David A. Leiman

Survey of gastroenterologists' awareness and implementation of AGA guidelines on osteoporosis in inflammatory bowel disease patients: Are the guidelines being used and what are the barriers to their use?†

Background: The American Gastroenterology Association (AGA) published guidelines to assist clinicians in the evaluation and management of osteoporosis in inflammatory bowel disease (IBD) patients. Two studies suggest that when clinicians utilized the guidelines, the majority of their IBD patients were appropriately screened and treated for metabolic bone disease. The aim was to study whether physicians who say they use the AGA Guidelines are, in fact, following the recommendations, and to assess the barriers preventing the use of the guidelines in the management of osteoporosis in their IBD patients. Methods: In all, 1000 physicians were selected from the AGA membership list and mailed a survey inquiring into awareness and implementation of the guidelines on osteoporosis in IBD patients. The barriers to implementation of the guidelines were also assessed. The sum of 21 self‐reported clinical practices (absence = 0, presence = 1) was used to evaluate adherence to the guidelines. A value of 0 implied no adherence while a score of 21 meant complete adherence. Results: Of 304 responders, 27 fellows, 8 retirees, and 11 incomplete responses were not included in the analysis; thus, 258 respondents were the subject of this analysis. Slightly less than half of the responders used the guidelines in decision‐making (126, 49%) or in the management (110, 42%) of their IBD patients. Using the scoring system described above, clinicians self‐reporting use of the guidelines had a significantly higher clinical practice score than those who did not use the guidelines (Wilcoxon rank sum test; P < 0.0001). Only 18% (12 of 68) of clinicians whose practice was comprised of ≤25% IBD patients used the guidelines compared to 60% (113/187) physicians who cared for more IBD patients (chi‐square test; P < 0.0001). Physicians who saw more IBD patients (>25%) were also more likely (97/187 = 52%) to assess and treat osteoporosis in their IBD patients. Conversely, only 16% (11/68) of physicians who saw ≤25% IBD patients treated osteoporosis (chi‐square test; P < 0.0001). The main reason physicians (n = 115) gave for not utilizing the guidelines was because they felt that IBD should be the focus of the visit (48, 42%); 34 (30%) reported that osteoporosis should be managed by another physician. Other barriers cited were lack of time (13, 11%), cost (10, 9%), and lack of knowledge (10, 9%). Conclusions: Most of the responding physicians do not utilize the AGA Guidelines on metabolic bone disease in IBD patients. The physicians who self‐reported utilizing the guidelines were actually adhering to the recommendations. Further education regarding the impact of metabolic bone disease in IBD patients and the importance of the guidelines is needed, particularly as it addresses the barriers set forth above.

Public attitudes to the storage of blood left over from routine general practice tests and its use in research

Objective: There is increasing international interest in DNA biobanks but relatively little evidence concerning appropriate recruitment methods for these repositories of genetic information linked to patient-specific phenotypic data. To this end, our study aimed to investigate the attitudes of members of the public recruited through general practices to the donation and storage of blood left over from routine clinical tests in general practice. Methods: A questionnaire was mailed to 2600 individuals randomly selected from two general practice patient lists in Dundee, Scotland. Using a 7-point Likert scale, respondents rated their attitudes toward DNA biobanks in general, and procurement of blood samples specifically. Results: Overall, 841 (34%) of 2471 delivered questionnaires were returned. Compared with patients on the practice lists, respondents were older and more likely to be women. A majority of respondents (61%) were unequivocally positive about storing blood left over from routine tests. Despite general support for this collection method, when asked about open-ended consent, respondents expressed concern about future uses. Respondents’ increasing age and level of deprivation had significant adverse effects on attitudes towards making leftover routine biological samples available for research (P = 0.013 and P = 0.034, respectively). The study had three main limitations: there was a low response rate (34%) such that respondents were not entirely respresentative of the survey population; some respondents had difficulty with the questionnaire; and the study was somewhat underpowered for some comparisons. Conclusion: Despite its limitations, this first survey of a general practice population suggests that the majority would be willing to consider giving open-ended consent for the use of blood left over from routine clinical tests in general practice to be stored and used later for medical research.

Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction.

Helicobacter pylori infects half the worlds population, and carriage is lifelong without antibiotic therapy. Current regimens prescribed to prevent infection-associated diseases such as gastroduodenal ulcers and gastric cancer can be thwarted by antibiotic resistance. We reported that administration of 1% d,l-α-difluoromethylornithine (DFMO) to mice infected with H. pylori reduces gastritis and colonization, which we attributed to enhanced host immune response due to inhibition of macrophage ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Although no ODC has been identified in any H. pylori genome, we sought to determine if DFMO has direct effects on the bacterium. We found that DFMO significantly reduced the growth rate of H. pylori in a polyamine-independent manner. Two other Gram-negative pathogens possessing ODC, Escherichia coli and Citrobacter rodentium, were resistant to the DFMO effect. The effect of DFMO on H. pylori required continuous exposure to the drug and was reversible when removed, with recovery of growth rate in vitro and the ability to colonize mice. H. pylori exposed to DFMO were significantly shorter in length than those untreated and they contained greater internal levels of ATP, suggesting severe effects on bacterial metabolism. DFMO inhibited expression of the H. pylori virulence factor cytotoxin associated gene A, and its translocation and phosphorylation in gastric epithelial cells, which was associated with a reduction in interleukin-8 expression. These findings suggest that DFMO has effects on H. pylori that may contribute to its effectiveness in reducing gastritis and colonization and may be a useful addition to anti-H. pylori therapies.

Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis

In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some patients, especially those with nonerosive reflux disease or atypical GERD symptoms, acid-suppressive therapy with PPIs is not as successful. Alginates are medications that work through an alternative mechanism by displacing the postprandial gastric acid pocket. This study performed a systematic review and meta-analysis to examine the benefit of alginate-containing compounds in the treatment of patients with symptoms of GERD. PubMed/MEDLINE, Embase, and the Cochrane library electronic databases were searched through October 2015 for randomized controlled trials comparing alginate-containing compounds to placebo, antacids, histamine-2 receptor antagonists (H2RAs), or PPIs for the treatment of GERD symptoms. Additional studies were identified through a bibliography review. Non-English studies and those with pediatric patients were excluded. Meta-analyses were performed using random-effect models to calculate odds ratios (OR). Heterogeneity between studies was estimated using the I2 statistic. Analyses were stratified by type of comparator. The search strategy yielded 665 studies and 15 (2.3%) met inclusion criteria. Fourteen were included in the meta-analysis (N = 2095 subjects). Alginate-based therapies increased the odds of resolution of GERD symptoms when compared to placebo or antacids (OR: 4.42; 95% CI 2.45-7.97) with a moderate degree of heterogeneity between studies (I2 = 71%, P = .001). Compared to PPIs or H2RAs, alginates appear less effective but the pooled estimate was not statistically significant (OR: 0.58; 95% CI 0.27-1.22). Alginates are more effective than placebo or antacids for treating GERD symptoms.

Therapy of inflammatory bowel disease: what to expect in the next decade.

Purpose of review The increased understanding of the molecular mechanisms that are responsible for inflammatory bowel disease (IBD) has led to a wide range of potential therapeutic targets for this condition. Physicians treating individuals with Crohns disease and ulcerative colitis have a growing armamentarium of options to choose from in managing these patients. This article aims to summarize the relevant literature in the area of emerging therapy in IBD. Recent findings The widespread use of antitumor necrosis factor medications brought a landmark change in the treatment of IBD. More recently, several drugs have been shown to provide benefit in IBD in phase III studies by blocking other antiinflammatory pathways. The most likely new medications that will be available include vedolizumab for ulcerative colitis and ustekinumab for Crohns disease, which target cellular adhesion and inflammatory cell signaling, respectively. Other promising drugs focus on blockade of Janus kinase, inhibition of various chemokines, and biologic therapy such as hematopoietic stem cell transplants and mesenchymal cell infusions. Summary The growing understanding of the pathogenesis of IBD has led to new molecular targets for therapy. Over the next decade, the number of treatments available will grow, targeting cellular adhesion, protein regulation, inflammatory signal pathways, and immune tolerance.

US and Scottish Health Professionals' Attitudes toward DNA Biobanking

BACKGROUND The authors define a DNA biobank as a repository of genetic information correlated with patient medical records. DNA biobanks may assist in the research and identification of genetic factors influencing disease and drug interactions, but may raise ethical issues. How healthcare providers perceive DNA biobanks is unknown. OBJECTIVES To determine how useful healthcare professionals believe DNA biobanks will be and whether these attitudes differ between private and socialized healthcare systems. DESIGN The authors surveyed 200 healthcare professionals, including research and non-research focused doctors, nurses and other staff from medical centers and independent practice in both the United States and Scotland. The survey included fifteen items evaluated for general receptiveness toward biobanks, presumed usefulness of biobanks and perceived attitudes in recruiting patients for a biobank. MEASUREMENTS A total of 81 (45%) of 179 eligible participants responded: 41 from the U.S. and 40 from Scotland. Of these respondents, most (70%) were from academic centers. RESULTS Results indicate that there is a broadly favorable attitude in both locations toward the creation of a DNA biobank (83%) and its perceived benefit (75%). This enthusiasm is tempered in Scotland when respondents evaluated their comfort in consenting patients for entry into a biobank; 16 of 40 respondents (40%) were uncomfortable doing so, representing a significant difference from those in the U.S. (p=0.001). CONCLUSIONS Despite systematic differences in healthcare practice between the U.S. and Scotland, health care professionals in both nations believe DNA biobanks will be useful in curing disease. This finding appears to support further development of such a research tool.

Inflammatory Bowel Disease Patients’ Willingness to Accept Medication Risk to Avoid Future Disease Relapse

Objectives:Biomarkers, endoscopy and imaging tests can identify patients at increased risk for early recurrence of symptomatic inflammatory bowel disease (IBD). However, patients may be unwilling to accept additional medical therapy risks related to therapy escalation to avoid a future disease relapse. We sought to quantify IBD patients’ willingness to accept medication risk to avoid future disease relapse.Methods:We conducted a discrete-choice experiment among 202 patients with IBD who were offered choices of therapies with varying risks of lymphoma and infection, and varying time to next IBD relapse. Random parameters logit was used to estimate patients’ willingness to accept tradeoffs among treatment features in selecting medication therapy to avoid future disease relapse.Results:To avoid a disease relapse over the next 5 years, IBD patients were willing to accept an average of a 28% chance of a serious infection; and an average of 1.8% chance of developing lymphoma. These results did not significantly change when patients were offered 10 years until their next disease relapse, but were lower (11 and 0.7%, respectively) when offered 1.5 years until the next disease relapse. Patients with active disease symptoms were significantly less willing to accept medication risk for time in remission.Conclusions:IBD patients are willing to accept high levels of lymphoma and serious infection risk to maintain disease remission. These preferences are congruent with the treatment paradigms emphasizing mucosal healing and early aggressive therapy and highlight patients’ strong preferences for therapies resulting in durable remission of at least 5 years.

A Novel Electronic Medical Record–Based Workflow to Measure and Report Colonoscopy Quality Measures

When I was in private practice, pulling adenoma detection rates (ADRs) by physician was easy. In 2007, we developed a method to calculate ADRs, which was a bit cumbersome but effective, and we began tracking them by physician. We provided every partner with his or her ADR as part of a package of quarterly performance metrics. By 2009, we had incorporated endoscopy and pathology into our electronic medical record (EMR) so ADR analysis became automatic. This allowed us to begin publishing our results on our website and ultimately in peer-reviewed journals (Clin Gastroenterol Hepatol 2009;7:1335–1340 and Gastroenterology 2015;149:952–957). I then moved to an academic medical center where the enterprise-wide EMR (Epic) did not interface with either our endoscopy reporting software or pathology results, and all hope of routine ADR measurement vanished. Everyone working in similar situations can relate to my frustration. In this month’s Road Ahead column, Leiman and colleagues provide a straightforward method to extract ADRs from an Epic EMR. While this still requires physician input, it helps those of us in large health systems measure what is important in our ongoing efforts to reduce the incidence of colon cancer.

Glasgow Blatchford Score of limited benefit for low-risk urban patients: a mixed methods study

Background and study aims  Most patients with upper gastrointestinal bleeding (UGIB) are hospitalized. Risk-stratifying UGIB with scoring tools may decrease avoidable admissions, thereby reducing the cost of care. We sought to describe how frequently low-risk UGIB patients present to urban emergency departments (ED) and the proportion who are admitted to examine how incorporating risk scores into decision support might diminish healthcare utilization in this population. Patients and methods  This is a retrospective cohort study of ED patients presenting from 2009 – 2013 to three urban hospitals that do not use electronic UGIB decision support. We used ED disposition diagnosis codes (ICD-9) to identify patients followed by manual chart review for verification and additional data collection. Patients with a Glasgow Blatchford Score (GBS) of 0 were classified as low risk. We also surveyed ED physicians at these hospitals to assess their beliefs about UGIB decision support. Results  Over the study period, 66 patients (13.2 per year) presented to the ED with low-risk UGIB. Of these, 10 patients (15.2 %) were admitted and none required endoscopic hemostasis. Most survey respondents (55.6 %, n = 20) were aware of UGIB risk scores but a minority (19.4 %, n = 7) used one. Conclusions  Low-risk UGIB patients infrequently present to the ED and only a minority are admitted. Despite advocacy to incorporate decision support into routine clinical care, ED physicians independently identified low risk patients. There is insufficient evidence to suggest the magnitude of this problem is large enough to warrant implementation of decision support for low risk UGIB.

Weight Gain in Zollinger-Ellison Syndrome After Acid Suppression:

Objectives Zollinger-Ellison syndrome (ZES) is characterized by hypergastrinemia and gastric acid hypersecretion resulting in peptic ulcer disease, diarrhea, and weight loss. Acid secretion can be controlled with medication, and biochemical cure is possible with surgery. Data on how these interventions affect patients’ weight are lacking. We aimed to determine how medical and surgical acid control affects weight over time. Methods We performed a retrospective cohort study on 60 ZES patients. Acid control was achieved with appropriate-dose proton pump inhibitor (PPI) therapy. Surgery was performed for curative intent when appropriate. Weight change was assessed versus pre–acid control or immediate preoperative weights and expressed as absolute and percent change from baseline at 6, 12, 18, and 24 months. Results A total of 30 PPI-controlled patients and 20 surgery-controlled patients were analyzed. Weight gain was noted at all time points while on appropriate-dose PPI therapy (P < 0.005). Of patients who had surgery with curative intent, weight gain was noted at 12 months (7.9%, P = 0.013) and 18 months (7.1%, P = 0.007). There was a trend toward weight gain seen at all time points in the patients who were surgically cured. Conclusions These data represent a novel description of weight gain after acid suppression in ZES.