bluuebunny/crossref_metadata_2025 huggingface dataset:
Histological benefits of virological response to peginterferon alfa‐2a monotherapy in patients with hepatitis C and advanced fibrosis or compensated cirrhosis
Authors: EVERSON G. T. , BALART L. , LEE S. S. , REINDOLLAR R. W. , SHIFFMAN M. L. , MINUK G. Y. , POCKROS P. J. , GOVINDARAJAN S. , LENTZ E. , HEATHCOTE E. J.
Published: July 2010

Background  Patients with chronic hepatitis C virus and advanced fibrosis or cirrhosis are at risk for disease progression and hepatic decompensation.

Aim  To determine the effects on hepatic histology of treatment with peginterferon alfa‐2a (90 or 180 μg/week) or interferon alfa‐2a (3 million units three times weekly) for 48 weeks in patients with paired biopsies.

Methods  Liver biopsies were obtained at baseline and 6 months after end of treatment. Histological and virological responses were compared.

Results  Patients attaining sustained virological response (n = 40) demonstrated the greatest improvements in fibrosis (−1.0, P < 0.0001) and inflammation (−0.65, P < 0.0001). Patients who cleared hepatitis C virus during treatment, but later relapsed (n = 59), experienced less improvement in fibrosis (−0.04, P < 0.0001) and inflammation (−0.14, P = 0.0768). Nonresponders (n = 85) showed no significant improvement in inflammation or fibrosis. Multiple regression analysis showed that the only factors contributing to improvement in fibrosis were sustained virological response (vs. nonresponder, P = 0.0005; vs. relapse, P = 0.7525) and body mass index ≤30 kg/m2 (P = 0.0995).

Conclusions  These findings indicate that virological response to peginterferon alfa‐2a improves inflammation and fibrosis in hepatitis C virus patients with advanced fibrosis or cirrhosis. Improving virological response and maintaining ideal body weight are critical for achieving optimal histological outcomes in hepatitis C virus patients.
Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation
Authors: JOHANSON J. F. , DROSSMAN D. A. , PANAS R. , WAHLE A. , UENO R.
Published: July 2010

Background  Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation.

Aim  To assess the efficacy and safety of three lubiprostone doses for irritable bowel syndrome with constipation.

Methods  195 irritable bowel syndrome with constipation patients received daily doses of 16 [8 μg twice daily (b.d.)], 32 (16 μg b.d.) or 48 μg (24 μg b.d.) lubiprostone or placebo b.d. for 3 months. Gastrointestinal parameters were recorded in diaries daily by patients.

Results  After 1 month, lubiprostone showed significantly greater improvements in mean abdominal discomfort/pain scores vs. placebo (P = 0.023). After 2 months, all lubiprostone groups showed significantly greater improvements in mean abdominal discomfort/pain scores (P ≤ 0.039). After 3 months of treatment, the improvement in each lubiprostone arm was greater than placebo, but the test for trend was no longer significant. Treatment with lubiprostone showed significantly higher rates of gastrointestinal adverse events (P = 0.020), especially diarrhoea and nausea.

Conclusion  Lubiprostone significantly improved gastrointestinal symptoms of irritable bowel syndrome with constipation at all doses. Higher doses of lubiprostone, especially the 48 μg/day group, were associated with more gastrointestinal adverse events. From these data, the 16 μg/day dose demonstrated the optimal combination of efficacy and safety. These results warrant further study of lubiprostone for treatment of irritable bowel syndrome with constipation patients.
Intravenous esomeprazole for prevention of peptic ulcer re‐bleeding: rationale/design of Peptic Ulcer Bleed study
Authors: SUNG J. J. Y. , MÖSSNER J. , BARKUN A. , KUIPERS E. J. , LAU J. , JENSEN D. , STUART R. , JUNGHARD O. , OLSSON G. ,   ON BEHALF OF THE PUB STUDY GROUP
Published: July 2010

Background  A limited number of trials have investigated the efficacy of proton pump inhibitors for peptic ulcer bleeding, and some study design issues have been identified.

Aim  To present the design of a large trial evaluating the effects of intravenous esomeprazole on clinical outcomes in high‐risk patients who have undergone endoscopic haemostasis for peptic ulcer bleeding.

Methods  The Peptic Ulcer Bleed study is an international, randomized, double‐blind, placebo‐controlled trial comparing either esomeprazole 80 mg intravenous bolus infusion for 30 min followed by esomeprazole 8 mg/h intravenously for 71.5 h, or placebo infusion for 72 h, after successful endoscopic haemostasis in patients with peptic ulcer bleeding and associated high‐risk stigmata. All patients will receive once daily oral esomeprazole 40 mg for 27 days after intravenous therapy. The primary end point is the rate of clinically significant re‐bleeding during the first 72 h after endoscopy. Secondary end points include: rate of re‐bleeding during the first 7 and 30 days after treatment; length of hospitalization; mortality; blood transfusion; endoscopic re‐treatment and surgery.

Results  Expected 2008.

Conclusions  The carefully designed protocol and quality control measures represent a pragmatic approach to contemporary challenges in peptic ulcer bleeding management and, it is hoped, qualify the Peptic Ulcer Bleed study as a new standard for future interventional studies.
Systematic review: tranexamic acid for upper gastrointestinal bleeding
Authors: GLUUD L. L. , KLINGENBERG S. L. , LANGHOLZ S. E.
Published: July 2010

Background  Tranexamic acid may reduce upper gastrointestinal bleeding and stabilize patients before endoscopic treatments.

Aim  To review randomized trials on tranexamic acid for upper gastrointestinal bleeding.

Methods  Manual and electronic searches of The Cochrane Library, MEDLINE, EMBASE and Science Citation Index were combined. Intention‐to‐treat random effect meta‐analyses were performed and results presented as RRs with 95% confidence intervals.

Results  Seven double‐blind randomized trials on tranexamic acid vs. placebo were included. Of 1754 patients randomized, 21% were excluded. Only one trial included endoscopic treatments or proton pump inhibitors. Five per cent of patients on tranexamic acid and 8% of controls died (RR: 0.61, 95% CI: 0.42–0.89). No significant differences were found on bleeding, bleeding‐related mortality, surgery or transfusion requirements. Adverse events were unclearly reported. Data from three of the included trials suggested that tranexamic acid did not significantly increase the risk of thromboembolic disease.

Conclusions  The present review suggests that tranexamic acid may reduce all‐cause mortality. However, because of limitations in the internal and external validity of included trials, additional evidence is needed before treatment recommendations can be made.
Validation of a brief symptom questionnaire (ReQuest in Practice) for patients with gastro‐oesophageal reflux disease
Authors: RUBIN G. , UEBEL P. , BRIMO‐HAYEK A. , HEY K. H. , DOERFLER H. , HEADING R. C.
Published: July 2010

Background  A clinical need exists for a means of assessing symptom control in patients with gastro‐oesophageal reflux disease. The ReQuest questionnaire has been extensively validated for symptom assessment in both erosive and non‐erosive gastro‐oesophageal reflux disease but was designed for research purposes. We derived a shorter version (ReQuest in Practice) that would be more convenient for clinical practice.

Aim  To validate ReQuest in Practice in patients suffering from gastro‐oesophageal reflux disease.

Methods  Multicentre, non‐interventional, crossover comparison. Patients completed ReQuest in Practice followed by ReQuest or vice versa. Before and after a planned endoscopy, patients completed the health‐related quality of life questionnaire GERDyzer. Internal consistency and the Intraclass Correlation Coefficient were calculated. Construct validity was evaluated by correlation with ReQuest and GERDyzer.

Results  There was high internal consistency of ReQuest in Practice (Cronbach’s alpha: 0.9) and a high Intraclass Correlation Coefficient of 0.99. The measurement error of ReQuest in Practice was 4.1. High correlation between ReQuest in Practice and ReQuest (Spearman correlation coefficient: 0.9) and GERDyzer (Spearman correlation coefficient: 0.8) demonstrated construct validity.

Conclusions  ReQuest in Practice was proven to be valid and reliable. Its close correlation with ReQuest makes it a promising tool to guide the clinical management of patients across the full spectrum of both erosive and non‐erosive gastro‐oesophageal reflux disease.
Meta‐analysis: ertapenem for complicated intra‐abdominal infections
Authors: FALAGAS M. E. , PEPPAS G. , MAKRIS G. C. , KARAGEORGOPOULOS D. E. , MATTHAIOU D. K.
Published: July 2010

Background  Ertapenem is a new member of the carbapenem class of antibiotics, with a favourable pharmacokinetic profile, but a narrower spectrum of antimicrobial activity, compared with older representatives of this class.

Aim  To evaluate the effectiveness and safety of ertapenem for treatment of complicated intra‐abdominal infections.

Methods  We performed a meta‐analysis of randomized‐controlled trials identified in PubMed, Cochrane and Scopus that compared ertapenem with other antimicrobial regimens, in patients of all ages, with complicated intra‐abdominal infections. The primary outcomes evaluated were clinical success (cure or improvement) in the modified intention‐to‐treat population and clinical adverse events.

Results  Six randomized‐controlled trials involving patients with complicated intra‐abdominal infections, mainly of mild‐to‐moderate severity (three with a double‐blind design; one performed in children) that compared ertapenem treatment (once daily) against piperacillin/tazobactam, ceftriaxone plus metronidazole and ticarcillin/clavulanic acid (in three, two and one randomized‐controlled trials respectively) were included. No difference was found between adult patients with complicated intra‐abdominal infections treated with ertapenem vs. comparators, regarding clinical success (five randomized‐controlled trials, 2002 patients, fixed‐effect model, odds ratio: 1.11, 95% confidence interval (CI): 0.89–1.39); clinical adverse events (four randomized‐controlled trials, 1530 patients, fixed‐effect model, OR: 0.86, 95% CI: 0.61–1.20); microbiological success; mortality and withdrawals because of adverse events. Ertapenem was associated with more laboratory adverse events (four randomized‐controlled trials, 1530 patients, fixed‐effect model, OR: 1.73, 95% CI: 1.14–2.61), but none was reported as serious.

Conclusion  This meta‐analysis provides additional evidence that ertapenem can be used as effectively and safely, as other recommended antimicrobial regimens, for the treatment of complicated intra‐abdominal infections, particularly of mild‐to‐moderate severity.
Review article: use of antitumour necrosis factor therapy in inflammatory bowel disease during pregnancy and conception
Authors: O'DONNELL S. , O'MORAIN C.
Published: July 2010

Background  One of the most frequently asked questions during consultation with those affected by inflammatory bowel disease is what are its effects on pregnancy, and how the treatment will impact on conception and pregnancy outcomes.

Aim  To review available data regarding the safety of biological therapies during pregnancy, primarily in woman with inflammatory bowel disease.

Methods A Medline search was performed and available original research and review articles relating to the use of biological (antitumour necrosis factor‐α) therapies in inflammatory bowel disease were reviewed. Where information regarding the use of a drug in inflammatory bowel disease during pregnancy was limited, articles referring to its use for other indications, such as rheumatoid arthritis, were reviewed.

Conclusions Based on available data, biological therapies appear to be safe in pregnancy. Most studies looking at the effects of any one medication on pregnancy in inflammatory bowel disease are confounded by the fact that most patients are on multiple medications and have varying levels of disease activity. Stopping therapy in the third trimester should be considered. Large registries with longer follow‐up periods will be necessary before firm conclusions about the safety of antitumour necrosis factor‐α therapies during conception and pregnancy can be drawn.
Effects of therapeutic doses of lactulose vs. polyethylene glycol on isotopic colonic transit
Authors: JOUËT P. , SABATE J.‐M. , FLOURIE B. , CUILLERIER E. , GAMBINI D. , LEMANN M. , JIAN R. , COFFIN B.
Published: July 2010

Background  Lactulose and polyethylene glycol are osmotic agents used to treat idiopathic chronic constipation.

Aim  To compare the effects of low doses of lactulose and PEG 4000 on transit time measured by scintigraphy in normal subjects.

Methods  For 5 days, 10 healthy subjects received either 10 g b.d. of lactulose or PEG 4000 in a randomized, double‐blind, crossover study. On the evening of day 4, they took a capsule containing Amberlite resin pellets labelled with 111In. On day 5, after a 1000 kcal test meal labelled with 99Tcm, gastric, small bowel and colonic transits were measured.

Results  Gastric emptying and small bowel transit time were not different. Ascending colon emptying curve was significantly accelerated with lactulose in comparison with polyethylene glycol (P = 0.001) and, respectively, 50 ± 18% vs. 35 ± 18% of the radioactivity had left the ascending colon at the end of the study (P < 0.05). The descending colon filling curves, variations in the geometric centre and numbers of scintigraphic movements were not different.

Conclusions  In healthy subjects, in comparison to PEG 4000, usual therapeutic doses of lactulose significantly accelerate ascending colon emptying. This result supports a stimulating motor effect of colonic fermentation of lactulose.
Short‐term treatment with infliximab in chronic refractory pouchitis and ileitis
Authors: CALABRESE C. , GIONCHETTI P. , RIZZELLO F. , LIGUORI G. , GABUSI V. , TAMBASCO R. , POGGIOLI G. , PIERANGELI F. , CAMPIERI M. , DI FEBO G.
Published: July 2010

Background  Chronic refractory pouchitis is a long‐term complication after ileal pouch‐anal anastomosis and it may be associated with ileal inflammation.

Aim  To determine the efficacy of infliximab in treatment of chronic refractory pouchitis complicated by ileitis, using a wireless capsule endoscopy.

Methods  Sixteen patients with chronic refractory pouchitis complicated by ileitis were enrolled. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. Ileitis was documented using wireless capsule endoscopy. Duodenum–jejunum and proximal–middle ileum were evaluated and the presence of small lesions and large lesions were noted. Crohn’s disease, intestinal infections were excluded in all patients. Patients were treated with infliximab and clinical response was recorded. Wireless capsule endoscopy was repeated at week 10 and Pouchitis Disease Activity Index score was determined.

Results  Ten patients were enrolled and completed the study. Clinical remission was achieved in nine patients. At wireless capsule endoscopy and pouch endoscopy, a complete recovery of lesions was observed in eight patients. One patient presented four small lesions of the ileum at the 6 weeks of treatment and one patient did not show any modification. Clinical and endoscopic remission was maintained in these eight patients at least 6 months.

Conclusion  These preliminary results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated by ileitis.
Effectiveness of pegylated interferon/ribavirin combination in ‘real world’ patients with chronic hepatitis C virus infection
Authors: BORRONI G. , ANDREOLETTI M. , CASIRAGHI M. A. , CERIANI R. , GUERZONI P. , OMAZZI B. , TERRENI N. , SALERNO F.
Published: July 2010

Background  Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54–63% of patients with chronic hepatitis C virus infection, but its effectiveness in day‐to‐day clinical practice is less clear.

Aim  To verify if the efficacy of pegylated interferon/ribavirin combination in ‘real world’ patients is comparable to that observed in trials.

Methods  The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti‐viral treatment.

Results  The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2–3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for ≥80% of the planned duration of treatment.

Conclusion  The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized‐controlled studies.
Access to care, socioeconomic deprivation and colon cancer survival
Authors: DEJARDIN O. , BOUVIER A. M. , FAIVRE J. , BOUTREUX S. , DE POUVOURVILLE G. , LAUNOY G.
Published: July 2010

Background  The influence of socioeconomic environment on cancer survival has been established in numerous studies in the EU and the US, prognosis being constantly poorer for the most underprivileged patients.

Aim  To investigate the influence of distance to care centre and deprivation on colon cancer survival, using a multilevel Cox model and taking into account cancer stage at diagnosis and treatment modalities.

Methods  The study population comprised all cases of colon cancer diagnosed between 1997 and 2000 in two French areas covered by specialized cancer registries (n = 2066).

Results  Road distance to the nearest reference care centre was associated with poorer prognosis even after adjustment for stage at diagnosis (P for trend = 0.01). Subgroups analysis showed that this association was maximal for patients with advanced cancer [RR = 1.27 (1.04–1.51); P for trend = 0.015] for whom access to chemotherapy varying according to distance explained the major part of geographic inequalities in survival.

Conclusions  The major effect of distance from reference care centre on survival suggests that current regional health planning does not guarantee equity in cancer management. Improvement in access to adjuvant therapy, especially for patients with advanced cancers, seems crucial for reducing geographic disparities in colon cancer survival.
Systematic review: glucocorticosteroids for alcoholic hepatitis – a Cochrane Hepato‐Biliary Group systematic review with meta‐analyses and trial sequential analyses of randomized clinical trials
Authors: RAMBALDI A. , SACONATO H. H. , CHRISTENSEN E. , THORLUND K. , WETTERSLEV J. , GLUUD C.
Published: July 2010

Background  Glucocorticosteroids versus placebo or no intervention for patients with alcoholic hepatitis have been evaluated for more than 35 years. However, the results of randomized trials and meta‐analyses differ substantially.

Aim  To review all randomized clinical trials of glucocorticosteroids vs. placebo or no intervention for patients with alcoholic hepatitis.

Methods  We searched for randomized trials published before July 2007. The trials were assessed for risk of bias.

Results  We included 15 trials with a total of 721 randomized patients. The overall mortality rate was 39.5%. Twelve of the fifteen trials were at risk of bias. Glucocorticosteroids did not statistically reduce mortality compared with placebo or no intervention (relative risk 0.83, 95% CI 0.63–1.11). Glucocorticosteroids significantly reduced mortality in the subgroup of trials with patients with Maddrey’s score of at least 32 or hepatic encephalopathy and with low‐bias risk. In all analyses, heterogeneity was significant and substantial. Trial sequential analyses using heterogeneity‐adjusted information size demonstrated no significant effect of glucocorticosteroids on mortality. Weighted logistic regression analyses taking prognostic factors at randomization into consideration found no significant effect of glucocorticosteroids on mortality.

Conclusions  The current evidence base of mainly heterogeneous with high bias risk trials does not support the use of glucocorticosteroids in alcoholic hepatitis. Large, low‐bias risk placebo‐controlled randomized trials are needed.
Systematic review: combination therapies for treatment‐naïve chronic hepatitis B
Authors: KUMAR M. , SARIN S. K.
Published: July 2010

Background  There is a renewed interest in use of combination therapies in treatment‐naïve chronic hepatitis B (CHB) because of limitations of monotherapies.

Aim  To discuss the current status of combination therapies in treatment‐naïve CHB.

Methods  PubMed search was done using ‘combination’, ‘sequential’ and ‘chronic hepatitis B’ as the search terms.

Results  The two most popular combination therapies include ‘combination of nucleos(t)ide analogues’ and ‘combination of interferons and nucleos(t)ide analogues’. Combination therapies using two nucleos(t)ide analogues do not lead to higher long‐term efficacy. However, addition of a nucleos(t)ide analogue with a good resistance profile to a nucleos(t)ide analogue with a lower genetic barrier to resistance decreases the risk of emergent resistance to the latter. Greater sustained virological, biochemical and seroconversion rates are observed with addition of lamivudine to conventional interferon, but pegylated‐interferon monotherapy is equally effective as combination with lamivudine. Again, resistance to lamivudine is lower with its combination with interferons.

Conclusions  The answer to the question whether hepatitis B can be treated better with combination or monotherapy remains largely unknown. Additional trials are warranted of combination therapies of peginterferon and potent nucleos(t)ide analogues or therapies with the combined use of nucleos(t)ide analogues or immunomodulators.
Review article: medication non‐adherence in ulcerative colitis – strategies to improve adherence with mesalazine and other maintenance therapies
Authors: HAWTHORNE A. B. , RUBIN G. , GHOSH S.
Published: July 2010

Background  Significant number of patients with ulcerative colitis (UC) fail to comply with treatment.

Aims  To review issues surrounding medication non‐adherence in inflammatory bowel disease (IBD), including the clinical and health service implications in the UK, and discuss strategies for optimizing medication adherence.

Methods  Articles cited were identified via a PubMed search, utilizing the words IBD, adherence, compliance, medication and UC.

Results  Medication non‐adherence is multifactorial involving factors other than dosing frequency. Male gender (OR: 2.06), new patient status (OR: 2.14), work and travel pressures (OR: 4.9) and shorter disease duration (OR: 2.1), among others are proven predictors of non‐adherence in UC. These indicators can identify ‘at‐risk’ patients and allow an individually tailored treatment approach to be introduced that optimizes medication adherence. A collaborative relationship between physician and patient is important; several strategies for improving adherence have been proven effective including open dialogue that takes into consideration the patient’s health beliefs and concerns, providing educational (e.g. verbal/written information, self‐management programmes) and behavioural interventions (e.g. calendar blister packs, cues/reminders).

Conclusions  Educational and behavioural interventions tailored to individual patients can optimize medication adherence. Additional studies combining educational and behavioural interventions may provide further strategies for improving medication adherence rates in UC.
Review article: molecular, pathological and therapeutic features of human enteric neuropathies
Authors: DI NARDO G. , BLANDIZZI C. , VOLTA U. , COLUCCI R. , STANGHELLINI V. , BARBARA G. , DEL TACCA M. , TONINI M. , CORINALDESI R. , DE GIORGIO R.
Published: July 2010

Background  Considerable information has been gathered on the functional organization of enteric neuronal circuitries regulating gastrointestinal motility. However, little is known about the neuropathophysiological mechanisms underlying gastrointestinal motor disorders.

Aim  To analyse the most important pathological findings, clinical implications and therapeutic management of idiopathic enteric neuropathies.

Methods  PubMed searches were used to retrieve the literature inherent to molecular determinants, pathophysiological bases and therapeutics of gastrointestinal dysmotility, such as achalasia, gastroparesis, chronic intestinal pseudo‐obstruction, Hirschsprung’s disease and slow transit constipation, to unravel advances on digestive disorders resulting from enteric neuropathies.

Results  Current data on molecular and pathological features of enteric neuropathies indicate that degenerative and inflammatory abnormalities can compromise the morpho‐functional integrity of the enteric nervous system. These alterations lead to a massive impairment in gut transit and result in severe abdominal symptoms with associated high morbidity, poor quality of life for patients and established mortality. Many pathophysiological aspects of these severe conditions remain obscure, and therefore treatment options are quite limited and often unsatisfactory.

Conclusions  This review of enteric nervous system abnormalities provides a framework to better understand the pathological processes underlying gut dysmotility, to translate this knowledge into clinical management and to foster the development of targeted therapeutic strategies.
Epidemiological study of gastro‐oesophageal reflux disease: reflux in spouse as a risk factor
Authors: NASSERI‐MOGHADDAM S. , MOFID A. , GHOTBI M.‐H. , RAZJOUYAN H. , NOURAIE M. , RAMARD A.‐R. , ZAER‐REZAIE H. , HABIBI R. , RAFAT‐ZAND K. , MALEKZADEH R.
Published: July 2010

Background  Gastro‐oesophageal reflux disease (GERD) is a growing health‐care problem with variable distribution.

Aim  To assess GERD prevalence and risk factors and their possible correlation with pathophysiology in a population‐based study.

Methods  Individuals aged 18–65 years were enrolled through random cluster sampling in Tehran. Previously validated self‐administered questionnaires were used.

Results  Of the 2500 questionnaires, 2057 were analysed (mean age: 34.8 ± 13.0 years, 55.1% female). Frequent GERD was seen in 18.2%. Minor symptoms increased prevalence. Female gender (OR: 1.55, 95% CI: 1.01–2.41), BMI >30 kg/m2 (OR: 1.79, 95% CI: 1.03–3.12), less education (OR: 1.52, 95% CI: 1.02–2.27), smoking (OR: 1.83, 95% CI: 1.12–2.99), NSAID use (OR: 4.23, 95% CI: 1.66–10.74) and GERD in spouse (OR: 1.82, 95% CI: 1.18–2.82) were associated with frequent GERD on multivariable analysis. GERD in first‐degree relatives (OR: 1.73, 95% CI: 1.23–2.43) and asthma (OR: 4.09, 95% CI: 1.27–13.15) correlated with infrequent GERD. Minor symptoms correlated with GERD history in first‐degree relatives, coffee consumption and NSAID use. Prevalence in the past 3 months was similar to that in the past 12 months (P < 0.05).

Conclusions  Gastro‐oesophageal reflux disease is common in Tehran. The association of ‘infrequent symptoms’ with GERD history in first‐degree relatives and ‘frequent symptoms’ with GERD history in spouse may point to the presence of yet unknown precipitating environmental factors inducing GERD in a genetically susceptible host. Minor GERD symptoms seem to have independent contribution to GERD. Assessing GERD in the past 3 months predicts prevalence in the past year.
Prospective evaluation of transient elastography for the diagnosis of hepatic fibrosis in Asians: comparison with liver biopsy and aspartate transaminase platelet ratio index
Authors: CHANG P.‐E. , LUI H.‐F. , CHAU Y.‐P. , LIM K.‐H. , YAP W.‐M. , TAN C.‐K. , CHOW W.‐C.
Published: July 2010

Background  Transient elastography (TE) is a reliable non‐invasive predictor of hepatic fibrosis, but data on TE in Asians are limited.

Aim  To evaluate prospectively the accuracy of TE for diagnosis of hepatic fibrosis in Asians compared with APRI (aspartate transaminase to platelet ratio index).

Methods  One hundred and twenty consecutive patients who underwent liver biopsy were enrolled. TE (Fibroscan) was performed by two independent operators. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) were used to evaluate the accuracy of TE and APRI in diagnosing significant fibrosis (F ≥ 2) and cirrhosis (F4).

Results  Predominant aetiologies were hepatitis B (48%), non‐alcoholic steatohepatitis (14%) and hepatitis C (8%). TE was unsuccessful in five patients (4.2%) because of small inter‐costal space (three patients), obesity and ascites. There was good correlation between TE and fibrosis (r = 0.606). AUROC for diagnosis of significant fibrosis was 0.856 (95% CI 0.779–0.932) for TE and 0.673 (95% CI 0.568–0.777) for APRI. AUROC for diagnosis of cirrhosis was 0.924 (95% CI 0.857–0.990) for TE and 0.626 (95% CI 0.437–0.815) for APRI. Optimal TE value was 9.0 kPa for diagnosis of significant fibrosis and 16.0 kPa for cirrhosis with specificity/sensitivity/PPV/NPV/accuracy of 82.6%/85.2%/80.9%/86.7%/84.1% and 88.9%/82.7%/32.0%/98.8%/83.2%, respectively.

Conclusions  Transient elastography is a reliable predictor of hepatic fibrosis in Asians. Failure of TE in Asians is commonly because of small inter‐costal space. TE is superior to APRI for non‐invasive diagnosis of hepatic fibrosis and cirrhosis.
Underutilization of gastroprotective strategies in aspirin users at increased risk of upper gastrointestinal complications
Authors: TARGOWNIK L. E. , METGE C. J. , LEUNG S.
Published: July 2010

Background  Aspirin use is with an increased risk of upper gastrointestinal complications (UGICs). Proton pump inhibitors (PPIs) decrease the risk of UGICs among aspirin users. The distribution of risk factors for UGIC and PPI utilization among aspirin users remains uncharacterized.

Aim  To determine the prevalence and predictors of PPI use in high‐risk aspirin users.

Methods  Using questionnaires and administrative records, we collected information on aspirin and PPI utilization and risk factors for UGICs from a stratified random sample of subjects with established cardiovascular disease. We calculated the proportion of aspirin users with UGIC risk factors and determined the prevalence of PPI use among aspirin users with risk factors. Regression analysis was used to determine predictors of PPI use among aspirin users.

Results  Overall response rate was 35%, of whom 86% were regular aspirin users. Seventy‐one per cent of aspirin users had at least one risk factor (in addition to cardiac disease) for the development of UGICs. Although a history of UGIC was predictive of PPI use, 44% of aspirin users with a prior history of UGICs did not receive a concomitant PPI, and only 23% of subjects with additional UGIC risk factors were prescribed a PPI.

Conclusion  There is a high prevalence of UGIC risk factors among aspirin users, and many are not prescribed PPIs as a gastroprotective strategy.
Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic‐associated diarrhoea in children
Authors: RUSZCZYŃSKI M. , RADZIKOWSKI A. , SZAJEWSKA H.
Published: July 2010

Background  Convincing evidence that probiotic administration can lower the risk of antibiotic‐associated diarrhoea is limited to certain micro‐organisms.

Aim  To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic‐associated diarrhoea in children.

Methods  Children (aged 3 months to 14 years) with common infections were enrolled in a double‐blind, randomized, placebo‐controlled trial in which they received standard antibiotic treatment plus 2 × 1010 colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.

Results  Any diarrhoea (≥3 loose or watery stools/day for ≥48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2–0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1–1.06). No adverse events were observed.

Conclusion  Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.
Pilot study: Gelafundin (polygeline) 4% plus antibiotics in the treatment of high‐risk cirrhotic patients with spontaneous bacterial peritonitis
Authors: Cartier M. , Terg R. , Lucero R. , Muñoz A. , Romero G. , Levi D. , Miguez C. , Abecasis R.
Published: July 2010

Aliment Pharmacol Ther2010;32:43–48

Background Cirrhotic patients with spontaneous bacterial peritonitis (SBP) have elevated rates of renal impairment and mortality. It has been shown that cefotaxime plus albumin infusion decrease renal impairment compared with antibiotic treatment alone, in patients with serum bilirubin >4 mg/dL or creatinine >1 mg/dL.

Aim To assess clinical outcomes of high‐risk cirrhotic patients with SBP who were treated with antibiotics associated with Gelafundin (polygeline) 4%.

Methods Twenty nine cirrhotic patients with SBP and serum bilirubin >4 mg/dL or creatinine >1 mg/dL were enrolled. Ceftriaxone was administered in doses of 2 g/day and Gelafundin 4% was given intravenously at 1.5 g/kg of body weight at the time of the diagnosis, followed by 1 g/kg on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization.

Results Eight patients (27.5%) had basal renal failure. Infection resolved in 28 (96.6%) patients. Renal impairment occurred in four patients (13.8%), and three patients (10.4%) died during hospitalization. Mortality within 90 days after discharge was 34.5% (10 patients).

Conclusion The rates of renal impairment and mortality in high‐risk patients with SBP suggest that Gelafundin 4% administration given with ceftriaxone may be a less expensive therapeutic alternative to albumin.
Intestinal B cell‐activating factor: an indicator of non‐IgE‐mediated hypersensitivity reactions to food?
Authors: Lied G. Arslan , Lillestøl K. , Valeur J. , Berstad A.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 66–73

Background  Medically confirmed hypersensitivity reactions to food are usually IgE‐mediated. Non‐IgE‐mediated reactions are not only seldom recognized but also more difficult to diagnose.

Aim  To examine B cell‐activating factor (BAFF) in serum and gut lavage fluid of patients with self‐reported food hypersensitivity, and to study its relationship to atopic disease.

Methods  Gut lavage fluid was obtained from 60 and serum from another 17 patients with self‐reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non‐atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid.

Results  B cell‐activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non‐atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE.

Conclusions  The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non‐atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non‐IgE‐mediated reactions.
Asynchronous independent lung ventilation
Authors: STOW P. J. , GRANT I.
Published: July 2010

The use of asynchronous independent lung ventilation is described in a patient presenting with acute respiratory failure due to a severe unilateral pneumonia. A polyvinyl chloride (Portex) doublelumen tube was inserted through a tracheostomy and the lungs ventilated independently using a combination of a Cape ventilator and a Servo 900 B ventilator.
Mapping and characterization of the DQ subregion of the ovine MHC
Authors: Wright H , Ballingall K T
Published: July 2010

A map of the ovine MHC class II DQ subregion has been constructed from overlapping cosmid clones. This region consists of two loci linked on a linear tract of 130 kb DNA. Each locus consists of a DQA and a DQB gene in a tail‐to‐tail orientation. The genes in each locus are transcribed but only those designated DQ1 express class II molecules at the surface of mouse L cells following DNA‐mediated gene transfection. The DQA1 and DQB1 genes are separated by 11kb while the DQA2 and B2 genes are 25 kb apart. The loci are separated by 22 kb.
Toll-like receptor (TLR)-9 genetics and function in sarcoidosis
Authors: Veltkamp M , Van Moorsel C H M , Rijkers G T , Ruven H J T , Van Den Bosch J M M , Grutters J C
Published: July 2010

Sarcoidosis is a systemic disorder characterized by the formation of non-caseating granulomas in variable organs. Toll-like receptor (TLR)-9 is important in the innate immune response against both Mycobacterium tuberculosis and Propionibacterium acnes, candidate causative agents in sarcoidosis. The aim of our study was to investigate possible genetic and functional differences in TLR-9 between patients and controls. TLR-9 single nucleotide polymorphisms were genotyped in 533 patients and divided into a study cohort and validation cohort and 185 healthy controls. Furthermore, part of the promotor as well as the entire coding region of the TLR-9 gene were sequenced in 20 patients in order to detect new mutations. No genetic differences were found between patients and controls. In order to test TLR-9 function, peripheral blood mononuclear cells (PBMCs) of 12 healthy controls and 12 sarcoidosis patients were stimulated with a TLR-9 agonist and the induction of interleukin (IL)-6, interferon (IFN)-γ and IL-23 was measured. Sarcoidosis patients produce significantly less IFN-γ upon stimulation with different stimuli. Regarding IL-23 production, a significant difference between patients and controls was found only after stimulation with the TLR-9 agonist. In conclusion, we did not find genetic differences in the TLR-9 gene between sarcoidosis patients and controls. Sarcoidosis patients produce less IFN-γ regardless of the stimulating agent, probably reflecting the anergic state often seen in their peripheral blood T lymphocytes. The differences in TLR-9-induced IL-23 production could indicate that functional defects in the TLR-9 pathway of sarcoidosis patients play a role in disease susceptibility or evolution.
Copy number variation in chemokine superfamily: the complex scene ofCCL3L–CCL4Lgenes in health and disease
Authors: Colobran R , Pedrosa E , Carretero-Iglesia L , Juan M
Published: July 2010

Genome copy number changes (copy number variations: CNVs) include inherited, de novo and somatically acquired deviations from a diploid state within a particular chromosomal segment. CNVs are frequent in higher eukaryotes and associated with a substantial portion of inherited and acquired risk for various human diseases. CNVs are distributed widely in the genomes of apparently healthy individuals and thus constitute significant amounts of population-based genomic variation. Human CNV loci are enriched for immune genes and one of the most striking examples of CNV in humans involves a genomic region containing the chemokine genes CCL3L and CCL4L. The CCL3L–CCL4L copy number variable region (CNVR) shows extensive architectural complexity, with smaller CNVs within the larger ones and with interindividual variation in breakpoints. Furthermore, the individual genes embedded in this CNVR account for an additional level of genetic and mRNA complexity: CCL4L1 and CCL4L2 have identical exonic sequences but produce a different pattern of mRNAs. CCL3L2 was considered previously as a CCL3L1 pseudogene, but is actually transcribed. Since 2005, CCL3L-CCL4L CNV has been associated extensively with various human immunodeficiency virus-related outcomes, but some recent studies called these associations into question. This controversy may be due in part to the differences in alternative methods for quantifying gene copy number and differentiating the individual genes. This review summarizes and discusses the current knowledge about CCL3L–CCL4L CNV and points out that elucidating their complete phenotypic impact requires dissecting the combinatorial genomic complexity posed by various proportions of distinct CCL3L and CCL4L genes among individuals.
Constrained tomography of realistic velocity models in microseismic monitoring using calibration shots
Authors: Bardainne T. , Gaucher E.
Published: July 2010

The knowledge of the velocity model in microseismic jobs is critical to achieving statistically reliable microseismic event locations. The design of microseismic networks and the limited sources for calibration do not allow for a full tomographic inversion. We propose optimizing a priori velocity models using a few active shots and a non‐linear inversion, suitable to poorly constrained systems. The considered models can be described by several layers with different P‐ and S‐wave velocities. The velocities may be constant or have 3D gradients; the layer interfaces may be simple dipping planes or more complex 3D surfaces. In this process the P‐ and S‐ wave arrival times and polarizations measured on the seismograms constitute the observed data set. They are used to estimate two misfit functions: i) one based on the measurement residuals and ii) one based on the inaccuracy of the source relocation. These two functions are minimized thanks to a simulated annealing scheme, which decreases the risk of converging to a local solution within the velocity model.

The case study used to illustrate this methodology highlights the ability of this technique to constrain a velocity model with dipping layers. This was performed by jointly using sixteen perforation shots recorded during a multi‐stage fracturing operation from a single string of 3C‐receivers. This decreased the location inaccuracies and the residuals by a factor of six. In addition, the retrieved layer dip was consistent with the pseudo‐horizontal trajectories of the wells and the background information provided by the customer. Finally, the theoretical position of each calibration shot was contained in the uncertainty domain of the relocation of each shot. In contrast, single‐stage inversions provided different velocity models that were neither consistent between each other nor with the well trajectories. This example showed that it is essential to perform a multi‐stage inversion to derive a better updated velocity model.
Prescribing in a hospital for the mentally retarded
Authors: FISCHBACHER E.
Published: July 2010

ABSTRACT. This paper presents an analysis of the picture which emerged from a study of drug prescribing in a hospital for the mentally handicapped.
Nocturnal periodic breathing in adults with Down's syndrome
Authors: TELAKIVI T. , PARTINEN M. , SALMI T. , LEINONEN L. , HÄRKÖNEN T.
Published: July 2010

ABSTRACT. Nineteen adults with Down's syndrome were studied with the static charge sensitive bed (SCSBl method. A single whole‐night recording was made of each subject. Two different periodic breathing indices (PBIf and PBI%) were calculated from a computerized analysis of these recordings. A polygraphic recording was also made of one subject, a 52‐year‐old male. The EEC, the EOG, the EMG, nasal and oral airflow, and diaphragmatic movement were recorded, the latter with an abdominal strain gauge and with the SCSB‐method simultaneously. Good correlation was found between the recording with the SCSB and the strain gauge. The apnoea index (AI calculated from the polygraphic recording was 23.3, while the PBIf of this patient recorded on another night and analysed automatically was 45 and the PBI% was 78.6. The patient group was divided into those aged 40 or older (n= 10) and those aged 39 or younger (n=9). The mean PBI% of the older group was 24.0 while that of the younger group was 5.4 (t = 2.23; P<0.05). The mean PBIf of the older group was 16.7 and that of the younger was 3.6 (i=2.70; P=<0.02). The mean body mass index (BMI) of the younger group was significantly higher than the mean BMI of the older group. The mean BMI of those patients, whose FBI values were considered to be normal (PBI% <3, PBIf <7), did not significantly differ from the BMI of those patients, whose PBI‐values were abnormal. There were four patients with tonsillar or lingual hypertrophy in the older age group and five in the younger. The mean FBI‐values between those with and those without narrowing of the upper airways did not differ significantly. The study thus indicated that age is the most significant factor favouring the development of periodic breathing during sleep in patients with Down's syndrome.
Changes in life expectancy of mentally retarded persons in Canadian institutions: a 12‐year comparison
Authors: WOLF L. C. , WRIGHT R. E.
Published: July 2010

ABSTRACT. A 12‐year comparison of changes in the distribution of age, sex and level of functioning, as well as in life expectancy for menially retarded persons in Canadian institutions has been reported. The major findings of the study corroborate, for the most part, studies from other parts of the developed world despite differences in measures of mortality. Several trends have emerged from the data which will have implications for long‐termplanning.
Self‐injurious behaviour in people with mental handicap: a total population study
Authors: OLIVER C. , MURPHY G. H. , CORBETT J. A.
Published: July 2010

ABSTRACT. A survey of self‐injurious behaviour in people receiving services for mental handicap was carried out in one health region. Six hundred and sixteen adults and children were found to have engaged in self‐injurious behaviour sufficient to have caused tissue damage in the previous 4 months and 596 of these were screened. Half were resident in hospital while 28% were in non‐hospital residential care and the remainder (21%) were living at home. Nearly one‐fifth (19%) showed self‐injurious behaviour, of one or more types, at a rate of at least once per hour and a further 13% wore protective or restraining devices for all or part of the day or night. Only 2% were enrolled on formal psychological treatment programmes but nearly half were receiving psychotropic drugs (excluding anticonvulsants).
Intestinal obstruction as a cause of death in the mentally handicapped
Authors: ROY A. , SIMON G. B.
Published: July 2010

ABSTRACT. This paper reviews the occurrence of symptoms of intestinal obstruction in mentally handicapped people. A retrospective study was done on all residents dying in mental handicap hospitals over a 7‐year period. It was noticed that people dying of intestinal obstruction were younger, male, gave a history of constipation, other gastrointestinal problems and dietary indiscretion.
Use of a restricted protein diet in the treatment of behaviour disorderin a severely mentally retarded adult female phenylketonuric patient
Authors: HARPER M. , REID A. H.
Published: July 2010

ABSTRACT. A 54‐year‐old profoundly mentally retarded female patient with phenylketonuria and a severe behaviour problem was treated with a restricted protein and high energy diet. After several weeks of dietary intervention the patient's behaviour improved significantly.