Michael D. Brown

Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea

BACKGROUND/AIMS Diarrhea is a significant problem in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine octreotide effectiveness in refractory AIDS-associated diarrhea. METHODS In a 3-week protocol, 129 patients with a stool weight of > 500 g/day despite standard antidiarrheal therapy were randomized to receive octreotide or placebo (3:2 ratio). Octreotide dose was increased 100 micrograms weekly to a maximum of 300 micrograms three times a day based on weekly 72-hour stool collections. Subsequently, patients received open-label octreotide at doses of up to 500 micrograms three times a day. RESULTS A 30% decrease in stool weight defined response. After 3 weeks, 48% of octreotide- and 39% of placebo-treated patients had responded (P = 0.43). At 300 micrograms three times a day, 50% of octreotide- and 30.1% of placebo-treated patients responded (P = 0.12). At a baseline stool weight of 1000-2000 g/day, 57% of octreotide- and 25% of placebo-treated patients responded (P = 0.06). Response rates based on CD4 counts, diarrhea duration, body weight, human immunodeficiency virus risk factor, and presence or absence of pathogens showed no benefit of octreotide. Adverse events were more frequent in the octreotide-treated group. CONCLUSION In the doses studied, octreotide was not more effective than placebo in patients with refractory AIDS-associated diarrhea. This lack of effectiveness may be attributable to inadequate sample size, doses, and duration of study treatment.

Inpatient capsule endoscopy leads to frequent incomplete small bowel examinations

AIM To examine the predictive factors of capsule endoscopy (CE) completion rate (CECR) including the effect of inpatient and outpatient status. METHODS We identified 355 consecutive patients who completed CE at Rush University Medical Center between March 2003 and October 2005. Subjects for CE had either nothing by mouth or clear liquids for the afternoon and evening of the day before the procedure. CE exams were reviewed by two physicians who were unaware of the study hypotheses. After retrospective analysis, 21 cases were excluded due to capsule malfunction, prior gastric surgery, endoscopic capsule placement or insufficient data. Of the remaining 334 exams [264 out-patient (OP), 70 in-patient (IP)], CE indications, findings, location of the patients [IP vs OP and intensive care unit (ICU) vs general medical floor (GMF)] and gastrointestinal transit times were analyzed. Statistical analysis was completed using SPSS version 17 (Chicago, IL). Chi-square, t test or fisher exact-tests were used as appropriate. Multivariate logistic regression analysis was used to identify variables associated with incomplete CE exams. RESULTS The mean age for the entire study population was 54.7 years. Sixty-one percent of the study population was female, and gender was not different between IPs vs OPs (P = 0.07). The overall incomplete CECR was 14% in our study. Overt obscure gastrointestinal bleeding (OGB) was significantly more common for the IP CE (P = 0.0001), while abdominal pain and assessment of IBD were more frequent indications for the OP CE exams (P = 0.002 and P = 0.01, respectively). Occult OGB was the most common indication and arteriovenous malformations were the most common finding both in the IPs and OPs. The capsule did not enter the small bowel (SB) in 6/70 IPs and 8/264 OPs (P = 0.04). The capsule never reached the cecum in 31.4% (22/70) of IP vs 9.5% (25/ 264) of OP examinations (P < 0.001). The mean gastric transit time (GTT) was delayed in IPs compared to OPs, 98.5 ± 139.5 min vs 60.4 ± 92.6 min (P = 0.008). Minimal SB transit time was significantly prolonged in the IP compared to the OP setting [IP = 275.1 ± 111.6 min vs OP = 244.0 ± 104.3 min (P = 0.037)]. CECR was also significantly higher in the subgroup of patients with OGB who had OP vs IP exams (95% vs 80% respectively, P = 0.001). The proportion of patients with incomplete exams was higher in the ICU (n = 7/13, 54%) as compared to the GMF (n = 15/57, 26%) (P = 0.05). There was only a single permanent SB retention case which was secondary to a previously unknown SB stricture, and the remaining incomplete SB exams were due to slow transit. Medications which affect gastrointestinal system motility were tested both individually and also in aggregate in univariate analysis in hospitalized patients (ICU and GMF) and were not predictive of incomplete capsule passage (P > 0.05). Patient location (IP vs OP) and GTT were independent predictors of incomplete CE exams (P < 0.001 and P = 0.008, respectively). CONCLUSION Incomplete CE is a multifactorial problem. Patient location and related factors such as severity of illness and sedentary status may contribute to incomplete exams.

Paraduodenal hernia presenting as unexplained recurrent abdominal pain

We present a case of a 29-yr-old female nurse who presented with an 8-h history of abdominal pain. She had had similar episodes (twice/yr) over the last 5 yr, and the pain had usually resolved spontaneously. Prior investigations including laboratory studies, plain films of the abdomen, an abdominal and pelvic ultrasound, and a CT scan yielded no diagnosis. Her pain was previously considered to be either psychosomatic or a variant of irritable bowel syndrome. On this admission, an evaluation and subsequent enteroclysis revealed a left paraduodenal hernia. The importance of considering paraduodenal hernias in the differential diagnosis of unexplained intermittent abdominal pain is discussed here.

Hepatitis B vaccination in patients with inflammatory bowel disease

AIM To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD). METHODS This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination. RESULTS About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313). CONCLUSION The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.

Starch-entrapped microsphere fibers improve bowel habit but do not exhibit prebiotic capacity in those with unsatisfactory bowel habits: a phase I, randomized, double-blind, controlled human trial

Approximately one-third of individuals in the United States experience unsatisfactory bowel habits, and dietary intake, especially one low in fiber, could be partly responsible. We hypothesized that intake of a fermentable fiber (starch-entrapped microspheres, SM) that has a delayed, slow fermentation profile in vitro would improve bowel habit while exhibiting prebiotic capacity in those with self-described unsatisfactory bowel habits, all with minimal adverse effects. A total of 43 healthy volunteers completed a 3-month, double-blind, parallel-arm randomized clinical trial to assess the ability of a daily dose (9 or 12 g) of SM vs psyllium (12 g) to improve bowel habit, including stool consistency and frequency, and modify gut milieu through changes in stool microbiota and short-chain fatty acids while remaining tolerable through minimal gastrointestinal symptoms. All outcomes were compared before and after fiber treatment. Stool frequency significantly improved (P=.0003) in all groups after 3 months, but stool consistency improved only in both SM groups compared with psyllium. In addition, all groups self-reported a similar improvement in overall bowel habit with fiber intake. Both SM and psyllium resulted in minimal changes in microbiota composition and short-chain fatty acid concentrations. The present study suggests that supplementation with a delayed and slow-fermenting fiber in vitro may improve bowel habit in those with constipation, but further investigation is warranted to determine capacity to alter microbiota and fermentation profiles in humans. This trial was registered at ClinicalTrials.gov as NCT01210625.

Polyethylene Glycol-3350 (Miralax®)+1.9-L sports drink (Gatorade®)+2 tablets of bisacodyl results in inferior bowel preparation for colonoscopy compared with Polyethylene Glycol-Ascorbic Acid (MoviPrep®)

BACKGROUND/AIMS Polyethylene glycol (PEG)-3350, approved by Food and Drug Administration (FDA) only for constipation, combined with 1.9 L of sports drink (SD) (GatoradeR) and bisacodyl (B) is commonly used in outpatient practice for bowel preparation due to cited patient satisfaction and tolerability of this specific regimen. We aim to compare PEG-3350 (MiralaxR) with PEG-AA-based (MoviPrepR) in terms of efficacy, patient satisfaction, and the effects of these two regimen on serum electrolytes. MATERIALS AND METHODS This study is a prospective, single-blinded, block randomized trial comparing single-dose PEG-3350+SD+B to split-dose 2-L PEG-AA in the outpatient endoscopy unit in patients undergoing colonoscopy. Basic metabolic profiles were checked on the day of randomization and on the day of procedure. Patients completed a survey on the day of procedure. Bowel preparation quality was assessed using the Boston Bowel Preparation Scale (BBPS) by two endoscopists and a nurse present during the procedure. RESULTS We randomized 150 patients (74 PEG-3350+SD+B and 76 PEG-AA). The PEG-AA group had significantly higher BBPS scores in the right colon by Endoscopist 1, Nurse, and Endoscopist 2 (p 0.005, <0.000, 0.001) and in the left and transverse colon by Nurse and Endoscopist 2 (p 0.004, 0.26, 0.000, 0.006). There was no statistically significant difference in patient satisfaction or change in serum electrolytes between the two groups. CONCLUSION Use of single-dose PEG-3350+SD+B results in inferior bowel preparation for colonoscopy compared with split-dose PEGAA and does not provide any advantage in regards to patient satisfaction. We therefore recommend discontinuing the use of PEG 3350 for bowel preparation.

Breath Methane Levels Are Associated With Diverticulosis and Bacterial Overgrowth but Not BMI

Background: Methanogenic archae have been implicated in the pathogenesis of obesity and it is postulated that methanogens regulate the speed with which hydrogen is generated in the colon. Whether there is an association between methanogens and GI tract disease is largely unknown. Aim: To determine if there is an association between breath methane levels (BML) on hydrogen breath testing (HBT) and BMI, or GI tract pathology in human subjects Methods: 406 human subjects who have underwent HBT at Rush University from 2003 to 2010 were randomly identified using the HBT database at Rush. For HBT subjects received either 25 gm of lactose or 20 gm of lactulose. Two baseline breath samples and samples every 15 mins were taken upto 150 min. Breath samples were then analyzed using the Quinton Microlyzer for methane, carbon dioxide and hydrogen. The clinical patient characteristics and the HBT results were obtained with chart review and were analyzed with chi-square or Fisher exact tests for categorical data and T-tests for continuous variables. Methane producers were defined as having a baseline fasting BML>5ppm. Pearson correlation coefficients between BMI and methane levels and univariate linear regression analyses were calculated using SPSS v17.0. Results: The two baseline BML as well as follow up BML were highly correlated (n=406, Pearson Corr. Coef. > 0.87 for all). Therefore the first baseline BML was used for further analyses. When methane producers (n=83) were compared to non-producers (n=323), there were no significant differences in clinical variables such as age, gender, ethnicity, presenting symptoms, medication use, social and family history, frequency of bowel movements, and hemoglobin or albumin levels. Methane producers were more likely to have bacterial overgrowth (26.3% vs 13.3%, p=0.006), were prescribed antibiotics more often after HBT (26.2% vs 12.8%, p=0.002) and responded more often with a complete resolution of symptoms (15/49 (30.6%) vs 24/124 (19.3%), p=0.044). Methane producers had a higher incidence of diverticulosis on a recent colonoscopy (n= 264, 27/53(50.9%) vs 72/211(34.1%), p=0.021) but were not older (mean age= 51.5 vs 51.1, p=0.813) or having less frequent BMs (mean BM/day=2.7 vs 2.6, p=0.835). There was no correlation between BML and BMI in all patients or methane producers (n=262 and 43, Pearson Corr. Coef. =-0.016 and -0.148 respectively). Obesity (i.e. BMI>30) was not more frequent among methane producers (13/43 (30.2%) vs. 67/219(30.6%), p=0.963) Conclusions: Breath methane production is associated with diverticulosis and bacterial overgrowth. There is no correlation between BMI and methane producing status in symptomatic patients undergoing HBT.