Latest from Gut

Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes [INFLAMMATORY BOWEL DISEASE]

Mon, 1 Jul 2013 00:00:00 +0000

BackgroundMultiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. ObjectiveTo identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. DesignDNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. ResultsAcross the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of <5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within NOD2: the previously described R702W variant was the sole NOD2 variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the GSDMB, ERAP2 and SEC16A genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the BACH2 and IL10 genes not seen in other patients. ConclusionFor each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.

What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectiveEvaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. DesignA prospective observational study. Setting11 UK primary care practices. ParticipantsPatients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Main outcome measuresPatients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. ResultsRegression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. ConclusionsThe LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.

The Crohn's disease: associated ATG16L1 variant and Salmonella invasion [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectiveA common genetic coding variant in the core autophagy gene ATG16L1 is associated with increased susceptibility to Crohn's disease (CD). The variant encodes an amino acid change in ATG16L1 such that the threonine at position 300 is substituted with an alanine (ATG16L1 T300A). How this variant contributes to increased risk of CD is not known, but studies with transfected cell lines and gene-targeted mice have demonstrated that ATG16L1 is required for autophagy, control of interleukin-1-{beta} and autophagic clearance of intracellular microbes. In addition, studies with human cells expressing ATG16L1 T300A indicate that this variant reduces the autophagic clearance of intracellular microbes. Design/ResultsWe demonstrate, using somatically gene-targeted human cells that the ATG16L1 T300A variant confers protection from cellular invasion by Salmonella. In addition, we show that ATG16L1-deficient cells are resistant to bacterial invasion. ConclusionsThese results suggest that cellular expression of ATG16L1 facilitates bacterial invasion and that the CD-associated ATG16L1 T300A variant may confer protection from bacterial infection.

Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet [GUT MICROBIOTA]

Thu, 13 Jun 2013 00:00:00 +0000

ObjectiveTo characterise the influence of diet on abdominal symptoms, anal gas evacuation, intestinal gas distribution and colonic microbiota in patients complaining of flatulence. DesignPatients complaining of flatulence (n=30) and healthy subjects (n=20) were instructed to follow their usual diet for 3 days (basal phase) and to consume a high-flatulogenic diet for another 3 days (challenge phase). ResultsDuring basal phase, patients recorded more abdominal symptoms than healthy subjects in daily questionnaires (5.8{+/-}0.3 vs 0.4{+/-}0.2 mean discomfort/pain score, respectively; p=<0.0001) and more gas evacuations by an event marker (21.9{+/-}2.8 vs 7.4{+/-}1.0 daytime evacuations, respectively; p=0.0001), without differences in the volume of gas evacuated after a standard meal (262{+/-}22 and 265{+/-}25 mL, respectively). On flatulogenic diet, both groups recorded more abdominal symptoms (7.9{+/-}0.3 and 2.8{+/-}0.4 discomfort/pain, respectively), number of gas evacuations (44.4{+/-}5.3 and 21.7{+/-}2.9 daytime evacuations, respectively) and had more gas production (656{+/-}52 and 673{+/-}78 mL, respectively; p<0.05 vs basal diet for all). When challenged with flatulogenic diet, patients' microbiota developed instability in composition, exhibiting variations in the main phyla and reduction of microbial diversity, whereas healthy subjects' microbiota were stable. Taxa from Bacteroides fragilis or Bilophila wadsworthia correlated with number of gas evacuations or volume of gas evacuated, respectively. ConclusionsPatients complaining of flatulence have a poor tolerance of intestinal gas, which is associated with instability of the microbial ecosystem.

A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma [HEPATOLOGY]

Thu, 13 Jun 2013 00:00:00 +0000

ObjectiveHepatocellular carcinoma (HCC) is a heterogeneous tumour displaying a complex variety of genetic and epigenetic changes. In human cancers, aberrant post-transcriptional modifications, such as alternative splicing and RNA editing, may lead to tumour specific transcriptome diversity. DesignBy utilising large scale transcriptome sequencing of three paired HCC clinical specimens and their adjacent non-tumour (NT) tissue counterparts at depth, we discovered an average of 20 007 inferred A to I (adenosine to inosine) RNA editing events in transcripts. The roles of the double stranded RNA specific ADAR (Adenosine DeAminase that act on RNA) family members (ADARs) and the altered gene specific editing patterns were investigated in clinical specimens, cell models and mice. ResultsHCC displays a severely disrupted A to I RNA editing balance. ADAR1 and ADAR2 manipulate the A to I imbalance of HCC via their differential expression in HCC compared with NT liver tissues. Patients with ADAR1 overexpression and ADAR2 downregulation in tumours demonstrated an increased risk of liver cirrhosis and postoperative recurrence and had poor prognoses. Due to the differentially expressed ADAR1 and ADAR2 in tumours, the altered gene specific editing activities, which was reflected by the hyper-editing of FLNB (filamin B, {beta}) and the hypo-editing of COPA (coatomer protein complex, subunit ), are closely associated with HCC pathogenesis. In vitro and in vivo functional assays prove that ADAR1 functions as an oncogene while ADAR2 has tumour suppressive ability in HCC. ConclusionsThese findings highlight the fact that the differentially expressed ADARs in tumours, which are responsible for an A to I editing imbalance, has great prognostic value and diagnostic potential for HCC.

Observations suggesting bioactive Fgf15 is not present in mouse blood [POSTSCRIPT]

Sat, 8 Jun 2013 00:00:00 +0000

I read with interest the paper by Uriarte et al,1 in which the authors conclude that Fgf15 is a key mediator of the liver growth-promoting effects of bile acids.' There are reasons to question the conclusions drawn in this paper. Due to space limit I forward three issues. (1) Fgf15 exerts its effects via FGFR4 as mentioned. The authors have not recognised a report by Yu et al2 showing that deletion of FGFR4 does not alter the ability of the liver to regenerate after partial hepatectomy. How can circulating Fgf15 (derived from the gut as currently often believed, and as also these authors claim) be crucial for liver regeneration, when FGFR4 has no role in liver regeneration2? This discrepancy strongly suggests that the inability of the liver to regenerate in Fgf15KO mice is independent of FGFR4, and by consequence, must be explained ...

Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants [COELIAC DISEASE]

Fri, 7 Jun 2013 00:00:00 +0000

BackgroundThe majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. ObjectiveWe explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. DesignWe developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. ResultsAdding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. ConclusionsPredicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.

Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts [GUIDELINES]

Sat, 1 Jun 2013 00:00:00 +0000

Lynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. In 2007, a group of European experts (the Mallorca group) published guidelines for the clinical management of LS. Since then substantial new information has become available necessitating an update of the guidelines. In 2011 and 2012 workshops were organised in Palma de Mallorca. A total of 35 specialists from 13 countries participated in the meetings. The first step was to formulate important clinical questions. Then a systematic literature search was performed using the Pubmed database and manual searches of relevant articles. During the workshops the outcome of the literature search was discussed in detail. The guidelines described in this paper may be helpful for the appropriate management of families with LS. Prospective controlled studies should be undertaken to improve further the care of these families.

Endoscopic retrograde cholangiopancreatography: utilisation and outcomes in a 10-year population-based cohort [RESEARCH]

Fri, 31 May 2013 00:00:00 +0000

ObjectiveTo determine utilisation of endoscopic retrograde cholangiopancreatography (ERCP); incidence of inpatient admissions for complications occurring within 30 days of ERCP and risk factors for procedural-related complications, in a population-based study. DesignRetrospective cohort study. SettingOlmsted County, Minnesota. ParticipantsAll adult residents of Olmsted County, Minnesota, who underwent ERCP from 1997 to 2006. InterventionsDiagnostic and therapeutic ERCPs were assessed. Primary and secondary outcome measuresPatient and procedural characteristics and complications within 30 days; and rates of ERCP utilisation and unplanned admissions and risk factors for admissions. ResultsIn 10 years, 1072 ERCPs were performed on 827 individual patients. Average utilisation of ERCP was 83.1 ERCPs/100 000 persons/year, with an increase from 58 to 104.8 ERCPs/100 000 persons/year over time, driven by increases in therapeutic procedures. Within 30 days after 236 procedures, 62 admissions were definitely related to the index ERCP. The complication rate was 5.3%, including pancreatitis (26, 2.4%), infection/cholangitis (16, 1.5%), bleeding (15, 1.4%) and perforation (4, 0.37%). 30-day mortality was 2.4%, none of which was directly related to the ERCP or complications thereof. Risk factors identified through multivariate analysis to be associated with adverse events included: age <45 years (p=0.0498); body mass index [≥]35 (p=0.0024); pancreatic duct cannulation (p=0.0026); outpatient procedure (p<0.0001); intraprocedure sphincterotomy bleeding (p<0.0001); difficulty grade (p=0.115) and patient's first ERCP (p=0.0394). LimitationsRetrospective study. ConclusionsPopulation utilisation of ERCP rose during the study period, specifically in therapeutic procedures. Admissions within 30 days of ERCP are common but often unrelated. Complications of ERCP remain infrequent and deaths quite unusual.

A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer [RESEARCH]

Tue, 28 May 2013 00:00:00 +0000

ObjectivesThe categorisation of colon cancer (CC) into right-sided (RCC) and left-sided (LCC) disease may not capture more subtle variances in aetiology and prognosis. In a nationwide study, we investigated differences in clinical characteristics and survival of RCC versus LCC and of the complete range of CC subsites. DesignProspective nationwide cohort study. SettingThe database of the Danish Colorectal Cancer Group (DCCG). Participants23 487 CC patients. Outcome measuresOverall survival (Kaplan-Meier plots) and mortality (HR from Cox proportional hazards regression analysis) according to CC localisation. For adjustment and stratification, we used age, sex, ASA score (the American Society of Anaesthesiologists score), tumour location and stage, number of lymph nodes harvested at operation, number of lymph nodes with metastases and presence of distant metastases. ResultsPatients with RCC had a higher median age at diagnosis (74.3 years) than patients with LCC (71.8 years; p<0.0001). Overall, the proportion of patients who were women increased the closer the tumour site was to the small intestine. Although RCC patients had higher ASA scores than LCC patients (p<0.0001), the highest ASA scores were observed in patients with cancer in the transverse and descending colon and at both colon flexures. While RCCs overall were more advanced than LCCs (p<0.0001), the most advanced CCs were those of the descending colon, splenic flexure and caecum. RCC mortality was higher than LCC mortality only during the first 2 years (women: HR 1.13; 95% CI 1.06 to 1.20; men: HR 1.27; 95% CI 1.20 to 1.35), and relative to mortality from sigmoid CC, the highest mortality was observed from splenic flexure cancer (HR 1.75; 95% CI 1.54 to 2.00). ConclusionsThe present data challenge the simple categorisation of CC into RCC and LCC.

Mathematical modelling to restore circulating IGF-1 concentrations in children with Crohn's disease-induced growth failure: a pharmacokinetic study [RESEARCH]

Tue, 28 May 2013 00:00:00 +0000

ObjectivesChildren with Crohn's disease grow poorly, and inflammation depresses the response of insulin-like growth factor-1 (IGF-1) to growth hormone. Correcting the inflammation normalises growth velocity; however, removing inflammation cannot be achieved in all children. Our lack of understanding of IGF-1 kinetics has hampered its use, particularly as high IGF-1 concentrations over long periods may predispose to colon cancer. We hypothesised that mathematical modelling of IGF-1 would define dosing regimes that return IGF-1 concentrations into the normal range, without reaching values that risk cancer. DesignPharmacokinetic intervention study. SettingTertiary paediatric gastroenterology unit. Participants8 children (M:F; 4:4) entered the study. All completed: 5 South Asian British; 2 White British; 1 African British. Inclusion criteria: Children over 10 years with active Crohn's disease (C reactive protein >10 mg/l or erythrocyte sedimentation rate >25 mm/h) and height velocity <-2 SD score. Exclusion criteria: closed epiphyses; corticosteroids within 3 months; neoplasia or known hypersensitivity to recombinant human IGF-1 (rhIGF-1). InterventionsSubcutaneous rhIGF-1 (120 g/kg) per dose over two admissions: the first as a single dose and the second as twice daily doses over 5 days. Primary outcomeSignificant increase in circulating IGF-1. Secondary outcomesIncidence of side effects of IGF-1. A mathematical model of circulating IGF-1 (Ac) was developed to include parameters of endogenous synthesis (Ksyn); exogenous uptake (Ka) from the subcutaneous dose (As): and IGF-1 clearance: where dAc/dt=Ksyn - KoutxAc+KaxAs. ResultsSubcutaneous IGF-1 increased concentrations, which were maintained on twice daily doses. In covariate analysis, disease activity reduced Ksyn (p<0.001). Optimal dosing was derived from least squares regression fitted to a dataset of 384 Crohn's patients, with model parameters assigned by simulation. ConclusionsBy using age, weight and disease activity scaling in IGF-1 dosing, over 95% of children will have normalised IGF-1 concentrations below +2.5 SDs of the normal population mean, a level not associated with cancer risk.

Pulmonary metastasectomy in colorectal cancer: a prospective study of demography and clinical characteristics of 543 patients in the Spanish colorectal metastasectomy registry (GECMP-CCR) [RESEARCH]

Tue, 28 May 2013 00:00:00 +0000

ObjectivesTo capture an accurate contemporary description of the practice of pulmonary metastasectomy for colorectal carcinoma in one national healthcare system. DesignA national registry set up in Spain by Grupo Espanol de Cirugia Metastasis Pulmonares de Carcinoma Colo-Rectal (GECMP-CCR). Setting32 Spanish thoracic units. ParticipantsAll patients with one or more histologically proven lung metastasis removed by surgery between March 2008 and February 2010. InterventionsPulmonary metastasectomy for one or more pulmonary nodules proven to be metastatic colorectal carcinoma. Primary and secondary outcome measuresThe age and sex of the patients having this surgery were recorded with the number of metastases removed, the interval between the primary colorectal cancer operation and the pulmonary metastasectomy, and the carcinoembryonic antigen level. Also recorded were the practices with respect to mediastinal lymphadenopathy and coexisting liver metastases. ResultsData were available on 543 patients from 32 units (6-43/unit). They were aged 32-88 (mean 65) years, and 65% were men. In 55% of patients, there was a solitary metastasis. The median interval between the primary cancer resection and metastasectomy was 28 months and the serum carcinoembryonic antigen was low/normal in the majority. Liver metastatic disease was present in 29% of patients at some point prior to pulmonary metastasectomy. Mediastinal lymphadenectomy varied from 9% to 100% of patients. ConclusionsThe data represent a prospective comprehensive national data collection on pulmonary metastasectomy. The practice is more conservative than the impression gained when members of the European Society of Thoracic Surgeons were surveyed in 2006/2007 but is more inclusive than would be recommended on the basis of recent outcome analyses. Further analyses on the morbidity associated with this surgery and the correlation between imaging studies and pathological findings are being published separately by GECMP-CCR.

Clinical implementation of a new antibiotic prophylaxis regimen for percutaneous endoscopic gastrostomy [RESEARCH]

Tue, 28 May 2013 00:00:00 +0000

ObjectivesThis study was undertaken to test the extent to which a new antibiotic prophylaxis regimen for percutaneous endoscopic gastrostomy (PEG), identified as a justified and simpler alternative to conventional regimen in a randomised clinical trial, has been adopted in clinical practice. DesignA Swedish nationwide implementation survey, conducted in February 2013, assessed the level of clinical implementation of a 20 ml dose of oral solution of sulfamethoxazole and trimethoprim deposited in the PEG catheter immediately after insertion. All hospitals inserting at least five PEGs annually were identified from the Swedish Patient Registry. A clinician involved in the PEG insertions at each hospital participated in a structured telephone interview addressing their routine use of antibiotic prophylaxis. SettingAll Swedish hospitals inserting PEGs (n=60). ParticipantsRepresentatives of PEG insertions at each of the 60 eligible hospitals participated (100% participation). Main outcome measuresUse of routine antibiotic prophylaxis for PEG. ResultsA total of 32 (53%) of the 60 hospitals had adopted the new regimen. It was more frequently adopted in university hospitals (67%) than in community hospitals (41%). An annual total of 1813 (70%) of 2573 patients received the new regimen. Higher annual hospital volume was associated with a higher level of adoption of the new regimen (80% in the highest vs 31% in the lowest). ConclusionsThe clinical implementation of the new antibiotic prophylaxis regimen for PEG was high and rapid (70% of all patients within 3 years), particularly in large hospitals.

Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants [COELIAC DISEASE]

Thu, 23 May 2013 00:00:00 +0000

Investigation of the atypical FBXW7 mutation spectrum in human tumours by conditional expression of a heterozygous propellor tip missense allele in the mouse intestines [COLORECTAL CANCER]

Wed, 15 May 2013 00:00:00 +0000

ObjectiveFBXW7 encodes the substrate recognition component of a ubiquitin ligase that degrades targets such as Notch1, c-Jun, c-Myc and cyclin E. FBXW7 mutations occur in several tumour types, including colorectal cancers. The FBXW7 mutation spectrum in cancers is unusual. Some tumours have biallelic loss of function mutations but most have monoallelic missense mutations involving specific arginine residues at {beta}-propellor tips involved in substrate recognition. DesignFBXW7 functional studies have generally used null systems. In order to analyse the most common mutations in human tumours, we created a Fbxw7fl(R482Q)/+ mouse and conditionally expressed this mutation in the intestines using Vill-Cre. We compared these mice with heterozygous null (Fbxw7+/-) mutants. ResultsA few sizeable intestinal adenomas occurred in approximately 30% of R482Q/+ and Fbxw7+/- mice at age >300 days. Breeding the R482Q allele onto Apc mutant backgrounds led to accelerated morbidity and increased polyp numbers and size. Within the small bowel, polyp distribution was shifted proximally. Elevated levels of two particular Fbxw7 substrates, Klf5 and Tgif1, were found in normal intestine and adenomas of R482Q/+, R482Q/R482Q and Fbxw7-/- mice, but not Fbxw7+/- animals. On the Apc mutant background, Fbxw7+/- mutants had a phenotype intermediate between Fbxw7 wild-type and R482Q/+ mice. ConclusionsHeterozygous Fbxw7 propellor tip (R482Q) mutations promote intestinal tumorigenesis on an Apc mutant background. Klf5 and Tgif1 are strong candidates for mediating this effect. Although heterozygous null Fbxw7 mutations also promote tumour growth, these have a weaker effect than R482Q. These findings explain the FBXW7 mutation spectrum found in human cancers, and emphasise the need for animal models faithfully to reflect human disease.

The paradox of NKp46+ natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon {alpha} treatment [VIRAL HEPATITIS]

Sat, 11 May 2013 00:00:00 +0000

ObjectiveThere is evidence that natural killer (NK) cells help control persistent viral infections including hepatitis C virus (HCV). The phenotype and function of blood and intrahepatic NK cells, in steady state and after interferon (IFN) treatment has not been fully elucidated. DesignWe performed a comparison of NK cells derived from blood and intrahepatic compartments in multiple paired samples from patients with a variety of chronic liver diseases. Furthermore, we obtained serial paired samples from an average of five time points in HCV patients treated with IFN. ResultsLiver NK cells demonstrate a distinct activated phenotype compared to blood manifested as downregulation of the NK cell activation receptors CD16, NKG2D, and NKp30; with increased spontaneous degranulation and IFN production. In contrast, NKp46 expression was not downregulated. Indeed, NKp46-rich NK populations were the most activated, correlating closely with the severity of liver inflammation. Following initiation of IFN treatment there was a significant increase in the proportion of intrahepatic NK cells at days 1 and 3. NKp46-rich NK populations demonstrated no reserve activation capacity with IFN treatment and were associated with poor viral control on treatment and treatment failure. ConclusionsNKp46 marks out pathologically activated NK cells, which may result from a loss of homeostatic control of activating receptor expression in HCV. Paradoxically these pathological NK cells do not appear to be involved in viral control in IFN-treated individuals and, indeed, predict slower rates of viral clearance.

Body mass index and perioperative complications after oesophagectomy for adenocarcinoma: a systematic database review [RESEARCH]

Thu, 2 May 2013 00:00:00 +0000

ObjectiveGiven the increasing rate of obesity, the effects of excessive body weight on surgical outcomes constitute a relevant quality of care concern. Our aim was to determine the relationship between preoperative body mass index (BMI) on perioperative complications after oesophagectomy for adenocarcinoma of the oesophagus. DesignRetrospective database review. SettingSingle institution high volume oncological tertiary care referral centre. ParticipantsFrom our comprehensive oesophageal cancer database consisting of 709 patients, we stratified patients according to BMI: 155 normal-weight (BMI 20-24), 198 overweight (BMI 25-29) and 187 obese (BMI [≥]30) patients. InterventionsAll patients underwent oesophagectomy for cancer. Primary and secondary outcome measuresIncidences of preoperative risk factors and perioperative complications in each group were analysed. ResultsThe patient cohort consisted of 474 men and 66 women with a mean age of 64.3 years (28-86). They were similar in terms of demographics and comorbidities, with the exception of a younger age (65.2 vs 65.4 vs 62.5 years, p=0.0094), and a higher incidence of diabetes (9.1% vs 13.2% vs 22.7%, p=0.001), hiatal hernia (16.8% vs 17.8% vs 28.8%, p=0.009) and Barrett oesophagus (24.7% vs 25.4% vs 36.2%, p=0.025) for obese patients. The type of surgery performed, overall blood loss, extent of lymphadenectomy, R0 resections and complications were not influenced by BMI on univariate and multivariate analysis. ConclusionsIn our experience, patients with an elevated BMI and oesophageal adenocarcinoma do not experience an increase in morbidity and mortality after oesophagectomy as stated in previous reports, when performed at a high volume centre. Additionally, BMI did not affect the quality of oncological resection as determined by number of harvested lymph-nodes and rates of R0 resections. Trial RegistrationMCC 15030, IRB 105286.

The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention [HELICOBACTER PYLORI]

Wed, 1 May 2013 00:00:00 +0000

ObjectiveTo evaluate the benefit of mass eradication of Helicobacter pylori infection in reducing premalignant gastric lesions. DesignMass eradication of H pylori infection was started from 2004 for a Taiwanese population with prevalent H pylori infection, who were >30 years of age. Participants positive for the 13C-urea breath test underwent endoscopic screening and 1-week clarithromycin-based triple therapy. For subjects whose initial treatment failed, 10-day levofloxacin-based triple therapy was administered. The main outcome measures were changes in the prevalence of H pylori infection and premalignant gastric lesions, and changes in the incidence of premalignant gastric lesions and gastric cancer before (1995-2003) and after (2004-2008) chemoprevention using various comparators. ResultsThe reduction in H pylori infection was 78.7% (95% CI 76.8% to 80.7%), and the estimated incidence of re-infection/recrudescence was 1% (95% CI 0.6% to 1.4%) per person-year. The effectiveness of reducing the incidence of gastric atrophy resulting from chemoprevention was significant at 77.2% (95% CI 72.3% to 81.2%), while the reduction in intestinal metaplasia was not significant. Compared with the 5-year period before chemoprevention and in the absence of endoscopic screening, the effectiveness in reducing gastric cancer incidence during the chemoprevention period was 25% (rate ratio 0.753, 95% CI 0.372 to 1.524). The reduction in peptic ulcer disease was 67.4% (95% CI 52.2% to 77.8%), while the incidence of oesophagitis was 6% (95% CI 5.1% to 6.9%) after treatment. ConclusionsPopulation-based eradication of H pylori infection has led to a significant reduction in gastric atrophy at the expense of increased oesophagitis. The ultimate benefit in reducing gastric cancer incidence and its mortality should be validated by a further long-term follow-up. Trial registration numberNCT00155389.

Consumption of analgesics before a marathon and the incidence of cardiovascular, gastrointestinal and renal problems: a cohort study [RESEARCH]

Fri, 19 Apr 2013 00:00:00 +0000

ObjectivesTo prevent pain inhibiting their performance, many athletes ingest over-the-counter (OTC) analgesics before competing. We aimed at defining the use of analgesics and the relation between OTC analgesic use/dose and adverse events (AEs) during and after the race, a relation that has not been investigated to date. DesignProspective (non-interventional) cohort study, using an online questionnaire. SettingThe Bonn marathon 2010. Participants3913 of 7048 participants in the Bonn marathon 2010 returned their questionnaires. Primary and secondary outcomesIntensity of analgesic consumption before sports; incidence of AEs in the cohort of analgesic users as compared to non-users. ResultsThere was no significant difference between the premature race withdrawal rate in the analgesics cohort and the cohort who did not take analgesics ( controls'). However, race withdrawal because of gastrointestinal AEs was significantly more frequent in the analgesics cohort than in the control. Conversely, withdrawal because of muscle cramps was rare, but it was significantly more frequent in controls. The analgesics cohort had an almost 5 times higher incidence of AEs (overall risk difference of 13%). This incidence increased significantly with increasing analgesic dose. Nine respondents reported temporary hospital admittance: three for temporary kidney failure (post-ibuprofen ingestion), four with bleeds (post-aspirin ingestion) and two cardiac infarctions (post-aspirin ingestion). None of the control reported hospital admittance. ConclusionsThe use of analgesics before participating in endurance sports may cause many potentially serious, unwanted AEs that increase with increasing analgesic dose. Analgesic use before endurance sports appears to pose an unrecognised medical problem as yet. If verifiable in other endurance sports, it requires the attention of physicians and regulatory authorities.

Cost-effectiveness and quality of life in surgeon versus general practitioner-organised colon cancer surveillance: a randomised controlled trial [RESEARCH]

Thu, 18 Apr 2013 00:00:00 +0000

ObjectiveTo assess whether colon cancer follow-up can be organised by general practitioners (GPs) without a decline in the patient's quality of life (QoL) and increase in cost or time to cancer diagnoses, compared to hospital follow-up. DesignRandomised controlled trial. SettingNorthern Norway Health Authority Trust, 4 trusts, 11 hospitals and 88 local communities. ParticipantsPatients surgically treated for colon cancer, hospital surgeons and community GPs. Intervention24-month follow-up according to national guidelines at the community GP office. To ensure a high follow-up guideline adherence, a decision support tool for patients and GPs were used. Main outcome measuresPrimary outcomes were QoL, measured by the global health scales of the European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ C-30) and EuroQol-5D (EQ-5D). Secondary outcomes were cost-effectiveness and time to cancer diagnoses. Results110 patients were randomised to intervention (n=55) or control (n=55), and followed by 78 GPs (942 follow-up months) and 70 surgeons (942 follow-up months), respectively. Compared to baseline, there was a significant improvement in postoperative QoL (p=0.003), but no differences between groups were revealed (mean difference at 1, 3, 6, 9, 12, 15, 18, 21 and 24-month follow-up appointments): Global Health; {Delta}-2.23, p=0.20; EQ-5D index; {Delta}-0.10, p=0.48, EQ-5D VAS; {Delta}-1.1, p=0.44. There were no differences in time to recurrent cancer diagnosis (GP 35 days vs surgeon 45 days, p=0.46); 14 recurrences were detected (GP 6 vs surgeon 8) and 7 metastases surgeries performed (GP 3 vs surgeon 4). The follow-up programme initiated 1186 healthcare contacts (GP 678 vs surgeon 508), 1105 diagnostic tests (GP 592 vs surgeon 513) and 778 hospital travels (GP 250 vs surgeon 528). GP organised follow-up was associated with societal cost savings ({pound}8233 vs {pound}9889, p<0.001). ConclusionsGP-organised follow-up was associated with no decline in QoL, no increase in time to recurrent cancer diagnosis and cost savings. Trial registrationClinicalTrials.gov identifier NCT00572143.

Developing a community-based intervention to improve quality of life in people with colorectal cancer: a complex intervention development study [RESEARCH]

Thu, 11 Apr 2013 00:00:00 +0000

ObjectivesTo develop and pilot a theory and evidence-based intervention to improve quality of life (QoL) in people with colorectal cancer. DesignA complex intervention development study. SettingNorth East Scotland and Glasgow. ParticipantsSemistructured interviews with people with colorectal cancer (n=28), cancer specialists (n=16) and primary care health professionals (n=14) and pilot testing with patients (n=12). InterventionsA single, 1 h nurse home visit 6-12 weeks after diagnosis, and telephone follow-up 1 week later (with a view to ongoing follow-up in future). Primary and secondary outcome measuresQualitative assessment of intervention feasibility and acceptability. ResultsModifiable predictors of QoL identified previously were symptoms (fatigue, pain, diarrhoea, shortness of breath, insomnia, anorexia/cachexia, poor psychological well-being, sexual problems) and impaired activities. To modify these symptoms and activities, an intervention based on Control Theory was developed to help participants identify personally important symptoms and activities; set appropriate goals; use action planning to progress towards goals; self-monitor progress and identify (and tackle) barriers limiting progress. Interview responses were generally favourable and included recommendations about timing and style of delivery that were incorporated into the intervention. The pilot study demonstrated the feasibility of intervention delivery. ConclusionsThrough multidisciplinary collaboration, a theory-based, acceptable and feasible intervention to improve QoL in colorectal cancer patients was developed, and can now be evaluated.

The varying role of the GP in the pathway between colonoscopy and surgery for colorectal cancer: a retrospective cohort study [RESEARCH]

Wed, 6 Mar 2013 00:00:00 +0000

ObjectivesTo describe general practitioner (GP) involvement in the treatment referral pathway for colorectal cancer (CRC) patients. DesignA retrospective cohort analysis of linked data. SettingA population-based sample of CRC patients diagnosed from August 2004 to December 2007 in New South Wales, Australia, using the 45 and Up Study, cancer registry diagnosis records, inpatient hospital records and Medicare claims records. Participants407 CRC patients who had a colonoscopy followed by surgery. Primary outcome measuresPatterns of GP consultations between colonoscopy and surgery (ie, between diagnosis and treatment). We investigated whether consulting a GP presurgery was associated with time to surgery, postsurgical GP consultations or rectal cancer cases having surgery in a centre with radiotherapy facilities. ResultsOf the 407 patients, 43% (n=175) had at least one GP consultation between colonoscopy and surgery. The median time from colonoscopy to surgery was 27 days for those with an intervening GP consultation and 15 days for those without the consultation. 55% (n=223) had a GP consultation up to 30 days postsurgery; it was more common in cases of patients who consulted a GP presurgery than for those who did not (65% and 47%, respectively, adjusted OR 2.71, 95% CI 1.50 to 4.89, p=0.001). Of the 142 rectal cancer cases, 23% (n=33) had their surgery in a centre with radiotherapy facilities, with no difference between those who did and did not consult a GP presurgery (21% and 25% respectively, adjusted OR 0.84, 95% CI 0.27 to 2.63, p=0.76). ConclusionsConsulting a GP between colonoscopy and surgery was associated with a longer interval between diagnosis and treatment, and with further GP consultations postsurgery, but for rectal cancer cases it was not associated with treatment in a centre with radiotherapy facilities. GPs might require a more defined and systematic approach to CRC management.

Thirty-day complications after laparoscopic or open cholecystectomy: a population-based cohort study in Italy [RESEARCH]

Wed, 13 Feb 2013 00:00:00 +0000

ObjectiveThe objective of the study is to evaluate short-term complications after laparoscopic (LC) or open cholecystectomy (OC) in patients with gallstones by using linked hospital discharge data. DesignPopulation-based cohort study. SettingData were obtained from the Regional Hospital Discharge Registry Lazio Region in Central Italy (around 5 million inhabitants) in 2007-2008. ParticipantsAll patients admitted to hospitals of Lazio with symptomatic gallstones (International Classification of disease, 9th Revision, Clinical Modification (ICD-9-CM)=574) who underwent LC (ICD-9-CM 51.23) or OC (ICD-9-CM 51.22). Outcome measures(1) 30-day surgical-related complications' defined as any complication of the biliary tract (including postoperative infection, haemorrhage or haematoma or seroma complicating a procedure, persistent postoperative fistula, perforation of bile duct and disruption of wound). (2) 30-day systemic complications' defined as any complications of other organs (including sepsis, infections from other organs, major cardiovascular events and selected adverse events). Results13 651 patients were included; 86.1% had LC, 13.9% OC. 2.0% experienced surgical-related complications (SRC), 2.1% systemic complications (SC). The OR of complications after LC versus OC was 0.60 (p<0.001) for SRC and 0.52 (p<0.001) for SC. In relation to SRC, the advantage of LC was consistent across age categories, severity of gallstones and previous upper abdominal surgery, whereas there was no advantage among people with emergency admission (OR=0.94, p=0.764). For SC, no significant advantage of LC was seen among very old people (OR=0.99, p=0.975) and among those with previous upper abdominal surgery (OR=0.86, p=0.905). ConclusionsThis large observational study confirms that LC is more effective than OC with respect to 30-day complications. Population-based linkage of administrative datasets can enlarge evidence of treatment benefits in clinical practice.

Impact of route to diagnosis on treatment intent and 1-year survival in patients diagnosed with oesophagogastric cancer in England: a prospective cohort study [RESEARCH]

Wed, 13 Feb 2013 00:00:00 +0000

ObjectiveTo investigate the relationship between the route to diagnosis, patient characteristics, treatment intent and 1 -year survival among patients with oesophagogastric (O-G) cancer. SettingCohort study in 142 English NHS trusts and 30 cancer networks. ParticipantsPatients diagnosed with O-G cancer between October 2007 and June 2009. DesignProspective cohort study. Route to diagnosis defined as general practitioner (GP) referral--urgent (suspected cancer) or non-urgent, hospital consultant referral, or after an emergency admission. Logistic regression was used to estimate associations and adjust for differences in casemix. Main outcome measuresProportion of patients diagnosed by route of diagnosis; proportion of patients selected for curative treatment; 1-year survival. ResultsAmong 14 102 cancer patients, 66.3% were diagnosed after a GP referral, 16.4% after an emergency admission and 17.4% after a hospital consultant referral. Of the 9351 GP referrals, 68.8% were urgent. Compared to urgent GP referrals, a markedly lower proportion of patients diagnosed after emergency admission had a curative treatment plan (36% vs 16%; adjusted OR=0.62, 95% CI 0.52 to 0.74) and a lower proportion survived 1 year (43% vs 27%; OR 0.78; 95% CI 0.68 to 0.89). Urgency of GP referral did not affect treatment intent or survival. Routes to diagnosis varied across cancer networks, with the adjusted proportion of patients diagnosed after emergency admission ranging from 8.7 to 32.3%. ConclusionsOutcomes for cancer patients are worse if diagnosed after emergency admission. Primary care and hospital services should work together to reduce rates of diagnosis after emergency admission and the variation across cancer networks.

Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn's disease: a retrospective cohort study [RESEARCH]

Fri, 8 Feb 2013 00:00:00 +0000

ObjectiveStress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake. DesignA retrospective cohort study. Settings13 hospitals in Japan. Participants546 ulcerative colitis (UC) and 357 Crohn's disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patient's clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records. Primary outcomeWe evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined active' as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD). ResultsAmong the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p<0.0001). A total of 86 patients relapsed (relapse rate=15.8%). The relapse rate was about twice that of the corresponding period in the previous year. Among the CD patients, 86 patients had active disease and 271 had inactive disease before the earthquake. After the earthquake, the activity indices changed little. A total of 25 patients experienced a relapse (relapse rate=7%). The relapse rate did not differ from that of the corresponding period in the previous year. Multivariate analyses revealed that UC, changes in dietary oral intake and anxiety about family finances were associated with the relapse. ConclusionsLife-event stress induced by the Great East Japan Earthquake was associated with relapse in UC but not CD.

Dietary patterns and colorectal cancer recurrence and survival: a cohort study [RESEARCH]

Thu, 7 Feb 2013 00:00:00 +0000

ObjectiveTo examine the association between dietary patterns and colorectal cancer (CRC) survival. DesignCohort study. SettingA familial CRC registry in Newfoundland. Participants529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010. Outcome measureParticipants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates. ResultsDisease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men). ConclusionsThe processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC.

Use of non-steroidal anti-inflammatory drugs and proton pump inhibitors in correlation with incidence, recurrence and death of peptic ulcer bleeding: an ecological study [RESEARCH]

Wed, 30 Jan 2013 00:00:00 +0000

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are regarded as two types of drugs that respectively increase and decrease the risk of peptic ulcer bleeding. However, their relation to occurrence, recurrence and death of bleeding in the population level is not clear. Study objectiveTo clarify recent calendar-time correlations between sales of NSAIDs and PPIs and the occurrence of peptic ulcer bleeding, re-bleeding and death. DesignEcological study. ResultsThe time trend of peptic ulcer bleeding did not correlate with PPI sales but did correlate with NSAIDs in mem (Rmale=0.6571, Pmale=0.05). Sales of PPIs (inverse) and NSAIDs correlated with re-bleeding in women (Rmale=-0.8754, Pmale=0.002 and Rfemale=0.7161, Pfemale=0.03, respectively), but not in men. An inverse correlation between PPI sales and 30-day death after bleeding was found (Rmale=-0.9392, Pmale=0.0002 and Rfemale=-0.8561, Pfemale=0.003), and NSAID sales were found to correlate with increased death after bleeding ((Rmale=0.7278, Pmale=0.03, Rfemale=0.7858, Pfemale=0.01). ConclusionsThe sales of NSAIDs and PPIs correlate with recurrence of peptic ulcer bleeding in women and death after peptic ulcer bleeding in both genders in the population level.

Methodology of a large prospective, randomised, open, blinded endpoint streamlined safety study of celecoxib versus traditional non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis: protocol of the standard care versus celecoxib outcome trial (SCOT) [PROTOCOL]

Tue, 29 Jan 2013 00:00:00 +0000

IntroductionCyclooxygenase 2 (COX-2) inhibitors have less upper gastrointestinal toxicity than traditional non-steroidal anti-inflammatory drugs (NSAIDs). However, both COX-2 inhibitors and traditional NSAIDs may be associated with adverse cardiovascular side effects. Data from randomised and observational studies suggest that celecoxib has similar cardiovascular toxicity to traditional NSAIDs. The overall safety balance of a strategy of celecoxib therapy versus traditional NSAID therapy is unknown. The European Medicines Agency requested studies of the cardiovascular safety of celecoxib within Europe. The Standard care versus Celecoxib Outcome Trial (SCOT) compares the cardiovascular safety of celecoxib with traditional NSAID therapy in the setting of the European Union healthcare system. Methods and analysisSCOT is a large streamlined safety study conducted in Scotland, England, Denmark and the Netherlands using the Prospective Randomised Open Blinded Endpoint design. Patients aged over 60 years with osteoarthritis or rheumatoid arthritis, free from established cardiovascular disease and requiring chronic NSAID therapy, are randomised to celecoxib or their previous traditional NSAID. They are then followed up for events by record-linkage within their normal healthcare setting. The hypothesis is non-inferiority with a confidence limit of 1.4. The primary endpoint is the first occurrence of hospitalisation or death for the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are (1) first hospitalisation or death for upper gastrointestinal ulcer complications (bleeding, perforation or obstruction); (2) first occurrence of hospitalised upper gastrointestinal ulcer complications or APTC endpoint; (3) first hospitalisation for heart failure; (4) first hospitalisation for APTC endpoint plus heart failure; (5) all-cause mortality and (6) first hospitalisation for new or worsening renal failure. Ethics and disseminationSCOT has been approved by the relevant ethics committees. The trial results will be published in a peer-reviewed scientific journal. Clinical trials registration numberClinicaltrials.gov (NCT00447759).

The use of individual patient-level data (IPD) to quantify the impact of pretreatment predictors of response to treatment in chronic hepatitis B patients [RESEARCH]

Thu, 24 Jan 2013 00:00:00 +0000

ObjectivesEvidence synthesis is an integral part decision-making by reimbursement agencies. When direct evidence is not available, network-meta-analysis (NMA) techniques are commonly used. This approach assumes that the trials are sufficiently similar in terms of treatment-effect modifiers. When imbalances in potential treatment-effect modifiers exist, the NMA approach may not produce fair comparisons. The objective of this study was to identify and quantify the interaction between treatment-effect and potential treatment-effect modifiers, including time-of-response measurement and baseline viral load in chronic hepatitis B (CHB) patients. DesignRetrospective patient-level data econometric analysis. Participants1353 individuals from two randomised controlled trials of nucleoside-naive CHB taking 0.5 mg entecavir (n=679) or 100 mg lamivudine (n=668) daily for 48 weeks. InterventionsHepatitis B virus (HBV) DNA levels for both drugs were measured at baseline and weeks 24, 36 and 48. Generalised estimating equation for repeated binary responses was used to identify treatment-effect modifiers for response defined at [≤]400 or [≤]300 copies/ml. Primary outcome measuresOR at 48 weeks. ResultsThe OR for the time-of-response measurement and treatment-effect interaction term was 1.039 (p=0.00) and 1.035 (p=0.00) when response was defined at [≤]400 or [≤]300 copies/ml, respectively. The baseline HBV DNA and treatment-effect interaction OR was 0.94 (p=0.047) and 0.95 (p=0.096), respectively, for the two response definitions suggesting evidence of interaction between baseline disease activity and treatment effect. The interaction between HBeAg status and treatment effect was not statistically significant. ConclusionsThe measurement time point seems to modify the relative treatment effect of entacavir compared to lamivudine, measured on the OR scale. Evidence also suggested that differences in baseline viral load may also alter relative treatment effect. Meta-analyses should account for such modifiers when generating relative efficacy estimates.

Independent association between low serum amylase and non-alcoholic fatty liver disease in asymptomatic adults: a cross-sectional observational study [RESEARCH]

Thu, 3 Jan 2013 00:00:00 +0000

ObjectivesLow serum amylase (LSA) was reported to be associated with obesity, metabolic syndrome (MetS) and diabetes. However, it is unknown as to whether LSA is associated with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of MetS and insulin resistance. Therefore, we performed a clinical epidemiological study to investigate this potential association. DesignA cross-sectional observational study with multivariate analysis. SettingSubjects were recruited in a healthcare centre in Saitama, an eastern district of Japan, near Tokyo. ParticipantsA total of 1475 asymptomatic adults aged 30-79 years who underwent detailed medical check-ups and who regularly consumed small amounts of alcohol (<20 g/day). Outcome measuresSerum amylase, cardiometabolic risk factors, NAFLD determined by ultrasound, MetS determined by Adult Treatment Panel-III criteria and diabetes were assessed. ResultsThe prevalence of NAFLD increased significantly from 22.5% to 42.4% (all grades) and from 9.2% to 24.0% (moderate or severe grade) from the highest to the lowest quartile of serum amylase. Multiple logistic regression analysis showed that, compared with the highest quartile of serum amylase, the lowest quartile of serum amylase was significantly associated with any-grade NAFLD and with moderate-to-severe NAFLD, even after adjusting for MetS or diabetes. The association between LSA and any-grade NAFLD disappeared after further adjustment for body mass index or waist circumference, whereas the association between LSA and moderate or severe NAFLD remained statistically significant (ORs (95%CI), 2.01 (1.07 to 3.78) and 2.06 (1.09 to 3.87), respectively, both p=0.01). ConclusionsOur results suggest that LSA may be associated with moderate or severe NAFLD in asymptomatic adults independent of MetS, diabetes and obesity. These results warrant confirmation in further studies.

A cross-sectional study of the appropriateness of colonoscopy requests in the Spanish region of Catalonia [PROTOCOL]

Fri, 30 Nov 2012 00:00:00 +0000

IntroductionColonoscopies are being requested with increasing frequency in the last few years, as they are used both as a diagnostic and therapeutic procedure in several gastrointestinal diseases. Our purpose is to describe the appropriateness of colonoscopy requests issued both from primary care centres and from hospitals, according to the EPAGE II guidelines (European Panel on the Appropriateness of Gastrointestinal Endoscopy). Methods and analysisCross-sectional study. Colonoscopy requests issued since January 2011 and received at the endoscopy units of all six reference hospitals serving the primary care centres of the South Metropolitan and Central Catalonia districts will be collected (total=1500 requests). Variables to be collected include gender, date of birth, origin of the request and reference hospital, priority of the procedure, type of clinician requesting the procedure, date and indication of request, abdominal examination performed, anal inspection examination performed, date of last colonoscopy if applicable, diagnosis and date of diagnosis. Using the available information and the EPAGE II website, colonoscopy requests will be assigned as an appropriateness score. The association between the variables collected and the EPAGE II scores will be assessed using a Student's t test and a {chi}2 test. A multilevel logistic model will be generated on the factors associated with the appropriateness of the requests. Ethics and disseminationColonoscopy is a costly procedure and not free from complications. In order to increase cost effectiveness, reduce waiting lists and optimise resources, it is necessary to use tools such as the EPAGE II guidelines, which establish criteria to assess the appropriateness of colonoscopies. The purpose of this study is to describe the current situation and to discuss whether current clinical practice is appropriate. The results of the study will be published in the next few years. In consideration of the ethical principles and methods of the research study, approval was granted for the project.

SULF2 expression by immunohistochemistry and overall survival in oesophageal cancer: a cohort study [RESEARCH]

Fri, 23 Nov 2012 00:00:00 +0000

ObjectivesOesophageal cancer is the eighth most commonly diagnosed cancer worldwide, and there is a need for biomarkers to improve diagnosis, prognosis and treatment. Sulfatases 2 (SULF2) is an extracellular endosulphatase that regulates several signalling pathways in carcinogenesis and has been associated with poor prognosis. This study evaluates the relationship between SULF2 expression by immunohistochemistry and overall survival in patients with oesophageal cancer. DesignCohort study. SettingSingle tertiary care centre. ParticipantsWe included patients who underwent esophagectomy for invasive oesophageal adenocarcinoma and squamous cell carcinoma at a tertiary care centre from 1997 to 2006. We excluded patients with recurrent oesophageal cancer or less than 3 mm invasive tumour on H&E stained slide. A section from each paraffin-embedded tissue specimen was stained with an anti-SULF2 monoclonal antibody. Outcome measuresA pathologist blinded to overall survival determined the percentage and intensity of tumour cells staining. Vital status was obtained through the Social Security Death Master File, and overall survival was calculated from the date of surgery. ResultsOne-hundred patients with invasive oesophageal cancer were identified, including 75 patients with adenocarcinoma and 25 patients with squamous cell carcinoma. The squamous cell carcinoma samples had a higher mean percentage and intensity of tumour cells staining compared with the adenocarcinoma samples. After adjusting for age, sex, race, histological type, stage and neoadjuvant therapy, for every 10% increase in percentage of tumour cells staining for SULF2, the HR for death increased by 13% (95% CI 1.01 to 1.25; p=0.03). ConclusionsThe majority of adenocarcinoma samples and all of the squamous cell carcinoma samples had SULF2 staining. The percentage of tumour cells staining for SULF2 was significantly associated with overall survival. Thus, SULF2 is a potential biomarker in oesophageal cancer and may have an important role in the management of patients with this disease.

Have serological tests changed the face of childhood coeliac disease? A retrospective cohort study [RESEARCH]

Thu, 22 Nov 2012 00:00:00 +0000

ObjectivesThe aim of this study was to evaluate if the use of antitransglutaminase (tTG) and antiendomysium (EM) antibodies has modified the profile of coeliac disease (CD) in children. DesignRetrospective cohort study. SettingMonocentric study, in one major tertiary centre in Paris. Two cohorts of patients were compared; the first included patients before the use of antibodies, and the second included patients after the use of antibodies. ParticipantsAll patients from the same physician diagnosed with a CD between 1976 and 1992 (historical cohort), and between 1994 and 2007, were included in the study. 56 patients were included in the historical cohort, 59 in the recent cohort. Primary and secondary outcome measuresClinical, biological and histological profiles at diagnosis have been studied. ResultsThe recent cohort diagnosis of CD was based in 27% on a systematic screening (type I diabetes, n=10; CD in siblings, n=6). On comparison of CD patients in the historical to the recent cohort, the following significant differences were observed: Median age at diagnosis increased from 1 year to 2.7 years (p<0.0001). Patients in the historical cohort had more gastrointestinal symptoms (93% vs 63%, p=0.0001) and failure to thrive (98% vs 80%, p=0.0025). Nutritional deficiencies and morphological lesions were more severe in the historical cohort (90% subtotal or total villous atrophy vs 51%, p<0.0001). Differences observed between the two cohorts were mainly due to the presence of screened patients. ConclusionsA new type of patients, with a paucisymptomatic or asymptomatic CD, has been identified using serological tests. Silent disease has been diagnosed by screening in a target population. In the other patients of the recent cohort, symptoms were similar but less severe than those observed before. Long-term risks of untreated silent CD are not well determined as yet, and have to be evaluated in prospective studies.

A randomised controlled trial of hospital-based case management to improve colorectal cancer patients' health-related quality of life and evaluations of care [RESEARCH]

Wed, 21 Nov 2012 00:00:00 +0000

ObjectiveTo analyse the effectiveness of hospital-based case management (CM) in terms of patient-reported outcomes. DesignRandomised controlled trial allocating participants 1 : 1 to either a CM intervention or a control group. Allocation status was evident to participants and case managers, but blinded to researchers. SettingPatients were recruited at a Danish surgical department where the case managers were situated. ParticipantsColorectal cancer patients who were to undergo further investigation or treatment. Exclusion criteria were participation in another study, poor Danish language skills or apparent cognitive impairment. 140 participants were randomised to each group. Recruitment period was 11 March 2009 to 29 December 2010. InterventionsControl group patients had usual care. Intervention group patients had usual care supplemented by hospital-based CM started at first visit to the out-patient clinic (before treatment start) and ended 4 weeks after completed cancer treatment. CM was conducted by nurse case managers who undertook care pathway supervision, information dissemination to health professionals and outreaching patient support. Outcome measuresPatient-reported global quality of life measured with the EORTC QLQ-C30 and eight ad hoc, piloted patient evaluation items assessed at eight, 30 and 52 weeks after randomisation. ResultsThe two groups were comparable as to questionnaire response rates and completed scales/items. There were no statistically significant group differences on any of the health-related quality of life subscales at eight, 30 or 52 weeks. In patient evaluations, all point estimates favoured CM at week 8 and 30; at week 52, 6 of 7 estimates favoured CM. ConclusionsWe found no evidence that CM influenced colorectal cancer patients' health-related quality of life. Patients allocated to CM evaluated their care more positively than patients receiving usual care. Trial registrationClinicaltrials.gov identifier: NCT00845247.

Timing of gastrostomy insertion in children with a neurodisability: a cross-sectional study of early versus late intervention [RESEARCH]

Wed, 21 Nov 2012 00:00:00 +0000

ObjectivesThe aim of the study was to assess whether gastrostomy placement before 18 months of age results in a greater increase in z-score for weight and to assess whether admission rates were reduced postgastrostomy in this age group. DesignRetrospective cross-sectional study. SettingSingle-centre secondary care District General Hospital. ParticipantsAll children with a neurodisability with a gastrostomy in situ in September 2011 were included. Those with primary neoplasia and undergoing chemo or radiotherapy or being palliated for an aggressive neurodegenerative disorder were excluded. Those with cystic fibrosis, primary congenital heart disease or Inflammatory bowel disease were also excluded. Forty-one children underwent final analysis. Twenty-four children underwent gastrostomy insertion less than 18 months and 17 children were older than 18 months. Primary and secondary outcome measuresPrimary outcome was z-scores for weight immediately pregastrostomy and 12 months postgastrostomy. Secondary outcomes were hospital admission rates pregastrostomy and postgastrostomy. Values were compared for those with gastrostomy insertion less than or equal to 18 months against those older than 18 months at insertion. ResultsZ-score for weight increased significantly in both age groups. There was significantly increased mean difference in the z-score for weight of +1.33 pregastrostomy and postgastrostomy in the less than 18 months age group as compared with an increased mean difference in the z-score for weight of +0.45 in the older age group (p=0.021). There was no significant difference in the admission rates postgastrostomy insertion in either age group. ConclusionsGastrostomy insertion before 18 months of age results in greater z-score for weight gain in children with a neurodisability. This conclusion is limited by the lack of height and skin-fold thickness measurements. Further long-term matched control studies are required to determine the neurodevelopmental and clinical benefit of early gastrostomy placement in such children.

Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials [RESEARCH]

Mon, 22 Oct 2012 00:00:00 +0000

ObjectivesTo determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C. DesignSystematic review and meta-analyses of randomised controlled trials. Prospective cohort studies were included in sensitivity analyses. Data SourcesEligible trials were identified through electronic and manual searches. Study SelectionEight randomised controlled trials comparing antiviral therapy (interferon or pegylated interferon alone or with ribavirin) versus placebo or no intervention were included. Data extraction and synthesisTwo independent reviewers assessed the methodological quality of studies and extracted data. Random effects meta-analyses were performed. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate sources of intertrial heterogeneity, the risk of bias and the robustness of the results after adjusting for multiple testing. ResultsRandom effects meta-analysis showed that antiviral therapy reduced the risk of HCC (81/1156 vs 129/1174; risk ratio 0.53, 95% CI 0.34 to 0.81). In subgroup analyses, antiviral therapy was more beneficial (test for subgroup differences p=0.03) in virological responders (0.15, 0.05 to 0.45) than in non-responders (0.57; 0.37 to 0.85). No evidence of bias was seen in regression analyses. Sequential analysis confirmed the overall result. The sensitivity analyses showed that the cohort studies found that antiviral therapy reduced the risk of HCC. There was clear statistical evidence of bias in the cohort studies (p=0.02). ConclusionsAntiviral therapy may reduce the risk of HCC in hepatitis C-related fibrosis and cirrhosis. The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.

Retrospective study of patients with acute pancreatitis: is serum amylase still required? [RESEARCH]

Fri, 21 Sep 2012 00:00:00 +0000

ObjectivesTo assess the role of serum amylase and lipase in the diagnosis of acute pancreatitis. Secondary aims were to perform a cost analysis of these enzyme assays in patients admitted to the surgical admissions unit. DesignCohort study. SettingSecondary care. ParticipantsPatients admitted with pancreatitis to the acute surgical admissions unit from January to December 2010 were included in the study. MethodsData collated included demographics, laboratory results and aetiology. The cost of measuring a single enzyme assay was {pound}0.69 and both assays were {pound}0.99. ResultsOf the 151 patients included, 117 patients had acute pancreatitis with gallstones (n=51) as the most common cause. The majority of patients with acute pancreatitis had raised levels of both amylase and lipase. Raised lipase levels only were observed in additional 12% and 23% of patients with gallstone-induced and alcohol-induced pancreatitis, respectively. Overall, raised lipase levels were seen in between 95% and 100% of patients depending on aetiology. Sensitivity and specificity of lipase in the diagnosis of acute pancreatitis was 96.6% and 99.4%, respectively. In contrast, the sensitivity and specificity of amylase in diagnosing acute pancreatitis were 78.6% and 99.1%, respectively. Single lipase assay in all patients presenting with abdominal pain to the surgical admission unit would result in a potential saving of {pound}893.70/year. ConclusionsDetermining serum lipase level alone is sufficient to diagnose acute pancreatitis and substantial savings can be made if measured alone.

Prevalence of anal incontinence among Norwegian women: a cross-sectional study [RESEARCH]

Mon, 30 Jul 2012 00:00:00 +0000

ObjectiveAnal incontinence (AI) is a symptom associated with age, bowel symptoms and obstetric injuries. Primary aim of the study was to establish the prevalence of AI among women and secondarily to evaluate the impact on daily life and conditions associated with AI. DesignA cross-sectional study. SettingParticipants attended research stations located in different parts of Nord-Trondelag county, Norway. Data were collected through interviews, questionnaires and clinical examinations. ParticipantsIn total, 40 955 community-dwelling women aged 30 years and older were invited. A total of 25 037 women participated, giving a participation rate of 61.1%. Primary and secondary outcome measuresFecal incontinence and flatal incontinence was defined as involuntary loss of feces and flatus weekly or more, respectively. AI was defined as the involuntary loss of feces and/or flatus weekly or more. Urgency was defined as the inability to defer defecation for 15 min. Statistical methods included prevalence estimates and logistic regression analysis. ResultsQuestions about AI were completed by 20 391 (82.4%) women. Among the 20 391 women, AI was reported by 19.1% (95% CI 18.6% to 19.7%) and fecal incontinence was reported by 3.0% (95% CI 2.8% to 3.2%). Urgency was experienced by 2586 women (12.7%, 95% CI 12.2 to 13.1). Impact on daily life was stated by 794 (26.0%, 95% CI 24.4 to 27.5) women with AI. In bivariate age-adjusted analysis of AI, OR and CI for urgency (OR 3.19, 95% CI 2.92 to 3.49) and diarrhoea (OR 3.81, 95% CI 3.32 to 4.38) revealed strongest associations with AI. ConclusionsAI affects one in five women older than 30 years. Strongest associated symptoms are urgency and diarrhoea. Trial registration numberThe study was approved by the Regional Committee for Medical and Health Research Ethics (No. 2009/1214) and followed the Declaration of Helsinki.

Antiemetic treatment for acute gastroenteritis in children: an updated Cochrane systematic review with meta-analysis and mixed treatment comparison in a Bayesian framework [RESEARCH]

Thu, 19 Jul 2012 00:00:00 +0000

ObjectiveTo assess the evidence for the safety and effectiveness of antiemetics on gastroenteritis-induced vomiting in children and adolescents. DesignSystematic review. Data SourcesThe Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE searched from 1980 to March 2012. MethodsMethods included comprehensive searches, data synthesis, meta-analysis and mixed treatment comparisons (MTC). Review methodsReference lists were checked, and missing or inconsistent data were sought from trial investigators. Randomised controlled trials comparing antiemetics in participants younger than 18 years and who were vomiting due to acute gastroenteritis. Four meta-analyses and three MTC were carried out. Results10 trials (1479 participants) and five treatments were included: dexamethasone, dimenhydrinate, granisetron, metoclopramide and ondansetron. There was clear evidence that ondansetron (oral or intravenous) compared with placebo increased the proportion of patients with cessation of vomiting (orally administered) (RR 1.44, 95% CI 1.29 to 1.61), reduced the immediate hospital admission rate (orally administered) (RR 0.40, 95% CI 0.19 to 0.83) and the need for intravenous rehydration therapy (orally administered) (RR 0.41, 95% CI 0.29 to 0.59). No significant difference was noted in the revisit rates, but ondansetron was associated with an increase in episodes of diarrhoea. There was no evidence for the use of dexamethasone or metoclopramide and limited evidence that dimenhydrinate or granisetron increased the cessation of vomiting. The MTC analysis suggested that ondansetron was the most likely treatment to stop the child vomiting. Nine studies were carried out in secondary care and one in primary care. ConclusionsThis systematic review used a method novel to this clinical area and found clear evidence that ondansetron was the most likely treatment to allow oral rehydration therapy to commence. Given the significance of these results, the authors urge healthcare policy makers to consider the wider use of ondansetron in secondary care. Furthermore, randomised controlled trials are needed to investigate the effectiveness of antiemetic treatment in primary care (including ambulatory care interventions).

A descriptive analysis of notifiable gastrointestinal illness in the Northwest Territories, Canada, 1991-2008 [RESEARCH]

Mon, 2 Jul 2012 00:00:00 +0000

ObjectivesTo describe the major characteristics of reported notifiable gastrointestinal illness (NGI) data in the Northwest Territories (NWT) from January 1991 through December 2008. DesignDescriptive analysis of 708 reported cases of NGI extracted from the Northwest Territories Communicable Disease Registry (NWT CDR). SettingPrimary, secondary and tertiary health care centres across all 33 communities of the NWT. PopulationNWT residents of all ages with confirmed NGI reported to the NWT CDR from January 1991 through December 2008. Main outcome measureLaboratory-confirmed NGI, with a particular emphasis on campylobacteriosis, giardiasis and salmonellosis. ResultsCampylobacteriosis, giardiasis and salmonellosis were the most commonly identified types of NGI in the territory. Seasonal peaks for all three diseases were observed in late summer to autumn (p<0.01). Higher rates of NGI (all 15 diseases/infections) were found in the 0-9-year age group and in men (p<0.01). Similarly, rates of giardiasis were higher in the 0-9-year age group and in men (p<0.02). A disproportionate burden of salmonellosis was found in people aged 60 years and older and in women (p<0.02). Although not significant, the incidence of campylobacteriosis was greater in the 20-29-years age group and in men (p<0.07). The health authority with the highest incidence of NGI was Yellowknife (p<0.01), while for salmonellosis and campylobacteriosis, it was Tlicho (p<0.01) and for giardiasis, the Sahtu region (p<0.01). Overall, disease rates were higher in urban areas (p<0.01). Contaminated eggs, poultry and untreated water were believed by health practitioners to be important sources of infection in cases of salmonellosis, campylobacteriosis and giardiasis, respectively. ConclusionsThe general patterns of these findings suggest that environmental and behavioural risk factors played key roles in infection. Further research into potential individual and community-level risk factors is warranted.

Barriers and facilitators to change in the organisation and delivery of endoscopy services in England and Wales: a focus group study [RESEARCH]

Mon, 25 Jun 2012 00:00:00 +0000

ObjectiveExplore professional views of changes to gastroenterology service organisation and delivery and barriers and facilitators impacting on change. The work was undertaken as part of an evaluation in endoscopy service provision catalysed by the Modernising Endoscopy Services Programme of the Modernisation Agency. DesignFocus groups followed by analysis and group-working activities identifying key themes. SettingEnglish and Welsh secondary care gastroenterology units. Participants20 professionals working in gastroenterology in England and Wales. Medical, surgical and nursing specialists including endoscopy nurses. Opportunistic sampling to include senior people in leadership and management roles who were directly involved in service modernisation, excluding those involved in the Modernisation Endoscopy Services Programme. ResultsFour 1.5 h focus groups took place in 2007. Summative and thematic analyses captured essential aspects of text and achieved consensus on key themes. 4 themes were revealed: loss of personal autonomy and erosion of professionalism', lack of senior management understanding', barriers and facilitators to change' and differences between English and Welsh units'. Themes indicated that low staff morale, lack of funding and senior management support were barriers to effective change. Limitations to the study include the disproportionately low number of focus group attendees from English units and the time delay in reporting these findings. ConclusionsDespite ambitions to implement change, ineffective management support continued to hamper modernisation of service organisation and delivery. While the National Health Service Modernisation Agency Modernising Endoscopy Services Programme acted as a catalyst for change, affecting the way staff work, communicate and think, it was not effective in heralding change itself. However, gastroenterologists were keen to consider the potential for change and future service modernisation. The methodological framework of innovative qualitative enquiry offers comprehensive and rigorous enhancement of quantitative studies, including randomised trials, when a mixed methods approach is needed.

Socio-demographic and other patient characteristics associated with time between colonoscopy and surgery, and choice of treatment centre for colorectal cancer: a retrospective cohort study [RESEARCH]

Sat, 26 May 2012 00:00:00 +0000

ObjectivesTo investigate key patient clinical and demographic characteristics associated with time between colonoscopy and surgery, and choice of treatment centre for colorectal cancer (CRC) patients. This will add to the little published research examining the pathway following CRC diagnosis and prior to surgery. DesignRetrospective cohort analysis of linked data. SettingA population-based sample of people diagnosed August 2004 to December 2007 in New South Wales, Australia. Participants569 CRC patients, of whom 407 (72%, 95% CI 68% to 75%) had colonoscopy followed by surgery. Primary outcome measuresTime between colonoscopy and surgery, and whether the surgery took place in a specialist cancer centre. ResultsAmong the 407 eligible patients analysed, the median time from colonoscopy to surgery was 19 days (IQR 12-29 days). After adjusting for key demographic and clinical characteristics such as age and disease stage, the time was longer for rectal cancer patients and those reporting fair/poor health, although differences in medians were <5 days. 24% (95% CI 20% to 28%) had surgery in a specialist cancer centre, which was more common among people resident in metropolitan areas (37% vs 14% for others, adjusted p=0.001) and those without private health insurance (30% vs 21% for others, adjusted p=0.03). ConclusionsThere do not appear to be systemic issues affecting time from colonoscopy to surgery related to patients' socio-demographic characteristics. However, patients with private insurance and those living in rural areas may be less likely to receive optimal specialist treatment. A more systematic approach might be needed to ensure cancer patients are treated in specialist cancer centres, particularly patients requiring more specialised treatment.

Antidopaminergic drugs and acute pancreatitis: a population-based study [RESEARCH]

Fri, 11 May 2012 00:00:00 +0000

ObjectivesTo evaluate the suggested association between antidopaminergic drugs and acute pancreatitis. DesignA large population-based nested case-control study. SettingSwedish nationwide study from 2006 to 2008. ParticipantsThe Patient Register was used to identify 6161 cases of acute pancreatitis. The 61 637 control subjects were randomly selected from the Register of the Total Population by frequency-based density sampling, matched for age, sex and calendar year. ExposureExposure data were extracted from the Prescribed Drug Register. Antidopaminergic drugs were grouped into antiemetic/anxiolytic and other antipsychotics. Current use of antidopaminergic drugs was defined as filling a prescription 1-114 days before index date, while previous use was 115 days to 3.5 years before index date. Main outcome measuresCases were defined as being diagnosed as having acute pancreatitis. ORs and 95% CIs were calculated using unconditional logistic regression. ResultsThe unadjusted OR indicated an increased risk of acute pancreatitis among current users of antiemetic/anxiolytics (OR 1.9, 95% CI 1.4 to 2.6), but not in the multivariable model adjusting for alcohol-related comorbidity, chronic obstructive lung disease, ischaemic heart disease, obesity, diabetes, opioid use, gallstone disease, educational level, marital status and number of concomitant medications (OR 0.9, 95% CI 0.6 to 1.2). Similarly, among current users of other antipsychotics, the unadjusted OR was 1.4 (95% CI 1.1 to 1.6), while the adjusted OR was 0.8 (95% CI 0.6 to 0.9). Results regarding previous use of antidopaminergic drugs followed a similar risk pattern as for current use. ConclusionsThe lack of association between antidopaminergic drugs and acute pancreatitis after adjustment for confounding factors in this study suggests that the previously reported positive associations might be explained by confounding.

Social and geographical factors affecting access to treatment of colorectal cancer: a cancer registry study [RESEARCH]

Tue, 24 Apr 2012 00:00:00 +0000

ObjectiveCancer outcomes vary between and within countries with patients from deprived backgrounds known to have inferior survival. The authors set out to explore the effect of deprivation in relation to the accessibility of hospitals offering diagnostic and therapeutic services on stage at presentation and receipt of treatment. DesignAnalysis of a Cancer Registry Database. Data included stage and treatment details from the first 6 months. The socioeconomic status of the immediate area of residence and the travel time from home to hospital was derived from the postcode. SettingPopulation-based study of patients resident in a large area in the north of England. Participants39 619 patients with colorectal cancer diagnosed between 1994 and 2002. Outcomes measuredStage of diagnosis and receipt of treatment in relation to deprivation and distance from hospital. ResultsPatients in the most deprived quartile were significantly more likely to be diagnosed at stage 4 for rectal cancer (OR 1.516, p<0.05) but less so for colonic cancer. There was a trend for both sites for patients in the most deprived quartile to be less likely to receive chemotherapy for stage 4 disease. Patients with colonic cancer were very significantly less likely to receive any treatment if they came from any but the most affluent area (ORs 0.639, 0.603 and 0.544 in increasingly deprived quartiles), this may have been exacerbated if the hospital was distant from their residence (OR for forth quartile for both travel and deprivation 0.731, not significant). The effect was less for rectal cancer and no effect of distance was seen. ConclusionsResiding in a deprived area is associated with tendencies to higher stage at diagnosis and especially in the case of colonic cancer to reduced receipt of treatment. These observations are consistent with other findings and indicate that access to diagnosis requires further investigation.

Do pacifiers increase the risk of nosocomial diarrhoea? A cohort study [RESEARCH]

Mon, 16 Apr 2012 00:00:00 +0000

DesignProspective cohort study. SettingTeaching paediatric hospital--Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Northeast Brazil. Participants378 of 536 infants admitted in paediatric wards from April to October 2009 were daily assessed during hospital stay until the first episode of nosocomial diarrhoea (ND), death or discharge. Infants with community-acquired diarrhoea, respiratory or haemodynamic instability and who stayed in hospital for <24 h were excluded. Primary and secondary outcome measuresIncidence and risk factors for ND and rates of pacifier faecal contamination. Results33 ND episodes occurred in 378 infants, with a cumulative incidence of 8.7% and density of 11.25/1000 patients-day. ND occurred in 8.2% (16/194) of pacifier users compared with 9.2% (17/184) in non-users (adjusted OR=0.88, 95% CI 0.43 to 1.80). In multivariate logistic regression analysis, duration of oxygen use (OR=1.61; 95% CI 1.18 to 2.20) and days of antimicrobial use (OR=1.62, 95% CI 1.34 to 1.94) were associated with higher risk of ND, whereas being breast fed (OR=0.40, 95% CI 0.17 to 0.93) and each day of hospital stay (OR=0.65, 95% CI 0.53 to 0.80) were protective factors. Faecal coliforms were isolated in 16% (27/169) of tested pacifiers, 77.8% of which had more than 100 000 CFU/ml. The probability of a child remaining free of an episode of diarrhoea up to the seventh day of hospitalisation in the ward was 91.2% (95% CI 87.7% to 94.9%). The log-rank test showed no statistical difference between pacifier users and non-users. ConclusionsND is a frequent healthcare-associated infection in paediatric wards, but the use of pacifiers during the stay in hospital does not seem to affect the incidence of ND in infants in many settings where the burden of diarrhoea is still high.

Thirty-day mortality after elective and emergency total colectomy in Danish patients with inflammatory bowel disease: a population-based nationwide cohort study [RESEARCH]

Thu, 5 Apr 2012 00:00:00 +0000

ObjectivesThe purpose of this investigation was to assess 30-day mortality among Danish inflammatory bowel diseases (IBD) patients and to examine the prognostic impact of hospital total colectomy volume, age, gender and comorbidity. DesignCohort study. SettingThe authors compared 30-day survival over the period 1996-2010 among 2889 IBD patients with total colectomy identified in the Danish National Registry of Patients. This registry covers all hospitals in Denmark. Postoperative survival patterns for patients with ulcerative colitis and Crohn's disease were compared, using proportional hazard regression. The regression model accounted for the timing of surgery, hospital total colectomy volume, age, gender and comorbidity. ParticipantsPatients were enrolled in the study if they had a hospital registry diagnosis of IBD, with accompanying procedure codes for total colectomy (see codes in online appendix table 1). Hospitalisations were described as elective or emergency, and patients were categorised as having Crohn's disease, ulcerative colitis or as a mixed group. Outcome measuresPrimary outcome measure was 30-day mortality. ResultsAmong 2889 IBD patients with total colectomy, 1439 (50%) underwent surgery during an emergency hospitalisation. Thirty-day mortality was 5.3% (76/1439) among emergency cases compared with 1% (14/1450) among elective cases. The highest mortality (8.1%; 11 of 136) was observed among Crohn's patients undergoing emergency surgery. The mortality of patients with ulcerative colitis undergoing emergency surgery was 5.2% (55/1056). After elective surgery, the 30-day mortality was 0.9% (8/938) among patients with ulcerative colitis and 1.5% (3/201) among Crohn's disease patients. Low hospital total colectomy volume, comorbidity and high age were associated with increased 30-day mortality in ulcerative colitis patients undergoing emergency surgery. ConclusionEmergency total colectomy among patients with ulcerative colitis and particularly Crohn's disease is associated with substantial 30-day mortality.

Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study [RESEARCH]

Thu, 8 Mar 2012 00:00:00 +0000

ObjectiveSerum -fetoprotein (AFP) is the most commonly used biomarker for screening hepatocellular carcinoma (HCC) but fails to detect about half of the patients. Thus, we investigated if circulating microRNAs (miRNAs) could outperform AFP for HCC detection. DesignA retrospective cohort study. SettingTwo clinical centres in China. ParticipantsThe exploration phase included 96 patients with HCC who received primary curative hepatectomy, and the validation phase included 29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls. Main outcome measuresExpression of miRNAs was measured by real-time quantitative reverse transcription-PCR. Areas under receiver operating characteristic curves were used to determine the feasibility of using serum miRNA concentration as a diagnostic marker for defining HCC. A multivariate logistic regression analysis was used to evaluate performances of combined serum miRNAs. ResultsIn the exploration phase, miRNA profiling on resected tumour/adjacent non-tumour tissues identified miR-15b, miR-21, miR-130b and miR-183 highly expressed in tumours. These miRNAs were also detectable in culture supernatants of HCC cell lines and in serum samples of patients. Remarkably, these serum miRNAs were markedly reduced after surgery, indicating the tumour-derived source of these circulating miRNAs. In a cross-centre validation study, combined miR-15b and miR-130b demonstrated as a classifier for HCC detection, yielding a receiver operating characteristic curve area of 0.98 (98.2% sensitivity and 91.5% specificity). The detection sensitivity of the classifier in a subgroup of HCCs with low AFP (<20 ng/ml) was 96.7%. The classifier also identified early-stage HCC cases that could not be detected by AFP. ConclusionThe combined miR-15b and miR-130b classifier is a serum biomarker with clinical value for HCC screening.

Fall in peptic ulcer mortality associated with increased consultant input, prompt surgery and use of high dependency care identified through peer-review audit [RESEARCH]

Wed, 22 Feb 2012 00:00:00 +0000

ObjectivesPatients with peptic ulceration continue to present to surgeons with complications of bleeding or perforation and to die under surgical care. This study sought to examine whether improved consultant input, timely interventions and perioperative care could reduce mortality from peptic ulcer. DesignProspective collection of peer-review mortality data using Scottish Audit of Surgical Mortality methodologies (http://www.SASM.org) and analysed using SPSS. SettingSecondary care; all hospitals in Scotland, UK, admitting surgical patients over 13 years (1994-2006). Participants42 736 patients admitted (38 782 operative and 3954 non-operative) with peptic ulcer disease; 1952 patients died (1338 operative and 614 non-operative deaths) with a diagnosis of peptic ulcer. Primary and secondary outcome measuresAdverse events; consultant presence at operation, operations performed within 2 h and high dependency/intensive therapy unit (HDU/ITU) use. ResultsAnnual mortality fell from 251 in 1994 to 83 in 2006, proportionately greater than the reduction in hospital admissions with peptic ulcer. Adverse events declined over time and were rare for non-operative patients. Consultant surgeon presence at operation rose from 40.0% in 1994 to 73.4% in 2006, operations performed within 2 h of admission from 10.3% in 1994 to 28.1% in 2006 and HDU/ITU use from 52.7% in 1994 to 84.4% in 2006. Consultant involvement (p=0.005) and HDU/ITU care (p=0.026) were significantly associated with a reduction in operative deaths. ConclusionPatients with complications of peptic ulceration admitted under surgical care should be offered consultant surgeon input, timely surgery and HDU/ITU care.

Eosinophils in the oesophageal mucosa: clinical, pathological and epidemiological relevance in children: a cohort study [RESEARCH]

Thu, 12 Jan 2012 00:00:00 +0000

ObjectivesEosinophilic oesophagitis (EO) shows eosinophilic infiltration of the mucosa and can present with symptoms indistinguishable from gastrooesophageal reflux disease (GORD). The authors describe the clinical, endoscopic and histopathological features of all cases of histological EO presenting during 2007-2008 with a 2-year follow-up. The incidence of paediatric EO and the features of a subgroup with features of both GORD and EO ( overlap' syndrome (OS)) are described. DesignBiopsies with an average of 15 eosinophils/high-power field (HPF) were reviewed in the cohort. OS was suggested when there was coexistence of clinical and histological features of EO and GORD (abnormal pH study), which improved with proton pump inhibitors. SettingTertiary care. ParticipantsAll cases with [≥]15 eosinophils/HPF entered the study. Primary outcome measuresPatients with EO had an average of 15 eosinophils/HPF. Secondary outcome measuresOther histological features of EO included microabscesses, dilated intercellular spaces, basal cell hyperplasia, papillary elongation, etc. Results24 cases of EO were identified, 13 men and 11 women. The incidence of paediatric oesophageal eosinophilia in the region was 9/100 000 children. 11 of the 24 patients (46%) presented with some form of allergy, six with poor feeding/food aversion, five with dysphagia and four with vomiting. After follow-up, 56.5% were confirmed to have EO, 30.5% responded to treatment for GORD and were categorised as OS, 9% developed eosinophilic gastroenteritis and 4% did not have further upper gastrointestinal symptoms. ConclusionsAccurate diagnosis of EO, especially the differentiation from GORD, requires appropriate clinicopathological correlation. A significant proportion of patients with eosinophilia in the mucosa also have GORD (OS). These patients improve after treating the underlying GORD. The study was registered as a Service Evaluation with the Trust (number SE74).

Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

ObjectivesTo evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. MethodsRandomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. ConclusionThe quality of registration of randomised controlled trials still needs improvement.

Is there an association between wheezing and constipation in preschool children? Explanations from a longitudinal birth cohort [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

ObjectiveTo assess whether wheezing and atopic dermatitis were associated with constipation in preschool children and to what extent shared risk factors contribute to this relationship. MethodsA population-based sample of 4651 preschool children was used. At the age of 24, 36 and 48 months, a parental report of functional constipation was available according to the Rome II criteria, and data on atopic dermatitis and wheezing were available using age-adapted questionnaires from the International Study of Asthma and Allergies in Childhood. Stepwise multivariate analyses were performed to assess whether body mass index, infection exposure, food allergy and infant nutrition, and parental stress explained the association between wheezing, atopic dermatitis and constipation. ResultsOut of 4651 children, 12-17% had functional constipation between 24 and 48 months. Symptoms of wheezing decreased from 20% to 12% and atopic dermatitis decreased from 30% to 18% at the age of 24 and 48 months respectively. Between the age of 24 and 48 months, wheezing symptoms were significantly associated with functional constipation (OR 1.17; 1.02 to 1.34) but these results were mainly explained by the child's exposure to infections and use of antibiotics (adjusted odds ratio 1.08; 95% CI 0.95 to 1.24). No significant association was found between symptoms of atopic dermatitis and functional constipation (OR 1.08; 95% CI 0.94 to 1.23). ConclusionsThese findings suggest that functional constipation coexists with wheezing in childhood but is mainly explained by the child's infection exposure and use of antibiotics. Therefore, an independent association between respiratory symptoms and functional bowel disorders as suggested in previous studies is questionable.

Viusid, a nutritional supplement, increases survival and reduces disease progression in HCV-related decompensated cirrhosis: a randomised and controlled trial [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

ObjectivesViusid is a nutritional supplement with recognised antioxidant and immunomodulatory properties which could have beneficial effects on cirrhosis-related clinical outcomes such as survival, disease progression and development of hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of viusid in patients with HCV-related decompensated cirrhosis. DesignA randomised double-blind and placebo-controlled study was conducted in a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). The authors randomly assigned 100 patients with HCV-related decompensated cirrhosis to receive viusid (three oral sachets daily, n=50) or placebo (n=50) during 96 weeks. The primary outcome of the study was overall survival at 96 weeks, and the secondary outcomes included time to disease progression, time to HCC diagnosis, time to worsening of the prognostic scoring systems Child-Pugh and Model for End-Stage Liver Disease, and time to a new occurrence or relapse for each one of the main clinical complications secondary to portal hypertension at 96 weeks. ResultsViusid led to a significant improvement in overall survival (90%) versus placebo (74%) (HR 0.27, 95% CI 0.08 to 0.92; p=0.036). A similar improvement in disease progression was seen in viusid-treated patients (28%), compared with placebo-treated patients (48%) (HR 0.47, 95% CI 0.22 to 0.89; p=0.044). However, the beneficial effects of viusid were wholly observed among patients with Child-Pugh classes B or C, but not among patients with Child-Pugh class A. The cumulative incidence of HCC was significantly reduced in patients treated with viusid (2%) as compared with placebo (12%) (HR 0.15, 95% CI 0.019 to 0.90; p=0.046). Viusid was well tolerated. ConclusionsThe results indicate that treatment with viusid leads to a notable improvement in overall clinical outcomes such as survival, disease progression and development of HCC in patients with HCV-related decompensated cirrhosis. Trial registration numberhttp://ClinicalTrials.gov (NCT00502086).

The European lactase persistence genotype determines the lactase persistence state and correlates with gastrointestinal symptoms in the Hispanic and Amerindian Chilean population: a case-control and population-based study [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundThe lactase persistent (LP) or lactase non-persistent (LNP) state in European adults is genetically determined by a single nucleotide polymorphism (SNP) located 13.9 kb upstream of the lactase (LCT) gene, known as LCT C>T-13910 (rs4988235). The LNP condition leads to an inability to digest the milk sugar lactose leading to gastrointestinal symptoms and can affect nutrient and calcium intake in certain populations. ObjectivesThe authors studied a group of 51 Chilean patients to assess whether this SNP influences the LP/LNP state in this population, and determined the prevalence of LCT C>T-13910 genotypes in a representative sample of 216 Hispanics and 43 Amerindians with correlation to digestive symptoms. DesignCase-control study done in Chilean patients with clinical suspicion of LNP that were assessed using clinical survey, hydrogen breath test (HBT) and SNP genotyping. The population sample of Hispanics and Amerindians was assessed by clinical survey and SNP genotyping. ResultsOf the 51 patients with clinical suspicion of LNP, 29 were HBT-positive. The CC genotype (LNP) was present in 89.7% of the patients with positive HBT and in only 4.7% of those with negative HBT. The prevalence of the CC genotype was 56.9% in the Hispanic population and 88.3% in Amerindians, and was associated with a higher self-reported clinical intolerance to ingestion of dairy products. ConclusionThe LP/LNP state is determined by the LCT C>T-13910 variant in Chileans. This variant predicts digestive symptoms associated with the ingestion of lactose and is a good tool for the diagnosis of primary adult hypolactasia. The LCT T-13910 allele is rare in the Amerindian population and is suggestive of European ancestry in this contemporary population.

The NOTA study: non-operative treatment for acute appendicitis: prospective study on the efficacy and safety of antibiotic treatment (amoxicillin and clavulanic acid) in patients with right sided lower abdominal pain [PROTOCOL]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundCase control studies that randomly assign patients with diagnosis of acute appendicitis to either surgical or non-surgical treatment yield a relapse rate of approximately 14% at one year. It would be useful to know the relapse rate of patients who have, instead, been selected for a given treatment based on a thorough clinical evaluation, including physical examination and laboratory results (Alvarado Score) as well as radiological exams if needed or deemed helpful. If this clinical evaluation is useful, the investigators would expect patient selection to be better than chance, and relapse rate to be lower than 14%. Once the investigators have established the utility of this evaluation, the investigators can begin to identify those components that have predictive value (such as blood analysis, or US/CT findings). This is the first step toward developing an accurate diagnostic-therapeutic algorithm which will avoid risks and costs of needless surgery. Methods/designThis will be a single-cohort prospective observational study. It will not interfere with the usual pathway, consisting of clinical examination in the Emergency Department (ED) and execution of the following exams at the physician's discretion: full blood count with differential, C reactive protein, abdominal ultrasound, abdominal CT. Patients admitted to an ED with lower abdominal pain and suspicion of acute appendicitis and not needing immediate surgery, are requested by informed consent to undergo observation and non operative treatment with antibiotic therapy (Amoxicillin and Clavulanic Acid). The patients by protocol should not have received any previous antibiotic treatment during the same clinical episode. Patients not undergoing surgery will be physically examined 5 days later. Further follow-up will be conducted at 7, 15 days, 6 months and 12 months. The study will conform to clinical practice guidelines and will follow the recommendations of the Declaration of Helsinki. The protocol was approved on November 2009 by Maggiore Hospital Ethical Review Board (ID CE09079). Trial RegistrationClinicalTrials.gov identifier: NCT01096927.

A survey of acute self-reported infections in pregnancy [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveThe objective of this study was to estimate the weekly prevalence of self-reported recently acquired infections in women at least 20 weeks pregnant. DesignWe conducted a cross-sectional survey of pregnant women in a hospital antenatal clinic in Sydney, Australia between August 2008 and April 2009. Women were asked to report whether they had onset of a new infection in the 7 days before completing the questionnaire, and were asked for details of symptoms and medication taken. Results737 women at least 20 weeks pregnant completed the survey (94% of women approached). Five per cent of the completed questionnaires reported the onset of an infection in the 7 days prior to survey completion. When symptoms were analysed, 3.5% of women were classified as having a moderate or severe infection in the past 7 days. The most common infection reported was a cold/upper respiratory tract infection followed by gastroenteritis. Women pregnant with their first child had a lower rate of self-reported infection than women who had other children (2.9% vs 7.2%). ConclusionsThese results can be used to inform future research examining acute infection as a trigger for pregnancy complications.

Early closure of temporary ileostomy--the EASY trial: protocol for a randomised controlled trial [PROTOCOL]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveThe objective is to evaluate efficiency based on data on morbidity and mortality, health-related quality of life and healthcare-related costs after early reversal of temporary ileostomy after rectal resection for cancer compared with the standard procedure (late reversal). BackgroundReversal of a temporary ileostomy is generally associated with a low morbidity and mortality. However, ostomy reversal may cause complications requiring reoperation with subsequent major complications, in ranges from 0% to 7-9% and minor complications varying from 4-5% to 30%. Based on studies exploring and describing the time of closure in previous studies which are mostly of low quality, a recent review concluded that closing a temporary stoma within 2 weeks did not seem to be associated with an increase in morbidity and mortality. Design and methodsEarly closure of temporary ileostomy (EASY), a randomised controlled trial, is a prospective randomised controlled multicentre study which is performed within the framework of the Scandinavian Surgical Outcomes Research Group (http://www.ssorg.net/) and plans to include 200 patients from Danish and Swedish hospitals. The primary end-point of the study is the frequency of complications 0-12 months after surgery (the stoma creation operation). The secondary end-points of the study are (1) comparison of the total costs of the two groups at 6 and 12 months after surgery (stoma creation); (2) comparison of health-related quality of life in the two groups evaluated with the 36-item short-form and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29/CR30 at 3, 6 and 12 months after surgery (stoma creation); and (3) comparison of disease-specific quality of life in the two groups at 3, 6 and 12 months after surgery (stoma creation). DiscussionThe aim of the EASY trial is to evaluate the efficiency of early reversal of temporary ileostomy after surgery for rectal cancer versus late reversal. The EASY trial is expected to have a huge impact on patient safety as well as an improvement in patient-reported outcome. Clinical trials identifierNCT01287637.

Hollow spheroids beyond the invasive margin indicate the malignant potential of colorectal cancer [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveTumour budding formed by histologically undifferentiated cancer cells beyond the border of the tumour margin is associated with lymph node metastasis. However, hollow tumour nests, a possible histologically advanced phenotype of tumour budding, have not been discussed. We examined whether hollow spheroids exist beyond the border of the invasive margin and are associated with metastasis and prognosis. Moreover, we suggest that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) isoform balance is associated with hollow spheroid formation. MethodsImmunohistochemical analyses with CEACAM1 and M30 as an apoptosis marker were performed to examine the importance of hollow spheroid CEACAM1 expression and central cell apoptosis in hollow spheroid formation. The correlations between the presence of hollow spheroids beyond the invasive margin and the clinicopathological characteristics of 314 patients with colorectal cancer were retrospectively evaluated. A 3D culture with colorectal cancer cells transfected with CEACAM1 cDNA or shRNA was used to determine whether CEACAM1 isoform balance controls colorectal hollow spheroid formation. ResultsHollow spheroid formation accompanying central cell apoptosis was confirmed by M30 staining and serial section with CEACAM1 staining. Of the 314 patients, 96 (30.4%) were classified as having hollow spheroids. The presence of hollow spheroids is an independent risk factor for metastases and shorter survival. In 3D culture, CEACAM1 isoform balance modulated hollow spheroid formation of colorectal cancer cells. ConclusionsHollow spheroid formation beyond the border of the tumour margin in colorectal cancer is more important than tumour budding for the prediction of malignant potential.