Use Of Proton Pump Inhibitor Therapy Research Articles

Rebuilding trust in proton pump inhibitor therapy.

Introduction of proton pump inhibitor (PPI) therapy into clinical practice has revolutionized treatment approach to acid-related diseases. With its clinical success came a widespread use of PPI therapy. Subsequently, several studies found that PPIs were oftentimes overprescribed in primary care and emergency setting, likely attributed to seemingly low side-effect profile and physicians having low threshold to initiate therapy. However, now there is a growing concern over PPI side-effect profile among both patients and providers. We would like to bring more awareness to the currently available guidelines on PPI use, discuss clinical indications for PPIs and the evidence behind the reported side-effects. We hope that increased awareness of proper PPI use will make the initiation or continuation of therapy a well informed and an evidence-based decision between patient and physician. We also hope that discussing evidence behind the reported side-effect profile will help clarify the growing concerns over PPI therapy.

Proton pump inhibitor therapy usage and associated hospitalization rates and critical care outcomes of COVID-19 patients

Proton Pump Inhibitors (PPI) are one of the most prescribed medications in the United States. However, PPIs have been shown to increase the risk of enteric infections. Our study aims to evaluate the correlation between PPI and COVID-19 severity. We performed a retrospective cohort study on patients who tested positive for SARS-CoV-2 from March to August 2020. Patients were categorized based on PPI user status. Primary outcomes included need for hospital or ICU admission and 30-day mortality. Secondary outcomes looked to determine the severity of COVID-19 infection and effect of comorbid conditions. 2,594 patients were reviewed. The primary outcomes of our study found that neither active nor past PPI use was associated with increased hospital admission or 30-day mortality following completion of multivariate analysis. Additionally, there was no association between COVID-19 infection and the strength of PPI dosing (low, standard, high). However, the following covariates were independently and significantly associated with increased admission: age, male gender, diabetes, COPD, composite cardiovascular disease, kidney disease, and obesity. The following covariates were associated with increased mortality: age, male gender, COPD, and kidney disease. In conclusion, the high risk features and comorbidities of PPI users were found to have a stronger correlation to severe COVID-19 infection and poor outcomes as opposed to the use of PPI therapy.

Analisa Minimalisasi Biaya Terapi PPI (Proton Pump Inhibitor) pada Pasien Rawat Inap Bedah di RSUD Dr. Zainoel Abidin Menggunakan Form Restriksi

Based on data on the use of PPI class drugs for the last 6 months, at December 2020-May 2021 at RSUDZA, the PPI drug class is among the drugs that are widely used every year, it is also prescribed for use other than cases of gastric acid secretion disorders and hematemesis melena, it can have an impact on optimization of drug spending costs so that if the hospital cannot control the drug spending budget and it can have an impact on the hospital's cash flow. This study aims to analyze the cost minimization of PPI (proton pump inhibitor) therapy in surgical inpatients at RSUD dr. Zainoel Abidin uses a restriction form. This study is an analytical intervention study with a prospective method and based on inclusion criteria by looking at the medical records of inpatients Neurosurgery and Orthopedics in Raudhah 3,4, and 5 by filling out the research tool used is the request sheet for restriction drugs of the PPI (Proton Pump Inhibitor) class., data collection was carried out from July-October 2021 using purposive sampling. The cost analysis used in this study is CMA (Cost Minimization Analysis), Chi-Square test to see the effect between two groups of variables, Kolmogorov Smirnove normality test to analyze data normality, and Mann Whitney to see the mean difference between groups pretest-posttest.
 The results showed that the use of PPI therapy in this study mostly used Omeprazole 40 mg iv therapy is 98%. There was an effect of giving a PPI restriction form to decrease the frequency of using Omeprazole 40 mg iv to every 24 hours for prophylactic statistically (p<0.000). Analysis of the cost of CMA in neurosurgery patients found that there was no decrease in the cost of Omeprazole 40 mg iv therapy in the restriction form treatment group, analysis of the cost of CMA in orthopedic surgery patients found a decrease in the cost of Omeprazole 40 mg iv therapy in the treatment group using the restriction form. Factors that influence the cost analysis in this study are length of stay, types of other drug items obtained during treatment, type of surgery, and duration of use of PPI class therapy.

Long-term Treatment With Proton Pump Inhibitor Is Effective in Children With Eosinophilic Esophagitis

To evaluate the long-term efficacy and safety of proton pump inhibitors (PPIs) in pediatric eosinophilic esophagitis (EoE).One hundred and nine children between 1 month and 15 years of age with esophageal symptoms and EoE were recruited at 2 pediatric hospitals in Madrid between February 2013 and August 2017. All patients were treated with esomeprazole for 8 weeks, and 72 (66%) achieved histologic remission. Of the 72, 57 children were enrolled in this 1-year study.This was a prospective study of 57 children (73.7% boys, median age 11 years) with EoE who reached complete or partial histologic remission after an 8-week esomeprazole trial (1 mg/kg per dose, twice daily). Esomeprazole was continued at 1 mg/kg per day (max 40 mg daily) for 1 year. Patients were closely monitored every 3 months for symptom recurrence, clinical outcomes, and adverse events. Follow-up endoscopy was performed at 1 year or before, if symptoms recurred. Complete histologic remission was defined as ≤5 eosinophils per high-power field, and partial remission was defined as >5 and <15 eosinophils per high-power field. Patients were not treated with concomitant dietary restrictions or topical steroids.After 12 months of PPI maintenance therapy, histologic remission continued in 70.1% (n = 40) of children. Long-term remission was observed more frequently in children with initial complete histologic remission compared with those with partial remission (81% vs 50%, P = .014). There were no other clinical, endoscopic, or histologic data to predict remission on PPI therapy. Eleven of 12 children (91.6%) who remained on esomeprazole at a lower maintenance dose (0.5 mg/kg per day) for an additional 12 months also sustained histologic remission. Five children developed adverse events on esomeprazole (0.7–2 mg/kg per day), including diarrhea, urticaria, and headache. All adverse events self-resolved or improved by substituting for another PPI.Long-term PPI therapy is safe and effective for the treatment of pediatric EoE. At 1 year follow-up, 70% of children with PPI-responsive EoE remained in histologic and clinical remission on a low-dose maintenance regimen. Patients with complete histologic remission after an 8-week trial of PPI were more likely to maintain histologic remission with maintenance PPI.This is a landmark prospective study supporting the use of PPI therapy for the long-term treatment of EoE in a subset of pediatric patients. Seventy percent efficacy after 12 months of PPI is comparable or higher than reported remission rates for alternative EoE therapies, such as dietary restriction or swallowed corticosteroids. Future studies will need to compare therapies and determine if PPI dose escalation can lead to improved remission rates.

Is There a Reason for the Proton Pump Inhibitor? An Assessment of Prescribing for Residential Care Patients in British Columbia

The use of proton pump inhibitors (PPIs) may cause significant harm to patients in the residential care setting, as these patients are often frail with multiple morbidities. The extent of non-evidence-based use of PPIs in residential care sites of the Fraser Health Authority in British Columbia is unknown. To determine the proportion of non-evidence-based use of PPI therapy for residential care patients of the Fraser Health Authority. This retrospective cross-sectional study was conducted in 6 Fraser Health residential care facilities in British Columbia between April 1, 2015, and March 31, 2016. Two definitions of "evidence-based indications" were used. The first definition encompassed broad evidence-based indications for PPI use, specifically gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis, esophagitis, Barrett esophagus, and gastrointestinal protection from concurrent oral steroids, oral nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. The second definition involved common evidence-based indications for PPI use, specifically GERD or PUD. Descriptive statistics were used to evaluate the primary outcome: the proportion of PPI orders without a documented broad or common evidence-based indication for PPI treatment. A total of 331 residential care patients and 407 PPI orders were assessed. The proportion of PPI orders without a documented broad evidence-based indication was 16.2% (66/407). The proportion of PPI orders without a documented common evidence-based indication was 43.7% (178/407). The most frequently documented reason for a PPI order was GERD (214/407 or 52.6%). PPI orders for patients with GERD and gastrointestinal bleeding had the longest duration of therapy during residential care admission, averaging 205.1 and 218.1 days, respectively. About 1 in 6 PPI orders for Fraser Health residential care patients did not have a documented broad evidence-based indication, and about 2 in 5 PPI orders did not have a documented common evidence-based indication. These results indicate a need to assess the appropriateness of therapy for every patient with an active PPI order in residential care facilities.

Clinical Outcomes by Treatment Strategy in Eosinophilic Esophagitis

Introduction: Eosinophilic esophagitis (EoE) is an increasingly recognized disease in children and adults. EoE likely has a multifactorial etiology with genetic, immunologic and environmental components. Treatment of EoE consists of therapies including proton pump inhibitors (PPIs), swallowed steroids, and food elimination diets. There is heterogeneity in the chronic care of patients as there are no clear guidelines for long-term management. In a group of adult outpatients with chronic EoE, an evaluation of the relative contribution of each of these therapies on symptom control was the aim of this study. Methods: We conducted a retrospective chart review on patients with biopsy-proven EoE who had been seen by an allergist and were referred from gastroenterologists after endoscopic diagnosis. A telephone survey was conducted to determine current symptoms, a history of treatment regimens, and follow-up. A validated patient-response outcome (PRO) instrument and scoring system for EoE (Schoepfer, et al. Development and Validation of a Symptom-Based Activity Index for Adults with Eosinophilic Esophagitis. Gastro 2014;147:1255-66) was utilized. Results: There were 26 patients who had been diagnosed on average 4.4 years prior to data collection (range 1-10, 18 (69%) were male with an average age of 40 (range 23-59). At the time of the survey, 18 were taking a PPI for maintenance, 15 were using swallowed steroids, and 16 were avoiding foods. Patients who were maintained on a PPI were just as likely as those off PPI to remain symptomatic, defined as PRO>0 (OR 0.8, 95% CI 0.15 to 4.2, P=0.8). Similarly, the use of swallowed steroids for maintenance was not associated with symptoms (OR 1.1, 95% CI 0.22 to 5.0, P=0.95). Avoidance of foods due to triggering of symptoms or food allergies also did not correlate with symptoms (OR 3.0, 95% CI 0.56 to 16, P=0.20). While the majority of patients continued follow up with a gastroenterologist (n=17, 65%), very few continued to see an allergist (n=6, 23%). Conclusion: There is no predominant treatment strategy among the three most commonly utilized for the long-term management of adult patients with EoE. In our study, there was similar use of PPI therapy, swallowed steroids, and dietary avoidance, none of which were individually correlated with symptom-free remission. The heterogeneity in treatment plans and lack of correlation with symptoms emphasize the importance of further studies to determine the ideal long-term management plans for patients with EoE.

Adverse effects of proton-pump inhibitor use in older adults: a review of the evidence.

Proton-pump inhibitors (PPIs) are a widely prescribed class of medications used to treat acid-related disorders and use has significantly increased over the last few decades. PPIs are often inappropriately prescribed and since they have been on the market, a number of post-marketing studies have been published demonstrating associations between longer duration of PPI therapy and a number of adverse effects that are a concern in older adults. The objective of this review is to discuss the existing literature of potential adverse effects with long-term PPI use in older adults and to summarize the implications in clinical practice. A PubMed search was conducted to identify studies evaluating the potential long-term adverse effects of PPI therapy in older adults, and publications were selected based on relevant criteria. PPIs have been associated with an increased risk of a number of adverse effects including osteoporotic-related fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin B12 deficiency, kidney disease, and dementia, demonstrated by a number of case-control, cohort studies, and meta-analyses. Older adults should be periodically evaluated for the need for continued use of PPI therapy given the number of potential adverse effects associated with long-term use.

Analysis of gastrointestinal prophylaxis in patients receiving dual antiplatelet therapy with aspirin and clopidogrel.

Dual antiplatelet therapy (DAPT) has been found to reduce the risk of cardiac death, myocardial infarction, stroke, and stent thrombosis following acute coronary syndrome and percutaneous coronary intervention. However, this therapy has also been shown to increase the risk of gastrointestinal (GI) bleeding as high as 2-fold, especially in patients with multiple risk factors. Proton pump inhibitor (PPI) therapy decreases this risk. The current consensus document on reducing GI risks associated with antiplatelet agents no longer recommends PPI therapy for all patients receiving aspirin (ASA) and clopidogrel. The consensus recommendation reserves PPI therapy for patients receiving DAPT with a history of upper GI bleeding or prespecified risk factors for GI bleeding. To (a) describe the use of GI prophylaxis in patients on DAPT with ASA and clopidogrel and (b) assess the incidence of adverse outcomes that occurred during readmissions within 6 months of the index hospitalization. A retrospective chart review of patients receiving DAPT between February 1, 2011, and October 15, 2011, was performed to assess the appropriateness of GI prophylaxis based on the current consensus document. Therapy was defined as appropriate if an indication for prophylaxis was present and PPI therapy was prescribed, or if no indication was present and no GI prophylaxis was given. Inappropriate prophylaxis was defined as no indication for GI prophylaxis yet therapy received, or prophylaxis indicated but incorrect prophylaxis prescribed. Incorrect prophylaxis included no prophylaxis, histamine H2 blocker therapy, antacid, or combination therapy. During subsequent hospitalizations in the 6-month period following discharge from the index admission, patients were assessed for the development of vascular-, GI-, and PPI-related adverse events. 250 patients receiving DAPT during the study period were evaluated. Gastrointestinal prophylaxis was appropriate in 48% (119/250) of patients. Of the remaining patients, 56.4% (74/131) met guideline criteria for GI prophylaxis but did not receive a PPI at discharge, whereas 43.5% (57/131) of patients received GI prophylaxis when not indicated. Thirty-three adverse events were identified during readmissions, with the most common type being vascular followed by GI and PPI adverse events, respectively. More than half of the patients did not receive GI prophylaxis appropriately. The most common reason for nonadherence to the consensus document was no prophylaxis when indicated. Vascular events could not be directly attributed to PPI use, and GI events occurred despite prophylaxis. Overall, there was a low incidence of adverse events related to the use of PPI therapy.

Use of proton pump inhibitors and the risk of coronary events in new users of low-dose acetylsalicylic acid in UK primary care

This study evaluated the risk of cardiovascular events associated with the use of proton pump inhibitors (PPIs) in new users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. Two cohorts of patients aged 50-84 years were identified from UK primary care databases: individuals with a first prescription for ASA (75-300 mg/day) for secondary prevention of cardiovascular events (n = 39,513; CVD cohort) or with a record of hospitalisation for an acute coronary event (n = 42,542; ACS cohort) in 2000-2007. Cases of non-fatal myocardial infarction (MI) and coronary death were identified: 1,222 in the CVD cohort and 604 among new users of ASA in the ACS cohort. A nested case-control analysis estimated the relative risk (RR) of non-fatal MI or coronary death associated with use vs non-use of PPI therapy. Current continuous use of PPI therapy was not associated with a significant increase in RR overall: in the CVD cohort (RR=1.14 [95% confidence interval = 0.91-1.43]); in the ACS cohort (0.88 [0.66-1.18]); or among current continuous users of ASA as antiplatelet monotherapy (CVD cohort: 1.15 [0.80-1.66]; ACS cohort: 0.73 [0.43-1.23]; pooled analysis of both cohorts: 0.96 [0.62-1.48]). Inconclusion, among first-time users of ASA for the secondary prevention of cardiovascular events, PPI use was not shown to be associated with an increased risk of non-fatal MI or coronary death.

Impact of Pharmacy Intervention on the Use of Proton-Pump Inhibitors in the Hospital Setting

Determine effectiveness of pharmacy-driven medical staff training regarding proton-pump inhibitor (PPI) therapy. This study was performed in two parts. Part I evaluated baseline PPI usage within the hospital. Part II evaluated the effect of pharmacy-driven medical staff education on PPI prescribing patterns. Data were collected retrospectively via electronic chart review. Passavant Area Hospital in Jacksonville, Illinois, is a 99-bed community hospital. Patients' profiles were selected if administration of at least one PPI was electronically charted during their hospital stay. Patients discharged from the emergency department were not included in the study. There were a total of 1,089 charts reviewed (Part I: N=565; Part II: N=524). The average patient age was 66.5 years. Part I results were presented to the pharmacy and therapeutics (P&T) committee and medical staff. A series of three educational presentations were subsequently given to medical staff. Part II results were reported to the P&T committee, with further interventions to be determined after consulting with hospital administration and medical staff. Improvement of appropriate acute PPI therapy. Secondary outcome measures included duration of acute therapy and continuation of chronic therapy. There was improvement in the appropriate usage of PPI for stress ulcer prophylaxis (SUP) (P=0.1216), decreased chronic PPI therapy (P=0.0054), and increased documentation of PPI indication (P=0.0365). A decrease of appropriate acute duration of PPI for SUP was also observed (P<0.0001). Appropriate initiation of acute and continuation of chronic PPI therapies improved. Appropriate duration of use declined in SUP patients. Pharmacy interventions have an overall positive impact on appropriate use of PPI therapy.

A Retrospective Chart Review on Outcomes after Impedance-pH Monitoring (MII-pH) in Patients with Non-acid Reflux Disease

Purpose: Proton pump inhibitors (PPIs) are known to be effective treatment for gastro-esophageal reflux disease (GERD). There are a number of patients, however, who continue to have symptoms despite the use of PPI therapy. Impedance-pH monitoring (MII-pH) can be performed to rule in or out non-acid reflux (NAR) as the etiology of these symptoms. There is limited data available on the management of these cases. The objective of this study was to evaluate patient characteristics and management outcomes in those patients diagnosed with NAR and positive symptom association. Methods: This was a retrospective chart review of patients who underwent M II- pH testing for symptoms refractory to PPI therapy at our institution. Patient characteristics and treatment outcomes were evaluated for those specifically associated with a positive Symptom Index (SI) for non-acid reflux events (SI score ≥ 50%). Results: Of 140 MII-pH studies reviewed, 23 patients were found to have + SI score for NAR with an abnormal total number of reflux episodes (15%). All patients were considered to have “refractory GERD,” and had been treated with PPI therapy (10 QD dosing and 13 BID dosing). Two patients had previous Nissen fundoplications and were being evaluated for increasing symptoms. There were 15 female and eight male patients, with a mean age of 60 years and mean BMI of 27. Primary symptoms for which the studies were done included: heartburn, cough, and regurgitation. High-resolution manometry revealed decreased distal esophageal amplitude peristalsis in eight patients. Hiatal hernias were noted in 13 patients, and no patients had esophagitis on endoscopy. Two patients were treated with visceral pain modulators, with improvement in symptoms. Five patients were referred for surgical fundoplication and two for surgical revision with reported improvement in their symptoms noted 6-12 months post-operatively. Fifteen patients remained on PPI, six in conjunction with antidepressants. A third of these patients were able to be contacted on a follow-up phone interview, and all of them reported that their symptoms continued. One patient was placed on baclofen, but ultimately underwent surgical fundoplication. Conclusion: Treatment of patients with symptomatic reflux symptoms associated with NAR remains limited. Most patients in this study were kept on PPIs with no resolution of symptoms. Continuing the PPI appeared insufficient for these patients. Anti-reflux surgery may be an option in well selected patients. MII-pH testing will help determine the best strategy of treatment in these patients.

Effects of Omeprazole on Iron Absorption: Preliminary Study

Increasing numbers of pediatric and adult patients are being treated with proton pump inhibitors (PPIs). PPIs are known to inhibit gastric acid secretion. Nonheme iron requires gastric acid for conversion to the ferrous form for absorption. Ninety percent of dietary and 100% of oral iron therapy is in the nonheme form. To the best of our knowledge, the effect of PPIs on iron absorption has not been studied in humans. Our study assessed the relationship between omeprazole therapy and iron absorption in healthy subjects. We recruited 9 healthy volunteers between June 2010 and March 2011. Subjects with chronic illness, anemia, or use of PPI therapy were excluded. Serum iron concentrations were measured 1, 2, and 3 h after the ingestion of iron (control group). The measurements were repeated on a subsequent visit after 4 daily oral administrations of omeprazole at a dose of 40 mg (treatment group). One female and 8 male volunteers were enrolled in the study with a mean age of 33 years. There was no statistical difference detected between baseline, 1-h, 2-h, and 3-h iron levels between control and treatment groups. Administration of omeprazole for a short duration does not affect absorption of orally administered iron in healthy individuals. None declared.

Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis

Recent advances in eosinophilic oesophagitis (EoE) have confirmed the existence of a new disease phenotype, proton pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-REE). To summarise evidence supporting the use of PPI therapy in patients with suspected EoE (oesophageal dysfunction plus >15 eos/HPF in oesophageal biopsies). A literature search was conducted through MEDLINE, using the MeSH search terms 'eosinophilic oesophagitis', 'proton pump inhibitors' and 'oesophageal eosinophilia'. Relevant articles and their reference lists were identified through manual review. Ten articles, including 258 patients with suspected EoE (152 children, 106 adults) undergoing clinico-histological re-evaluation after PPI therapy, were identified. In children, clinical response ranged from 78% to 86% and histological remission from 23% to 40%. In adults, symptom response ranged from 25% to 80% and histological remission from 33% to 61%. Among PPI-REE patients with oesophageal pH-monitoring, 35 showed pathological and 10 normal studies. PPI-REE was significantly commoner with documented gastro-oesophageal reflux disease (GERD) when compared to patients with negative pH monitoring (70% vs. 29%, P<0.001). Symptom improvement/resolution occurred in 50-85% of patients without histological remission on PPI therapy. Six PPI-REE patients demonstrated clinico-histological relapse on PPI therapy. At least one third of patients with suspected EoE achieve clinico-histological remission on PPI therapy. Response is more limited in children compared with that in adults. pH monitoring does not accurately predict response to PPI therapy, albeit histological remission is significantly higher, up to 70%, upon documented GERD. Symptom improvement is common with PPI therapy despite persistent eosinophilic infiltration.

Canadian Association of Gastroenterology Position Statement: Hip Fracture and Proton Pump Inhibitor Therapy – a 2013 Update

Health Canada recently provided an information update on proton pump inhibitor (PPI) therapy and risk of fracture in April 2013 (1) stating “Several scientific studies suggest that PPI therapy may be associated with a small increased risk for fractures of the hip, wrist, or spine related to osteoporosis, a disease resulting in the weakening of bones. The risk of fracture was higher in patients who received multiple daily doses of PPIs and therapy for a year or longer. Additional risk factors for osteoporosis, such as age, gender and the presence of other health conditions, may also contribute to the increased risk of fractures. At Health Canada’s request, manufacturers of all PPIs marketed in Canada have updated the drug labels for their products to include information on this risk.” The Canadian Association of Gastroenterology (CAG) provided a position statement on PPI therapy and risk of hip fracture in 2008 (2) and we have updated this in light of the recent Health Canada statement. Large administrative databases are a useful tool to assess possible benefit or harms of health care interventions; however, given that billions of associations can be measured with these databases, highly statistically significant findings will inevitably occur by chance. Added to this problem is that any association may simply be due to confounding factors and not due to the health care intervention causing the disease (eg, a database study may find that steroid inhaler therapy increases the risk of lung cancer but this may simply be due to smokers being more likely to have lung disease [and be given steroid inhalers] and smoking causes lung cancer). Associations between health care interventions and risk of harm are, therefore, being reported almost every week and it is, therefore, very difficult for the clinician to know what associations are likely to be causal and what are likely to be spurious. There is no simple answer to this problem because epidemiological data can never prove or disprove a hypothesis. Hill (3) described nine factors that make an association more likely to be causal. We have previously evaluated the evidence for PPI therapy and risk of fracture according to the most important of these factors, namely, strength of the association, biological plausibility, specificity, consistency of the association and evidence of a dose response relationship (4). We have conducted an updated systematic review evaluating PPI therapy and risk of fracture that will be submitted to a peer reviewed journal and have used these data to assess the CAG’s position on the use of PPI therapy and risk of fracture.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial

To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

Long Term Proton Pump Inhibitor Therapy and its Association with Fundic Gastric Polyps

Purpose: Proton pump inhibitors (PPI) have been effectively used to treat acid peptic disease for a few decades now. Recent studies have associated long term PPI use with osteoporosis, increased incidence of Clostridium difficile colitis, Vitamin B12 deficiency and more recently with development of Fundic Gastric Polyps (FGPs). The association of PPIs with FGPs continues to be controversial and poorly understood. The purpose of this study was to present in detail a series of three cases that developed FGPs with long term PPI therapy and had complete resolution after discontinuation of the PPI. Methods: In this longitudinal study, three patients (average 57 years; range 52 to 66 years) with documented Gastroesophageal Reflux Disease (GERD) with long term PPI therapy (average 9 years; range 6 to 13 years) were included. Each patient had well documented endoscopy with mucosal biopsies prior to PPI therapy, during and following discontinuation of PPI therapy. Helicobacter pylori testing was performed on the mucosal biopsies using standard techniques. Results: No polyps were observed in the body of the stomach in all three cases prior to PPI therapy. After long term PPI therapy (6 to 12 years), a follow-up endoscopy performed to evaluate persistent GERD symptoms revealed presence of multiple sessile polyps. At this point of time, association of FGPs with PPI use was considered and therefore PPI therapy was discontinued. Repeat endoscopies 1 to 2 years after discontinuation of PPI therapy revealed near complete disappearance of these FGPs in all three cases. All three cases were negative for Helicobacter pylori infection. Conclusion: These observations suggest that long term use of PPI therapy in a select group of patients may be associated with development of numerous fundic polyps in the stomach. This phenomenon seems to be reversible with discontinuation of PPI therapy.

Bacterial Overgrowth and Irritable Bowel Syndrome: Unifying Hypothesis or a Spurious Consequence of Proton Pump Inhibitors?

Some studies indicate that small intestinal bacterial overgrowth (SIBO), as measured by hydrogen breath tests (HBT), is more prevalent in patients with irritable bowel syndrome (IBS) vs. matched controls without IBS. Although the data are conflicting, this observation has led to the hypothesis that SIBO may be a primary cause of IBS. Yet, it remains unclear whether SIBO is truly fundamental to the pathophysiology of IBS, or is instead a mere epiphenomenon or bystander of something else altogether. We hypothesize that SIBO might be a byproduct of the disproportionate use of proton pump inhibitors (PPIs) in IBS, as follows: (1) IBS patients are more likely than controls to receive PPI therapy; (2) PPI therapy may promote varying forms of SIBO by eliminating gastric acid; and (3) existing studies linking SIBO to IBS have not adjusted for or excluded the use of PPI therapy. When linked together, these premises form the basis for a simple and testable hypothesis: the relationship between SIBO and IBS may be confounded by PPIs. Our article explores these premises, lays out the argument supporting this "PPI hypothesis," discusses potential implications, and outlines next steps to further investigate this possibility.

Proton-Pump Inhibitor Use and the Risk for Community-Acquired Pneumonia

Recent studies suggest that proton-pump inhibitors (PPIs) may increase the risk for community-acquired pneumonia (CAP). To examine the association between PPI use and CAP in adults followed in general practices in the United Kingdom. Nested case-control study. The General Practice Research Database (1987 to 2002) in the United Kingdom. Patients age 18 years or older with at least 6 months of initial pneumonia-free follow-up in the database. Case patients (n = 80 066) were defined as those who received an incident diagnosis of CAP. Control participants (n = 799 881) were selected by using incidence density sampling, matching on practice site, calendar period, and follow-up duration. Use of PPIs within 30 days before the index date. Adjusted odds ratios (ORs) were estimated by using conditional logistic regression, adjusting for potential confounders. Overall, current PPI use was not associated with an increased risk for CAP (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) or risk for CAP that required hospitalization (adjusted OR, 1.01 [CI, 0.91 to 1.12]). There was a strong increase in risk for CAP associated with current use of PPI therapy that was started within the previous 2 days (adjusted OR, 6.53 [CI, 3.95 to 10.80]), 7 days (adjusted OR, 3.79 [CI, 2.66 to 5.42]), and 14 days (adjusted OR, 3.21 [CI, 2.46 to 4.18]), but there was no statistically significant association for longer-term current PPI therapy. A separate matched case-control analysis, which included the 3 strongest confounders as additional matching factors, yielded similar results as the primary analysis (adjusted OR, 0.96 [CI, 0.91 to 1.02]). Adherence to PPI prescription was assumed to be 100%. No radiographic evidence was available to corroborate a diagnosis of CAP. Proton-pump inhibitor therapy started within the past 30 days was associated with an increased risk for CAP, whereas longer-term current use was not.

Gastroesophageal Reflux Disease (GERD): Is There More to the Story?

Gastroesophageal reflux disease (GERD) affects both men and women worldwide, with the most common symptom of GERD being frequent heartburn. If left untreated, more serious diseases including esophagitis and/or esophageal cancer may result. GERD has been commonly held to be the result of gastric acid refluxing into the esophagus. Recent work, however, has shown that there are acid-producing cells in the upper aerodigestive tract. In addition, acid-producing bacteria located within the upper gastrointestinal tract and oral cavity may also be a contributing factor in the onset of GERD. Proton pump inhibitors (PPIs) are commonly prescribed for treating GERD; these drugs are designed to stop the production of gastric acid by shutting down the H(+)/K(+)-ATPase enzyme located in parietal cells. PPI treatment is systemic and therefore significantly different than traditional antacids. Although a popular treatment choice, PPIs exhibit substantial interpatient variability and commonly fail to provide a complete cure to the disease. Recent studies have shown that H(+)/K(+)-ATPases are expressed in tissues outside the stomach, and the effects of PPIs in these nongastric tissues have not been fully explored. Likewise, acid-producing bacteria containing proton pumps are present in both the oral cavity and esophagus, and PPI use may also adversely affect these bacteria. The use of PPI therapy is further complicated by the two philosophical approaches to treating this disease: to treat only symptoms or to treat continuously. The latter approach frequently results in unwanted side effects which may be due to the PPIs acting on nongastric tissues or the microbes which colonize the upper aerodigestive tract.

Hip Fracture and Proton Pump Inhibitor Therapy: Position Statement

Hip Fracture and Proton Pump Inhibitor Therapy: Position Statement