bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: the clinical importance of growth in children with inflammatory bowel disease: is it important to the gastroenterologist?
Authors: TAMINIAU J. A.
Published: July 2010

Background  Growth in children with inflammatory bowel disease is often compromised.

Aim  To explore the origins of growth retardation in paediatric inflammatory bowel disease and to consider management strategies.

Methods  Relevant literature was identified and reviewed.

Results  A combination of the following factors results in growth retardation: insufficient food intake, malabsorption, increased catabolism, disease activity, disease extension, complications of disease and the side‐effects of treatment.

Conclusions  Failure of normal growth in a child with inflammatory bowel disease is an indicator of insufficient and unsuccessful therapy. The major causative factor is chronic anorexia because of chronic catabolic illness. Growth resumes to normal after effective control of the disease and nutritional intake. Regular follow‐up of growth in these children is mandatory, and the measurement of both height and weight is an ideal indication of effective treatment. Failure of sustained growth in a child or adolescent with inflammatory bowel disease is a warning to consider a change of clinical strategy.
Review article: detection and management of hereditary non‐polyposis colorectal cancer (Lynch syndrome)
Authors: RAMSOEKH D. , VAN LEERDAM M. E. , WAGNER A. , KUIPERS E. J.
Published: July 2010

Background  The most common hereditary colorectal cancer syndrome is hereditary non‐polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. Diagnosis of this syndrome is difficult, because of lack of specific diagnostic fatures.

Aim  To discuss the diagnostic criteria and laboratory work up for HNPCC. Furthermore, survelillance programs for HNPCC and treatment of HNPCC associated colorectal cancer are discussed.

Results  Current diagnostic criteria, including the Amsterdam II and Bethesda criteria, are suboptimal for the detection of HNPCC. Molecular screening by microsatellite instability (MSI) and immunohistochemistry (IHC) is useful in the diagnosis of HNPCC. Both techniques have a higher sensitivity compared to the Amsterdam II and Bethesda criteria. A combination of both MSI and IHC provides the most optimal selection for mutation analysis. After identification of a mutation in an affected individual, genetic counselling and presymptomatic mutation analysis should be offered to relatives. Furthermore, colonoscopic surveillance should be performed in proven mutation carriers.

Conclusions  Identification of HNPCC is a clinical challenge involving many clinicians. Identification of persons at risk can be achieved by a combination of a detailed family history, testing with molecular and mutation analysis.
Coeliac disease in chronic hepatitis C: a French multicentre prospective study
Authors: THEVENOT T. , DENIS J. , JOUANNAUD V. , MONNET E. , RENOU C. , LABADIE H. , ABDELLI N. , NGUYEN‐KHAC E. , DUMOUCHEL P. , BRESSON‐HADNI S. , CHOUSTERMAN M. , DI MARTINO V. , CADRANEL J.‐F.
Published: July 2010

Background  A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship.

Aim  To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)‐infected patients.

Methods  Between June 2003 and November 2005, 624 consecutive HCV‐positive out‐patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies.

Results  Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected.

Conclusions  The prevalence of CD in HCV‐positive patients was 0% (95% confidence interval: 0–0.59%), but there is a low prevalence of CD in the whole French population.
Hepatic steatosis in HIV‐HCV coinfected patients in France: comparison with HCV monoinfected patients matched for body mass index and HCV genotype
Authors: CASTÉRA L. , LOKO M. A. , LE BAIL B. , COFFIE P. , DE LEDINGHEN V. , TRIMOULET P. , WINNOCK M. , DABIS F. , NEAU D. ,   THE GROUPE D’EPIDÉMIOLOGIE CLINIQUE DU SIDA EN AQUITAINE (GECSA)
Published: July 2010

Background  Significance of steatosis in HIV‐HCV coinfection remains controversial.

Aim  To compare the prevalence and predictors of hepatic steatosis between HIV‐HCV and HCV patients matched for steatosis known determinants.

Methods  A total of 564 HCV‐naive patients undergoing liver biopsy were studied: 137 with HIV‐HCV coinfection and 427 with HCV monoinfection, among whom 137 were matched for age, gender, body mass index and HCV genotype.

Results  Steatosis of any grade (67.1% vs. 41.6%, P < 0.0001), mixed steatosis (55.4% vs. 21.1%, P < 0.0001), severe histological activity (A2‐A3: 78.1% vs. 55.5%, P < 0.0001) and severe fibrosis (F3‐F4: 33.1% vs. 15.3%, P < 0.0001) were significantly more common in coinfected than in matched monoinfected patients. In multivariate analysis, steatosis was associated only with severe histological activity [odds ratio (OR): 3.1 (95% CI: 1.3–7.1)] in coinfected patients and with elevated body mass index [OR; 1.3 (1.1–1.5)], HCV genotype 3 [OR: 5.6 (2.3–13.9)], severe histological activity [OR: 3.1 (1.3–7.3)] and severe fibrosis [OR: 4.7 (1.3–17.3)] in monoinfected patients.

Conclusions  Steatosis is significantly more common and severe in HIV‐HCV coinfected than in HCV monoinfected French patients, even after matching for body mass index and HCV genotype. Steatosis is associated only with severe histological activity in coinfected patients and with previously reported factors in monoinfected patients, thus suggesting different underlying mechanisms.
Meta‐analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non‐steroidal anti‐inflammatory drugs
Authors: LOKE Y. K. , TRIVEDI A. N. , SINGH S.
Published: July 2010

Background  Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal haemorrhage (UGIH) but the magnitude and characteristics of this reaction and possible interaction with concurrent Non‐Steroidal Anti‐Inflammatory Drug (NSAID) therapy are unknown.

Aim  To evaluate systematically the risk of UGIH with SSRIs, including interaction with NSAIDs.

Methods  We searched PubMED, Science Citation Index, and trial registries for data on SSRIs, NSAIDs and UGIH. We evaluated spontaneous case reports from pharmacovigilance databases.

Results  Random effects meta‐analysis of four observational studies involving 153 000 patients showed an odds ratio of 2.36 (95% CI: 1.44–3.85; P = 0.0006) for SSRI associated UGIH. The odds ratio increased to 6.33 (95% CI: 3.40–11.8; P < 0.00001) with concomitant NSAIDs. In patients aged above 50 years with no UGIH risk factors, the Number‐Needed‐to‐Harm per year is 411 for SSRIs alone, and 106 with concomitant NSAIDs. Analysis of 101 spontaneous reports showed that UGIH occurred after a median of 25 weeks with SSRIs. Around 67% of these patients were on NSAIDs.

Conclusions  Selective serotonin reuptake inhibitor use, alone and in combination with NSAIDs, substantially increases the risk of UGIH. Clinicians should consider this when managing patients at risk of, or presenting with UGIH.
Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota
Authors: KAJANDER K. , MYLLYLUOMA E. , RAJILIĆ‐STOJANOVIĆ M. , KYRÖNPALO S. , RASMUSSEN M. , JÄRVENPÄÄ S. , ZOETENDAL E. G. , DE VOS W. M. , VAPAATALO H. , KORPELA R.
Published: July 2010

Background  Irritable bowel syndrome is the most common diagnosis in gastroenterology. Trials suggest certain probiotics to be beneficial.

Aim  To investigate the effects of multispecies probiotic supplementation (Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium animalis ssp. lactis Bb12) on abdominal symptoms, quality of life, intestinal microbiota and inflammatory markers in irritable bowel syndrome.

Methods  Eighty‐six irritable bowel syndrome patients (Rome II criteria) participated in this randomized, placebo‐controlled 5‐month intervention. Patients were randomized to receive daily either multispecies probiotic supplementation or placebo. Irritable bowel syndrome symptoms, quality of life, microarray‐based intestinal microbiota stability (n = 20), serum cytokines and sensitive C‐reactive protein were monitored.

Results  The composite irritable bowel syndrome score had at 5 months decreased 14 points (95% CI: −19 to −9) from baseline with the multispecies probiotic vs. three points (95% CI: −8 to 1) with placebo (P = 0.0083). Especially, distension and abdominal pain were affected. A stabilization of the microbiota was observed, as the microbiota similarity index increased with the probiotic supplementation (1.9 ± 3.1), while it decreased with placebo (−2.9 ± 1.7). No differences were seen in C‐reactive protein.

Conclusions  This multispecies probiotic seems to be an effective and safe option to alleviate symptoms of irritable bowel syndrome, and to stabilize the intestinal microbiota.
The association of MYO9B gene in Italian patients with inflammatory bowel diseases
Authors: LATIANO A. , PALMIERI O. , VALVANO M. R. , D’INCÀ R. , CAPRILLI R. , CUCCHIARA S. , STURNIOLO G. C. , BOSSA F. , ANDRIULLI A. , ANNESE V.
Published: July 2010

Background  Variants of myosin IXB (MYO9B) gene, encoding for a motor protein implicated in epithelial permeability, have been recently associated with inflammatory bowel disease.

Aims  To investigate the contribution of three polymorphisms of MYO9B gene for predisposition to Crohn’s disease and ulcerative colitis, their association with clinical phenotypes, particularly intestinal permeability, and possible interaction with the CARD15 gene.

Methods  549 Crohn’s disease patients, 658 ulcerative colitis patients and 674 controls were genotyped for the rs962917, rs1545620 and rs2305764 single nucleotide polymorphisms.

Results  Highly significant genotypic association with Crohn’s disease and ulcerative colitis was shown for all three single nucleotide polymorphisms, with odds ratio ranging from 1.5 to 1.7 (P‐value: <0.01 to <0.002). A significant difference in allele frequencies was also observed in inflammatory bowel disease patients, with the single most significant association for rs1545620, detected in 47% of Crohn’s disease, 47% of ulcerative colitis patients and 42% of controls (P < 0.005). No association with specific sub‐phenotypes was found, with the exception of a trend towards an abnormal intestinal permeability (P = 0.043) in Crohn’s disease carrying the rs1545620 risk allele.

Conclusions  Our findings confirm the association between the MYO9B polymorphisms and susceptibility to both ulcerative colitis and Crohn’s disease, with a weak influence on sub‐phenotypic expression.
Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis
Authors: RHODES J. M. , ROBINSON R. , BEALES I. , PUGH S. , DICKINSON R. , DRONFIELD M. , SPEIRS C. J. , WILKINSON P. , WILKINSON S. P.
Published: July 2010

Background  Systemic corticosteroids are effective in ulcerative colitis but commonly cause side effects.

Aim  To compare the safety and efficacy of a sparingly absorbed formulation of prednisolone metasulfobenzoate (Predocol) with a conventional tapering course of oral prednisolone.

Method  In a double‐blind randomized study, 59 active ulcerative colitis patients received Predocol 40 mg/day for 6 months, 61 received Predocol 60 mg/day for 6 months and 61 received prednisolone 40 mg/day for 2 weeks, tapered to week 8, followed by placebo until 6 months.

Results  Steroid‐related side effects assessed using a 10‐cm visual analogue scale were fewer at 2 months with Predocol 40 mg [VAS 8.1 cm (2.6), mean (s.d.)], or 60 mg [8.1 (2.1)] compared with prednisolone [6.7 (2.7); P = 0.01]. Mood changes affected 43% receiving prednisolone at 4 weeks vs. 8% for Predocol 40 mg (P = 0.001). Remission rates (Powell‐Tuck ≤2) at 2 months were Predocol 40 mg 46%, Predocol 60 mg 28% and tapering prednisolone 41% (P = 0.13). Visual analogue scale for efficacy also showed non‐inferiority for Predocol 40 mg/day. Remission rates at 6 months were Predocol 40 mg 51%, Predocol 60 mg 38% and tapering prednisolone 32% (P = 0.08).

Conclusion  Predocol 40 mg/day has similar efficacy but markedly fewer side effects than a conventional tapering prednisolone regimen (ISRCTN14133410).
The incidence of Crohn’s disease in Cardiff over the last 75 years: an update for 1996–2005
Authors: GUNESH S. , THOMAS G. A. O. , WILLIAMS G. T. , ROBERTS A. , HAWTHORNE A. B.
Published: July 2010

Background The incidence of Crohn's disease rose rapidly in industralized countries over the past 50 years, but it is unclear whether the incidence is still rising or has reached a plateau.

Aims  To update the long‐term incidence study of Crohn’s disease in Cardiff for 1996–2005, to investigate whether incidence is still rising and to study changes in disease characteristics over time.

Method  Crohn’s cases identified by retrospective analysis of hospital records as in previous studies in Cardiff.

Results  Two hundred and twelve cases were identified. Corrected incidence for this decade was 66 × 106 per year (95% confidence interval: 58–76), showing a continuing rise compared to previous decades. The proportion with colonic disease at presentation continues to rise (43%) with a corresponding fall in those with terminal ileal disease. There remains a strong female preponderance (F:M 1.6:1) as in previous studies. The incidence in children under age 16 continues to rise, and the median age at diagnosis has fallen slightly.

Conclusion  Crohn’s disease incidence continues to rise slowly in Cardiff with a continuing increase in those presenting with colonic disease, which is now the commonest disease pattern.
Factors predicting survival in patients with advanced oesophageal cancer: a prospective multicentre evaluation
Authors: BERGQUIST H. , JOHNSSON Å. , HAMMERLID E. , WENGER U. , LUNDELL L. , RUTH M.
Published: July 2010

Background  Oesophageal cancer is often diagnosed at an advanced stage, with poor prognosis and severe morbidity. In majority of cases, palliative treatment is the only option available.

Aim  To find factors that can predict survival for patients with incurable cancer of the oesophagus or gastro‐oesophageal junction and hence aid in the choice of treatment.

Methods  Ninety‐six patients were included. Health‐related quality of life questionnaires (EORTC QLQ C‐30 and QLQ OES18) were administered and computerized tomography‐derived size assessment of the primary tumours was performed. Univariate and multivariate Cox‐regression analyses were used to determine potential predictors of survival.

Results  Karnofsky Index, occurrence of metastases (M‐stage), Union International Contre le Cancer‐stage, computerized tomography‐derived tumour size assessment and 10 of 25 scales and single items from the health‐related quality of life questionnaires were found to be related to survival. In the multivariate analysis, three of the health‐related quality of life questionnaire scales (physical functioning, fatigue and reflux) were found to add prognostic information to M‐stage, the single strongest predictor (HR 1.9, P < 0.01).

Conclusion  In addition to M‐stage, the outcome of health‐related quality of life questionnaires can sharpen the prediction of survival in patients with advanced cancer of the oesophagus or gastro‐oesophageal junction and thus aid in the choice of palliative treatment strategy.
Review article: endoscopic antireflux procedures – an unfulfilled promise?
Authors: PACE F. , COSTAMAGNA G. , PENAGINI R. , REPICI A. , ANNESE V.
Published: July 2010

Background  Most published reviews concerning the endoscopic treatment of gastro‐oesophageal reflux disease date back to 2005.

Aim  To provide an updated review that includes all papers published up to 2007.

Methods  A Medline search from January 2005 to June 2007 was performed regarding endoscopic procedures aiming at treating gastro‐oesophageal reflux disease. In addition, we retrieved the abstracts presented at Digestive Disease Week during the last 3 years. We included in the review both ‘mechanistic’ studies – that is, papers exploring the potential mechanism of action of the procedure/device – and studies trying to assess its clinical efficacy.

Results  During the last 3 years, the number of published papers has declined, and some devices are not available any more. The alleged mechanism(s) of action of the various devices or procedures is (are) still not completely elucidated; however, some concerns have arisen as far as durability and potential detrimental effects. Moreover, all the aspects of endoscopic therapy, except for its safety, are either insufficiently explored or not investigated at all, or assessed only in particularly selected patient subgroups.

Conclusions  None of the proposed antireflux therapies has fulfilled the criteria of efficacy, safety, cost, durability and, possibly, of reversibility. There is at present no definite indication for endoscopic therapy of gastro‐oesophageal reflux disease. We suggest a list of recommendations to be followed when a new endoscopic therapeutic procedure is to be assessed for use in clinical practice.
The clinical spectrum of cytomegalovirus colitis in adults
Authors: EINBINDER Y. , WOLF D. G. , PAPPO O. , MIGDAL A. , TSVANG E. , ACKERMAN Z.
Published: July 2010

Background  Colonic cytomegalovirus reactivation rarely occurs in adults without inflammatory bowel disease or a known immunosuppressive state.

Aim  To describe our experience with such patients.

Methods  All consecutive admissions of patients with possible cytomegalovirus colitis, between 1995 and 2006, were reviewed retrospectively.

Results  Nineteen patients were studied. Most of the patients were elderly with multiple co‐morbidities. Three main forms of disease presentation were recognized: acute diarrhoea, chronic diarrhoea and lower gastrointestinal bleeding. Colonic mucosal intranuclear inclusion bodies were found in 12 patients. Thirteen patients had cytomegalovirus viraemia (either by polymerase chain reaction and/or by white blood cell‐cytomegalovirus antigenaemia test). Ganciclovir therapy was given to only eight patients; only five of these patients survived. The other subgroup of 11 patients received only supportive therapy. Most of the patients from this subgroup had a prolonged and complicated hospital course; only nine patients survived. Follow‐up colonoscopies were performed only in five patients (out of the 14 patients who survived). In four of these patients, chronic mucosal inflammatory changes were noted.

Conclusions  Cytomegalovirus colitis occurs rarely in adult individuals. The disease may have various and multiple acute and/or chronic clinical manifestations. Clinical awareness of this condition is needed.
Review article: evolving concepts in treatment and disease modification in ulcerative colitis
Authors: HANAUER S. B.
Published: July 2010

Background  More than two‐thirds of ulcerative colitis patients experience at least one relapse over a period of 10 years. Treatments that reduce the likelihood of relapses also reduce the risk of long‐term complications.

Aim  To review three topics: the current standard of treatment for ulcerative colitis, evolving concepts in treatment, and disease modification as a treatment goal of the future.

Results  Currently, 5‐aminosalicylates are the standard treatment for the induction and maintenance of remission in mild‐to‐moderate ulcerative colitis patients. Evidence suggests that patients who take oral 5‐aminosalicylates regularly are nearly six times more likely to experience regression in disease severity than those who do not. Additional treatment options such as corticosteroids, immunomodulators, biological therapies and ciclosporin are available for moderate‐to‐severe ulcerative colitis patients, or those who do not respond to 5‐aminosalicylate. Surgery becomes pertinent for more than one‐third of ulcerative colitis patients during the course of their disease. With the availability of a variety of therapies, advances in surgery and improved management strategies, a better understanding of patient treatment expectations can help improve the quality of care for ulcerative colitis patients.

Conclusions  Disease modification is increasingly becoming a treatment goal in the management of ulcerative colitis. However, long‐term studies are needed to examine further the disease modifying role of 5‐aminosalicylates.
Impairment of health‐related quality of life in functional dyspepsia and chronic liver disease: the influence of depression and anxiety
Authors: HAAG S. , SENF W. , HÄUSER W. , TAGAY S. , GRANDT D. , HEUFT G. , GERKEN G. , TALLEY N. J. , HOLTMANN G.
Published: July 2010

Background  Health‐related quality of life (HRQOL) is a marker of disease severity. Data on the relative impairment of HRQOL in chronic liver disease (CLD) and functional gastrointestinal disorders are lacking and no studies have assessed the link between impairment of HRQOL and psychosocial factors yet.

Aim  To assess predictors for, and the impairment of, HRQOL in CLD and FD.

Methods  In 181 functional dyspepsia (FD) patients, 204 CLD patients and 337 healthy blood donors, HRQOL was assessed with the Short Form‐36 (mental and physical component), and anxiety and depression utilizing the Hospital Anxiety and Depression Scale.

Results  Compared with HC, HRQOL is significantly lower in FD and CLD (P‐value for all <0.001). The mental but not physical component of HRQOL was significantly more impaired in FD compared with CLD (P < 0.05). After adjusting for confounders, impairment of mental (P < 0.001) and physical (P = 0.005) component of HRQOL was associated with the severity of CLD and FD. In FD, the multivariate analysis revealed depression and severity of symptoms as the most important predictors of HRQOL (R2 = 21.9 and 7.1). In CLD, the mental component of HRQOL was associated with depression and anxiety (R2 = 9.9 and 9.7).

Conclusions  In tertiary care, HRQOL is more severely impaired in FD compared with CLD. Co‐morbid psychiatric conditions significantly contribute to the impairment of HRQOL.
Review article: gastrointestinal sensory and motor disturbances in inflammatory bowel disease – clinical relevance and pathophysiological mechanisms
Authors: DE SCHEPPER H. U. , DE MAN J. G. , MOREELS T. G. , PELCKMANS P. A. , DE WINTER B. Y.
Published: July 2010

Background  It is well known that inflammation has a profound impact on the neuromuscular apparatus of the gastrointestinal tract during the inflammatory insult and in periods of remission, at the site of inflammation and at distance from this site. The importance of this interaction is illustrated by the higher prevalence of functional gut disorders in patients with inflammatory bowel disease.

Aims  To document the epidemiological and clinical significance of functional alterations of gut motility and sensitivity in patients with inflammatory bowel disease and to formulate potential pathophysiological mechanisms.

Results and conclusions  Functional gut disorders occur frequently in patients with inflammatory bowel disease, both during inflammatory episodes and in periods of remission, and have a major impact on their quality of life. The clinical manifestations of these motility and sensitivity disorders vary and are often difficult to treat, mainly because therapeutic guidelines and specific diagnostic tests to distinguish inflammatory bowel disease from functional gut disorders are lacking. Chronic bowel inflammation results in a complicated interaction between neuroendocrine serotonin‐predominant cells of the mucosa, inflammatory cells (particularly mast cells) in the submucosa, the intrinsic and extrinsic innervation and the muscular apparatus including the interstitial cells of Cajal. The outcome of this interaction is a perturbation of gastrointestinal motor function, both locally and at distance from the site of inflammation and during both acute inflammation and remission.
Review article: self‐report measures to evaluate constipation
Authors: MCCREA G. L. , MIASKOWSKI C. , STOTTS N. A. , MACERA L. , HART S. A. , VARMA M. G.
Published: July 2010

Background  Constipation is a subjective phenomenon, and as such must be evaluated using patient self‐report. Valid and reliable measures of constipation are essential to standardize the diagnosis, assess the severity and evaluate the effectiveness of treatments.

Aim  To compare and contrast published self‐report measures of constipation in terms of development, content, general characteristics, psychometric properties and clinical utility.

Methods  MEDLINE (1966–2007), CINAHL (1980–2007), Cochrane (1993–2007) and Web of Science (1995–2007) were searched to identify self‐report measures of constipation. Measures of constipation were selected if they: (i) were self‐report measures that measured only constipation; (ii) had undergone psychometric testing; (iii) were used in adults and (iv) were written in English.

Results  Seven self‐report measures of constipation were identified. The content areas evaluated by these measures varied. Only two measures had adequate validity and reliability, sensitivity to change, or were tested in more than one sample.

Conclusions  Findings from this review suggest that the Chinese Constipation Questionnaire and the Patient Assessment of Constipation‐Symptom Questionnaire demonstrate adequate psychometric properties for a constipation measure. Additional research is warranted to refine or develop a more comprehensive self‐report measure to evaluate constipation in adults.
Review article: novel therapeutic options for chronic hepatitis C
Authors: CHOLONGITAS E. , PAPATHEODORIDIS G. V.
Published: July 2010

Background  The efficacy of treatment against hepatitis C virus has improved, but it is still far from ideal. Thus, new antihepatitis C virus therapies are required.

Aim  To evaluate the data on antihepatitis C virus approaches beyond the current standard combination of pegylated interferon‐alpha and ribavirin.

Method  We reviewed the available literature regarding novel antihepatitis C virus options, given alone or in combination with existing agents.

Results  New interferons and ribavirin alternatives have been tried aiming to improve the efficacy and the safety/tolerability profile of standard agents. The hepatitis C virus polymerase and NS3/4A protease have been rather popular targets for new antihepatitis C virus agents. The combination of such inhibitors with pegylated interferon‐alpha and ribavirin seems to act synergistically and to prevent viral resistance, compared to monotherapies. Several novel immunomodulators are currently evaluated and may be useful in combination therapies. Alternative strategies (inhibition of hepatitis C virus protein translation, assembly/release or binding) or agents with different modes of action (statins, S‐adenosylmethionine and herbs) need further evaluation.

Conclusions  Many novel promising antihepatitis C virus agents are being developed, offering hope for future therapies that may target multiple points of the viral life cycle and/or host immune response. Newer approaches should ideally provide safe, effective and more tolerable therapy to all chronic hepatitis C virus patients.
Systematic review: prevention of travellers’ diarrhoea
Authors: DUPONT H. L.
Published: July 2010

Background  Renewed interest in the use of antibiotics to prevent travellers’ diarrhoea has occurred with the availability of non‐absorbed (<0.4%) rifaximin, and with evidence that a subgroup of travellers with diarrhoea have progression of their illnesses to postinfectious irritable bowel syndrome.

Aim  To summarize recently published information and make recommendations on travellers' diarrhoea prevention.

Methods  PubMed was reviewed on 2 January 2008 for 255 articles on the topic of ‘travellers diarrhoea’ published beginning with 2000 along with the author’s extensive file on prevention of travellers’ diarrhoea.

Results  Exercising care in food and beverage selection, while of unproven value, is recommended during travel to high‐risk areas of Latin America, Southern Asia or Africa. An algorithm is presented to identify future travellers, for which chemoprophylaxis is appropriate. The preferred drug for prevention of travellers’ diarrhoea is rifaximin, with bismuth subsalicylate or a fluoroquinolone also being effective. Vaccines against the principal cause of travellers’ diarrhoea, enterotoxigenic Escherichia coli, are being developed.

Conclusions  Research is needed to determine the relative effectiveness of exercising care on food and beverage selection and chemoprophylaxis in preventing travellers’ diarrhoea and postinfectious irritable bowel syndrome during high‐risk travel. Enterotoxigenic E. coli vaccines appear to be a promising addition to travel medicine.
The citrulline generation test: proposal for a new enterocyte function test
Authors: PETERS J. H. C. , WIERDSMA N. J. , TEERLINK T. , VAN LEEUWEN P. A. M. , MULDER C. J. J. , VAN BODEGRAVEN A. A.
Published: July 2010

Background The amino acid citrulline is mainly produced by enterocytes from conversion of glutamine. As fasting plasma citrulline proved disappointing as a biomarker for enterocyte dysfunction in clinical practice, we propose a citrulline generation test (CGT) to assess enterocyte function.

Aim To assess the feasibility of a CGT in healthy subjects and patients with decreased enterocyte mass.

Methods Nineteen healthy subjects, 16 patients with intestinal villous atrophy and nine patients with short bowel syndrome (SBS) were given an oral bolus of 20 g of the dipeptide alanine–glutamine. Subsequent changes in plasma citrulline and other amino acid concentrations were determined using reverse‐phase high‐performance liquid chromatography.

Results Following the oral bolus of alanine–glutamine, plasma citrulline concentrations showed a time dependent rise in healthy subjects of 44 ± 13% (38–55 μmol/L,P < 0.0001). The slope from baseline plasma citrulline to peak concentrations was 0.22 ± 0.08, 0.13 ± 0.04 and 0.09 ± 0.04 μmol/L/min in healthy subjects, patients with coeliac disease (CeD) and refractory CeD, respectively (healthy subjects vs. CeDP < 0.05, healthy subjects vs. refractory CeDP < 0.001). In patients with SBS, the CGT was able to distinguish between non‐adapted and adapted SBS by means of the incremental area under the CGT curve till 90 min (iAUC T90). The iAUC T90 was 447 ± 179 and 1039 ± 178 μmol/L/min in non‐adapted and adapted SBS, respectively (P = 0.04).

Conclusion An oral bolus of alanine–glutamine induces a time‐dependent rise in plasma citrulline concentration to an extent dependent on the existence of villous atrophy or enterocyte hyperplasia in CeD, and adapted SBS, respectively.
Evaluating anti‐viral drug selection and treatment duration in HBeAg‐negative chronic hepatitis B: a cost‐effectiveness analysis
Authors: VEENSTRA D. L. , SPACKMAN D. E. , BISCEGLIE A. , KOWDLEY K. V. , GISH R. G.
Published: July 2010

Background Several anti‐viral treatments are now available for HBeAg‐negative chronic hepatitis B (CHB), but the clinical and economic outcomes of potential treatment strategies and durations are unclear.

Aim To examine the clinical and economic outcomes of potential treatment strategies and durations for HBeAg‐negative CHB.

Methods We conducted a cost‐utility analysis from a payer perspective over a lifetime time horizon. Disease progression probabilities, costs and quality of life data were derived from the literature. We evaluated 5‐year, 10‐year, lifetime and 5 on–1 off treatment durations. For each of these treatment durations, we evaluated initial therapy with entecavir, lamivudine or adefovir, with addition of adefovir or entecavir for patients who developed virological breakthrough because of resistance (12 strategies total).

Results Increasing treatment duration improved quality‐adjusted life‐years (QALYs) and was generally cost‐effective for all three drugs. However, a 5 on–1 off strategy was the most cost‐effective: lifetime vs. 5 on–1 off entecavir had an ICER of $148 200/QALY. In probabilistic sensitivity analyses, entecavir 5 on–1 off was the preferred strategy over the range of commonly reimbursed cost‐effectiveness thresholds. Lifetime treatment was preferred to a 5 on–1 off strategy, if treatment durability was <10%.

Conclusion The results of our analysis suggest that in HBeAg‐negative CHB infection, a 5 on–1 off treatment strategy with entecavir improves health outcomes in a cost‐effective manner compared to alternative strategies.
Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems
Authors: CAMMÀ C. , MARCO V. DI , CABIBBO G. , LATTERI F. , SANDONATO L. , PARISI P. , ENEA M. , ATTANASIO M. , GALIA M. , ALESSI N. , LICATA A. , LATTERI M. A. , CRAXÌ A.
Published: July 2010

Background  A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately.

Aim  To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC.

Methods  We included 406 consecutive patients with cirrhosis and HCC. Seventy‐eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model.

Results  One‐hundred and seventy‐eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha‐fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients.

Conclusions  Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients.
Clinical trial design in adult reflux disease: a methodological workshop
Authors: DENT J. , KAHRILAS P. J. , VAKIL N. , VAN ZANTEN S. VELDHUYZEN , BYTZER P. , DELANEY B. , HARUMA K. , HATLEBAKK J. , MCCOLL E. , MOAYYEDI P. , STANGHELLINI V. , TACK J. , VAEZI M.
Published: July 2010

Background  The development of well‐tolerated acid suppressant drugs has stimulated substantial growth in the number of trials assessing therapy options for gastro‐oesophageal reflux disease (GERD).

Aim  To develop consensus statements to inform clinical trial design in adult patients with GERD.

Methods  Draft statements were developed employing a systematic literature review. A modified Delphi process including three rounds of voting was used to reach consensus. Between voting, statements were revised based on feedback from the Working Group and additional literature reviews. The final vote was at a face‐to‐face meeting that included discussion time. Voting was conducted using a six‐point scale.

Results  At the last vote, 93% of the final 102 statements achieved consensus (defined a priori as being supported by ≥75% of the votes). The Working Group strongly supported the development of validated patient‐reported outcome instruments. Symptom assessments carried out by the investigator were considered unacceptable. There was agreement that exclusion from clinical trials should be minimized to improve generalizability, that prospective evaluation ideally requires electronic timed/dated methods and that endoscopists should be blinded to patient symptom status.

Conclusions  Implementation of the consensus statements will improve the quality and comparability of trials, and make them compatible with regulatory requirements.
The haemodynamic response to propranolol in cirrhosis with arterial hypertension: a comparative analysis with normotensive cirrhotic patients
Authors: Sharma P. , Kumar A. , Jha S. , Mishra S. R. , Sharma B. C. , Sarin S. K.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 105–112

Background  Cirrhosis with arterial hypertension is not uncommon. Haemodynamic alterations in these patients and the effects of beta‐blocker on hepatic venous pressure gradient (HVPG) and systemic haemodynamics have not been evaluated.

Aims  To compare the systemic haemodynamic alterations in hypertensive and normotensive cirrhotics, and to investigate the effects of propranolol on these parameters.

Methods  A retrospective analysis of consecutive hypertensive cirrhotic patients (n = 33) who underwent haemodynamic assessment and paired HVPG measurement was done. Normotensive cirrhotics (n = 50) served as controls.

Results  Hypertensive patients had a significantly higher heart rate, systemic (SVRI), and pulmonary vascular resistance. There was a significant reduction in mean arterial pressure (MAP) in the hypertensive cirrhotic group from 112 (107–130) mmHg to 95 (77–114) mmHg (P < 0.01), but no change in the normotensives. SVRI remained the same in the hypertensive cirrhotic group, but it increased in the normotensives. There was no correlation between MAP reduction and HVPG reduction.

Conclusions  The frequency of HVPG response with propranolol treatment in hypertensive cirrhotics is similar to normotensive cirrhotics. Propranolol treatment reduces MAP significantly in hypertensive patients with cirrhosis. Treatment with a nonselective beta‐blocker is a good strategy for hypertensive cirrhotic patients.
A comparison of the acceptance of immunochemical faecal occult blood test and colonoscopy in colorectal cancer screening: a prospective study among Chinese
Authors: Wong M. C. S. , Tsoi K. K. F. , Ng S. S. M. , Lou V. W. Q. , Choi S. Y. P. , Ling K. W. K. , Chan F. K. L. , Griffiths S. M. , Sung J. J. Y.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 74–82

Background  Preferences to choose immunochemical faecal occult blood test (FIT) and colonoscopy as colorectal cancer (CRC) screening modalities among asymptomatic Chinese subjects remain unknown.

Aim  To evaluate the preference of choosing colonoscopy vs. FIT among CRC screening participants.

Methods  From a community‐based CRC screening programme for asymptomatic Hong Kong Chinese aged 50–70 years, participants attended standardized educational sessions and chose the options of annual FIT for 5 years or direct colonoscopy once. Factors associated with choosing colonoscopy were evaluated by multivariate regression analysis.

Results  Among 3430 participants [mean age 56.8 years (s.d. 5.0); female 55.1%, male 44.9%], 51.3% chose colonoscopy and 48.7% chose FIT. Older participants (65–70 years) were less likely to choose colonoscopy [adjusted odds ratio (aOR) 0.731, P = 0.041]. Subjects who chose colonoscopy were those disagreed screening would lead to discomfort (aOR 1.356, P < 0.001), had relatives or friends who had CRC (first degree relatives aOR 1.679, P < 0.001; second degree relatives aOR 1.304, P = 0.019; friends or others aOR 1.252, P = 0.026) and those who self‐perceived their health as poor (aOR 1.529, P = 0.025).

Conclusions  Faecal occult blood test and direct colonoscopy were equally preferable to Chinese. Colonoscopy was preferred among the younger subjects, those with positive family history of CRC and self‐perceived poor health status.
Buprenorphine versus morphine. A comparison of intra‐operative and postoperative analgesia
Authors: Green D.W. , Sinclair J.R. , Mikhael M.S.
Published: July 2010

A randomised double‐blind trial comparing morphine and buprenorphine for intra‐operative and postoperative analgesia combined with droperidol was conducted in 60 patients. Compared with morphine, taken as the standard analgesic, buprenorphine was shown to be a satisfactory analgesic for major surgery, with no difference in the incidence of unwanted effects.
Plasma volume estimation using indocyanine green
Authors: BUSSE M. W. , ZISOWSKY S. , HENSCHEN S. , PANNING B. , PIEPENBROCK S.
Published: July 2010

The validity and reliability of plasma volume estimation using indocyanine green were investigated in five in vitro experiments and in three in vivo series. The in vitro measurements reflected real volumes with an error of about 1%. Comparative measurements in the same patients using indocyanine green or Cr51 labelled red cells differed by 1.7% (r = 0.97). The mean (SD) plasma volume difference between two successive plasma volume measurements using indocyanine green was 38 (43) ml (r = 0.99). Plasma volume measured before and about 7 min after a hyperosmolar saline bolus (100 ml, 1 molar) was increased by 223 (102) ml and 286 (49) ml when determined by indocyanine green and plasma protein changes respectively. Nevertheless, the necessity for central venous injection and arterial sampling restricts the possible application of the method to intra‐operative or emergency care use.
Atelectasis and oxygenation in major surgery with either propofol with or without nitrous oxide or isoflurane anaesthesia
Authors: Jensen A. G. , Kalman S. H. , Eintrei C. , Fransson S.‐G. , Morales O.
Published: July 2010

Forty‐two patients undergoing major colonic surgery were assigned at random to receive isoflurane‐fentanyl anaesthesia with nitrous oxide in oxygen, propofol‐fentanyl anaesthesia with air in oxygen or propofol‐fentanyl anaesthesia with nitrous oxide in oxygen. The groups were comparable in demographic data. Atelectases were identified, and the area measured by computerised tomography of the chest 203±69 min after extubation. and oxygenation was determined by arterial blood gas samples taken during operation at 30, 60, 90 and 120 min after extubation and on postoperative days 1, 2 and 3. Atelectases were seen in all three groups with no differences in the mean area between groups. After operation, the effect of 4 l.min−1 of oxygen by nasal catheter on Pao2 was similar in all groups. A significant decrease in PaO2 was found during the first 3 days after surgery, and was also the same in all groups. There was no correlation between area of atelectasis and postoperative PaO2. We conclude there is no difference in the incidence of postoperative atelectasis or oxygenation when using propofol, with or without nitrous oxide or isoflurane.
Mortality after spinal and general anaesthesia for surgical fixation of hip fractures
Authors: Sutcliffe A. J. , Parker M.
Published: July 2010

One thousand, three hundred and thirty three patients who underwent anaesthesia for surgical fixation of a hip fracture were studied prospectively to assess the effects on outcome of general and spinal anaesthesia. There were no significant differences between the groups in risk factors, length of hospital stay or mortality rates after 30 days or one year. The data presented may be useful for those wishing to audit anaesthetic services provided to patients with hip fracture.
Cardiovascular changes after achieving constant effect site concentration of propofol*
Authors: Jack E. S. , Shaw M. , Harten J. M. , Anderson K. , Kinsella J.
Published: July 2010

Target controlled infusions of propofol use a pharmacokinetic/pharmacodynamic model to calculate an effect site concentration of the drug. We assessed the cardiovascular stability of 10 healthy patients using non‐invasive thoracic bioimpedance and their ‘depth’ of anaesthesia using the Bispectral index after they had been anaesthetised to a constant effect site concentration of propofol (6.5 min from starting). Each patient had no surgical stimulus and received no intravenous fluid during the study period. The patients also received effect site target controlled remifentanil (steady state 2.5 min from starting) and a bolus of vecuronium to facilitate intubation and ventilation. We mathematically calculated when each measured parameter would reach a state of stability (i.e. with 95% certainty). Heart rate levelled off at 20 min, Bispectral index at 32 min, and cardiac index and mean arterial pressure at 47 min after achieving effect site stability, the final levels being, respectively, 21%, 47%, 14% and 28% lower than those at effect site stability. We conclude that cardiovascular parameters continue to change to a clinically significant degree after achieving a constant effect site concentration of propofol via target controlled infusions.
Canine plasma alkaline phosphatase polymorphism and its relationship with the canine Tr blood group system
Authors: SYMONS M. , BELL K.
Published: July 2010

Summary. A canine blood group antigen, QN, which was detected by a naturally occurring alloantibody in the antiglobulin test, was shown to be antigenically related to the human A and cattle J antigens by absorption experiments. Family studies supported a dominant mode of inheritance with the gene controlling the production of QN being dominant to the gene responsible for its absence. Frequencies of the QN and Tr antigens and serological data strongly suggested that the two antigens are identical. Two canine plasma alkaline phosphatase variants, F and S, were detected by starch gel electrophoresis, pH 8.65. Assuming genetic control of two codominant alleles, ALPF and ALPS, the distributions of types in families differed significantly from expectation. A relationship between the ALP and Tr(QN) systems was demonstrated with Tr‐positive animals having a significant deficiency of S alkaline phosphatase types.
Comparative study of pig‐rodent somatic cell hybrids
Authors: Zijlstra C. , Bosma A. A. , de Haan N. A.
Published: July 2010

The pig chromosome complement of six different types of pig‐rodent hybrid cell lines was examined by means of fluorescence in situ hybridization with a porcine SINE probe. The cell lines were obtained by fusing pig lymphocytes with cells of the Chinese hamster cell lines wg3h, BK14‐150 and E36, and of the mouse cell lines NSO, PU and LMTK‐. The hybrids were analysed with respect to: (1) the number of pig chromosomes, (2) the type of pig chromosomes, (3) the occurrence of pig‐rodent chromosome trans‐locations, and (4) the presence of pig chromsome fragments. The results show that the number of pig chromosomes varied within and among hybrid cell lines. The pig‐hamster hybrids mainly retained nontelocentric pig chromosomes, whereas the pig‐mouse hybrids also retained telocentric pig chromosomes. Pig‐rodent chromosome translocations were found in all types of hybrids, but the incidence was in general low. Chromosome fragments were abundant in BK14‐150 hybrids, and rare in most other hybrid cell lines. It is concluded that the SINE probe is a useful tool to make a preliminary characterization of the porcine chromosome complement of pig‐rodent somatic cell hybrids. The results of this characterization can be used to select hybrids for further cytogenetic analysis. Furthermore, our data show that different rodent cell lines will have to be used as fusion partners for the production of hybrids when constructing a panel informative for all pig chromosomes.