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740 Concomitant use of a Proton Pump Inhibitor Does Not Increase the Risk of Recurrent Myocardial Infarction Among Clopidogrel Users
741 Evaluation of Potential Correlations Between Serum Adalimumab Concentration and Remission in Patients With Crohn's Disease in Classic I and II JianLing Li, Susan K. Paulson, Yi-Lin Chiu, Anne Robinson, Kathleen G. Lomax, Paul F. Pollack Aim: Adalimumab (ADA), a fully human anti-TNF monoclonal antibody, is approved for treating patients with moderate to severe Crohn's disease (CD). The aim was to evaluate the correlation between serum ADA concentration and clinical remission status in subjects with CD and to determine if there is a threshold concentration that could reliably predict remission. Materials and Methods: CD patients who received ADA in either CLASSIC I or CLASSIC II and who had available trough serum ADA concentrations were evaluated. Clinical remission (Crohn's Disease Activity Index score <150) and serum ADA concentration correlations were assessed by logistic regression analyses at week 4 in CLASSIC I (3 ADA dose groups) and at weeks 4, 24, and 56 in CLASSIC II (all ADA dose groups combined). Additionally, a threshold analysis was used to determine if there is a minimum serum ADA concentration threshold that is associated with clinical remission. Results: Serum trough concentrations from 258 subjects were evaluated. In CLASSIC I and CLASSIC II there was considerable overlap in serum ADA concentrations in subjects who achieved remission and those who did not (figures). At week 4 of CLASSIC I, there was a small but statistically significant association between ADA concentration and remission (logistic regression p=.01; Spearman correlation =.173). For CLASSIC II, ADA concentration did not correlate with the probability of achieving remission (logistic regression p=.102, .123, and .091 for weeks 4, 24, and 56, respectively). The threshold analysis did not reveal a serum trough concentration that could predict remission status. Conclusion: A dose-exposure-response relationship was identified for ADA induction in CLASSIC I, but the overlap in serum ADA concentrations within dose groups precludes a pharmacokinetic measurement as a useful predictor of clinical remission following induction. Serum ADA concentrations did not consistently correlate with clinical remission status in CLASSIC II throughout 56 weeks of maintenance therapy, suggesting that therapeutic decisions based upon a serum ADA concentration may have limited value.
739 The Effect of Bowel Preparation Status on the Polyp Missing Rate During Colonoscopy: Prospective Study Using Tandem Colonoscopic Evaluation Sung Noh Hong, Jeong Hwan Kim, In Kyung Sung, Hyung-Seok Park, Byung Kook Kim, Jung Hyun Lee, Dong Choon Seol, Chan Sup Shim Purpose: High quality bowel cleaning preparation was most important prerequisites of an accurate colonoscopy, because even a small amount of residual fecal matter can obscure small polyps. Until now, several studies evaluated the impact of bowel preparation on the quality of colonoscopy using comparison of the polyp detection rate in patients with adequate bowel preparation status to that in patients with inadequate bowel preparation status during colonoscopy. Polyp missing rate is most accurate measurement for the quality of colonoscopy. However, there was no direct measurement about the effect of bowel preparation status on the polyp missing rate. Method: This prospective study was performed on the patients underwent initial colonoscopy and 2nd stage colonoscopic polypectomy from May 2009 to October 2009 at Konkuk University Hospital, Seoul, Korea. Six endoscopists were participated this study and attain an inter-observer agreement for bowel preparation status according to Aronchick's scale and Ottawa bowel preparation quality scale. During initial colonoscopy, all patients were recorded the polyp characteristics (size, number, shape and location), indication of colonoscopy, withdrawal time, endoscopist's career, as well as bowel preparation status. Results: After two consensus meeting, interclass correlation coefficient for Aronchick and Ottawa scale reached 0.882 and 0.903, respectively. A total 98 patients were enrolled. Initial colonoscopies detected 252 polyps, of which 62 polyps in 30 patients were larger than 1cm. During 2nd stage colonoscopy, additional 50 polyps were detected in 30 patients, of which 8 polyps were larger than 1cm. The overall polyp missing rate was 16.6% and missing rate of polyp larger than 1cm was 11.4%. As the bowel preparation was inadequate, the miss rate decreased significantly (p=0.021 for Aronchick's scale, p=0.017 for Ottawa scale). Using multivariate analysis adjusted with colonoscopic withdrawal time, endoscopist's career, indication for colonoscopy, initially detected polyp number, bowel preparation status was significant factor for overall polyp missing rate (Aronchick's scale: OR, 1.93; 95% CI, 1.09-3.40, Ottawa scale: OR, 1.27; 95% CI, 1.07-1.52) and for missing rate of polyp larger than 1cm (Aronchick's scale: OR, 6.39; 95% CI, 1.47-27.28, Ottawa scale: OR, 1.46; 95% CI, 1.09-1.95). Conclusion: Polyp missing rates were affected by bowel preparation. Therefore, it is proper strategy that the shortening colonoscopy follow-up interval is appropriate strategy in case that the inadequate bowel preparation.
742 Adenomatous and Serrated Lesions: Co-Factors in Colorectal Carcinogenesis? Eveline Rondagh, Mariëlle Bouwens, Bjorn Winkens, Robert Riedl, Adriaan P. de Bruine, Ad Masclee, Silvia Sanduleanu Background: It is generally accepted that the majority of colorectal cancers (CRC) originate from adenomatous colorectal lesions, via the classic APC-pathway. However, recent data indicate that at least some of the hyperplastic lesions may also play a role in the development of CRC, via a serrated pathway. In a long-term, retrospective study, we have shown that patients with large, right-sided hyperplastic lesions have an increased risk for development of CRC. The precise underlying mechanism remains unclear. Methods: The aim of this cross-sectional study was to investigate the relationship between serrated lesions (SLs) and synchronous advanced colorectal neoplasia. To this end, 2310 consecutive patients attending for routine colonoscopy at our endoscopy unit, between February 2008 and February 2009, were prospectively included. Clinical, endoscopical records and histopathology of removed colorectal lesions were obtained. During colonoscopy, size, location and morphology of the colorectal lesions were registered using a standardized reporting system (including digital photographic documentation). SLs were categorized into i) high-risk SLs, defined as large (≥6 mm), right-sided hyperplastic lesions or serrated adenomas or ii) low-risk SLs, including the remaining hyperplastic lesions. Advanced colorectal neoplasia were defined as presence of at least one of the following features: multiple (≥3), large (≥10 mm), high-grade dysplastic adenomas or CRC. Results: The prevalence of SLs was 13.3% (307) and the prevalence of high-risk SLs was 2.5% (57). Of the high-risk SLs, 44.8% displayed a flat morphology during endoscopy. In total, 322 patients (13.9%) had advanced colorectal neoplasia. Importantly, patients with high-risk SLs harbored more frequently synchronous advanced colorectal neoplasia, compared to patients with low-risk SLs or without SLs: 40.4% vs. 15.6% vs. 13.0%, respectively. Multiple logistic regression analysis showed that presence of high-risk SLs was an independent risk factor for presence of synchronous advanced colorectal neoplasia (odds ratio 4.0, 95% CI 2.3-7.0, p<0.001). Conclusions: 1. High-risk serrated lesions are relatively uncommon lesions. 2. However, about 40% of these high-risk serrated lesions display flat morphology, which makes them prone to under-detection. 3. Patients with highrisk serrated lesions are 4-times more likely to harbor synchronous advanced colorectal adenomas and/or CRCs. This association suggests parallel progression to CRC, via the classic APC-pathway and the serrated pathway.
740 Concomitant use of a Proton Pump Inhibitor Does Not Increase the Risk of Recurrent Myocardial Infarction Among Clopidogrel Users Vera E. Valkhoff, Eva M. van Soest, Miriam C. Sturkenboom, Ernst J. Kuipers Background: Both clopidogrel and proton pump inhibitor (PPI) drug metabolisms involve cytochrome P450 (CYP) enzymes, which could lead to drug competition on the CYP2C19 level. It has been hypothesized that concurrent use of PPIs may diminish clopidogrel efficacy. The US Food and Drug Administration therefore recommends to discourage the concurrent use of CYP2C19 inhibiting drugs. However, evidence on the association between cardiovascular events and co-administration of PPIs with clopidogrel remains inconclusive. Aim: To assess the association between concomitant use of PPIs and recurrent myocardial infarction (MI) in patients using clopidogrel. Methods: We conducted a nested case-control study within the PHARMO Record Linkage System (1999-2008), which includes data on hospitalisations and drug utilisation (both in- and outpatient) from >2 million residents from the Netherlands. The cohort consisted of patients hospitalized for acute MI, followed by a clopidogrel prescription within 90 days. Cases with a readmission for acute MI while using clopidogrel were matched to controls on age, gender, and calendar time (index date). Exposure to PPI was categorized as current (within 30 days prior to the index-date), past (31-180 days prior to the index-date), remote (>181 days prior to the index-date) or never use. Use of histamine-2-receptor antagonists (H2RAs) was also assessed. Multivariate conditional logistic regression analysis was used to calculate adjusted odds ratios (OR) with 95%-confidence intervals (95%CI). Results: Among 9,077 patients prescribed clopidogrel following acute MI, we identified 151 cases readmitted for MI while still using clopidogrel and 9351 clopidogrel-using matched controls. Cases were more likely to have co-morbidities and to have had used aspirin. Controls were more likely to have undergone a percutaneous coronary intervention after first MI. Sixty (39.7%) of the cases and 3,107 (33.2%) of the controls used PPIs and 3 (2.0%) of the cases and 207 (2.2%) of the controls used H2RAs prior to recurrent MI. Both current use of PPIs and current use of H2RAs were not associated with a significantly increased risk of recurrent MI (OR: 1.30, 95%CI: 0.91-1.85 and OR: 1.00, 95%CI: 0.31-3.25, respectively) compared to never users. Of all PPIs, pantoprazole was used most frequently (49.5%), followed by omeprazole (28.1%). In a stratified analysis, none of the PPIs was significantly associated with an increased risk of recurrent MI. Conclusions: In this population-based observational study, concomitant use of PPIs with clopidogrel did not increase the risk of recurrent MI. This is in line with results from recent randomized clinical trials.
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AGA Abstracts
AGA Abstracts
4.5- 10 hrs in the PM colonoscopy groups. The mean cleansing score was significantly worse in NaP group (4.7 ± 2.9) compared to the other 3 groups: 4L PEG (3.5 ± 2.9), 2L PEG + B (3.3 ± 2.7) and PS + MC (3.4 ± 2.7) (p=0.033). NaP resulted in a significantly higher proportion of inadequate preparations. The mean cleansing scores were significantly worse in AM than PM colonoscopy, a finding which was consistent in all 4 groups. NaP and PS + MC were the best tolerated regimens. 6% of patients who took NaP had hyperphosphatemia, which was not seen in other groups. 11% of patients who took NaP developed hypokelemia, a proportion which was significantly higher than the other groups. Conclusions: 2L of PEG + B or PS + MC was as efficacious as 4L PEG and superior to NaP in bowel cleansing. Better bowel preparation was achieved with split dosing and a shorter interval between completion of bowel preparation and start of colonoscopy, irrespective of bowel preparation regimens. 2L of PEG + B and PS + MC were as safe as 4L PEG and better tolerated than 4L PEG.
739 The Effect of Bowel Preparation Status on the Polyp Missing Rate During Colonoscopy: Prospective Study Using Tandem Colonoscopic Evaluation Sung Noh Hong, Jeong Hwan Kim, In Kyung Sung, Hyung-Seok Park, Byung Kook Kim, Jung Hyun Lee, Dong Choon Seol, Chan Sup Shim Purpose: High quality bowel cleaning preparation was most important prerequisites of an accurate colonoscopy, because even a small amount of residual fecal matter can obscure small polyps. Until now, several studies evaluated the impact of bowel preparation on the quality of colonoscopy using comparison of the polyp detection rate in patients with adequate bowel preparation status to that in patients with inadequate bowel preparation status during colonoscopy. Polyp missing rate is most accurate measurement for the quality of colonoscopy. However, there was no direct measurement about the effect of bowel preparation status on the polyp missing rate. Method: This prospective study was performed on the patients underwent initial colonoscopy and 2nd stage colonoscopic polypectomy from May 2009 to October 2009 at Konkuk University Hospital, Seoul, Korea. Six endoscopists were participated this study and attain an inter-observer agreement for bowel preparation status according to Aronchick's scale and Ottawa bowel preparation quality scale. During initial colonoscopy, all patients were recorded the polyp characteristics (size, number, shape and location), indication of colonoscopy, withdrawal time, endoscopist's career, as well as bowel preparation status. Results: After two consensus meeting, interclass correlation coefficient for Aronchick and Ottawa scale reached 0.882 and 0.903, respectively. A total 98 patients were enrolled. Initial colonoscopies detected 252 polyps, of which 62 polyps in 30 patients were larger than 1cm. During 2nd stage colonoscopy, additional 50 polyps were detected in 30 patients, of which 8 polyps were larger than 1cm. The overall polyp missing rate was 16.6% and missing rate of polyp larger than 1cm was 11.4%. As the bowel preparation was inadequate, the miss rate decreased significantly (p=0.021 for Aronchick's scale, p=0.017 for Ottawa scale). Using multivariate analysis adjusted with colonoscopic withdrawal time, endoscopist's career, indication for colonoscopy, initially detected polyp number, bowel preparation status was significant factor for overall polyp missing rate (Aronchick's scale: OR, 1.93; 95% CI, 1.09-3.40, Ottawa scale: OR, 1.27; 95% CI, 1.07-1.52) and for missing rate of polyp larger than 1cm (Aronchick's scale: OR, 6.39; 95% CI, 1.47-27.28, Ottawa scale: OR, 1.46; 95% CI, 1.09-1.95). Conclusion: Polyp missing rates were affected by bowel preparation. Therefore, it is proper strategy that the shortening colonoscopy follow-up interval is appropriate strategy in case that the inadequate bowel preparation.
742 Adenomatous and Serrated Lesions: Co-Factors in Colorectal Carcinogenesis? Eveline Rondagh, Mariëlle Bouwens, Bjorn Winkens, Robert Riedl, Adriaan P. de Bruine, Ad Masclee, Silvia Sanduleanu Background: It is generally accepted that the majority of colorectal cancers (CRC) originate from adenomatous colorectal lesions, via the classic APC-pathway. However, recent data indicate that at least some of the hyperplastic lesions may also play a role in the development of CRC, via a serrated pathway. In a long-term, retrospective study, we have shown that patients with large, right-sided hyperplastic lesions have an increased risk for development of CRC. The precise underlying mechanism remains unclear. Methods: The aim of this cross-sectional study was to investigate the relationship between serrated lesions (SLs) and synchronous advanced colorectal neoplasia. To this end, 2310 consecutive patients attending for routine colonoscopy at our endoscopy unit, between February 2008 and February 2009, were prospectively included. Clinical, endoscopical records and histopathology of removed colorectal lesions were obtained. During colonoscopy, size, location and morphology of the colorectal lesions were registered using a standardized reporting system (including digital photographic documentation). SLs were categorized into i) high-risk SLs, defined as large (≥6 mm), right-sided hyperplastic lesions or serrated adenomas or ii) low-risk SLs, including the remaining hyperplastic lesions. Advanced colorectal neoplasia were defined as presence of at least one of the following features: multiple (≥3), large (≥10 mm), high-grade dysplastic adenomas or CRC. Results: The prevalence of SLs was 13.3% (307) and the prevalence of high-risk SLs was 2.5% (57). Of the high-risk SLs, 44.8% displayed a flat morphology during endoscopy. In total, 322 patients (13.9%) had advanced colorectal neoplasia. Importantly, patients with high-risk SLs harbored more frequently synchronous advanced colorectal neoplasia, compared to patients with low-risk SLs or without SLs: 40.4% vs. 15.6% vs. 13.0%, respectively. Multiple logistic regression analysis showed that presence of high-risk SLs was an independent risk factor for presence of synchronous advanced colorectal neoplasia (odds ratio 4.0, 95% CI 2.3-7.0, p<0.001). Conclusions: 1. High-risk serrated lesions are relatively uncommon lesions. 2. However, about 40% of these high-risk serrated lesions display flat morphology, which makes them prone to under-detection. 3. Patients with highrisk serrated lesions are 4-times more likely to harbor synchronous advanced colorectal adenomas and/or CRCs. This association suggests parallel progression to CRC, via the classic APC-pathway and the serrated pathway.
740 Concomitant use of a Proton Pump Inhibitor Does Not Increase the Risk of Recurrent Myocardial Infarction Among Clopidogrel Users Vera E. Valkhoff, Eva M. van Soest, Miriam C. Sturkenboom, Ernst J. Kuipers Background: Both clopidogrel and proton pump inhibitor (PPI) drug metabolisms involve cytochrome P450 (CYP) enzymes, which could lead to drug competition on the CYP2C19 level. It has been hypothesized that concurrent use of PPIs may diminish clopidogrel efficacy. The US Food and Drug Administration therefore recommends to discourage the concurrent use of CYP2C19 inhibiting drugs. However, evidence on the association between cardiovascular events and co-administration of PPIs with clopidogrel remains inconclusive. Aim: To assess the association between concomitant use of PPIs and recurrent myocardial infarction (MI) in patients using clopidogrel. Methods: We conducted a nested case-control study within the PHARMO Record Linkage System (1999-2008), which includes data on hospitalisations and drug utilisation (both in- and outpatient) from >2 million residents from the Netherlands. The cohort consisted of patients hospitalized for acute MI, followed by a clopidogrel prescription within 90 days. Cases with a readmission for acute MI while using clopidogrel were matched to controls on age, gender, and calendar time (index date). Exposure to PPI was categorized as current (within 30 days prior to the index-date), past (31-180 days prior to the index-date), remote (>181 days prior to the index-date) or never use. Use of histamine-2-receptor antagonists (H2RAs) was also assessed. Multivariate conditional logistic regression analysis was used to calculate adjusted odds ratios (OR) with 95%-confidence intervals (95%CI). Results: Among 9,077 patients prescribed clopidogrel following acute MI, we identified 151 cases readmitted for MI while still using clopidogrel and 9351 clopidogrel-using matched controls. Cases were more likely to have co-morbidities and to have had used aspirin. Controls were more likely to have undergone a percutaneous coronary intervention after first MI. Sixty (39.7%) of the cases and 3,107 (33.2%) of the controls used PPIs and 3 (2.0%) of the cases and 207 (2.2%) of the controls used H2RAs prior to recurrent MI. Both current use of PPIs and current use of H2RAs were not associated with a significantly increased risk of recurrent MI (OR: 1.30, 95%CI: 0.91-1.85 and OR: 1.00, 95%CI: 0.31-3.25, respectively) compared to never users. Of all PPIs, pantoprazole was used most frequently (49.5%), followed by omeprazole (28.1%). In a stratified analysis, none of the PPIs was significantly associated with an increased risk of recurrent MI. Conclusions: In this population-based observational study, concomitant use of PPIs with clopidogrel did not increase the risk of recurrent MI. This is in line with results from recent randomized clinical trials.
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AGA Abstracts
AGA Abstracts
4.5- 10 hrs in the PM colonoscopy groups. The mean cleansing score was significantly worse in NaP group (4.7 ± 2.9) compared to the other 3 groups: 4L PEG (3.5 ± 2.9), 2L PEG + B (3.3 ± 2.7) and PS + MC (3.4 ± 2.7) (p=0.033). NaP resulted in a significantly higher proportion of inadequate preparations. The mean cleansing scores were significantly worse in AM than PM colonoscopy, a finding which was consistent in all 4 groups. NaP and PS + MC were the best tolerated regimens. 6% of patients who took NaP had hyperphosphatemia, which was not seen in other groups. 11% of patients who took NaP developed hypokelemia, a proportion which was significantly higher than the other groups. Conclusions: 2L of PEG + B or PS + MC was as efficacious as 4L PEG and superior to NaP in bowel cleansing. Better bowel preparation was achieved with split dosing and a shorter interval between completion of bowel preparation and start of colonoscopy, irrespective of bowel preparation regimens. 2L of PEG + B and PS + MC were as safe as 4L PEG and better tolerated than 4L PEG.