bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of non‐steroidal anti‐inflammatory drug gastrointestinal complications – review and recommendations based on risk assessment
Authors: Chan F. K. L. , Graham D. Y. 
Published: May 2004

SummaryThe incidence of non‐steroidal anti‐inflammatory drug‐related ulcer complications remains high despite the availability of potent anti‐ulcer drugs and selective cyclo‐oxygenase‐2 inhibitors. Non‐steroidal anti‐inflammatory drug‐related ulcer complications can be minimized by prospective assessment of patients’ baseline risk, rational choice and use of non‐steroidal anti‐inflammatory drugs, and selective use of co‐therapy strategies with gastroprotectives. Current recommendations regarding strategies using anti‐ulcer drugs and cyclo‐oxygenase‐2 inhibitors for prevention of clinical non‐steroidal anti‐inflammatory drug upper gastrointestinal events are largely derived from studies using surrogates such as endoscopic ulcers, erosions, and symptoms in low‐ to average‐risk patients. Conclusions based on surrogate and potentially manipulatable end‐points are increasingly suspect with regard to applicability to clinical situations. This article reviews the risks associated with non‐steroidal anti‐inflammatory drugs including aspirin and includes the effect of the patients’ baseline risk, and the confounding effects of Helicobacter pylori infection. In addition, uncertainties regarding the clinical efficacy of anti‐ulcer drugs and cyclo‐oxygenase‐2 inhibitors against non‐steroidal anti‐inflammatory drug‐related ulcer complications are put into perspective. We propose management strategies based on the risk category: low risk (absence of risk factors) (least ulcerogenic non‐steroidal anti‐inflammatory drug at lowest effective dose), moderate risk (one to two risk factors) (as above, plus an antisecretory agent or misoprostol or a cyclo‐oxygenase‐2 inhibitor), high risk (multiple risk factors or patients using concomitant low‐dose aspirin, steroids, or anticoagulants) (cyclo‐oxygenase‐2 inhibitor alone with steroids, plus misoprostol with warfarin, or plus a proton pump inhibitors or misoprostol with aspirin), and very high risk (history of ulcer complications) (avoid all non‐steroidal anti‐inflammatory drugs, if possible or a cyclo‐oxygenase‐2 plus a proton pump inhibitors and/or misoprostol). The presence of H. pylori infection increases the risk of upper gastrointestinal complications in non‐steroidal anti‐inflammatory drug users by two‐ to fourfold suggesting that all patients requiring regular non‐steroidal anti‐inflammatory drug therapy be tested for H. pylori.
Health‐related quality of life in patients with cardiovascular disease – the effect of upper gastrointestinal symptom treatment
Authors: van Rossum L. G. M. , Laheij R. J. F. , Vlemmix F. , Jansen J. B. M. J. , Verheugt F. W. A. 
Published: May 2004

SummaryBackground : Upper gastrointestinal discomfort decreases the already impaired health status of patients with cardiovascular disease.Aim : To evaluate whether acid suppressive therapy improves health‐related quality of life in patients who developed upper gastrointestinal symptoms after starting low‐dose acetylsalicylic acid.Methods : In a double‐blind, placebo‐controlled randomized trail, cardiac patients using low‐dose (80 mg) acetylsalicylic acid with (n = 142) and without (n = 90) upper gastrointestinal symptoms were included. Patients with symptoms were treated with rabeprazole or placebo for 4 weeks. At baseline and 4 weeks information about gastrointestinal symptoms and health‐related quality of life was assessed.Results : The 73 patients assigned to rabeprazole when compared with 69 patients given placebo reported the same quality of life scores 4 weeks after randomization. The differences in quality of life scores between patients with and without symptoms at baseline remained after 4 weeks. Patients in whom treatment led to complete symptom relief or those who remained symptom‐free reported significantly higher scores for Physical Component Summary (P < 0.01) and Mental Component Summary (P < 0.01), when compared to those with persistent symptoms or new onset symptoms.Conclusion : Proton‐pump inhibitor therapy did not improve quality of life. Upper gastrointestinal symptom relief in itself considerably increased quality of life.
The effect of an empirical trial of high‐dose lansoprazole on symptom response of patients with non‐cardiac chest pain – a randomized, double‐blind, placebo‐controlled, crossover trial
Authors: Bautista J. , Fullerton H. , Briseno M. , Cui H. , Fass R. 
Published: May 2004

SummaryBackground : Empirical trial with high‐dose omeprazole has been shown to be a sensitive tool for diagnosing patients with gastro‐oesophageal reflux disease‐related non‐cardiac chest pain.Aim : To determine the clinical value of an empirical trial of high‐dose lansoprazole in detecting patients with gastro‐oesophageal reflux disease‐related non‐cardiac chest pain.Methods : Patients who were referred by a cardiologist after a comprehensive evaluation, with at least three episodes per week of unexplained chest pain as the predominant symptom, were enrolled into the study. Oesophageal mucosal disease was determined by upper endoscopy followed by 24‐h oesophageal pH monitoring to assess acid exposure. Patients were then randomized to either placebo or lansoprazole 60 mg am and 30 mg pm for 7 days. After a washout period of 1 week, patients crossed over to the other arm of the study for an additional 7 days. Patients completed a daily diary assessing severity and frequency of chest pain as the predominant symptom throughout the baseline treatment and washout periods. The lansoprazole empirical trial was considered diagnostic if chest pain score improved ≥50% than baseline.Results : Of the 40 patients with non‐cardiac chest pain that were enrolled, 18 (45%) had erosive oesophagitis and/or abnormal pH test (gastro‐oesophageal reflux disease‐positive) and 22 (55%) had both tests negative (gastro‐oesophageal reflux disease‐negative). Of the gastro‐oesophageal reflux disease‐positive patients, 14 (78%) had significantly higher symptom improvement on lansoprazole than on placebo (22%) (P = 0.0143). Of the gastro‐oesophageal reflux disease‐negative group, two (9.1%) markedly improved on the medication and eight (36.3%) on placebo (P = 0.75). The sensitivity and specificity of the lansoprazole empirical trial was 78 and 80%, respectively. By day 2, 12 (85.7%) of the gastro‐oesophageal reflux disease‐related non‐cardiac chest pain responders had either complete or almost complete symptom resolution.Conclusions : The lansoprazole empirical trial is highly sensitive and specific for diagnosing gastro‐oesophageal reflux disease‐related non‐cardiac chest pain patients. The trial enables diagnosing most of the responders within the first 2 days and thus a shorter duration of therapy may be considered in a subset of non‐cardiac chest pain patients.
Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole
Authors: Freston J. W. , Pilmer B. L. , Chiu Y.‐L. , Wang Q. , Stolle J. C. , Griffin J. S. , Lee C. Q. 
Published: May 2004

SummaryAim : To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally.Methods : Twenty‐nine subjects received lansoprazole orally on days 1–7 and intravenous lansoprazole in NaCl on days 8–14. Blood samples were collected on days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin‐stimulated maximal acid output were determined on days −1, 8, 9 and 15. Thirty‐six different subjects received one of four regimen sequences: intravenous lansoprazole in NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo, each for 5 days. Twenty‐four hour intragastric pH was recorded on days 1 and 5.Results : Intravenous and per oral lansoprazole for 7 days produced equivalent basal acid output and maximal acid output suppression. Pharmacokinetics and mean pH values with intravenous lansoprazole in NaCl or polyethylene glycol were equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6 that were significantly greater than did per orally.Conclusions : Intravenous lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene glycol, and its onset of action is faster than per oral lansoprazole.
Laboratory markers predict bone loss in Crohn's disease: relationship to blood mononuclear cell function and nutritional status
Authors: Trebble T. M. , Wootton S. A. , Stroud M. A. , Mullee M. A. , Calder P. C. , Fine D. R. , Moniz C. , Arden N. K. 
Published: May 2004

SummaryBackground : Crohn's disease is associated with reduced bone density. The power of simple markers of systemic inflammation to identify higher rates of bone loss, in Crohn's disease, is uncertain. This relationship and the role of circulating (peripheral blood) mononuclear cells were investigated in a case–control study.Methods : Urinary deoxypyridinoline/creatinine and serum osteocalcin concentrations were compared in male and premenopausal females with ‘active’ Crohn's disease (C‐reactive protein ≥ 10 and/or erythrocyte sedimentation rate ≥ 20) (n = 22) and controls with ‘quiescent’ Crohn's disease (C‐reactive protein < 10 and erythrocyte sedimentation rate < 20) (n = 21). No patients were receiving corticosteroid therapy. Production of tumour necrosis factor‐α, interferon‐γ and prostaglandin E2 by peripheral blood mononuclear cells were measured.Results : Active Crohn's disease was associated with a higher deoxypyridinoline/creatinine (P = 0.02) and deoxypyridinoline/creatinine:osteocalcin ratio (P =0.01) compared with quiescent Crohn's disease, but similar osteocalcin (P = 0.24). These were not explained by vitamin D status, dietary intake or nutritional status. However, production of interferon‐γ by concanavalin A‐stimulated peripheral blood mononuclear cells was lower in active Crohn's disease (P = 0.02) and correlated negatively with the deoxypyridinoline/creatinine:osteocalcin ratio (r = −0.40, P = 0.004).Conclusion : In Crohn's disease, raised C‐reactive protein and erythrocyte sedimentation rate may indicate higher rates of bone loss and, if persistent, the need to assess bone mass even where disease symptoms are mild. This may be partly explained by altered production of interferon‐γ by peripheral blood mononuclear cells.
Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second‐line medical therapy or surgery
Authors: Ho G. T. , Mowat C. , Goddard C. J. R. , Fennell J. M. , Shah N. B. , Prescott R. J. , Satsangi J. 
Published: May 2004

SummaryBackground : The failure rate of medical therapy in severe ulcerative colitis is high. A risk index, to aid the identification of patients of not responding at an early stage to intravenous corticosteroid therapy, would be useful to facilitate second‐line treatment or surgery.Methods : We recruited 167 consecutive patients with severe ulcerative colitis between January 1995 and March 2002; and employed multiple logistic regression to analyse parameters within the first 3 days of medical therapy. We applied statistical modelling to formulate a risk score according to the likelihood of medical failure.Results : Sixty‐seven (40%) patients failed to respond to medical therapy. Multiple logistic regression analysis identified mean stool frequency and colonic dilatation within the first 3 days and hypoalbuminaemia as independent predictors of outcome (P < 0.001, 0.001 and 0.002 respectively). A numerical risk score was formulated based on these variables. Patients with scores of 0–1, 2–3 and ≥4 had a medical therapy failure rate of 11%, 43% and 85% respectively. Receiver–operator characteristic analysis of this score yielded area under curve of 0.88, with a sensitivity of 85% and specificity of 75% using score ≥4 in predicting non‐response.Conclusion : This risk score allows the early identification of patients with severe ulcerative colitis who would be suitable for second‐line medical therapy or surgery.
Effect of splitting the dose of esomeprazole on gastric acidity and nocturnal acid breakthrough
Authors: Hammer J. , Schmidt B. 
Published: May 2004

SummaryBackground : Twice‐daily dosing is increasingly used to improve gastric acid control, although not all proton‐pump inhibitors are more effective when doses are split. Standard dose esomeprazole provides better gastric acid control than other standard dose proton‐pump inhibitors.Aims : To compare the effect of standard dose esomeprazole (1 × 40 mg) with 20 mg b.d. on gastric acidity.Methods : Thirteen healthy subjects participated in this crossover study, receiving esomeprazole 2 × 20 mg and 1 × 40 mg for 7 days in random order with a washout period of at least 7 days. Gastric 24‐h pH was measured on days 1, 2 and 6.Results : Median gastric 24‐h pH was higher during 2  × 20 mg esomeprazole on day 2 (P < 0.01), no differences were detected on day 6. Night‐time gastric acid suppression was significantly improved by 2 × 20 mg esomeprazole on all study days (P < 0.05). Nocturnal acid breakthrough was observed on all study days in subjects receiving 1 × 40 mg, but in only 85% (first night), 64% (second night), and 45% of subjects (sixth night) with 2 × 20 mg (P < 0.05).Conclusion : Splitting the esomeprazole dose improves initial acid suppression, this effect starts at the first night. Maximal benefit is achieved on day 2, while the effect on night‐time acid control is detectable during the entire first week of treatment.
New pharmacological agents for the treatment of gastro‐oesophageal reflux disease
Authors: Vakil N. 
Published: May 2004

SummaryProton pump inhibitors, which act at the terminal point of acid secretion – the H+, K+‐ATPase – are currently the most effective pharmacological treatments available for reflux disease. Despite the efficacy of the proton pump inhibitors, there is still potential for clinical improvement in gastro‐oesophageal reflux disease pharmacotherapy. Faster onset of complete acid inhibition and improved duration of efficacy are two potential areas for improvement A number of novel pharmaceutical agents are currently undergoing clinical evaluation for the treatment of gastro‐oesophageal reflux disease. These include transient lower oesophageal sphincter relaxation‐reducing agents, serotonergic agents/prokinetics, potassium‐competitive acid blockers, mucosal protectants, histamine H3 agonists and anti‐gastrin agents. One or more of these drug groups may represent the future medical therapy for gastro‐oesophageal reflux disease, should they prove effective in the clinical setting. This review summarizes the state of the art with these agents.
Comparative pharmacokinetics of equimolar doses of 5‐aminosalicylate administered as oral mesalamine (Asacol) and balsalazide: a randomized, single‐dose, crossover study in healthy volunteers1
Authors: Sandborn W. J. , Hanauer S. B. , Buch A. 
Published: May 2004

SummaryBackground : Existing pharmacokinetic data are insufficient to determine whether a delayed‐release formulation of mesalamine (Asacol) results in greater systemic exposure to 5‐aminosalicylic acid and its major metabolite N‐acetyl‐5‐aminosalicylic acid than a prodrug (balsalazide).Aim : To determine the pharmacokinetic parameters of 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid from equimolar doses of 5‐aminosalicylic acid administered as Asacol and balsalazide.Methods : Nineteen healthy volunteers completed an open‐label, single‐dose, randomized, crossover study comparing the pharmacokinetics of 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid from equimolar doses of 5‐aminosalicylic acid (800 mg) administered as Asacol (800 mg) and balsalazide (2250 mg). Plasma and urine samples were analysed for 5‐aminosalicylic acid, N‐acetyl‐5‐aminosalicylic acid, and balsalazide (urine only) using high‐performance liquid chromatography methods with mass spectrometric detection. Pharmacokinetic parameters assessed for 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid included: percentage of dose excreted in urine (Ae%), area under the plasma concentration–time curve (AUCtlast); and maximum plasma concentration (Cmax).Results : The geometric mean total (5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid) urinary excretion values (Ae%) of Asacol and balsalazide were 19.26 and 19.31% (P = 0.98). The geometric mean Ae% values of 5‐aminosalicylic acid for Asacol and balsalazide were 0.39 and 0.37% (P = 0.78); the geometric mean Ae% values of N‐acetyl‐5‐aminosalicylic acid for Asacol and balsalazide were 18.78 and 18.83% (P = 0.98). The geometric mean 5‐aminosalicylic acid AUC(tlast) values for Asacol and balsalazide were 3295 and 3449 ng h/mL (P = 0.85); the geometric mean N‐acetyl‐5‐aminosalicylic acid AUC(tlast) values for Asacol and balsalazide were 15 364 and 16 050 ng h/mL (P = 0.69). The geometric mean 5‐5‐aminosalicylic acid Cmax values for Asacol and balsalazide were 319 and 348 ng/mL (P = 0.80); the geometric mean N‐acetyl‐5‐aminosalicylic acid Cmax values for Asacol and balsalazide 927 and 1009 ng/mL (P = 0.67).Conclusions : The systemic absorption of 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid from Asacol and balsalazide are comparable based upon plasma pharmacokinetic parameters and urinary excretion values.
Mutations in the NOD2/CARD15 gene in Crohn's disease are associated with ileocecal resection and are a risk factor for reoperation
Authors: Büning C. , Genschel J. , Bühner S. , Krüger S. , Kling K. , Dignass A. , Baier P. , Bochow B. , Ockenga J. , Schmidt H. H.‐J. , Lochs H. 
Published: May 2004

SummaryBackground : Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease.Aims : To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease.Methods : We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters.Results : In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01).Conclusions : Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.
Fluoride, calcium and magnesium intake in children living in a high‐fluoride area in Ethiopia. Intake through food
Authors: Malde M. K. , Zerihun L. , Julshamn K. , Bjorvatn K. 
Published: May 2004

Summary.  Objective.  The aim of this study was to assess the daily dietary fluoride intake in children living in two neighbouring villages in the Wonji Shoa Sugar Estate, a rural part of the Ethiopian Rift Valley.Methods.  The villages depended on water from different sources: Village A used either river water (Awash River, with 1·8 mg F‐/L) or ground water (2·1 mg F‐/L), while village K was served ground water with 14 mg F‐/L. Fifteen fully weaned children below the age of 5 years were selected in each of the villages. Over a four‐day period the total food intake for these children was assessed by using a duplicate portion technique. The food was analysed for fluoride by using a fluoride ion‐selective electrode after the dry ashing. Furthermore, the energy of the food was measured, as well as the calcium and magnesium contents (atomic absorption spectrometry after microwave digestion with nitric acid and hydrogen peroxide). The mothers gave a description of the ingredients used for preparing the food. Relevant background information concerning food habits, etc. was collected through a food frequency questionnaire.Results.  This study shows that considerable amounts of fluoride may be retained in food prepared on high‐fluoride water. In village A, food contributed 2·3 mg F‐/day, while a dietary fluoride intake of 4·8 mg/day was found in children in village K. Interestingly, the sevenfold higher fluoride concentration of the water used for food preparation in village K compared to village A, gave only a doubling in fluoride intake through food. Calcium intake was relatively low while magnesium intake was above the recommended level.Conclusion.  As the energy intake by both groups was low, some systematic underreporting might be suspected. Thus, the fluoride intake in the group may be even higher than what was actually found in this study.
Comparison of the efficacy of chemomechanical caries removal (Carisolv‘) with that of conventional excavation in reducing the cariogenic flora
Authors: Azrak B. , Callaway A. , Grundheber A. , Stender E. , Willershausen B. 
Published: May 2004

Summary.  Objectives.   The usage of minimally invasive procedures and attention to patient comfort are of great importance, especially for dental treatment in small children. This has led to the development of chemomechanical methods for caries removal. The aim of this study was to compare the efficacy of chemomechanical caries removal with that of conventional excavation in reducing the count of the cariogenic flora.Design and setting.  Subjects for this study were chosen from children admitted to dental clinic for restorative procedures under general anaesthesia.Samples and methods.  Twenty‐one children (mean age 43·5 ± 12·0 months) with early childhood caries were included in this study. Two primary teeth with comparable degrees of carious destruction were chosen in each child (n = 42) for caries removal with Carisolv‘ or by means of rotary instruments. Samples from carious dentine were taken with a sterile scraping instrument, then all softened dentine was removed and a second sample was taken. All samples (n = 84) were serially diluted and plated on two different nutrient agar plates.Results.  After 24 h of incubation, colony forming units were determined for total bacterial counts and lactobacilli. Twelve per cent of the samples from carious dentine contained more than 106 bacteria, 23·8% contained more than 105 lactobacilli. Both methods of caries removal produced a statistically significant reduction in the bacterial counts (P = 0·0001). In at least 90·5% of the samples taken after the removal, the total bacterial count was below 102, and in 95·2% lactobacilli fell below 102.Conclusion.  These results indicate that the efficacy of chemomechanical removal of carious dentine in children by means of Carisolv‘ is comparable to the results obtained by conventional methods, and thus might serve as a suitable alternative.