Proton Pump Inhibitor Therapy Research Articles

A study on appropriate use and stewardship of proton pump inhibitors

Objective: To analyze the prescribing pattern of use of PPI with respect to “FDA-Approved Indications and Doses for PPI Therapy.” Materials and Methods: After obtaining approval from the Institutional Ethics Committee, a cross-sectional study was carried out among 400 inpatients in a tertiary care hospital in Bangalore. The data were collected from the patient case profile and prescriptions and noted in a self-designed data collection form. The statistical analysis of the collected data was performed using SPSS software and Excel. Results: The study, conducted on 400 patients, revealed a male majority (60%) and a female representation of 40%. Proton Pump Inhibitors (PPIs), mainly Pantoprazole (74.70%), were frequently prescribed, notably in General Medicine (220 patients). PPI use was generally appropriate: indication (99%), dose (97%), frequency (92.8%), and duration (91.8%). However, irrational prescriptions were noted: indication (1%), dose (3%), frequency (7.3%), and duration (8.3%). 139 drug interactions were identified, categorized into Major (39.6%), Moderate (46%), and Minor (14.4%). For example, Ondansetron and tramadol exhibited a major interaction. Among PPI combinations, 93.75% could affect CYP2C19 metabolism, and 6.3% had additive/synergistic toxicity potential.

Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

Longitudinal microbiome changes in children exposed to proton pump inhibitors.

Proton pump inhibitor (PPI) use has been associated with an increased risk of gastrointestinal and upper respiratory infections in children. There are limited longitudinal data on the effect of PPI in children. The goal of this prospective observational study was to compare the stool and oropharyngeal microbiome of children before and after starting PPIs. We prospectively recruited participants from a gastroenterology clinic. Consented pariticpants provided stool samples and oropharyngeal swabs at baseline and after eight weeks of PPI therapy. Microbiome changes were measured by analyzing 16S sequencing from both body sites at both timepoints. Thirty-four participants completed the study and provided samples both at baseline and after eight weeks on PPI therapy. Of those, 24 participants had sufficient sequencing from both stool and oropharyngeal samples at both time points. There were no differences between the pre- vs post-PPI samples using beta-diversity metrics in either the oropharynx or stool. There were, however, significant changes in specific taxa. There was an enrichment of Streptococcus in the stool in after PPI-use and a reduction in the relative abundance of Bifidobacterium, Peptostreptococcus and Turicibacter (p-values < 0.01). Furthermore, there was an increase in the relative abundance of oropharyngeal bacteria in the stool after PPI therapy. This enrichment of oropharyngeal bacteria in the stool was most prominent in younger participants. Further investigation is needed to determine the clinical and microbial factors that predispose or protect against microbiome changes due to PPI-use, and why young children are more susceptible to this PPI effect.

Long-Term Intake of Proton-Pump Inhibitors Could Be Associated with an Increased Incidence of Liver Cancer in Women.

Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06-1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09-1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09-1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21-3.26). Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication.

Comparison of vonoprazan dual therapy, quadruple therapy and standard quadruple therapy for Helicobacter pylori infection in Hainan: a single-center, open-label, non-inferiority, randomized controlled trial

ObjectiveTo compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province.MethodsA single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18–75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT).ResultsThe eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%–95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%–98.4%), 92.7% (38/41, 95%CI 84.4%–101.0%),88.4% (38/43，95%CI 78.4%–98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy.ConclusionVPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior.

Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Incidence, Clinical Characteristics, and Outcomes of Clostridium difficile Infection in a Tertiary Care Center in Bahrain.

Background Clostridioides difficile infection (CDI) represents a significant healthcare challenge associated with antibiotic use and healthcare settings. While healthcare facility-onset CDI (HO-CDI) rates have been extensively studied, the incidence and risk factors of CDI in various settings, including the community, require further investigation. Aim This study aims to examine the incidence rates of CDI in a major governmental hospital in Bahrain, identify risk factors for CDI, and assess the effectiveness of infection control measures. Method We conducted a retrospective study at the Salmaniya Medical Complex (SMC), analyzing all confirmed cases of CDI over a 30-month period from January 2021 to June 2023. CDI cases were screened using glutamine dehydrogenase antigen detection and confirmed using molecular assays like polymerase chain reaction and/or toxin assaysfor confirmation.The study categorized CDI cases based on their onset (hospital or community) and explored associated risk factors, including antibiotic use, proton pump inhibitor (PPI) therapy, and patient demographics. Infection control practices were also evaluated for their role in managing CDI. Results About 57 new CDI cases were identified during the study period, with a HO-CDI incidence rate of 0.5 per 10,000 patient days. While HO-CDI rates remained stable, community-onset (CO)-CDI cases increased. The median patient age was 61.8 years, without notable differences between genders. Key risk factors for CDI were antimicrobial therapy, use of acid-reducing agents, age, and underlying comorbidities. The mortality rate stood at 35.1%. The ATLAS score (i.e., age, treatment with antibiotics, leukocyte count, albumin level, and serum creatinine) was a reliable predictor of mortality. Critical care admission and low albumin levels emerged as significant independent risk factors for mortality. Conclusions The study demonstrates a low incidence rate of HO-CDI at SMC, attributed to effective infection control and antibiotic stewardship programs. The overall CDI rate increased during the study period, driven by a rise in CO cases; further investigating the risk factors among this category in our study revealed that most patients were exposed to antibiotic therapy within the past three months of their CDI diagnosis. The rise in CO-CDI cases underscores the need for broader community-based interventions and awareness regarding antibiotic and PPI use.

Comparison of Vonoprazan versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding after Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial

High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aims to compare the efficacy of vonoprazan versus PPI for preventing high-risk PU rebleeding after hemostasis. A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20-mg BID for 3 days, then 20-mg OD for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/hour for 3 days, then omeprazole 20-mg BID for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3-and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable among the two groups. The 30-day rebleeding rate in vonoprazan and PPI groups were 7.1% (7/98) and 10.4% (10/96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference= -3.3; 95% confidence interval = -11.2, 4.7; P<0.001). The 3-day and 7-day rebleeding rates in vonoprazan group remained noninferior to PPI (P< 0.001 by Farrington and Manning test). All secondary outcomes were also comparable between the two groups. In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI.

Proton pump inhibitors: rational use and use-reduction. The Windsor Workshop.

Despite deprescribing initiatives to curb overutilisation of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge. An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction. • Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. • When commencing a PPI, patients should understand the reason for treatment, planned duration and review date. • PPI use at hospital discharge should not be continued without a recognised indication for long-term treatment. • Long-term PPI therapy should be reviewed at least annually. • PPI use-reduction should be based on the lack of a rational indication for long-term PPI use, not concern for PPI-associated adverse events. • PPI use-reduction strategies involving switching to on-demand PPI or dose tapering, with rescue therapy for rebound symptoms, are more likely to succeed than abrupt cessation.

The Role of Proton Pump Inhibitors in the Realm of Idiopathic Pulmonary Fibrosis and its Associated Comorbidities: A Systematic Review.

As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management ofpatients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITYand ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic reviewand meta-analysison antacid and antireflux surgery in IPFnegate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.

Proton Pump Inhibitors Do Not Affect the Bioavailability of a Novel Liquid Formulation of Levothyroxine

ObjectiveThis study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of levothyroxine (LT4) solution (Tirosint-SOL). MethodsThis was a randomized, 3-way crossover, comparative bioavailability study in 36 healthy adults under fasting conditions.Omeprazole 40 mg delayed-release capsule was administered once daily from day 1 to 6 (mornings, treatment-A; evenings, treatment-B; none, treatment-C) to increase and stabilize gastric pH. In the morning of day 5, a single dose of LT4 solution 600 mcg was administered. Blood samples were collected 0 to 48 hours post-LT4 administration. Noncompartmental pharmacokinetics parameters were calculated for total serum thyroxine using baseline-corrected data. Maximum concentration (Cmax) and area under the concentration-time curve (AUC0-48) were included in an analysis of variance to obtain geometric mean ratios and 90% confidence intervals. ResultsFor both comparisons (A/C and B/C), geometric mean ratio and 90% confidence intervals for all parameters were within the equivalence boundaries (80%-125%), indicating bioequivalence: for A/C, AUC0-48 98.98% [94%-104%], and Cmax 91.68% [87%-97%]; for B/C, AUC0-48 98.94% [95%-103%], and Cmax 94.90% [90%-100%]. Median Tmax was similar across treatments. ConclusionThis study demonstrated that Tirosint-SOL bioavailability is unaffected by coadministration of a representative PPI, given simultaneously or staggered by about 12 hours, compared to administration of LT4 solution alone. For hypothyroid patients on PPI therapy, administration of LT4 solution may reduce variations in thyroid stimulating hormone levels related to intermittent use of acid-reducing drugs and consequently the need for dose adjustments.

A210 ESOPHAGEAL SQUAMOUS PAPILLOMATOSIS AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION

Abstract Background Squamous papillomatosis is a rare benign epithelial finding, generally found incidentally in the distal esophagus. The pathophysiology is not well understood but felt to be secondary to reflux and chemical irritation leading to leukoplakia and verrucous hyperplasia of the epithelium and papilloma formation. Aims To present a case of esophageal squamous papillomatosis after endoscopic submucosal dissection (ESD) and radiofrequency ablation (RFA) of Barrett’s esophagus (BE) and early esophageal cancer. Methods Case report and review of the literature Results A 78-year-old male with C3M3 BE and previous band mucosectomy for nodular dysplasia was referred for ESD of an early esophageal cancer. ESD was successfully performed, with histopathology identifying a low-risk well-differentiated intramucosal adenocarcinoma without lymphovascular invasion and negative margins. Radiofrequency ablation was performed 3-months post-resection for residual BE. Subsequent surveillance gastroscopy 6 months post-resection identified extensive fleshy pink granulation tissue at the ESD scar, histopathology revealing SP. This was confirmed on subsequent repeat gastroscopy and biopsy. Compliance with double dose proton pump inhibitor therapy was confirmed. Conclusions To our knowledge, this is the first reported case of SP developing post-ESD and RFA; further expanding our knowledge of potential Barrett’s endotherapy-related adverse events. Funding Agencies None

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease

Abstract Background The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). Aims To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. Methods This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Results Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. Conclusion CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

Adherence to prescription proton pump inhibitor therapy amongst individuals diagnosed with Barrett's esophagus.

In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described. We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups. 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year. Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.

Refractory Gastroesophageal Reflux Disease: Diagnosis and Management.

Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.

Association Between Risk of Clostridium difficile Infection and Duration of Proton Pump Inhibitor or H2-Receptor Antagonist Use in Hospitalized Patients.

Limited studies have evaluated the association between Clostridium difficile infection (CDI) and the duration of proton pump inhibitor (PPI) or histamine H2-receptor blocker (H2RA) use and provided a cutoff duration for PPI or H2RA use to mitigate a substantially increased risk of CDI. We aimed to evaluate these associations in hospitalized patients using a nationwide insurance claims database. We conducted a nested case-control study to identify cases with a first ever record of CDI in a study cohort undergoing PPI or H2RA therapy from the National Health Insurance Database from 2012 to 2018. Each case was matched with one control by age, sex, and calendar year. We used conditional logistic regression to estimate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC ROC). Youden's Jstatistic was used to identify the optimal cutoff duration in days for PPI or H2RA use. In the main analysis, the AUC ROC was 0.64 (95%CI 0.63-0.66) and optimal cutoff duration was 15days for PPI users. The AUC ROC was 0.63 (95%CI 0.62-0.64) and optimal cutoff duration was 16days for H2RA users. In the sensitivity analyses, the results were similar to those of the main analysis, and the optimal cutoff duration was in the range of 14-15days. The optimal cutoff duration for PPI and H2RA use was about 2weeks. It is necessary to be cautious regarding the risk of CDI in patients taking PPIs or H2RAs for longer than 2weeks.

Effectiveness of Proton Pump Inhibitor Therapy in Children with Chronic Otitis Media: an Evidence-Based Case Report

Introduction: In Indonesia, 82% of children with otitis media have experienced chronic otitis media (COM). COM has a high recurrency rate and is multifactorial, one of which is caused by acid reflux. Proton pump inhibitor (PPI) therapy has been used to treat acid reflux and gives excellent result. Purpose: Reporting one case of a child with COM and laryngopharyngeal reflux (LPR) who received PPI therapy. An evidence-based literature review was done to evaluate the effectiveness of PPI therapy in patient with COM and LPR.Methods: Literature searching was done through 3 databases. Critical appraisal based on the Oxford Center for Evidence Based Medicine Checklists 2011.Results: After we sorted out duplications and screened articles according to our inclusion and exclusion criteria, we retrieved one article. This article is valid and applicable, yet PPI therapy did not give significant clinical improvement because of some reasons.Conclusion: From the literature review, PPI therapy on patient with COM did not give significant clinical improvement such as to stop middle ear discharge, yet in our case, PPI therapy could produce a clinical improvement and in line with previous experimental studies. Therefore, PPI therapy could still be considered given in children with COM.

Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study.

Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality. Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up. A total of 591,207 patient datasets of a German healthcare insurer were screened. We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation. The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge. Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15-1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08-1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23-1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08-1.27; p = 0.006). These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P=0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P=0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P=0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P=0.003) and specific aeroallergens correlated with PPI-nr-EoE. Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Clostridium Difficile Infection in Rectal Cancer Patients after Diverted Loop Ileostomy Closure.

Clostridium difficile infection is a cause of increased morbidity and mortality in hospitals, particularly in patients with cancer pathology. There are several factors favouring the development of Clostridium difficile infection among cancer patients, including age, exposure to antibiotic and proton pump inhibitors therapy, and chemotherapy. This study was conducted to observe the prevalence of Clostridium difficile infection after the reversal of ileostomy loop for rectal cancer surgery, which were initially operated either open or laparoscopic. A retrospective study was performed on patients who were operated in a single surgical team for rectal cancer who benefited of a diverted loop ileostomy over a 4-year period. Results: 23 patients were documented with Clostridium difficile infection out of a total of 63. All 23 patients underwent ileostomy closure later than 3 months after primary surgery, and postoperatively received antibiotic therapy associated with proton pump inhibitors in the first 24 hours. Conclusions: Closure of ileostomy later than 3 months after primary surgery, combined with chemotherapy, antibiotic therapy and proton pump inhibitors, increases the risk of developing Clostridium difficile infection.