Nabil M. Mansour

Alcohol consumption is a risk factor for colonic diverticulosis.

Background and Aim: The exact factors predisposing to colonic diverticulosis other than age are unknown. Methods: Cross-sectional study of asymptomatic subjects undergoing screening colonoscopy. A detailed dietary and social questionnaire was completed on all participants. A worldwide review of the literature was performed to further investigate any association between identified risk factors and diverticulosis. Results: Seven hundred forty-six consecutive individuals were enrolled (mean age, 61.1±8.3 y; female: male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5-36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and 22.7% of affected subjects, respectively. On univariate analysis, age, sex, adenomatous polyps, advanced neoplasia (adenoma≥1 cm, villous histology, or cancer), aspirin, and alcohol use were significantly associated with diverticulosis. Diet, body mass index, physical activity, and bowel habits were not associated with the disease. On multivariate analysis, increasing age (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were significantly associated with diverticulosis. The adjusted odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing prevalence with higher alcohol consumption (P-value for trend=0.001). When the prevalence of diverticulosis reported from 18 countries was analyzed against alcohol use, there was a strong correlation with national per-capita alcohol consumption rates (Pearson correlation coefficient r=0.68; P=0.002). Conclusions: Alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing East-West paradox in disease prevalence and phenotype. Further studies are needed to investigate this association and its putative pathophysiological mechanisms.

Proton pump inhibitors have no measurable effect on calcium and bone metabolism in healthy young males: A prospective matched controlled study

OBJECTIVES Proton pump inhibitors (PPIs) are associated with an increased risk of bone fractures. This study sought to evaluate the effect of PPIs on biochemical markers of calcium and bone metabolism. METHODS Prospective matched controlled study involving healthy adult males (age 18-50years) suffering from frequent heartburn. Patients received standard-dose PPI for 12weeks and were matched by age with healthy controls. Blood studies were taken at 0, 1 and 3months for biochemical markers of mineral and bone metabolism. Two-way (time and PPI treatment) repeated measures analysis of variance (RM-ANOVA) and multiple linear regression were used for analysis. RESULTS A total of 58 participants (29 per group) completed the study. Mean age of participants was 33.2±7.5years. Baseline characteristics and biomarkers were similar for both groups except for higher BMI (28.6 vs. 25.6kg/m(2), p=0.008) and serum C-terminal cross linked telopeptides of type I collagen [CrossLaps, (300 vs. 228pg/ml, p=0.028)] in the PPI group. There was no difference in parathormone (PTH), ionized calcium, vitamin D, osteocalcin and CrossLaps between the PPI and control subjects (all non-significant; 2-way RM-ANOVA). Multiple linear regression modeling showed no effect of PPIs on any of the studied calcium or bone metabolism biomarkers. CONCLUSION PPI intake for 12weeks has no measurable effect on calcium or bone metabolism in healthy young males.

Persistent snoring under conscious sedation during colonoscopy is a predictor of obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) is characterized by cessation of breathing during sleep. Conscious sedation (CS) induces sleep and may uncover sleep-related breathing disorders. OBJECTIVE To determine whether snoring during CS is a sensitive predictor of OSA. DESIGN Matched cohort study. SETTING University-based ambulatory endoscopy center. PATIENTS Consecutive patients undergoing colonoscopy completed a detailed sleep questionnaire and physical examination geared toward detecting OSA (body mass index [BMI], neck circumference, and the presence of craniofacial abnormalities). The endoscopist was blinded to the information. INTERVENTIONS Portable nocturnal polysomnography. MAIN OUTCOME MEASUREMENTS Patients who snored during CS in the left lateral decubitus position for 10 seconds or longer were referred for polysomnography. Sex- and BMI-matched patients who did not snore served as control subjects. RESULTS A total of 131 patients were enrolled, and 24 (18.3%) of them snored. These patients (22 men, 2 women) had a predominance of Mallampati grade III/IV, higher Stanford and Epworth scale scores, and greater BMI and neck circumference and were more likely to report daytime sleepiness, decreased vigilance, and personality and mood changes (all P values <.05). All investigated patients who snored during CS had evidence of OSA versus 4 of 18 control subjects (mean apnea-hypopnea index: 40 events vs 5 events; P < .0001) (100% positive predictive value; 77.8% negative predictive value). Moderate or severe OSA was detected in 14 of 20 patients versus 1 of 18 control subjects (P < .001; 70% positive predictive value; 94.4% negative predictive value, 93% sensitivity, 74% specificity). Data obtained from sleep questionnaires and physical examination failed to accurately predict OSA. LIMITATIONS Single-center nature and relatively small number of patients developing the outcome variable. CONCLUSIONS Snoring during CS is a strong predictor of OSA. Given the medical and financial burden of undiagnosed OSA, these patients should be carefully identified and referred for sleep medication evaluation.

Duration of Pain Is Correlated With Elevation in Liver Function Tests in Patients With Symptomatic Choledocholithiasis

BACKGROUND & AIMS We assessed the temporal relationship between abdominal pain and elevation in liver function tests (LFTs) in patients with acute symptomatic choledocholithiasis. METHODS Retrospective study of patients that presented within 12 hours of pain onset and were subsequently found to have choledocholithiasis. RESULTS We identified 40 patients with complete medical records. Levels of aspartate and alanine aminotransferases (AST and ALT) correlated with duration of pain (Pearson correlation, r = 0.633 and 0.622 respectively, P < .001 for both); the correlation was not as strong for γ-glutamyl transpeptidase (GGT) (r = 0.326, P = .046) and was not significant for alkaline phosphatase or bilirubin. This temporal association was stronger in patients that had undergone cholecystectomy versus those with intact gallbladders (for ALT, r = 0.603 vs r = 0.311, respectively). Eighteen patients, evaluated within 6 hours of pain, had normal or minimal alterations in LFTs; transabdominal ultrasound was abnormal in 6 (sensitivity 33.3%). All had repeat LFTs within 24 hours (mean 10.3 ± 6.9 hours later) and large increases in ALT and aspartate aminotransferase levels (mean 10.5- and 6.8-fold respectively; P < .01 for both), intermediate increases in glutamyl transpeptidase levels, (mean 4-fold, P < .05), and no changes in alkaline phosphatase levels. This significant increase in LFTs was the only indication of biliary pathology before endoscopy in 11/18 patients. CONCLUSIONS Increasing duration of pain is associated with increasing LFTs (particularly transaminases) in patients with acute symptomatic choledocholithiasis. Patients with normal LFTs and ultrasound upon presentation should have repeat LFTs if biliary pain is suspected. The absence of significant biochemical abnormalities within the first 24 hours makes the diagnosis of symptomatic choledocholithiasis unlikely.

A Prospective Randomized Trial of Mosapride vs. Placebo in Constipation-Predominant Irritable Bowel Syndrome

To the Editor: Irritable bowel syndrome (IBS) is a common disorder affecting ~5% of adults and comprising 28% of gastroenterology practice (1,2). Treatment of IBS remains a challenge because of its poorly defined pathophysiology, high placebo response, and variable symptomatology (3). Mosapride citrate, a selective partial 5–HT4 receptor agonist, which enhances gastrointestinal motility after accelerating the release of acetylcholine from nerves in the gastrointestinal tract (4), has been shown to accelerate colonic motility in animals (5). A small Japanese study (6) involving 11 patients with constipation-predominant IBS (C-IBS) showed that mosapride reduced abdominal pain and distention, decreased flatus, shortened bowel transit time, and produced looser stools, suggesting that mosapride may be useful in C-IBS.

Challenging the dogma: a randomized trial of standard vs. half-dose concomitant nonbismuth quadruple therapy for Helicobacter pylori infection

Background Current treatment of Helicobacter pylori consists of three or four drugs for 7–14 days with important associated cost and adverse events. Aims This study compared efficacy and safety of standard dose vs. half-dose concomitant nonbismuth quadruple therapy (NBQT) for 7 days. The standard dose consisted of twice daily rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg. Methods This was a prospective randomized trial. 14C-urea breath test was performed ≥4 weeks after treatment and ≥2 weeks off acid suppressive therapy. Compliance and adverse events were monitored during treatment. Results A total of 200 consecutive treatment-naïve patients were enrolled. Baseline characteristics were similar between groups, with 15.5% of subjects reporting prior macrolide use. Eradication occurred in 78% (95% CI 68.6–85.7%) in both groups on intention-to-treat analysis. Per-protocol rates were 82.1 vs. 83.9% for standard-dose patients vs. half-dose patients, respectively (p = NS). Adverse events (only mild) were reported in 57 vs. 41% of standard-dose patients vs. half-dose patients (p = 0.024), with metallic taste and nausea notably less frequent in the latter (36 vs. 12% and 18 vs. 7%, respectively; p < 0.05 for both). Overall, eradication failed in 38.7% of prior macrolide users vs. 18.9% without such exposure (p = 0.019). On multivariate logistic regression, prior macrolide exposure was the only factor associated with failed eradication (OR 2.60, 95% CI 1.06–6.39; p = 0.038). Treatment was cheaper with the half-dose regimen. Interpretation A 50% reduction in antibiotic dosage does not diminish efficacy of concomitant nonbismuth quadruple therapy but leads to significant reduction in cost and adverse events. Seven-day concomitant NBQT is suboptimal for H. pylori independent of prior macrolide exposure.

CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel.

Abstract: The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7% ± 21.9% in the C group, 19.1% ± 20.9% in the CR group, and 24.5% ± 22.9% in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI >50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

A randomized trial of standard-dose versus half-dose rabeprazole, clarithromycin, and amoxicillin in the treatment of Helicobacter pylori infection.

Objectives To evaluate the efficacy and safety of a standard-dose versus half-dose 10-day triple regimen for the eradication of Helicobacter pylori infection. Methods A total of 115 consecutive patients with documented infection were enrolled in this open-label trial. Group A (standard dose) received rabeprazole (20 mg), amoxicillin (1 g), and clarithromycin (500 mg), all twice daily for 10 days. Group B (half dose) received rabeprazole (10 mg), amoxicillin (500 mg), and clarithromycin (250 mg), all twice daily for 10 days. 14C urea breath tests were performed a minimum of 4 weeks after treatment and a minimum of 2 weeks off any acid-suppressive therapy. Compliance and adverse effects were evaluated throughout the treatment period. Results A total of 115 patients were enrolled (59 women and 56 men; mean age 47.1±14.0 years). Eradication occurred in 45 of 58 patients [77.6%; 95% confidence interval (CI): 66.9–88.3%] in the standard-dose group versus 44 of 57 in the half-dose group (77.2%; 95% CI: 66.3–88.1%) on an intent-to-treat (ITT) analysis (P=1.00). Per protocol eradication rates were 45 of 57 (78.9%; 95% CI: 68.4–85.9%) and 44 of 54 (81.5%; 95% CI: 71.1–91.8%), respectively (P=0.81). The number of patients reporting any adverse effect was significantly higher in the standard-dose group (64.9 vs. 40.4%; P=0.014). The cost of treatment was significantly less in patients receiving the half-dose regimen (ITT analysis; P<0.05). The number needed to harm to suffer one additional failure in the half-dose over the standard-dose arm was 250 (ITT analysis). Conclusion A half-dose 10-day regimen of rabeprazole, amoxicillin, and clarithromycin is equally effective but cheaper and better tolerated than its standard-dose regimen in the treatment of Helicobacter pylori. Eradication rates of both regimens are, however, suboptimal compared with accepted standards.

Prophylaxis with Ertapenem in Patients with Obstructive Jaundice Undergoing Endoscopic Retrograde Cholangiopancreatography: Safety, Efficacy, and Biliary Penetration

Background: Cholangitis and biliary sepsis are rare but serious complications of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study is to investigate the safety, efficacy, and biliary penetration of ertapenem, a newer carbapenem with a long half-life and broad-spectrum antimicrobial activity, for ERCP prophylaxis. Methods: Patients with obstructive jaundice without cholangitis received a single dose of ertapenem equal to 1 gram intravenously prior to ERCP. A 2–3 mL bile sample was collected after cannulation and prior to contrast injection. Patients were observed for 72 hours for cholangitis or drug-related adverse events. Biliary ertapenem levels were measured using high-performance liquid chromatography (HPLC). Results: Twenty-eight patients (ages 18–87 years, M/F ratio 1:1) were enrolled. Seven had no cholestasis and were included to study ertapenem penetration in unobstructed biliary trees. Cannulation was achieved in all patients. One patient (3.6%) with persistent intrahepatic stones developed cholangitis. No drug-related adverse events were noted. The mean time from ertapenem administration to bile collection was 60 ± 24 minutes. There was a significant negative correlation between serum bilirubin and biliary ertapenem levels (r = −0.542, P = 0.003) with the highest level (6.25 &mgr;g/mL) noted in unobstructed biliary systems. Conclusion: Ertapenem appears to be a safe and effective prophylaxis in patients with obstructive jaundice undergoing ERCP despite a limited biliary penetration in patients with high-grade obstruction.

Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.