Jana G. Hashash

A randomized, controlled, double-blind trial of the adjunct use of tegaserod in whole-dose or split-dose polyethylene glycol electrolyte solution for colonoscopy preparation

BACKGROUND Problems of compliance, quality, and safety of colon preparation regimens have prompted continued investigation with alternative forms of cleansing. OBJECTIVE To evaluate the efficacy of tegaserod as an adjunct to a polyethylene glycol electrolyte solution (PEG-E), given as a whole dose or split dose, in colonoscopy preparation. DESIGN Randomized, placebo-controlled, double-blind trial. SETTING A single university-based hospital. PATIENTS Patients who were undergoing elective colonoscopy. INTERVENTIONS A 4-arm randomization scheme that compared tegaserod with a placebo, each with whole-dose or split-dose PEG-E preparation. MAIN OUTCOME MEASUREMENTS Efficacy of colon cleansing was the primary outcome. Secondary outcomes included adherence, tolerability, adverse effects, and patient perceptions of their preparation quality. RESULTS A total of 382 patients completed the trial. Patients who received the split-dose preparation had significantly better colon cleansing than those who received the whole-dose preparation (88.9% vs 42.6%, P < .001). The addition of tegaserod did not significantly improve the overall colonoscopy preparation quality compared with a placebo. However, there were fewer poor preparations in the whole-dose PEG-E group (12.4% vs 1.1%, P = .002, Bonferroni correction removes significance) and more excellent preparations in the split-dose group (53.3% vs 38.3%, P = .035, Bonferroni correction removes significance) in favor of tegaserod. Interobserver and intraobserver variability analysis showed substantial agreement among endoscopists. Adherence was significantly lower in the whole-dose group versus the split-dose PEG-E group (68.8% vs 91%, P < .001), independent of the use of tegaserod. Adverse effects were not different between study groups. LIMITATIONS A 4-arm randomization and the single-center nature of the study. CONCLUSIONS Tegaserod has a marginal effect on the quality of colonoscopy preparation when used as an adjuvant to PEG-E. The split-dose PEG-E was superior to the whole-dose PEG-E and resulted in better colon cleansing, adherence, and tolerance.

The role of rifaximin in the primary prophylaxis of spontaneous bacterial peritonitis in patients with liver cirrhosis.

Background: Primary prophylaxis of spontaneous bacterial peritonitis (SBP) may provide a survival advantage in cirrhotic patients with ascites and has become an integral part of clinical practice. Rifaximin is a poorly absorbable antibiotic with a broad spectrum of antibacterial action and has low risk of introducing bacterial resistance. Aim: To determine whether rifaximin is associated with decreasing the risk of SBP and improving transplant-free survival in cirrhotic patients with ascites. Methods: The medical records of all adult patients with liver cirrhosis and large ascites justifying paracentesis evaluated in our clinic (2003 to 2007) were reviewed. Patients were stratified into 2 groups by the use of rifaximin. Patients were excluded if they had received another antibiotic for SBP prophylaxis or had a history of SBP before rifaximin therapy. Results: A total of 404 patients were included, of whom 49 (12%) received rifaximin. The rifaximin and nonrifaximin groups were comparable with regards to age, sex, and race. The median follow-up time was 4.2 [1.0, 17.1] months. During this time period, 89% of patients on rifaximin remained SBP free compared with 68% of those not on rifaximin (P=0.002). After adjusting for Model of End-Stage Liver Disease score, Child-Pugh score, serum sodium, and ascitic fluid total protein, there was a 72% reduction in the rate of SBP in the rifaximin group (hazard ratio=0.28; 95% confidence interval, 0.11-0.71; P=0.007). The group treated with rifaximin also demonstrated a transplant-free survival benefit compared with those not on rifaximin (72% vs. 57%, P=0.045). Conclusions: Intestinal decontamination with rifaximin may prevent SBP in cirrhotic patients with ascites. Prospective randomized controlled trials are needed to confirm this finding.

Late Perforation by Cardiac Implantable Electronic Device Leads: Clinical Presentation, Diagnostic Clues, and Management

Late intracardiac lead perforation is defined as migration and perforation of an implanted lead after 1 month of cardiac electronic device implantation. It is an under‐recognized complication with significant morbidity and mortality, particularly if not recognized early. Two patients with late perforation caused by passive‐fixation leads are reported and the clinical features of their presentation and management are reviewed. We conducted a thorough review of the available English language literature pertaining to this complication to draw relevant conclusions regarding presentation, diagnosis, and management. Early recognition of this complication is important as the indications for and numbers of patients who receive cardiac implantable electronic devices continue to expand. Copyright

Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study.

OBJECTIVES:Emerging data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). Prospective data evaluating the association of vitamin D serum status and disease course are lacking. We sought to determine the relationship between vitamin D status and clinical course of IBD over a multiyear time period.METHODS:IBD patients with up to 5-year follow-up from a longitudinal IBD natural history registry were included. Patients were categorized according to their mean serum 25-OH vitamin D level. IBD clinical status was approximated with patterns of medication use, health-care utilization, biochemical markers of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), pain and clinical disease activity scores, and health-related quality of life.RESULTS:A total of 965 IBD patients (61.9% Crohn’s disease, 38.1% ulcerative colitis) formed the study population (mean age 44 years, 52.3% female). Among them, 29.9% had low mean vitamin D levels. Over the 5-year study period, subjects with low mean vitamin D required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions, and surgery compared with subjects with normal mean vitamin D levels (P<0.05). Moreover, subjects with low vitamin D levels had worse pain, disease activity scores, and quality of life (P<0.05). Finally, subjects who received vitamin D supplements had a significant reduction in their health-care utilization.CONCLUSIONS:Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.

Gastrointestinal bleeding in the setting of anticoagulation and antiplatelet therapy.

Goal To review the literature on the significance, risk factors, and management of occult and gross gastrointestinal (GI) bleeding in patients on antiplatelets and/or anticoagulants. Study Relevant original and review articles and their bibliographies were analyzed. Estimates of risks and therapeutic outcomes were obtained from randomized trials, whereas risk factor identification was gathered from cross-control and prospective cohort studies. Results Antiplatelets and anticoagulants do not diminish the positive predictive value of fecal occult blood testing to find GI pathology. They increase the risk of gross GI bleeding, and predictors of hemorrhage include history of GI bleeding or ulcer disease, higher intensity of anticoagulation, combination therapy, and presence of comorbid conditions. A bleeding site is identified in most patients with peptic ulcer being the most common. In case of significant bleeding, complete or partial reversal of anticoagulation is undertaken on the basis of the balance of risks between bleeding and thromboembolic events. Early endoscopy can reveal lesions requiring endoscopic hemostasis, which can be performed in the setting of low-intensity anticoagulation. In patients with history of peptic disease or bleeding from an acid-related lesion, proton-pump inhibitors and Helicobacter pylori eradication reduce the risk of upper GI bleeding even when antiplatelet therapy is continued. Conclusions Predictors of bleeding on antiplatelets and/or antithrombotics therapy have been identified, but formulation and validation of a GI bleeding index for stratification of risk in individual patients is suggested. Reversal of anticoagulation in bleeding patients is associated with a low risk of thromboembolic events and permits the performance of diagnostic and therapeutic endoscopy. Proton-pump inhibitors and H. pylori eradication reduce the risk of rebleeding in those with acid-related disease.

Impact of Obesity on the Management and Clinical Course of Patients with Inflammatory Bowel Disease.

Background:Obesity has been linked with a proinflammatory state and the development of inflammatory diseases. Data on the clinical course and treatment of obese patients with inflammatory bowel disease (IBD) are limited. We used an institutional IBD registry to investigate the impact of obesity on IBD severity and treatment. Methods:This was a retrospective analysis of prospectively collected data for 3 years (2009–2011). Patients with IBD were categorized by body mass index (BMI). IBD-related quality of life, biochemical markers of inflammation, comorbidities, health care utilization, and treatment were characterized. Obesity was defined as a BMI ≥30 (type I: 30–34.9, type II: 35–39.9, and type III ≥40). Results:Among 1494 patients with IBD, 71.9% were above their ideal BMI and 31.5% were obese. Obesity was more common in ulcerative colitis compared with patients with Crohns disease (P = 0.04). Obese class II and class III patients were predominantly female. Obesity in IBD was associated with female gender (P < 0.0001), diabetes mellitus (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P < 0.001), poor quality of life (P < 0.0001), and increased rates of C-reactive protein elevation (P = 0.008). In logistic regression analysis, quality of life and C-reactive protein elevation were not independently correlated with obesity. There was no association between increasing BMI and annual prednisone use, emergency department visits, hospitalization, and surgery. Obesity was associated with lower milligrams per kilogram doses of purine analogs and biologics. Conclusions:Obesity in IBD is not associated with increased health care utilization and IBD-related surgeries. Optimal regimens for drug dosing in obese patients with IBD have yet to be defined.

Clinical trial: a randomized controlled cross‐over study of flupenthixol + melitracen in functional dyspepsia

Background  Functional dyspepsia is a prevalent condition associated with diminished quality of life (QoL) and high economic burden.

Gross Lower Gastrointestinal Bleeding in Patients on Anticoagulant and/or Antiplatelet Therapy: Endoscopic Findings, Management, and Clinical Outcomes

Objectives Gross gastrointestinal (GI) bleeding is a serious complication of anticoagulant/antiplatelet drug therapy. This study compares the frequencies of colorectal pathologies, endoscopic and resuscitative management measures, and clinical outcomes of patients hospitalized with lower GI bleeding (LGIB) while using anticoagulants/antiplatelets with those of patients not using them. Methods A retrospective review of the records of 166 admissions for patients with gross LGIB over 12 years was conducted. The colonoscopic findings, management measures, and clinical outcomes were compared between 2 groups. Group A composed of 100 patients using any antiplatelet/anticoagulant, and group B 66 patients not using any such drugs. Independent t tests and χ2 were used to test for association between taking antiplatelet/anticoagulant and other variables. Results Patients in group A were older and had more comorbidities than patients in group B. Severe LGIB occurred in 55.1% and 35.4% in groups A and B, respectively (P=0.01). Severity was not related to old age or the presence of comorbidities. A higher percentage of patients in group A had a hospital stay ≥6 days (44% vs. 27.3%; P<0.03), required blood transfusions (68% vs. 51.5%; P=0.03), and had in-hospital complications (37% vs. 22.7%; P=0.052). The most common source of bleeding was diverticulosis in both groups. Colorectal abnormalities were present in most patients; and in those using warfarin, colon cancer was common. Conclusions Use of antiplatelets/anticoagulant drugs is an independent predictor of severe LGIB and is associated with adverse outcomes. Colonoscopy is required in patients who bleed while using such drugs.

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.

Demographic and Clinical Predictors of High Healthcare Use in Patients with Inflammatory Bowel Disease.

Background:Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory condition requiring significant healthcare expenditure. Subgroups of individuals contribute disproportionately to spending. We aimed to determine demographic and clinical factors predictive of high healthcare expenditures for IBD patients followed over a multiyear period. Methods:This was a registry analysis using a prospective observational, consented, natural history registry from a tertiary IBD center and associated medical charges, not including pharmacy expenses. The 100 patients with the highest medical charges (top 5%) were compared with the median 300 patients. Logistic regression determined demographic and clinical factors associated with high charge patients. Results:IBD patients in the high charge group had significantly more unemployment (P < 0.0001), were of black race (P = 0.013), comorbid psychiatric illness (P = 0.002), hypertension (P = 0.01), diabetes (P = 0.004), opiate use (P < 0.0001), perianal involvement (P = 0.002), penetrating disease (P < 0.0001), and extensive colitis (P = 0.01). In multivariate analysis, unemployment (Crohns disease [CD]: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.32–7.02; ulcerative colitis [UC]: OR, 2.68; 95% CI, 1.20–5.99), psychiatric illness (UC: OR, 2.08; 95% CI, 1.03–4.19), opiates (CD: OR, 5.61; 95% CI, 2.67–11.82; UC: OR, 5.14; 95% CI, 2.52–10.48), prior surgery (CD: OR, 3.29; 95% CI, 1.59–6.82; UC: OR, 2.72; 95% CI, 1.39–5.32), penetrating CD (OR, 3.29; 95% CI, 1.02–10.62), and corticosteroid requirement (CD: OR, 3.78; 95% CI, 1.86–7.65; UC: OR, 2.98; 95% CI, 1.51–5.90) remained independently associated with high charges. Conclusions:High expenditure IBD patients were affected by more severe disease. The high prevalence of depression, anxiety, and chronic pain in these patients suggests the need for focused treatment of these comorbidities ultimately to reduce financial burden.