐week treatment period, significantly fewer patients (1/22, 4.5%, 95% confidence interval [CI] 0–23) in the lansoprazole group compared with the group that received H. pylori eradication alone (9/21, 42.9%, 95% CI 22–66) developed recurrence of symptomatic and complicated ulcers (log rank test P = 0.0025).

Conclusions : Lansoprazole significantly reduced the cumulative relapse of symptomatic and complicated ulcers in patients requiring NSAIDs after eradication of H. pylori.
Meta‐analysis: proton pump inhibitors vs. H2‐receptor antagonists — their efficacy with antibiotics in Helicobacter pylori eradication
Authors: Gisbert J. P. , Khorrami S. , Calvet X. , Gabriel R. , Carballo F. , Pajares J. M.
Published: December 2004

Background : It is unknown whether proton pump inhibitors are superior to H2‐receptor antagonists in Helicobacter pylori eradication regimens.

Aim : To perform a meta‐analysis comparing the efficacy of both antisecretors when co‐prescribed with antibiotics.

Methods : Randomized clinical trials comparing proton pump inhibitors vs. H2‐receptor antagonists with the same antibiotics were selected. Data sources included PubMed, the Cochrane Controlled Trials Register and abstracts from congresses up to January 2002. A meta‐analysis was performed by combining the odds ratios.

Results : Twenty studies fulfilled the inclusion criteria. In the intention‐to‐treat analysis, the mean eradication rates with proton pump inhibitors and H2‐receptor antagonists plus antibiotics were 74% [95% confidence interval (CI), 71–76%] and 69% (95% CI, 66–71%), respectively. The odds ratio for this comparison was 1.31 (95% CI, 1.09–1.58). The number needed to treat with proton pump inhibitors to achieve eradication success, compared with H2‐receptor antagonists, was 25. When studies prescribing very high doses of H2‐receptor antagonists (two of the outliers) were excluded, the odds ratio (for proton pump inhibitors vs. H2‐receptor antagonists) increased to 1.37, the number needed to treat decreased to 20 and the heterogeneity between the studies decreased.

Conclusions : Overall, proton pump inhibitors are more effective than H2‐receptor antagonists when prescribed at usual doses with antibiotics to eradicate H. pylori infection.
Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non‐erosive reflux disease
Authors: Frazzoni M. , De Micheli E. , Savarino V.
Published: December 2004

Background : The reason why less than one‐half of patients with gastro‐oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking.

Aim : To clarify whether high levels of supine nocturnal oesophageal acid exposure are associated with complicated reflux disease.

Methods : Ambulatory 24‐h oesophageal pH monitoring was performed in 220 patients with gastro‐oesophageal reflux disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis and 88 with non‐erosive reflux disease). The total, supine nocturnal and upright diurnal percentage acid reflux times were calculated.

Results : The total percentage acid reflux time was significantly greater in complicated reflux disease than in either erosive reflux oesophagitis (P = 0.024) or non‐erosive reflux disease (P = 0.000). These differences were entirely due to a greater supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000, respectively), whereas no difference was observed in the upright diurnal percentage acid reflux time.

Conclusions : Complicated reflux disease is characterized by high levels of supine nocturnal percentage acid reflux time. Prospective studies would be appropriate to clarify whether the normalization of this parameter is relevant to the effective management of this subset of patients with gastro‐oesophageal reflux disease.
Symptoms of gastro‐oesophageal reflux: prevalence, severity, duration and associated factors in a Spanish population
Authors: Diaz‐Rubio M. , Moreno‐Elola‐Olaso C. , Rey E. , Locke G. R. , Rodriguez‐Artalejo F.
Published: December 2004

Aim : To measure the prevalence of gastro‐oesophageal reflux symptoms and to identify associated factors in a representative sample of the Spanish population.

Methods : A telephone survey of 2500 subjects was performed using a validated questionnaire. The association of gastro‐oesophageal reflux symptoms (defined as the presence of heartburn or acid regurgitation) and their clinical characteristics with potential risk factors was summarized using the odds ratios (OR) obtained by multiple logistic regression.

Results : The response rate was 71.2%. The annual prevalence of gastro‐oesophageal reflux symptoms was 31.6%[95% confidence interval (CI), 29.8–33.4] and the weekly prevalence was 9.8% (95% CI, 8.6–10.9). Gastro‐oesophageal reflux symptoms were associated with excess weight (OR, 1.53; 95% CI, 1.23–1.92), obesity (OR, 1.74; 95% CI, 1.30–2.32), the psychosomatic symptom score (OR, 2.98; 95% CI, 2.41–3.67) and the presence of gastro‐oesophageal reflux symptoms in a direct family member (OR, 1.61; 95% CI, 1.17–2.23). Gastro‐oesophageal reflux symptoms of ≥ 10 years' duration were more frequent in obese subjects (OR, 1.92; 95% CI, 1.14–3.22) and those with a direct family member with gastro‐oesophageal reflux symptoms (OR, 2.42; 95% CI, 1.44–4.06). Factors associated with gastro‐oesophageal reflux symptoms of ≤ 1 year duration were a spouse with gastro‐oesophageal reflux symptoms (OR, 2.33; 95% CI, 1.39–3.9) and the consumption of 1–5 aspirins/week (OR, 1.70; 95% CI, 1.01–2.86).

Conclusions : The prevalence of frequent gastro‐oesophageal reflux symptoms in Spain is lower than that observed in other Western populations. The psychosomatic symptom score is the factor most strongly associated with gastro‐oesophageal reflux symptoms. Long‐term gastro‐oesophageal reflux symptoms are associated with certain genetic factors (obesity, family history of gastro‐oesophageal reflux symptoms), whereas short‐term gastro‐oesophageal reflux symptoms are associated with factors of probable environmental nature.
Quality of life in relation to symptoms in patients with gastro‐oesophageal reflux disease — an analysis based on the ProGERD initiative
Authors: Kulig M. , Leodolter A. , Vieth M. , Schulte E. , Jaspersen D. , Labenz J. , Lind T. , Meyer‐Sabellek W. , Malfertheiner P. , Stolte M. , Willich S. N.
Published: December 2004

Aims : To determine the impact of gastro‐oesophageal reflux disease (GERD) on the quality of life, to assess changes in the quality of life during treatment with esomeprazole and to define factors that can predict these changes.

Methods : Patients with GERD (n = 6215) were included in a prospective cohort study (ProGERD). All patients underwent endoscopy and received esomeprazole. At baseline and after 2 weeks of treatment, symptoms and quality of life were assessed. Factors that influenced changes in the quality of life were determined by multiple regression analyses.

Results : At baseline, the quality of life in GERD patients was lower than that in the general population, and was similar to that in patients after acute coronary events. No differences in symptoms or quality of life were observed between the subgroups of patients with non‐erosive GERD, erosive GERD and Barrett's oesophagus. After treatment with esomeprazole, the symptoms and quality of life were improved in all subscales within 2 weeks (P < 0.001). The mean score of the disease‐specific quality of life instrument (Quality of Life in Reflux and Dyspepsia Patients) increased from 4.6 to 6.2 points, representing a highly relevant clinical improvement. The generic quality of life (SF‐36) reached levels similar to those in the general population, but, again, no difference was found between the three different subgroups of GERD patients. The main factors associated with an improvement in the quality of life after treatment were symptom relief, severe erosive reflux disease, absence of extra‐oesophageal disorders, avoidance of non‐steroidal anti‐inflammatory drug intake and positive Helicobacter pylori status.

Conclusions : GERD causes a significant impairment in the quality of life that can be attenuated or normalized within a time period as short as 2 weeks by treatment with esomeprazole. These findings were similar across the whole GERD patient spectrum.
Assessment of oesophageal motor function in patients with dysphagia or chest pain — the Clinical Outcomes Research Initiative experience
Authors: Dekel R. , Pearson T. , Wendel C. , De Garmo P. , Fennerty M. B. , Fass R.
Published: December 2004

Background : Available prospectively acquired data on the distribution of oesophageal motor abnormalities in patients being evaluated for non‐cardiac chest pain and/or dysphagia are relatively scarce.

Aim : To evaluate the distribution of oesophageal motor abnormalities in patients with dysphagia, non‐cardiac chest pain or both using the national Clinical Outcomes Research Initiative (CORI) database.

Methods : The CORI oesophageal motility database originates from 19 community, university and VA medical centres. Data were collected using a computerized motility report‐generating program, combined with the CORI module. Data from each site were encrypted and sent to the CORI National Repository for analysis. The database includes the assessment of the lower and upper oesophageal sphincter function and the motor activity of the oesophageal body.

Results : Five hundred and eighty‐seven consecutive patients who underwent motility studies between 1998 and 2001 were included in the CORI database and analysed for this report. Four hundred and three patients (69%) had dysphagia as their primary indicator for the examination, 140 patients (24%) had non‐cardiac chest pain and 44 patients (7%) had both dysphagia and non‐cardiac chest pain. In all three groups, a normal motility study was the most frequent finding (dysphagia, 53%; chest pain, 70%; both, 55%). The most common motility abnormality in the group with non‐cardiac chest pain was a hypotensive lower oesophageal sphincter (61%). Nutcracker oesophagus and non‐specific oesophageal motility disorders were each diagnosed in only 10% of patients with non‐cardiac chest pain. In patients with dysphagia, ineffective peristalsis was the most common oesophageal dysmotility (27%), followed by achalasia and non‐specific oesophageal motility disorders (18% and 14%, respectively). Achalasia and non‐specific oesophageal motility disorders were the most common oesophageal motility abnormalities in patients with both chest pain and dysphagia (35% and 25%, respectively).

Conclusions : The most common oesophageal motility abnormality in patients with non‐cardiac chest pain is a hypotensive lower oesophageal sphincter; nutcracker oesophagus and non‐specific oesophageal motility disorders are relatively uncommon; the most common oesophageal motility abnormality in patients with dysphagia is ineffective peristalsis and, for those with both dysphagia and non‐cardiac chest pain, it is achalasia.
Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's disease
Authors: Dejaco C. , Harrer M. , Waldhoer T. , Miehsler W. , Vogelsang H. , Reinisch W.
Published: December 2004

Background : Antibiotics and thiopurines have been employed in the management of fistulizing Crohn's disease, although evidence of their efficacy is rare.

Aim : To evaluate, in a prospective, open‐label study, the influence of antibiotics and azathioprine on the clinical outcome of perianal fistulas in patients with Crohn's disease.

Methods : Fifty‐two patients entered the study, starting with an 8‐week regimen of ciprofloxacin (500–1000 mg/day) and/or metronidazole (1000–1500 mg/day). Seventeen patients had already received daily azathioprine (2–2.5 mg/kg) at enrolment, whereas in 14 patients azathioprine was initiated after 8 weeks of antibiotic treatment. Outcome was evaluated by Fistula Drainage Assessment and the Perianal Disease Activity Index at weeks 8 and 20.

Results : Overall, 26 patients (50%) responded to antibiotic treatment, with complete healing in 25% of patients at week 8. The Perianal Disease Activity Index decreased significantly from 8.4 ± 2.9 to 6.0 ± 4.0 (P < 0.0001). At week 20, the outcome was assessed in 49 patients (94%), 29 of whom (59%) had received azathioprine. Response was noted in 17 of the 49 patients (35%), with complete healing in nine patients (18%). Patients who received azathioprine were more likely to achieve a response (48%) than those without immunosuppression (15%) (P = 0.03). The Perianal Disease Activity Index was closely associated with treatment response and perianal disease activity.

Conclusion : Antibiotics are useful to induce a short‐term response in perianal Crohn's disease, and may provide a bridging strategy to azathioprine, which seems to be essential for the maintenance of fistula improvement.
Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn's disease
Authors: Castiglione F. , Rispo A. , Di Girolamo E. , Cozzolino A. , Manguso F. , Grassia R. , Mazzacca G.
Published: December 2004

Background : Small bowel bacterial overgrowth is common in Crohn's disease but its treatment is not clearly defined. Metronidazole and ciprofloxacin are effective antibiotics in active Crohn's disease.

Aim : To investigate the efficacy of metronidazole and ciprofloxacin in the treatment of bacterial overgrowth in patients with Crohn's disease.

Patients and methods : We performed the lactulose breath test in 145 consecutive patients affected by Crohn's disease. Patients positive to the lactulose breath test underwent a glucose breath test to confirm the overgrowth. These patients were randomized in two treatment groups: metronidazole 250 mg t.d.s. (Group A) and ciprofloxacin 500 mg b.d. (Group B), both orally for 10 days. The glucose breath test was repeated at the end of treatment. The clinical outcome after therapy was also recorded.

Results : Bacterial overgrowth was present in 29 patients (20%). Breath test normalization occurred in 13 out of 15 patients treated by metronidazole and in all 14 patients treated by ciprofloxacin (P = ns). In both groups antibiotic treatment induced an improvement of intestinal symptoms: bloating (Group A 85% and Group B 83%), stool softness (44% and 50%), and abdominal pain (50% and 43%).

Conclusions : Small bowel bacterial overgrowth is a frequent condition in Crohn's disease which can be effectively treated by metronidazole or ciprofloxacin.
Glucocorticoid receptor expression in inflammatory bowel disease: evidence for a mucosal down‐regulation in steroid‐unresponsive ulcerative colitis
Authors: Raddatz D. , Middel P. , Bockemühl M. , Benöhr P. , Wissmann C. , Schwörer H. , Ramadori G.
Published: December 2004

Background : Glucocorticoids (GC) play a major role in the attenuation of inflammation. Glucocorticoid receptor (GR) expression is an important determinant of steroid sensitivity.

Aims : To investigate whether GR mRNA expression is altered in inflammatory bowel disease, and whether GR mRNA expression correlates with disease activity and may predict response to GC therapy.

Methods : Mucosal biopsies were taken from 33 patients with ulcerative colitis, 21 with Crohn's disease and 11 controls. Peripheral blood mononuclear cells were isolated from 24 ulcerative colitis and 18 Crohn's disease patients and 11 controls. GR mRNA was measured by quantitative reverse transcriptase polymerase chain reaction (RT‐PCR), and correlated to endoscopic findings, clinical activity and outcome of GC therapy. In a subset of subjects GR localisation was shown by immunohistochemistry.

Results : In patients with inflammatory bowel disease GR expression was not different from controls. However, GR was decreased in biopsies from ulcerative colitis patients with impaired GC response. The inhibitory subtype GRβ was expressed 100–1000 times lower than GRα. GR immunoreactivity was identified in immune and epithelial cells except for colonic crypts.

Conclusion : In inflammatory bowel disease systemic and mucosal GR mRNA expression is not altered. However, in ulcerative colitis patients, low mucosal GR expression may predict the outcome of GC therapy. The low expression of GRβ challenges its role in steroid refractoriness in inflammatory bowel disease.
Empirically derived symptom sub‐groups correspond poorly with diagnostic criteria for functional dyspepsia and irritable bowel syndrome. A factor and cluster analysis of a patient sample
Authors: Eslick G. D. , Howell S. C. , Hammer J. , Talley N. J.
Published: December 2004

Aim : To determine how clusters (groups) of patients with respect to symptoms compare with a clinical diagnosis in patients with irritable bowel syndrome and non‐ulcer dyspepsia.

Methods : All patients who attended a gastroenterology practice at Nepean Hospital were included in the study. All patients received the previously validated Bowel Disease Questionnaire, and were independently assessed by the gastroenterologist. Factor analysis and a k‐means cluster analysis were completed.

Results : The study population comprised 897 patients [320 males (36%) and 577 females (64%)]. Factor analysis identified nine symptom factors: (1) diarrhoea; (2) constipation; (3) dysmotility; (4) dyspepsia/reflux; (5) nausea/vomiting; (6) bowel; (7) meal‐related pain; (8) weight loss; and (9) abdominal pain. A k‐means cluster analysis identified seven distinct subject groups, which included an undifferentiated group: (1) diarrhoea; (2) meal‐related pain; (3) abdominal pain; (4) faecal indicators; (5) nausea/vomiting/weight loss; and (6) constipation. The majority of irritable bowel syndrome patients fitted into two cluster groups [diarrhoea (25%) and constipation (20%)], whereas those with non‐ulcer dyspepsia predominantly fitted into the undifferentiated cluster (34%) and the nausea/vomiting cluster (18%).

Conclusion : This study supports the concept of symptom subgroups, including the subdivision of patients into diarrhoea‐ and constipation‐predominant irritable bowel syndrome.