Ahmad Malli

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.

Prediction of celiac disease at endoscopy

BACKGROUND AND STUDY AIMS Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

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.

Association of Streptococcus bovis endocarditis and advanced colorectal neoplasia: a case-control study.

To study the association between Streptococcus bovis (S. bovis) endocarditis and advanced colorectal neoplasia.

Opposing effects of aspirin and anticoagulants on morbidity and mortality in patients with upper gastrointestinal bleeding

We aimed to determine the effect of antithrombotics on in‐hospital mortality and morbidity in patients with peptic ulcer disease‐related upper gastrointestinal bleeding (PUD‐related UGIB).

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.

Homozygosity for Non-H1069Q Missense Mutations in ATP7B Gene and Early Severe Liver Disease: Report of Two Families and a Meta-analysis

Most patients with Wilsons disease (WD) are compound heterozygote, which complicates establishing genotype-phenotype correlations. We identified five patients who presented with early and/or severe hepatic disease who are homozygous for W939C missense mutation on exon 12 of ATP7B. We therefore conducted a meta-analysis to determine the phenotype of patients homozygous for missense or nonsense mutations in all ATP7B exons.The meta-analysis showed that 69% and 31% of patients are homozygous for H1069Q and non-H1069Q mutations, respectively. Compared to patients with H1069Q, those with non-H1069Q mutations were significantly more likely to have a hepatic phenotype, severe liver disease, a mixed phenotype, and less likely to have a neurologic phenotype. Compared to patients with nonsense mutations, those with non-H1069Q ones were equally likely to present with a hepatic phenotype and to have severe liver disease. Mean age at symptom onset in the non-H1069Q versus the H1069Q group was 15.5 versus 20.5years (p<0.001).Our data suggest that mutation W939C and other non-H1069Q missense mutations are associated with early disease onset, a hepatic phenotype, and a high risk of hepatic failure in homozygous patients. Early identification of such patients by genetic screening is important for timely initiation of treatment and prevention of complications.

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.