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Proton pump inhibitors (PPIs) are widely prescribed and are indicated for the treatment of several gastrointestinal disorders. Allergists may prescribe PPIs as a result of the coincidence of gastroesophageal reflux disease with asthma or rhinitis, or when gastroesophageal reflux disease presents as chronic cough. Furthermore, long-term, high-dose PPI therapy is a recommended option for managing eosinophilic esophagitis, resulting in histologic remission in approximately 40% of patients. Here, we discuss current recommendations for PPI use, its deescalation, and its side effect profile. We review evidence supporting the epidemiologic link between the use of acid-suppressant medication and the subsequent development of allergic disorders.

Potentially inappropriate prescribing (PIP) in elderly patients is highly prevalent and is associated with an increased risk of adverse drug events, morbidity, and mortality. Accordingly, this study aimed to evaluate the PIP encountered in a geriatric setting and to highlight the role of the clinical pharmacists in this context.A retrospective observational study was conducted during March and April 2018 in an elderly daycare in Beirut area. Patients' files were screened to evaluate each patient's clinical status using a developed tool that included the Medication Appropriateness Index. Statistical analysis was performed using SPSS (version 20). The results were considered significant at P0.05.The results showed a high incidence of hypertension, schizophrenia, and diabetes among the studied sample with percentages of 41.7%, 35.3%, and 26.6%, respectively. As for the PIP, drug therapy duration and cost were the most encountered problems followed by medication indication, dosage, and drug-drug interaction. Moreover, PIP increased with the number of prescribed medications (P0.05). Proton pump inhibitors, low dose aspirin, and antidiabetic medications' users had a significantly higher Medication Appropriateness Index score as compared to non-users.As a conclusion, suboptimal care is proved in this study empowering the collaboration between clinical pharmacists and physicians in minimizing the PIPs in elderly daycares.

Posaconazole is a broad-spectrum triazole antifungal, with activity against various clinically important fungi. The delayed release (DR) tablet of posaconazole has been shown to have a superior pharmacokinetic profile in comparison with the oral suspension.We retrospectively analyzed the factors associated with posaconazole levels1.25 μg/ml in 164 patients receiving the DR tablet for therapeutic purposes.Of the 164 patients, 53 (32.3%) showed subtherapeutic trough levels of posaconazole. The use of proton pump inhibitors (95% CI 1.41-3.91; P-value = 0.028) and the presence of diarrhea (95% CI 1.95-6.93; P-value = 0.001) were significantly associated with subtherapeutic levels. A total of 13 of the 21 patients receiving posaconazole tablets through a nasogastric tube had therapeutic levels.This is the largest study from India that analyzed factors associated with subtherapeutic levels of the DR tablet of posaconazole. These findings reinforce the importance of therapeutic drug monitoring. Unlike in previous studies, obesity and hypoalbuminemia were not found to be significant factors in our settings. The use of proton pump inhibitors and diarrhea remained significant factors, as found in previous studies. Administering the DR tablet of posaconazole through a nasogastric tube may be a viable option.

Introduction Studies assessing the management of laryngopharyngeal reflux by otolaryngologists have reported an important heterogeneity regarding the definition, diagnosis, and treatment, which leads to discrepancies in the management of the patient. Information about the current knowledge and practices of Brazilian otolaryngologists in laryngopharyngeal reflux is lacking. Objective To investigate the trends in management of laryngopharyngeal reflux disease among Brazilian otolaryngologists. Methods A survey was sent by email to the members of the Brazilian Association of Otolaryngology-Head Neck Surgery. This survey has initially been conducted by the laryngopharyngeal reflux study group of young otolaryngologists of the International Federation of Otolaryngological Societies. Results According to the survey responders, the prevalence of laryngopharyngeal reflux was estimated to be 26.8% of patients consulting in otolaryngology and the most common symptoms were globus sensation, throat clearing, cough and stomach acid reflux. Nasal obstruction, Eustachian tube dysfunction, acute and chronic otitis media, vocal fold nodules and hemorrhage were considered not associated with laryngopharyngeal reflux by the majority of responders. About 2/3 of Brazilian otolaryngologists based the diagnosis of laryngopharyngeal reflux on the assessment of both symptoms and findings and a positive response to empiric therapeutic trials. Proton pump inhibitor utilized once or twice daily, was the most commonly used therapeutic scheme. Only 21.4% of Brazilian otolaryngologists have heard about nonacid and mixed laryngopharyngeal reflux and the awareness about the usefulness of multichannel intraluminal impedance pH monitoring (MII-pH) was minimal; 30.5% of responders did not consider themselves as well-informed about laryngopharyngeal reflux. Conclusion Although the laryngopharyngeal reflux-related symptoms, main diagnostic and treatment approaches referred by Brazilian otolaryngologists are consistent with the literature, the survey identified some limitations, such as the insufficient awareness of the role of laryngopharyngeal reflux in many otolaryngological conditions and of the possibility of non-acid or mixed reflux in refractory cases. Future studies are needed to establish international recommendations for the management of laryngopharyngeal reflux disease.

Proton pump inhibitors (PPI) may influence the gut microbiome and thus impact the effectiveness of immune checkpoint inhibitors (ICI). The effect of PPIs on the outcomes of ICI has not been fully explored and investigated in metastatic renal cell carcinoma (mRCC).This retrospective analysis used prospectively collected data from the GETUG-AFU 26 NIVOREN (NCT03013335) phase II study which enrolled 729 mRCC patients of whom 720 were treated with nivolumab. The main objective of this analysis was to evaluate the impact of PPI on the efficacy and safety outcomes of mRCC patients. PPI use was defined as PPI administration on the day of ICI initiation.Of the 707 patients with mRCC analyzed in this study, 196 (27.7%) were PPI users. The majority of PPI users were males (80.6%), had an ECOG performance status of 0-1 (78.9%) and a nephrectomy (82.1%). Almost two-thirds of the patients had a favorable and intermediate IMDC risk category and 52% received nivolumab in the third line and beyond. PPI use did not correlate with PFS or OS (HR = 0.89, 95% CI 0.74-1.08 and HR = 1.24; 95% CI, 0.98-1.58, respectively). Grade 3-5 nivolumab-related adverse events were more common among PPI users (25.5% vs. 15.3%).This real-world study suggests that PPI use in patients with mRCC does not impact the efficacy outcomes but may influence the safety of nivolumab which warrants further investigations.

While patients with Barrett's esophagus without dysplasia may benefit from endoscopic surveillance, those with low-grade dysplasia may be managed with either endoscopic surveillance or endoscopic eradication. Patients with Barrett's esophagus with high-grade dysplasia and/or intramucosal adenocarcinoma will generally require endoscopic eradication therapy. The management of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma is predominantly endoscopic, with multiple effective methods available for the resection of raised neoplasia and ablation of flat neoplasia. High-dose proton-pump inhibitor therapy is advised during the treatment of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma. After the endoscopic eradication of Barrett's esophagus and associated neoplasia, surveillance is required for the diagnosis and retreatment of recurrence or progression.

BACKGROUND/PURPOSE Clarithromycin-based standard triple therapy is still commonly adopted by 81.4% of physicians in real-world practice but yields low eradication rates. Therefore, we conducted this study to compare the efficacy of gastric juice-guided therapy for first-line eradication with the standard triple therapy, in order to provide an alternative to real-world practice. METHODS A total of 182 treatment-naive Hp-infected patients were included and randomly allocated to either susceptibility-guided therapy (SGT) with gastric juice PCR or Clarithromycin-based standard triple therapy (STT) for 7 days. RESULTS The intention-to-treat eradication rates were 89% (81/91) in SGT and 75.8% in STT (p < 0.031). The per-protocol eradication rates were 91.0% (81/89) in SGT and 79.3% (69/87) in STT (p < 0.034). Among the subgroups of different antibiotic resistance, patients with SGT demonstrated superior eradication rates (91.7% vs 45.5%, p < 0.027) in the subgroup of both clarithromycin resistance and levofloxacin resistance. CONCLUSION This prospective randomized controlled trial demonstrated the reliable efficacy of susceptibility-guided therapy via gastric juice PCR for the first-line Hp eradication. In Asia-Pacific area, where standard triple therapy is still adopted by the majority of the physicians, it is a recommended alternative to overcome the increasing antibiotic resistance.

Long-term, high-dose, daily proton pump inhibitors (PPI) may impact outcomes associated with distal radius fractures (DRF). The hypothesis was that differences existed in patient demographics, but there existed no differences in injury patterns, interventions, post-operative complications, and patient-reported outcomes between patients not on a PPI and patients on a PPI with a DRF.An IRB-approved, post-hoc analysis of patients with DRF from 2012 through 2018 was performed. Patients included were age ≥18 years, sustained a DRF, had completed medical and medication records, Quick Disabilities of the Arm, Shoulder and Hand (DASH) scores, Global Assessment of Functioning (GAF) scores, visual analogue scale (VAS) pain scores, and a minimum of 1-year follow-up. Patients were stratified into two cohorts. Cohort one patients had no prescription or over-the-counter PPI use (no PPI cohort). Cohort two patients had adherence to a long-term, high-dose, daily PPI (PPI cohort).Two hundred and eighty-one DRF patients were included. Of these 281 patients, 240 were in the no PPI cohort and 41 were in the PPI cohort. Patients in the PPI cohort had more median nerve injuries (12% versus 3%, p = 0.025) and radial shaft fractures (5% versus 0%, p = 0.020), less contralateral upper extremity injuries (0% versus 4%, p = 0.001), and more post-operative nonunions (7% versus 1%, p = 0.029) compared to patients in the no PPI cohort.Long-term, high-dose, daily PPI's may be associated with more median nerve injuries and radial shaft fractures, less contralateral upper extremity injuries, and more post-operative nonunions compared to DRF patients not on a PPI.

Helicobacter pylori infection affects approximately 70% of the Chilean population. It is a public health problem whose eradication treatment is part of the explicit health guarantees in Chile.Characterize the most widely used H. pylori first-line eradication therapies in our environment and evaluate their efficacy.A retrospective observational study was carried out where, in patients with certified H. pylori infection, the eradication therapy indicated by the treating physician, its efficacy, adherence and adverse effects, in addition to the eradication certification method used, were evaluated.242 patients and 4 main therapies were analyzed: standard triple therapy, dual therapy, concomitant therapy, and bismuth quadruple therapy. Eradication rates of 81.9% (95% CI 74.44-87.63), 88.5% (95% CI 73.13-95.67), 93.7% (95% CI 78.07-98.44) and 97.6% (95% CI 84.81-99.67) were observed respectively, with concomitant therapy (RR: 1.14; 95% CI 1.01-1.29; p=.028) and quadruple therapy with bismuth (RR: 1.19; 95% CI 1.09-1.31; p.001) being significantly more effective than standard triple therapy. Regarding the rate of reported adverse effects, it was 58.5% (95% CI 50.66-65.92), 35.4% (95% CI 24.6-48.11), 22.9% (95% CI 81-37.14) and 63.4% (95% CI 47.8-76.64), having the dual and concomitant therapy significantly fewer adverse effects compared with standard therapy.Quadruple therapies are superior to standard triple therapy and should be considered as first-line treatment in Chile. Dual therapy is promising. More studies will be required to determine which therapies are most cost-effective.

The aim of this study was to clarify the correlation between gastrin receptor (GR) expression in the gastric oxyntic mucosa and fundic gland polyps (FGPs) and the histological and immunohistochemical findings of the mucosa as well as the history of proton pump inhibitor (PPI) administration. The unique membranous linear positivity of GR in parietal cells was reproducibly observed by immunohistochemistry, which was also validated by immunofluorescence. Further histological and immunohistochemical examination of 34 oxyntic mucosae and 43 FGPs revealed the following: 1) parietal cells (PCs) with membranous linear GR expression (mGR) were observed to be limited to the isthmus-neck region in the normal state; 2) appearance of PCs with mGR in the deep oxyntic gland regions was significantly related to the PPI medication history; 3) PCs with mGR were more frequently observed in the deep oxyntic gland regions when the oxyntic mucosa showed derangement of mucosal component cell compartmentalization revealed by MUC5AC and MUC6 immunohistochemistry, which was also significantly related to the PPI use; and 4) PCs with intense membranous linear positivity of GR were observed to be diffusely distributed in all of the cases of FGPs. In conclusion, the distribution of unique GR membranous linear expression in PCs of the oxyntic mucosa under PPI medication and FGPs could reflect the pathologic mucosal state characterized by derangement of the compartmentalization of mucosal component cells, which could be another basis for evaluating physiologic and/or pathophysiologic conditions of the gastric mucosa.

BACKGROUND/PURPOSE This study aimed to explore the anatomical and physiological characteristics of patients with laryngopharyngeal reflux (LPR) symptoms, such as hoarseness, throat clearing, throat pain, globus, and chronic cough, with the novel high-resolution impedance manometry (HRIM). METHODS Consecutive patients exhibited at least one LPR symptom for ≥4 weeks after 2-month proton-pump inhibitor treatment were enrolled during November 2014 and March 2018 from single tertiary medical center. All patients completed validated symptom questionnaires, esophagogastroduodenoscopy, and HRIM. Healthy volunteers were also recruited for comparison of esophageal parameters on HRIM. RESULTS Eighty-nine LPR patients and 63 healthy volunteers were analyzed. Compared with healthy volunteers, LPR patients had significantly shorter upper and lower esophageal sphincters (UES and LES), a shorter intraabdominal esophagus (all P

The use of proton pump inhibitors has increased exponentially over the past 20 years. Several side effects have been reported and concerns exist about the consequences of long-term proton pump inhibitors on health, leading to limitation of their use. The present study analyzed prescriptions of proton pump inhibitors at inpatient units and assessed their compliance with current recommendations.This single-center, observational, retrospective study reviewed medical file of patients hospitalized at the pediatric medical departments of the Bordeaux University Hospital between April 1 and September 30, 2019. Patients younger than 18 years, hospitalized in the pediatric hospital units and treated with proton pump inhibitors were included. Prescriptions of proton pump inhibitors were compared with French and international guidelines.Proton pump inhibitors were prescribed for 251 of 2237 children (11%), mainly for gastroesophageal reflux disease (47%) and prevention of peptic ulcer disease (32.7%). Proton pump inhibitor prescription complied to recommendations in 34.5% of cases, less often in children aged younger than 1 year (13.5%) than in older children. Compliance to recommendations was lower when proton pump inhibitors were indicated for the prevention of peptic disease (5%) than for gastroesophageal reflux disease (48%).Proton pump inhibitors are frequently prescribed for hospitalized children, and indications comply with recommendations in only 35% of the cases. Efforts in spreading awareness of the recommendations on the use of proton pump inhibitors in children are mandatory among hospital pediatricians.

Background: Elevated levels of Chromogranin A (CgA) may be indicative of a neuroendocrine tumour (NET), but increased levels are also observed after intake of proton pump inhibitors (PPIs). The incidence of diagnostic confusion because of this drug-laboratory test interaction (DLTI) was examined. Methods: Medical records of 238 patients with elevated CgA concentrations were obtained from three hospitals. The following data were extracted: PPI prescription at the time of CgA measurement, medical decision making based on elevated CgA concentrations, final diagnosis, comorbidity and other prescribed drugs. Results: From 238 patients with elevated CgA concentrations, 132 used PPIs. Of these patients, 57 patients did not have a NET. In 9 of these 57 patients (16%), diagnostic work up revealed no medical cause of an elevated CgA concentration. Somatostatin receptor imaging was ordered in 4 out of 9 cases, with no abnormalities observed. In 6 out of 9 cases, CgA measurement was repeated after PPI discontinuation resulting in normalisation of CgA concentrations. Conclusion: In this retrospective patient record study we observed that part of the elevated CgA concentrations in patients could be caused by the usage of PPIs causing unnecessary diagnostic work-up for the exclusion of a NET. These observations illustrate the need for better DLTI awareness.

Pemetrexed is associated with hematological toxicity. Drug-drug interactions (DDIs) between methotrexate and proton pump inhibitors (PPIs) induce a higher risk of hematological toxicity due to the inhibition of methotrexate excretion by PPIs. As pemetrexed and methotrexate are both excreted by human organic anion transporter 3 (hOAT3), this study investigates the hypothetical DDI between pemetrexed and PPIs in lung cancer patients. The primary objective was the occurrence of severe (grade ≥ 3) hematological toxicity. The secondary objectives were to describe the type of hematological toxicity and associated clinical consequences (NCT03537833).PPI consumption was collected for each patient receiving pemetrexed-based anticancer chemotherapy from May 2018 to October 2020 in a prospective multicentric observational and nonrandomized study. Multivariate Cox regression and propensity score (PS) adjustment, PS matching and inverse weighting on PS (IPTW) methods were used.PPI consumption (55 among 156 included patients) was associated with a significantly higher risk of severe hematological toxicity in the multivariable Cox regression model (hazard ratio HR = 2.51, 95% confidence interval [1.47-4.26]; p = 0.005). Similar results were found with PS adjustment (HR = 1.91 CI95% [1.14-3.20]; p = 0.002), PS-matching (HR = 1.93 CI95% [1.08-3.45]; p = 0.02) and IPTW method (HR = 2.06 CI95% [1.27-3.35]; p = 0.004). Severe neutropenia and anemia occurred in 32.7% and 14.1% of patients, respectively. This resulted in 48 anticancer chemotherapy postponements and 24 dose adjustments, 26 growth factor prescriptions, 24 red blood cell transfusions, and 20 hospitalizations.The results strongly suggest an association between PPI consumption and pemetrexed-related severe hematological toxicity. Deprescription of PPIs when feasible should be considered to prevent this DDI.

To evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT).This study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score-matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding.Of these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04).In China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted.clinicaltrials.gov Identifier: NCT02306616.

Proton pump inhibitors are widely used throughout the world for the treatment of gastrointestinal disorders that are related to acid secretion, such as peptic ulcer disease and dyspepsia. Another common indication for proton pump inhibitors is stress ulcer prophylaxis. Proton pump inhibitors have proven efficacy for the treatment of acid-related gastrointestinal disorders, but there is concern that their use may be associated with the development of significant complications, such as fractures, Clostridium difficile infection, acute kidney injury, chronic kidney disease, and hypomagnesemia. Proton pump inhibitors are overused in the hospital setting, both for stress ulcer prophylaxis and gastrointestinal bleeding, and then they are often inappropriately continued after discharge from the hospital. This narrative review article outlines the evidence surrounding appropriate proton pump inhibitor use for stress ulcer prophylaxis and peptic ulcer bleeding.

Background Multidrug-resistant organisms (MDROs) are a reality that can alter the paradigm of treatment and prevention of infection in patients with liver cirrhosis (LC). Objective Identify risk factors for the occurrence of MDROs in patients with LC. Patients and methods Prospective study from October 2017 to March 2018 in consecutively hospitalized patients with decompensated LC with infection. Blood, urine and ascitic fluid cultures were analyzed. A p-value ≤0.05 was considered statistically significant. Results MDROs isolated in 18 of 52 episodes of infection. MDROs were associated with the use of proton pump inhibitors (PPIs) (p = 0.0312), antibiotic therapy in the last 90 days (p = 0.0033) and discharge within preceding 30 days or current hospitalization above 48 h (p = 0.0082). There was higher 90-day mortality in patients with MDROs infection (71.4% versus 35.7%, p = 0.0316). Conclusion MDROs infections were prevalent in this cohort and associated with 90-day mortality. Use of PPIs and antibiotics increased the risk of MDROs infections, suggesting that its prescription should be restricted to formal indication. Hospitalization was associated with the onset of MDROs, so LC patients should stay at the hospital the least possible. It is relevant to investigate other factors predisposing to the emergence of these microorganisms, in order to prevent it.

Proton pump inhibitors (PPIs) may be linked to implant failure by affecting bone metabolism and osseointegration. This study evaluated how PPIs influence long-term implant failure and peri-implantitis in PPI users and nonusers.This was a retrospective cohort study of patients treated at the Philadelphia Veterans Affairs Medical Center between 2006 and 2013. The primary predictor variable was PPI use. Outcome variables were long-term implant failure and the presence of peri-implantitis. Data gathered included demographic characteristics, medical comorbidities, implant location, and dimensions. Multivariate regression models measured independent factor associations. The final study cohort contained 933 implants placed in 284 patients. A total of 323 (32.6%) implants were placed in patients with ongoing PPI use. PPI users were less likely to smoke (22.1% vs 31.9%; P.01) and use illicit drugs (5.0% vs 9.7%; P = .01) and more likely to have undergone prior bone grafting (18.3% vs 12.9%; P = .03).PPI use lost significance after controlling for confounding factors and was not an independent predictor of implant failure (odds ratio [OR], 0.801; 95% confidence interval [CI], 0.56-1.15; P = .24) or peri-implantitis (OR, 0.801; 95% CI, 0.56-1.15; P = .24).Our study found no independent associations between PPI use and implant failure or peri-implantitis. Contrary to published literature, PPIs may not influence implant health.

Functional and motility gastrointestinal disorders are the most common complaints to the pediatric gastroenterologist. Disorders affecting the small intestine carry a significant morbidity and mortality due to the severe limitation of therapeutic interventions available and the complications associated with such interventions. Congenital colorectal disorders are rare but also carry significant morbidity and poor quality of life plus the social stigma associated with its complications. In this review, we summarize the clinical presentation, diagnostic evaluations, and the therapeutic interventions available for the most common and severe gastrointestinal functional and motility disorders of the small bowel, colon, and anorectum.

Background Non-bismuth containing quadruple therapy (concomitant therapy) is an alternative treatment for Helicobacter pylori (H. pylori) eradication with increasing clarithromycin-resistant strains over times. This study compared the efficacies of non-bismuth containing quadruple therapy (concomitant therapy) in the treatment of first-line anti-Helicobacter Pylori between two time intervals (January 2013 to June 2014 and June 2016 to December 2017). Methods H. pylori-infected patients were recruited in the intention-to-treat (ITT analysis) and divided into EACM-A group (enrolled from January 2013 to June 2014, N = 98) and EACM-B group (enrolled from June 2016 to December 2017, N = 99). Patients were prescribed with 7-day esomeprazole 40 mg bid., clarithromycin 500 mg bid., amoxicillin 1 g bid. and metronidazole 500 mg bid. Ninety patients and 93 patients were analyzed in the per protocol (PP) analysis (8 and 6 patients lost follow-up in each group). Urea breath tests were performed 4–8 weeks thereafter. Results The eradication rates for EACM-A and EACM-B groups were 87.8% (95% confidence interval [CI] = 79.7%–93.5%) and 84.8% (95% CI = 76.2%–91.2%) (p = 0.55) in intention-to-treat (ITT) analysis; 95.6% (95% CI = 89.1%–98.8%) and 90.3% (95% CI = 82.4%–95.5%) (p = 0.17) in per protocol (PP) analysis. The adverse event rates were 16.7% vs. 10.8% in the 2 groups (p = 0. 0.24). The antibiotic resistance rates between the 2 groups were amoxicillin (0%), tetracycline (0%); clarithromycin (11.8% vs. 17.8%, p = 0.46); metronidazole (32.4% vs. 33.3%, p = 0.93) and levofloxacin (14.7% vs. 37.8%, p = 0.02). Conclusion The success rate of 7-days concomitant therapy encountered an approximately 5% decrease across 4-year time interval (2013–2017) with the changes of clarithromycin resistance from 11.8% to 17.8% in Taiwan.

Long-standing inflammation leads to esophageal remodeling with stricture formation in patients with eosinophilic esophagitis (EoE). The ability of proton pump inhibitors (PPI) to reverse endoscopic features of fibrosis is still unknown.To investigate the effect of a short course of PPI treatment in reducing endoscopic findings indicative of esophageal fibrosis in EoE patients.Cross-sectional analysis of the EoE CONNECT registry. Patients who received PPI to induce EoE remission were evaluated. Endoscopic features were graded using the EoE Endoscopic Reference Score (EREFS), with rings and strictures indicating fibrosis. Results were compared to those from patients treated with swallowed topic corticosteroids (STC).Clinico-histological remission was achieved in 83/166 adult patients treated with PPI (50%) and in 65/79 (82%) treated with STC; among responders, 60 (36%) and 57 (72%) patients respectively achieved deep histological remission (5 eosinophils/hpf). At baseline, mean±SD EREFS was lower in patients treated with PPI compared to those who received STC (p 0.001). Short term treatment significantly reduced EREFS scores in patients treated either with PPI or STC as well as rings and strictures. Among patients treated with PPI, deep histological remission (5 eosinophils/hpf) provided further reduction in total EREFS score.Effective PPI therapy for EoE significantly reduced endoscopic esophageal fibrosis in the short term.

Proton pump inhibitors (PPI) are widely used and implicated in the progression of chronic kidney disease (CKD). We evaluated the relation between chronic PPI use in veterans with CKD G3a to G4 and the rate of decline in renal function.We accessed the Veteran Affairs Informatics and Computing Infrastructure national database to evaluate the relation between chronic PPI use and rate of decline in renal function in veterans with CKD (eGFR60 ml/min1.73 m2). We applied Propensity Score Matching to match the PPI group and the no-PPI control group on age, sex, race, and Charlson Comorbidity Index. The final sample included 1406 patients (age: 62.07±7.82, 62.02% Caucasian) in the PPI cohort with a median 4.7 years follow-up and 1425 patients (age: 65.45±6.58, 71.16% Caucasian) in the control cohort with a median 3.9 years follow-up. Kaplan-Meier curve and Cox regression were performed to analyze the associations of PPI use with dialysis, all-cause mortality, metabolic acidosis, and CKD progression.The PPI group had a significantly increased risk of CKD progression, dialysis and all-cause mortality (aHR, 1.83; 95% CI, 1.53 to 2.19; aHR, 1.84; 95% CI, 1.26 to 2.67; and aHR, 1.34; 95% CI, 1.08 to 1.65, respectively). The PPI cohort also had a trend for development of metabolic acidosis (aHR, 1.34; 95% CI, 0.998 to 1.80), although the difference was not statistically significant.The data suggest that chronic PPI use accelerates progression of kidney disease and is associated with increased mortality in CKD patients.

Background Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. Objectives To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. Methods Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008–2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value

Objective To determine the prevalence and risk factors for inappropriate discharge on proton pump inhibitor (PPI) therapy started in the intensive care unit (ICU) for stress ulcer prophylaxis. Patients and Methods This was a retrospective cohort study of adults initiated on treatment with a PPI in any of 9 affiliated ICUs from January 1, 2014, to December 31, 2018. Patients were excluded if they had an appropriate long-term PPI indication. Logistic regression modeling was used to identify characteristics associated with discharge on treatment with an inappropriate PPI. Results Of 24,751 patients admitted to an ICU, 4127 were initiated on treatment with a new PPI, with 2467 (60%) lacking a long-term PPI indication. Of these 2467, a total of 1122 (45%) were continued on PPI therapy after transfer to the floor and 668 (27%) were discharged on PPI therapy. On multivariable analysis, risk factors for inappropriate discharge on PPI therapy included having an upper endoscopy (adjusted odds ratio [aOR], 1.70; 95% CI, 1.08-2.66), admission to the surgical compared with medical ICU (aOR, 2.03; 95% CI, 1.32-3.10), and discharge to a nursing home or rehabilitation facility (aOR, 1.43; 95% CI, 1.04-1.96; and aOR, 2.29; 95% CI, 1.62-3.24, respectively). Conclusion Among patients started on treatment with a PPI in the ICU without an indication for outpatient PPI use, 27% (668 of 2467) were nonetheless discharged on PPI therapy. Medically complex and surgical ICU patients are at increased risk for receiving PPIs without appropriate documented indications, and careful review of medication lists at discharge should occur in these high-risk groups.

Background For the past two decades, dispute on whether proton pump inhibitor (PPI) leads to digestive tract cancer remains, and emerging studies in recent years still demonstrate inconsistent results, which continues to perpetuate concerns over the safety of PPI use. We performed a systematic review and meta-analysis, with comprehensive evaluation by Bradford Hill criteria of causation, to assess the effect of PPI use on digestive tract cancers. Methods Medline, Embase and Web of Science databases were searched for observational studies published up to 15th January 2021. Pooled relative risks (RRs) were estimated via random effects models. Cumulative defined daily dose- and duration-risk relationships using restricted cubic spline and fractional polynomial models were investigated. Bradford Hill criteria were applied to evaluate causation. PROSPERO Registration: CRD42020211103. Results Thirty-two publications containing 4,355,254 participants were included. PPI use is associated with an increased risk of overall digestive tract cancers (RR = 1.63, 95% confidence interval (CI) 1.33 to 2.00). PPI use is correlated with increased risks of gastric cancer (RR = 1.78, 95% CI 1.38 to 2.31), pancreatic cancer (RR = 1.72, 95% CI 1.05 to 2.82) and liver cancer (RR = 1.62, 95% CI 1.04 to 2.52), but not of esophageal cancer (RR = 2.06, 95% CI 0.65 to 6.57) and colorectal cancer (RR = 1.24, 95% CI 0.93 to 1.66). The association between PPI and digestive tract cancers is stronger in people with minimal exposure. When cumulative defined daily dose or duration increases, the risks decline and become non-significant. Evaluation by Bradford Hill criteria indicates weak evidence of causation. Conclusions A causal relationship between PPI use and digestive tract cancers is not supported by the evidence in the current review. Concerns over carcinogenic side-effects of PPI might be unfounded.

Summary Background Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. Methods In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT04030780 . Findings Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07–4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. Interpretation In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. Funding MY HEALTH.

Eosinophilic esophagitis (EoE) is an antigen-triggered chronic disease of increasing prevalence in children and adults. Untreated or therapy-resistant EoE leads to complications of esophageal food impactions and luminal narrowing. The past decade has seen a number of new clinical trials for EoE therapies including elimination diets, proton pump inhibitors, swallowed topical corticosteroids, and biologics. In this review, we comment on the current state of the art for dietary and pharmacologic management of EoE and the need for future clinical trials to help tailor therapies to individual patients with this chronic disease.

Purpose Proton pump inhibitor (PPI) use is a potential risk factor for hepatic encephalopathy (HE), but few studies have examined the effect on post-TIPS HE. The purpose of this study was to determine whether PPIs are associated with increased rates of post-TIPS HE in an independent patient cohort. Materials and methods This single-institution retrospective study analyzed 86 patients (54 male, mean age 58.2) following TIPS from 1/1/2017 to 12/31/2019. Dates of PPI usage and episodes of new or worsening HE were recorded. Poisson regression with generalized estimating equations was used to test for association between PPI use and post-TIPS HE and to test for dose dependence. Post-TIPS HE was also analyzed using the Andersen-Gill survival model for recurrent events. Results There were 1.88 episodes of new or worsening post-TIPS HE per person-year among 35 patients on uninterrupted PPIs therapy, 1.95 on PPIs and 0.94 off PPIs among 35 patients on intermittent therapy, and 0.47 among 16 patients never on PPIs. PPI use was significantly associated with post-TIPS HE in both univariable (incidence rate ratio (IRR) = 2.62; CI = 1.41–4.84; p = 0.002) and multivariable (IRR = 2.31; CI = 1.37–3.89; p = 0.002) regression. Analysis of only those patients on PPIs showed increased rates of HE with higher doses (IRR = 1.17 per 10 mg omeprazole equivalent; CI = 1.04–1.33; p = 0.011). Recurrent events survival analysis supported the association between PPI use and HE in univariable (hazard ratio (HR) = 2.17; CI = 1.19–3.95; p = 0.011) and multivariable (HR = 1.87; CI = 1.12–3.13; p = 0.017) analysis. Conclusion In an independent patient cohort PPI use was associated with increased rates of new or worsening post-TIPS HE.

Objective Although histamine-2 receptor antagonists (H2RAs) have been shown to be more likely to cause delirium than proton pump inhibitors (PPIs), these results were not adjusted for potential confounding factors. Accordingly, we investigated whether H2RAs and PPIs are risk factors for delirium, even when adjusting for other risk factors by analyzing adverse drug event reports compiled in the post-marketing stages of drugs provided by the Japanese regulatory authorities. Method We analyzed 577,431 reports in the Japanese Adverse Drug Event Report database from April 2004 to July 2020. Results Of all reports analyzed, 2532 described delirium, and 574,899 described other adverse events. Delirium was associated with H2RAs (crude reporting odds ratio, ROR, 4.17; 95% CI, 3.34–5.22) but not PPIs (crude ROR 0.62; 95% CI 0.43–0.90). Even with adjustment for age, sex, history of dementia or depression, and concomitant drugs reported as risk factors for delirium, the use of H2RAs showed a significantly higher adjusted ROR than that of PPIs (H2RAs: adjusted ROR 3.99; 95% CI 3.18–5.01 and PPIs: adjusted ROR 0.58; 95%CI 0.40–0.84). Conclusions These results suggest that, from a cognitive perspective, PPIs may be preferable to H2RAs for patients with or at risk for delirium.

Background The ongoing Coronavirus Infectious Disease (COVID-19) pandemic is a global health crisis that has had a magnanimous worldwide impact on all aspects of people's lives. Several observational studies investigated the relationship between Proton Pump Inhibitors use and the risk of COVID-19 development and mortality. Aim of the Study The aim of this meta-analysis is to investigate the association between current PPIs use and the development of COVID-19 as well as its mortality. Methods Pubmed, Google Scholar, ScienceDirect and medRxiv were searched until November 21, 2020 using the following keywords: proton pump inhibitors and COVID-19 as well as their related MESH terms. The studies considered in the meta-analysis were either cohort or case-control in design and adjusted for confounding factors. The quality of the studies included in this meta-analysis was assessed using the Newcastle-Ottawa Scale. In addition, a random-effects model was used to calculate the pooled Odds Ratio (ORs) and the corresponding confidence interval (95% CI). Heterogeneity was evaluated using The Cochran's Q heterogeneity test and I2 statistic. Results Six observational studies with 195,230 participants were included. In this meta-analysis, current use of PPIs increased risk of COVID-19 development (OR = 1.19; 95% CI: 0.62-2.28) and mortality (OR = 1.67; 95% CI: 1.41-1.97). Conclusions Our meta-analysis indicates that current PPIs use significantly increased the risk of COVID-19 mortality, but it did not reach a significant threshold in regards to the risk of COVID-19 development.

Human fatty acid synthase (FASN) is the sole cytosolic enzyme responsible for de novo lipid synthesis. FASN is essential for cancer cell survival and contributes to drug and radiation resistance by up-regulating DNA damage repair but not required for most non-lipogenic tissues. Thus, FASN is an attractive target for drug discovery. However, despite decades of effort in targeting FASN, no FASN inhibitors have been approved due to poor pharmacokinetics or toxicities. Here, we show that the FDA-approved proton pump inhibitors (PPIs) effectively inhibit FASN and suppress breast cancer cell survival. PPI inhibition of FASN leads to suppression of non-homologous end joining repair of DNA damages by reducing FASN-mediated PARP1 expression, resulting in apoptosis from oxidative DNA damages and sensitization of cellular resistance to doxorubicin and ionizing radiation. Mining electronic medical records of 6754 breast cancer patients showed that PPI usage significantly increased overall survival and reduced disease recurrence of these patients. Hence, PPIs may be repurposed as anticancer drugs for breast cancer treatments by targeting FASN to overcome drug and radiation resistance.

Background and Study Aims Endoscopic submucosal dissection (ESD) is the most effective treatment for early gastric cancer or gastric adenoma . However, ESD results in iatrogenic ulcers and postoperative bleeding from ulcers. This study aimed to evaluate the effect of using a proton pump inhibitor (PPI) alone, a PPI + rebamipide combination therapy, and an H2 receptor antagonist (H2RA) + rebamipide combination therapy on ulcer healing after ESD. Patients and Methods A total of 204 patients who underwent ESD from April 2014 to July 2017 at Dong-A University Hospital were randomly assigned to the following groups: PPI-alone group, PPI + rebamipide combination therapy group, and H2RA + rebamipide combination therapy group. However, only 156 patients were studied since we excluded those who were lost to follow-up or had diseases other than early gastric cancer or gastric adenoma. Twenty-eight days after ESD, we evaluated the ulcer residual ratio, S stage rates, ulcer bleeding ratio, and gastric pH. Results This study included 156 patients (PPI-alone group: 52 patients; PPI + rebamipide group: 52 patients; H2RA + rebamipide group: 52 patients). The ulcer residual ratios were 24.3 ± 14.2%, 17.0 ± 12.1%, and 21.0 ± 13.8% in the PPI alone, PPI + rebamipide, and H2RA + rebamipide groups, respectively (P = 0.048). Conclusions PPI + rebamipide was more effective in reducing the ulcer residual ratio after ESD. There was no statistical difference in ulcer stage and delayed bleeding after ESD among the groups. These findings showed that PPI + rebamipide had limited benefits after ESD.

The prevalence of peptic ulcer diseases has decreased over the past decades. The contribution of Helicobacter pylori to these changes has not been clearly delineated. Two cohorts of patients receiving esophagogastroduodenoscopy examination together with urease test were enrolled, 1 from year 2001 (n = 1030), the other from year 2019 (n = 600). The prevalence changes of peptic ulcer diseases as well as the associated clinical factors were analyzed. An independent cohort of gastric biopsy samples (n = 151) positive for H. pylori were retrieved for ureC gene genotype analysis. Comparison between the patients recruited from 2001 and 2019 revealed significant decrease in H. pylori infection (P0.001), duodenal ulcer prevalence (P0.001) and gastric ulcer prevalence (P0.001). Multivariate analysis showed that the decreases of these factors were independent (adjusted P0.001 for all). Intriguingly, in H. pylori positive patients, the prevalence of duodenal ulcer still decreased with year (P0.001), which was not found in gastric ulcer (P = 0.345). Genetic analysis of H. pylori urease gene showed that MboI-restriction fragment length polymorphism-defined genotype 3 UreC was significantly more prevalent in gastric ulcer patients than in others (P = 0.022). Independent decreases of H. pylori infection, gastric ulcer and duodenal ulcer over decades were found. In H. pylori positive patients, duodenal ulcer prevalence decreased overtime while gastric ulcer prevalence remained unchanged. Gastric ulcer/cancer had a higher prevalence of MboI-defined genotype 3 UreC gene.

Background: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This ‘drug score’ was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1–2 and poor risk with score 3–4. Methods: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non–small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy). Results: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab cohort (p < 0.0001), and 6.2 months, 6.2 months and 4.3 months, respectively, within the chemotherapy cohort (p = 0.0280). Among the pembrolizumab-treated patients, the median overall survival (OS) for good, intermediate and poor risk patients was 31.4 months, 14.5 months and 5.8 months, respectively, (p < 0.0001), whereas among the chemotherapy-treated patients, it was 18.3 months, 16.8 months and 10.6 months, respectively (p = 0.0003). A similar trend was reported considering the two entire populations. At the pooled analysis, the interaction term between the score and the therapeutic modality was statistically significant with respect to ORR (p = 0.0052), PFS (p = 0.0003) and OS (p < 0.0001), confirming the significantly different effect of the score within the two cohorts. Conclusion: Our ‘drug score’ showed a predictive ability with respect to ORR in the immunotherapy cohort only, suggesting it might be a useful tool for identifying patients unlikely to benefit from first-line single-agent pembrolizumab. In addition, the prognostic stratification in terms of PFS and OS was significantly more pronounced among the pembrolizumab-treated patients.

BACKGROUND AND AIMS: The impact of proton pump inhibitory (PPI) medications on adverse outcomes in cirrhosis remains controversial. We aimed to evaluate the association between PPI exposure and all-cause mortality, infection, and decompensation in a large national cohort. METHODS: This was a retrospective study of patients with cirrhosis in the Veterans Health Administration. PPI exposure was classified as a time-updating variable from the index time of cirrhosis diagnosis. Inverse probability treatment weighting-adjusted Cox regression was performed with additional adjustment for key time-varying covariates including cardiovascular comorbidities, gastrointestinal bleeding (GIB), and statin exposure. RESULTS: Of 76,251 included patients, 23,628 were on a PPI at baseline. In adjusted models, binary (yes/no) PPI exposure was associated with reduced hazard of all-cause mortality in patients with hospitalization for GIB (HR 0.88, 95% CI 0.84–0.91, p

PURPOSE To investigate the association between the use of proton pump inhibitors (PPIs) and the risk of early biliary infection (EBI) after the placement of percutaneous transhepatic biliary stents (PTBS) in patients with unresectable malignant biliary obstruction (MBO). MATERIALS AND METHODS A total of 136 patients with unresectable MBO (82 males and 54 females) treated with PTBS were included in this multicenter retrospective study. PPIs were prescribed to MBO patients with dyspepsia. The risk factors for EBI were identified by univariate and multivariate analyses. The association between the use of PPIs and EBI was assessed by logistic analyses. RESULTS A total of 72 (53%) patients were regular users of PPIs, and 33 (24%) patients developed EBI after PTBS. Univariate and multivariate analyses revealed that diabetes (hazard ratio [HR], 20.3; 95% confidence interval [CI], 5.6-72.9; P

Background and study aims The present study was designed to evaluate the safety, efficacy, and tolerability of antofloxacin-based bismuth quadruple therapy in Chinese patients with Helicobacter pylori infection. Patients and methods Total 290 patients with H. pylori infection were randomly and equally divided into two groups as per different bismuth quadruple therapies for 14 d: colloidal bismuth pectin 200 mg thrice a day, lansoprazole 30 mg twice a day, amoxicillin 1 g twice a day, and antofloxacin 200 mg once a day (ACLA group) or levofloxacin 500 mg once a day (LCLA group). Eradication was assessed with 13C-urea breath test 6 wk after treatment completion; the primary endpoint was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. The minimum inhibitory concentration was measured with the PDM epsilometer test to assess the susceptibility of H. pylori strains on gastric biopsy specimens to antofloxacin and levofloxacin. Results The eradication rates of H. pylori in the ACLA group were 93.8% and 97.8% for the ITT and PP analysis, respectively; these rates were significantly higher than those in the LCLA group, at 86.2% and 92.6%, respectively (p = 0.031 and 0.041, respectively). The total incidence of adverse events during the eradication therapy did not significantly differ between the ACLA and LCLA groups (31.7% vs. 37.9%%, p = 0.267), and the two groups displayed similar severity of adverse events (p = 0.156) and compliance rate (100% by ACLA vs. 97.8% by LCLA, p = 0.080). The eradication rate with the antofloxacin susceptible strains in the ACLA group was significantly higher than that with the resistant strains (99.2% vs. 66.7%, p = 0.045). Moreover, the eradication rate with the levofloxacin susceptible strains in the LCLA group was significantly higher than that with the resistant strains (95.3% vs. 80.0%, p = 0.013). Conclusion Antofloxacin is safe and effective for H. pylori eradication. Antofloxacin-based bismuth quadruple therapy could be an alternative treatment for H. pylori eradication.

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

OBJECTIVE: To examine associations of cumulative exposure to proton pump inhibitors (PPIs) with total cardiovascular disease (CVD; comprised of stroke, coronary heart disease, and heart failure [HF]) and HF alone in a cohort study of white and African American participants: the Atherosclerosis Risk in Communities Study. PATIENTS AND METHODS: PPI use was assessed via pill bottle inspection at Visit 1 (January 1, 1987– 1989) and up to 10 additional times before baseline (Visit 5; 2011–13). We calculated cumulative exposure to PPIs as days of use from Visit 1 to baseline. Participants (n=4346 free of total CVD at Visit 5; mean age=75) were followed for incident total CVD and HF events through December 31, 2016. We used Cox regression to measure associations of PPIs with total CVD and HF. RESULTS: After adjustment for potential confounding variables, participants with a cumulative exposure to PPIs of >5.1 years had a 2.02-fold higher risk of total CVD (95% confidence interval [CI], 1.50–2.72) and a 2.21-fold higher risk of HF (95% CI, 1.51–3.23) than nonusers. CONCLUSIONS: Long-term PPI use was associated with twice the risk of total CVD and HF compared to nonusers. Our findings are in concordance with other research and suggest another reason to be cautious of PPI overuse.

Advanced age, history of peptic ulcer disease, Helicobacter pylori, coadministration of nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, anticoagulation, and antiplatelets are risk factors for gastrointestinal bleeding in the elderly. Awareness of these risks and appropriate use of NSAIDs, particularly in those needing antiplatelet or anticoagulant therapy, is critical to optimal management. Careful selection of elderly patients requiring antiplatelet, anticoagulation, or chronic NSAID therapy for cotherapy with proton pump inhibitors can significantly reduce morbidity and mortality from gastrointestinal bleeding.

A range of gastroprotective drugs are available for the treatment of esophagitis and gastroduodenal mucosal injury including acid suppressants (ie, histamine-2 receptor antagonists, proton pump inhibitors), coating agents, prostaglandin analogs, and antacids. Of these, the proton pump inhibitors are the most effective drugs for the medical treatment of upper gastrointestinal injury. However, proton pump inhibitors are not effective for all causes of upper gastrointestinal injury. The choice of gastroprotective drug should be guided by the cause and location of gastrointestinal injury and the potential for adverse effects.

Dyspepsia affects a large percentage of the general population and can lead to lost work productivity and reduced quality of life. Patients with dyspepsia younger than 60 should not routinely undergo endoscopy but instead should pursue Helicobacter pylori test-and-treat approach. For patients 60 and older, endoscopy should be performed. Patients without any identifiable cause for their symptoms are diagnosed with functional dyspepsia. Guideline-based treatment includes H pylori eradication and proton pump inhibitor use. If acid suppression is not adequate, treatment with a tricyclic antidepressant followed by a prokinetic agent and psychological therapy are considered. Complementary therapies are not recommended due to limited evidence.

X-ray is an ionizing-radiation and it has been used in many processes due to the developing technology. For security purposes, X-ray instruments are been using at the entrance of the airports, shopping centers, etc. In this study, potential effects of X-ray were investigated on five different types of drugs: analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), proton pump inhibitors (lansoprazole, pantoprazole sodium sesquihydrate), anti-diabetics (metformin HCl, pioglitazone), heart failure drugs (verapamil HCl, spironolactone) and anti-hypertensives (losartan, clopidogrel hydrogen sulphate) by several different methods. In our previous study these drugs were analyzed by ESR before and after X-ray irradiation (0,24; 1,2; 58 mGy). According to the ESR results, acetylsalicylic acid tablets were affected after 58 mGy irradiation due to coated polymer (HPMC). In conclusion, these drugs were investigated before and after 0,24; 1,2 and 58 mGy X-ray irradiation by UV-spectrophotometry, dissolution test, SEM, FT-IR, DSC/TGA in this article. As a result of this study, X-ray did not cause a significant effect on drugs generally. Only a few significant differences were detected by different studies (for metformin HCl by DSC/TGA, for acetylsalicylic acid by dissolution test, and for acetaminophen and acetylsalicylic acid by UV spectrophotometry were detected significantly difference before and after irradiation).

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

New mucosal resective and ablative endoscopic procedures based on gastric cardiac remodeling to prevent reflux have appeared. We aimed to evaluate the feasibility of a new ablative technique named antireflux ablation therapy (ARAT) for control of GERD in patients without hiatal hernia.Patients with proton pump inhibitor (PPI)-refractory GERD without hiatal hernia underwent ARAT between January 2016 and October 2019. Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL), upper endoscopy, 24-hour pH monitoring, and PPI use were documented at 3, 6, 12, 24, and 36 months after ARAT.One hundred eight patients were included (61 men [56.5%]; median age, 36.5 years; range, 18-78 years). ARAT was performed on all patients. At the 36-month evaluation, 84 patients had completed the protocol. Median ARAT time was 35.5 minutes (range, 22-51 minutes), and median circumference ablation was 300° (range, 270°-320°). No major adverse events occurred, and 14 of 108 patients (12.9%) presented with stenosis that was responsive to balloon dilation (5 sessions). At the 3-month evaluation, the acid exposure time (AET), DeMeester score, and GERD-HRQL score had decreased from 18.8% to 2.8% (P = .001), 42.5 to 9.1 (P = .001), and 36.5 to 10 (P = .02), respectively, and these values were maintained up to 36 months. Success (AET 4%) was achieved in 89% and 72.2% at 3 and 36 months, respectively. Related factors at 36 months were as follows: pre-ARAT Hill type II (odds ratio [OR], 3.212; 95% confidence interval [CI], 1.431-5.951; P = .033), post-ARAT 3-month Hill type I (OR, 4.101; 95% CI, 1.812-9.121; P = .042), and AET 4% at 3 months (OR, 5.512; 95% CI, 1.451-7.621; P = .021).ARAT is a feasible, safe, and effective therapy for early and mid-term treatment of GERD in patients without a sliding hiatal hernia. However, longer follow-up evaluations and randomized comparative studies are needed to clarify its real role. (Clinical trial registration number: NCT03548298.).