In grade C/D erosive esophagitis, vonoprazan ranks highest among PPIs and P-CABs for healing and maintaining remission.

SOURCE CITATION: Zhuang Q, Chen S, Zhou X, et al. Comparative efficacy of P-CAB vs proton pump inhibitors for grade C/D esophagitis: a systematic review and network meta-analysis. Am J Gastroenterol. 2024;119:803-813. 38345252.

Biomarker risk assessment model identified high-risk patients with cancer who benefit from thromboprophylaxis.

SOURCE CITATION: Alexander M, Harris S, Underhill C, et al. Risk-directed ambulatory thromboprophylaxis in lung and gastrointestinal cancers: the TARGET-TP randomized clinical trial. JAMA Oncol. 2023;9:1536-1545. 37733336.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study.

BACKGROUND & AIMS: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results. METHODS: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time. RESULTS: The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32). CONCLUSIONS: Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods.

Adversity in childhood and depression in pregnancy.

Adverse childhood experiences (ACEs) have been found to be associated with various health conditions; however, there is dearth of evidence on the relationship between ACEs and prenatal depression. This study was conducted to determine the association between overall ACE score and prenatal depression symptoms, assess the moderating effect of social support and partner support on this relationship, and determine the association between individual ACE scores and prenatal depression. A secondary analysis was conducted of data from an RCT that assessed the feasibility of e-screening for maternal mental health among 636 pregnant women recruited from antenatal clinics. Two logistic regression models were built to reach our objectives. Over 80% of the participants were older than 25 years and had education beyond high school. Eighteen percent of the women had an ACE score of four or more. Univariable analysis found a 2.5-fold increase in the odds of prenatal depression for women with an ACEs score of ≥ 4. When examining the overall ACE score, lack of social support during pregnancy [AOR = 4.16; 95%CI (2.10-10.35)] and partner's relationship [AOR = 2.23; 95%CI (1.12-4.44)] were associated with prenatal depression while among the individual ACE scores, living with a person who went to prison was found to be associated with prenatal depression even when controlled for all variables. No moderating effect was found. These findings suggest for the improvement of partner's relationship and provision of social support before women conceive, in order to mitigate the effect of these adversities.

Burden of disease from Helicobacter pylori infection in western Canadian Arctic communities.

BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.

The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults.

BACKGROUND & AIMS: Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to provide a review of the literature and specific, updated recommendations for eradication therapy in adults. METHODS: A systematic literature search identified studies on H pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized, and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. RESULTS: Because of increasing failure of therapy, the consensus group strongly recommends that all H pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant nonbismuth quadruple therapy (proton pump inhibitor [PPI] + amoxicillin + metronidazole + clarithromycin [PAMC]) and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline [PBMT]). PPI triple therapy (PPI + clarithromycin + either amoxicillin or metronidazole) is restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin). Rifabutin regimens should be restricted to patients who have failed to respond to at least 3 prior options. CONCLUSIONS: Optimal treatment of H pylori infection requires careful attention to local antibiotic resistance and eradication patterns. The quadruple therapies PAMC or PBMT should play a more prominent role in eradication of H pylori infection, and all treatments should be given for 14 days.

Upper gastrointestinal bleeding due to peptic ulcer disease is not associated with air pollution: a case-crossover study.

BACKGROUND: Recent studies have demonstrated an association between short-term elevations in air pollution and an increased risk of exacerbating gastrointestinal disease. The objective of the study was to evaluate if day-to-day increases in air pollution concentrations were positively associated with upper gastrointestinal bleeding (UGIB) secondary to peptic ulcer disease (PUD). METHODS: A time-stratified case-crossover study design was used. Adults presenting to hospitals with their first UGIB secondary to PUD from 2004-2010 were identified using administrative databases from Calgary (n = 1374; discovery cohort) and Edmonton (n = 1159; replication cohort). Daily concentrations of ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and particulate matter (PM10 and PM2.5) were estimated in these two cities. Conditional logistic regression models were employed, adjusting for temperature and humidity. Odds ratios (OR) with 95 % confidence intervals (CI) were expressed relative to an interquartile range increase in the concentration of each pollutant. RESULTS: No statistically significant associations were observed for any of the individual pollutants based on same-day, or 1-day lag effects within the Calgary discovery cohort. When the air pollution exposures were assessed as 3-, 5-, and 7-day averages, some pollutants were inversely associated with UGIB in the discovery cohort; for example, 5-day averages of nitrogen dioxide (OR = 0.68; 95 % CI: 0.53-0.88), and particulate matter <2.5 µm (OR = 0.75; 95 % CI: 0.61-0.90). However, these findings could not be reproduced in the replication cohort. CONCLUSION: Our findings suggest that short-term elevations in the level of ambient air pollutants does not increase the incidence of UGIB secondary to PUD.

Patients with cirrhosis and denied liver transplants rarely receive adequate palliative care or appropriate management.

BACKGROUND & AIMS: Patients with cirrhosis who are receiving palliative care and are not eligible for liver transplantation (LT) are often hospitalized multiple times, with lack of expectations or understanding of death and dying. We evaluated how frequently these patients received appropriate and palliative care. METHODS: We performed a retrospective study of 102 consecutive adult patients (67% men; mean age, 55 years) who were removed from the list for or declined LT from January 2005 through December 2010 at the University of Alberta, Canada. Patients' medical records were reviewed to determine their access to palliative care and relief of symptoms, the appropriateness of the goals for their care, and their requirements for acute care services. RESULTS: The patients' median Model for End-stage Liver Disease score was 20, and median time from denial of LT to death was 52 days (range, 10-332 days). The most common reasons that patients were removed from the transplant wait list were noncompliance or substance abuse (26%) and severe illness or organ dysfunction (25%). After patients were removed from the list, 17% received renal replacement therapy, and 48% were subsequently admitted to the intensive care unit. Patients spent a median of 14 days (range, 6-33 days) in the hospital after they were removed from the transplant wait list. On the basis of the Edmonton Symptom Assessment System, 65% of patients had evidence of pain, 58% had evidence of nausea, 10% had depression, 36% had anxiety, 48% had dyspnea, and 49% had symptoms of anorexia. Twenty-eight percent of all the patients had documentation of do not resuscitate status on their charts, and only 11% were referred for palliative care. CONCLUSIONS: Patients with cirrhosis who have been removed from the wait list for LT are infrequently referred for palliative care (∼ 10% of cases), although a high percentage have pain or nausea. Goals of care and do not resuscitate status are rarely discussed. Improved planning of goals of care and access to palliative services are required for these patients.

Success of Helicobacter pylori Guideline-based Treatment of Newly Diagnosed and Previously Treated Patients During 2007-2021 in Edmonton, Alberta.

Background: Updated 2016 Helicobacter pylori consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days. Objectives: This was a retrospective cohort study to describe and compare the efficacy of anti-Helicobacter treatment regimens over the periods 2007-2015 and 2016-2021 as well as antibiotic resistance. Methods: A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed H. pylori treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients. Results: H. pylori-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016-2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) (P < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7-26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016-2021 and sequential therapy in 2007-2015 (83% [66/80]) (P = 0.535, RD 4%, 95% CI -8.5-16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016-2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007-2015 to 2016-2021 (28% [13/46] to 61% [35/57], P < 0.05, RD 33%, 95% CI 11.6-54.4%). Conclusions: Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures H. pylori in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50-57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in H. pylori is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.

Differences in utilisation of gastroprotective drugs between 2001 and 2005 in Australia and Nova Scotia, Canada.

PURPOSE: This study aimed to compare use of histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), 2001-2005, in the elderly and social security beneficiaries in Australia (AUS) and Nova Scotia, Canada (NS). METHODS: Prescription dispensing data were collected for all subsidised H2RAs and PPIs. In AUS, dispensing data for concession beneficiaries were obtained from the Pharmaceutical Benefits Scheme database. In NS, data were sourced from the Pharmacare database. Relevant population data were used to convert to World Health Organisation Anatomic Therapeutic Chemical defined daily doses (2005) per 1000 beneficiaries per day (DDD/1000/day). RESULTS: Overall use of gastroprotective agents was similar and rising in NS and AUS (100-160 DDD/1000/day) over this 5-year time window. However, the proportion of this use accounted for by PPIs was far higher in AUS (over 85% by 2005) than in NS (23% rising to 35% over the 5 years). In AUS, PPI use rose from 50 to about 140 DDD/1000/day over the 5 years, whereas PPI use in NS rose slowly to less than 60 DDD/1000/day by 2005. H2RA use in NS was always high (over 100 DDD/1000/day), whereas in AUS, H2RA use fell from 54 to around 24 DDD/1000/day over this period. CONCLUSIONS: AUS had much higher use of PPIs than NS over 2001-2005. The proportion of PPIs in all gastroprotective agents rose in AUS to be nearly 90%. The differences in utilisation during this time window could lead to differences in health outcomes from either lower gastro-intestinal bleeding risk or higher long-term adverse effects of PPIs.

The sensitivity and specificity of guaiac and immunochemical fecal occult blood tests for the detection of advanced colonic adenomas and cancer.

PURPOSE: Fecal immunochemical tests (FITs) have been developed to address analytical problems inherent in the older guaiac-based fecal occult blood tests (g-FOBTs). Our aim was to compare the performance characteristics of one g-FOBT (Hemoccult II) and two FITs (the Hemoccult ICT and MagStream HemSp) relative to colonoscopy for the detection of colorectal cancer and significant precursor lesions. We also examined whether a 1-day collection strategy would negatively impact test diagnostic performance. METHODS: We used a prospective observational cohort design in a Canadian population eligible for screening. All participants received colonoscopy after performing the occult blood tests. RESULTS: One thousand seventy-five individuals were enrolled (mean age 56.3 years, 53.8 % females). Using colonoscopy as the gold standard, the sensitivity for screen-relevant neoplasm was determined for Hemoccult II (7.2, 95 % CI: 1.1-13.4), Hemoccult ICT (23.2 %: 13.2-33.1), and MagStream HemSp using 67 µg/gram stool as the cut-off (23.2 %: 13.2-33.1). The Magstream HemSp, using a cut-off threshold of 30 µg/gram stool, had the lowest specificity at 87.6 % (85.4-89.6), while the Hemoccult II had the highest at 98.8 % (98.1-99.5). Single-day stool testing reduced the false-positive rates of all tests without significantly reducing the sensitivity. CONCLUSION: We found that FITs have a significantly increased sensitivity but reduced specificity for screen-relevant neoplasm compared to g-FOBT using colonoscopy as the gold standard. Optimal threshold levels for hemoglobin detection depend on the desired trade off between sensitivity and false-positive rate. Single-day testing with an FIT may be an option to enhance population compliance with screening.

The 'natural history' of declined outpatient gastroenterology referrals.

OBJECTIVE: To evaluate the 'natural history' of outpatients who were referred to the Division of Gastroenterology at the University of Alberta Hospital (Edmonton, Alberta) for gastrointestinal problems and were subsequently declined. METHODS: Patients were tracked for 12 months after they were referred and declined for the following indications: abdominal pain, rectal bleeding, fecal occult blood test-positive stools and iron deficiency. For each patient, data regarding consultations by other gastroenterologists or surgeons working in the region, clinically relevant diagnoses and the number of gastrointestinal-related x-rays performed were obtained. RESULTS: Of a total sample size of 230 patients, 110 (47.8%) were seen by another gastroenterologist or surgeon after decline. A significant diagnosis was made in 21 patients (9.1%), which had immediate clinical consequences in 29%. Forty per cent of patients underwent one or more gastointestinal-related x-rays before being declined, which increased to 55% after decline. CONCLUSION: Approximately 50% of declined patients were seen by other gastroenterologists or surgeons in the region. In 9.1% of these patients, a clinically important diagnosis was made, of which one-quarter had immediate medical consequences.

Anti-Inflammatory Diet Prevents Subclinical Colonic Inflammation and Alters Metabolomic Profile of Ulcerative Colitis Patients in Clinical Remission.

A relationship between ulcerative colitis (UC) and diet has been shown in epidemiological and experimental studies. In a 6-month, open-label, randomized, placebo-controlled trial, adult UC patients in clinical remission were randomized to either an "Anti-inflammatory Diet (AID)" or "Canada's Food Guide (CFG)". Menu plans in the AID were designed to increase the dietary intake of dietary fiber, probiotics, antioxidants, and omega-3 fatty acids and to decrease the intake of red meat, processed meat, and added sugar. Stool was collected for fecal calprotectin (FCP) and microbial analysis. Metabolomic analysis was performed on urine, serum, and stool samples at the baseline and study endpoint. In this study, 53 patients were randomized. Five (19.2%) patients in the AID and 8 (29.6%) patients in the CFG experienced a clinical relapse. The subclinical response to the intervention (defined as FCP < 150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02). The patients in the AID group had an increased intake of zinc, phosphorus, selenium, yogurt, and seafood versus the control group. Adherence to the AID was associated with significant changes in the metabolome, with decreased fecal acetone and xanthine levels along with increased fecal taurine and urinary carnosine and p-hydroxybenzoic acid levels. The AID subjects also had increases in fecal Bifidobacteriaceae, Lachnospiraceae, and Ruminococcaceae. In this study, we found thatdietary modifications involving the increased intake of anti-inflammatory foods combined with a decreased intake of pro-inflammatory foods were associated with metabolic and microbial changes in UC patients in clinical remission and were effective in preventing subclinical inflammation.

Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: an updated meta-analysis.

BACKGROUND AND AIM: Uncertainty remains about the best test to evaluate patients with obscure gastrointestinal bleeding (OGIB). Previous meta-analyses demonstrated similar diagnostic yields with capsule endoscopy (CE) and double balloon enteroscopy (DBE) but relied primarily on data from abstracts and were not limited to bleeding patients. Many studies have since been published. Therefore, we performed a new meta-analysis comparing CE and DBE focused specifically on OGIB. METHODS: A comprehensive literature search was performed of comparative studies using both CE and DBE in patients with OGIB. Data were extracted and analyzed to determine the weighted pooled diagnostic yields of each method and the odds ratio for the successful localization of a bleeding source. RESULTS: Ten eligible studies were identified. The pooled diagnostic yield for CE was 62% (95% confidence interval [CI] 47.3-76.1) and for DBE was 56% (95% CI 48.9-62.1), with an odds ratio for CE compared with DBE of 1.39 (95% CI 0.88-2.20; P = 0.16). Subgroup analysis demonstrated the yield for DBE performed after a previously positive CE was 75.0% (95% CI 60.1-90.0), with the odds ratio for successful diagnosis with DBE after a positive CE compared with DBE in all patients of 1.79 (95% CI 1.09-2.96; P = 0.02). In contrast, the yield for DBE after a previously negative CE was only 27.5% (95% CI 16.7-37.8). CONCLUSIONS: Capsule endoscopy and double balloon enteroscopy provide similar diagnostic yields in patients with OGIB. However, the diagnostic yield of DBE is significantly higher when performed in patients with a positive CE.

Systematic review of the quality of patient information on the internet regarding inflammatory bowel disease treatments.

BACKGROUND & AIMS: Patients use the Internet as a resource for information about their diseases. A systematic review evaluating the quality of information available for inflammatory bowel disease patients on the Internet regarding treatment options was performed. METHODS: Google was used to identify 50 websites on 3 occasions. A data quality score (DQS) (potential score, 0-76) was developed to evaluate the content of websites that scores patient information on indications, efficacy, and side effects of treatment. Other outcome measures were a 5-point global quality score, a drug category quality score, the DISCERN instrument, a reading grade level score, and information about integrity. RESULTS: The median DQS was 22, range 0-74, median global quality score was 2.0, and median Flesch-Kincaid reading grade level was 12.0, range 6.9-13.7. Eight websites achieved a global quality score of 4 or 5. The DQS was highly associated with the global quality score (r = 0.82) and the DISCERN instrument (r = 0.89). There was poor association between the DQS and the rank order in all 3 Google searches. Information on funding source (59%) and date of last update (74%) were often lacking. CONCLUSIONS: There is marked variation in the quality of available patient information on websites about the treatment options for Crohn's disease and ulcerative colitis. Few websites provided high quality information. There is a need for high quality accredited websites that provide patient-oriented information on treatment options, and these sites need to be updated regularly.