- Email: [email protected]
816 Alterations of Human Gastric Microbiota in Patients With H. pylori Infection and Different Stages of Gastric Carcinogenesis
AGA Abstracts
test for H. pylori, 3. cardiothrombotic diseases, and 4. anticipated regular use of NSAIDs for the duration of the trial. We excluded patients who used concomitant anticoagulants, had a history of gastroduodenal surgery other than a patch repair, gastric outlet obstruction, renal failure (serum creatinine level >200 µmol/L), pregnancy, terminal illness, or cancer. After providing written informed consent, all eligible patients received esomeprazole 20 mg once daily. They were randomized to receive either celecoxib 100 mg twice daily or naproxen 500 mg twice daily for up to 18 months. Patients were prescribed or asked to continue low-dose aspirin 80 mg once daily. The primary endpoint was recurrent ulcer bleeding within 18 months, which was defined as hematemesis, melena, or a decrease in the hemoglobin level of at least 2.0 g per deciliter with ulcers or bleeding erosions as adjudicated by an independent committee. Results: The intention-to treat population included 512 patients (256 celecoxib, 256 naproxen) who took at least one dose of study drug; 368 patients received concomitant low-dose aspirin (72.3% in the celecoxib group, 71.5% in the naproxen group). The demographic characteristics such as sex, age, type of arthritis, smoking, alcohol use, hemoglobin and creatinine levels were comparable between two groups. Fifteen patients (7.2%) receiving celecoxib and 31 (15.9%) receiving naproxen met the criteria for the primary endpoint (adjusted hazard ratio, 0.45; 95% CI, 0.26-0.84; p=0.01). Conclusion: Among patients with cardiothrombotic disease and a history of ulcer bleeding, combination of a COX-2 selective NSAID and a PPI is superior to a nonselective NSAID plus a PPI in preventing recurrent ulcer bleeding. Acknowledgment: This study was supported by a competitive grant from the Research Grant Council of Hong Kong (RGC project references: 460909 and 460910)
Table 1: Baseline characteristics of patients with erosive (ERD) and non-erosive (NERD) reflux disease, and of healthy controls (HC)
ERD=erosive reflux disease; NERD=non-erosive reflux disease; HC=healthy controls; BMI= body mass index; EAET=esophageal acid exposure time; SD=standard deviation: PSPW= post-reflux swallow-induced peristaltic wave; MNBI=mean nocturnal baseline impedance. * for HC as compared with ERD and NERD
Non-erosive reflux disease (NERD) diagnosis as confirmed by pH-only criteria (75% of cases) and by impedance-pH criteria (98% of cases). Cumulative incidence of recurrent ulcer bleeding of naproxen+aspirin+esomeprazole (upper curve) vs. celecoxib+aspirin+esomeprazole (lower curve) p=0.01
816 Alterations of Human Gastric Microbiota in Patients With H. pylori Infection and Different Stages of Gastric Carcinogenesis Tung Hiu Li, Youwen Qin, Pak C. Sham, Wai K. Leung
815
Introduction: Apart from H. pylori (HP), the distribution and significance of other bacteria in human stomach remains largely unknown. This study aims to characterize the gastric microbiota in individuals with and without HP infections; to determine the changes in gastric microbiota after HP eradication; and to demonstrate the difference in gastric microbiota in individuals with different histological stages of gastric carcinogenesis. Methods: Endoscopic gastric biopsies were obtained from patients during scheduled endoscopy. All patients provided informed consent for participation into this study. HP status was determined by rapid urease test and histology. Bacterial 16S r RNA was sequenced on next generation sequencing platform (454 pyrosequencing or Illumina MiSeq). Operational taxonomic unit (OTU) clustering, diversity indexes calculation, taxonomic classification, PCoA and statistical analyses were performed after quality control and raw sequence processing. Hierarchical clustering based on weighted UniFrac distance of samples using Ward's algorithm was implemented. Results: Hierarchical clustering of samples obtained from 13 HP-positive patients and 14 HP-negative individuals demonstrated two cluster groups. The first cluster (cluster A) contained mostly HP-negative samples while the other cluster (cluster B) comprised exclusively of HP-positive samples. Cluster A has markedly increased microbial species diversity (average Shannon diversity index, 4.08 (SD 0.50) vs 1.95 (SD 0.46); p < 0.01). Same analyses were applied to 8 HP-positive patients who had serial biopsies taken before and after HP eradication therapy. All post-treatment samples, except one with failed eradication, had increased bacterial diversity. In the post-treatment group, non-HP Proteobacteria (p <0.01), Fusobacteria (p < 0.01) and Bacteriodetes (p < 0.01) were found to be increased. To assess the alterations of gastric microbiota in different histological stages of gastric carcinogenesis, we recruited another 8 patients with HP gastritis, 9 with gastric intestinal metaplasia (IM), 7 gastric carcinoma and 8 normal controls who were negative for HP. Hierarchical clustering of these samples showed that they were mainly segregated by the presence of HP rather than by histological stages (Figure). Gastric cancer samples however had reduced bacterial diversity as compared to other histological groups. There were also significant differences in the abundance of different bacterial families between IM and cancer samples, but not between normal and IM samples. Conclusion: H. pylori colonization results in alteration in gastric microbiota and reduction in bacterial diversity, which could possibly be restored by antibiotic treatment. There are significant changes in the relative abundance of different bacterial species in the stomach during progression from IM to cancer.
Novel Impedance Parameters Improve the Diagnostic Yield of Impedance-pH Monitoring in Gastroesophageal Reflux Disease. A Multicenter Study Marzio Frazzoni, Edoardo V. Savarino, Nicola de Bortoli, Irene Martinucci, Manuele Furnari, Leonardo Frazzoni, Vincenzo G. Mirante, Helga Bertani, Rita Conigliaro, Santino Marchi, Vincenzo Savarino Objective: Novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI) have been recently proposed to improve the diagnostic accuracy of impedance-pH monitoring. We aimed to assess their diagnostic accuracy in typical gastroesophageal reflux disease (GERD). Methods: Impedance-pH tracings from 289 patients with proton pump inhibitor (PPI) responsive heartburn and from 50 healthy controls were reviewed. The PSPW index, the MNBI, the percentage esophageal acid exposure time (EAET), the number of total refluxes, and the percentage bolus exposure were calculated, as well as the symptom association probability (SAP) and the symptom index (SI). Results: The PSPW index had the highest overall accuracy in 68 patients with erosive and in 221 patients with non-erosive reflux disease (NERD) (99% and 85%). Concerning NERD, in 118 pH-positive and in 103 pH-negative patients the PSPW index and the MNBI had the highest overall accuracy among impedance parameters (99% and 81%, and 73% and 44%, respectively). Diagnosis was confirmed by pH-only criteria, including SAP/SI positivity, in165/221 (75%) and by impedance-pH criteria in 202/221 (91%) NERD cases ( P = 0.001). At ROC analysis, the AUC of the PSPW index (0.977, 95% CI 0.961-0.993) was significantly higher than that of the other impedance-pH parameters (P < 0.001). Conclusions: In typical GERD the PSPW index and the MNBI demonstrate a high diagnostic accuracy, the former significantly higher than traditional impedance-pH parameters. By evaluating the PSPW index and the MNBI, impedance-pH criteria ensure a significant diagnostic gain compared to pH-only criteria.
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817 The SURF-Trial Pre-Assessment Cohort: A Multivariable Model Accurately Predicts Neoplastic Progression in Barrett's Esophagus Patients With LowGrade Dysplasia Lucas C. Duits, Cary C. Cotton, Kai Yi N. Phoa, Fiebo T. Ten Kate, Cees A. Seldenrijk, Johan Offerhaus, Mike Visser, Sybren L. Meijer, Rosalie C. Mallant-Hent, Kausilia K. Krishnadath, Roos E. Pouw, Jan Tijssen, Nicholas J. Shaheen, Jacques J. Bergman
Figure 1. Receiver operating characteristic curve comparing the basic clinical model (gender, age, circumferential Barrett's extent, time since Barrett's diagnosis) with the full predictive model (basic model plus number of expert pathologists confirming low-grade dysplasia (LGD) and number of levels with LGD).
Background The SURF trial was a randomized trial demonstrating that ablation of Barrett's esophagus (BE) with confirmed low-grade dysplasia (LGD) reduces progression to highgrade dysplasia (HGD) or esophageal adenocarcinoma (EAC) from 26.5% to 1.5%. However, the diagnosis of LGD is subjective and reported outcomes in LGD vary widely. We now report a model to predict the risk of developing HGD/EAC in BE patients diagnosed with LGD. Methods Three expert pathologists independently reviewed all histological specimens of 299 patients who were screened for the SURF trial. Patients were eligible for the current study if at least 1 pathologist diagnosed the patient with LGD. Each level of biopsies from the BE segment was independently evaluated by all three pathologists. The primary endpoint of this analysis was development of any HGD or EAC during endoscopic follow-up (FU). We performed bivariate Cox proportional hazards regression to assess the relationship between neoplastic progression and the number of pathologists confirming LGD, as well as the relationship between progression and multifocality of LGD in the segment. We performed multivariate logistic regression to estimate the cumulative incidence of progression to HGD/ EAC, adjusting for multiple potential confounders. The accuracy of the logistic regression model in discriminating between patients with and without neoplastic progression was assessed by C-statistic. Results In 107/299 screened patients multiple biopsy levels could be assessed separately and at least 1 pathologist confirmed the diagnosis LGD (79% men; mean age 63 years ±9.7), median duration of FU was 38 months (IQR 24-60). 31/107 patients (29%) developed HGD/EAC during FU. The number of expert pathologists confirming LGD and the number of levels with LGD were both strongly associated with an increased risk of progression, with a maximum hazard ratio of 19.7 and 10.3, respectively (table 1). The predictive model included gender, circumferential BE extent, age, time since BE diagnosis and the two novel histology-based predictors. When the number of expert pathologists confirming LGD and the number of levels with LGD were added to the model, the discriminatory ability (C-statistic) improved from 0.70 to 0.87 (figure 1). Conclusions A risk prediction model including clinical risk factors of progression and novel histology-based risk factors accurately predicts the risk of neoplastic progression in BE patients with LGD. The number of pathologists confirming LGD and multilevel LGD greatly contributed to the model. If the findings of this model are validated, assessment of pathology by multiple pathologists, and acquisition of samples in 2 cm segments of BE will allow these novel risk factors to provide marked improvement in risk stratification in LGD. Table 1. Unadjusted hazard ratios (HR) for histological covariates included in the full predictive model.
818 Use of COX-2 Specific NSAIDs Is Associated With Decreased Rates of GI Related Health Care Utilization in the General Population: A Population Based Analysis Laura Targownik, Lin Yan, Lisa Lix, Dan Chateau Background: Cyclo-oxygenase-2-specific NSAIDS, or coxibs are known to impart a lower risk of major gastrointestinal complications when compared to traditional NSAIDs (tNSAIDs), particularly among high-risk cohorts. Furthermore, coxib use has been shown to decrease the incidence of gastrointestinal symptoms and incident anemia, both of which may drive costly gastrointestinal related health care utilizations. We sought to determine the potential benefits in reducing GI related HCU by using coxibs in place of tNSAIDs among a complete population of new NSAID users. Methods: We used the Manitoba Health Population Health Research Data repository, which contains comprehensive health care utilization data on all Manitoban residents, to identify all new users age >=40 of traditional NSAIDs and coxibs between 2001 and 2011. We considered a person to be a new long-term user if there were at least 2 dispensations filled covering 30 days or greater, and no previous use of NSAIDs or coxibs at all in the 90 days prior to this date, and no use exceeding 30 days in the previous 3 years. Subjects were followed forward for the next 365 days to determine the frequency of GI related endoscopic and radiographic procedures, GI related physician visits, and overall hospitalizations. Outcomes were analyzed on an intention-to-treat assumption. Propensity scores for likelihood of receiving coxibs versus traditional NSAIDs were generated with a high-dimensional model assessing all medical diagnosis, demographic criteria and drug utilization over the year prior to entry. Inverse probability treatment weighting based on the generated propensity scores were used to create hypothetical cohorts of traditional NSAID users and coxib users balanced for baseline risk for the outcome events. Results: We identified 127,279 new long-term NSAID users (67230 coxib, 60049 tNSAID) who met entry criteria. Mean duration of NSAID use was 162 days for coxib users, and 108 days for tNSAID users. In the unadjusted analysis, the population of coxib users consumes GI-related health care resources and overall hospitalizations at a higher rate than a tNSAID using population. However, after adjusting for baseline risk, the population wide use of coxibs would result in statistically significant reductions in the use of lower endoscopy, overall endoscopy, physician and specialist visits for GI indications, GI related radiographic procedures, and overall hospitalizations. (See Table). Conclusions: Using coxibs in place of tNSAIDs would lead to statistically significant reductions in the rate of many aspects of GI-specific resource utilization. This may be sufficient to offset the higher direct drug-related costs of coxibs. Further work is required to calculate costs to determine if the more widespread use of coxibs over tNSAIDs is economically justified. Relative Rate of Outcome Events
LGD, low-grade dysplasia
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test for H. pylori, 3. cardiothrombotic diseases, and 4. anticipated regular use of NSAIDs for the duration of the trial. We excluded patients who used concomitant anticoagulants, had a history of gastroduodenal surgery other than a patch repair, gastric outlet obstruction, renal failure (serum creatinine level >200 µmol/L), pregnancy, terminal illness, or cancer. After providing written informed consent, all eligible patients received esomeprazole 20 mg once daily. They were randomized to receive either celecoxib 100 mg twice daily or naproxen 500 mg twice daily for up to 18 months. Patients were prescribed or asked to continue low-dose aspirin 80 mg once daily. The primary endpoint was recurrent ulcer bleeding within 18 months, which was defined as hematemesis, melena, or a decrease in the hemoglobin level of at least 2.0 g per deciliter with ulcers or bleeding erosions as adjudicated by an independent committee. Results: The intention-to treat population included 512 patients (256 celecoxib, 256 naproxen) who took at least one dose of study drug; 368 patients received concomitant low-dose aspirin (72.3% in the celecoxib group, 71.5% in the naproxen group). The demographic characteristics such as sex, age, type of arthritis, smoking, alcohol use, hemoglobin and creatinine levels were comparable between two groups. Fifteen patients (7.2%) receiving celecoxib and 31 (15.9%) receiving naproxen met the criteria for the primary endpoint (adjusted hazard ratio, 0.45; 95% CI, 0.26-0.84; p=0.01). Conclusion: Among patients with cardiothrombotic disease and a history of ulcer bleeding, combination of a COX-2 selective NSAID and a PPI is superior to a nonselective NSAID plus a PPI in preventing recurrent ulcer bleeding. Acknowledgment: This study was supported by a competitive grant from the Research Grant Council of Hong Kong (RGC project references: 460909 and 460910)
Table 1: Baseline characteristics of patients with erosive (ERD) and non-erosive (NERD) reflux disease, and of healthy controls (HC)
ERD=erosive reflux disease; NERD=non-erosive reflux disease; HC=healthy controls; BMI= body mass index; EAET=esophageal acid exposure time; SD=standard deviation: PSPW= post-reflux swallow-induced peristaltic wave; MNBI=mean nocturnal baseline impedance. * for HC as compared with ERD and NERD
Non-erosive reflux disease (NERD) diagnosis as confirmed by pH-only criteria (75% of cases) and by impedance-pH criteria (98% of cases). Cumulative incidence of recurrent ulcer bleeding of naproxen+aspirin+esomeprazole (upper curve) vs. celecoxib+aspirin+esomeprazole (lower curve) p=0.01
816 Alterations of Human Gastric Microbiota in Patients With H. pylori Infection and Different Stages of Gastric Carcinogenesis Tung Hiu Li, Youwen Qin, Pak C. Sham, Wai K. Leung
815
Introduction: Apart from H. pylori (HP), the distribution and significance of other bacteria in human stomach remains largely unknown. This study aims to characterize the gastric microbiota in individuals with and without HP infections; to determine the changes in gastric microbiota after HP eradication; and to demonstrate the difference in gastric microbiota in individuals with different histological stages of gastric carcinogenesis. Methods: Endoscopic gastric biopsies were obtained from patients during scheduled endoscopy. All patients provided informed consent for participation into this study. HP status was determined by rapid urease test and histology. Bacterial 16S r RNA was sequenced on next generation sequencing platform (454 pyrosequencing or Illumina MiSeq). Operational taxonomic unit (OTU) clustering, diversity indexes calculation, taxonomic classification, PCoA and statistical analyses were performed after quality control and raw sequence processing. Hierarchical clustering based on weighted UniFrac distance of samples using Ward's algorithm was implemented. Results: Hierarchical clustering of samples obtained from 13 HP-positive patients and 14 HP-negative individuals demonstrated two cluster groups. The first cluster (cluster A) contained mostly HP-negative samples while the other cluster (cluster B) comprised exclusively of HP-positive samples. Cluster A has markedly increased microbial species diversity (average Shannon diversity index, 4.08 (SD 0.50) vs 1.95 (SD 0.46); p < 0.01). Same analyses were applied to 8 HP-positive patients who had serial biopsies taken before and after HP eradication therapy. All post-treatment samples, except one with failed eradication, had increased bacterial diversity. In the post-treatment group, non-HP Proteobacteria (p <0.01), Fusobacteria (p < 0.01) and Bacteriodetes (p < 0.01) were found to be increased. To assess the alterations of gastric microbiota in different histological stages of gastric carcinogenesis, we recruited another 8 patients with HP gastritis, 9 with gastric intestinal metaplasia (IM), 7 gastric carcinoma and 8 normal controls who were negative for HP. Hierarchical clustering of these samples showed that they were mainly segregated by the presence of HP rather than by histological stages (Figure). Gastric cancer samples however had reduced bacterial diversity as compared to other histological groups. There were also significant differences in the abundance of different bacterial families between IM and cancer samples, but not between normal and IM samples. Conclusion: H. pylori colonization results in alteration in gastric microbiota and reduction in bacterial diversity, which could possibly be restored by antibiotic treatment. There are significant changes in the relative abundance of different bacterial species in the stomach during progression from IM to cancer.
Novel Impedance Parameters Improve the Diagnostic Yield of Impedance-pH Monitoring in Gastroesophageal Reflux Disease. A Multicenter Study Marzio Frazzoni, Edoardo V. Savarino, Nicola de Bortoli, Irene Martinucci, Manuele Furnari, Leonardo Frazzoni, Vincenzo G. Mirante, Helga Bertani, Rita Conigliaro, Santino Marchi, Vincenzo Savarino Objective: Novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI) have been recently proposed to improve the diagnostic accuracy of impedance-pH monitoring. We aimed to assess their diagnostic accuracy in typical gastroesophageal reflux disease (GERD). Methods: Impedance-pH tracings from 289 patients with proton pump inhibitor (PPI) responsive heartburn and from 50 healthy controls were reviewed. The PSPW index, the MNBI, the percentage esophageal acid exposure time (EAET), the number of total refluxes, and the percentage bolus exposure were calculated, as well as the symptom association probability (SAP) and the symptom index (SI). Results: The PSPW index had the highest overall accuracy in 68 patients with erosive and in 221 patients with non-erosive reflux disease (NERD) (99% and 85%). Concerning NERD, in 118 pH-positive and in 103 pH-negative patients the PSPW index and the MNBI had the highest overall accuracy among impedance parameters (99% and 81%, and 73% and 44%, respectively). Diagnosis was confirmed by pH-only criteria, including SAP/SI positivity, in165/221 (75%) and by impedance-pH criteria in 202/221 (91%) NERD cases ( P = 0.001). At ROC analysis, the AUC of the PSPW index (0.977, 95% CI 0.961-0.993) was significantly higher than that of the other impedance-pH parameters (P < 0.001). Conclusions: In typical GERD the PSPW index and the MNBI demonstrate a high diagnostic accuracy, the former significantly higher than traditional impedance-pH parameters. By evaluating the PSPW index and the MNBI, impedance-pH criteria ensure a significant diagnostic gain compared to pH-only criteria.
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817 The SURF-Trial Pre-Assessment Cohort: A Multivariable Model Accurately Predicts Neoplastic Progression in Barrett's Esophagus Patients With LowGrade Dysplasia Lucas C. Duits, Cary C. Cotton, Kai Yi N. Phoa, Fiebo T. Ten Kate, Cees A. Seldenrijk, Johan Offerhaus, Mike Visser, Sybren L. Meijer, Rosalie C. Mallant-Hent, Kausilia K. Krishnadath, Roos E. Pouw, Jan Tijssen, Nicholas J. Shaheen, Jacques J. Bergman
Figure 1. Receiver operating characteristic curve comparing the basic clinical model (gender, age, circumferential Barrett's extent, time since Barrett's diagnosis) with the full predictive model (basic model plus number of expert pathologists confirming low-grade dysplasia (LGD) and number of levels with LGD).
Background The SURF trial was a randomized trial demonstrating that ablation of Barrett's esophagus (BE) with confirmed low-grade dysplasia (LGD) reduces progression to highgrade dysplasia (HGD) or esophageal adenocarcinoma (EAC) from 26.5% to 1.5%. However, the diagnosis of LGD is subjective and reported outcomes in LGD vary widely. We now report a model to predict the risk of developing HGD/EAC in BE patients diagnosed with LGD. Methods Three expert pathologists independently reviewed all histological specimens of 299 patients who were screened for the SURF trial. Patients were eligible for the current study if at least 1 pathologist diagnosed the patient with LGD. Each level of biopsies from the BE segment was independently evaluated by all three pathologists. The primary endpoint of this analysis was development of any HGD or EAC during endoscopic follow-up (FU). We performed bivariate Cox proportional hazards regression to assess the relationship between neoplastic progression and the number of pathologists confirming LGD, as well as the relationship between progression and multifocality of LGD in the segment. We performed multivariate logistic regression to estimate the cumulative incidence of progression to HGD/ EAC, adjusting for multiple potential confounders. The accuracy of the logistic regression model in discriminating between patients with and without neoplastic progression was assessed by C-statistic. Results In 107/299 screened patients multiple biopsy levels could be assessed separately and at least 1 pathologist confirmed the diagnosis LGD (79% men; mean age 63 years ±9.7), median duration of FU was 38 months (IQR 24-60). 31/107 patients (29%) developed HGD/EAC during FU. The number of expert pathologists confirming LGD and the number of levels with LGD were both strongly associated with an increased risk of progression, with a maximum hazard ratio of 19.7 and 10.3, respectively (table 1). The predictive model included gender, circumferential BE extent, age, time since BE diagnosis and the two novel histology-based predictors. When the number of expert pathologists confirming LGD and the number of levels with LGD were added to the model, the discriminatory ability (C-statistic) improved from 0.70 to 0.87 (figure 1). Conclusions A risk prediction model including clinical risk factors of progression and novel histology-based risk factors accurately predicts the risk of neoplastic progression in BE patients with LGD. The number of pathologists confirming LGD and multilevel LGD greatly contributed to the model. If the findings of this model are validated, assessment of pathology by multiple pathologists, and acquisition of samples in 2 cm segments of BE will allow these novel risk factors to provide marked improvement in risk stratification in LGD. Table 1. Unadjusted hazard ratios (HR) for histological covariates included in the full predictive model.
818 Use of COX-2 Specific NSAIDs Is Associated With Decreased Rates of GI Related Health Care Utilization in the General Population: A Population Based Analysis Laura Targownik, Lin Yan, Lisa Lix, Dan Chateau Background: Cyclo-oxygenase-2-specific NSAIDS, or coxibs are known to impart a lower risk of major gastrointestinal complications when compared to traditional NSAIDs (tNSAIDs), particularly among high-risk cohorts. Furthermore, coxib use has been shown to decrease the incidence of gastrointestinal symptoms and incident anemia, both of which may drive costly gastrointestinal related health care utilizations. We sought to determine the potential benefits in reducing GI related HCU by using coxibs in place of tNSAIDs among a complete population of new NSAID users. Methods: We used the Manitoba Health Population Health Research Data repository, which contains comprehensive health care utilization data on all Manitoban residents, to identify all new users age >=40 of traditional NSAIDs and coxibs between 2001 and 2011. We considered a person to be a new long-term user if there were at least 2 dispensations filled covering 30 days or greater, and no previous use of NSAIDs or coxibs at all in the 90 days prior to this date, and no use exceeding 30 days in the previous 3 years. Subjects were followed forward for the next 365 days to determine the frequency of GI related endoscopic and radiographic procedures, GI related physician visits, and overall hospitalizations. Outcomes were analyzed on an intention-to-treat assumption. Propensity scores for likelihood of receiving coxibs versus traditional NSAIDs were generated with a high-dimensional model assessing all medical diagnosis, demographic criteria and drug utilization over the year prior to entry. Inverse probability treatment weighting based on the generated propensity scores were used to create hypothetical cohorts of traditional NSAID users and coxib users balanced for baseline risk for the outcome events. Results: We identified 127,279 new long-term NSAID users (67230 coxib, 60049 tNSAID) who met entry criteria. Mean duration of NSAID use was 162 days for coxib users, and 108 days for tNSAID users. In the unadjusted analysis, the population of coxib users consumes GI-related health care resources and overall hospitalizations at a higher rate than a tNSAID using population. However, after adjusting for baseline risk, the population wide use of coxibs would result in statistically significant reductions in the use of lower endoscopy, overall endoscopy, physician and specialist visits for GI indications, GI related radiographic procedures, and overall hospitalizations. (See Table). Conclusions: Using coxibs in place of tNSAIDs would lead to statistically significant reductions in the rate of many aspects of GI-specific resource utilization. This may be sufficient to offset the higher direct drug-related costs of coxibs. Further work is required to calculate costs to determine if the more widespread use of coxibs over tNSAIDs is economically justified. Relative Rate of Outcome Events
LGD, low-grade dysplasia
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