Effect Of Proton Pump Inhibitors Research Articles

Awareness of Proton Pump Inhibitor Adverse Events and Treatment Pattern Change According to Physician Practice: A National Questionnaire Study in Korea.

Although adverse events of proton pump inhibitors (PPIs) have been reported, there are few studies on physicians' perceptions. We aimed to investigate physicians' awareness of PPI-related adverse events and changes in treatment patterns according to their practice. We conducted an online survey of physicians using a 15-item questionnaire. The survey queried respondents' demographic information, PPI prescription patterns, perceptions, and concerns on the reported PPI-related adverse events. Concerns regarding the adverse events of PPI were assessed by dividing them into possibilities and medical causality. Of the 450 respondents, 430 were specialists, and 232 were gastroenterologists. A total of 87.8% of the respondents were generally or well aware of the adverse effects of PPI, 29.1% considered side effects when prescribing PPI, and 14.6% explained them to patients. Specialists were more aware of the side effects of PPI than general practitioners (p = 0.005), and gastroenterologists were more aware of the side effects of PPI than non-gastroenterologists (p < 0.001). However, gastroenterologists explained less to patients (p = 0.001) and preferred to reduce the dose of PPI rather than discontinue it. The adverse events that were recognized as having the highest probability of occurrence and strongest association with PPI use were bone diseases, Clostridium difficile infection, gastrointestinal infection, pneumonia, and interactions with anti-thrombotic drugs. Physicians' awareness of PPI-related adverse events and treatment patterns differed significantly according to their positions and practice. Although a number of adverse events of PPIs were reported, physicians seem to accept their significance differently according to their specialty and practice patterns.

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.

The effect of rabeprazole on the secretory and motor function of the gastrointestinal tract

Parietal cell proton pump inhibitors (PPIs) have become firmly established in clinician practice. When discussing the features of their action, as a rule, researchers focus on their antisecretory effect. In the available literature, we found only a single report on the effect of PPIs on the motor-evacuation function of the gastrointestinal tract (GIT). We have found that the PPI rabeprazole not only has an antisecretory effect, but also normalizes the motor-evacuation function of all parts of the gastrointestinal tract. In this regard, it can be used in patients with gastric hypersecretion in functional gastrointestinal disorders (FGID) with impaired motor-evacuation function. Aim. To study the effect of the antisecretory drug rabeprazole on the state of gastrointestinal motility in patients suffering from FGID of the gastrointestinal tract and overlap syndrome (overlap syndrome) with functional dyspepsia (FD) with gastric hypersecretion and irritable bowel syndrome (IBS). Material and methods. We examined 30 patients suffering from FGID of the gastrointestinal tract and cross syndrome - FD with gastric hypersecretion and IBS. To relieve clinical symptoms of FD, the drug rabeprazole 20 mg was prescribed once a day for 14 days. Before and after the start of treatment, patients were examined with VAS and SF-36 tests, intragastric pH-metry and peripheral electrogastroenterocolography (EGECG) were performed. Results. In all 30 patients with FGID of the gastrointestinal tract with FD and overlap syndrome with IBS, gastric hypersecretion was eliminated within 3 hours after taking 20 mg of rabeprazole. 2 weeks after the start of treatment, abdominal pain and heartburn were completely eliminated in 28 (93.3%) patients. In all (100%) patients with FGID of the gastrointestinal tract with gastric hypersecretion and overlap syndrome, after two weeks of treatment, sour belching disappeared, and nausea disappeared in 23 (77%) patients. Rabeprazole therapy in the examined individuals was accompanied by a marked improvement in the quality of life in all assessed SF-36 parameters. 2 weeks after starting rabeprazole, in patients with FGID of the gastrointestinal tract and overlap syndrome of FD and IBS, the frequency of bowel movements and stool quality were normalized, and according to the results of EGECG, the relative myoelectric activity (P(i)/PS) of the gastrointestinal tract and the rhythmicity coefficient (Kritm) were normalized. Conclusion. Rabeprazole quickly neutralizes gastric secretion and helps eliminate symptoms of FD. It also has a beneficial effect on the motor-evacuation function of all parts of the gastrointestinal tract, normalizing the frequency of bowel movements, stool quality and myoelectric activity of all parts of the gastrointestinal tract according to EGECG. Rabeprazole can be used in patients with FGID with FD with gastric hypersecretion and overlap syndrome with IBS.

Inappropriate use of proton pump inhibitors in hospitalized patients with lower gastrointestinal bleeding

ABSTRACT Objectives Use of proton pump inhibitors (PPIs) is a mainstay in treating upper gastrointestinal bleeding (UGIB). However, the beneficial effects of PPIs are not anticipated to extend beyond the duodenum and may actually contribute to the risk of lower gastrointestinal bleeding (LGIB). However, in practice, PPIs are often used for inpatients with LGIB where no benefit exists. Methods A retrospective chart review was performed on inpatients during a 2-year period at an urban academic teaching hospital. Inpatients with consults to the gastroenterology (GI) service with confirmed or highly suspected LGIB were included. Outcomes regarding PPI use and the GI consulting service recommendations in these 225 patients were evaluated. Results About 37.8% of patients were started on a PPI during their inpatient course. Of those, 46% patients started on a PPI had no indication for PPI and 85% had no recommendation by the GI consultants to start a PPI. Of the 85 patients started on PPI, the GI consultants recommended stopping it in two (2.3%) patients. Lastly, 20 patients (9%) were discharged on PPI without an indication for PPI. Conclusion To our knowledge, this is the first study that looked at the inappropriate utilization of PPIs in patients admitted for LGIBs utilizing GI consultant recommendations. Given the large proportion of patients started on PPI without a clinical indication and continued at discharge and the paucity of GI recommendations to discontinue inappropriate use, we found that clinical care may be improved with formal GI recommendations regarding use of PPI.

Proton pump inhibitors, bone and phosphocalcic metabolism

Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders; however, concerns have arisen about their prolonged and inappropriate use. Although generally considered safe, recent evidence has linked PPI use with an increased risk of kidney disease, stomach cancer, pneumonia, dementia, cardiovascular events and potential bone health problems. This systematic review examines the effects of PPIs on bone health, including osteoporosis and changes in phosphocalcic and magnesium metabolism, through a comprehensive analysis of the recent literature. The relationship between PPIs, bone mineral density and fracture risk, especially in populations with comorbidities, is complex and we propose a focus based on recent data. Studies of the effect of PPI use on bone mineral density have shown mixed results and require further investigation. Observational studies have indicated an increased risk of fractures, particularly vertebral fractures, associated with PPI use. Recent meta-analyses have confirmed an association between PPI use and hip fractures with a dose-dependent effect. More recently, PPIs have been associated with serious disturbances in phosphocalcic and magnesium metabolism that require careful management and discontinuation. Proton pump inhibitor-induced hypomagnesemia (PPIH) is a well-established phenomenon. In addition, hypocalcemia secondary to severe hypomagnesemia has been described. Despite growing evidence of PPI-related risks, further research is essential to better understand the complex mechanisms, as most data are from observational studies and do not establish a causal relationship. This review emphasizes the need for judicious prescription practices, particularly in long-term use scenarios and rheumatological contexts.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Proton pump inhibitors in esophageal atresia: A systematic review and meta-analysis.

Gastroesophageal reflux disease (GERD) is frequent and prolonged in esophageal atresia (EA) pediatric patients requiring routine use of proton pump inhibitors (PPIs). However, there are still controversies on the prophylactic use of PPIs and the efficacy of PPIs on GERD and EA complications in this special condition. The aim of the study is to assess the prophylactic use of PPIs in pediatric patients with EAand its complications. We, therefore, performed a systematic review including all reports on the subject from 1980 to 2022. We conducted meta-analysis of the pooled proportion of PPI-and no PPI groups using random effect model, meta-regression, and estimate heterogeneity by heterogeneity index I2 . Thirty-eight reports on the topic met the criteria selection, representing a cumulative 6044 patients with EA. Prophylactic PPI prescription during the first year of life does not appear to prevent GERD persistence at follow-up and is not associated with a significantly reduced rate of antireflux surgical procedures (ARP). PPIs improve peptic esophagitis and induce remission of eosinophilic esophagitis at a rate of 50%. Their effect on other GERD outcomes is uncertain. Evidence suggests that PPIs do not prevent anastomotic stricture, Barrett's esophagus, or respiratory complications. PPI use in EA can improve peptic and eosinophilic esophagitis but is ineffective on the other EA complications. Side effects of PPIs in EA are almost unknown.

Deleterious association between proton pump inhibitor and protein kinase inhibitor exposure and survival for patients with lung cancer: A nationwide cohort study

IntroductionPrevious studies have identified an interaction between protein kinase inhibitors (PKIs) and proton pump inhibitors (PPIs) in patients with lung cancer. This type of interaction may reduce the efficacy of PKIs. However, the effect of PKI-PPI interaction on patient mortality remains controversial. This study set out to determine the impact of PKI-PPI interaction on overall survival for lung cancer patients. Materials and methodsThis study was conducted using data from the French National Health Care Database from January 1, 2011 to December 31, 2021. We identified patients with: (i) an age equal to or greater than 18 years; (ii) lung cancer; and (iii) at least one reimbursement for one of the following drugs: erlotinib, gefitinib, afatinib and osimertinib. Patients were followed-up between the first date of PKI reimbursement and either December 31, 2021 or if they died, the date on which death occurred. The cumulative exposure to PPI duration during PKI treatment was calculated as the ratio between the number of concomitant exposure days to PKI and PPI and the number of exposure days to PKI. A survival analysis using a Cox proportional hazards model was then performed to assess the risk of death following exposure to a PKI-PPI interaction. Results34,048 patients received at least one reimbursement for PKIs of interest in our study: 26,133 (76.8 %) were exposed to erlotinib; 3,142 (9.2 %) to gefitinib; 1,417 (4.2 %) to afatinib; and 3,356 (9.9 %) to osimertinib. Patients with concomitant exposure to PKI-PPI interaction during 20 % or more of the PKI treatment period demonstrated an increased risk of death (HR, 1.60 [95 % CI, 1.57–1.64]) compared to other patients. When this cut-off varied from 10 % to 80 %, the estimated HR ranged from 1.46 [95 % CI, 1.43–1.50] to 2.19 [95 % CI, 2.12–2.25]. Discussion/ConclusionIn our study, an elevated risk of death was observed in patients exposed to PKI-PPI interaction. Finally, we were able to identify a dose-dependent effect for this interaction. This deleterious effect of osimertinib and PPI was revealed for the first time in real life conditions.

Patients' Knowledge and Pharmacists' Practice Regarding the Long-Term Side Effects of Proton Pump Inhibitors; a Cross-sectional Study.

Proton pump inhibitors (PPI) are a commonly prescribed medication, but recent evidence suggests that their long-term use may lead to several adverse events. To address this issue, our study aims to assess patient awareness and pharmacist practices in educating patients about the potential risks associated with prolonged PPI use. Two questionnaires were developed by researchers and administered in the United Arab Emirates from June to August 2021 to gather insights from patients and pharmacists about the use of PPIs, their knowledge of potential side effects, and their experiences and attitudes toward receiving education about PPI side effects. The patients' knowledge was evaluated based on their cumulative correct answers to questions related to PPI's long-term adverse effects including increased fracture risk and hypocalcemia, vitamin B12 deficiency, hypomagnesemia, and the caution of abrupt withdrawal. All statistical analyses were conducted using SPSS 25.0 software. Overall, 348 participants with a median age of 40 years participated in the survey, among them, 91 (26.14%) used various forms of PPI with 38% of users taking PPI as over-the-counter drugs. Patients had low knowledge about PPI side effects and their proper discontinuation with a median knowledge score of 0 (Interquartile range: 0-2) and only 22.2% of patients were familiar with at least three out of five asked harms. Those with lower knowledge were more likely to be Emirati compared to other nations (p=0.004) and aged over 30 years compared to their younger counterparts (p = 0.016). Few patients have obtained the relevant information from their physicians (25%) or pharmacists (7%). Inquiring 136 pharmacists, it was shown that the most common education was concerning vitamin B12 deficiency (62.5%) followed by fracture risk(58.09%) yet less than half (48%) of pharmacists instructed patients about the potential risk of hypomagnesemia. Almost all pharmacists (99%) agreed that there is a requirement for additional education on the possible harmful consequences of PPIs. The present study has established that a considerable proportion of PPI users in the UAE lack the necessary awareness about the potential adverse effects of PPI despite their extensive use in this country. The current pharmacist practice is inefficient for inculcating the potential harms of chronic PPI use and they are required to optimize their efforts to educate patients and bridge the knowledge gaps.

The Effect of Proton-Pump Inhibitors the on Development of Arrhythmia and Hypomagnesemia After Off-Pump Coronary Artery Bypass Surgery

Background: Long-term use of proton-pump inhibitors (PPI) can result in hypomagnesemia and arrhythmia. This study aimed to compare the effect of PPI and histamine 2-receptor antagonists (H2 RA) on the incidence of hypomagnesemia and arrhythmia in patients following off-pump coronary artery bypass surgery (CABG). Method: In this randomized-controlled clinical trial 290 patients admitted to the ICU after off-pump CABG were randomly divided into two groups of H2 RA (n=145) and PPI (n=145). For patients in the H2 RA group, 50 mg intravenous ranitidine was prescribed every 8 hours after the nothing by mouth (NPO) period, followed by 40 mg famotidine tablets after starting the oral regimen (PO). The PPI group received 40 mg pantozol IV injections every 12 hours during the NPO period and 40 mg pantozol tablets once daily after becoming PO. The patients were investigated for the development of hypomagnesemia and associated arrhythmia. Results: In total 271 patients with a mean age of 59.3±10 years completed the study (female/male=32.8%). Hypomagnesemia occurred in 60.1% of the patients, 76 (56.7%) in the H2 RA group and 87 (63.5%) in the PPI group (P=0.245), whereas arrhythmia had a prevalence of 12 (9.6%) and 15 (11.1%) cases, respectively (P=0.690). The mean time of occurrence of hypomagnesemia and arrhythmia was 1.75±1.08 and 3.0±0.9 days after the operation in the H2 RA group (P=0.111) and 1.47±0.7 and 2.9±1.5 days in the PPI group (P=0.897), respectively. Conclusion: Our study revealed that the short-term use of PPIs does not result in higher rates of hypomagnesemia and associated arrhythmia in comparison to H2 RA consumption after off-pump CABG.

Testing Lansoprazole on Human Gut Microbiota using a Gastroesophageal Reflux Model In Vitro

One in five Americans experience Gastroesophageal Reflux Disease, but the disease has multiple treatments, such as Proton Pump Inhibitors (PPI). However, the effects of PPIs may induce more harmful effects on the gut microbiome, and less treatable symptoms such as inflammatory bowel disease, diabetes, obesity, and even cancer may occur. PPIs reduce acid secretion within the stomach and reduce stomach acid in the esophagus. The side effects of PPIs on the gut microbiome have yet to be researched extensively. This study suggests that Lansoprazole, a PPI, may cause significant changes in gut bacteria growth. An adapted method of in vitro digestion modeled the digestive systems of a human. Solutions replicating the environment of the mouth, stomach, and intestines were combined with a human dosage of Lansoprazole, and the pH was adjusted at different segments to model the low pH environments of the stomach and the neutral pH of the intestines. The respective solutions were then exposed to gut bacteria, E. coli, and S. epidermidis. These gut bacterias represent specific bacteria species within the intestinal tract. Data indicated that E. coli grew approximately 50% as much as the control at 20-minutes and less than 25% as much as the control at 40-minutes. S. epidermidis grew significantly less than the control, with approximately 60% as much at 20-minutes and approximately 15% as much at 40-minutes. In conclusion, studies indicate Lansoprazole treats GERD, but side effects from consuming the drug may cause gut dysbiosis, which may lead to the side effects previously mentioned.

Proton Pump Inhibitors Ameliorate Oxaliplatin-induced Peripheral Neuropathy: Retrospective Analysis of Two Real-world Clinical Databases.

Chemotherapy-induced peripheral neuropathy (CIPN) due to oxaliplatin (L-OHP) is a major clinical problem. Effective and safe preventive strategies for CIPN are urgently needed. Although proton pump inhibitors (PPIs) have various off-target effects, their clinical impact on L-OHP-induced CIPN remains unclear. In the present study, we investigated the effects of PPIs on L-OHP-induced CIPN in patients using two real-world clinical databases. We retrospectively analyzed the electronic medical records of Osaka University Hospital to examine the effect of PPIs on CIPN development in 217 patients who received XELOX (L-OHP plus capecitabine) therapy for colorectal cancer. In addition, the Japanese Adverse Drug Event Report (JADER) database was used to validate the effects of PPIs on L-OHP-induced CIPN. The incidences of CIPN (grade ≥2) and discontinuation of L-OHP were significantly lower in patients with PPIs than in those without PPIs. Multivariate analysis showed that concomitant PPIs use was an independent factor that significantly contributed to the prevention of grade ≥2 CIPN (odds ratio=0.054, p<0.001). Kaplan-Meier analysis showed that the time to onset of grade ≥2 CIPN was significantly prolonged in patients with PPIs without affecting the therapeutic efficacy of L-OHP (p=0.004). Moreover, JADER database analyses revealed that the reporting odds ratio of any PPI for L-OHP-induced CIPN was 0.485. Concomitant PPI use ameliorated L-OHP-induced CIPN in patients with colorectal cancer.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Background: Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint®) would obviate the effect of PPIs on LT4 absorption. The objective was achieved by assessing the effects of a switch from a conventional LT4 tablet form to the same dose as soft capsules in thyroidectomized patients on treatment with LT4 and PPIs. Methods: Patients with history of hypothyroidism due to total thyroidectomy on stable treatment with LT4 tablets, and with gastrointestinal disease treated with PPIs, were switched to a 12-week treatment with Tirosint at the same dose of the LT4 tablets, while maintaining treatment with PPIs. Serum thyrotropin (TSH) levels were the primary endpoint of the study. Secondary efficacy endpoints were: serum levels of free thyroxine (fT4), total thyroxine (TT4), free triiodothyronine (fT3), total triiodothyronine (TT3), creatine-phosphokinase (CPK), sex-hormone binding globulin, ferritin, angiotensin converting enzyme, and a lipid panel. Results: Forty-seven patients (36 females and 11 males, mean age 55.4 years) were enrolled and 45 of them completed the study (2 patients withdrew consent). During treatment with Tirosint, mean TSH levels demonstrated a statistically significant decrease (mean changes from baseline: -0.32 mIU/L at week 6 and -0.68 mIU/L at week 12) and concomitant increases in thyroid hormone (TH) levels from baseline to week 12, which were statistically significant for fT3 and TT3 (mean changes from baseline: 0.26 pmol/L and 0.10 nmol/L, respectively). Significant decreases of serum low-density lipoprotein, total cholesterol, and CPK levels were observed at week 12. No signs/symptoms arose during the study that could be specifically correlated to either hypo- or hyperthyroidism. Conclusions: In thyroidectomized patients taking PPIs and replacement LT4, a switch from conventional LT4 tablets to LT4 soft capsules at the same dose was associated with a significant decrease in TSH and increase in TH, indicating that LT4 absorption may be less affected by PPIs when given in the form of soft capsules. Clinical Trial Registration: NCT03094416.

Trends of Proton Pump Inhibitor Uses among Pharmaceutical Promotional Workers

Background: Proton pump inhibitors (PPIs) are one of the most frequently used drugs in the world for the management of gastric- acid related diseases. The aim of this study was to assess the trend of PPIs uses among the pharmaceutical promotional workers in Bangladesh. Methods: A questionnaire-based survey was conducted on pharmaceutical promotional workers from different regions in Bangladesh. The study data were collected which includes demographics, PPIs uses in terms of duration, dose, generics, symptoms for which they took PPIs and effects of PPIs on symptoms. Drugs or diseases that influenced the intake of PPIs were also recorded. Results: Among six hundred surveys issued for the study, 581 valid questionnaires were returned. Among the respondents 520 individuals (89.5%) were male and 61 individuals (10.5%) were female. Common indications for taking PPIs were abdominal discomfort (51.5%), vomiting (34.1%) and abdominal pain (24.6%). Two hundred seventy (48.56%) respondents had satisfactory relief of symptoms, 125 (22.48%) had symptoms reappeared after stopping PPIs and 77 (13.85%) had complete cure of symptoms. Most of the participants (42.60%) were on PPIs therapy for up to one year. Most of the participants (64.49%) took PPI once daily. Most of the participants (60.75%) started PPI by themselves. Esomeprazole (40.1%) and rabeprazole (30.1%) were the most frequently used PPIs. Conclusion: PPI is found to be a frequently used medication among pharmaceutical promotional workers. Further well-designed study with adequate work up may be designed to see misuse and overuse of PPI among workers of pharmaceutical sector as well as general population. Sir Salimullah Med Coll J 2023; 31: 41-46

Is proton-pump inhibitor effective in preventing postoperative bleeding after esophageal endoscopic submucosal dissection?

Although proton-pump inhibitor (PPI) administration was reported to be effective in preventing delayed bleeding after gastric endoscopic submucosal dissection (ESD), its effectiveness in esophageal ESD is still unknown. We assessed whether PPI or vonoprazan administration was effective in preventing posterior hemorrhage after esophageal ESD. This retrospective cohort study used the Japanese Diagnosis Procedure Combination (DPC) database, and patients who underwent esophageal ESD between January 2012 and December 2020 were enrolled. The participants were divided into two groups: patients who were prescribed PPI or vonoprazan (PPI or vonoprazan group) and those who were not prescribed PPI (no acid suppression). Propensity score matching analysis was performed, and the delayed bleeding rate was compared between the groups. We analyzed 54,345 patients, of whom 8237 (15.16%) were in the no acid suppression group and 46,108 (84.84%) in the PPI or vonoprazan group (PPI: 34,380 and vonoprazan: 11,728). Delayed bleeding occurred in 1126 patients (2.07%). A total of 8237 pairs were created after matching. Delayed bleeding was not significantly different between the no acid suppression group and PPI or vonoprazan group, respectively (odds ratio: 1.20, 95% confidential interval: 0.93-1.54, P = 0.227). A sub-analysis according to the dose of PPI or vonoprazan, tumor location, and prescription of antithrombotic or anticoagulant medications was performed, but no significant effects of PPI or vonoprazan administration were found. PPI or vonoprazan did not prevent delayed bleeding; thus, the prescription of PPI and vonoprazan after esophageal ESD may not be recommended for the prevention of delayed bleeding.

Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome.

Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI-], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. The median (IQR) age of our cohort was 14 years (12-16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI-, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI- and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.

Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population?

Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI's effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.

Model based assessment of food and acid reducing agent effects on oral absorption of mezigdomide (CC-92480), a novel cereblon E3 ligase modulator.

Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD) agent with enhanced autonomous cell-killing activity in multiple myeloma (MM) cells, and promising immunomodulatory and antitumor activity in patients with MM. We developed a population pharmacokinetics (PKs) model for mezigdomide in healthy subjects (HSs), and quantified effects of high-fat meal and proton pump inhibitor (PPI) on human disposition parameters. Plasma concentrations from 64 HS in two phase I clinical studies (NCT03803644 and NCT04211545) were used to develop a population PK model. The HSs received single oral doses of 0.4-3.2 mg mezigdomide with full PK profiles collected. A two-compartment linear PK model with first-order absorption and lag time best described mezigdomide PK profiles in HSs. The population PK parameters of absorption rate constant, lag time, central volume of distribution, clearance, peripheral volume of distribution, and intercompartmental clearance were estimated to be 1.18 h-1 (interoccasion variability [IOV]: 65%), 0.423 h (IOV: 31%), 440 L (interindividual variability [IIV]: 63%), 35.1 L/h (IIV: 40%), 243 L (IIV: 26%), and 36.8 L/h (IIV: 26%), respectively. High-fat meal increased oral bioavailability by ~30% and PPI co-administration decreased oral bioavailability by ~64%. Mezigdomide demonstrated a linear dose-exposure relationship in HSs. The PK model suggests a modest effect of high-fat meal, and a substantial effect of PPIs on mezigdomide oral bioavailability. This population PK model enables data integration across studies to identify important covariate effects and is being used to guide dose selection in clinical study designs for mezigdomide in patients with MM.

Cost-effectiveness of alginic acid in combination with proton pump inhibitor for the treatment of gastroesophageal reflux disease in systemic sclerosis patients.

Systemic sclerosis (SSc) patients often become refractory to proton pump inhibitors (PPI)-a standard treatment for gastroesophageal reflux disease (GERD)-and intolerant to PPI in combination with domperidone. PPI with alginic acid is an alternative treatment option, but alginic acid is costly. We compared the costs and effectiveness of alginic acid plus PPI versus standard treatments (PPI with/without antacids as needed and lifestyle modifications) for GERD in SSc patients unsuitable for, or intolerant to, domperidone. An economic evaluation using the Markov model was conducted among SSc patients aged between 40 and 65 years with GERD, having a partial or non-response to 4 weeks of standard-dose omeprazole (40 mg/day) and being unsuitable for or intolerant to domperidone. Using a societal perspective, we computed the incremental cost-effectiveness ratios (ICERs) in terms of Thai baht (THB) per quality-adjusted life-year (QALY) between a combination of alginic acid plus PPI and standard treatment for GERD. The lifetime time horizon was used. The ICER for alginic acid plus PPI versus standard treatments was 377 101 THB/QALY. According to the one-way sensitivity analysis, the cost of alginic acid was the most impactful parameter. If the market prices of alginic acid plus PPI were reduced by 61%, this treatment option would become cost-effective at the willingness-to-pay threshold of 160 000 THB/QALY (34.68 THB/USD data on 25 May 2023). Furthermore, if alginic acid were included in the public health insurance program, the national budget would be increased by 66 313 THB per patient, resulting in an overall budget increase of 5 106 101 to 8 885 942 THB compared with the standard treatment. Alginic acid plus PPI does not represent good value for money compared with the standard treatment among such SSc patients in Thailand unless its price is reduced significantly.

Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial

BackgroundCritically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection.MethodsThe ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.DiscussionProphylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.Trial registrationREVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].