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Background The transition from pediatric to adult care is associated with changes centered around the patient taking responsibility for their health. As the incidence of childhood-onset inflammatory bowel disease (IBD) is increasing, it is important to address gaps in transition literature—specifically, the indicators signifying achievement of transition success. The study objective was to define transition success according to patients, parents, and health care providers involved in IBD transition. Methods This study used the method of qualitative description to conduct semi-structured interviews with patients, parents, and health care providers. During interviews, demographic information was collected, and interviews were recorded and transcribed. Data analysis was conducted independently of each group using latent content analysis. Participant recruitment continued until thematic saturation was reached within each group. Results Patients, parents, and health care providers all defined transition success with the theme of independence in one’s care. The theme of disease management emerged within parent and provider groups, whereas the theme of relationship with/ trust in adult care team was common to patients and parents. Additional themes of care team management, general knowledge, care stability, and health outcomes emerged within specific groups. Conclusion This study demonstrated differences between how patients, parents, and health care providers view transition success. This finding reveals the value of using a multifaceted definition of transition success with input from all stakeholders. Further research should prioritize the identification of factors common to patients who do not reach transition success as defined by patients, their parents, and providers.

Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region., This work was supported by “Consejo Nacional de Ciencia y Tecnología” (CONACYT; no. 576951) grant to ZYM-R, and by Magnus Bergvalls Foundation and Swedish Society for Medical Research (SSMF) to KT. SKS and BP are funded by the Medical Research Council (MR/L015080/1). Supported in part by the US National Cancer Institute National Cancer Institute to DRM (P01 CA028842, R01 CA190612, K07 CA125588, P30 CA068485). We are very grateful to Daniel Falush (Unit of Statistical Genetics of Bacteria, Institut Pasteur of Shanghai) for his critical input during the analysis of the presented data. We acknowledge the Aklavik H. pylori Project Planning Committee (Northwest Territories, Canada) for providing input on our presentation of this analysis.

Background. Methylmercury contamination of the environment represents a substantial environmental health concern. Human exposure to methylmercury occurs primarily through consumption of fish and marine mammals. Heavily exposed subgroups include sport or subsistence fishers residing in Arctic communities. We aimed to estimate the association of fish/whale consumption patterns of Canadian Arctic subsistence fishers with the internal dose of methylmercury as measured in hair. Methods. This research was conducted within ongoing community projects led by the CANHelp Working Group in Aklavik and Fort McPherson, Northwest Territories and Old Crow, Yukon. We interviewed each participant using a fish-focused food-frequency questionnaire during September-November 2016 and collected hair samples concurrently. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively-coupled plasma-mass spectrometry. Multivariable linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption on hair-methylmercury concentrations. Results. Among 101 participants who provided hair samples and diet data, the mean number of fish/whale species eaten was 3.5 (SD:1.9). The mean hair-methylmercury concentration was 0.60μg/g (SD:0.47). Fish/whale consumption was positively associated with hair-methylmercury concentration, after adjusting for sex, hair length and use of permanent hair treatments. Hair-methylmercury concentrations among participants who consumed the most fish/whale in each season ranged from 0.30- 0.50μg/g higher than those who consumed Conclusions. In this population of Canadian Arctic subsistence fishers, hair-methylmercury concentration increased with fish/whale consumption, but the maximum concentrations were below Health Canada’s 6.0μg/g threshold for safe exposure.

Background Our community-driven projects address concerns of Canadian Arctic Indigenous communities about Helicobacter pylori (Hp) infection, responsible for elevated gastric cancer mortality in the region. Community research partners wished to learn whether bacterial characteristics determine severity of Hp-related disease in their communities. We aimed to describe gastric histopathology by cagA genotype of Hp isolated from residents of 7 Indigenous communities in the Northwest Territories and Yukon. Methods Participants underwent gastroscopy with 5-6 biopsies taken for histopathological assessment and 2 biopsies taken for tissue culture during 2008-2017. We used multiple PCR reactions and DNA sequence analysis to classify Hp genotypes as cagA+ or cagA-. A single pathologist used the updated Sydney classification system to grade severity of 5 gastric pathology outcomes: Hp density; chronic gastritis; active gastritis; atrophy; and intestinal metaplasia. We estimated prevalence of each outcome with 95% confidence intervals (CI) by gastric subsite and cagA status. Results Of 262 Hp isolates assessed, 142 (54%) were cagA+. Prevalence of moderate-high Hp density, severe chronic gastritis, moderate-severe active gastritis, atrophy, and metaplasia were (%[CI]): respectively, 78[70-85], 44[36-53], 65[56-72], 55[46-63], 25[18-33] in cagA+ participants and 61[52-70], 35[27-44], 31[23-40], 32[23-41], 8[4-15] in cagA- participants. cagA+ participants had higher prevalence of all outcomes in antrum and corpus. Conclusion Hp-infected Indigenous residents of Arctic Canada who harbored cagA-positive strains had higher prevalence of more severe gastric pathology than those with cagA-negative strains. Key messages Community-driven research answers questions posed by those who bear the disease burden.

Background Community-driven projects that aim to address public concerns about health risks from H. pylori infection in Indigenous Arctic communities (estimated H. pylori prevalence = 64%) show frequent failure of treatment to eliminate the bacterium. Among project participants, treatment effectiveness is reduced by antibiotic resistance of infecting H. pylori strains, which in turn, is associated with frequent exposure to antibiotics used to treat other infections. This analysis compares antibiotic dispensation rates in Canadian Arctic communities to rates in urban and rural populations in Alberta, a southern Canadian province. Methods Project staff collected antibiotic exposure histories for 297 participants enrolled during 2007–2012 in Aklavik, Tuktoyaktuk, and Fort McPherson in the Northwest Territories, and Old Crow, Yukon. Medical chart reviews collected data on systemic antibiotic dispensations for the 5-year period before enrolment for each participant. Antibiotic dispensation data for urban Edmonton, Alberta (average population ~ 860,000) and rural northern Alberta (average population ~ 450,000) during 2010–2013 were obtained from the Alberta Government Interactive Health Data Application. Results Antibiotic dispensation rates, estimated as dispensations/person-years (95% confidence interval) were: in Arctic communities, 0.89 (0.84, 0.94); in Edmonton, 0.55 (0.55, 0.56); in rural northern Alberta, 0.63 (0.62, 0.63). Antibiotic dispensation rates were higher in women and older age groups in all regions. In all regions, the highest dispensation rates occurred for β-lactam and macrolide antibiotic classes. Conclusions These results show more frequent antibiotic dispensation in Arctic communities relative to an urban and rural southern Canadian population.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

An analysis of drawings made by Indigenous children in the Arctic hamlet of Fort McPherson, Canada, serves the dual purpose of contributing children’s perspectives to community-driven research on H...

Background The incidence of childhood-onset inflammatory bowel disease (IBD) diagnoses is increasing in Canada; therefore, more patients will need to transition from pediatric into adult care. The literature on transition in IBD patients has focused mainly on preparation and while transition success is often referenced, it is not clearly defined. Prior research on IBD transition success has only focused on the perspectives of the health care providers. Taking into consideration that transition is a process that greatly relies on patient involvement, patient perspectives should be represented in defining its success. Aims The primary aim is to understand patients’ perspectives on the outcomes that characterize a successful transition from pediatric to adult care. Methods This study paired a theoretical position of naturalistic inquiry with the method of qualitative description. Purposive sampling was used to recruit patients from IBD clinics at the University of Alberta and the University of Calgary. Inclusion criteria included transition within the last two years, diagnoses with IBD for at least a year prior to transitioning, and absence of comorbidities. Virtual semi-structured interviews were conducted using an established interview guide. Interviews were transcribed verbatim and then analyzed concurrently with data collection by latent content analysis using NVivo computer software. Participant recruitment and data analysis continued until no further themes emerged from the data, which signaled that thematic saturation was achieved. Results Thematic saturation was achieved after 17 interviews. Among participants, 58.8% were female; 47% had a diagnosis of Crohn’s, 47% of ulcerative colitis, and one individual was diagnosed with both. The median age at diagnosis was 15 years (IQR, 3.5). The majority (94%) of participants viewed their transition as being successful. Overall, the major themes that emerged from the data were: 1. relationship with one’s adult care team, characterized predominantly as the patient being comfortable with their new team; 2. health outcomes, characterized by disease remaining stable, and medication adherence; 3. independence in one’s care, characterized by making and attending appointments on their own, asking questions and in general having an awareness about your health and disease; 4. care stability, characterized by no drop off in care, and regular contact and follow up by their provider. Conclusions Young adults with IBD define pediatric transition success in four themes: relationship with care team, health outcomes, independence in one’s care, and care stability. Through understanding what transition success looks like from the patients’ perspectives, health care providers can help patients achieve success as they define it. Funding Agencies None

Indigenous Arctic Canadians have a higher prevalence of gastric neoplasms relative to North Americans of European ancestry. We investigated the hypothesis that low-dose methylmercury exposure from eating fish/whale increases the risk of gastric cancer in Arctic communities. We used intermediate endpoints from an established model of gastric carcinogenesis: intestinal metaplasia, atrophy, and severe chronic gastritis. During 2008–2012, we obtained gastric biopsies from participants of community-driven projects in 3 communities. In 2016, we collected hair samples to measure methylmercury levels and interviewed them about diet. In cross-sectional analysis, logistic regression estimated odds ratios for the estimated effect of hair-methylmercury concentration on the prevalence of each pathology outcome stratified by selenium intake. Among 80 participants, prevalence of intestinal metaplasia, atrophy and severe chronic gastritis was 17, 29 and 38%, respectively. Adjusted Odds of severe chronic gastritis and atrophy were highest at hair-methylmercury concentrations ≥1μg/g when estimated selenium intake was 0, and approached 0 for all methylmercury levels as estimated selenium intake increased. Gastric pathology increased with methylmercury exposure when selenium intake was low. Though limited by small numbers, these findings suggest selenium ingested by eating fish/whale may counter harmful effects of methylmercury exposure in Arctic populations.

Background Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. Methods A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. Results The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. Conclusions The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

BACKGROUND: FMT is highly effective in the treatment of RCDI. Delivery of FMT by upper route and lower routes has been utilized, achieving cure rate of at least 80%. However, the ideal route of delivering FMT has not been determined. AIMS: To compare 1) the cure rate of RCDI; 2) safety; 3) patient satisfaction, preference and changes in quality of life between capsule vs colonoscopy delivered FMT. METHODS: Adult patients who had at least 3 documented episodes of CDI were randomized to FMT administered by either capsule or colonoscopy at 1:1 ratio. Key exclusion criteria included severe and complicated CDI; inflammatory bowel disease (IBD), unless stable symptoms for ≥ 3 months; dysphagia. Seven volunteer stool donors provided stool for FMT. RESULTS: 116 patients (57 in capsule and 59 in colonoscopy arm) were randomized between Oct 2014 - Aug 2016 in Edmonton and Calgary. Participant baseline characteristics were shown in Table 1. The cure rate of RCDI was 96.2% in the capsule arm and 95.9% in the colonoscopy arm after a single FMT (non-inferiority p value 0.5). The proportion of patients rating treatment “not at all unpleasant” was higher in the capsule arm (67%; 95% CI:56–78%) than the colonoscopy arm (44%; 95% CI: 31–59%). CONCLUSIONS: FMT administered by capsules was as efficacious as colonoscopy. No serious AE attributable to FMT was identified with either delivery modality. Fewer minor AEs were seen with capsule. Both FMT delivery methods improved quality of life, but fewer patients found capsule to be an unpleasant treatment modality. FUNDING AGENCIES: Alberta Health Services

Summary of Problem Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations1, 2. Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology3. It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people4; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex5. In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.

Increasingly, public health research standards call for engaging communities who live with health issues under investigation to help ensure that results translate into effective public health measures. Here, we share guiding principles for community-driven epidemiologic research developed over a decade conducting research sought and controlled by participating communities. These principles provide a roadmap for epidemiologic research that effectively addresses community priorities while meeting academic standards: research questions are developed collaboratively in community-university partnerships; knowledge takes shape from information donated by participants through methods that turn information into scientifically useful data and analysis that reveals data patterns that address research questions; thus, knowledge is generated collaboratively by academic researchers and community partners; academic researchers are bound by ethical, professional, scientific, contractual, and other legal standards to be responsible stewards of information donated by participants; community review protocols ensure that interpretation and presentation of research results reflect the voices of all partners; meaningful community review creates the trust needed for open access to research results as required of academic researchers; all partners share credit for achievements. Lacking models for operationalizing these principles, we developed specific guidelines for research project initiation, data use, authorship, acknowledgment, and data dissemination. Conventions in academia present formidable challenges to effective community engagement and are often at odds with calls from community organizations and funding agencies to conduct research driven by community priorities and values. We hope others can benefit from time and effort we have spent crafting solutions that bridge this divide.

Background. Methylmercury contamination of the environment represents a substantial environmental health concern. Human exposure to methylmercury occurs primarily through consumption of fish and marine mammals. Heavily exposed subgroups include sport or subsistence fishers residing in Arctic communities. We aimed to estimate the association of fish/whale consumption patterns of Canadian Arctic subsistence fishers with the internal dose of methylmercury as measured in hair. Methods. This research was conducted within ongoing community projects led by the CANHelp Working Group in Aklavik and Fort McPherson, Northwest Territories and Old Crow, YT. We interviewed each participant using a fish-focused food-frequency questionnaire during September-November 2016 and collected hair samples concurrently. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively-coupled plasma-mass spectrometry. Multivariable random-effects linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption on hair-methylmercury concentrations. Results. In total, 101 participants provided hair samples and diet data. The mean number of fish/whale species eaten by participants was 3.5 (SD:1.9). The mean hair-methylmercury concentration was 0.60μg/g (SD:0.47). Fish/whale consumption was positively associated with hair-methylmercury concentration, after adjusting for sex, hair length and use of permanent hair treatments. Hair-methylmercury concentrations among participants who consumed the most fish/whale in each season ranged from 0.30- 0.50μg/g higher than those who consumed

Community H. pylori (Hp) projects conducted by the CANHelp Working Group during 2007- 2018 generated local evidence of relevance to clinical decision-making about Hp infection in Arctic Indigenous communities. We used this information to adapt current Canadian guidelines for northern and Indigenous populations in Canada. Following the guidelines, we present the context and rationale for their development. Because evidence is limited for many of the recommendations we present, due weight should be given to the individual patient’s motivation, values, preferences, and circumstances.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the intestines likely induced by abnormal immune response to resident intestinal bacteria in genetically susceptible hosts. Probiotics, prebiotics and dietary fibres alter the gut microbiota and improve its function, thus potentially counteracting the development of inflammation. Although the role of these compounds in the prevention and management of IBD is relatively understudied, anecdotal evidence suggests widespread, undocumented use of these supplements by patients. Investigating the use of probiotics and prebiotics by IBD patients and association with disease severity may allow for optimization of therapy and improved clinical outcomes. AIMS: To assess if the self-motivated intake of probiotics, prebiotics and dietary fibre supplements is associated with the disease severity in patients with IBD. METHODS: We conducted a cross-sectional study of patients with a diagnosis of IBD in the University of Alberta IBD clinic. Using a 20-item questionnaire we collected data from patients on demographics, disease characteristics and knowledge and use of probiotics, prebiotics and dietary fibre supplements. We used a chart review to ascertain the occurrence of flares, disease duration and objective markers of inflammation such as fecal calprotectin (FCP) as indicators of disease severity. RESULTS: In this study, 100 participants (45% females) with a known diagnosis of IBD (47% Crohn’s disease, 34% ulcerative colitis, 19% IBD-unclassified) completed questionnaires. Large proportions of participants were knowledgeable about probiotics (88%) and dietary fibres (76%), but less about prebiotics (42%). The majority of users had Crohn’s disease (42% CD vs. 35% UC, p=0.33). 66% of surveyed patients had used these products as an alternate therapy. Disease flares in the last two years did not have an effect on usage (73% users vs. 71% non-users, p=0.8). The use of alternative therapies was higher in patients with longer history of IBD (77% in those with a duration >5 years vs. 22% in those with a duration 250 µg/g (an indicator of acute disease) during the preceding six months reported supplement use, compared to 52% with FCP values below this value (P=0.11). CONCLUSIONS: This study shows that a large proportion of IBD patients are interested in alternative therapies for IBD. Increased flare frequency and objective markers of inflammation did not have an effect on usage. However, longer disease history was the main factor influencing the search for a “cure” by the patients. These microbiota-altering strategies have the ability to affect disease outcomes, therefore clinicians and researchers should identify and document their use. FUNDING AGENCIES: CIHR

BACKGROUND: Helicobacter pylori (Hp) infection is a health concern in Arctic Canada, where prevalence of Hp and gastric cancer rates are high. The Canadian North Helicobacter pylori (CANHelp) Working Group conducts community projects to address public concerns, describe the disease burden, and inform regional health policy. Projects were launched projects during 2007–2017 in Aklavik, Tuktoyaktuk, Fort McPherson, and Inuvik in the Northwest Territories and Old Crow, Teslin, Ross River, Carmacks, and Pelly Crossing in Yukon. AIMS: To provide summary data on success of anti-Hp therapies in the NWT and Yukon METHODS: In each community, a planning committee guided the research design and conduct. Projects included UBT screening, upper GI endoscopy, treatment, and knowledge exchange. All Hp-positive participants ≥15 years old could enroll in a series of randomized treatment trials to one of the following anti-Hp therapies: - CA: 10-day combination of proton pump inhibitor (PPI), clarithromycin and amoxicillin - Sequential therapy (ST) 10 day: PPI and amoxicillin for days 1–5, followed by PPI, clarithromycin and metronidazole for days 6–10 - BMT quadruple (BMT): 10–14 day bismuth quadruple therapy with PPI, bismuth, metronidazole, and tetracycline - CAM 14 day quadruple therapy with PPI, clarithromycin, amoxicillin, and metronidazole - AL: 14 day PPI, amoxicillin and levofloxacin Treatment adjustments: CA therapy was discontinued in 2008 after initial results showed poor effectiveness. Based on ST results and new Canadian guidelines ST was replaced by CAM in 2015 and treatment duration became 14 days. Treatment success is defined as a negative UBT at >=10 weeks post treatment. RESULTS: To date, of 1421 community Hp project participants, 1305 were tested for Hp by UBT (positivity=52%), 398 had endoscopy with gastric biopsy, 268 enrolled in the treatment trial, and 225 had a post-treatment UBT. In 5 patients the UBT was equivocal and these were excluded. TREATMENT TRIAL RESULTS: Of trial participants with a follow-up UBT, the proportion with treatment success was: PPI-CA 62% (29/47; 95%CI 46–75%); ST 72% (70/97; 95%CI 62–81%); BMT 92% (56/61; 95%CI 82–97%) and 100% (15/15; 95%CI 82–100%) of those randomized to CAM. Of 68 participants treated outside the clinical trial with a follow-up UBT, the proportion with treatment success was: PPI-CA 41% (7/17; 95%CI 18–67%); ST 47% (8/17; 95%CI 23–72%); BMT 92% (15/18; 95%CI 59–96%), CAM 67% (2/3; 95%CI 9–99%)and AL 3/3(100%, 95%CI 37–100%), In 10 patients the treatment was unknown. CONCLUSIONS: While treatment success estimates from this treatment trial in Canadian Arctic communities are somewhat imprecise, results demonstrate superiority of bismuth based quadruple and non-bismuth quadruple (CAM) therapies to sequential or triple therapy. Compliance with follow up UBT testing is suboptimal. FUNDING AGENCIES: CIHRInuvialuit Regional Corporation, Alberta Innovates Health Solutions, ArcticNet

SUMMARYHelicobacter pyloriinfection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to ‘test and treat’ those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment ofH. pyloriin high-prevalence countries. They concluded that in Arctic countries whereH. pyloriprevalence exceeds 60%, treatment of persons withH. pyloriinfection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.

Article first published online 3 April 2015., Background: Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD. Methods: Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission. Results: A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 μg/g, median ITLs 7.3 μg/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197–0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536–1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254–0.742) and objective remission (AUC = 0.773; 95% CI, 0.622–0.924). Conclusions: Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy.

Globally, gastric cancer incidence shows remarkable international variation and demonstrates distinct characteristics by the two major topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global incidence estimates by subsite are lacking, we aimed to describe the worldwide incidence patterns of CGC and NCGC separately.Using Cancer Incidence in Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC by country, sex and age group (65 and ≥65 years). These derived proportions were applied to GLOBOCAN 2012 data to estimate country-specific age-standardised CGC and NCGC incidence rates (ASR). Regional proportions were used to estimate rates for countries not included in CI5X.According to our estimates, in 2012, there were 260,000 cases of CGC (ASR 3.3 per 100,000) and 691,000 cases of NCGC (ASR 8.8) worldwide. The highest regional rates of both gastric cancer subsites were in Eastern/Southeastern Asia (in men, ASRs: 8.7 and 21.7 for CGC and NCGC, respectively). In most countries NCGC occurred more frequently than CGC with an average ratio of 2:1; however, in some populations where NCGC incidence rates were lower than the global average, CGC rates were similar or higher than NCGC rates. Men had higher rates than women for both subsites but particularly for CGC (male-to-female ratio 3:1).This study has, for the first time, quantified global incidence patterns of CGC and NCGC providing new insights into the global burden of these cancers. Country-specific estimates are provided; however, these should be interpreted with caution. This work will support future investigations across populations.

BACKGROUND: Women with inflammatory bowel disease (IBD) may choose to remain childless due to a lack of IBD-specific reproductive knowledge.OBJECTIVES: To examine the effects of IBD-specific reproductive knowledge and discussion of family planning with a physician on childlessness among women with IBD.METHODS: Female IBD patients 18 to 45 years of age completed the Crohn’s and Colitis Pregnancy Knowledge questionnaire (CCPKnow), and answered questions regarding reproductive history, plans to have children and discussion of family planning with a physician. CCPKnow scores were grouped according to poor (0 to 7), adequate (8 to 10), good (11 to 13) and very good (14 to 17).RESULTS: Of 434 eligible women, 248 (57.1%) completed the questionnaires. Of these 248 women, 51.6% were childless and, among these, 12.9% were voluntarily childless and 12.1% were trying to become pregnant. Childless women had a lower median CCPKnow score than women with children (6.0 versus 8.0; P=0.001). After adjusting for current age and marital status, each one point increase in the CCPKnow score corresponded to 8% lower odds of childlessness (OR 0.92 [95% CI 0.86 to 0.99]), 9% lower odds of voluntary child-lessness (OR 0.91 [95% CI 0.79 to 1.0]) and 20% higher odds of trying to become pregnant (OR 1.2 [95% CI 1.0 to 1.4]). Discussion of family planning with a gastroenterologist corresponded to 72% lower odds of a poor CCPKnow score (OR 0.28 [95% CI 0.15 to 0.53]) and of voluntary childlessness (OR 0.28 [95% CI 0.057 to 1.3]).CONCLUSION: In the present study, higher IBD-specific reproductive knowledge lowered the odds of childlessness among women with IBD. Discussion of family planning with a physician was associated with higher CCPKnow scores and lower odds of voluntary childlessness.

The transition of inflammatory bowel disease (IBD) patients from pediatric to adult care can be challenging. Developing an effective transition intervention requires assessing the current transition experience for potential improvements, determining preferred content and format, and assessing patients' transition skills.This mixed-methods study of 20 transitioned IBD patients (ages 17-20 years) used semistructured interviews and validated assessments of self-management/self-advocacy and IBD knowledge. Interviews were analyzed thematically. Assessment scores were compared with published reference data by estimating proportion or mean differences and 95% confidence intervals (CIs).The concept of a transition intervention was well-received by participants. Preferred content centered on medications, disease and what to expect. Preferred ways to acquire knowledge were one-on-one instruction, handouts, and websites. Identified themes were "individualized and multifaceted," "teach about transition," and "support the shift in responsibility." Among participants, 95% did not achieve 90% mastery of transition skills (0.6% higher [95% CI -10.7% to 9.5%] than the reference estimate) and the mean knowledge score was 15.15 (3.86 [95% CI 2.27 to 5.45] points higher than the reference estimate).We have identified preferred intervention formats and content as well as skill areas to target for improvement. As a result of this work, we will design a website intervention pertaining to identified themes.

The role of environmental reservoirs in H. pylori transmission remains uncertain due to technical difficulties in detecting living organisms in sources outside the stomach. Residents of some Canadian Arctic communities worry that contamination of the natural environment is responsible for the high prevalence of H. pylori infection in the region. This analysis aims to estimate associations between exposure to potential environmental sources of biological contamination and prevalence of H. pylori infection in Arctic Canada. Using data from 3 community-driven H. pylori projects in the Northwest and Yukon Territories, we estimated effects of environmental exposures on H. pylori prevalence, using odds ratios (OR) and 95% confidence intervals (CI) from multilevel logistic regression models to adjust for household and community effects. Investigated exposures include: untreated drinking water; livestock; dogs; cats; mice or mouse droppings in the home; cleaning fish or game. Our analysis did not identify environmental exposures associated clearly with increased H. pylori prevalence, except any exposure to mice or mouse droppings (OR = 4.6, CI = 1.2–18), reported by 11% of participants. Our multilevel models showed H. pylori clustering within households, but environmental exposures accounted for little of this clustering; instead, much of it was accounted for by household composition (especially: having infected household members; number of children). Like the scientific literature on this topic, our results do not clearly implicate or rule out environmental reservoirs of H. pylori; thus, the topic remains a priority for future research. Meanwhile, H. pylori prevention research should seek strategies for reducing direct transmission from person to person.

BACKGROUND: Infliximab (IFX) induces and maintains remission in Crohn’s Disease (CD) and Ulcerative Colitis (UC). Secondary loss of response occurs in up to 45% of CD and 60% of UC patients on maintenance IFX. Studies are inconclusive on ideal IFX trough levels (ITLs) to prevent loss of response; recommendations range from “detectable” up to 10μg/mL. Patients with adequate ITLs still lose response, suggesting they still have gastrointestinal (GI) inflammation. Fecal Calprotectin (FCP), a marker of neutrophilic infiltration into the GI tract, when elevated predicts loss of response to maintenance IFX (sensitivity 0.80, specificity 0.82). We previously showed clinicians would alter decisions based on ITLs and FCP levels. There are no studies on using ITLs and FCP levels in conjunction with clinical presentation. AIMS: To determine if 6 month outcomes in IBD outpatients on IFX maintenance could be improved if clinicians had knowledge of both ITLs and FCP levels in addition to clinical data. METHODS: This was a pilot, retrospective case series of adult IBD outpatients on maintenance IFX, who prior to having levels drawn were in clinical remission. Actual clinical decisions were based on clinical presentation and standard labs. All subjects had blood ITLs drawn. A subset (Group 2) provided stools for FCP levels. An expert clinician panel made hypothetical clinical decisions with ITLs and FCP levels. Interval (between ITL and 6-months) and final 6-month outcomes were recorded. Comparisons were made between: actual clinical decisions and what ITLs should prompt (Group 1); and actual clinical decisions, what ITLs and FCP levels should prompt, and hypothetical clinical decisions (Group 2). Statistical analyses included: medians with interquartile ranges (IQRs); proportions; percentages; chi-squared and non-parametric analyses. RESULTS: Table 1 captures baseline demographics. There were no statistically significant differences in demographics between the two groups. Table 2 highlights patients in (a) Group 1 and (b) Group 2 in whom ITL and/or FCP levels could have impacted clinical decision making. Of note, 2 out of the 6 patients (Group 2) had “adequate” ITLs but elevated FCP. Table 2 further summarizes what could have been done to prevent the clinical outcomes that occurred without these levels. CONCLUSIONS: While previous studies have explored the use of ITLs and FCP levels in isolation, the results of this study demonstrate that knowledge of ITLs and FCP levels together, in addition to the patient’s clinical presentation, can aid clinicians to optimize management and improve outcomes of IBD outpatients on IFX maintenance. FUNDING AGENCIES: NoneN/A

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the intestines that are believed to be induced by abnormal activation of the immune cells in response to resident intestinal bacteria in genetically susceptible hosts. Probiotics, prebiotics and dietary fibres alter the gut microbiota and improve its function, thus potentially counteracting the development of inflammation. Unlike the current standard medications for IBD, these supplements are relatively safe. As such they are suggested as promising novel adjuvant modalities in the treatment of IBD. Although the role of these compounds in the prevention and treatment of IBD is understudied, there seems to be a widespread, undocumented use of these supplements by patients. Identification of usage of probiotics and prebiotics in IBD patients, will allow for optimization of therapy, and improved clinical outcomes. AIMS: To assess the intake of probiotics, prebiotics and dietary fibre supplements in patients with IBD in Edmonton, Alberta. METHODS: A cross-sectional, observational study using a 20-item survey questionnaire was used in patients with a diagnosis of IBD in the IBD Clinic at the University of Alberta. Data regarding demographics, disease characteristics, use and knowledge of probiotics, prebiotics and dietary fibre supplements was collected and analyzed using Fisher’s exact test. RESULTS: In this pilot study, 23 participants with a known diagnosis of IBD (57% ulcerative colitis, 39% Crohn’s disease, 4% indeterminate colitis) completed survey questionnaires. Statistical analysis demonstrated that a large number of participants were knowledgeable about probiotics and dietary fibres, but less about prebiotics (87% probiotics, 74% fibres, 43% prebiotics, P < 0.38). Sixty five per cent of surveyed patients have used these products in the past. However, regular usage (in the last year), was much lower (48% probiotics, 28% fibres, 4% prebiotics). Of those who used these alternative treatments in the past, 31% of patients experienced an increase in quality of life (QoL). Those without a university degree were more likely to use these products (67%, P < 0.37). The effect of gender on usage was negligible (53% males, 47% females, P < 1.0). Preliminary results did not reach statistical significance. CONCLUSIONS: This pilot study shows that a large proportion of IBD patients have used probiotics, prebiotics and dietary fibre supplements in the past despite the lack of well-proven efficacy. Since these microbiota targeting strategies have a great potential to improve disease outcomes, it is important that clinicians and researchers document their use. FUNDING AGENCIES: CIHR

BACKGROUND:Helicobacter pyloriinfection occurs more frequently in Arctic Aboriginal settings than elsewhere in North America and Europe. Research aimed at reducing health risks fromH pyloriinfection has been conducted in the Aboriginal community of Aklavik, Northwest Territories.OBJECTIVE: To compare the effectiveness of the Canadian standard therapy with an alternative therapy for eliminatingH pyloriinfection in Aklavik.METHODS: Treatment-naiveH pylori-positive individuals were randomly assigned to a 10-day regimen (oral twice-daily doses) with rabeprazole (20 mg): standard triple therapy (proton pump inhibitor, added clarithromycin [500 mg] and amoxicillin [1 g] [PPI-CA]); sequential therapy (ST) added amoxicillin (1 g) on days 1 to 5, and metronidazole (500 mg) and clarithromycin (500 mg) on days 6 to 10. Participants with clarithromycin-resistantH pyloriwere randomly assigned to ST or quadruple therapy. Treatment effectiveness was estimated as per cent (95% CI) with a negative urea breath test at least 10 weeks after treatment.RESULTS: Of 104 (53 PPI-CA, 51 ST) randomized participants, 89 (49 PPI-CA, 40 ST) had post-treatment results. Per-protocol treatment effectiveness was 59% (95% CI 45% to 73%) for PPI-CA and 73% (95% CI 58% to 87%) for ST. Based on intention to treat, effectiveness was 55% (95% CI 41% to 69%) for PPI-CA and 57% (95% CI 43% to 71%) for ST. Of 77 participants (43 PPI-CA, 34 ST) with 100% adherence, effectiveness was 63% (95% CI 43% to 82%) for PPI-CA and 81% (95% CI 63% to 99%) for ST.CONCLUSIONS: While additional evidence is needed to confirm that ST is more effective for Arctic Aboriginal communities than the Canadian standardH pyloritreatment, these results show standard PPI-CA treatment to be inadequate for communities such as Aklavik.

Background.Inflammatory bowel disease (IBD) affects patients in their young reproductive years. Women with IBD require maintenance therapies during pregnancy and breastfeeding. However, physician management of IBD during pregnancy and breastfeeding has not been well characterized.Objective.To characterize physician perceptions and management of IBD during pregnancy and breastfeeding.Methods.A cross-sectional survey of Canadian physicians who are involved in the care of women with IBD was conducted. The survey included multiple-choice and Likert scale questions about perceptions and practice patterns regarding the management of IBD during pregnancy and breastfeeding.Results.183 practicing physicians completed the questionnaire: 97/183 (53.0%) gastroenterologists; 75/183 (41.0%) general practitioners; and 11/183 (6.0%) other physicians. Almost half (87/183, 47.5%) of the physicians felt comfortable managing pregnant IBD patients. For specified IBD medications, proportions of physicians who indicated they would continue them during pregnancy were as follows: sulfasalazine, 47.4%; oral mesalamine, 67.0%; topical mesalamine, 70.3%; oral prednisone, 68.0%; topical prednisone, 78.0%; oral budesonide, 61.6%; topical budesonide, 75.0%; ciprofloxacin, 15.3%; metronidazole, 31.4%; azathioprine, 57.1%; methotrexate, 2.8%; infliximab, 55.6%; adalimumab, 78.1%. Similar proportions of physicians would continue these medications during breastfeeding. A higher proportion of gastroenterologists than nongastroenterologists indicated appropriate use of these IBD medications during pregnancy and breastfeeding.Conclusions.Physician management of IBD during pregnancy and breastfeeding varies widely. Relative to other physicians, responses of gastroenterologists more frequently reflected best practices pertaining to medications for control of IBD during pregnancy and breastfeeding. There is a need for further education regarding the management of IBD during pregnancy and breastfeeding.

The aim of the present study was to estimate the incidence and spontaneous clearance rate of Helicobacter pylori infection and the effect of some variables on these outcomes in schoolchildren.From May 2005 to December 2010, 718 schoolchildren enrolled in 3 public boarding schools in Mexico City participated in the follow-up. At the beginning of the study and every 6 months thereafter, breath samples were taken to detect H pylori infection; blood samples and anthropometric measurements were taken to evaluate nutritional status. Data on sociodemographic characteristics were collected.The prevalence of H pylori infection was 38%. The incidence rate was 6.36%/year. Schoolchildren with anemia or iron deficiency at the beginning of the study (who received iron supplements) showed a higher infection acquisition rate than those with normal iron nutritional status, hazard ratio (HR) 12.52 (95% confidence interval [CI] 4.01%-39.12%), P0.001 and HR 2.05 (95% CI 1.09%-3.87%), P = 0.027, respectively. The spontaneous clearance rate of the infection was 4.74%/year. The spontaneous clearance rate was higher in children who had iron deficiency (who received iron supplements), HR 5.02 (95% CI 1.33%-18.99%), P = 0.017, compared with those with normal nutritional iron status. It was lower in schoolchildren with ≥ 2 siblings compared with schoolchildren with 1 or no siblings, HR 0.23 (95% CI 0.08%-0.63%), P = 0.004.H pylori infection status is dynamic in schoolchildren. Variables related to health status and infection transmission, such as iron status and number of siblings, are important for the incidence and spontaneous clearance of H pylori infection.

Background: Immunosuppressive agents, used commonly to treat inflammatory bowel disease (IBD), are associated with an increased risk of infections, including those preventable by immunization. This study aimed to describe physician and patient values and knowledge regarding immunization and immunization histories. Methods: In all, 167 IBD patients and 43 gastroenterologists completed mail-out questionnaires. Patients were asked 15 questions about their immunization histories and attitudes towards immunization. Gastroenterologists were asked nine questions about immunization for the immunocompromised host. Results: The questionnaire return rate was 45.7% (43/94) for gastroenterologists and 25.2% (167/661) for patients. Only 14.3% (6/42) of gastroenterologists reported taking an immunization history from most or all of their patients. Only 5.4% (9/167) of patients recalled being asked by their gastroenterologist whether their immunizations were up to date, and just 0.6% (1/164) recalled being asked for a detailed immunization history. Overall, 21.7% (35/161) of patients had refused to be immunized in the past; 18.6% (8/43) of gastroenterologists did not know if up-to-date immunizations were important prior to starting immunosuppressive therapy. Of note, 23.1% (9/39) of gastroenterologists and 46.7% (35/161) of patients did not know whether live vaccines should be avoided by those in the immunosuppressed state, and 42.9% (18/43) of gastroenterologists acknowledged they did not know which specific immunizations should be avoided for immunosuppressed patients. Conclusions: Gastroenterologists have limited knowledge of their IBD patients' immunization status and rarely take an adequate immunization history. Substantial proportions of IBD patients and gastroenterologists lack adequate knowledge of established immunization guidelines prior to initiation of immunosuppressive therapy. (Inflamm Bowel Dis 2011;)

Objective: As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe. Methods: An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system. Results: A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection. Conclusions: These clinical practice guidelines represent updated, bestavailable evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.

OBJECTIVE: The goal was to compare the frequency of children's antibiotic intake, emphasizing antibiotics with anti-Helicobacter pylori effects, in El Paso, Texas, and Juarez, Mexico. METHODS: Hispanic children were enrolled prenatally at mother-child clinics in El Paso, and Juarez, in 1998–2000, to identify determinants of H pylori infection. During follow-up examinations targeted every 6 months from 6 to 84 months of age, caretakers reported medication use during the preceding interval. Courses of any systemic and H pylori-effective antibiotics were compared for US and Mexican children. RESULTS: Antibiotic data were available for 602 children, from 2938 follow-up visits. Overall antibiotic intake was higher in Juarez, where 84% of children received ≥1 course during the follow-up period (52% of visits), compared with El Paso, where 76% of children received ≥1 course (40% of visits). In contrast, the intake of H pylori-effective antibiotics was higher in El Paso, where 65% of children received ≥1 course during the follow-up period (27% of visits), compared with Juarez, where 44% of children received ≥1 course (16% of visits). Of H pylori-effective courses, 94% contained amoxicillin and 2% each clarithromycin, metronidazole, and furazolidone; uses were primarily for throat and ear infections, diarrhea, and cold/flu. CONCLUSIONS: Pediatric antibiotic use was higher in Mexico than on the US side of the border. Apparent misuse of H pylori-effective antibiotics was more frequent in Juarez but also occurred in El Paso. Such misuse of antibiotics may lead to drug resistance and may impair the control of H pylori infection in this region.

BACKGROUND: The optimal topical anesthesia regimen for unsedated transnasal endoscopy is unknown. The addition of a nasal decongestant, such as xylometazoline (X), to a topical anesthestic may improve patient comfort.OBJECTIVE: To determine the effectiveness of lidocaine (L) versus L plus X (LX) for anesthesia in unsedated transnasal endoscopy.METHODS: Consecutive participants of the AklavikHelicobacter pyloriproject were prospectively randomly assigned to receive LX or L for unsedated transnasal 4.9 mm ultrathin endoscopy. The primary outcome was overall procedure discomfort on a validated 10-point visual analogue scale (1 = no discomfort, 10 = severe discomfort). Secondary outcomes included pain, endoscope insertion difficulty, gagging, adverse events and encounter times. Results were presented as mean ± SD, difference in mean, 95% CI.RESULTS: A total of 181 patients were randomly assigned to receive LX (n=94) and L (n=87). Baseline characteristics between the two groups were similar (mean age 40 years, 59% women). Overall, patient procedural discomfort with LX and L were 4.2±2.4 versus 3.9±2.1, respectively (0.29; 95% CI −0.39 to 0.96). Transnasal insertion difficulty was significantly lower with LX than with L (2.4±2.1 versus 3.2±2.8, respectively [−0.80; 95% CI −1.54 to −0.06]). Compared with L, the use of LX was associated with significantly less time needed to apply anesthesia (2.4±1.8 min versus 3.5±2.2 min, respectively [−1.10; 95% CI −1.71 min to −0.50 min]) and less time for insertion (3.2±1.8 min versus 3.9±2.2 min, respectively [−0.70 min; 95% CI −1.30 min to −0.10 min]). Epistaxis was rare but occurred less frequently with LX (1.1%) than with L (4.6%) (P=0.19).CONCLUSIONS: LX did not improve patient comfort for transnasal endoscopy compared with L alone. However, LX was associated with less difficulty with endoscope transnasal insertion and reduced insertion time. Further studies on the optimal regimen and dosing of anesthesia are required.