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Are Proton Pump Inhibitors a True Risk Factor in Clostridium difficile Infection?: A Longitudinal Cohort Study
study entry. Patients were limited to those diagnosed as H. pylori-negative by urinary antibody measurement, with any of the following upper abdominal symptoms: epigastric pain, heartburn, sensation of gastric acid reflux, heavy stomach, nausea, belching, early feeling of satiety, and sensation of abdominal distension. One hundred and ninety-five patients (72 males and 123 females; age, 18-88 years; average age, 44.0 years) meeting the above criteria were included in the study. Patients who had undergone gastrectomy, eradication of H. pylori, or oral NSAID treatment and other ineligible patients were excluded. Methods: The patients were randomly divided into three groups: A continuous omeprazole 20mg treatment group (OPZ20); a continuous omeprazole 10mg treatment group (OPZ10); and an ondemand omeprazole 20mg treatment group (On-demand). After four-week administration of the drug, symptom improvement rates were evaluated with GOS scores. During the study period, other gastric acid secretion inhibitors, defense factor enhancement drugs, and antacids were prohibited. Results: The patients were assigned to three groups: 61 patients, OPZ20 group; 72, OPZ10 group; and 62, On-demand group. The rates of symptom improvement after four-week administration were 65.6% (40/61) in the OPZ20 group, 47.2% (34/72) in the OPZ10 group, and 50.0% (31/62) in the On-demand group. The OPZ20 group exhibited a significantly higher improvement rate (p=0.034) of upper abdominal symptoms than the OPZ10 group. The improvement in the OPZ10 group was almost the same as that in the On-demand group. Analysis of improvement effects by symptom showed that the OPZ20 group had significant improvements in sensation of gastric acid reflux, heavy stomach, nausea, and sensation of abdominal distension compared with the OPZ10 group. Conclusions: Efficacy of PPIs in treating upper abdominal symptoms was observed. In particular, OPZ 20 mg was more effective for sensation of gastric acid reflux, heavy stomach, nausea, and sensation of abdominal distention than the other treatments examined.
372 Pediatric Intestinal Failure in the Intestinal Transplant Era: A Retrospective Review of 272 Infants Robert Squires, Christopher Duggan, Daniel H. Teitelbaum, Paul W. Wales, Jane Balint, Robert Venick, Sue Rhee, Debra L. Sudan, David F. Mercer, J Andres Martinez, Beth A. Carter, Jason Soden, Simon Horslen, Jeffrey A. Rudolph, Samuel A. Kocoshis, Riccardo A. Superina, Steven H. Belle Background. Pediatric intestinal failure (IF) is a rare but devastating condition defined as the inability of the intestine to support growth and development without supplemental parenteral nutrition (PN). A retrospective study was performed to provide the foundation for the first prospective study of IF in North America. Methods. PIFCon includes 14 sites with multi-disciplinary IF management teams; 9 are also intestinal transplant (ITx) centers. Infants <12 mo receiving PN for > 60 continuous days for IF were included. Demographic, clinical, biochemical, nutritional and outcome data were abstracted from medical charts. Values are presented as median (25th, 75th percentiles) or as (n, %). Enteral autonomy (EA) was defined as the discontinuation of PN for > 3 consecutive mo. Results. 272 infants with a gestational age of 34 wks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 mo (11.2, 40.9). The majority were male (156, 57%) and Caucasian (204, 75%). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), intestinal atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), intestinal aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). The cumulative proportions achieving EA at 1 and 3 yr were 0.31 and 0.43, respectively. Commonly used medications were oral antibiotics (207, 76%), H2 blockers (187, 69%), and PPIs (156, 57%). Breast milk was given to 52 (19%); the cumulative probabilities of oral solid feeding were .67 at 1 yr and .85 at 3 yr. 25 different infant formulas were used as initial diet; 40 different formulas were used overall. 3.3 new catheter related blood stream infections occurred per person year (PPY) on PN and 0.2 intestinal bleeding episodes PPY of observation. 28 bowel lengthening procedures were performed. Cumulative probability of survival (CPS) was 0.84 at 1 yr and 0.74 at 3 yr. 58 died before and 10 died after ITx. Following study entry, time to death without ITx was 8.2 mo (4.8, 12.6). 137 were alive without ITx when the last data were abstracted from the medical record. 60 received ITx, the cumulative incidence of ITx at 1 and 3 years was .087 and .229, respectively. The CPS 1 year after ITx was 0.84. Conclusions. Children with IF suffer a high rate of mortality and morbidity. EA may require years to achieve. Substantial practice variability is noted among sites. Improved medical, nutritional, and surgical management of IF may reduce time on PN, mortality and need for ITx. Grant support: NIH/NIDDK R21 DK081059-01
375 Cardiovascular Implications of Proton Pump Inhibitors and Clopidogrel Interaction: A Meta-Analysis of Randomized Controlled Trials Sandhya Shukla, Sushovan Guha Introduction: Dual antiplatelet therapy (DAP) with Clopidogrel (C) and Aspirin (ASA) has been the standard of therapy for the secondary prevention of coronary events in patients treated medically or by intervention for acute coronary syndrome (ACS). Due to risk of adverse gastrointestinal (GI) events such as bleeding proton pump inhibitors (PPI) are frequently prescribed with DAP. However, many studies recently have reported decreased efficacy of C due to its interaction with PPI leading to adverse cardiovascular (CV) outcomes. Most of these studies have been observational and thus limited in design. We therefore, undertook a meta-analysis of Randomized Controlled Trials to evaluate if there are more adverse CV outcomes in users of C+PPI compared to use of C alone. Methods: Two independent reviewers searched MEDLINE, EMBASE, Cochrane central register and abstracts of pertinent scientific meetings (ACC, AHA, DDW and ACG; 2006-2010). Inclusion Criteria: 1) Randomized controlled trial. 2) Study should have reported clinical outcomes in patients who received C+PPI in comparison to C alone. 3) Study conducted in humans in English language only. The primary outcome evaluated was any adverse cardiovascular event (myocardial infarction, revascularization, stroke, death). The results of these studies were combined and a pooled relative risk ratio (RR) and 95% confidence interval (95% CI) and heterogeneity were derived using random effects estimate. Results: Three studies with 11609 patients met our pre-specified criteria of which 4309 were randomized to C and PPI while 7300 to C alone. The relative risk of adverse cardiovascular events in C + PPI group was 1.10 with 95% CI 0.75 - 1.61, p = 0.6 in comparison to use of C alone. Heterogeneity estimated by chi-square was 8.87, p = 0.012 and I square was 77.5%. Conclusion: The results of our meta-analysis show no increased adverse CV events in patients on concurrent C and PPI compared with C alone. These results differ from those of most observational studies but consistent with the most recent published RCT. Future study designs should focus on well powered prospective randomized trials to better understand the clinical implications of concurrent use of these two drugs.
373 Are Proton Pump Inhibitors a True Risk Factor in Clostridium difficile Infection?: A Longitudinal Cohort Study Kyoung Sup Hong, Seung Joo Kang, Jong Pil Im, Joo Sung Kim Background/Aims: Several recent studies have associated proton pump inhibitors (PPIs) with a 2- to 3-fold increase in the risk of C. difficile infection (CDI). However, a case-control design is highly dependent on the comparability of the control group and the role of PPIs in the pathogenesis of CDI is still controversial. We aimed to evaluate the effect of treatment duration on CDI development among PPIs-treated patients. Methods: We identified all patients who were more than 20 years old and took a prescription of PPIs among those who visited the Seoul National University Hospital from January 1, 2005, to December 31, 2009, based on information from clinical data warehouse. CDI was defined as a positive C. difficile toxin assay result. The patients were divided into three groups according to the treatment duration (group 1: < 3 months; group 2: 3~12 months; group 3: > 12 months) and followed from the time to take the first prescription of PPIs until the last visit. Cox proportional hazard regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates. Results: Among 61,833 patients exposed to PPIs (50,534 in group 1; 9122 in group 2; 2177 in group 3), 534 patients diagnosed as CDI during 124,274 person-years of follow-up (319 in group 1; 177 in group 2; 38 in group 3). Longer duration of PPIs therapy was associated with increased risk of CDI (RR: 2.70; 95% CI: 2.24-3.25 in group 2, RR: 1.85; 95% CI: 1.31-2.60 in group 3, p-value for trend: <0.01), after adjusted for age, gender, antibiotics use, and co-morbidities. Conclusions: There is a fair association between long term PPIs therapy and CDI risk, but CDI risk in group 2 was higher than that in group 3. These results suggest that PPIs may be a risk factor and simultaneously an important confounder in CDI development.
376 Esomeprazole Plus Aspirin Compared With Esomeprazole Alone for the Treatment of Aspirin-Related Peptic Ulcers/Erosions Ping-I Hsu Background: The use of aspirin is associated with an increased risk of peptic ulcer development. Aims: To compare esomeprazole plus aspirin with esomeprazole alone in the treatment of aspirin-related ulcers/erosions and to investigate the independent factors predicting the healing of aspirin-related ulcers/erosions. Methods: Patients with aspirin-related peptic ulcer/ erosions were randomized to receive esomeprazole (40 mg/day) plus aspirin (100 mg/day) or esomeprazole (40 mg/day) alone for 8 weeks. The subjects with H pylori infection were treated by a 7-day standard triple therapy. Success was defined as healing of ulcer/erosion at the eighth week. Results: One hundred and forty-three patients (72 assigned to receive esomeprazole plus aspirin and 71 to receive esomeprazole alone) were enrolled for the clinical study. The healing rate of ulcers/erosions by intention-to-treat analysis was 73.6% (95% confidence interval [CI], 63.4 to 83.8%) among patients treated with esomeprazole plus aspirin, and 81.7% (95% CI, 72.7 to 90.7%) among patients treated with esomeprazole alone (Difference, 8.1%; 95% CI for the difference, -5.5 to 21.7%, P = 0.246). Multivariate analysis disclosed that the female gender (odds ratio [OR]: 3.2, 95% CI, 1.3 - 8.2), smoking (OR: 3.7, 95% CI, 1.3 - 10.8) and persistent H pylori infection (OR: 14.1, 95% CI, 1.3 149.9) were independent factors predicting failure of ulcer/erosion healing. Conclusion: Continuing use of aspirin does not significantly impair healing of aspirin-related peptic ulcers/erosions under proton pump inhibitor therapy. Abstaining from smoking and effective H pylori eradication are important factors for the healing of aspirin-related peptic ulcers/erosions.
374 A Study of the Efficacy of Proton Pump Inhibitors in Treating Upper Abdominal Symptoms Tomoari Kamada, Yoshinori Fujimura, Kensuke Goto, Noriaki Manabe, Hiroshi Imamura, Naohito Yamashita, Hiroaki Kusunoki, Kazuhiko Inoue, Akiko Shiotani, Jiro Hata, Ken Haruma Background and aim: Functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) are mainly treated with drugs such as gastrointestinal prokinetic agents, gastric acid secretion inhibitors, and antianxiety agents, but there have been few studies of the efficacy of proton pump inhibitors (PPI) and the doses of them required to treat upper abdominal symptoms frequently seen in clinical practice without endoscopy. Patients: The subjects were patients with chronic or recurrent upper abdominal symptoms within the past three months who had not undergone endoscopy within the past three months, and who had one or more symptoms with not smaller than a Global Overall Severity (GOS) score of 4 at the time of
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AGA Abstracts
AGA Abstracts
medication exposures varied between the sub-groups. Conclusions: Genetic variants in IL27, JAK2, and STAT3 which increase risk for CD are also associated with serum GM-CSF Ab concentration.
372 Pediatric Intestinal Failure in the Intestinal Transplant Era: A Retrospective Review of 272 Infants Robert Squires, Christopher Duggan, Daniel H. Teitelbaum, Paul W. Wales, Jane Balint, Robert Venick, Sue Rhee, Debra L. Sudan, David F. Mercer, J Andres Martinez, Beth A. Carter, Jason Soden, Simon Horslen, Jeffrey A. Rudolph, Samuel A. Kocoshis, Riccardo A. Superina, Steven H. Belle Background. Pediatric intestinal failure (IF) is a rare but devastating condition defined as the inability of the intestine to support growth and development without supplemental parenteral nutrition (PN). A retrospective study was performed to provide the foundation for the first prospective study of IF in North America. Methods. PIFCon includes 14 sites with multi-disciplinary IF management teams; 9 are also intestinal transplant (ITx) centers. Infants <12 mo receiving PN for > 60 continuous days for IF were included. Demographic, clinical, biochemical, nutritional and outcome data were abstracted from medical charts. Values are presented as median (25th, 75th percentiles) or as (n, %). Enteral autonomy (EA) was defined as the discontinuation of PN for > 3 consecutive mo. Results. 272 infants with a gestational age of 34 wks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 mo (11.2, 40.9). The majority were male (156, 57%) and Caucasian (204, 75%). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), intestinal atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), intestinal aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). The cumulative proportions achieving EA at 1 and 3 yr were 0.31 and 0.43, respectively. Commonly used medications were oral antibiotics (207, 76%), H2 blockers (187, 69%), and PPIs (156, 57%). Breast milk was given to 52 (19%); the cumulative probabilities of oral solid feeding were .67 at 1 yr and .85 at 3 yr. 25 different infant formulas were used as initial diet; 40 different formulas were used overall. 3.3 new catheter related blood stream infections occurred per person year (PPY) on PN and 0.2 intestinal bleeding episodes PPY of observation. 28 bowel lengthening procedures were performed. Cumulative probability of survival (CPS) was 0.84 at 1 yr and 0.74 at 3 yr. 58 died before and 10 died after ITx. Following study entry, time to death without ITx was 8.2 mo (4.8, 12.6). 137 were alive without ITx when the last data were abstracted from the medical record. 60 received ITx, the cumulative incidence of ITx at 1 and 3 years was .087 and .229, respectively. The CPS 1 year after ITx was 0.84. Conclusions. Children with IF suffer a high rate of mortality and morbidity. EA may require years to achieve. Substantial practice variability is noted among sites. Improved medical, nutritional, and surgical management of IF may reduce time on PN, mortality and need for ITx. Grant support: NIH/NIDDK R21 DK081059-01
375 Cardiovascular Implications of Proton Pump Inhibitors and Clopidogrel Interaction: A Meta-Analysis of Randomized Controlled Trials Sandhya Shukla, Sushovan Guha Introduction: Dual antiplatelet therapy (DAP) with Clopidogrel (C) and Aspirin (ASA) has been the standard of therapy for the secondary prevention of coronary events in patients treated medically or by intervention for acute coronary syndrome (ACS). Due to risk of adverse gastrointestinal (GI) events such as bleeding proton pump inhibitors (PPI) are frequently prescribed with DAP. However, many studies recently have reported decreased efficacy of C due to its interaction with PPI leading to adverse cardiovascular (CV) outcomes. Most of these studies have been observational and thus limited in design. We therefore, undertook a meta-analysis of Randomized Controlled Trials to evaluate if there are more adverse CV outcomes in users of C+PPI compared to use of C alone. Methods: Two independent reviewers searched MEDLINE, EMBASE, Cochrane central register and abstracts of pertinent scientific meetings (ACC, AHA, DDW and ACG; 2006-2010). Inclusion Criteria: 1) Randomized controlled trial. 2) Study should have reported clinical outcomes in patients who received C+PPI in comparison to C alone. 3) Study conducted in humans in English language only. The primary outcome evaluated was any adverse cardiovascular event (myocardial infarction, revascularization, stroke, death). The results of these studies were combined and a pooled relative risk ratio (RR) and 95% confidence interval (95% CI) and heterogeneity were derived using random effects estimate. Results: Three studies with 11609 patients met our pre-specified criteria of which 4309 were randomized to C and PPI while 7300 to C alone. The relative risk of adverse cardiovascular events in C + PPI group was 1.10 with 95% CI 0.75 - 1.61, p = 0.6 in comparison to use of C alone. Heterogeneity estimated by chi-square was 8.87, p = 0.012 and I square was 77.5%. Conclusion: The results of our meta-analysis show no increased adverse CV events in patients on concurrent C and PPI compared with C alone. These results differ from those of most observational studies but consistent with the most recent published RCT. Future study designs should focus on well powered prospective randomized trials to better understand the clinical implications of concurrent use of these two drugs.
373 Are Proton Pump Inhibitors a True Risk Factor in Clostridium difficile Infection?: A Longitudinal Cohort Study Kyoung Sup Hong, Seung Joo Kang, Jong Pil Im, Joo Sung Kim Background/Aims: Several recent studies have associated proton pump inhibitors (PPIs) with a 2- to 3-fold increase in the risk of C. difficile infection (CDI). However, a case-control design is highly dependent on the comparability of the control group and the role of PPIs in the pathogenesis of CDI is still controversial. We aimed to evaluate the effect of treatment duration on CDI development among PPIs-treated patients. Methods: We identified all patients who were more than 20 years old and took a prescription of PPIs among those who visited the Seoul National University Hospital from January 1, 2005, to December 31, 2009, based on information from clinical data warehouse. CDI was defined as a positive C. difficile toxin assay result. The patients were divided into three groups according to the treatment duration (group 1: < 3 months; group 2: 3~12 months; group 3: > 12 months) and followed from the time to take the first prescription of PPIs until the last visit. Cox proportional hazard regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates. Results: Among 61,833 patients exposed to PPIs (50,534 in group 1; 9122 in group 2; 2177 in group 3), 534 patients diagnosed as CDI during 124,274 person-years of follow-up (319 in group 1; 177 in group 2; 38 in group 3). Longer duration of PPIs therapy was associated with increased risk of CDI (RR: 2.70; 95% CI: 2.24-3.25 in group 2, RR: 1.85; 95% CI: 1.31-2.60 in group 3, p-value for trend: <0.01), after adjusted for age, gender, antibiotics use, and co-morbidities. Conclusions: There is a fair association between long term PPIs therapy and CDI risk, but CDI risk in group 2 was higher than that in group 3. These results suggest that PPIs may be a risk factor and simultaneously an important confounder in CDI development.
376 Esomeprazole Plus Aspirin Compared With Esomeprazole Alone for the Treatment of Aspirin-Related Peptic Ulcers/Erosions Ping-I Hsu Background: The use of aspirin is associated with an increased risk of peptic ulcer development. Aims: To compare esomeprazole plus aspirin with esomeprazole alone in the treatment of aspirin-related ulcers/erosions and to investigate the independent factors predicting the healing of aspirin-related ulcers/erosions. Methods: Patients with aspirin-related peptic ulcer/ erosions were randomized to receive esomeprazole (40 mg/day) plus aspirin (100 mg/day) or esomeprazole (40 mg/day) alone for 8 weeks. The subjects with H pylori infection were treated by a 7-day standard triple therapy. Success was defined as healing of ulcer/erosion at the eighth week. Results: One hundred and forty-three patients (72 assigned to receive esomeprazole plus aspirin and 71 to receive esomeprazole alone) were enrolled for the clinical study. The healing rate of ulcers/erosions by intention-to-treat analysis was 73.6% (95% confidence interval [CI], 63.4 to 83.8%) among patients treated with esomeprazole plus aspirin, and 81.7% (95% CI, 72.7 to 90.7%) among patients treated with esomeprazole alone (Difference, 8.1%; 95% CI for the difference, -5.5 to 21.7%, P = 0.246). Multivariate analysis disclosed that the female gender (odds ratio [OR]: 3.2, 95% CI, 1.3 - 8.2), smoking (OR: 3.7, 95% CI, 1.3 - 10.8) and persistent H pylori infection (OR: 14.1, 95% CI, 1.3 149.9) were independent factors predicting failure of ulcer/erosion healing. Conclusion: Continuing use of aspirin does not significantly impair healing of aspirin-related peptic ulcers/erosions under proton pump inhibitor therapy. Abstaining from smoking and effective H pylori eradication are important factors for the healing of aspirin-related peptic ulcers/erosions.
374 A Study of the Efficacy of Proton Pump Inhibitors in Treating Upper Abdominal Symptoms Tomoari Kamada, Yoshinori Fujimura, Kensuke Goto, Noriaki Manabe, Hiroshi Imamura, Naohito Yamashita, Hiroaki Kusunoki, Kazuhiko Inoue, Akiko Shiotani, Jiro Hata, Ken Haruma Background and aim: Functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) are mainly treated with drugs such as gastrointestinal prokinetic agents, gastric acid secretion inhibitors, and antianxiety agents, but there have been few studies of the efficacy of proton pump inhibitors (PPI) and the doses of them required to treat upper abdominal symptoms frequently seen in clinical practice without endoscopy. Patients: The subjects were patients with chronic or recurrent upper abdominal symptoms within the past three months who had not undergone endoscopy within the past three months, and who had one or more symptoms with not smaller than a Global Overall Severity (GOS) score of 4 at the time of
S-79
AGA Abstracts
AGA Abstracts
medication exposures varied between the sub-groups. Conclusions: Genetic variants in IL27, JAK2, and STAT3 which increase risk for CD are also associated with serum GM-CSF Ab concentration.