bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta‐analysis: Lactobacillus GG for treating acute diarrhoea in children
Authors: SZAJEWSKA H. , SKÓRKA A. , RUSZCZYŃSKI M. , GIERUSZCZAK‐BIAŁEK D.
Published: July 2010

Aim To review evidence for the effectiveness of Lactobacillus GG (LGG) in treating acute infectious diarrhoea in children.

Methods The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and LGG: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized‐controlled trials (RCTs) were included.

Results Eight RCTs (988 participants) met the inclusion criteria. Compared with controls, LGG had no effect on the total stool volume (two RCTs, n = 303). However, LGG was associated with a significant reduction in diarrhoea duration (seven RCTs, 876 infants, weighted mean difference, WMD −1.1 days (95% confidence interval, CI −1.9 to −0.3), particularly of rotavirus etiology (WMD −2.1 days, 95% CI −3.6 to −0.6), risk of diarrhoea >7 days (one RCT, n = 287, relative risk 0.25, 95% CI 0.09–0.75) and duration of hospitalization (three RCTs, n = 535, WMD −0.58, 95% CI −0.8 to −0.4; significance was lost in the random effect model). There was no reduction in the number of stools at any time interval.

Conclusions The use of LGG is associated with moderate clinical benefits in the treatment of acute diarrhoea in children. These findings should be interpreted with caution due to the important methodological limitations and heterogeneity of most of the studies.
Early changes in rectal nitric oxide and mucosal inflammatory mediators in Crohn’s colitis in response to infliximab treatment
Authors: LJUNG T. , AXELSSON L.‐G. , HERULF M. , LUNDBERG J. O. , HELLSTRÖM P. M.
Published: July 2010

Background Treatment with tumor necrosis factor‐α monoclonal antibody (infliximab) reduces clinical activity and intestinal inflammation in Crohn’s disease.

Aim To study the time‐course of the effects of infliximab with reference to mucosal cytokine and inducible nitric oxide synthase expression.

Methods Thirty‐two patients with Crohn’s disease were treated with single dose infliximab (5 mg/kg). Disease activity was assessed days 1, 3, 7 and 28 using Harvey–Bradshaw index. Rectal nitric oxide levels were determined and rectal biopsies collected before treatment, 1 h after infusion and on days 3, 7 and 28. Immunohistochemical staining against inducible nitric oxide synthase, tumor necrosis factor‐α, interleukin‐1β and interferon‐γ were performed.

Results Clinical response was seen in 14 patients with down‐regulation of global immunohistochemistry expression, reaching nadir day 3. Rectal nitric oxide was increased at baseline (3578 ± 1199 parts per billion, ppb) compared with controls (89 ± 13 ppb) (P < 0.001). In patients with clinical response, rectal nitric oxide decreased from 3926 ± 1687 ppb to 1050 ± 428 ppb day 28 (P < 0.05).

Conclusions Down‐regulation of mucosal inflammatory mediators occurs after infliximab. Rectal nitric oxide levels parallel down‐regulation of inducible nitric oxide synthase, tumor necrosis factor‐α, interleukin‐1β and interferon‐γ and may serve as a quantitative biomarker of intestinal inflammation.
Continuous infusion of high‐dose omeprazole is more effective than standard‐dose omeprazole in patients with high‐risk peptic ulcer bleeding: a retrospective study
Authors: SIMON‐RUDLER M. , MASSARD J. , BERNARD‐CHABERT B. , DI MARTINO V. , RATZIU V. , POYNARD T. , THABUT D.
Published: July 2010

High‐dose omeprazole reduces the rate of recurrent bleeding after endoscopic treatment of peptic ulcer bleeding. However, the effectiveness of high‐dose vs. standard‐dose omeprazole in peptic ulcer bleeding has never been shown.

Aim To compare the benefits of high‐dose vs. standard‐dose omeprazole in peptic ulcer bleeding.

Methods We reviewed the medical files of patients admitted between 1997 and 2004 for high‐risk peptic ulcer bleeding who had undergone successful endoscopic treatment. We distinguished 2 periods: before 2001, standard‐dose omeprazole (40 mg/day intravenously until alimentation was possible, then 40 mg/day orally for 1 week); after 2001, high‐dose omeprazole (80 mg bolus injection, then 8 mg/h continuous infusion for 72 h, then 40 mg/day orally for 1 week). During both periods, patients subsequently received omeprazole, 20 mg/day, orally for 3 weeks.

Results We enrolled 114 patients (period 1, n = 45, period 2, n = 69). Therapy with high‐dose omeprazole significantly decreased the occurrence of poor outcome (27 vs. 12%, P = 0.04), rebleeding (24 vs. 7%, P = 0.01), mortality due to haemorrhagic shock (11 vs. 0%, P < 0.001) and need for surgery (9 vs. 1%, P = 0.05).

Conclusions In this retrospective study, high‐dose omeprazole reduced the occurrence of rebleeding, need for surgery and mortality due to hemorrhagic shock in patients with high‐risk peptic ulcer bleeding, as compared with standard‐dose omeprazole.
The microbiological impact of pre‐operative biliary drainage on patients undergoing hepato‐biliary‐pancreatic (HPB) surgery
Authors: JETHWA P. , BREUNING E. , BHATI C. , BUCKLES J. , MIRZA D. , BRAMHALL S.
Published: July 2010

Background The merit of pre‐operative biliary drainage in managing hepatic, biliary or pancreatic patients remains unclear with previous studies demonstrating significant increases in bacterobilia.

Aims To establish if pre‐operative biliary drainage was associated with (i) a change in bacterial flora, (ii) post‐operative sepsis and (iii) to ascertain if a modification of antibiotic prophylaxis was warranted.

Methods Data were collected on 331 patients undergoing hepatic, biliary or pancreatic surgery for malignant obstruction between August 2000 and June 2005. Microbiological data from intra‐operative bile, post‐operative wounds, blood cultures, urine and sputum were analysed. All episodes of pre‐operative endoscopic retrograde cholangiopancreatography (ERCP), stenting and percutaneous drainage were documented.

Results One hundred and sixty two patients had ERCP prior to surgery and 154 had surgery only. In comparison to patients who had surgery alone stented patients had significantly increased rates of bacterobilia (40 vs. 85%) and fungobilia (8 vs. 34%, both P < 0.001). Pre‐operative biliary drainage significantly increased post‐operative sepsis, wound infections and prolonged in‐patient stay (P < 0.05). The most common organisms cultured were coliforms and enterococcus with percutaneous transhepatic cholangiography (PTC) highly significant for the development of MRSA sepsis.

Conclusions Pre‐operative biliary drainage is associated with a high incidence of bacterobilia and fungal colonization. Pre‐operative biliary drainage should be utilized selectively, with modification of antibiotic prophylaxis according to patient characteristics.
Elastomer implants in faecal incontinence: a blind, randomized placebo‐controlled study
Authors: SIPROUDHIS L. , MORCET J. , LAINÉ F.
Published: July 2010

Aim To test efficacy and safety of polydimethylsiloxane elastomer implants, a silicone biomaterial, in patients with severe faecal incontinence related to an impaired internal anal sphincter.

Methods Subjects were randomized to receive three injections of 2.5 mL of either physiological saline or polydimethylsiloxane elastomer. After local anaesthesia, an 18 gauge, 2.5‐in needle was inserted through the perianal skin and laid down into the intersphincteric space. Treatment (saline or polydimethylsiloxane elastomer) was administered by means of a ratchet gun. Three injections of 2.5 mL each were performed in the area of the internal anal sphincter at 3, 7 and 11 o’clock positions. Main end point was the percentage of subjects in each treatment arm experiencing a successful treatment, defined as a Cleveland Clinic Florida‐Faecal Incontinence score <8, 3 months after treatment. Secondary end points were quality of life scores, weekly number of faecal incontinence episodes, subject acceptance and adverse events rate. Both patients and end point assessments were blinded to treatment.

Results 44 women (64.3 ± 9 years) with a baseline Cleveland Clinic Florida‐Faecal Incontinence score ≥8 were enrolled prospectively; 22 received polydimethylsiloxane elastomer and 22 saline treatment. Treatment was well tolerated. At 3 months, the percentage of subjects experiencing a successful treatment was not different between polydimethylsiloxane elastomer and saline groups (23% vs. 27%, respectively, P = 0.73). Moreover, Cleveland Clinic Florida‐Faecal Incontinence score was not significantly different between polydimethylsiloxane elastomer and saline groups (11.7 ± 4.7 vs. 11.4 ± 4.5, respectively, P = 0.79).

Conclusions Polydimethylsiloxane elastomer implants cannot be recommended for treatment of severe faecal incontinence related to impaired internal anal sphincter.
A 5‐year prospective study of the late resolution of chronic hepatitis C after antiviral therapy
Authors: ANNICCHIARICO B. E. , SICILIANO M. , AVOLIO A. W. , GRILLO R. L. , BOMBARDIERI G.
Published: July 2010

Background Persistence of hepatitis C virus (HCV) in serum is assured after any course of antiviral therapy that failed to obtain a sustained virological response.

Aim To evaluate the long‐term effect on serum HCV‐RNA of a course of pegylated‐interferon and ribavirin therapy that was unable to obtain sustained response.

Methods Serum HCV‐RNA was determined at monthly intervals in 68 non‐responders, breakthroughs or relapsers and in 52 naïve controls enrolled in a five‐year study.

Results Five genotype 2 or 3 patients (one non‐responder, three breakthroughs, one relapser) cleared HCV‐RNA after the end of therapy or relapse, and remained negative until the end of follow‐up. HCV‐RNA clearance rate in genotype 2 and 3 non‐responders, breakthroughs or relapsers was higher than in controls with the same genotypes (22.7% vs. 0%; log‐rank 9.62; P < 0.002). HCV‐RNA at the end of treatment or at relapse was <105 IU/mL in the five subjects who cleared the virus and <104 IU/mL in four of them. None of genotype 1 or 4 subjects cleared HCV‐RNA during follow‐up.

Conclusions Late resolution of HCV infection is possible in genotype 2 or 3 patients with low viral load at the end of therapy or at relapse. In these subjects, HCV‐RNA monitoring is advisable during the first year after therapy.
Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease
Authors: KAUKINEN K. , PERÄAHO M. , LINDFORS K. , PARTANEN J. , WOOLLEY N. , PIKKARAINEN P. , KARVONEN A.‐L. , LAASANEN T. , SIEVÄNEN H. , MÄKI M. , COLLIN P.
Published: July 2010

Background  Refractory sprue with malabsorption carries a risk of lymphoma.

Aim  To examine whether a good clinical but poor histological response during a strict gluten‐free diet predicts a poor outcome.

Methods  The study involved all coeliac patients who showed no histological recovery within 2 years on a strict gluten‐free diet. Small intestinal biopsy and bone mineral density were investigated in 2001 and clinical features were followed up until 2005. The results were compared to those in 18 coeliac patients with a good histological recovery.

Results  Thirteen coeliac patients had persistent small intestinal villous atrophy despite maintaining gluten‐free diet. All had demonstrated a good clinical response. Osteoporosis was found in 58% and 22% of the non‐responders and responders, respectively (P = 0.04). In 2005, two of the non‐responders had developed symptomatic refractory sprue, one died of lymphoma and one of carcinoid tumour, and one gastric adenocarcinoma was operated. None of the 18 controls had developed refractory sprue or malignancy. The frequency of histological non‐responsive disease was 1.9%.

Conclusions  Persistent villous atrophy in adult coeliac disease, even in the absence of symptoms, carries a risk of subsequent severe complications. The follow‐up biopsy is important in detecting these individuals.
Systematic review: the application of molecular pathogenesis to prevention and treatment of oesophageal adenocarcinoma
Authors: PETERS C. J. , FITZGERALD R. C.
Published: July 2010

Background

Oesophageal adenocarcinoma is an increasingly common cancer with a poor prognosis. It develops in a stepwise progression from Barrett’s metaplasia to dysplasia, and then adenocarcinoma followed by metastasis.

Aim

To outline the key molecular changes in oesophageal adenocarcinoma and to summarize the chemopreventative and therapeutic strategies proposed.

Methods

A literature search was performed to identify appropriate research papers in the field. Search terms included: Barrett’s (o)esophagus, intestinal metaplasia, (o)esophageal adenocarcinoma, molecular changes, genetic changes, pathogenesis, chemoprevention, therapeutic strategies and treatment. The search was restricted to English language articles.

Results

A large number of molecular changes have been identified in the progression from Barrett’s oesophagus to oesophageal adenocarcinoma although there does not appear to be an obligate order of events. Potential chemoprevention strategies include acid suppression, anti‐inflammatory agents and antioxidants. In established adenocarcinoma, targeted treatments under evaluation include receptor tyrosine kinase inhibitors of EGFR and cyclin‐dependent kinase inhibitors, which may benefit a subgroup of patients.

Conclusions

Advances in molecular methodology have led to a greater understanding of the oesophageal adenocarcinoma pathways, which provides opportunities for chemoprevention and therapeutic strategies with a mechanistic basis. More work is required to assess both the safety and efficacy of these new treatments.
Review article: the diagnosis and management of Crohn’s disease in populations with high‐risk rates for tuberculosis
Authors: EPSTEIN D. , WATERMEYER G. , KIRSCH R.
Published: July 2010

Background  Distinguishing Crohn’s disease from intestinal tuberculosis in endemic areas is challenging as both conditions have overlapping clinical, radiological, endoscopic and histological characteristics. Furthermore, high rates of latent tuberculosis confer a considerable risk of reactivation once therapy for established Crohn’s disease is started.

Aim  To review current strategies in differentiating these two conditions, and in managing Crohn’s disease, in populations with high rates of tuberculosis.

Methods  Literature review and clinical experience.

Results  While various clinical, radiological, endoscopic and histological parameters may aid in differentiating Crohn’s disease from intestinal tuberculosis, these remain imperfect and as treatment options differ misdiagnosis has grave consequences. We propose a diagnostic algorithm, based on currently available evidence and experience, to aid in this dilemma. We also discuss approaches to the management of Crohn’s disease, including agents targeting tumour necrosis factor‐α, in patients at risk of developing tuberculosis.

Conclusions  A diagnosis of Crohn’s disease in individuals at risk for tuberculosis should only be made after careful interpretation of clinical signs, abdominal imaging and systematic endoscopic and histological assessment. Newer techniques for the diagnosis of latent tuberculosis still need to be validated in this environment, and guidelines on the treatment of latent tuberculosis in this setting require clarification.
Intestinal chemo‐ and mechano‐sensitivity: selective modification of small intestinal sensitivity by lipids
Authors: HAMMER J. , FÜHRER M.
Published: July 2010

Background Intestinal chemo‐nociception is a recently described mechanism of perception of intraluminal stimuli that might involve pathways independent from mechano‐nociception.

Aim To investigate whether intraluminal lipids not only modify mechano‐sensitivity, but also influence chemo‐sensitivity.

Method Nineteen healthy volunteers ingested an orojejunal tube assembly for mechanical and chemical stimulation of the proximal jejunum. Volume‐controlled distension of a jejunal balloon and capsaicin perfusion were performed during simultaneous infusion of saline or a 10% lipid emulsion. A standard questionnaire evaluated quality and intensity of symptoms induced by intestinal stimulation.

Results Balloon volumes to induce perception thresholds were significantly reduced during lipid perfusion (P < 0.05), while balloon pressures remained unaltered (P > 0.05). Saline infusion (2.5 mL/min) did not alter thresholds of perception. Lipid infusion also increased intensity of perception during given distension volumes (P < 0.05). Lipid infusion did neither affect perception quality induced by capsaicin, nor perception thresholds, nor intensity of perception during capsaicin perfusion (P > 0.05). The quality of sensations induced by capsaicin perfusion was similar to sensations during distension, except of sensation of warmth, that was almost exclusively reported during capsaicin perfusion.

Conclusions Intraluminal lipids selectively modify intestinal mechano‐perception and do not alter chemo‐perception. Intestinal chemo‐nociception and mechano‐nociception are two mechanisms of intestinal perception that involve distinct sensory pathways.
Role of intra‐oesophageal impedance monitoring in the evaluation of endoscopic gastroplication for gastro‐oesophageal reflux disease
Authors: CONCHILLO J. M. , SCHWARTZ M. P. , SELIMAH M. , SAMSOM M. , ARTS J. , TACK J. , SIFRIM D. , SMOUT A. J. P. M.
Published: July 2010

Background In the evaluation of several endoscopic antireflux procedures, a discrepancy in the degree of improvement between symptoms and objective reflux parameters as measured by pH‐metry has been reported.

Aim To assess the additional value of impedance monitoring in the evaluation of endoscopic gastroplication for gastro‐oesophageal reflux disease.

Methods Eighteen patients with gastro‐oesophageal reflux disease were treated with three endoscopic gastroplications, and underwent 24 h pH‐impedance monitoring before and 3 months after treatment.

Results Total reflux exposure time as assessed by pH‐metry and impedance monitoring was significantly decreased after treatment (P = 0.047 and <0.001, respectively). When assessed with impedance monitoring, the mean number of reflux episodes was significantly decreased after the procedure (82 vs. 56, pre vs. post, P < 0.001). Furthermore, the mean numbers of liquid and acid reflux episodes in patients with symptomatic improvement were significantly reduced after treatment (P = 0.04 and 0.02, respectively). After treatment, mean volume clearance time (s) and mean number of proximal reflux episodes were significantly decreased (P < 0.001 and 0.002, respectively).

Conclusions Impedance monitoring can identify the specific effect of endoscopic gastroplication on the different types of reflux episodes with regard to gas–liquid composition and pH, as well as on volume clearance and the proximal extent of the refluxate.
Overlap of gastro‐oesophageal reflux disease and irritable bowel syndrome: prevalence and risk factors in the general population
Authors: JUNG H.‐K. , HALDER S. , MCNALLY M. , LOCKE III G. R. , SCHLECK C. D. , ZINSMEISTER A. R. , TALLEY N. J.
Published: July 2010

Background  Gastro‐oesophageal reflux disease (GERD) and irritable bowel syndrome may occur more often than expected by chance, but little community data exists and risk factors are unknown.

Aim  To determine prevalence and risk factors for overlap of GERD and irritable bowel disease.

Methods  Population‐based, cross‐sectional survey was conducted by mailing a valid symptom questionnaire to eligible residents of Olmsted County, MN, aged 30–95 years. Irritable bowel syndrome were defined by Rome III; GERD was defined by weekly or more frequent heartburn and/or acid regurgitation.

Results  2298 questionnaires returned (women 52%, 55% response). Irritable bowel syndrome and GERD occurred together more commonly than expected by chance; the prevalence of irritable bowel syndrome–GERD overlap, GERD alone and irritable bowel syndrome alone were 3%, 15% and 5% in men, and 4%, 14% and 10% in women, respectively. Predictors of irritable bowel syndrome–GERD overlap vs. irritable bowel syndrome alone, and separately, GERD alone, were insomnia (OR 1.3, 95% CI: 1.06–1.70; OR 1.5, 95% CI: 1.13–1.90, respectively) and frequent abdominal pain (OR 3.9, 2.2–6.7; OR 1.8, 1.02–3.2, respectively). An additional predictor of irritable bowel syndrome–GERD overlap vs. GERD alone was higher somatization (OR 1.7, 1.1–2.4) and for irritable bowel syndrome–GERD overlap vs. irritable bowel syndrome alone was a higher body mass index (OR 1.0, 1.003–1.07).

Conclusions  Irritable bowel syndrome and GERD overlap is common in the population and does not occur by chance.
Portal‐systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt
Authors: EVERSON G. T. , MARTUCCI M. A. , SHIFFMAN M. L. , STERLING R. K. , MORGAN T. R. , HOEFS J. C. ,   THE HALT‐C TRIAL GROUP
Published: July 2010

Background Measurement of portal inflow and portal‐systemic shunt using cholate clearances could be useful in monitoring patients with liver disease.

Aim To examine relationships of cholate clearances and shunt to cirrhosis and varices and to define minimal sampling requirements.

Methods Five hundred forty‐eight studies were performed in 282 patients enrolled in the Hepatitis C Antiviral Long‐term Treatment to prevent Cirrhosis (HALT‐C) trial. Stable, non‐radioactive isotopes of cholate were administered intravenously and orally, clearances (Clivand Cloral) were calculated from [dose/area under curve (AUC)] and cholate shunt from [(AUCoral:AUCiv) x (Doseiv:Doseoral) x 100%].

Results Cholate Cloraland cholate shunt correlated with prevalences of both cirrhosis and varices (P < 0.0001 for all). Peripheral venous sampling at 5, 20, 45, 60 and 90 min defined the minimal model. Linear regression of cholate shunt determined from five points within 90 min vs. the standard method of 14 points over 3 h yielded slope of 1.0 and intercept 0.5% (r2 = 0.98,P < 0.0001). Results were identical in the 189 validation studies (slope 1.0, intercept 0.5%,r2 = 0.99,P < 0.0001).

Conclusions Cholate Cloraland cholate shunt may be useful in monitoring patients with liver disease. The 5‐point model enhances application of cholate Cloraland cholate shunt in the non‐invasive assessment of the portal circulation.
Systematic review: proton pump inhibitor‐associated acute interstitial nephritis
Authors: SIERRA F. , SUAREZ M. , REY M. , VELA M. F.
Published: July 2010

Background  A number of recent case reports and case series suggest that proton pump inhibitors may cause acute interstitial nephritis.

Aim  To establish the nature of the relationship (cause or association) between proton pump inhibitor use and development of interstitial nephritis.

Methods  Data collection: Two researchers independently searched electronic databases (MEDLINE, EMBASE, GOOGLE, LILACS, COCHRANE) for articles from 1970 to 2006, including all study designs, populations and languages. Two independent reviewers assessed study quality and collected the data. Selection criteria: absence of baseline renal failure, development of interstitial nephritis after proton pump inhibitor exposure, nephritis confirmed by creatinine plus either renal biopsy or recurrence upon reinitiating proton pump inhibitor.

Results  Sixty four cases (60% females, mean age 78 years) of proton pump inhibitor‐associated interstitial nephritis were found, 60 included in this review (59 confirmed by renal biopsy, one by recurrence upon reinitiating proton pump inhibitor). The most common symptoms were non‐specific. The mean proton pump inhibitor treatment duration before diagnosing nephritis was 13 weeks, average recovery time was 35.5 weeks, one patient required permanent dialysis, there were no deaths.

Conclusion  Proton pump inhibitor‐related interstitial nephritis is rare, idiosyncratic and difficult to predict. It requires a high level of clinical suspicion. While there is not sufficient evidence to establish a causal relationship with certainty, there does appear to be a low‐prevalence association.
Severe gastro‐oesophageal reflux symptoms in relation to anxiety, depression and coping in a population‐based study
Authors: JANSSON C. , NORDENSTEDT H. , WALLANDER M.‐A. , JOHANSSON S. , JOHNSEN R. , HVEEM K. , LAGERGREN J.
Published: July 2010

Background

The association between psychiatric disorders and gastro‐oesophageal reflux symptoms is uncertain, and few population‐based studies are available.

Aim

To examine the association between psychiatric and psychological factors and reflux symptoms.

Methods

Population‐based, cross‐sectional, case–control study based on two health surveys conducted in the Norwegian county Nord‐Trondelag in 1984–1986 and 1995–1997. Reflux symptoms were assessed in the second survey, including 65 333 participants (70% of the county’s adult population). 3153 subjects reporting severe reflux symptoms were defined as cases and 40 210 subjects without symptoms were defined as controls. Data were collected in questionnaires. Odds ratio with 95% confidence intervals were estimated using unconditional logistic regression, in adjusted models.

Results

Subjects reporting anxiety without depression had a 3.2‐fold (95% CI: 2.7–3.8) increased risk of reflux, subjects with depression without anxiety had a 1.7‐fold (95% CI: 1.4–2.1) increased risk and subjects with both anxiety and depression had a 2.8‐fold (95% CI: 2.4–3.2) increased risk, compared to subjects without anxiety/depression. We observed a weak inverse association between one measure of covert coping and risk of reflux and a weak positive association between another coping measure and risk of reflux.

Conclusions

This population‐based study indicates that anxiety and depression are strongly associated with reflux symptoms, while no consistent association regarding coping and reflux was found.
Meta‐analysis: inosine triphosphate pyrophosphatase polymorphisms and thiopurine toxicity in the treatment of inflammatory bowel disease
Authors: VAN DIEREN J. M. , HANSEN B. E. , KUIPERS E. J. , NIEUWENHUIS E. E. S. , VAN DER WOUDE C. J.
Published: July 2010

Background

Thiopurines are widely used for the treatment of inflammatory bowel disease, but are associated with the development of side effects. It has been suggested that the enzyme inosine triphosphate pyrophosphatase (ITPA) plays a role in the digestion of thiopurines and that defective activity resulting from polymorphisms in the inosine triphosphate pyrophosphatase encoding genes may be associated with thiopurine‐induced side effects. Current studies are controversial regarding this hypothesis.

Aim

To perform a meta‐analysis and gain more insight into a possible correlation between thiopurine‐induced side effects and ITPA polymorphisms.

Methods

We explored Medline for articles on ITPA polymorphisms and thiopurine toxicity. Studies that compared ITPA polymorphism frequencies among thiopurine‐tolerant and ‐intolerant adult inflammatory bowel disease patients were included in this meta‐analysis.

Results

Nine published studies investigated associations between ITPA polymorphisms and thiopurine toxicity. Six studies (with 751 patients included) met our inclusion criteria and were processed in the meta‐analysis. This analysis demonstrates that the ITPA 94C→A polymorphism, is not significantly associated with any of the studied side effect parameters.

Conclusions

This meta‐analysis does not prove a correlation between the development of thiopurine toxicity and the ITPA 94C→A polymorphism. This implies that there is no clinical relevance to determine ITPA polymorphisms in thiopurine‐treated patients.
Virtual vs. optical colonoscopy in symptomatic gastroenterology out‐patients: the case for virtual imaging followed by targeted diagnostic or therapeutic colonoscopy1
Authors: BOSE M. , BELL J. , JACKSON L. , CASEY P. , SAUNDERS J. , EPSTEIN O.
Published: July 2010

Aim

To compare virtual colonoscopy with optical colonoscopy findings in symptomatic patients.

Background

Computer tomographic colonography is an alternative to optical colonoscopy. Studies have shown that two‐dimensional computer tomographic colonography does not have sufficient sensitivity. Three‐dimensional computerized tomographic virtual colonoscopy compares well with optical colonoscopy for colorectal neoplasia screening in asymptomatic individuals.

Methods

One hundred patients aged 50 and older underwent same day virtual colonoscopy and optical colonoscopy. The endoscopists were unaware of the radiologist's report until the withdrawal phase of the endoscopy when segmental unblinding occurred. The virtual colonoscopy and optical colonoscopy findings were compared by using the unblinded optical colonoscopy as the reference standard.

Results

Pancolonic endoluminal virtual colonoscopy was achieved in 99 patients. Optical colonoscopy caecal intubation occurred in 91 patients. Direct comparison was possible in 90 patients. Both techniques revealed the three cancers detected. Virtual colonoscopy revealed 11 polyps ≥6mm diameter in nine patients. Optical colonoscopy revealed 10 polyps ≥6mm diameter in nine patients with a further 15‐mm polyp discovered after segmental unblinding.

Conclusion

In symptomatic patients, three‐dimensional virtual colonoscopy is equivalent to optical colonoscopy for diagnosing colon cancer and clinically significant polyps. A case can be made for three‐dimensional virtual colonoscopy as a primary modality followed if necessary by same day‐targeted optical colonoscopy.
Sequential evaluation of thiopurine methyltransferase, inosine triphosphate pyrophosphatase, and HPRT1 genes polymorphisms to explain thiopurines' toxicity and efficacy
Authors: PALMIERI O. , LATIANO A. , BOSSA F. , VECCHI M. , D’INCÀ R. , GUAGNOZZI D. , TONELLI F. , CUCCHIARA S. , VALVANO M. R. , LATIANO T. , ANDRIULLI A. , ANNESE V.
Published: July 2010

Aim

To evaluate the polymorphisms of several genes involved in the azathioprine and mercaptopurine metabolism, in an attempt to explain their toxicity and efficacy in Crohn’s disease and ulcerative colitis.

Methods

In 422 consecutive patients (250 with Crohn’s disease and 172 with ulcerative colitis) and 245 healthy controls, single nucleotide polymorphisms of thiopurine methyltransferase, inosine triphosphate pyrophosphatase and hypoxanthine phosphoribosyl transferase (HPRT1) genes were related to the occurrence of adverse drug reactions (ADRs) and efficacy of therapy.

Results

Seventy‐three patients reported 81 episodes of ADRs; 45 patients did not respond to therapy. Frequency of thiopurine methyltransferase risk haplotypes was significantly increased in patients with leucopenia (26% vs. 5.7% in patients without ADRs, and 4% of controls) (P < 0.001); no correlation with other ADRs and efficacy of therapy was found. Conversely, the frequency of inosine triphosphate pyrophosphatase and HPRT1 risk genotypes was not significantly different in patients with ADRs (included leucopenia). Non‐responders had an increased frequency of inosine triphosphate pyrophosphatase risk genotypes (P = 0.03).

Conclusions

The majority of azathioprine/mercaptopurine‐induced ADRs and efficacy of therapy are not explained by the investigated gene polymorphisms. The combined evaluation of all three genes enhanced the correlation with leucopenia (43.5% vs. 23% in controls) (P = 0.008), at the expense of a reduced accuracy (60%).
Subtyping the irritable bowel syndrome by predominant bowel habit: Rome II versus Rome III
Authors: ERSRYD A. , POSSERUD I. , ABRAHAMSSON H. , SIMRÉN M.
Published: July 2010

Background

The agreement between subtyping irritable bowel syndrome (IBS) patients based on Rome II criteria versus Rome III criteria is unknown.

Aim

To compare IBS subtyping based on Rome II versus III criteria.

Methods

The Rome II Modular Questionnaire and the Bristol Stool Form Scale (one‐week diary cards) were completed by 249 IBS patients. Based on the Rome II criteria, patients were defined as having diarrhoea‐ or constipation‐predominant IBS, or alternating IBS. Based on the Rome III criteria, patients were divided into IBS with constipation, IBS with diarrhoea, mixed IBS or unsubtyped IBS. Agreement between Rome II and Rome III was assessed with kappa statistics.

Results

Based on Rome II there were 92 diarrhoea‐predominant IBS, 45 constipation‐predominant IBS and 112 alternating IBS, and based on Rome III 97 IBS with diarrhoea, 77 IBS with constipation, 16 mixed IBS and 59 unsubtyped IBS. The agreement between Rome II and Rome III subgroups was 46% (kappa = 0.19). Changes from the constipation to the diarrhoea subgroups and vice versa were uncommon (8% of patients). The majority of changes occurred from/to the alternating IBS, mixed IBS and unsubtyped IBS subgroups.

Conclusion

There is poor agreement between subtyping of IBS patients based on Rome II versus Rome III criteria.
Persisting symptoms and decreased health‐related quality‐of‐life in a cross‐sectional study of treated achalasia patients
Authors: FRANKHUISEN R. , VAN HERWAARDEN M. A. , HEIJKOOP R. , SMOUT A. J. P. M. , BARON A. , VERMEIJDEN J. R. , GOOSZEN H. G. , SAMSOM M.
Published: July 2010

Background

Little is known about symptom characteristics of treated achalasia patients and their effect on health‐related quality‐of‐life (HRQoL).

Aims

To examine clinical remission, achalasia‐associated symptoms and HRQoL in treated achalasia patients.

Methods

The Eckardt clinical symptom score, RAND‐36 and a disease‐specific HRQoL questionnaire were sent to 171 treated achalasia patients.

Results

76.6% of the patients returned their questionnaire. 44.9% of them were not in symptomatic remission. Prevalence of frequent dysphagia (at least daily) and chest pain (at least weekly) was 46% and 38%, respectively. Achalasia patients had lower general HRQoL scores than control subjects (all RAND‐36 subscales, except health change; P ≤ 0.002). Patients with frequent symptoms of chest pain and dysphagia showed lower HRQoL than patients with less frequent symptoms on three RAND‐36 subscales (pain, social functioning and general health perceptions; P < 0.003). Patients in clinical remission showed higher HRQoL than patients who were not, however HRQoL in the ‘remission group’ remained significantly impaired as compared to controls (all RAND‐36 subscales except emotional role limitations and mental health; P < 0.001).

Conclusions

Many achalasia patients remain severely symptomatic after treatment and have decreased HRQoL. Frequent symptoms are associated with lower HRQoL. Patients in clinical remission show substantially improved, but not restored HRQoL.
Health‐related quality of life in patients with non‐alcoholic fatty liver disease
Authors: DAN A. A. , KALLMAN J. B. , WHEELER A. , YOUNOSZAI Z. , COLLANTES R. , BONDINI S. , GERBER L. , YOUNOSSI Z. M.
Published: July 2010

Background

The relative impact of non‐alcoholic fatty liver disease (NAFLD) on health‐related quality of life (HRQL) compared to other chronic liver diseases has not been fully explored.

Aim

To compare the domain scores of the 29‐item Chronic Liver Disease Questionnaire (CLDQ) for patients with NAFLD to those with chronic hepatitis B and chronic hepatitis C.

Methods

A HRQL questionnaire, CLDQ, was routinely administered to patients attending a liver clinic. Additional clinical and laboratory data were obtained on patients with NAFLD, chronic hepatitis B, and chronic hepatitis C from our quality of life database. Scores for each of the six CLDQ domains were compared using one‐way anova and multiple regression.

Results

Complete data were available for 237 patients. NAFLD patients scored lowest on multiple CLDQ domains. Based on the bivariate data, NAFLD patients have the poorest HRQL, followed by chronic hepatitis C and chronic hepatitis B patients. Multivariate analysis showed that some specific domain score correlations remained significant for NAFLD diagnosis, cirrhosis, gender, and body mass index.

Conclusion

NAFLD patients had significantly lower quality of life scores compared with patients with hepatitis B or hepatitis C on multiple CLDQ domains, suggesting that HRQL was severely impaired in patients with NAFLD.
Chromogranin A in patients with acid hypersecretion and/or hypergastrinaemia
Authors: HIRSCHOWITZ B. I. , WORTHINGTON J. , MOHNEN J. , HABER M.
Published: July 2010

Background

Chromogranin has been proposed as a marker for gastrin‐dependent enterochromaffin‐like cell proliferation.

Aim

To examine this question in three populations: acid hypersecretors with gastrinoma (Zollinger–Ellison), or without gastrinoma (non‐Zollinger–Ellison), and also in pernicious anaemia with achlorhydria‐caused hypergastrinaemia.

Methods

We measured serum chromogranin, gastrin, gastric secretion and counted and quantified hyperplasia of enterochromaffin‐like cells in gastric biopsies from 38 Zollinger–Ellison and 13 non‐Zollinger–Ellison patients being treated with lansoprazole, for 5 years (median) and again 2.5 years later. We also studied 12 patients with pernicious anaemia, half with gastric enterochromaffin‐like cell carcinoids.

Results

Serum chromogranin was elevated in patients with gastrinoma, even without any enterochromaffin‐like cell proliferation, but not in non‐Zollinger–Ellison acid hypersecretors with normal gastrin (P < 0.001). In the hypersecretors chromogranin correlated well with serum gastrin (r = 0.82), but not with enterochromaffin‐like cell proliferation. Moreover, chromogranin was normal or near normal (<75 ng/mL) despite very high serum gastrin in five of six patients with pernicious anaemia and enterochromaffin‐like cell carcinoids.

Conclusions

Chromogranin is not a reliable marker for enterochromaffin‐like cell activity or proliferation up to and including carcinoid; chromogranin originates in the gastrinoma and, like gastrin, is a marker for gastrinoma in acid hypersecretors.
Quantifying exposure to diagnostic medical radiation in patients with inflammatory bowel disease: are we contributing to malignancy?
Authors: NEWNHAM E. , HAWKES E. , SURENDER A. , JAMES S. L. , GEARRY R. , GIBSON P. R.
Published: July 2010

Background  While potential risks of diagnostic medical radiation are acknowledged, actual exposure of patients in routine clinical practice is poorly documented.

Aim  To quantify such exposure to vulnerable abdominal organs in patients with inflammatory bowel disease who are already at risk of intestinal cancer.

Methods  All incidences of exposure to diagnostic medical radiation were documented in a consecutive series of 100 patients with inflammatory bowel disease (62 Crohn’s disease, 37 ulcerative colitis, 1 indeterminate colitis) attending a hospital‐based clinic. Total effective dose (mSv) was calculated using published tables. Predictors of high or no irradiation were evaluated by multivariate logistic regression analysis.

Results  Thirteen patients had no documented diagnostic irradiation. Twenty‐three patients received an effective dose greater than 25 mSv. An at‐risk effective dose >50 mSv was received by 11 patients. Dosage was higher in patients with Crohn’s disease than ulcerative colitis (P = 0.02) and in patients undergoing surgery (P = 0.004). However, no predictive factors for high radiation dosage or for no exposure were identified.

Conclusions  At‐risk irradiation from diagnostic medical radiation is common in patients with inflammatory bowel disease, and might potentially contribute to the elevated risk of intra‐abdominal and other cancers. The level of irradiation should be considered in clinical decisions regarding abdominal imaging.
Clinical trial: comparison of weekly once versus twice half‐dose weekly administration of pegylated interferon alpha 2b in combination with ribavirin for the treatment of HCV‐1 positive patients with chronic hepatitis C
Authors: SEBASTIANI G. , FERRARI A. , BOCCATO S. , PISTIS R. , ALBERTI A.
Published: July 2010

Background  Pegylated interferon (PEG‐IFN) alpha2b is currently used as a once weekly injection in combination with ribavirin for the treatment of chronic hepatitis C.

Aim  To test whether twice half‐dose weekly administration may improve the virological response in difficult‐to‐treat hepatitis C virus‐1 patients.

Methods  Thirty patients were treated with 1.5 μg/kg of PEG‐IFN alpha2b given once weekly for 48 weeks (group A) and were compared with 30 patients treated with the same dose of PEG‐IFN alpha2b divided in twice weekly doses of 0.75 μg/kg for the initial 4 weeks (group B). All patients were hepatitis C virus‐1 positive and received weight‐based ribavirin (800–1400 mg/daily).

Results  Weekly twice half‐dose administration of PEG‐IFN alpha2b for the first 4 weeks was associated with lower rates of biochemical and virological response at all time points compared with a once weekly schedule, and with significantly higher rates of in‐therapy breakthrough leading to significantly lower rates of end of therapy response (week 48). The rate of sustained virological response was of 56.7% in group A and 36.7% in group B.

Conclusions  Weekly twice half‐dose administration of PEG‐IFN alpha2b is not superior to the standard once weekly schedule, and might be less efficacious.
Clinical trial: an efficacy evaluation of reduced bisacodyl given as part of a polyethylene glycol electrolyte solution preparation prior to colonoscopy
Authors: DIPALMA J. A. , MCGOWAN J. , CLEVELAND M. Vb.
Published: July 2010

Background  In an attempt to further improve patient preparation experience with reduced volume gut lavage solutions using 2‐L sulphate‐free electrolyte lavage solution plus 20‐mg bisacodyl (HalfLytely with Bisacodyl Tablets Bowel Prep Kit, Braintree Laboratories, Inc., Braintree, MA, USA), a low bisacodyl dose preparation was developed using 10 mg bisacodyl.

Aim  To compare preparation methods using the 10‐ or 20‐mg bisacodyl with 2‐L sulphate‐free electrolyte lavage method.

Methods  At 10 US centres, 455 patients undergoing colonoscopy for routine clinical indications were equally randomized to receive 10‐ or 20‐mg bisacodyl with 2‐L sulphate‐free electrolyte lavage method. Colonoscopists rated the efficacy of colon cleansing, blinded to the preparation assignment.

Results  Physician assessment of colon cleansing showed no difference between those randomized to receive the 10‐ or 20‐mg bisacodyl preparations (P = 0.52). The 10‐mg preparation had lower symptom scores for cramping (P < 0.001) and overall discomfort (P = 0.001). Other reported adverse experiences were few, mild and not different between groups.

Conclusion  Two‐litre sulphate‐free electrolyte lavage method solution with 10‐mg bisacodyl is as effective as the 20‐mg bisacodyl preparation for cleansing the colon prior to colonoscopy. The 10‐mg bisacodyl regimen has an improved safety profile, with significantly reduced cramping, nausea and overall discomfort.
Clinical trial: healing of NSAID‐associated gastric ulcers in patients continuing NSAID therapy – a randomized study comparing ranitidine with esomeprazole
Authors: GOLDSTEIN J. L. , JOHANSON J. F. , HAWKEY C. J. , SUCHOWER L. J. , BROWN K. A.
Published: July 2010

Background  The use of non‐steroidal anti‐inflammatory drugs (NSAID) is associated with an increased risk of gastric ulcer (GU) development.

Methods  This multicentre, randomized, double‐blind, parallel‐group trial compared endoscopic healing rates at 4 and 8 weeks after treatment with oral esomeprazole 40 or 20 mg once daily, or ranitidine 150 mg twice daily, in patients with 1 baseline GU ≥5 mm but no GUs or duodenal ulcers >25 mm in diameter who received continued cyclooxygenase‐2–selective or non‐selective NSAID therapies. The primary outcome was the percentage of patients in each treatment group who had no GUs at week 8.

Results  Four hundred and forty patients were randomized to treatment. At week 8, GU healing rates (95% CI) with esomeprazole 40 mg, esomeprazole 20 mg and ranitidine were 85.7 (79.8–91.7)%, 84.8 (78.8–90.8)% and 76.3 (69.2–83.3)%, respectively; between‐group differences were not statistically significant. Week‐4 GU healing rates were 70.7 (62.9–78.4)% and 72.5 (65.0–79.9)% with esomeprazole 40 and 20 mg, respectively, and were significantly higher (P < 0.01 for both doses) than those with ranitidine [55.4 (47.1–63.7)%].

Conclusion  In patients who require continued NSAID therapy, GU healing rates at 8 weeks numerically favoured esomeprazole but were not significantly different from ranitidine.
The cost‐effectiveness and budget impact of competing therapies in hepatic encephalopathy – a decision analysis
Authors: HUANG E. , ESRAILIAN E. , SPIEGEL B. M. R.
Published: July 2010

Background Treatment options for hepatic encephalopathy have disparate risks and benefits. Non‐absorbable disaccharides and neomycin are limited by uncertain efficacy and common dose‐limiting side effects. In contrast, rifaximin is safe and effective in hepatic encephalopathy, but is more expensive.

Methods We conducted a decision analysis to calculate the cost‐effectiveness of six strategies in hepatic encephalopathy: (i) no hepatic encephalopathy treatment, (ii) lactulose monotherapy, (iii) lactitol monotherapy, (iv) neomycin monotherapy, (v) rifaximin monotherapy and (vi) up‐front lactulose with crossover to rifaximin if poor response or intolerance of lactulose (‘rifaximin salvage’). The primary outcome was cost per quality‐adjusted life‐year gained.

Results Under base‐case conditions, ‘do nothing’ was least effective and rifaximin salvage was most effective. Lactulose monotherapy was least expensive, and rifaximin monotherapy was most expensive. When balancing cost and effectiveness, lactulose monotherapy and rifaximin salvage dominated alternative strategies. Compared to lactulose monotherapy, rifaximin salvage cost an incremental US$2315 per quality‐adjusted life‐year‐gained. The cost of rifaximin had to fall below US$1.03/tab in order for rifaximin monotherapy to dominate lactulose monotherapy.

Conclusions Rifaximin monotherapy is not cost‐effective in the treatment of chronic hepatic encephalopathy at current average wholesale prices. However, a hybrid salvage strategy, reserving rifaximin for lactulose‐refractory patients, may be highly cost‐effective.
Review article: the endoscopic treatment of gastro‐oesophageal reflux disease
Authors: SCHWARTZ M. P. , SMOUT A. J. P. M.
Published: July 2010

Background  Over the last 10 years a number of endoscopic procedures for treating gastro‐oesophageal reflux disease (GORD) have been developed (suturing, injections, implants and radiofrequency ablation), thus obviating the need for long‐term proton pump inhibitors (PPI) and the potential morbidity of laparoscopic fundoplication.

Aim  To present an update of the literature studying the clinical efficacy of endoscopic antireflux procedures, and to discuss further developments.

Methods  A PubMed search was performed for endoscopic suturing, antireflux treatment, endoscopic gastroplication, polymer injection, radiofrequency ablation of GORD. Own recent research was compared with existing data. Information concerning GORD endotherapy were gathered.

Results  Uncontrolled studies have reported promising clinical results on the short to intermediate term for most endoscopic GORD procedures, but the placebo effect remained unknown. It is, therefore, commendable that the three main procedures (Endocinch, Stretta and Enteryx) have now all been tested against a sham procedure. Although all three techniques were able to improve symptoms, quality of life and PPI use, oesophageal acid reduction was unremarkable. Endocinch and Stretta are safe outpatient procedures. Concerns about the durability of Endocinch have risen. Polymer injection (Enteryx) and gel prosthesis implantation (Gatekeeper) were recalled for severe complications and lack of efficacy, respectively.

Conclusions  Endotherapy has shown the potential to treat (uncomplicated) GORD. However, some early procedures have failed or proven unsafe. Further developments and studies are necessary to determine what modifications to these techniques are required to produce optimal efficacy and durability. Until then, widespread clinical use of endotherapy for GORD should probably be avoided.