Gastric Acid Suppression Therapy Research Articles

Gastric Acid Suppression Therapy and Its Association with Peritoneal Dialysis-Associated Peritonitis in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

Peritonitis is a major peritoneal dialysis (PD) related complication. We determined whether gastric acid suppression (GAS) (proton pump inhibitor (PPI) or histamine-2 receptor antagonists (H2RA)) use was associated with all-cause and organism-specific peritonitis in PD patients. In the Peritoneal Dialysis Outcomes and Practice Patterns Study (595 facilities, 8 countries, years 2014-2022), associations between GAS use and time to first episode of all-cause peritonitis were examined using Cox proportional hazards models. The primary exposure of interest was GAS, and secondarily PPI or H2RA use. Secondary outcomes were organism-specific peritonitis, peritonitis cure rates, and death. Among patients (n=23 797) at study baseline, 6020 (25.3%) used PPIs, and 1382 (5.8%) used H2RAs. Overall risks of GAS use and peritonitis risk [adjusted hazard ratio (AHR)=1.05 (95% CI 0.98-1.13)], and use of PPI [AHR 1.06 (95% CI 0.99-1.14)] or H2RA [AHR 1.02 (95% CI 0.88-1.18)] did not reach statistical significance. In organism-specific analyses, GAS users displayed higher peritonitis risks for gram-negative (AHR 1.29, 95% CI 1.05-1.57), gram-positive (AHR 1.15, 95% CI 1.01-1.31), culture-negative (AHR 1.20, 95% CI 1.01-1.42), enteric (AHR 1.23, 95% CI 1.03-1.48), and particularly Streptococcal (AHR 1.47, 95% CI 1.15-1.89) peritonitis episodes. GAS was also associated with higher overall mortality [AHR 1.13 (95% CI 1.05-1.22)]. The association between GAS use and peritonitis risk was weaker (HR 1.05 [0.98-1.13]) than for streptococcal (HR 1.57 [1.15-1.89]) and gram-negative (HR 1.29 [1.05-1.57]) peritonitis. A better understanding of mechanisms surrounding the differential effects of GAS subtype on peritonitis risks is needed. Clinicians should be cautious when prescribing GAS. The impact of GAS deprescribing on peritonitis risk requires further evaluation.

S1606 A Retrospective Study of Doxycycline-Based Quadruple Therapy versus Tetracycline-Based Quadruple Therapy for the First Line Treatment of Helicobacter pylori

Introduction: The global prevalence of antimicrobial resistance has resulted in challenges with H. pylori eradication. Gastric acid suppression and antibiotic therapy are used to eradicate H. pylori. Cost and shortages inhibit use of tetracycline for first line treatment of H. pylori. Doxycycline represents a possible cost-effective alternative for treating H. pylori. We performed an analysis of first line doxycycline-based quadruple therapy in comparison to tetracycline-based quadruple therapy in the eradication of H. pylori. Methods: A retrospective chart review was conducted using the Advocate Aurora Health database, a multi-hospital community-based system consisting of sixteen hospitals and over 500 sites of care. All patients age 18 and older with documented H. pylori infection treated with either a first line doxycycline-based regimen (DOX) or tetracycline-based regimen (TCN) from January 2012 to April 2022 were included. In total, 3,384 patients were identified. Patients who received prior first-line treatment with other regimens were excluded. All cases were reviewed for confirmation of infection (either by biopsy, breath test or stool antigen testing), the treatment regimen used, and confirmation of H. Pylori eradication (either by biopsy, breath test, or stool antigen). Patients without confirmation of eradication or with pending eradication test results were excluded. Patient demographics were summarized and eradication rates determined. Results: Of the 3,384 reviewed cases, 628 cases met inclusion and exclusion criteria. Of these, 305 patients were treated with DOX and 323 patients were treated with TCN. Based on these numbers, a posteriori non-inferiority calculation with an assumed 85% eradication rate for the TCN and 80% for DOX and 90% power suggested 100 patents were needed per group (HyLown Consulting LLC, Statistical Calculators). The average age for DOX was 57 years and 193/305 (60%) were female. The average age for TCN was 58.5 years and 210/323 (69%) were female. Eradication rates were 87.6% for DOX and 88.2% for TCN (Table). Conclusion: Doxycycline-based quadruple therapy regimen is effective and appears to be non-inferior to tetracycline-based quadruple therapy regimens for first line treatment of H. pylori. Table 1. - The number of patients with tetracycline or doxycycline antibiotic regimens and the eradication rate Doxycycline Regimen # of Patients % of Patients Successful Eradication 283 87.6% Failed Eradication 40 12.4% Total 323 Tetracycline Regimen # of Patients % of Patients Successful Eradication 269 88.2% Failed Eradication 36 11.8% Total 305

98. Outcomes of Clinical Decision Support for Outpatient Management of Clostridioides difficile Infection

BackgroundOur antimicrobial stewardship program identified high rates of suboptimal metronidazole prescribing for Clostridioides difficile infection (CDI) within ambulatory clinics. An outpatient best practice advisory (BPA) was implemented to notify prescribers “Vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI. MethodsWe conducted an IRB approved quasi-experiment before and after implementation of the BPA on June 3, 2020. Inclusion: Adult patients diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between 11/1/2019 and 11/30/2020. Exclusion: fulminant CDI. Primary endpoint: guideline-concordant CDI therapy, defined as oral vancomycin or fidaxomicin. Oral metronidazole was considered guideline-concordant if prescribed due to cost barrier. Secondary endpoints: reasons for alternative CDI therapy, patient outcomes, prescriber response to the BPA. Descriptive and bivariate analyses were completed.Results189 patients were included in the study, 92 before and 97 after the BPA. Median age: 59 years, 31% male, 75% Caucasian, 30% with CDI-related comorbidities, 35% with healthcare exposure, 65% with antibiotic exposure, 44% with gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 out of 26 times and optimized the therapy of 16 patients in six months. Guideline-concordant therapy increased after implementation of the BPA (72% vs. 91%, p=0.001) (Figure 1). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA (Figure 2). Reasons for alternative CDI therapy included medication cost, lack of insurance coverage, and non-CDI infection. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs. 7%, p< 0.001). Figure 1. Guideline-concordant CDI therapy Figure 2. Specific CDI therapy ConclusionClinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.Disclosures Susan L. Davis, PharmD, Nothing to disclose Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

Outcomes of clinical decision support for outpatient management of Clostridioides difficile infection.

To determine the impact of clinical decision support on guideline-concordant Clostridioides difficile infection (CDI) treatment. Quasi-experimental study in >50 ambulatory clinics. Primary, specialty, and urgent-care clinics. Adult patients were eligible for inclusion if they were diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between November 1, 2019, and November 30, 2020. An outpatient best practice advisory (BPA) was implemented to notify prescribers that "vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection" when metronidazole was prescribed to a patient with CDI. In total, 189 patients were included in the study: 92 before the BPA and 97 after the BPA. Their median age was 59 years; 31% were male; 75% were white; 30% had CDI-related comorbidities; 35% had healthcare exposure; 65% had antibiotic exposure; 44% had gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. Guideline-concordant therapy increased after implementation of the BPA (72% vs 91%; P = .001). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs 7%; P < .001). Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.

As indicações da profilaxia de úlceras gástricas em pacientes pediátricos hospitalizados: uma revisão integrativa

OBJECTIVES: To determine the main indications for gastric ulcer prophylaxis in hospitalized pediatric patients and, through the analysis of scientific evidence, to point out the main complications of the indiscriminate use of this prophylaxis and to mention alternatives to the use of drugs in the prevention of stress ulcers. METHODS: We selected articles written in English and Portuguese, published between 2009 and 2019, which show the indications of stress ulcer prophylaxis in critically ill pediatric patients, as well as studies demonstrating the complications of gastric acid suppression therapy. The search was performed in the PubMed, LILACS and SciELO databases. RESULTS: In this integrative review, sixteen studies that met the previously established inclusion criteria were analyzed. Of the articles included in this study, four are prospective observational studies, eight are systematic reviews, seven with meta-analysis, two retrospective cohort studies, one case-control study, one expert-opinion guideline, and one case report. CONCLUSION: The indiscriminate use of stress ulcer prophylaxis is not recommended and should only be used when there is an accurate indication. However, even where therapy is recommended, the risk-benefit assessment should be assessed and caution should be exercised with acid-suppressing drugs, as this prophylaxis increases the risk of Clostridium difficile infection and pneumonia. It is also suggested the introduction of early enteral nutrition as an alternative to the use of gastric ulcer drug prophylaxis, as the evidence points to its efficacy in reducing adverse effects and maintaining gastric homeostasis.

Risk factors for Clostridioides difficile colonization among hospitalized adults: A meta-analysis and systematic review.

To identify risk factors for asymptomatic Clostridioides difficile colonization among hospitalized adults utilizing a meta-analysis, which may enable early identification of colonized patients at risk of spreading C. difficile. Meta-analysis and systematic review. We systematically searched MEDLINE, Scopus, Web of Science, and EMBASE from January 1, 1975, to February 15, 2020, for articles related to C. difficile colonization among hospitalized adults. Studies with multivariable analyses evaluating risk factors for asymptomatic colonization were eligible. Among 5,506 studies identified in the search, 19 studies met the inclusion criteria. Included studies reported 20,334 adult patients of whom 1,588 were asymptomatically colonized with C. difficile. Factors associated with an increased risk of colonization were hospitalization in the previous 6 months (OR, 2.18; 95% CI, 1.86-2.56; P < .001), use of gastric acid suppression therapy within the previous 8 weeks (OR, 1.42; 95% CI, 1.17-1.73; P < .001), tube feeding (OR, 2.02; 95% CI, 1.06-3.85; P = .03), and corticosteroid use in the previous 8 weeks (OR, 1.58; 95% CI, 1.14-2.17; P = .006). Receipt of antibiotics in the previous 3 months (OR, 1.37; 95% CI, 0.94-2.01; P = .10) was not associated with statistically significant effects on risk of colonization. C. difficile colonization was significantly associated with previous hospitalization, gastric acid suppression, tube feeding, and corticosteroid use. Recognition of these risk factors may assist in identifying asymptomatic carriers of C. difficile and taking appropriate measures to reduce transmission.

Administration of erlotinib in apple juice overcomes decreased absorption in a rat model of gastric acid suppression

Erlotinib shows pH-dependent solubility and its absorption is decreased in patients receiving gastric acid suppression therapy. Here, we examined whether administration of erlotinib in acidic solutions would improve its solubility and absorption characteristics. In vitro, the solubility of erlotinib in HCl solution increased with decreasing pH, and was far higher than that in tap water. The solubility in apple juice (pH 3.7) was higher than that in HCl solution of the same pH. In vivo, the absorption of erlotinib administered in tap water was decreased in omeprazole-treated (OP) rats, used as a model of gastric acid suppression, compared to control rats. In the OP rats, the plasma concentrations in the groups given erlotinib in apple juice and in HCl (pH 3.7) were significantly higher than in the tap water group in the initial phase of absorption. AUC in OP rats given erlotinib in apple juice was 1.69-fold larger than that of control rats given erlotinib in tap water, and 2.49-fold larger than that of OP rats given erlotinib in tap water. Thus, administration of erlotinib in an acidic beverage to patients receiving gastric acid suppression therapy might be effective to increase solubility and absorption.

Association of Gastric Acid Suppression and Sorafenib Efficacy in Advanced Hepatocellular Carcinoma.

Recent studies have revealed that coadministration of gastric acid suppressants reduces the efficacy of the tyrosine kinase inhibitors erlotinib and sunitinib in patients with non-small cell lung cancer and renal cell carcinoma, respectively. The authors have therefore assessed if the concurrent use of gastric acid suppressants and sorafenib impairs outcomes in patients with advanced hepatocellular carcinoma (HCC). A retrospective analysis was conducted on all patients treated with sorafenib for advanced HCC at a single tertiary referral unit in the United Kingdom, between January 2008 and January 2014. A multivariate Cox proportional hazard model was used to assess the effect of the concomitant use of gastric acid suppression and sorafenib on progression-free survival (PFS) and overall survival (OS). Data were collected from 197 patients, of which 182 could be assessed for this study; 77 (42%) were on concurrent gastric acid suppression therapy. After adjusting for imbalances between the groups, a Cox regression analysis gave an adjusted hazard ratio for the concurrent acid suppression group compared with the no acid suppression group of 5.4 (95% confidence interval, 3.6-7.9) for PFS and 1.85 (95% confidence interval, 1.3-2.6) for OS. This single-center experience shows that patients with advanced HCC taking sorafenib and concomitant gastric acid suppression therapy have significantly inferior PFS and OS. This is the first time that this negative interaction has been reported and further prospective validation is warranted.

Gastric Ulcers Developing during Gastric Acid Suppressive Therapy: Report of Three Cases

Gastric Ulcers Developing during Gastric Acid Suppressive Therapy: Report of Three Cases

2370. Risk Factors for Clostridioides difficile Colonization Among Adult Inpatients: A Meta-Analysis

Background Clostridioides difficile is one of the most common causes of healthcare-associated infections in the United States. The prevalence of asymptomatic C. difficile colonization has been demonstrated to range from 3 to 21% for hospitalized adults. Patients colonized with C. difficile may serve as potential reservoirs for transmission of C. difficile infection (CDI) within inpatient units. The purpose of this meta-analysis was to identify the risk factors for colonization at hospital admission among adult patients, to inform strategies for infection prevention.MethodsWe searched MEDLINE, Scopus, Web of Science, and Embase from inception to 2019 for articles related to C. difficile colonization on hospital admission. Studies with multivariate analyses evaluating risk factors for asymptomatic colonization in adult inpatients were eligible. Odds ratios were pooled using a random effects model. Study quality and publication bias analyses were also conducted.ResultsAmong 2,982 studies identified in the search, 21 studies met the inclusion criteria. Included studies reported 18,468 adult patients of which 1,243 were asymptomatically colonized with C.difficile. Factors associated with an increased risk of colonization were CDI in the last 3 months (OR 4.18, 95% CI 2.56–6.82, I2 = 0%), hospitalization in the last 6 months (OR 2.45, 95% CI 2.06–2.92, I2 = 0%) and use of gastric acid suppression therapy within the last 8 weeks (OR 1.46, 95% CI 1.17–1.73, I2 = 1%). Receipt of antibiotics in the last 3 months (OR 1.37, 95% CI 0.94–2.01, I2 = 48%) and use of non-steroidal anti-inflammatory drugs (OR 0.90, 95% CI 0.52–1.55, I2 = 65%) were not associated with statistically significant effects on risk of colonization. There were insufficient studies to determine the association between most antibiotic classes and the risk of colonization.ConclusionC.difficile colonization on hospital admission was significantly associated with previous CDI, recent hospitalization, and gastric acid suppression therapy. Recognition of these risk factors may assist in identifying potential carriers of C. difficile. These findings also emphasize the importance of judicious use of gastric acid suppression and other preventative measures in reducing C. difficile acquisition. Disclosures All authors: No reported disclosures.

P3.27: Gastric Acid Suppression May Lead to an Increased Risk of Vancomycin-Resistant Enterococcus Colonization

Introduction: Gastric acid suppression therapy has been reported to change the gastrointestinal microbiome, resulting in increased gastrointestinal infections. This may be of increased importance in intestinal transplantation subjects as immunosuppressive agents are associated with peptic ulcers, leading to increased gastric acid suppression therapy. Also, immunosuppressive therapy leads to a higher risk of vancomycin-resistant enterococcus (VRE) colonization. However, the effect of gastric acid suppression therapy on vancomycin-resistant enterococcus (VRE) colonization has not been investigated. Methods: Subjects who had surveillance rectal swabs for VRE at a university hospital were investigated. Surveillance was performed on subjects with prior hospitalization within 3months, history of VRE colonization/infection, or positive VRE findings from an adjacent patient. Gastric acid suppression therapy was defined as use of proton pump inhibitor or histamine-receptor-2 antagonists. Results: Of 886 subjects who underwent VRE screening, 452 were included with 69 VRE positive and 383 VRE negative subjects. In univariable analysis, gastric acid suppression therapy, antibiotics use, male gender and prior hospitalization were significant risk factors for VRE colonization. Multivariable analysis showed that gastric acid suppression therapy (OR 2.873, 95% CI 1.473–5.605, P=0.002) and antibiotics use (OR 3.896, 95% CI 2.019–7.520, P<0.001) significantly increased VRE risk. Of antibiotics, carbapenems (OR 3.836, 95% CI 1.603–9.182, P=0.003) glycopeptides (OR 2.784, 95% CI 1.155–6.712, P=0.023), and cephalosporins (OR 2.210, 95% CI 1.213–4.025, P=0.010) were most significantly associated with VRE colonization. The unfavorable effect of gastric acid suppression therapy on VRE colonization was consistent, regardless of antibiotics type. Conclusion: Gastric acid suppression therapy significantly increased VRE colonization risk. Gastric acid suppression should be administered according to strict guidelines. Physicians should be made aware of the increased VRE risk, and should consider VRE surveillance in those under long-term gastric suppression therapy.

Gastric Acid Suppression May Lead to an Increased Risk of Vancomycin-Resistant Enterococcus Colonization: Presidential Poster Award

Introduction: Gastric acid suppression therapy has been reported to change the gastrointestinal microbiome, resulting in increased gastrointestinal infections. However, the effect of gastric acid suppression therapy on vancomycin-resistant enterococcus (VRE) colonization has not been investigated. Methods: Subjects who had surveillance rectal swabs for VRE at a university hospital were investigated. Surveillance was performed on subjects with prior hospitalization within 3months, history of VRE colonization/infection, or positive VRE findings from an adjacent patient. Gastric acid suppression therapy was defined as use of proton pump inhibitor or histamine-receptor-2 antagonists. Results: Of 886 subjects who underwent VRE screening, 452 were included with 69 VRE positive and 383 VRE negative subjects. In univariable analysis, gastric acid suppression therapy, antibiotics use, male gender and prior hospitalization were significant risk factors for VRE colonization. Multivariable analysis showed that gastric acid suppression therapy (OR 2.873, 95% CI 1.473-5.605, P=0.002) and antibiotics use (OR 3.896, 95% CI 2.019-7.520, P<0.001) significantly increased VRE risk. Of antibiotics, carbapenems (OR 3.836, 95% CI 1.603-9.182, P=0.003) glycopeptides (OR 2.784, 95% CI 1.155-6.712, P=0.023), and cephalosporins (OR 2.210, 95% CI 1.213-4.025, P=0.010) were most significantly associated with VRE colonization. The unfavorable effect of gastric acid suppression therapy on VRE colonization was consistent, regardless of antibiotics type. Conclusion: Gastric acid suppression therapy significantly increased VRE colonization risk. Gastric acid suppression should be administered according to strict guidelines. Physicians should be made aware of the increased VRE risk, and should consider VRE surveillance in those under long-term gastric suppression therapy.1112_A Figure 1. Characteristics of the study subjects1112_B Figure 2. Antibiotics use in the study subjects1112_C Figure 3. Multivariable analysis of VRE risk factors

Electronically Available Comorbid Conditions for Risk Prediction of Healthcare-Associated Clostridium difficile Infection.

OBJECTIVE To analyze whether electronically available comorbid conditions are risk factors for Centers for Disease Control and Prevention (CDC)-defined, hospital-onset Clostridium difficile infection (CDI) after controlling for antibiotic and gastric acid suppression therapy use. PATIENTS Patients aged ≥18 years admitted to the University of Maryland Medical Center between November 7, 2015, and May 31, 2017. METHODS Comorbid conditions were assessed using the Elixhauser comorbidity index. The Elixhauser comorbidity index and the comorbid condition components were calculated using the International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes extracted from electronic medical records. Bivariate associations between CDI and potential covariates for multivariable regression, including antibiotic use, gastric acid suppression therapy use, as well as comorbid conditions, were estimated using log binomial multivariable regression. RESULTS After controlling for antibiotic use, age, proton-pump inhibitor use, and histamine-blocker use, the Elixhauser comorbidity index was a significant risk factor for predicting CDI. There was an increased risk of 1.26 (95% CI, 1.19-1.32) of having CDI for each additional Elixhauser point added to the total Elixhauser score. CONCLUSIONS An increase in Elixhauser score is associated with CDI. Our study and other studies have shown that comorbid conditions are important risk factors for CDI. Electronically available comorbid conditions and scores like the Elixhauser index should be considered for risk-adjustment of CDC CDI rates. Infect Control Hosp Epidemiol 2018;39:297-301.

Effect of gastric acid-suppressive therapy and biological variation of serum gastrin concentrations in dogs with chronic enteropathies

BackgroundSerum gastrin concentration can help diagnose gastrinomas in dogs if >3–10× the upper reference limit (URL), but antisecretory therapy and other conditions can also cause hypergastrinemia. Effects of antisecretory therapy (famotidine or ranitidine, omeprazole) on serum gastrin concentration in dogs with chronic enteropathy (CE) and its biological variation (BV) are unknown. Aim of the study was to evaluate serum gastrin in acid-suppressant-treated or -naïve CE dogs; test the association between serum gastrin and histopathologic findings in acid-suppressant-naïve CE dogs; and evaluate the BV of serum gastrin in dogs not receiving any gastric acid suppressive therapy. Samples from 231 dogs were used and serum gastrin was measured by chemiluminescence assay. Gastric and duodenal histologic lesions were evaluated and graded. BV of serum gastrin was evaluated in serial samples.ResultsSerum gastrin concentrations were significantly higher in acid-suppressant-treated than acid-suppressant-naïve dogs (P = 0.0245), with significantly higher concentrations in proton pump inhibitor (PPI)- than H2-antihistamine-treated patients (P = 0.0053). More PPI- than H2-antihistamine-treated dogs had gastrin concentrations above URL (P = 0.0205), but not >3× nor >10× the URL. Serum gastrin concentrations correlated with the severity of gastric antral epithelial injury (P = 0.0069) but not with any other lesions or the presence/numbers of spiral bacteria in gastric biopsies. Intra- and inter-individual BV were 43.4 and 21.6%, respectively, in acid-suppressant-naïve dogs, with a reciprocal individuality index of 0.49 and a critical difference of ≥29.5 ng/L.ConclusionsAntisecretory (particularly PPI) treatment leads to hypergastrinemia in CE dogs, but the concentrations seen in this study are unlikely to compromise a diagnosis of gastrinoma. Use of a population-based URL for canine serum gastrin and a URL of ≤27.8 ng/L are appropriate.

EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction.

BackgroundErlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients.ResultsThe AS usage rate was 35%. In the overall cohort, AS users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 – 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR = 1.37, 95% CI: 0.89 – 2.12, P = 0.16; median, 7.6 versus 8.7 months) compared with non-users in multivariate Cox regression analysis. However, subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities (Charlson comorbidity index ≤ 2), those with Karnofsky performance status < 90, and never-smokers.Materials and MethodsA retrospective database analysis of 157 patients given erlotinib or gefitinib for EGFR-mutant advanced NSCLC from two institutions was conducted. Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ≥ 30%. Overall survival (OS) and progression-free survival (PFS) were assessed according to AS usage.ConclusionsConcomitant AS therapy did not have an adverse impact on OS and/or PFS in the overall cohort. Our subgroup findings should be regarded exploratory and require replication in a large prospective cohort.

Exposure to Gastric Acid-Suppression Therapy Is Associated With Health Care- and Community-Associated Clostridium difficile Infection in Children.

The aim of the study was to determine whether gastric acid-suppression therapy is associated with Clostridium difficile infection (CDI) in both inpatient and outpatient pediatric populations. We conducted a retrospective case-control study at a 200-bed academic pediatric hospital and associated outpatient clinics during 2005-2010. We defined cases as children 1 to 18 years of age with a first positive test for C difficile toxin A/B, and matched each case to 2 controls without C difficile. We conducted chart review to elicit selected comorbidities and exposure to gastric acid-suppression therapy and antibiotics in the preceding 3 months of the infection or encounter date. We used bivariate and multivariable logistic regression to evaluate the association between antacid use and CDI, controlling for potential confounders. We identified 138 children with health care- or community-associated CDIs and 276 controls. The use of any acid suppression therapy was more common in cases compared with controls (34% vs 20%, P = 0.002). When adjusted for demographic variables and comorbidities, gastric acid-suppression therapy remained significantly associated with CDI (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.0-3.1). Antibiotic use (aOR 1.7, 95% CI 1.1-2.7) and immunosuppressed state were also associated with CDI in our adjusted model (aOR 2.5, 95% CI 1.2-5.2). Gastric acid-suppression therapy was associated with both health care- and community-associated CDIs in children. Larger pediatric studies are necessary to determine the role of proton pump inhibitors specifically in causing CDI in children.

975Exposure to Gastric Acid-Suppression Therapy is Associated with Healthcare-Associated and Community-Associated C. difficile Infection in Children

975Exposure to Gastric Acid-Suppression Therapy is Associated with Healthcare-Associated and Community-Associated C. difficile Infection in Children

The impact of gastric acid suppression therapy on tyrosine kinase inhibitors in advanced cancer patients.

2594 Background: Oral tyrosine kinase inhibitors (TKIs) are used across tumor subtypes. Oral drug absorption is dependent on numerous factors including gastric acidity. Few studies have examined ef...

520 Unconjugated but Not Conjugated Bile Acid Reduces Squamous Differentiation in Esophageal Cells Possibly Through Intracellular Mechanisms

Background: Barrett's Esophagus (BE) is a precancerous lesion in which the normal squamous epithelium of the esophagus undergoes columnar metaplasia as a result of protracted duodeno-esophageal reflux. Bile acid (BA) both conjugated and unconjugated at an acidic pH, forms the chief component of reflux and has the ability to affect cellular processes by virtue of its anionic detergent action or acting as a signaling molecule. Previously, our group had shown that the esophageal squamous epithelium loses the expression of genes involved in squamous differentiation following exposure to a cocktail containing conjugated and unconjugated BA at pH5. In this study, we aimed determining which BA component, whether conjugated or unconjugated, predominantly contributed to the down-regulation of squamous differentiation. Methods: Human telomerase-immortalized primary esophageal squamous cells (EPC1) were grown on polyester transwells and treated separately with conjugated or unconjugated BA at both pH7.4 and pH5, in 15 min pulses three times a day for six days. Trans-epithelial Electrical Resistance (TEER) was measured daily, and at the end of the treatment cells were harvested for mRNA and protein. Results: Unconjugated BA at pH5 reduced the expression of genes involved in squamous differentiation as well as the TEER in the EPC1 in transwells culture, whereas conjugated BA did not have any significant effect. Moreover, unconjugated BA at pH5 induced the expression of FGF-19, a transcription target of BA nuclear receptor FXR. Conclusions: Unconjugated BA at pH5 is unionized and can penetrate through cell membrane to enter EPC1 cells. On the other hand, EPC1 cell membrane is impermeable to conjugated BA due to the absence of apical BA transporters. Since the anionic detergent properties of BA increases with conjugation and ionization, these results implicate a possible intracellular signaling mechanism of action of BA to reduce the squamous differentiation in primary esophageal cells, as opposed to detergent action. Long term gastric acid suppression therapy might be putting patients at risk to BA induced altered cellular differentiation, as the therapy is known to increase bacterial deconjugation of BA.

523 Comparison of Hospital Charges Between Laparoscopic Heller Myotomy and POEM

Background: Barrett's Esophagus (BE) is a precancerous lesion in which the normal squamous epithelium of the esophagus undergoes columnar metaplasia as a result of protracted duodeno-esophageal reflux. Bile acid (BA) both conjugated and unconjugated at an acidic pH, forms the chief component of reflux and has the ability to affect cellular processes by virtue of its anionic detergent action or acting as a signaling molecule. Previously, our group had shown that the esophageal squamous epithelium loses the expression of genes involved in squamous differentiation following exposure to a cocktail containing conjugated and unconjugated BA at pH5. In this study, we aimed determining which BA component, whether conjugated or unconjugated, predominantly contributed to the down-regulation of squamous differentiation. Methods: Human telomerase-immortalized primary esophageal squamous cells (EPC1) were grown on polyester transwells and treated separately with conjugated or unconjugated BA at both pH7.4 and pH5, in 15 min pulses three times a day for six days. Trans-epithelial Electrical Resistance (TEER) was measured daily, and at the end of the treatment cells were harvested for mRNA and protein. Results: Unconjugated BA at pH5 reduced the expression of genes involved in squamous differentiation as well as the TEER in the EPC1 in transwells culture, whereas conjugated BA did not have any significant effect. Moreover, unconjugated BA at pH5 induced the expression of FGF-19, a transcription target of BA nuclear receptor FXR. Conclusions: Unconjugated BA at pH5 is unionized and can penetrate through cell membrane to enter EPC1 cells. On the other hand, EPC1 cell membrane is impermeable to conjugated BA due to the absence of apical BA transporters. Since the anionic detergent properties of BA increases with conjugation and ionization, these results implicate a possible intracellular signaling mechanism of action of BA to reduce the squamous differentiation in primary esophageal cells, as opposed to detergent action. Long term gastric acid suppression therapy might be putting patients at risk to BA induced altered cellular differentiation, as the therapy is known to increase bacterial deconjugation of BA.