Jean M. Chalhoub

Role of vitamins in gastrointestinal diseases

A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available.

Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort.

BACKGROUND & AIMS Chronic intake of proton pump inhibitors (PPI) has been associated with hypomagnesemia, but prevalence of PPI-associated hypomagnesemia is not known. METHODS We examined the prevalence of hypomagnesemia among long-term PPI recipients by using a large health maintenance organization database. We collected data on 10,167 participants eligible for chronic drug prescriptions from 2008 through 2013. Adult subjects receiving continuous PPI therapy for ≥ 6 months between 2008 and 2013 and ≥ 1 serum magnesium determination(s) were identified. Patients with any magnesium levels less than 1.6 mg/dL were selected for analysis; those with recognizable causes of altered magnesium homeostasis were excluded. RESULTS Five hundred ninety participants received long-term PPIs, and 414 (70.2%) met the inclusion criteria for a total exposure of 2293 PPI-years (average, 5.7 years/subject). Of these patients, 57 (13.8%) had ≥ 1 low serum magnesium; 5 were no longer on PPIs, and 44 had other recognizable causes for hypomagnesemia (25 receiving diuretics, 8 with chronic diarrhea, 8 with chronic kidney disease, and 3 with malignancies). Of the 8 remaining patients (7 female; mean age, 71.2 ± 13.4 years; mean daily medications, 5.4 ± 1.1), mild hypomagnesemia (range, 1.2-1.5 mg/dL) was noted in 13.9% of 289 measurements. All 8 patients had normal serum levels of magnesium at their final measurement. CONCLUSIONS In the absence of known precipitating factors, chronic PPI use does not appear to be associated with hypomagnesemia.

A Customized Mobile Application in Colonoscopy Preparation: A Randomized Controlled Trial

OBJECTIVES: Adherence with diet and prescribed purgative is essential for proper cleansing with low‐volume bowel preparations. The aim of this work was to assess the effect of a customized mobile application (App) on adherence and quality of bowel preparation. METHODS: One hundred and sixty (160) eligible patients scheduled for elective colonoscopy were randomly assigned to paper (control) or App‐based instructions. The preparation consisted of low‐fiber diet for 2 days, clear fluids for one day and split‐dose sodium picosulfate/magnesium citrate (SPS). Before colonoscopy, information was collected regarding adherence with, and utility of the provided instructions. The colonoscopists, blinded to assignment, graded bowel preparation using the Aronchick, Ottawa, and Chicago preparation scales. The primary endpoint was adherence with instructions. Quality of preparation was a secondary endpoint. RESULTS: No difference in overall adherence or bowel cleanliness was observed between the study arms. Adherence was reported in 82.4% of App vs. 73.4% of controls (P=0.40). An adequate bowel preparation on the Aronchick scale was noted in 77.2 vs. 82.5%, respectively (P=0.68). Mean scores on the Ottawa and Chicago scales were also similar. Gender, age, time of colonoscopy, and BMI did not influence preparation or adherence. Compliance with the clear fluid diet component was noted in 94% of patients with BMI<30 vs. 77% with BMI≥30 (P<0.01). SPS was well tolerated by 81.9% of patients. The App was user‐friendly and received higher overall rating in this respect than paper instructions (P<0.01). CONCLUSIONS: SPS is well tolerated and effective for bowel cleansing regardless of instruction method. Customized smartphone applications are effective, well‐accepted and could replace standard paper instructions for bowel preparation. ClinicalTrials.gov: NCT02410720

The burden of bowel preparations in patients undergoing elective colonoscopy

Background An adequate bowel preparation is an important quality measure for optimal colonoscopy. Aims The aim of this article is to study the burden of bowel preparations by examining seven specific variables (hunger, taste, volume, sleep, social, work, and adverse events (AEs)). Methods Ambulatory patients undergoing elective colonoscopy completed a questionnaire regarding their experience with the prescribed preparation. The seven study variables were graded using a numerical scale of 0–10 (best to worst). A score >6 was considered to indicate a significant impact and used as primary outcome. Patients were also asked to grade in descending order what they perceived as the worst aspect of the preparation. Results A total of 216 patients completed the survey. Preparations consisted of split-dose sodium picosulfate (SPS) (n = 49), split-dose 4 l PEG ± menthol (n = 49), full-dose PEG (n = 68), and 2 l split-dose PEG + ascorbic acid (n = 50). Except for work and AEs, all variables were considered to have a negative impact by >20% of patients (range 20.4–34.2). SPS was superior to PEG regimens in taste (4.1% vs. 35.9%) and volume (0% vs. 44.9%) (p < 0.05 for both) but inferior for hunger (30.6% vs. 19.2%; p = 0.09). The addition of menthol to PEG significantly improved taste (22.4% vs. 41.5%; p = 0.02). Sleep disturbances were most common with SPS and least with split-dose PEG (30.6% vs. 17.4%; p < 0.05). Overall, patients ranked volume, taste, and hunger as most burdensome. Conclusions The burden of bowel preparation is substantial. An informed personalized choice of preparation may improve adherence, tolerability and colon cleansing.

Split-dose menthol-enhanced PEG vs PEG-ascorbic acid for colonoscopy preparation.

AIM To compare the efficacy and palatability of 4 L polyethylene glycol electrolyte (PEG) plus sugar-free menthol candy (PEG + M) vs reduced-volume 2 L ascorbic acid-supplemented PEG (AscPEG). METHODS In a randomized controlled trial setting, ambulatory patients scheduled for elective colonoscopy were prospectively enrolled. Patients were randomized to receive either PEG + M or AscPEG, both split-dosed with minimal dietary restriction. Palatability was assessed on a linear scale of 1 to 5 (1 = disgusting; 5 = tasty). Quality of preparation was scored by assignment-blinded endoscopists using the modified Aronchick and Ottawa scales. The main outcomes were the palatability and efficacy of the preparation. Secondary outcomes included patient willingness to retake the same preparation again in the future and completion of the prescribed preparation. RESULTS Overall, 200 patients were enrolled (100 patients per arm). PEG + M was more palatable than AscPEG (76% vs 62%, P = 0.03). Completing the preparation was not different between study groups (91% PEG + M vs 86% AscPEG, P = 0.38) but more patients were willing to retake PEG + M (54% vs 40% respectively, P = 0.047). There was no significant difference between PEG + M vs AscPEG in adequate cleansing on both the modified Aronchick (82% vs 77%, P = 0.31) and the Ottawa scale (85% vs 74%, P = 0.054). However, PEG + M was superior in the left colon on the Ottawa subsegmental score (score 0-2: 94% for PEG + M vs 81% for AscPEG, P = 0.005) and received significantly more excellent ratings than AscPEG on the modified Aronchick scale (61% vs 43%, P = 0.009). Both preparations performed less well in afternoon vs morning examinations (inadequate: 29% vs 15.2%, P = 0.02). CONCLUSION 4 L PEG plus menthol has better palatability and acceptability than 2 L ascorbic acid- PEG and is associated with a higher rate of excellent preparations; Clinicaltrial.gov identifier: NCT01788709.

Systematic Review and Meta-analysis: Adalimumab Monotherapy Versus Combination Therapy with Immunomodulators for Induction and Maintenance of Remission and Response in Patients with Crohn's Disease

Background: It is unclear whether the combination of adalimumab (ADA) and immunomodulators is superior to ADA monotherapy in patients with Crohns disease. Methods: PubMed, Medline, Embase, Web of Science, and other databases were searched. Randomized controlled trials, open-label, prospective cohort, and retrospective studies, and pooled analyses were included. Primary outcomes were induction (⩽12 wk) and maintenance (up to 56 wk) of remission and response. Secondary outcomes were severe adverse events, opportunistic infections, and development of antibodies to adalimumab. Results: Twenty-four of 1194 articles were eligible for inclusion. No significant difference was noted between regimens for induction of remission (odds ratio [OR] 0.86; 95% confidence interval [CI]: 0.70–1.06; P = 0.19) and response (OR 1.01; 95% CI: 0.62–1.65; P = 0.96). Similarly, no difference was noted for maintenance of remission (OR 0.97; 95% CI: 0.79–1.14; P = 0.75) or response (OR 0.91; 95% CI: 0.54–1.54; P = 0.74). Severe adverse events and opportunistic infections were not different between arms. Patients on combination therapy had lower odds of developing antibodies to adalimumab (OR 0.24; 95% CI: 0.07–0.82; P = 0.02). Subgroup and sensitivity analyses showed significantly higher odds of successful induction (OR 1.26; 95% CI: 1.06–1.49, P = 0.008) and opportunistic infections (OR 2.44; 95% CI: 1.07–5.54, P = 0.03) in anti-TNF–experienced patients. Conclusions: The combination of ADA and immunomodulators does not seem superior to ADA monotherapy for induction and maintenance of remission and response in Crohns disease. Combination therapy is associated with lower immunogenicity. Analyses associating combination therapy with better induction of remission in anti-TNF–experienced patients and a higher rate of opportunistic infections deserve further evaluation.

Body mass index and quality of bowel preparation: Real life vs. clinical trials

BACKGROUND AND STUDY AIMS Obesity is a recognised risk factor for poor bowel preparation in retrospective studies whilst corresponding data in prospective trials are marginally reported. Aims are to evaluate the relation between body mass index (BMI) and preparation quality in retrospective and interventional prospective settings and within a single centre. PATIENTS AND METHODS Data from a recent colorectal cancer screening registry were retrospectively analysed for the relation between BMI and adequacy of preparation. Patients were categorised as underweight (BMI<20kg/m(2)), normal (20-25kg/m(2)), overweight (25-30kg/m(2)), and obese (>30kg/m(2)). Data from a recent prospective colon preparation trial were similarly analysed. RESULTS 541 registry patients were included. Multivariate analysis showed BMI to be an independent risk factor for inadequate preparation. Obesity was associated with odds ratio (OR) of 5.3 [95% confidence interval (CI) 1.4-19.8; p=0.01] compared to normal BMI. A significant difference was also noted in underweight but otherwise healthy individuals (OR=11.1, 95% CI 2-60; p=0.005). In the prospective study of 195 patients, obese patients had comparable rates of inadequate preparation to normal-weight individuals (OR=0.7, 95% CI 1.1-3.96; p=0.68). Underweight patients had a significantly worse preparation compared to normal BMI individuals (OR=8, 95% CI 1.1-58; p=0.04). CONCLUSIONS In real life, bowel preparations in obese individuals have a lower quality in comparison to normal individuals. This finding is not replicated in clinical trials. This discrepancy is likely the result of focused patient education suggesting that this is primarily a dietary compliance phenomenon. Underweight individuals appear to have worse quality of preparation independent of study design or setting.

Sensory characterization of bowel cleansing solutions

AIM To evaluate the sensory characteristics of commercial bowel cleansing preparations. METHODS Samples of 4 commercially available bowel cleansing preparations, namely polyethylene glycol electrolyte solution (PEG), PEG + ascorbic acid (PEG-Asc), sodium picosulfate (SPS), and oral sodium sulfate (OSS) were prepared according to the manufacturers instructions. Descriptive analysis was conducted (n = 14) using a 15-cm line scale with the Compusense at-hand(®) sensory evaluation software. Acceptability testing (n = 80) was conducted using the 9-point hedonic scale. In addition, a Just-About-Right (JAR) scale was included for the four basic tastes to determine their intensity compatibility with acceptability levels in the products. RESULTS Samples were significantly different, in descriptive analysis, for all attributes (P < 0.05) except for sweetness. SPS received the highest ratings for turbidity, viscosity appearance, orange odor and orange flavor; PEG-Asc for citrus odor and citrus flavor; OSS for sweetener taste, sweet aftertaste, bitterness, astringency, mouthcoating, bitter aftertaste and throatburn, and along with PEG-Asc, the highest ratings for saltiness, sourness and adhesiveness. Acceptability results showed significant differences between the various samples (P < 0.05). SPS received significantly higher ratings for overall acceptability, acceptability of taste, odor and mouthfeel (P < 0.05). JAR ratings showed that PEG and PEG-Asc were perceived as slightly too salty; SPS and OSS were slightly too sweet, while SPS, PEG-Asc and OSS were slightly too sour and OSS slightly too bitter. While using small sample volumes was necessary to avoid unwanted purgative effects, acceptability ratings do not reflect the true effect of large volumes intake thus limiting the generalization of the results. CONCLUSION Further improvements are needed to enhance the sensory profile and to optimize the acceptability for better compliance with these bowel cleansing solutions.

Prevalence of Barrett's esophagus in Lebanon

BACKGROUND/AIMS To determine the prevalence of Barretts Esophagus (BE) in a tertiary care center in Lebanon and to compare IT with regional and global data. MATERIALS AND METHODS All esophagogastroduodenoscopies (EGDs) performed between January 2003 and October 2013 at the American University of Beirut Medical Center (AUBMC) were reviewed, and cases of endoscopically suspected esophageal metaplasia (ESEM) were identified. Definite BE was considered only if histologically proven intestinal metaplasia was present. RESULTS Totally, 16,787 patients underwent EGD; 219 patients (1.3%) were labeled as having ESEM. Only 41 patients had biopsyproven BE (18.7% of ESEM and 0.24% of total patients). The mean age of the patients with BE was 58.1 years [Standard deviation (SD) =13.7] and 78% were men. Of the 41 patients, 14 (34.1%) had long-segment BE (LSBE) (>3 cm) while 27 had short segment Barretts Esophagus (SSBE) (≤3 cm). Hiatal hernia was identified in 54% of the patients, more commonly in those with LSBE. Only four patients had low-grade dysplasia, and none had high-grade dysplasia. CONCLUSION The prevalence of BE in Lebanon is much lower than that in Western countries. The reasons for this East-West divide are unknown and require further investigation.

Letter: clarithromycin dose for H. pylori therapy remains unresolved – authors’ reply

diagnostic testing, and for BioGaia regarding use of probiotics for H. pylori infections. Dr Graham has received royalties from Baylor College of Medicine patents covering materials related to C-urea breath test. Dr Gisbert declares associations with the following companies: Amirall, Astrazeneca, Janssen–Cilag and Nycomed. Declaration of funding interests: Dr Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grants DK067366 and DK56338, which funds the Texas Medical Center Digestive Diseases Center. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH.