bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous esomeprazole 40 mg vs. intravenous lansoprazole 30 mg for controlling intragastric acidity in healthy adults
Authors: PISEGNA J. R. , SOSTEK M. B. , MONYAK J. T. , MINER P. B. 
Published: July 2010

SummaryBackground  Intravenous (IV) formulations of proton pump inhibitors are effective for patients in whom oral therapy is not appropriate.Aim  To compare IV esomeprazole and IV lansoprazole for the control of intragastric pH.Methods  In this open‐label crossover study, healthy, Helicobacter pylori‐negative adults were randomized to one of two treatment sequences, each consisting of two 5‐day dosing periods of IV esomeprazole 40 mg or IV lansoprazole 30 mg. Twenty‐four‐hour intragastric pH monitoring was conducted on days 1 and 5 of each dosing period.Results  On days 1 and 5, intragastric pH was >4.0 significantly longer with esomeprazole than lansoprazole (least‐squares means: day 1, 40.0% vs. 33.6%; day 5, 61.9% vs. 45.4%; both P < 0.0001). During the first 4 h of pH monitoring, intragastric pH was >4.0 significantly longer on days 1 and 5 with esomeprazole than lansoprazole (P < 0.0001). Kaplan–Meier estimates of median hours to stable pH >4.0 were 4.92 for esomeprazole and 5.75 for lansoprazole (P = 0.0014 for test on Gehan scores).Conclusion  In healthy adults, IV esomeprazole 40 mg controlled intragastric acidity faster and more effectively than IV lansoprazole 30 mg.
The utility of flexible sigmoidoscopy after a computerized tomographic colonography revealing only rectosigmoid lesions
Authors: YOUNG P. E. , GENTRY A. B. , CASH B. D. 
Published: July 2010

SummaryBackground  Identifying polyps by computerized tomographic colonography typically prompts colonoscopy, increasing its cost, risk and inconvenience. Many polyps are confined to the rectosigmoid and theoretically amenable to resection via flexible sigmoidoscopy.Aim  To determine the prevalence of advanced proximal colonic neoplasia when computerized tomographic colonography reveals only rectosigmoid polyps, and characterize the yield of polypectomy via flexible sigmoidoscopy in such patients.Methods  Subjects underwent computerized tomographic colonography and colonoscopy with segmental unblinding. Patients with only rectosigmoid findings by computerized tomographic colonography were identified retrospectively. Flexible sigmoidoscopy findings were estimated by including lesions distal to the descending/sigmoid colon junction during colonoscopy. Proximal lesions were also reviewed. Advanced lesions were defined as: adenocarcinoma, tubular adenoma >1 cm, ≥3 tubular adenomas, tubulovillous histology or high‐grade dysplasia.Results  By computerized tomographic colonography, 15% (203 of 1372) had only rectosigmoid polyps. Concomitant lesions in the proximal colon were seen in 32% (64 of 203) during colonoscopy. Advanced proximal neoplasia occurred in 2% (three of 203) with only rectosigmoid polyps on computerized tomographic colonography.Conclusions  Using flexible sigmoidoscopy to follow‐up computerized tomographic colonography demonstrating only rectosigmoid polyps would eliminate 15% of subsequent colonoscopies. This strategy carries a small risk of missed proximal advanced neoplasia. This miss rate appears comparable to that of colonoscopy alone. Further study on the cost‐effectiveness of this approach is warranted.
Coeliac disease: a biopsy is not always necessary for diagnosis
Authors: HILL P. G. , HOLMES G. K. T. 
Published: July 2010

SummaryBackground  In view of the high diagnostic accuracy of immunoglobulin‐A‐tissue transglutaminase antibodies for detecting coeliac disease, we have explored whether a small bowel biopsy is always required to establish the diagnosis.Aim  To define the transglutaminase antibody level giving a positive predictive value for coeliac disease of 100% and to subsequently assess the proportion of new diagnoses of coeliac disease having such a result.Methods  The Celikey kit (Phadia GmbH, Frieburg, Germany) was used to measure transglutaminase antibody levels.Results  All patients with transglutaminase antibody levels >30 U/mL, i.e. 10 × upper limit of normal in 2002/2003 had characteristic small bowel mucosal lesions. In a subsequent audit, 58% of 112 new diagnoses of coeliac disease in 2004/2005 had levels above this cut‐off value.Conclusions  We have shown that a transglutaminase antibody level can be defined which gives a positive predictive value of 100% for coeliac disease. From published data, these observations can be extended to most second‐generation transglutaminase antibody kits. Our data provide further evidence that diagnostic guidelines could be modified so that small bowel biopsy is no longer regarded as mandatory in patients with such high transglutaminase antibody levels. This will avoid an invasive procedure and lead to a more rapid diagnosis and earlier treatment for over half of the new patients with coeliac disease.
Clinical trial: comparison of the gastrointestinal safety of lumiracoxib with traditional nonselective nonsteroidal anti‐inflammatory drugs early after the initiation of treatment – findings from the Therapeutic Arthritis Research and Gastrointestinal Event Trial
Authors: HAWKEY C. J. , WEINSTEIN W. M. , STRICKER K. , MURPHY V. , RICHARD D. , KRAMMER G. , REBULI R. 
Published: July 2010

SummaryBackground  The large (n = 18 325) Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) study demonstrated a significant gastrointestinal benefit with lumiracoxib 400 mg o.d. (4× the recommended dose in osteoarthritis) vs. naproxen 500 mg b.d. or ibuprofen 800 mg t.d.s.Aim  To investigate how early a reduction in ulcer complications could be detected with lumiracoxib vs. nonselective nonsteroidal anti‐inflammatory drugs in TARGET.Methods  Pointwise 95% confidence intervals were generated for the between‐treatment differences in Kaplan–Meier estimates for definite or probable upper gastrointestinal ulcer complications (ulcer complications) and for all ulcers.Results  In patients not on aspirin, there was a significant reduction in all ulcers by day 8 and in ulcer complications by day 16 with lumiracoxib compared with both nonselective nonsteroidal anti‐inflammatory drugs combined, by day 6 (all ulcers) and day 14 (ulcer complications) vs. naproxen and by day 32 (all ulcers) and day 33 (ulcer complications) vs. ibuprofen.Conclusion  Even with short‐term use, there are gastrointestinal safety benefits for lumiracoxib vs. nonselective nonsteroidal anti‐inflammatory drugs.
Clinical trial: individualized treatment duration for hepatitis C virus genotype 1 with peginterferon‐alpha 2a plus ribavirin
Authors: TANG K. H. , HERRMANN E. , PACHIADAKIS I. , PAULON E. , TATMAN N. , ZEUZEM S. , NAOUMOV N. V. 
Published: July 2010

SummaryBackground  Individualized treatment regimens, taking into account the heterogeneity of patients with chronic hepatitis C, are needed to improve treatment outcomes.Aim  To investigate prospectively the period of undetectable viraemia required for a high rate of sustained virological response in patients with chronic hepatitis C genotype 1 and the relationship to early viral kinetics.Methods  Forty‐five chronic hepatitis C genotype 1 patients were given peginterferon‐alpha 2a plus ribavirin. Viraemia and hepatocyte HCV‐RNA levels were quantified using a TaqMan assay. Beyond the first time point of undetectable viraemia (<20 IU/mL) between baseline and treatment week 12, 32 of 45 (71%) patients were randomized to additional 12 weeks (G12); 24 weeks (G24) or 36 weeks therapy (G36). The remaining 13 patients received 48 weeks’ treatment (G48).Results  The sustained virological response rates were: G12 – five of 11 (45%); G24 – eight of 10 (80%); G36 – eight of 11 (73%); G48 – four of 13 (31%). The anti‐viral efficacy (ε) and treatment‐induced loss of infected hepatocytes (Mδ), were significantly higher in patients with early viral clearance. In G12, patients with sustained virological response had lower baseline viraemia than those who relapsed.Conclusions  Early viraemia clearance is a better marker than baseline viral load and differentiates chronic hepatitis C genotype 1 with high or low probability of sustained virological response. In patients with viraemia clearance within 12 weeks of starting peg‐interferon/ribavirin therapy, an additional period of undetectable viraemia of minimum 24 weeks is required for high sustained virological response.
Genetic polymorphisms of tumour necrosis factor receptor superfamily 1A and 1B affect responses to infliximab in Japanese patients with Crohn’s disease
Authors: MATSUKURA H. , IKEDA S. , YOSHIMURA N. , TAKAZOE M. , MURAMATSU M. 
Published: July 2010

SummaryBackground  Tumour necrosis factor alpha is the key inflammatory cytokine involved in the pathogenesis of Crohn’s disease. Infliximab, a chimaeric monoclonal antibody of tumour necrosis factor‐α is successfully used for the treatment of Crohn’s disease, although the response to infliximab therapy differs among patients. The genetic background of the individual may partially explain the differences of the responsiveness.Aim  To investigate whether the polymorphisms in these genes are associated with the response to infliximab treatment as tumour necrosis factor‐α exerts its biological activity through TNF receptor superfamily 1A and 1B.Methods  Eighty Crohn’s disease patients were enrolled in the study and classified into responder and nonresponder according to the efficacy of infliximab treatment. Single nucleotide polymorphisms of TNF receptor superfamily 1A (rs767455 and rs4149570) and TNF receptor superfamily 1B (rs1061622, rs1061624 and rs3397) were determined.Results  The minor allele carrier of rs767455 showed a significant association with a lack of efficacy compared to the major genotype (OR = 0.26; 95% CI: 0.08–0.91). A TNF receptor superfamily 1B haplotype inferred by rs1061624 and rs3397 also showed significant differences in the distribution between responder and nonresponder (P = 0.01).Conclusion  These results suggest that tumour necrosis factor receptor genotypes may be involved in the different responses to infliximab in Japanese patients with Crohn’s disease.
Review article: gastroparesis
Authors: PATRICK A. , EPSTEIN O. 
Published: July 2010

SummaryBackground  Gastroparesis is a chronic disorder caused by stomach pump failure and characterized by profound nausea, vomiting and epigastric pain. Most often, the cause is unapparent and of the known associations, diabetes is the most common. Diagnosis is usually made using an isotope‐labelled test meal. Treatment is incremental and includes education, dietary support, prokinetic and antiemetic agents. There are novel approaches including gastric neurostimulation.Aim  To review current concepts of gastric motor function, aetiology, investigation and treatment of gastroparesis.Methods  A systematic web‐based review of the literature was undertaken using a lexicon of terms associated with gastroparesis.Results  There are few controlled studies of this condition. Little is known about causation or underlying nerve, muscle or pacemaker pathology. Idiopathic gastroparesis occurs most commonly in women and gastric emptying is often abnormal in diabetes. Isotopic gastric scintigraphy remains the gold standard investigation, but alternative tests are being developed. Treatment is multimodal and includes education, and nutritional support. There are no adequately powered controlled trials to support a particular drug regimen. In intractable gastroparesis, gastric neurostimulation appears to offer benefit.Conclusion  Despite a significant progress in the past decade, further controlled trials are required into the therapeutic options available for treating this intriguing condition.
Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug‐induced liver injury
Authors: GARCÍA‐CORTÉS M. , LUCENA M. I. , PACHKORIA K. , BORRAZ Y. , HIDALGO R. , ANDRADE R. J. ,   ON BEHALF OF THE SPANISH GROUP FOR THE STUDY OF DRUG‐INDUCED LIVER DISEASE (GRUPO DE ESTUDIO PARA LAS HEPATOPATÍAS ASOCIADAS A MEDICAMENTOS, GEHAM)
Published: July 2010

SummaryBackground  Causality assessment in hepatotoxicity is challenging. The current standard liver‐specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug‐induced liver injury.Aim  To compare the Naranjo method with the standard liver‐specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity.Methods  Two hundred and twenty‐five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between‐observer and between‐scale differences using percentages of agreement and the weighted kappa (κw) test.Results  A total of 249 ratings were generated. Between‐observer agreement was 45% with a κw value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, κw: 0.71). Concordance between the two scales was 24% (κw: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability.Conclusion  The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.
Response rate and predictors of response in a short‐term empirical trial of high‐dose rabeprazole in patients with globus
Authors: SINN D. H. , KIM J. H. , KIM S. , SON H. J. , KIM J. J. , RHEE J. C. , RHEE P.‐L. 
Published: July 2010

SummaryBackground  Although the aetiology of globus (the sensation of a lump in the throat) remains unclear, gastro‐oesophageal reflux disease is associated with globus. A short‐term trial with a high‐dose proton pump inhibitor has been shown to be a sensitive tool for diagnosing gastro‐oesophageal reflux disease.Aim  To see whether patients with globus symptom responded to short‐term high‐dose rabeprazole trial and assess predictors of symptom response.Methods  Sixty‐four patients with globus symptom were analysed. Patients received rabeprazole 20 mg b.d. for 14 days. Patients completed a daily diary assessing the severity and frequency of globus.Results  Forty‐one patients (64%) were diagnosed clinically with gastro‐oesophageal reflux disease. Based on the pH testing and endoscopy, the prevalence of gastro‐oesophageal reflux disease was 22% (14 of 64). The globus symptom score was significantly higher in patients with gastro‐oesophageal reflux disease compared with patients without gastro‐oesophageal reflux disease (P = 0.004). Two patients (3%) had complete resolution and 22 (34%) had more than a 50% improvement in the globus symptom score. Endoscopic findings (P = 0.714), pathological acid exposure on pH testing (P = 0.741) or baseline gastro‐oesophageal reflux disease symptoms (P = 0.606) were not associated with improvement of globus symptom.Conclusion  While gastro‐oesophageal reflux disease may be an aggravating factor in patients with globus, it does not appear to be the sole cause of globus symptom.
Clinical trial: randomized study of clarithromycin versus placebo in active Crohn’s disease
Authors: LEIPER K. , MARTIN K. , ELLIS A. , WATSON A. J. M. , MORRIS A. I. , RHODES J. M. 
Published: July 2010

SummaryBackground  Crohn’s disease is characterized by defective innate immune responses to intestinal bacteria. Clarithromycin is a broad‐spectrum antibiotic that has good penetration into macrophages.Aim  To assess the efficacy of clarithromycin in active Crohn’s disease.Methods  Patients with Crohn’s disease activity index > 200 and serum C‐reactive protein ≥ 10 mg/L were randomized to receive clarithromycin 1 g o.d. or placebo for 3 months. Patients taking more than 10 mg/day prednisolone or 3 mg/day budesonide were excluded. Primary outcome was remission (CDAI ≤ 150) or response (fall in CDAI ≥ 70 from pre‐treatment level) at 3 months.Results  The trial was stopped after 41 patients had been recruited because of poor overall efficacy. There was no difference in combined remission or response rates at 3 months between clarithromycin: 26% (five of 19) and placebo: 27% (six of 22) (P = 1.00). The mean (s.d.) fall in Crohn’s disease activity index was 35 (80) clarithromycin and −2 (114) placebo (P = 0.24). However, post hoc analysis showed a significant difference in response/remission determined by Crohn’s disease activity index after 1 month: 53% (10 of 19) clarithromycin vs. 14% (three of 22) placebo (P = 0.01).Conclusion  Clarithromycin 1 g for 3 months is ineffective in active Crohn’s disease but possible benefit was observed at 1 month, suggesting that an initial effect may be attenuated by subsequent bacterial resistance.
Stem cell mobilization and collection in patients with liver cirrhosis
Authors: LORENZINI S. , ISIDORI A. , CATANI L. , GRAMENZI A. , TALARICO S. , BONIFAZI F. , GIUDICE V. , CONTE R. , BACCARANI M. , BERNARDI M. , FORBES S. J. , LEMOLI R. M. , ANDREONE P. 
Published: July 2010

SummaryBackground  Bone marrow‐derived stem cells (BMSC) and granulocyte colony‐stimulating factor (G‐CSF) have been proved to contribute to tissue regeneration after liver injury.Aims  To test the safety of G‐CSF and define the exact dose capable of mobilizing BMSC in the majority of patients with liver cirrhosis; and to assess the feasibility of leukapheresis to collect BMSC from peripheral blood.Methods  In this study, we treated 18 patients affected by liver cirrhosis with increasing doses of G‐CSF to mobilize CD34+ and CD133+ BMSC into the peripheral blood.Results  The dose‐finding phase demonstrated that 15 μg/kg/day of G‐CSF is the optimal dose to mobilize both CD34+ and CD133+ stem cells. Circulating BMSC were collected by a single step leukapheresis in three patients and the mean number of CD34+ and CD133+ cells cryopreserved was 1.3 ± 0.7 and 1.2 ± 0.5 × 106/kg, respectively. No severe adverse events were observed during the drug administration and stem cell collection. Noteworthy is, none of the patients showed a significant modification of liver function.Conclusions  Our study demonstrates that G‐CSF administration and BMSC collection from the peripheral blood is possible and safe in patients with liver cirrhosis. The optimal dose to mobilize BMSC in cirrhotics is 15 μg/kg/day. At this dose, G‐CSF does not seem to modify the residual liver function in cirrhotic patients.
Time trends in first‐diagnosis rates of colorectal adenomas: a 24‐year population‐based study
Authors: COTTET V. , JOOSTE V. , BOUVIER A.‐M. , MICHIELS C. , FAIVRE J. , BONITHON‐KOPP C. 
Published: July 2010

SummaryBackground  Little is known about the descriptive epidemiology of colorectal adenomas diagnosed in the population.Aim  To describe time trends in the rate of first diagnosis of colorectal adenomas and estimate the proportion of adenoma‐bearing individuals detected over a 24‐year period.Methods  A total of 11 027 patients were first‐diagnosed with colorectal adenomas among Côte‐d’Or residents (France) between 1976 and 1999. Annual percentage changes were estimated using a Poisson regression model. The proportion of diagnosed adenoma‐bearing individuals was estimated using the prevalence of adenomas in an autopsy study performed in the area.Results  Standardized diagnosis rates were 89.6/100 000 men and 50.3/100 000 women. During the period 1976–1993, diagnosis rates significantly increased with annual percentage changes in men and women of respectively +17.1% and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2% and +8.0% for advanced adenomas. Changes were less marked during the period 1994–1999. The estimated proportion of adenoma‐bearing individuals diagnosed during the 24‐year period was 20.0% in men and 16.0% in women.Conclusion  Despite a marked increase in the rate of first adenoma diagnosis, the proportion of diagnosed adenoma‐bearing individuals seems too low to induce a significant decrease in colorectal cancer incidence.
Meta‐analysis: remission and response from control arms of randomized trials of biological therapies for active luminal Crohn’s disease
Authors: TINÈ F. , ROSSI F. , SFERRAZZA A. , ORLANDO A. , MOCCIARO F. , SCIMECA D. , OLIVO M. , COTTONE M. 
Published: July 2010

SummaryBackground  Remission and response are the main outcomes to evaluate the efficacy of new treatments for Crohn’s disease (CD).Aim  To explain variation of remission and response rates in active luminal CD.Methods  We studied control patients from trials of biological therapies through articles retrieved by MEDLINE search (from 1997 to 2007) and by bibliography review. Thousand nine hundred and thirteen control patients from 28 trials were identified; data were extracted by three independent observers and pooled by DerSimonian and Laird random effect model; factors influencing remission and clinical response were explored by metaregression for aggregated data.Results  The pooled control rates of remission and response were 17% and 33%, respectively, both with significant heterogeneity among studies (P < 0.0001). At metaregression, the time of primary outcome evaluation was associated with remission, whereas the trial’s criteria for defining response and publication year were predictors of response. CDAI score, CRP levels or other clinical variables related with disease activity or concomitant medications were not significant factors.Conclusions  Populations used as ‘add‐on’ treatment comparator in trials of biological therapies for active luminal CD are poorly characterized and outcomes are heterogeneous. Planning of future trials will require better description of patients and concomitant therapies, blinding of outcome assessors and homogeneous criteria of outcome definition.
Clinical trial: a phase II, randomized study evaluating the safety, pharmacokinetics and anti‐viral activity of clevudine for 12 weeks in patients with chronic hepatitis B
Authors: LIM S. G. , LEUNG N. , HANN H. W. L. , LAU G. K. K. , TREPO C. , MOMMEJA‐MARIN H. , MOXHAM C. , SORBEL J. , SNOW A. , BLUM M. R. , ROUSSEAU F. , MARCELLIN P. 
Published: July 2010

SummaryBackground  Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics.Aim  To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor.Methods  A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off‐treatment follow‐up. Patients had chronic HBV infection, were nucleoside‐naïve without co‐infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method.Results  A total of 31 patients were enrolled into the 10 mg (n = 10), 30 mg (n = 11) and 50 mg (n = 10) groups, respectively. At week 12, the median VL change was −3.2, −3.7 and −4.2 log10 copies/mL (−0.64, −0.74 and −0.84 log10 IU/mL) in the 10, 30 and 50 mg groups, respectively (P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half‐life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound.Conclusion  Clevudine appears to be a potent and tolerable (over 12 weeks) anti‐viral and the optimal dosage appears to be 30 mg once daily.