Pump Inhibitor Usage Research Articles

Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.

Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66). We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

Patterns and determinants of chemotherapy-associated Clostridium difficile infection among cancer patients in the United States: A population-based study.

e19111 Background: Elderly cancer patients comprise a population that is vulnerable for Clostridium difficile infection (CDI). In addition to the frequent hospitalizations, the administration of chemotherapeutic agents has been associated with the development of CDI. The objective of this study was to identify the patterns and determinants of chemotherapy-associated CDI (Chemo-CDI), in a nationwide sample of elderly patients. Methods: We used NCI’s Surveillance, Epidemiology, and End Results registry linked Medicare (SEER-Medicare) 2007-2012 files. We included patients’ aged ≥65 year, with diagnosis of lung/breast/ovarian/colorectal/prostate cancer, or lymphoma/multiple myeloma/leukemia during 2008-2011. We excluded those not receiving chemotherapy, with non-continuous Medicare enrollment, or HMO enrollment. Chemotherapy receipt was identified using appropriate ICD-9/HCPCS/CPT codes. Incidence of CDI following chemotherapy were determined by identifying any claim with primary/secondary diagnosis of CDI during the two-month follow-up period. Recurrent Chemo-CDI was identified by presence of any claim that was > 2 weeks and ≤8 weeks from the index CDI diagnosis date. Covariates including antibodies/proton pump inhibitors usage were captured and included in the analysis. Chi-square tests, and hierarchical generalized logistic models were conducted to identify determinants of Chemo-CDI. Results: We identified 41,470 elderly patients with lung/breast/ovarian/colorectal/prostate cancer, or lymphoma/multiple myeloma/leukemia diagnosis during the study years. While few (266) patients developed Chemo-CDI within one year of diagnosis, more than 50% (136) of those patients developed recurrent Chemo-CDI. Patient characteristics were not associated with risk of developing Chemo-CDI, however, significant differences were observed in antibiotics/proton pump inhibitors exposure across all cancer types (p < 0.001). Treatment for Chemo-CDI mostly comprised of Metronidazole and oral Vancomycin. Conclusions: While the incidence of Chemo-CDI is lower among patients receiving chemotherapy, the rate of recurrent Chemo-CDI was significantly higher. Strategies to prevent CDI recurrence in this population are therefore warranted. Future studies should also explore the association between increased disease burden and comorbidity, and the risk of developing Chemo-CDI.

A single centre experience of treatment outcomes for Helicobacter pylori infection among inner-city children and adolescents.

This study assessed treatment outcomes of Helicobacter pylori (Hpylori) infection among inner-city children. This was a retrospective study of patients aged 1-21years who underwent initial treatment for Hpylori infection from 2011 to 2015. We included patients who completed 2weeks of treatment with documented adequate compliance after Hpylori infection was diagnosed. Treatment outcomes were measured based on stool Hpylori antigen and/or histology. Of the total 261 patients diagnosed with Hpylori, 239 completed the first-line treatment. The regimens used included amoxicillin/clarithromycin/proton pump inhibitor (PPI) in 207/239 patients (86.6%), amoxicillin/metronidazole/PPI in 14/239 patients (5.8%) and other regimens in 18/239 patients (7.5%). Hpylori eradication status was tested in 111/207 (53.6%) patients treated with amoxicillin/clarithromycin/PPI, and the eradication was achieved in 84/111(75.7%) patients. The treatment success rates for amoxicillin/metronidazole/PPI and other regimens were 71.4% (5/7) and 63.6% (7/11), respectively. There was no statistical significance of post-treatment stool Hpylori antigen results between PPI (n=31) and no PPI (n=43) users. The study showed an eradication rate of 75.7% with the regimen amoxicillin/clarithromycin/PPI suggesting significant antibiotic resistance in our population. The use of PPI did not influence post-treatment stool Hpylori antigen results.

P080 A PROSPECTIVE LONGITUDINAL STUDY OF PROTON PUMP INHIBITORS EFFECT ON INFLAMMATORY BOWEL DISEASE FLARES AND ACTIVITY

Abstract Introduction Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications in the United States. Some recent studies have suggested that PPIs may have a negative effect on the gut microbiome. Dysbiosis of the gut microbiome has been linked with inflammatory bowel disease (IBD). We hypothesized that PPI use is associated with increased IBD flares and activity. This study was aimed to assess the effect of PPIs on IBD flares and activity. Methods We conducted a prospective longitudinal study of Veterans from the IBD clinic at the Michael E. DeBakey VA Medical Center from 2014 to 2018. Our eligibility criteria included patients who were at least 18 years of age, who were diagnosed with Crohn’s Disease (CD) or Ulcerative Colitis (UC), and who had at least 2 clinic visits. IBD flare was defined by patient self-report of IBD flare between clinical encounters. IBD activity was quantified using the partial Mayo Score (pMayo) for UC, and the Harvey Bradshaw Index (HBI) for CD. Remission was defined by pMayo< 2 for UC and HBI< 5 for CD. The exposure of PPI was confirmed by chart review. Associations of PPI use with IBD flare and activity were assessed using T-tests and Chi-squared tests. Results A total of 132 patients were included in the analysis of which 74 had CD and 58 had UC. 40 patients were PPI users, and IBD flares occurred in 60 patients. No significant association between PPI usage and IBD flares were observed: 42.5% of PPI users developed flares compared to 46.7% of non-PPI users who developed flares, p-value=0.658. In patients with CD, PPI use was associated with non-remission status (RR 2.53; 95% CI 1.04–6.15). In UC patients, PPI use was not associated with non-remission status (RR 1.10; 95% CI 0.67 - 1.79). 13 CD patients on PPIs discontinued the PPI between encounters, which was associated with a statistically significant decrease in HBI (3.62 to 2.54, p-value= 0.005). Among UC patients who discontinued PPIs, there was a non-significant trend towards decreased pMayo (2.26 to 1.59, p-value= 0.069). Discussion Amongst CD patients, PPI use was not associated with interval flare however it was associated with non-remission status. Cessation of PPIs was associated with a statistically significant decrease in HBI in CD patients. Amongst UC patients, no significant associations between PPI use and flare or activity were observed. Decreasing unnecessary PPI use in patients with CD may decrease disease severity.

Appropriateness of proton pump inhibitor use in patients admitted under the general medical unit

AbstractBackgroundProton pump inhibitors (PPI) are extensively prescribed internationally and in Australia. However, minimal information is available on the appropriateness of PPI use in the general medical population.AimThis study determined the proportion of general medical unit (GMU) inpatients taking a PPI on admission and evaluated the appropriateness of these PPI prescriptions.MethodsA single‐centre prospective observational study was conducted from 6 June to 11 July 2016. Consecutive patients were screened, and those taking a PPI prior to admission were included, whereas those not taking a PPI formed the control cohort. Appropriateness of PPI use was evaluated by: (1) reviewing for concordance with the Australian Therapeutic Guidelines and National Prescribing Service Guidelines on PPI use in gastro‐oesophageal reflux disease; (2) assessment of indication, dose and treatment duration by an expert panel consisting of two general physicians and one senior pharmacist.ResultsAmong 440 consecutive GMU patients, 198 (45.0%) were taking a PPI on admission. Of these, 66.2% had an inappropriate indication, dose or treatment duration. The largest category of inappropriate PPI use was excessive treatment duration (43.4%). In terms of comorbid conditions, PPI users had a higher prevalence of osteoporosis and/or history of fracture (42.9% vs 27.2%; p < 0.001) and hypomagnesaemia (10.6% vs 3.4%; p = 0.003).ConclusionInappropriate PPI use is highly prevalent among GMU inpatients. Given the potential for adverse effects, unnecessary health expenditure and pill burden, strategies should be developed to aid clinicians to consistently consider the utility of continuing long‐term PPI prescriptions in each patient's situation.

Stewardship for Appropriate Management of Proton Pump Inhibitors (PPI) Usage in GI Fellowsʼ Continuity Clinics: Presidential Poster Award

Stewardship for Appropriate Management of Proton Pump Inhibitors (PPI) Usage in GI Fellowsʼ Continuity Clinics: Presidential Poster Award

Covering the Cover

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Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden

ObjectiveProton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to...

Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans

ObjectiveProton pump inhibitors (PPIs) are widely used, and their use is associated with increased risk of adverse events. However, whether PPI use is associated with excess risk of death is...

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

ABSTRACTProton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.

Appropriateness of Proton Pump Inhibitor prescription in patients admitted to hospital: Attitudes of general practitioners and hospital physicians in Italy

IntroductionProton pump inhibitor (PPI) prescriptions have raised concern for both huge increase of health expenditure and possible long-term adverse effects. ObjectiveTo evaluate appropriateness of PPI prescription in ambulatory and hospital care. DesignObservational cohort study. PatientsPatients admitted to the Internal Medicine Unit of Bologna S. Orsola Hospital between 15/09/2013 and 15/12/2013. Data on clinical condition and drug therapy were collected at three time points: admission (reflecting GP's prescription), hospital stay and discharge. Main measuresAppropriateness of PPI use was evaluated as follows: (1) agreement between PPI use/non-use and appropriate clinical condition; (2) in PPI users, assessment of Medication Appropriateness Index (MAI). Differences in appropriateness among time points were analyzed by chi-square test. Logistic regression model was used to identify possible determinants of PPI appropriateness. Key resultsAmong 280 patients, 56% received PPI at least once in the three time points. Appropriateness, according to indication of use, was similar between admission and hospital stay (61% vs. 62%; p=0.82) and between hospital stay and discharge (62% vs. 59%; p=0.94). MAI score showed important, although statistically non-significant, change in appropriateness between admission and hospital stay (20% vs. 28%; p=0.16). Age≥65 was always associated with appropriate PPI use (up to OR=4.37; p<0.01), whereas cardiovascular comorbidity and conditions requiring analgesic treatment influenced appropriateness only at admission (OR=3.84; p<0.01 and OR=0.34; p<0.01, respectively). ConclusionsHospital clinicians only rarely reconsidered GP's choice to prescribe PPI. Room for improvement in PPI appropriateness is represented by (1) assessing gastrointestinal risk in each patient under analgesics and anti-inflammatory drugs, and (2) short-term re-evaluation of PPI prescription after discharge.

Proton pump inhibitors alter the composition of the gut microbiota

ObjectiveProton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have...

Proton pump inhibitors affect the gut microbiome

Background and aimsProton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections,...

The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: A prospective cohort study

ObjectivesProton pump inhibitors (PPIs) are among the most prescribed medications worldwide, however, there is growing concern regarding potential negative effects on bone health. The aim was to examine the effect of dose and type of PPI use on subsequent use of osteoporosis medication and fractures in older Australian women. MethodsData were included from 4432 participants (born 1921–26) in the 2002 survey of the Australian Longitudinal Study on Women's Health. Medication data were from the national pharmaceutical administrative database (2003–2012, inclusive). Fractures were sourced from linked hospital datasets available for four major States of Australia. Competing risk regression models used PPI exposure as a time-dependent covariate and either time to first osteoporosis medication prescription or fracture as the outcome, with death as a competing risk. ResultsOf the 2328 PPI users and 2104 PPI non-users, 827 (36%) and 550 (26%) became users of osteoporosis medication, respectively. PPI use was associated with an increased risk of subsequent use of osteoporosis medication (adjusted sub-hazard ratio [SHR]=1.28; 95% confidence interval [CI]=1.13–1.44) and subsequent fracture (SHR=1.29, CI=1.08–1.55). Analysis with PPI categorized according to defined daily dose (DDD), showed some evidence for a dose–response effect (osteoporosis medication: <400 DDD: SHR=1.23, CI=1.06–1.42 and ≥400 DDD: SHR=1.39, CI=1.17–1.65, compared with non-users; SHRs were in the same range for fractures). Esomeprazole was the most common PPI prescribed (22.9%). Analysis by type of PPI use showed an increased subsequent risk for: (1) use of osteoporosis medication for rabeprazole (SHR=1.51, CI=1.08–2.10) and esomeprazole (SHR=1.48, CI=1.17–1.88); and (2) fractures for rabeprazole (SHR=2.06, CI=1.37–3.10). Users of multiple types of PPI also had increased risks for use of osteoporosis medication and fractures. ConclusionAn appropriate benefit/risk assessment should be made when prescribing PPIs, especially for esomeprazole and rabeprazole, as osteoporosis and fracture risks were increased in this cohort of elderly females subsequent to PPI prescription.

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

Background and AimsProton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.MethodsUsing a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.ResultsIn multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.ConclusionsConsistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

Wireless pH-metry at the gastrojejunostomy after Roux-en-Y gastric bypass: a novel use of the BRAVO™ system

The number of gastric bypass operations being performed is increasing rapidly due to good weight loss and alleviation of comorbidities in combination with low mortality and morbidity. Stomal ulcers are, however, a clinical problem after gastric bypass, giving patients discomfort, risk of bleeding, or even perforation. To measure the acidity in the proximal jejunum, we adopted the wireless pH-metry (BRAVO™ system) developed for evaluating reflux esophagitis. Twenty-five patients (4 men; median age, 44 years; body mass index, 29.3) who had undergone Roux-en-Y gastric bypass (RYGBP) 4 years earlier were recruited. Twenty-one asymptomatic, non-proton pump inhibitor (PPI) users, and in addition, four symptomatic patients (ongoing or stopped PPI treatment) were studied. The wireless BRAVO™ capsule was positioned at the level of the gastrojejunal anastomosis under visual control with the endoscope. pH was registered for up to 48 h. Time with pH<4 was calculated. Two patients were studied with two capsules. Of the 25 recruited patients, capsule placement was successful in all but two patients, and in three patients a constant neutral environment was seen before a premature loss of signal, indicating early loss of position. Thus, 20 successful measurements were made. The mean time of registration was 25.7 (range, 6.1-47.4) h (n=20). In the 16 asymptomatic patients, median percentage of time with pH<4 at the gastrojejunostomy was 10.5% (range, 0.4-37.7%). When dividing the registration time in day (06.00-22.00) and night (22.00-06.00), the median percentage of time with pH<4 was 8.4 and 6.3, respectively (p=0.08). The two double measurements gave similar results indicating consistency. No complications occurred. Wireless pH measurements in the proximal jejunum after gastric bypass are feasible and safe. The acidity was significant (10.5% of the registration time) even in asymptomatic patients with small gastric pouches. The described method could be useful in evaluation of epigastralgia after gastric bypass and in appraisal of PPI treatment of stomal ulcer.

Population pharmacokinetics of posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome

Objective:The relationship between patient characteristics and posaconazole exposures was evaluated in a population pharmacokinetic (PK) model using trial data from neutropenic patients administered oral posaconazole suspension as antifungal prophylaxis.Methods:Data were analyzed using nonlinear mixed-effects modeling. Covariates were tested using the forward addition, Objective Function (OF) cut-off of 3.84, followed by the backward elimination (OF cut-off 10.88) steps in NONMEM. These covariates included demographics, mucositis, neutropenia, vomiting, diarrhea, proton pump inhibitor (PPI) or H2-receptor antagonist usage and baseline bilirubin or baseline gamma-glutamyl transferase (GGT) levels ≥2 × upper limit of normal (ULN). A correlation between posaconazole PK and the occurrence of invasive fungal infection (IFI) was also examined.Results:Statistically significant associations were demonstrated between posaconazole PK and diarrhea, PPI intake, race, and baseline GGT and bilirubin levels. These covariates did not predominate in patients who developed IFI.Conclusion:This analysis provides information regarding the correlation of patient covariates with posaconazole exposures estimated in a clinical setting. The results of this analysis agree with previously reported analyses. However, because of the successful prophylaxis and the low number of posaconazole-treated patients with IFI proven or probable (IFIPP), the absence of a statistically significant relationship between IFIPP and exposure may not mean this relationship does not exist. A meta-analysis of several efficacy trials or exploring alternate composite endpoints for efficacy may be needed to answer this question.

Risedronate Shows Consistent Reduction of The Risk of New Vertebral Fractures Over Three Years In Proton Pump Inhibitor (PPI) and H2-Receptor Antagonist (H2RA) Users

Risedronate Shows Consistent Reduction of The Risk of New Vertebral Fractures Over Three Years In Proton Pump Inhibitor (PPI) and H2-Receptor Antagonist (H2RA) Users

Indications for proton pump inhibitor (PPI) usage in patients admitted to nursing facilities

Indications for proton pump inhibitor (PPI) usage in patients admitted to nursing facilities