The role of defensive information processing in population-based colorectal cancer screening uptake.

BACKGROUND: Internationally, colorectal cancer screening participation remains low despite the availability of home-based testing and numerous interventions to increase uptake. To be effective, interventions should be based on an understanding of what influences individuals' decisions about screening participation. This study investigates the association of defensive information processing (DIP) with fecal immunochemical test (FIT)-based colorectal cancer screening uptake. METHODS: Regression modeling of data from a cross-sectional survey within a population-based FIT screening program was conducted. The survey included the seven subdomains of the McQueen DIP measure. The primary outcome variable was the uptake status (screening user or nonuser). Multivariable logistic regression was used to estimate the odds ratio (OR) for screening nonuse by DIP (sub)domain score, with adjustments made for sociodemographic and behavioral factors associated with uptake. RESULTS: Higher scores (equating to greater defensiveness) on all DIP domains were significantly associated with lower uptake in the model adjusted for sociodemographic factors. In the model with additional adjustments for behavioral factors, the suppression subdomains of "deny immediacy to be tested" (OR, 0.53; 95% confidence interval [CI], 0.43-0.65; p < .001) and "self-exemption" (OR, 0.80; 95% CI, 0.68-0.96; p < .001) independently predicted nonuse of FIT-based screening. CONCLUSIONS: This is the first study outside the United States that has identified DIP as a barrier to colorectal cancer screening uptake, and it is the first focused specifically on FIT-based screening. The findings suggest that two suppression barriers, namely denying the immediacy to be tested and self-exempting oneself from screening, may be promising targets for future interventions to improve uptake.

Negative emotions and cancer fatalism are independently associated with uptake of Faecal Immunochemical Test-based colorectal cancer screening: Results from a population-based study.

Although systematic colorectal cancer screening is efficacious, many programmes suffer from low uptake. Few behavioural or attitudinal factors have been identified as being associated with participation in colorectal cancer screening. We explored knowledge, beliefs about cancer, subjective health literacy, emotional attitudes to screening, and social influences among individuals invited to a population-based screening programme. Regression modelling of a cross-sectional survey of 2299 individuals (users and non-users) of a population-based Faecal Immunochemical Test (FIT) screening programme in Dublin was conducted. Questions were derived from previous theoretically-informed qualitative work and assessed using previously used and validated measures. The primary outcome variable was uptake status (User/Participation or Non-User/Non-participation); multivariable logistic regression was used to estimate the odds ratios (OR) for screening participation. Stronger fatalistic beliefs independently predicted lower uptake (OR = 0.94; 95% CI 0.90-0.98; P = 0.003). Those aged <65 who disagreed that "cancer can often be cured" also had lower uptake (OR = 0.43; 95% CI 0.22-0.82: P = 0.017). Agreement that the test was disgusting and tempting fate predicted lower uptake (OR = 0.16: 95% CI 0.10-0.27: p < 0.001), while the influence of a partner on decision to be screened was associated with higher uptake (OR = 1.32; 95% CI 1.15-1.50: P < 0.001). Negative cancer-related and screening-related beliefs and emotions are associated with non-participation in FIT (-based screening). Research is warranted to explore if these negative beliefs and emotions are modifiable and, if so, whether this would improve screening uptake. The association between the influence of a partner and screening participation present a challenge around improving uptake among those not in co-habiting relationships.

Protocol of the European Registry on the management of Helicobacter pylori infection (Hp-EuReg).

INTRODUCTION: Helicobacter pylori selectively infects the human stomach, being the most prevalent chronic infection in the world. H pylori presence causes chronic gastritis in 100% of infected patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease, and gastric cancer; it is for this reason that from a public health standpoint, it is considered a high-impact pathogen, responsible of a significant morbidity and mortality. Nowadays, there are consensus and clinical guidelines regarding the infection management at a European level and in most of European countries, but no data have shown the level of implementation of these recommendations. The high costs that this infection carries both socially and to the health system require the continuous and systematic assessment of the diagnostic and treatment strategies, as well as the accessibility to diagnostic methods and most efficient drugs. AIM: To register the diagnosis, management strategies, and treatment of H pylori-infected adult patients in the Digestive Services outpatient clinics throughout Europe. METHODS: Noninterventionist prospective multicentre international Registry promoted by the European Helicobacter and Microbiota Study Group. National Coordinators will select recruiting gastroenterologists in their country that will register the H pylori-related routine clinical practice consultations they receive in an electronic case report form (e-CRF) provided by AEG-REDCap. Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation, and outcome data. The database will allow researchers to perform specific subanalyses after approval by the Scientific Committee of the study.

Treatment of Helicobacter pylori infection in 2018.

Treatment options for the eradication of Helicobacter pylori continue to evolve. There have been many guidelines for H. pylori treatment published, which may lead to some confusion. However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines. Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance. Its best results are achieved when taken for a minimum of 10 days and with high-dose acid suppression. Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy. Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects. Levofloxacin second-line therapy is widely used; however bismuth, when available, is an increasingly successful option. Sequential therapy is challenging in terms of compliance and is no longer recommended. This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture-guided treatment, which may well represent the future of H. pylori treatment and prevent the inappropriate use of antibiotics.

Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer.

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach.

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening.

This study aimed to investigate the effects of sex and deprivation on participation in a population-based faecal immunochemical test (FIT) colorectal cancer screening programme. The study population included 9785 individuals invited to participate in two rounds of a population-based biennial FIT-based screening programme, in a relatively deprived area of Dublin, Ireland. Explanatory variables included in the analysis were sex, deprivation category of area of residence and age (at end of screening). The primary outcome variable modelled was participation status in both rounds combined (with "participation" defined as having taken part in either or both rounds of screening). Poisson regression with a log link and robust error variance was used to estimate relative risks (RR) for participation. As a sensitivity analysis, data were stratified by screening round. In both the univariable and multivariable models deprivation was strongly associated with participation. Increasing affluence was associated with higher participation; participation was 26% higher in people resident in the most affluent compared to the most deprived areas (multivariable RR=1.26: 95% CI 1.21-1.30). Participation was significantly lower in males (multivariable RR=0.96: 95%CI 0.95-0.97) and generally increased with increasing age (trend per age group, multivariable RR=1.02: 95%CI, 1.01-1.02). No significant interactions between the explanatory variables were found. The effects of deprivation and sex were similar by screening round. Deprivation and male gender are independently associated with lower uptake of population-based FIT colorectal cancer screening, even in a relatively deprived setting. Development of evidence-based interventions to increase uptake in these disadvantaged groups is urgently required.

Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn's Disease.

BACKGROUND: Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn's disease (CD) although as yet the exact mechanisms have not been fully elucidated. AIM: To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. METHODS: Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients' and pre- and post-treatment CD patients' sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. RESULTS: There was a significant increase in bone formation markers osteocalcin (P < 0.05) and procollagen type 1 N-terminal propeptide (P < 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption marker. No significant change was seen over time with other parameters measured. Serum from CD patients pre-treated with adalimumab showed increased osteoblast viability compared with that of post-treated patients at 6 months (P = 0.002) and controls. However, post-adalimumab treatment sera at 6 months appeared to increase osteoblast differentiation (P = 0.001), which is likely to be important in new bone formation. CONCLUSIONS: This first study evaluating the role of adalimumab as a possible bone protector in Crohn's disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.

Surveillance of gastric intestinal metaplasia for the prevention of gastric cancer.

BACKGROUND: Adenocarcinoma of the stomach is the second leading cause of cancer related death in the world. Gastric intestinal metaplasia (GIM) is a recognised premalignant condition of the stomach. It has been described as occurring in up to one in five patients in western countries. Although there is a definite risk of progression from GIM to cancer, published guidelines and statements differ as to the utility and structure of surveillance programs for this condition. OBJECTIVES: To see whether or not endoscopic or biochemical surveillance of patients with gastric intestinal metaplasia (GIM) could result in increased detection of dysplasia and early gastric cancer to decrease gastric cancer mortality. SEARCH METHODS: We performed a search of the following electronic databases from inception to October 2012: CENTRAL, EMBASE, MEDLINE and LILACS. We handsearched for abstracts from relevant conferences. SELECTION CRITERIA: Randomised controlled trials only were included. DATA COLLECTION AND ANALYSIS: No studies met the inclusion criteria. MAIN RESULTS: No studies met the inclusion criteria. AUTHORS' CONCLUSIONS: There is a lack of randomised data on the utility of surveillance of GIM. The observational data from non-randomised studies are discussed and would suggest that although a randomised trial would be a desirable undertaking to attain the highest grade of clinical evidence, given the ethical and acceptability issues involved, further non-randomised clinical studies focussing on surveillance protocols and the role of Helicobacter pylori eradication may be a more pragmatic means of addressing the core clinical question.

Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report.

Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.

Sequential therapy for Helicobacter pylori eradication: a critical review.

BACKGROUND: Alternative treatment regimens for standard triple therapy are urgently needed. AIM: To critically review the evidence on the role of "sequential" regimen for the treatment of Helicobacter pylori infection. METHODS: Bibliographical searches were performed in MEDLINE and international congresses. RESULTS: Several pooled-data analyses and meta-analyses have demonstrated that sequential regimen is more effective than standard triple therapy. Sequential therapy is not affected by bacterial (CagA status, infection density) and host factors (underlying disease, smoking). Clarithromycin resistance seems to be the only factor reducing their efficacy. However, even in these patients, an acceptable >75% eradication rate can be achieved. Unfortunately, almost all the studies have been performed in Italy. Whether it is necessary to provide the drugs sequentially or if the 4 components of sequential therapy can be given concurrently is unclear. Nonbismuth quadruple therapy seems to be an effective and safe alternative to triple therapy and is less complex than sequential therapy. CONCLUSIONS: Sequential therapy is a novel promising treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before sequential therapy could supplant existing treatment regimens and be generally recommended in clinical practice.

A historical perspective of Helicobacter gastroduodenitis and its complications.

The discovery of Helicobacter pylori was one of the most notable in gastroenterology - and indeed medicine. The century before Marshall and Warren's discovery is peppered with isolated accounts of spiral-shaped bacteria in the stomach. The discovery of H. pylori, and the recognition of its importance, came about as a consequence of combined clinical, pathological and microbiological work. The discovery has transformed the treatment of peptic ulcers and other related diseases.

Population screening and treatment of Helicobacter pylori infection.

Helicobacter pylori is an important human pathogen, associated with a substantial burden from both malignant and non-malignant diseases. The bacterium is classed as a human carcinogen, being strongly linked with gastric cancer, the third most common cause of cancer death worldwide and is also associated with common conditions such as dyspepsia and peptic ulcer. Eradication of H. pylori reduces the incidence of gastric cancer and peptic ulcer, as well as the prevalence and costs of managing dyspepsia. Economic analyses suggest that eradication of H. pylori as a means of controlling gastric cancer is cost-effective in high-risk populations. Even in populations at low risk of gastric cancer, there might be other benefits arising from screening and treatment, owing to the effects on non-malignant upper gastrointestinal diseases. However, public health authorities have been slow to consider the benefits of population-based screening and treatment as a means of reducing the morbidity and mortality associated with the infection. There are also concerns about widespread use of eradication therapy, including antimicrobial resistance and a rise in the prevalence of diseases that are negatively associated with H. pylori, such as GERD, Barrett oesophagus, asthma and obesity. This Review summarizes these issues.

Colorectal cancer screening.

Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can be accommodated within individual health care systems.

A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients.

OBJECTIVES: Infliximab (IFX) treatment has shown potentially beneficial effects on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to prospectively evaluate the impact of IFX treatment on bone metabolism in antitumour necrosis factor (TNF)-α-naive IBD patients using established bone metabolism markers and an in-vitro osteoblast model. MATERIALS AND METHODS: A total of 37 anti-TNFα-naive IBD patients and 20 healthy controls were included. All measurements were performed at baseline and repeated in IBD patients following IFX therapy. Bone mineral density was measured by dual-energy X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble receptor activator of nuclear factor B ligand and proinflammatory and anti-inflammatory cytokines were measured. Bone formation was measured using osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was measured using serum type 1 collage c-telopeptide. The effect of control and IBD patient sera on human osteoblast viability and differentiation was analysed. RESULTS: OC level was higher in controls than IBD patients (P=0.018). After IFX, OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011) and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX therapy, proinflammatory cytokines TNF-α, interleukin-6 and interleukin-13 decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6), respectively. Sera from IBD patients before IFX showed increased osteoblast viability compared with the controls (P=0.003 to P<0.005), but induced reduced osteoblast differentiation. After IFX, viability reduced to control levels, but osteoblast differentiation increased (P=0.041). CONCLUSION: IFX treatment induced beneficial effects on bone metabolism. Osteoblast culture results suggest that IBD patients may have increased osteoblast viability, but reduced differentiation, which has implications for bone strength.

Eradication of Helicobacter pylori: recent advances in treatment.

Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.

Motion--Helicobacter pylori worsens GERD: arguments for the motion.

There are several reasons for eradicating Helicobacter pylori in patients with chronic gastroesophageal reflux disease (GERD). Perhaps the most compelling is the evidence that chronic acid suppression therapy can lead to the development of atrophic gastritis, a premalignant condition, in patients with H pylori infection. Epidemiological data that suggest that H pylori is less prevalent in GERD patients than in control subjects may be susceptible to publication bias, and confounding social and environmental factors may also be involved. Although it has been thought that eradication of the organism might lead to increased esophageal acid exposure, this has not been demonstrated in practice. Studies that appeared to show that GERD could be provoked by antimicrobial therapy of duodenal ulcers also have methodological weaknesses. Underlying GERD symptoms might be unmasked after withdrawal of acid-suppression therapy, for reasons that are unrelated to H pylori. In fact, eradication of the organism has been shown to decrease heartburn in patients with peptic ulcer disease. When H pylori is successfully eradicated in patients with GERD, relapse rates are not increased, and the disease-free interval seems to be prolonged. Eradication of the organism is a wise policy in patients who face long term acid-suppression therapy for GERD.

Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue.

Triple therapy using proton-pump inhibitors (PPIs) in combination with oral antibiotics for the treatment of Helicobacter pylori-associated gastritis has shown increased efficacy for reasons that are still poorly understood. Possible explanations include a direct antibacterial effect of the PPIs or a PPI-mediated increase in bacterial susceptibility to antibiotics. Using an in-vitro model of rat gastric mucosa, we examined fluxes of a radiolabelled marker molecule through the interepithelial tight junctions under normal conditions and under the influence of an acid secretagogue (50 microM histamine) and a PPI (100 microM omeprazole). Paracellular fluxes of the radiolabel (represented by calculation of apparent permeability coefficients) were linear over 2 h. Fluxes of the marker increased significantly after treatment with histamine followed by omeprazole, but were unaltered in paired preparations exposed to the same drugs given in reverse order. Enhancements in paracellular permeability were mirrored in separate experiments using a detergent (Triton X-100), a bile salt (deoxycholate) and an agent that disrupts the cytoskeleton (cytochalasin D) to interfere with tight junctional integrity. The results suggest that exposure of acid-secreting gastric mucosa to omeprazole widens the interepithelial spacing in a manner that may facilitate enhanced macromolecular transport. Increases in antibiotic delivery from the blood to the gastric lumen via such a mechanism may account for the greater eradication rates observed with PPI-based triple therapy in H. pylori-associated gastritis.

The clinical significance of antimicrobial serologic responses within an Irish Crohn's disease population.

INTRODUCTION: A hyper-responsive adaptive immunologic response to a variety of microbial antigens has been described in Crohn's disease (CD) patients and elevated levels of a number of antibodies have been identified in the sera of CD patients. To date, the serological profiles of an Irish CD population have not been characterized. OBJECTIVES: The aim of this study is to determine the serological profile of Irish patients with CD. Second, we aim to assess the correlation, if any, between serological profile and disease phenotype within this cohort. METHODS: A total of 179 consecutive adults with CD attending a specialist inflammatory bowel disease clinic at a university hospital were recruited. Blood samples were taken and sera were analysed for the expression of pANCA and Crohn's related antibodies. RESULTS: pANCA was present in 47/179 (26.3%), anti-OmpC antibodies were present in 49/179 (27.4%), anti-Saccharomyces cervisiae (ASCA) in 64/179 (35.75%), ASCA IgA in 56/179 (31.28%) and ASCA IgG in 37/179 (20.67%), and anti-CBir antibodies in 97/179 (54.18%). The presence of ASCA IgA (P=0.031), ASCA IgG (P=0.007) and anti-CBir antibodies (P=0.003) were all significantly associated with small bowel involvement. Anti-OmpC, ASCA IgA and anti-CBir antibodies' positivity were all associated with complicated disease behaviour, whereas ANCA positivity was associated with inflammatory disease. CONCLUSION: Our study supports previous findings of an association between serological profiles and disease behaviour and a corresponding association with increased need for surgery. In this genetically homogenous Irish CD study group, the levels of specific antibody responses to commensal gut flora are lower than reported previously in other European and American populations.

Isolated active ileitis: is it a mild subtype of Crohn's disease?

BACKGROUND: Ileal intubation is being increasingly performed at colonoscopy and has in turn lead to an increasingly recognized subgroup of patients-those with mild terminal ileal inflammation, an entity that we have coined isolated active ileitis (IAI). The aims of this study were to define the natural history of IAI and determine if IAI shares a similar genetic and serologic profile with Crohn's disease (CD). METHODS: Patients with IAI were identified from our institution's histopathology and endoscopy databases. Cases attended for repeat colonoscopy and blood were analyzed for the expression of antineutrophil cytoplasmic antibody, anti-OmpC, anti-Saccharomyces cerevisiae antigen (ASCA) IgA, ASCA IgG, and anti-CBir antibodies and NOD2 genotyping. Age and sex-matched healthy controls, CD, and UC cases were also recruited. RESULTS: Sixty-three patients with IAI were recruited. There was no significant difference in the prevalence of antibodies between IAI cases and healthy controls for antineutrophil cytoplasmic antibody, OmpC, ASCA IgA, or ASCA IgG. The presence of all 5 antibodies was significantly higher in the CD group than the IAI group, P < 0.05. There were 28.6% of CD cases that carried one or more NOD2 variants, compared to 26.2% of the IAI cohort and 6.1% of healthy controls. Forty-three cases underwent follow-up ileocolonoscopy. Six of 43 cases (14%) had definite CD. CONCLUSIONS: A majority of IAI cases developed persistent symptoms and terminal ileal abnormalities; however, only 14% developed classical, histological, or radiological features of CD. Although patients with IAI have a low level of seropositivity, similar to healthy controls, they do share an excess of NOD2 mutations with CD cases.