MiraLAX vs. Golytely: is there a significant difference in the adenoma detection rate?

BACKGROUND: In recent clinical trials (RCT) of bowel preparation, Golytely was more efficacious than MiraLAX. We hypothesised that there is a difference in adenoma detection between Golytely and MiraLAX. AIMS: To compare the adenoma detection rate (ADR) between these bowel preparations, and to identify independent predictors of bowel preparation quality and adenoma detection. METHODS: This was a post hoc analysis of an RCT that assessed efficacy and patient tolerability of Golytely vs. MiraLAX/Gatorade in average risk screening colonoscopy patients. Bowel preparation quality was measured with the Boston Bowel Preparation Scale (BBPS). An excellent/good equivalent BBPS score was defined as ≥ 7. Polyp pathology review was performed. ADR was defined as the proportion of colonoscopies with an adenoma. Univariate and multivariate analyses were conducted. RESULTS: One hundred and ninety patients were prospectively enrolled (87 MiraLAX, 103 Golytely). Golytely had a higher rate of a BBPS score ≥ 7 (82.5% vs. MiraLAX 67.8%, P=0.02). The ADR in the Golytely cohort was 26.2% (27/103), and was 16.1% (14/87) for MiraLAX (P = 0.091). On multivariate analyses, Golytely was 2.13 × more likely to be associated with a BBPS ≥ 7 (95% CI 1.05-4.32, P = 0.04) and 2.28 × more likely to be associated with adenoma detection (95% CI 1.05-4.98, P = 0.04) than MiraLAX. CONCLUSIONS: Golytely was more efficacious than MiraLAX in bowel cleansing, and was independently associated with both bowel prep quality (BBPS ≥ 7) and higher adenoma detection. Golytely should be used as first line for bowel prep for colonoscopy. Studies with larger populations are needed to confirm these results.

Randomised clinical trial: MiraLAX vs. Golytely - a controlled study of efficacy and patient tolerability in bowel preparation for colonoscopy.

BACKGROUND: MiraLAX is gaining acceptance as a bowel cleanser for colonoscopy. We hypothesize that MiraLAX/Gatorade is as efficacious for bowel cleansing as Golytely and is more tolerable for patients undergoing screening colonoscopy. AIM: To compare bowel preparation scores of MiraLAX/Gatorade vs. Golytely and examine differences in patient tolerability. METHODS: Patients undergoing screening colonoscopy were randomized to 4 L Golytely or 238 g MiraLAX in 64 ounces Golytely and four bisacodyl tablets. Efficacy in bowel cleansing was assessed using the Boston Bowel Preparation Scale (BPPS). Subjects completed a brief survey assessing patient tolerability. RESULTS: A total of 190 patients were enrolled (85 male, 105 female; mean age 56.9 years, s.d. 6.3); 87 were randomized to MiraLAX, 103 to Golytely. There was no difference in age, gender or timing of colonoscopy between the bowel preparation groups. Golytely's median total BBPS score was significantly higher than that of MiraLAX [9 (IQR 7-9) vs. 8 (IQR 6-9), P = 0.034]. Golytely had a higher rate of an excellent equivalent BBPS score of 8 or 9 than MiraLAX (70% vs. 55%, P = 0.036). There was no difference in patient tolerability (P = 0.857). CONCLUSIONS: Golytely was more efficacious than MiraLAX/Gatorade in bowel cleansing; both preparations were equally tolerated by patients.

Does level of sedation impact detection of advanced neoplasia?

BACKGROUND AND AIMS: Two of the foremost issues in screening colonoscopy involve delivering quality and maximizing adenoma detection rates (ADR). Little is known about the impact of deep sedation on ADR. This study aims to compare the detection of advanced lesions during screening colonoscopy performed with moderate conscious sedation (MCS) versus deep sedation (DS). METHODS: A retrospective cohort study was performed using the Clinical Outcomes Research Initiative database. Average risk screening colonoscopies performed January 2000 to December 2005 were examined for practice setting, patient demographics, and findings, including detection of a polyp >9 mm and suspected malignant lesions. RESULTS: A total of 104,868 colonoscopies were examined, 97% of which were performed with MCS. Univariate analysis demonstrated that more polyps of any size were detected with MCS (38 vs. 34%, p < 0.0001) and more advanced lesions were found with DS compared with MCS (7 vs. 6%, p = 0.01). When exclusively examining sites that performed DS > 10% for all procedures, a more significant increase in advanced lesion detection when using DS was observed (7.5 vs. 5.7%, p = 0.003). When adjusted for age, gender, race/ethnicity, site, prep quality, and ASA group, DS was 25% more likely to detect an advanced lesion. CONCLUSIONS: Our data suggest that use of DS may be associated with a higher rate of advanced lesion detection. However, this retrospective design has limitations that necessitate follow-up with prospective studies. These follow-up studies would be essential to support any change in the standard practices of sedation.

Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy.

BACKGROUND: Small bowel mucosal injury associated with non-selective non-steroidal anti-inflammatory drugs is being increasingly recognized. AIM: To evaluate the incidence of small bowel injury in healthy subjects receiving celecoxib or ibuprofen plus omeprazole using video capsule endoscopy (VCE). METHODS: Subjects with normal baseline VCE were randomly assigned to receive celecoxib 200 mg b.d., ibuprofen 800 mg t.d.s. plus omeprazole 20 mg o.d. or placebo for 2 weeks. The primary end point was mean number of small bowel mucosal breaks per subject. Secondary end points included correlation of faecal calprotectin levels with the primary outcome. RESULTS: After treatment, the mean number of small bowel mucosal breaks per subject and the percentage of subjects with mucosal breaks were 0.7/25.9% for ibuprofen/omeprazole compared with 0.2/6.4% for celecoxib and 0.1/7.1% placebo (both comparisons P < 0.001). There were no significant differences between celecoxib and placebo in any measure. Mean increases in faecal calprotectin levels were higher in subjects receiving ibuprofen/omeprazole compared with celecoxib (P < 0.001), but no correlation was determined between these levels and small bowel mucosal breaks. CONCLUSIONS: Among healthy subjects with no baseline endoscopic lesions, celecoxib was associated with significantly fewer small bowel mucosal breaks than ibuprofen/omeprazole as assessed by VCE.

Risk factors for cardiopulmonary events during propofol-mediated upper endoscopy and colonoscopy.

BACKGROUND: Propofol-mediated sedation for endoscopy is popular because of its rapid onset and recovery profile. AIM: To examine procedure-specific occurrence and risk factors for cardiopulmonary events during propofol-mediated upper endoscopy (EGD) and colonoscopy. DESIGN: A cohort study using the Clinical Outcomes Research Initiative database was used to determine the frequency of cardiopulmonary events. Clinical Outcomes Research Initiative consisted of 69 practice sites comprising 593 US endoscopists. Multivariate logistic regression analysis used variables, such as age, ASA classification and propofol administration by monitored anaesthesia care or gastroenterologist-administered propofol to determine the risk of cardiopulmonary events. RESULTS: The overall cardiopulmonary event rate for 5928 EGDs and 11 683 colonoscopies was 11.7/1000 cases. For colonoscopy, ascending ASA classification was associated with an increased risk. Monitored anaesthesia care was associated with a decreased adjusted relative risk (0.5, 95% CI: 0.36-0.72). ASA I and II patients receiving monitored anaesthesia care for EGD exhibited a significantly lower relative risk (ARR 0.29, 95% CI: 0.14-0.64). For subjects with ASA class III or greater, there was no difference in the risk between monitored anaesthesia care and gastroenterologist-administered propofol. CONCLUSIONS: There are procedure-specific risk factors for cardiopulmonary events during propofol-mediated EGD and colonoscopy. These should be taken into account during future prospective comparative trials.

The accuracy of PillCam ESO capsule endoscopy versus conventional upper endoscopy for the diagnosis of esophageal varices: a prospective three-center pilot study.

BACKGROUND AND STUDY AIMS: Variceal bleeding is a major complication of cirrhosis, and is associated with a 20 % mortality at 6 weeks. Current international guidelines recommend that patients with cirrhosis are screened by conventional upper endoscopy (esophagogastroduodenoscopy, EGD) in order to detect esophageal varices. The recently developed PillCam ESO esophageal capsule endoscope has been shown to be an accurate diagnostic tool in the investigation of patients with gastroesophageal reflux and Barrett's esophagus. We compared the PillCam ESO capsule endoscope with EGD for the detection of esophagogastric varices and portal hypertensive gastropathy in patients with cirrhosis. PATIENTS AND METHODS: A pilot trial was conducted at three sites. Patients with cirrhosis who were undergoing clinically indicated EGD for screening or surveillance for esophageal varices underwent a PillCam ESO study followed by an EGD within 48 hours. Capsule videos were assessed by an investigator who was blinded to the patient's medical history and EGD findings. RESULTS: A total of 23 of the 32 enrolled patients were found to have esophageal varices at both EGD and PillCam ESO endoscopy. In one patient PillCam ESO detected small varices that were not seen at EGD. The overall concordance between PillCam ESO and EGD was 96.9 % for the diagnosis of esophageal varices and 90.6 % for the diagnosis of portal hypertensive gastropathy. There were no adverse events related to PillCam ESO endoscopy. CONCLUSIONS: In a high-prevalence population, PillCam ESO may represent an accurate noninvasive alternative to EGD for the detection of esophageal varices and portal hypertensive gastropathy. A large-scale trial is underway to validate and expand these findings.

A pooled analysis to evaluate results of capsule endoscopy trials.

BACKGROUND AND STUDY AIM: Capsule endoscopy is a new tool in the evaluation of the small intestine. To speed evaluation and acceptance of this technology, the manufacturer (Given Imaging Ltd, Yoqneam, Israel) funded several trials. The data from these trials were collected at a central repository using a standardized reporting tool. Presentation of this data to the US Food and Drug Administration (FDA) in July 2003 led to the removal of the adjunctive term with regard to indication for capsule endoscopy, recognizing that the method is of independent importance for evaluating the small bowel. The aim of the present study was to combine the data from several capsule trials to help determine the yield and miss rate of capsule endoscopy for different diseases, compared with alternative diagnostic modalities. METHODS: Capsule studies were identified from a master database of funded studies. Studies were included in the pooled analysis if they reported a prospective comparison with another modality for evaluation of the small intestine. RESULTS: 32 studies with a total of 691 patients were found in the master database, of which 24 studies, representing 530 patients, met inclusion criteria and were entered into the pooled analysis. Prior to study entry, patients had undergone a mean of 6.77 diagnostic procedures, without findings. Of these 24 studies, 14 (involving 310 patients) were categorized as "bleeding" studies, and 10 studies (220 patients) as "nonbleeding small-bowel disorders" studies. The comparison procedure was push enteroscopy in 300 patients (in 45 for nonbleeding disorders), small-bowel series in 140 patients (in 125 for non-bleeding disorders), and colonoscopy with ileoscopy in 90 patients (50 for nonbleeding disorders). Overall analysis per patient showed new findings from capsule endoscopy in 50 % of patients; 17 % had new findings from the comparison method; in 22 % there were similar findings; and in 11 % there were no findings. A total of 1349 instances of disease were identified in the 530 examinations. Capsule endoscopy solely detected 87 % of the disease instances, while the comparison method solely detected 13 %. The yield for push enteroscopy alone was 14.8 %, for small-bowel series it was 9.9 %, and for colonoscopy it was 13.2 %. Capsule endoscopy missed 146 disease instances for a miss rate of 10 %; 989 were missed by the comparison methods for a miss rate of 73 %; and 214 were detected by both methods. CONCLUSION: Capsule endoscopy is the state of the art method for noninvasive detection of small-bowel disease.

Meta-analysis: upper gastrointestinal tolerability of valdecoxib, a cyclooxygenase-2-specific inhibitor, compared with nonspecific nonsteroidal anti-inflammatory drugs among patients with osteoarthritis and rheumatoid arthritis.

AIM: To compare the incidence of abdominal pain, dyspepsia and/or nausea associated with valdecoxib, nonspecific nonsteroidal anti-inflammatory drugs and placebo in patients with rheumatoid arthritis and osteoarthritis. METHODS: Data from five randomized, double-blind 12-week trials were pooled. Independent risk factors for abdominal pain, dyspepsia and/or nausea were also determined. RESULTS: The final analysis consisted of 4394 patients. Nonspecific nonsteroidal anti-inflammatory drug users (n = 1185) received naproxen 1000 mg/day (n = 766), ibuprofen 2400 mg/day (n = 207) or diclofenac sodium 150 mg/day (n = 212). Valdecoxib users received 10 mg/day (n = 955), 20 mg/day (n = 851) or 40 mg/day (n = 430). A total of 973 patients received placebo. The nonspecific nonsteroidal anti-inflammatory drug group was most likely to report abdominal pain or dyspepsia, while the placebo group reported the highest incidence of nausea. The most important risk factors for abdominal pain, dyspepsia and/or nausea were nonspecific nonsteroidal anti-inflammatory drug use, gastrointestinal history of nonspecific nonsteroidal anti-inflammatory drug-related intolerance or gastroduodenal ulcers, osteoarthritis diagnosis, female gender and age <65 years. CONCLUSION: This pooled analysis demonstrates a clear decrease in dyspepsia and an improvement in upper gastrointestinal tolerability for patients with osteoarthritis and rheumatoid arthritis taking valdecoxib, even at supratherapeutic doses, compared with those taking nonspecific nonsteroidal anti-inflammatory drugs over 12 weeks.

A novel diagnostic tool for detecting oesophageal pathology: the PillCam oesophageal video capsule.

BACKGROUND: Gastro-oesophageal reflux disease is a common entity. Erosive oesophagitis, ulcers and Barrett's oesophagus, which is found in up to 10% of gastro-oesophageal reflux disease patients, characterize severe gastro-oesophageal reflux disease. Patients with Barrett's oesophagus have 0.5% per patient-year risk of developing oesophageal adenocarcinoma. Currently, it appears that a minority of those at risk for Barrett's oesophagus undergo screening in part because of the costs associated with endoscopy as well as risks of sedation. A new ingestible PillCam oesophageal capsule developed may offer an alternative office-based approach to visualize the oesophagus without sedation. AIM: To compare the oesophageal capsule to conventional upper endoscopy for detection of oesophageal pathologies. METHODS: A newly developed capsule, which acquires video images from both ends of the device at a 4 frame/s rate, was ingested by 17 fasting patients with suspected oesophageal disorders. An ingestion procedure aimed to lengthen capsule transit time in the oesophagus was utilized. Subsequently, a standard upper endoscopy was carried out. The investigator interpreting the capsule findings was blinded to the endoscopy results and vice versa. Patients with dysphagia, known Zenker's diverticulum, intestinal obstruction, cardiac pacemaker or pregnancy were excluded. RESULTS: Twelve of the 17 patients examined had oesophageal findings using the endoscope as the gold standard. Capsule endoscopy identified oesophageal pathology in all 12 of these patients and an additional pathology in one patient that was missed during endoscopy. For the purpose of this study, this finding was regarded as a false-positive. The mean oesophageal passage time was 189 +/- 280 s. The positive predictive value of the oesophageal capsule for any oesophageal pathology was 92% and the negative predictive value was 100%. Oesophageal capsule sensitivity was 100% and specificity 80%. There were neither swallowing difficulties nor complications subsequent to ingestion in any subjects. Seventy-three percentage of patients preferred the oesophageal capsule procedure on conventional endoscopy. Only one patient preferred oesophagogastroduodenoscopy. CONCLUSIONS: This pilot study has shown that oesophageal capsule endoscopy is an accurate, convenient, safe and well-tolerated method to screen patients for significant oesophageal disorders. No sedation is required, which may allow simple, office-based screening and assessment. Further, large-scale studies are necessary to more fully assess this novel diagnostic tool.

Reduced incidence of upper gastrointestinal ulcer complications with the COX-2 selective inhibitor, valdecoxib.

AIM: In a predefined analysis, data were pooled from eight blinded, randomized, controlled trials, and separately from three long-term, open-label trials to determine the rate of upper gastrointestinal ulcer complications with the cyclo-oxygenase-2 selective inhibitor, valdecoxib, vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: In randomized, controlled trials, 7434 osteoarthritis and rheumatoid arthritis patients received placebo (n = 973), valdecoxib 5-80 mg daily (n = 4362), or a non-selective non-steroidal anti-inflammatory drug (naproxen, ibuprofen or diclofenac; n = 2099) for 12-26 weeks. In long-term, open-label trials, 2871 patients received valdecoxib 10-80 mg daily for up to 1 year. All potential events were reviewed by a blinded, independent review committee based on a priori definitions of ulcer complications (perforations, obstructions, bleeds). RESULTS: In randomized, controlled trials, 19 of 955 potential events were adjudicated to be ulcer complications. Valdecoxib was associated with a significantly lower ulcer complication rate than non-selective non-steroidal anti-inflammatory drugs (0.68% vs. 1.96%, all patients; 0.29% vs. 2.08%, non-aspirin users; P < 0.05). In long-term, open-label trials, seven of 310 potential events were adjudicated to be ulcer complications; the annualized incidence for valdecoxib was 0.39% (seven of 1791 patient-years) for all patients and 0.2% (three of 1472 patient-years) for non-aspirin users. CONCLUSIONS: Valdecoxib, including above recommended doses, is associated with a significantly lower rate of upper gastrointestinal ulcer complications than therapeutic doses of non-selective non-steroidal anti-inflammatory drugs.

Dyspepsia tolerability from the patients' perspective: a comparison of celecoxib with diclofenac.

AIM: To compare celecoxib (800 mg/day, n=1997) with diclofenac (150 mg/day, n=1996) on dyspepsia-related tolerability. METHODS: In one of the two protocols comprising the Celecoxib Long-Term Arthritis Safety Study, a randomized double-blind trial, patients completed the Severity of Dyspepsia Assessment Questionnaire at baseline and at weeks 4, 13, 26 and 52 for the following three scales: Pain Intensity, Non-Pain Symptoms and Satisfaction with Dyspepsia-Related Health. RESULTS: For the Pain Intensity scale, patients given diclofenac had significantly higher (worsening dyspepsia) mean changes, defined as follow-up minus baseline, than patients given celecoxib (P < 0.001, at all assessments). The mean changes in the Pain Intensity scale (scale, 2-47; higher score is higher pain intensity) were 0.99 (95% confidence interval (CI): 0.50, 1.48) for celecoxib and 2.76 (95% CI: 2.28, 3.25) for diclofenac at 4 weeks. Satisfaction was superior with celecoxib at all assessments (P < 0.001). At 4 weeks, the mean changes in the Satisfaction scale (scale, 7-35; higher score is higher satisfaction) were 0.02 (95% CI: - 0.26, 0.29) for celecoxib and - 0.72 (95% CI: - 1.00, - 0.45) for diclofenac. Diclofenac patients had significantly higher Non-Pain Symptoms at 4 weeks (P=0.005). CONCLUSIONS: Celecoxib, at two to four times the recommended dose, demonstrated a superior dyspepsia-related tolerability and satisfaction compared with standard dosages of diclofenac.