PPI Use Research Articles

PPIs might reduce risk of neoplastic progression in Barrett oesophagus

PPIs have become a mainstay of treatment in patients with Barrett oesophagus. Whether PPIs reduce the risk of neoplastic progression in these patients, however, was unclear; concerns had also been raised about the costs and potential adverse effects of prolonged PPI use. New findings, published in Clinical Gastroenterology and Hepatology, have now provided clinical evidence that prolonged use of PPIs in patients with Barrett oesophagus is justified.

Commentary: the link between community‐acquired pneumonia and PPI use

Commentary: the link between community‐acquired pneumonia and <scp>PPI</scp> use

Does Probiotic Use Increase the Risk for Developing Small Intestinal Bacterial Overgrowth? Presidential Poster

Purpose: Small intestinal bacterial overgrowth (SIBO) results in diarrhea, bloating, and/or malabsorption. A previous review of patients undergoing duodenal culture in 2003 found 8% had SIBO. A recent, but small sample of patients undergoing aspirate culture showed a higher rate of 40%. We postulated that probiotics—which are not formulated for colonic release—may be a risk factor for SIBO. Specific Aims: 1) To estimate the prevalence of SIBO among patients referred for culture. 2) To identify the clinical risk factors for SIBO. 3) To examine whether probiotic use may be a risk factor for SIBO. Methods: A retrospective chart review of a random sample of 250 patients who had undergone duodenal aspirate culture at an academic medical center between January 2010 and October 2011 was performed. A positive culture was defined as culture counts >105 cfu/ml; an intermediate result was >0 but <105 cfu/ml; a negative result was no growth. Associations between clinical characteristics, medications, probiotic use, and aspirate results were assessed using multiple variable logistic regression analysis (response being 3 aspirate result categories, “negative” as the reference). Results: 221 (88%) patients had available aspirate results. The median age of the sample was 54 (range: 16-88) and 144 (65%) were females. 92 (42%) had positive cultures; 55 (25%) had no growth. Adjusted for age and gender, the following were associated with aspirate Results: age, PPI use, and narcotic use (Table, left column). Probiotic use (yogurt and supplement use), IBS, inflammatory bowel disease, pancreatitis, small bowel diverticula, GI surgery, and intestinal pseudoobstruction were not associated with aspirate result. Of the 48 patients using probiotics, 19 (40%) had a positive aspirate compared to 73 (42%) in those not using probiotics (N.S.). In the final model (Table, right column), increasing age increased the odds of a positive result, whereas both PPI use and narcotic use increased the odds of an intermediate and positive aspirate result. Conclusion: The prevalence of culture-positive SIBO has increased in the last several years. Based on this pilot study, the most important clinical features predictive of SIBO were increasing age, PPI use, and narcotic use, but not major GI comorbidity or probiotic use.Figure: [291]

Analysis of Prevalence and Risk Factors for Active Disease of Crohnʼs Disease Patients for Acute Exacerbation Symptoms

Purpose: Common GI tract complaints including abdominal discomfort, and diarrhea occur in up to 57% of patients with IBD in remission. Crohn's disease patients (CD) usually need multiple GI surgeries over a life-time due to complications. Subsequently surgical complications could also contribute to the GI symptoms. Patients will also have increased risk for small bowel bacterial overgrowth and bile acid malabsorption from the altered anatomy of the GI tract. Long term narcotic use could further complicate the clinical manifestations. The systemic analysis for the prevalence and risk factors for the active disease among CD patients with acute flare-up symptoms has not been done. Methods: Inclusion criteria were patients with (a) established diagnosis of Crohn's disease and (b) admission for diarrhea and/or abdominal pain from 2008 to 2011. Exclusion criteria were admissions due to issues like planned surgical intervention, significant systemic infections or unrelated to Crohn's disease. Total 231 eligible patients from our database were recruited. They were divided into 2 groups, one with endoscopic or radiological evidence of active inflammation in the GI tract or its complication e.g. abscess, fistula, stricture, perforation on admission, the other without evidence of above. The patients' demographic data were collected by chart review. Risk factors for the active disease were analyzed. Results: Among 231 eligible patients, 20.8% patients were found to have no active disease activity, 79.2% had activity. Univariable analysis showed the use of PPI, anti-depressant, and narcotics (all P≤0.05) were significantly more in the patients who had no active disease. The consequence from the active disease was reflected by the worse clinical outcomes including requirement for GI surgeries, rehospitalization within 12 months, and new treatment of immunosuppressants on discharge (all P<0.05). However, multivariable analysis did not identify the significant risk factors. Conclusion: 20% of Crohn's patients admitted for GI symptoms did not have active disease activity. Among these patients, more PPI, anti-depressant and narcotics use were noticed which could suggest the potential etiologies e.g. IBS, functional dyspepsia, surgical complications, chronic narcotic dependence etc on the background of Crohn's disease that was in remission. The small sample size could lead to non-significant result on the subsequent multivariable analysis. We believe that disease activity from the initial evaluation should be carefully documented prior to admission to better direct therapy.Table: Multivariable analysis for the risk factors for active diseaseTable: Analysis of demographic data and clinical outcomes

The Sensitivity and Specificity of Esophagogastroduodenoscopy (EGD) for the Small Caliber Esophagus in Esophageal Eosinophilic Infiltration (EEI)

Purpose: To determine the clinical usefulness of esophagram with calculation of esophageal diameter in patients with symptomatic esophageal eosinophilic infiltration (EEI). Methods: Patients who presented with dysphagia between 2004 and 2012 were identified. All patients had at least 15 eosinophils per high powered field on esophageal biopsy and were evaluated with an esophagram. In addition, all patients were clinically evaluated by a single investigator (JAA). A small caliber esophagus (SCE) was defined as an esophageal maximal diameter (EDmax) less than or equal to 21 mm. EGD sensitivity and specificity were evaluated against a gold standard of esophagram. Gender, food impaction and frequency, impaction requiring emergent endoscopic removal, PPI use at time of EGD, prior corticosteroid treatment, gross endoscopic findings, skin testing, body mass index and serum eosinophil count were evaluated as potential univariate predictors of small caliber esophagus using Fisher's exact test. The patient's clinical course was reviewed retrospectively. Results: Of the 63 patients identified, 30 had a small caliber esophagus using an EDmax of less than or equal to 21 mm. EGD had poor sensitivity (14.3%, 95% CI 4.8-30.3%) for detection of a small caliber esophagus and only modest specificity (82.1%, 95% CI 63.1-93.9%) (Table 1). Female gender (p=0.012), food impaction (p=0.041), food impaction frequency (p<0.001), emergency endoscopic removal of food impaction (p<0.024), endoscopic rings (p=0.031) were all predictors of a small caliber esophagus. Univariate variables that are not predictors of a small caliber esophagus include proton pump inhibitor treatment at the time of EGD, corticosteroid treatment prior to EGD, furrows on endoscopic exam, skin testing, age at time of EGD, body mass index, and serum eosinophil count (Table 2). 7 patients had persistent dysphagia post PPI and/or topical steroid therapy and eventually underwent esophageal dilation. At esophagram 5 had focal narrowing, 2 had diffuse SCE with an EDmax esophageal diameter of 15 mm; 5/7 were perceived as having normal esophageal diameter at EGD. 6/7 had a minimal diameter of less than or equal to 13 mm. All 6 patients on treatment (budesonide 5, PPI 1) had < 10 eos/hpf at the time of dilation. 6/7 reported clinical improvement in their dysphagia. The nonresponding patient had a concomitant esophageal motility disorder.Table: Sensitivity and specificity of EGDTable: [36] Univariate variables that do not predict small caliber esophagusConclusion: 1. SCE may be predicted by female gender, food impaction, food impaction frequency, emergent endoscopic removal of food impaction, and endoscopic rings. 2. Esophagography frequently detects clinically important SCE that is not detected with endoscopy.

CYP2C19 Genetic Polymorphism, Rabeprazole and Esomeprazole Have No Effect on the Anti-Platelet Action of Clopidogrel

Purpose: To investigate the effect of CYP2C19 genetic polymorphism and concomitant use of rabeprazole or esomeprazole on the anti-platelet effect of clopidogrel in vitro. Methods: Patients receiving a stable dose of clopidogrel 75 mg with or without rabeprazole or esomeprazole for > 2 weeks were recruited. Genotyping for CYP2C19 and VASP testing using flow cytometry to measure platelet reactivity index (PRI) were performed. A detailed questionnaire regarding the indication and duration of use of clopidogrel and PPI therapy was completed on all patients including a detailed concomitant drug history. Results: 239 consecutive patients (176M and 63F; mean age = 67.1±12.0) were enrolled after informed consent. 92 patients were on clopidogrel without concomitant PPI therapy (C group), 94 were on clopidogrel + rabeprazole (CR group), and 53 on clopidogrel + esomeprazole (CE group). The mean number of concomitant medications in addition to clopidogrel was 5.7± 3.0. The main indications for clopidogrel were cardiac, neurologic, and peripheral vascular disease (71.5, 25.5, and 2.5% respectively) and the mean duration of clopidogrel therapy was 33.1 ± 40.4 months. The indications for PPI use were considered appropriate in 30.6% of users. On CYP2C19 genotyping, 194 patients did not have loss of function polymorphism (LOF) while 45 had LOF (43 heterozygous and 2 homozygous mutant for CYP2C19*2).The mean PRI was 20.7±21.9% in the clopidogrel group, 19.1±20.9% in the CR group, and 24.5±22.9% in the CE group (p=0.386). High-on-treatment Platelet Reactivity (HPR) defined as PRI>50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, CE, respectively (p=0.608). A PRI of >30% was noted in 23 (25.0%), 22 (23.4%), and 20 (37.7%) patients on C, CR, CE respectively (p=0.144). In participants with no LOF alleles (194/239 or 81.2% of study population), a PRI>30% was noted in 21.9%, 22.1% and 38.6% of the C, CR and CE groups patients respectively (p=0.085) (p-value of 0.052 between the C and CE groups and p-value of 0.051 between the CR and CE groups). On multivariate logistic regression, neither the presence of CYP2C19 LOF alleles nor the use of esomeprazole or rabeprazole were associated with HPR. Conclusion: 14.4% of individuals on clopidogrel monotherapy have an unsatisfactory in vitro platelet inhibition independent of CYP2C19 polymorphism. Neither CYP2C19 LOF alleles, nor esomeprazole nor rabeprazole had a significant effect on the anti-platelet action of clopidogrel in vitro, although there was a trend for a relatively reduced platelet inhibition with esomeprazole compared to rabeprazole users or non-PPI users in patients without CYP2C19 LOF mutations.

Antibiomania Provoked by Helicobacter pylori Triple Therapy Treatment

Background: Antibiomania is a term used to describe antibiotic-induced psychosis. Triple therapy, including a PPI, amoxicillin, and clarithromycin, is commonly prescribed for patients infected with H. pylori. Acute psychotic episodes in patients undergoing this treatment regimen are found to have have been most often associated with clarithromycin. Onset of symptoms occurs within 7 days of therapy initiation and resolution occurring 24 to 48 hours after cessation. Case Presentation: A 49-year old male with no psychiatric history and recently diagnosed H. pylori gastritis was brought to the ER by his wife who noted strange behavior in the patient. The wife had found the patient on a toilet unresponsive with a blank stare. The patient abruptly stated he felt as if he was “leaving the planet” followed by cat-like screeching and movements. PMH was significant for GERD, controlled with omeprazole for 6 years. He was recently started on triple therapy for H. pylori gastritis, which included lanzoprazole, amoxicillin and clarithromycin 5 days prior. Physical Exam/Labs: In the ER, the patient was noted to have upper extremity jerky movements that resolved after 10 seconds without any intervention. Vital signs, lab studies, and CT of the head were unremarkable. The physical exam was benign except for disorientation to person and time. Hospital Course: The patient was admitted and all medications were discontinued. All organic causes were ruled out for a possible cause of acute psychosis. Symptoms began to subside within 24 hours of cessation of triple therapy with complete resolution in 36 hours. The patient became oriented and returned to his baseline mental status with no administration of anti-psychotics. Clinical Significance: Onset of psychosis days after initiation of treatment with rapid resolution with discontinuation of medications verified triple therapy to be the likely cause. Long-term PPI use disqualified this as a trigger. There have been minimal reports of amoxicillin inducing psychosis making this the less likely culprit. As widely reported, clarithromycin was the likely agent responsible for symptoms. Clarithromycin may be directly toxic to the CNS system via its lipid-soluble active metabolite 14-hydroxyclarithromycin. Clarithromycin has also been known to alter cortisol and prostaglandin metabolism, and interact with glutaminergic and GABA pathways possibly leading to CNS side effects. Though these are all plausible explanations, how clarithromycin causes psychosis remains a debate requiring further research. Clinicians should be cognizant of the psychiatric effects secondary to clarithromycin and discontinuation should be prompt for rapid recovery.

PPI use linked with risk for infection in decompensated cirrhosis

PPI use linked with risk for infection in decompensated cirrhosis

Chronic PPI use in smokers associated with hip fracture in postmeno pausal women

Chronic PPI use in smokers associated with hip fracture in postmeno pausal women

Qualitative analysis of prescriptions in the residents of three nursing homes in Loire-Atlantique

tatus. In vitro studies show that PPI affect IGF-bioactivity. Howver, the relationship between PPI use and IGF system is unknown. ethods.– To address this hypothesis we evaluated 903 older (536 omenand402men) subjects of the InCHIANTI Study,withdata on GF-1, IGF-binding protein-1 (IGFBP-1) andmedications. IGF-1 and GFBP-1 were measured by IRMA. Generalized Linear Models were sed to test the association between PPI use and IG Affirmations -1, IGFBP-1. esults.– Older subjects were categorized according to PPI use. 88 men and 515 women were PPI non users with 14 men and 1 women PPI users. Male PPI users were older (77.7±7.5 vs 4.6±6.9 years± SD) while female PPI users were younger than on-users (74.2±4.8 vs 76.6±7.8). After adjusting for age, male 107,01±69.6 vs 127.07±55.8, P<0.001) and female PPI users 87.6±29.1 vs 107.6±52.3, P=0.03) had lower levels of IGF-1 than on-users. No significant difference was observed in IGFBP-1 levls between two groups in both sexes. After adjustment for age, ex, BMI, liver function, caloric intake and IGFBP-1 the relationship etweenPPIuseand IGF-1was still negativeandalmost statistically ignificant (P=0.06). onclusions.– Use of PPI is negatively associated with IGF-1 levels n older subjects. isclosure.– No significant relationships.

Proton pump inhibitors in gastroesophageal reflux disease: a custom-tailored therapeutic regimen

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs.Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.

Endoscopic and pathological aspects of gastric polyps: a Turkish referral center study.

The aim of the present study was to retrospectively analyze all the polyps of patients undergoing endoscopic polypectomy or forceps biopsy according to their types, frequency, localization, number and gender distribution. Data from patients who underwent upper endoscopy in the Türkiye Yüksek Ihtisas Postgraduate Research Hospital between March 2007 and November 2009 were analyzed retrospectively. Forceps biopsy or polypectomy were performed for all polypoid lesions that were identified during the endoscopy. In the study period, 14,935 patients underwent 18,522 upper endoscopies. After excluding cirrhotic patients, and patients with a history of prior gastrectomy, chronic gastritis and edema or congestion, the remaining 124 (0.83%) patients with gastric polyps were included in the study. Histopathologically, the most frequently diagnosed polyps were hyperplastic polyps (55.6%). Fundic gland polyps (9.7%), foveolar hyperplasia (8.1%) and inflammatory polyps (7.3%) were also frequent. Adenocarcinoma was more frequently seen in males, whereas hyperplastic polyps and carcinoid tumors were found more often in females, and this difference was statistically significant (p<0.009). Results of the present study indicate that hyperplastic polyps make up the largest group. Although there is widespread PPI use, no increases in the frequency of fundic gland polyps were observed. However, increases in the ratio of carcinoid tumors suggest a suspicion of tumor development with PPI use.

WS13.1 The effect of PPI usage on bone health in children with cystic fibrosis (CF)

Introduction: The FDA recently issued a broad safety communication regarding the possible increased risk of osteoporosis-related bone fracture with the use of PPI’s. PPI’s are regularly used in CF for treatment of GORD and to help with the efficiency of PERT. And as osteoporosis is a co-morbidity of CF we aimed to assess if there was any relationship between PPI and bone density in children with CF. Methods: A retrospective review of PPI usage and dxa scans was conducted. Sixtyfour children with mean age of 11 (1.8 SD) were included in study. PPI usage and duration was recorded. Dxa scans were carried out on the Lunar DPXL-PED. Bone mineral density (BMD) was recorded and bone mineral apparent density (BMAD) was calculated. FEV1 was also recorded. Minitab Statistical Package was used to analyse the data. Results: Twenty-two (35%) of children were on PPI’s. Duration of use ranged from 1 to 4 years. PPI usage had a marginally significant negative effect on BMD [Z score mean of −0.31 (no PPI) and −0.94 (on PPI), p = 0.05]. PPI had no effect on BMAD [z score of 0.17 (no PPI) and −0.37 (on PPI), p = 0.08]. The duration of PPI had no influence on BMD or BMAD (p = 0.71 and p = 0.51). There was no difference in FEV1 between the two groups (means of 75% and 76%, p = 0.84). Conclusion: PPI’s may be prescribed more frequently in sicker patients and thus could explain the marginal difference found between groups. However this is not the case here as FEV1 did not differ. Therefore further larger studies are needed in this area. In the meantime, clinicians should be aware of their potential risk when considering PPI therapy and should use the lowest effective dose and duration necessary.

PWE-174 Proton pump inhibitors (PPI) use and Clostridium difficile infection: guilty or innocent bystander?

IntroductionPPIs have been implicated in predisposing to Clostridium difficile infection by causing hypochlorhydria. A 5–10% asymptomatic toxin burden in the community is also reported. The previously voluntary reporting of C...

PWE-165 CYP2C19*17 gain of function mutation is associated with peptic ulcer disease

IntroductionStudies show that single nucleotide polymorphisms (SNPs) in non-steroidal antiinflammatory drug (NSAID)-metabolising enzymes (mainly CYP2C9 and CYP2C8) may predispose NSAID-users to peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB),...

PMO-219 Higher than expected false negative CLO test in patients not taking PPI associated with regular alcohol intake and absence of endoscopic gastritis

IntroductionH pylori has a prevalence of around 40%–50% in the UK.1 Rapid urease test (CLO test) is commonly used in the endoscopy units around the UK to detect H pylori....

PWE-037 Proton pump inhibitors and hypomagnesaemia

IntroductionHypomagnesaemia is a rare and potentially serious complication of PPI therapy. About 30 cases of severe hypomagnesaemia have been reported in long term PPI users.1MethodsWe describe two cases recently admitted...

Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS)

BackgroundIn Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms.MethodsThis was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily). The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2). UMIN clinical trial registration number: UMIN000005399.ResultsOf 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverse events.ConclusionsThe favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss) should receive further investigation, including prompt referral for endoscopy.Trial registrationUMIN000005399.

1156 Influence of Body Mass Index on Gastroesophageal Reflux Disease in Patients With Sleep-Related Breathing Disorders

patients aged 1-17 years between 2000 and 2005; patients with a recorded diagnosis of gastroesophageal reflux disease (GERD) during the study period (n = 1809) and a cohort of patients without GERD (n = 5000). Non-GERD patients were frequency matched to GERD patients by age, sex and calendar year. Among GERD patients, 2 sub-cohorts of patients were identified according to whether they had been prescribed a PPI within 1 year of GERD diagnosis; there were 487 GERD PPI users and 1322 GERD PPI non-users. All patients (GERD and non-GERD) were followed-up for up to 1 year from the start date (date of first prescription for GERD PPI users, date of GERD diagnosis for GERD PPI non-users and a random date for non-GERD patients). A total of 118 patients with a recorded diagnosis of fracture were identified; their medical records were reviewed manually to ascertain incident cases. There were a total of 45 fracture cases among GERD patients; 11 among PPI users and 34 among PPI non-users. Adjusted incidence rate ratios (IRRs) for fracture risk associated with exposure to PPIs were calculated. We also conducted a nested case-control analysis, using all 118 cases of fracture identified in both GERD and non-GERD cohorts. All remaining patients without fracture at the end of follow-up in both cohorts served as controls (n = 6656). The index date was the date of diagnosis for fracture cases and a random date for controls. Data on PPI use were obtained and odds ratios (ORs) for fracture risk associated with PPI use were calculated by multivariate adjusted logistic regression models. Results. Among GERD patients, there was no association between fracture risk and current (IRR: 0.68; 95% CI: 0.24-1.94) or recent/past use (IRR: 0.90; 95% CI: 0.40-2.05) of PPIs compared with non-use of PPIs. Similarly, among all patients (with or without GERD), neither current (OR: 0.71; 95% CI: 0.25-2.04) nor recent/past use (OR: 0.95; 95% CI: 0.41-2.18) of PPIs was associated with an increased risk of fracture compared with non-use of PPIs. However, these estimates were based on only four currently exposed cases and seven recently/past exposed cases. Conclusion. The results of our study do not support an association between PPI use and risk of fracture in children and adolescents with or without a diagnosis of GERD. However, it should be noted that only a small number of cases were exposed to a PPI.

669 Chronic use of PPI and H2 Antagonists Decreases the Risk of Pouchitis After IPAA for Ulcerative Colitis

669 Chronic use of PPI and H2 Antagonists Decreases the Risk of Pouchitis After IPAA for Ulcerative Colitis