ABSTRACT
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.
Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , United States , Cross-Sectional Studies , Surveys and Questionnaires , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Mass Screening , Occult Blood , ColonoscopyABSTRACT
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.
Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Colorectal Neoplasms/diagnosis , Cross-Sectional Studies , Emotions , Humans , Mass Screening , Occult BloodABSTRACT
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.
Subject(s)
Diagnostic Tests, Routine/methods , Disease Management , Drug Therapy, Combination/methods , Helicobacter Infections/diagnosis , Helicobacter Infections/therapy , Practice Guidelines as Topic , Registries , Adult , Aged , Aged, 80 and over , Europe , Female , Humans , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
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.
Subject(s)
Helicobacter Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Helicobacter pylori/pathogenicity , Humans , Proton Pump Inhibitors/therapeutic useABSTRACT
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.
Subject(s)
Helicobacter Infections/diagnosis , Helicobacter pylori , Stomach Ulcer/diagnosis , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Cost-Benefit Analysis , Drug Therapy, Combination , Global Health , Helicobacter Infections/drug therapy , Humans , Mass Screening/economics , Stomach Ulcer/drug therapyABSTRACT
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.
Subject(s)
Colorectal Neoplasms , Mass Screening/statistics & numerical data , Occult Blood , Patient Participation/statistics & numerical data , Poverty , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Female , Humans , Immunohistochemistry/methods , Ireland , Male , Mass Screening/methods , Middle Aged , Sex FactorsABSTRACT
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.
Subject(s)
Bone Diseases, Metabolic/drug therapy , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Absorptiometry, Photon , Adolescent , Adult , Aged , Biomarkers/blood , Bone Density/drug effects , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/physiopathology , Bone Remodeling/drug effects , Bone and Bones/metabolism , C-Reactive Protein/metabolism , Case-Control Studies , Cell Survival/drug effects , Cells, Cultured , Cytokines/blood , Female , Gastrointestinal Agents/pharmacology , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/physiopathology , Infliximab/pharmacology , Male , Middle Aged , Osteoblasts/drug effects , Osteoblasts/physiology , Osteogenesis/drug effects , Prospective Studies , Severity of Illness Index , Young AdultABSTRACT
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.
Subject(s)
Biomarkers, Tumor/analysis , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Evaluation Studies as Topic , Mass Screening/methods , Occult Blood , Research Design , Case-Control Studies , Clinical Trials as Topic , Colonoscopy , False Positive Reactions , Humans , Practice Guidelines as Topic/standards , Reproducibility of Results , Sample SizeABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Bone Density/drug effects , Crohn Disease/drug therapy , Adalimumab , Adolescent , Adult , Biomarkers , Case-Control Studies , Cell Line , Female , Humans , Male , Middle Aged , Osteoblasts/drug effects , Young AdultABSTRACT
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.
Subject(s)
Antibodies, Bacterial/blood , Antibodies, Fungal/blood , Crohn Disease/immunology , Crohn Disease/microbiology , Adalimumab , Adult , Age Factors , Anti-Inflammatory Agents/therapeutic use , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antigens, Bacterial/immunology , Antigens, Fungal/immunology , Crohn Disease/drug therapy , Crohn Disease/pathology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Infliximab , Male , Middle Aged , Porins/immunology , Saccharomyces cerevisiae/immunology , Time Factors , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
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.
Subject(s)
Adenocarcinoma/prevention & control , Precancerous Conditions/diagnosis , Stomach Neoplasms/prevention & control , Stomach/pathology , Humans , Metaplasia/diagnosisABSTRACT
AIM: To investigate a possible genetic influence of claudin (CLDN)1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease. METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease -families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing. RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95%CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95%CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers. CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
Subject(s)
Claudins/genetics , Colitis, Ulcerative/genetics , Crohn Disease/genetics , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Analysis of Variance , Case-Control Studies , Chi-Square Distribution , Child , Child, Preschool , Claudin-1/genetics , Europe , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Odds Ratio , Pedigree , Phenotype , Risk Assessment , Risk Factors , Young AdultABSTRACT
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.
Subject(s)
Biomarkers/analysis , Colitis, Ulcerative/pathology , Crohn Disease/pathology , Ileitis/pathology , Adult , Antibodies, Antineutrophil Cytoplasmic/blood , Case-Control Studies , Colitis, Ulcerative/blood , Colitis, Ulcerative/genetics , Crohn Disease/blood , Crohn Disease/genetics , Female , Follow-Up Studies , Genotype , Humans , Ileitis/blood , Ileitis/genetics , Immunoglobulin A/blood , Immunoglobulin G/blood , Male , Middle Aged , Mutation/genetics , Nod2 Signaling Adaptor Protein/genetics , Phenotype , Polymerase Chain Reaction , Prognosis , Retrospective StudiesABSTRACT
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.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Clarithromycin/therapeutic use , Drug Therapy, Combination , Gastroesophageal Reflux/microbiology , Gastroscopy , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Humans , Prebiotics , Probiotics , Proton Pump Inhibitors/therapeutic use , Stomach Neoplasms/microbiology , Stomach Neoplasms/prevention & controlABSTRACT
Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticarcinogenic Agents/therapeutic use , Aspirin/therapeutic use , Colorectal Neoplasms/prevention & control , Animals , Anti-Inflammatory Agents, Non-Steroidal/economics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anticarcinogenic Agents/economics , Anticarcinogenic Agents/pharmacology , Aspirin/economics , Aspirin/pharmacology , Colorectal Neoplasms/economics , Cost-Benefit Analysis , HumansABSTRACT
Eosinophilic oesophagitis is a clinicopathological disease characterized by oesophageal eosinophilia and gastrointestinal symptoms. Currently, the optimal treatment regimens remain unclear. The pathogenesis of eosinophilic oesophagitis appears to involve immune dysregulation, while acid reflux may have a secondary role; the mainstays in treatment are aimed principally at these dual processes. While a trial of a PPI is worthwhile it is likely that PPI therapy is treating concurrent acid reflux rather than true eosinophilic oesophagitis. Dietary elimination with elemental feed is safe but poorly tolerated. Swallowed topical steroids are the mainstay of commercially available therapies. Both fluticasone and budesonide have been proven to be beneficial both symptomatically and in reducing oesophageal eosinophil counts in the short and medium term. Basic studies have determined a role for IL-5 in oesophageal remodelling in eosinophilic esophagitis. Initial clinical studies have shown single or multiple infusions of monoclonal antibody to IL-5 to be well tolerated and to cause a long-term decrease in both peripheral and sputum eosinophil count in these eosinophil driven conditions. At present, swallowed corticosteroids are the mainstay of treatment for patients with eosinophilic oesophagitis in patients failing PPI therapy. Studies have been heterogenous in their diagnostic criteria for eosinophilic oesophagitis and in the definition of response to therapy, making comparison of results difficult.
Subject(s)
Eosinophilic Esophagitis/drug therapy , Adrenal Cortex Hormones/therapeutic use , Androstadienes/therapeutic use , Budesonide/therapeutic use , Diet Therapy , Eosinophilic Esophagitis/diet therapy , Eosinophilic Esophagitis/immunology , Eosinophilic Esophagitis/physiopathology , Fluticasone , Humans , Proton Pump Inhibitors/therapeutic useABSTRACT
Inflammatory bowel disease (IBD) encompasses 2 independent but related entities: ulcerative colitis (UC) and Crohn's disease. Crohn's disease is characterised by transmural patchy inflammation which can involve any portion of the gastrointestinal tract. UC is characterised by superficial inflammation that begins in the rectum and extends proximally along the colon. In Europe, approximately 2.2 million people have a diagnosis of IBD. The aetiology of IBD is unknown, however, immune, environmental and genetic factors are thought to be involved. Individuals with IBD are at risk of developing osteoporosis. In line with this, there are clear guidelines that recommend vitamin D supplementation for IBD patients to prevent bone disease, especially when undergoing steroid treatment. Despite an established role for vitamin D in IBD, deficiency is common. More novel effects of vitamin D beyond bone are emerging. It is now well established that vitamin D is an important regulator of the immune system which may have implications for the development, severity and management of immune related disorders such as IBD. The efficacy of vitamin D as an immune modulator in IBD remains to be proven. This review aims to evaluate the evidence implicating vitamin D deficiency in IBD pathogenesis, to examine vitamin D's anti-inflammatory mechanisms and to explore its therapeutic potential, optimal serum levels and dietary intakes which may support immune function in this disease.
Subject(s)
Immunologic Factors/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Vitamin D/therapeutic use , Animals , Humans , Immunologic Factors/metabolism , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/metabolism , Vitamin D/analogs & derivatives , Vitamin D/metabolismABSTRACT
INTRODUCTION: Eosinophilic oesophagitis is a recently recognized oesophageal disorder characterized by a combination of clinical and endoscopic features as well as the histological finding on oesophageal biopsy of greater than 15 eosinophils per high powered field. Recent reports suggest eosinophilic oesophagitis is increasing in incidence and this increase cannot be fully explained by increased recognition of the disorder. The aim of this retrospective study was to assess the incidence of eosinophilic oesophagitis within the catchment area of a tertiary referral hospital in southwest Dublin, Ireland. METHODS: The histopathology database at the Adelaide and Meath Hospital was used to identify all oesophageal biopsies obtained between January 2000 and July 2008 reported to show evidence of oesophagitis. Biopsy samples with greater than 15 eosinophils per high powered field in at least two fields were highlighted as possible eosinophilic oesophagitis. The oesophageal biopsies of patients identified in this way were reviewed by a histopathologist with a special expertise in gastroenterology for features suggestive of eosinophilic oesophagitis. RESULTS: Twenty-five thousand three hundred and sixty-five upper gastrointestinal endoscopies were performed between January 2000 and July 2008. A total of 11 072 sets of oesophageal biopsies were taken and 1364 (12.3%) of these revealed evidence of oesophagitis. Only 13 (0.1%) patients had oesophageal biopsies showing greater than 15 eosinophils per high powered field. The median age of this patient group was 23 years (interquartile range 10.5-50.5 years), with 46% of patients under 18 years at the time of diagnosis. The male to female ratio was 5.5 : 1 compared with 1.1 : 1 in the oesophagitis group as a whole, (P=0.002). There was no significant association between endoscopic findings or presenting complaints and the average number of eosinophils per high powered field. The average number of biopsies taken in patients with endoscopic findings suggestive of eosinophilic oesophagitis was 3.75 compared with 1 in patients without those features, (P=0.01). CONCLUSION: Our findings suggest that eosinophilic oesophagitis is a rare disorder predominantly affecting young men.
Subject(s)
Eosinophilic Esophagitis/epidemiology , Adolescent , Adult , Age Distribution , Aged , Biopsy , Child , Endoscopy, Gastrointestinal , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/pathology , Esophagus/pathology , Female , Humans , Infant , Ireland/epidemiology , Male , Middle Aged , Retrospective Studies , Sex Distribution , Young AdultABSTRACT
UNLABELLED: Assessment of the long-term safety of anti-tumour necrosis factor therapies is vital for the safe treatment of inflammatory bowel disease, a disease affecting a young cohort of patients. AIMS: The aim of this retrospective study was to assess the safety and long-term outcome of infliximab use in clinical practice in our institution on an intention to treat basis over the 10-year period from December 1998 to 31 December 2008. METHODS: All cases receiving infliximab for ulcerative colitis or Crohn's disease over a 10-year period were identified from hospital pharmacy records. The study was based on a single centre cohort, with an unselected patient group. RESULTS: A total of 271 patients were identified as receiving infliximab for either Crohn's disease or ulcerative colitis over the 10-year study period. In total, 2169 infusions were given to the patient cohort. Fifty adverse events led to discontinuation of infliximab therapy in 47 cases. Two patients stopped due to neurological complications. There were six malignancies diagnosed within the cohort during the study period. Four of these were diagnosed while the individual was receiving Infliximab and two occurred at an interval of 21-52 months post their final infliximab infusion. A total of five deaths (1.5%) were observed during the study period. CONCLUSION: Infliximab therapy seems to be safe and efficacious in the long term. Although the development of malignancy remains a concern, we have not seen an increased risk of serious infection within our cohort.
Subject(s)
Antibodies, Monoclonal/adverse effects , Gastrointestinal Agents/adverse effects , Adenocarcinoma/chemically induced , Adenocarcinoma/diagnosis , Adenoma/chemically induced , Adenoma/diagnosis , Adult , Antibodies, Monoclonal/therapeutic use , Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/diagnosis , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/mortality , Colonic Neoplasms/chemically induced , Colonic Neoplasms/diagnosis , Crohn Disease/drug therapy , Crohn Disease/mortality , Demyelinating Diseases/chemically induced , Demyelinating Diseases/diagnosis , Female , Gastrointestinal Agents/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infliximab , Lung Neoplasms/chemically induced , Lung Neoplasms/diagnosis , Lymphoma/chemically induced , Lymphoma/diagnosis , Male , Middle Aged , Pancreatic Neoplasms/chemically induced , Pancreatic Neoplasms/diagnosis , Retrospective Studies , Smoking , Treatment Outcome , Young AdultABSTRACT
AIMS: The aims of this study were (1) to determine the measurement accuracy of a widely used guaiac faecal occult blood test (gFOBT) compared with an immunochemical faecal occult blood test (iFOBT) during in vitro studies, including their analytical stability over time at ambient temperature and at 4°C; and (2) to compare analytical imprecision and other characteristics between two commercially available iFOBT methods. METHODS: Faecal specimens from healthy volunteers negative for occult blood were spiked with red cell lysate to give concentrations of 0 (A), 2.5 (B) and 4.5 (C)1mg Hb/g faeces respectively. Samples from each pool were then tested by nine blinded assessors in order to determine the measurement accuracy. Sample stability for the gFOBT at ambient temperature (18°C) was determined by repeating the gFOBT analysis on faecal samples (A, B and C) consecutively for 7 days. Stability for the iFOBT was tested on spiked faecal samples stored at 4°C and also at ambient temperature (18°C). Testing for other analytical performance characteristics including sample carryover and imprecision was performed for both iFOBT methods. RESULTS: Nine blinded assessors using gFOBT achieved correct readings for eight of nine samples from Pool A, five of nine from Pool B and seven of nine from Pool C. Overall, the sensitivity and specificity of gFOBT were 67% and 89% respectively. No discrepant results were detected with iFOBT. Faecal samples applied to gFOBT cards immediately postcollection gave positive results for the next 7 days only for pool C. In contrast, the results of iFOBT remained stable up to 14 days at 18°C. The within-run imprecision and sample carryover showed robust results with both iFOBT methods. CONCLUSIONS: The superior analytical stability and measurement accuracy demonstrated by the iFOBT in this in vitro study confers advantages over traditional qualitative gFOBTs and supports their suitability for more widespread use in population-based colorectal-cancer screening programmes.