bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C patients’ self‐reported adherence to treatment with pegylated interferon and ribavirin
Authors: WEISS J. J. , BHATTI L. , DIETERICH D. T. , EDLIN B. R. , FISHBEIN D. A. , GOETZ M. B. , YU K. , WAGNER G. J. 
Published: October 2008

Aliment Pharmacol Ther 28, 289–293SummaryBackground  Prior research on adherence to hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients’ dose‐taking adherence.Aims  To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose‐taking adherence in clinic settings.Methods  One hundred and eighty patients on treatment for hepatitis C (23% co‐infected with HIV) completed a cross‐sectional survey at the site of their hepatitis C care.Results  Seven per cent of patients reported missing at least one injection of pegylated interferon in the last 4 weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose‐taking adherence was not associated with HCV viral load.Conclusions  Self‐reported dose non‐adherence to hepatitis C treatment occurs frequently. Further studies of dose non‐adherence (assessed by method other than self‐report) and its relationship to HCV virological outcome are warranted.
Bleeding ectopic varices in cirrhosis: the role of transjugular intrahepatic portosystemic stent shunts
Authors: KOCHAR N. , TRIPATHI D. , MCAVOY N. C. , IRELAND H. , REDHEAD D. N. , HAYES P. C. 
Published: October 2008

Aliment Pharmacol Ther 28, 294–303SummaryBackground  Bleeding from ectopic varices is uncommon but can be difficult to manage.Aim  To report our experience of the use of transjugular intrahepatic portosystemic stent shunts (TIPSS) in the management of uncontrolled bleeding from ectopic varices.Methods  A retrospective study of patients who had TIPSS for bleeding ectopic varices. Patients were selected from a dedicated data base.Results  Over 14 years, of 750 TIPSS insertions, 28 patients had TIPSS for bleeding ectopic varices (Child–Pugh score: 8.8 ± 1.8). Varices were rectal (12), stomal (8), duodenal (4) and at other sites (4). Concomitant variceal embolization was performed in five. Portal pressure gradient fell from 18.2 ± 6.4 to 7.2 ± 3.5 mmHg. TIPSS achieved haemostasis in six of nine patients who presented with active bleeding. Five patients rebled from ectopic varices. This was related to shunt dysfunction in two and responded to shunt interventions. Three patients rebled despite a functional shunt. Of these, thrombin controlled bleeding in one. Eight patients developed hepatic encephalopathy post‐TIPSS.Conclusions  Transjugular intrahepatic portosystemic stent shunt is a safe and effective treatment for bleeding ectopic varices. Rebleeding from ectopic varices related to shunt dysfunction responds to shunt intervention. A significant proportion of patients have rebleeding despite a patent shunt, when other adjunctive measures like thrombin injection may be tried.
Radioimmunological detection of anti‐transglutaminase autoantibodies in human saliva: a useful test to monitor coeliac disease follow‐up
Authors: BONAMICO M. , NENNA R. , LUPARIA R. P. L. , PERRICONE C. , MONTUORI M. , LUCANTONI F. , CASTRONOVO A. , MURA S. , TURCHETTI A. , STRAPPINI P. , TIBERTI C. 
Published: October 2008

Aliment Pharmacol Ther 28, 364–370SummaryBackground  Serum radioimmunoassay (RIA) tissue transglutaminase autoantibodies (tTG‐Abs) proved to be a sensitive test also during coeliac disease (CD) follow‐up. We demonstrated that RIA tTG‐Abs could be detected in human saliva.Aim  To evaluate salivary RIA tTG‐Abs in coeliac children on gluten‐free diet (GFD).Methods  Saliva and serum samples from 109 coeliac children were evaluated at diagnosis (group 1: 71 females, median age 9.4 years) and 58 of them on GFD: 36 after 3–6 months (group 2a), 34 at 9 months or more (group 2b). Two gender‐ and age‐matched control groups: 89 gastroenterological patients (group 3) and 49 healthy subjects (group 4) participated in the study. Saliva and serum tTG‐Abs were detected by RIA and compared with serum tTG‐Abs ELISA and IgA anti‐endomysium antibodies (EMA).Results  Salivary RIA tTG‐Abs were found in 94.5%, 66.7% and 50.0% of groups 1, 2a and 2b CD patients and in 98.2%, 72.2% and 50.0% of corresponding serum samples, respectively. tTG‐Abs decreased with GFD progression and a correlation was found between saliva and serum titres (r = 0.75, P = 0.0001). During the CD follow‐up, salivary and serum RIA sensitivities were comparable, and higher with respect to EMA and ELISA.Conclusions  This study demonstrates that it is possible to detect salivary tTG‐Abs with high sensitivity not only at CD diagnosis, but also during GFD.
Neural and psychological predictors of treatment response in irritable bowel syndrome patients with a 5‐HT3 receptor antagonist: a pilot study
Authors: JARCHO J. M. , CHANG L. , BERMAN S. M. , SUYENOBU B. , NALIBOFF B. D. , LIEBERMAN M. D. , AMEEN V. Z. , MANDELKERN M. A. , MAYER E. A. 
Published: October 2008

Aliment Pharmacol Ther 28, 344–352SummaryBackground  Symptom improvement in irritable bowel syndrome (IBS) treatment trials varies widely, with only 50–70% of patients qualifying as responders. Factors predicting treatment responsiveness are not known, although we have demonstrated that symptom improvement with the 5‐HT3R antagonist alosetron is correlated with reduced amygdala activity.Aim  To determine whether neural activity during rectal discomfort or psychological distress predicts symptom improvement following treatment with alosetron.Methods  Basal psychological distress and neural activity (15O PET) during uncomfortable rectal stimulation were measured in 17 nonconstipated IBS patients who then received 3 weeks of alosetron treatment.Results  Greater symptom improvement was predicted by less activity in bilateral orbitofrontal cortex (OFC) and medial temporal gyrus during pre‐treatment scans. Lower levels of interpersonal sensitivity predicted greater symptom improvement and were positively related to activity in left OFC. Connectivity analysis revealed a positive relationship between activity in the left OFC and right amygdala.Conclusions  Irritable bowel disease symptom improvement with 5‐HT3R antagonist alosetron is related to pre‐treatment reactivity of the left OFC, which may be partially captured by subjective measures of interpersonal sensitivity. The left OFC may fail to modulate amygdala response to visceral stimulation, thereby diminishing effectiveness of treatment. Psychological factors and their neurobiological correlates are plausible predictors of IBS treatment outcome.
Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long‐term outcome and survival
Authors: AL‐CHALABI T. , PORTMANN B. C. , BERNAL W. , MCFARLANE I. G. , HENEGHAN M. A. 
Published: October 2008

SummaryBackground  Primary sclerosing cholangitis/autoimmune hepatitis (PSC/AIH) and primary biliary cirrhosis/AIH (PBC/AIH) overlap syndromes are poorly defined variants of AIH. Few large patient series exist, and there are little data on long‐term outcomes.Aim  To compare presentation, clinical course and outcome of patients with PSC/AIH and PBC/AIH, with patients with definite AIH.Methods  Two hundred and thirty‐eight AIH patients were compared with 10 PBC/AIH patients and 16 PSC/AIH patients presenting consecutively between 1971 and 2005 at a single centre.Results  Autoimmune hepatitis patients were significantly more likely to present with jaundice (69.4% vs. 25%; P = 0.0145) than PBC/AIH patients. Median serum aspartate aminotransferase activity at presentation was higher in AIH patients compared with PBC/AIH and PSC/AIH patients respectively (620 vs. 94 vs. 224 IU/L; P < 0.05). PBC/AIH patients demonstrated no response to standard AIH therapy more frequently than AIH patients (25% vs. 0.8%; P = 0.0057). Significant reduction in survival was identified between patients with PSC/AIH and those without (hazard ratio: PSC/AIH vs. AIH = 2.08, PSC/AIH vs. PBC/AIH = 2.14; P = 0.039).Conclusions  Patients with PSC/AIH have severe disease and significantly worse prognosis than patients with AIH or PBC/AIH. Recognition and close follow‐up of this cohort are warranted.
Clinical trial: insulin‐sensitizing agents may reduce consequences of insulin resistance in individuals with non‐alcoholic steatohepatitis
Authors: IDILMAN R. , MIZRAK D. , CORAPCIOGLU D. , BEKTAS M. , DOGANAY B. , SAYKI M. , COBAN S. , ERDEN E. , SOYKAN I. , EMRAL R. , UYSAL A. R. , OZDEN A. 
Published: October 2008

SummaryBackground  Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non‐alcoholic steatohepatitis.Aim  To investigate the role of insulin sensitizers in the treatment of individuals with non‐alcoholic steatohepatitis (NASH).Methods  A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 ± 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers.Results  With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment‐insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 ± 24.2 to 33.3 ± 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 ± 46.3 to 47.3 ± 34.5 IU/L, P < 0.001] and histological features (median non‐alcoholic fatty liver disease activity score: 5.0–3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 ± 11.1 to 30.0 ± 8.6 IU/L, P < 0.01; ALT: 66.9 ± 28.9 to 42.0 ± 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high‐sensitivity C‐reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed.Conclusion  Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.
Predictable prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904‐Z
Authors: HUNT R. H. , ARMSTRONG D. , YAGHOOBI M. , JAMES C. , CHEN Y. , LEONARD J. , SHIN J. M. , LEE E. , TANG‐LIU D. , SACHS G. 
Published: October 2008

SummaryBackground  AGN 201904‐Z is a new, slowly absorbed, acid‐stable pro‐proton pump inhibitor (pro‐PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time.Aim  To investigate pharmacodynamics and pharmacokinetics of AGN 201904‐Z compared to esomeprazole.Methods  A randomized, open‐label, parallel group, investigator‐blinded intragastric pH study was conducted in 24 healthy Helicobacter pylori negative male volunteers. AGN 201904‐Z enteric‐coated capsules (600 mg/day) or esomeprazole delayed‐release tablets (40 mg/day) were administered for 5 days. Twenty‐four‐hour intragastric pH recordings were acquired at baseline, days 1, 3 and 5 with blood levels of omeprazole, AGN 201904‐Z and gastrin.Results  On day 1, median nocturnal pH and proportion of nocturnal time with pH ≥4 and 24‐h and nocturnal time pH ≥5 were significantly higher with AGN 201904‐Z than esomeprazole. At day 5, 24‐h and median nocturnal pH were significantly higher for AGN 201904‐Z than esomeprazole (P < 0.0001). There was also a marked reduction in periods of nocturnal pH <4.0. Area under curve of the AGN 201904‐Z active metabolite (omeprazole) in the blood was twice that of esomeprazole at day 5.Conclusions  AGN 201904‐Z produced a significantly greater and more prolonged acid suppression than esomeprazole, and nocturnal acid suppression was more prolonged over all 5 days. AGN 201904‐Z should provide true once‐a‐day treatment and better clinical efficacy than current PPIs.
Clinical trial: single‐ and multiple‐dose pharmacokinetics of polyethylene glycol (PEG‐3350) in healthy young and elderly subjects
Authors: PELHAM R. W. , NIX L. C. , CHAVIRA R. E. , CLEVELAND M. VB. , STETSON P. 
Published: October 2008

SummaryBackground  The pharmacokinetics of polyethylene glycol 3350 (PEG‐3350) have not been fully described because of lack of a sufficiently sensitive analytical method.Aim  To describe the pharmacokinetics of PEG‐3350 in humans.Methods  A highly sensitive, high performance liquid chromatography with mass spectrometry (HPLC/MS/MS) method was developed for PEG‐3350 in urine, plasma and faeces with quantification limits of 30 ng/mL, 100 ng/mL and 500 μg/g respectively. Noncompartmental pharmacokinetics methods were used and the effects of gender, age, renal status and dosing frequency were examined after the oral administration of 17 g to healthy volunteers.Results  Peak PEG‐3350 plasma concentrations occurred at 2–4 h and declined to nonquantifiable levels usually within 18 h after single and multiple doses, with a half‐life of about 4–6 h. Steady state was reached within 5 days of dosing. Mean urinary excretion of the administered dose ranged from 0.19% to 0.25%. Age, gender or mild kidney impairment did not alter the pharmacokinetics of PEG‐3350. Mean faecal excretion of the administered dose was 93% in young subjects.Conclusions  For the first time, a highly sensitive assay allowed comprehensive pharmacokinetics studies of PEG‐3350 in humans. These studies confirmed that orally administered PEG‐3350 is minimally absorbed, rapidly excreted and primarily eliminated via faeces.
Comparison of the enteral and intravenous lansoprazole pharmacodynamic responses in critically ill patients
Authors: OLSEN K. M. , DEVLIN J. W. 
Published: October 2008

Aliment Pharmacol Ther 28, 326–333SummaryBackground  While proton pump inhibitors are frequently administered in the intensive care unit, the pharmacodynamic response of acid suppression between the enteral and intravenous (IV) route is unknown.Aim  To compare the pharmacodynamic response between enteral and IV lansoprazole in intensive care unit patients requiring stress ulcer prophylaxis therapy.Methods  Adult mechanically ventilated patients were randomized to receive 72 h of daily enteral [lansoprazole oral disintegrating tablet (LODT) 30 mg mixed in 10 mL of water via a nasal gastric tube] or IV lansoprazole (30 mg over 30 min) therapy. Serial blood samples were collected after the first and third dose and analysed for pharmacokinetic parameters. Pharmacodynamic determination of intragastric pHmetry began prior to the first dose and continued for 72 h using a single channel pH micro‐electrode.Results  Nineteen intensive care unit patients were randomized [LODT (n = 10); IV‐L (n = 9)]. LODT bioavailability was 76%. LODT maintained gastric pH > 4 longer than IV‐L at both 24 h (7.4 vs. 5.9 h; P = 0.039) and 72 h (10.4 and 8.9 h; P = 0.046) and resulted in a greater average pH over the first 24 h (3.67 vs. 2.89; P = 0.03).Conclusion  Despite a lower bioavailability, enteral lansoprazole suppresses acid in intensive care unit patients to a greater extent than IV lansoprazole.
Review article: the modern management of portal hypertension – primary and secondary prophylaxis of variceal bleeding in cirrhotic patients
Authors: GARCIA‐PAGAN J. C. , DE GOTTARDI A. , BOSCH J. 
Published: October 2008

SummaryBackground  Variceal bleeding is a life–threatening complication of liver cirrhosis with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory.Aim  To provide an overview of the current knowledge on the best evidence‐based therapeutic options to prevent first or recurrent bleeding from oesophageal varices in patients with cirrhosis.Methods  For the preparation of this narrative review, we sought to analyse randomized controlled trials that examined the efficacy and side effects of pharmacological or endoscopic therapy for the primary and secondary prophylaxis of oesophageal variceal bleeding.Results  Endoscopic band ligation (EBL) and nonselective β‐blockers are both effective in preventing first bleeding. Until more long‐term data are available, nonselective β‐blockers should be the first treatment option because of less severe side effects. EBL is an alternative when β‐blockers are contraindicated or not tolerated. Patient preference may also be considered. For prevention of rebleeding, nonselective β‐blockers (preferably in association with isosorbide‐5‐mononitrate) or EBL are both effective and good alternative treatments. A combination of both treatments may be the best alternative.Conclusions  A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.
Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome
Authors: MANGEL A. W. , BORNSTEIN J. D. , HAMM L. R. , BUDA J. , WANG J. , IRISH W. , URSO D. 
Published: October 2008

SummaryBackground  In models of irritable bowel syndrome (IBS), asimadoline, a kappa‐opioid agonist, improves pain and abnormal bowel function.Aim  To evaluate the effects of three doses of asimadoline and placebo in subjects with IBS through a double‐blind, randomized, placebo‐controlled trial.Methods  Patients were randomly assigned to receive asimadoline 0.15, 0.5, 1.0 mg or placebo BID for 12 weeks. The primary efficacy measure was number of months of adequate relief of IBS pain or discomfort, with a prospective plan to evaluate adequate relief data by entry baseline pain and subtype. Several other endpoints were also evaluated.Results  Five hundred and ninety‐six patients were randomized. In the ITT population, statistically significant improvement on the primary endpoint was not seen. However, in diarrhoea‐predominant IBS patients with at least baseline moderate pain, asimadoline (0.5 mg) produced significant improvement on total number of months with adequate relief of IBS pain or discomfort (46.7% vs. 20.0%), adequate relief of IBS symptoms (46.7% vs. 23.0%), pain scores (week 12: −1.6 vs. −0.7), pain free days (42.9% vs. 18.0%), urgency and stool frequency (−2.3 vs. −0.3). In patients with alternating IBS, significant improvement was seen on adequate relief endpoints. Asimadoline was well tolerated.Conclusion  Asimadoline warrants further evaluation as a treatment for IBS.
Review article: current antiviral therapy of chronic hepatitis B
Authors: AYOUB W. S. , KEEFFE E. B. 
Published: October 2008

SummaryBackground  The long‐term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma.Aim  To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses.Methods  A systematic review of the literature, with a focus on recent guidelines, was undertaken.Results  Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa‐2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on‐treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross‐resistant is critical to restore suppression of viral replication.Conclusions  Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance.
Comparative effectiveness of azathioprine in Crohn’s disease and ulcerative colitis: prospective, long‐term, follow‐up study of 394 patients
Authors: GISBERT J. P. , NIÑO P. , CARA C. , RODRIGO L. 
Published: October 2008

SummaryBackground The long‐term efficiacy for thiopurinic drugs in Crohn’s disease (CD), and particularly in ulcerative colitis (UC), has been insufficiently studied.Aim To evaluate prospectively and compare the long‐term effectiveness of azathioprine (AZA) in CD and UC.Methods Three hundred and ninety‐four AZA treated patients were included consecutively included. Truelove‐modified index and CDAI were used to assess effectiveness. Hospitalizations and surgical procedures were recorded.Results Two hundred and thirty‐eight patients with CD and 156 with UC received AZA for a median of 38 months. Effectiveness: Partial response/remission was achieved in 34%/49% of CD patients and in 47%/42% of UC (nonstatistically significant differences). Steroid treatment: Prior to AZA, 49% of CD patients were receiving steroids, whereas only 8% needed steroids after therapy (P < 0.001). Corresponding figures in UC patients were 39% vs. 9% (P < 0.001). Hospitalizations: Prior to AZA, the rate of hospitalizations in CD was 0.190 per‐patient‐year, while after treatment, it decreased to 0.099 (P < 0.001). Corresponding hospitalization rates in UC were 0.108 vs. 0.038 (P < 0.001). Surgery: The rate of surgery in CD prior/after AZA was 0.038/0.011 per‐patient‐year (P < 0.001). The number of surgical interventions in UC prior/after AZA treatment was 26/0 (the rate per‐patient‐year was 0.018/0) (P < 0.001).Conclusions Our results confirm the effectiveness of AZA in inflammatory bowel disease, not only in the short term but also in the long term, resulting in a steroid sparing effect and in both a reduction in the number of hospitalizations and surgical procedures. AZA is similarly effective for both CD and UC patients.
Ninety‐six‐hour wireless oesophageal pH monitoring following proton pump inhibitor administration in NERD patients
Authors: CALABRESE C. , LIGUORI G. , GABUSI V. , GIONCHETTI P. , RIZZELLO F. , STRAFORINI G. , BRUGNERA R. , DI FEBO G. 
Published: October 2008

SummaryBackground  Comparative studies of proton pump inhibitors (PPIs) have revealed that acid reflux is influenced by PPI treatment, formulations and dosing regimens. Wireless pH capsules have circumvented some of the limitations of conventional catheter‐based pH testing with the additional advantage of 96‐h recording periods.Aim  To clarify the effectiveness of intra‐oesophageal acid suppression by omeprazole, pantoprazole and lansoprazole in non‐erosive reflux disease patients through a 4‐day monitoring of oesophageal pH and related symptoms.Methods  Twenty‐four patients with typical symptoms of gastro‐oesophageal reflux disease were enrolled and administered upper endoscopy and placement of a wireless pH capsule. Patients randomly received omeprazole, pantoprazole or lansoprazole for 3 days after the first 24 h. Symptom–reflux associations were expressed using the symptom index (SI).Results  All patients completed the study. Significant decrease in acid exposure occurred on day 2 and in each successive day in all groups. Pantoprazole and omeprazole are more effective than lansoprazole at inducing a normalization of intra‐oesophageal acid exposure at days 2 and 3. Significant reduction in SI at day 2 was observed.Conclusions  Four‐day ambulatory oesophageal pH monitoring is feasible and safe. Omeprazole, pantoprazole and lansoprazole have an equivalent potency for normalizing intra‐oesophageal acid exposure after 3 days of treatment in non‐erosive reflux disease patients.