Gastric Acid Suppression Research Articles

Pharmacokinetics and Pharmacodynamics of YYD601, a Dual Delayed-Release Formulation of Esomeprazole, Following Single and Multiple Doses in Healthy Adult Volunteers Under Fasting and Fed Conditions.

BackgroundYYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression.PurposeThe pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule.MethodsIn the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days. Blood samples were collected for PK analysis, before and up to 24 h after dosing. For PD characteristics of YYD601, the percentages of time with intragastric pH > 4 over a 24-h period and during night-time following multiple oral administrations were evaluated.ResultsA total of 27 subjects completed the study. YYD601 showed a dual-peak PK profile under fasting condition, with delayed Tmax, compared with conventional formulation. There were no significant differences in the AUC values adjusted for dose between the three YYD601 dosage groups and the conventional esomeprazole 40 mg. The esomeprazole AUC following single and multiple administration decreased with food intake by approximately 33%. YYD601 showed a linear pharmacokinetic profile in the dose range studied. There was no statistically significant difference in increase in mean percentage of time with intragastric pH > 4 for 24-hour and during night-time between the three different doses of YYD601 and the conventional formulation. The treatments were well-tolerated during the study and no serious adverse events were observed.ConclusionYYD601 30 mg has a comparable effect on gastric acid inhibition as conventional esomeprazole 40 mg following once daily oral administration. Single and multiple oral dosing of YYD601 up to 60 mg were safe and well-tolerated throughout the study.Clinical Trial Registryhttp://clinicaltrials.gov, NCT03558477 (date of registration: June 15, 2018; study period: between October 2017 and February 2018).

Gastroprotective Effect of Microencapsulated Myrtus communis Essential Oil against Ethanol/HCl-Induced Acute Gastric Lesions.

Myrtus communis L. essential oil (EO), mainly composed of myrtenyl acetate (30.6%), linalool (14.9%), α-pinene (11.10%) and 1,8-cineole or eucalyptol (9.9%), was microencapsulated with maltodextrin by emulsification and spray-drying, reaching a yield and efficiency of 43.7 and 48.7%, respectively. The microencapsulated myrtle EO (MMEO) was then evaluated regarding its gastroprotective activity in a model of ethanol/HCl-induced acute gastric ulcer in Wistar rats. Pretreatment with MMEO induced a remarkable inhibition of gastric lesions and acidity, correlated to high healing and protection percentages. Moreover, it exerted a potent anti-inflammatory effect on the gastric mucosa, counteracting EtOH-induced gastric lipoperoxidation and preventing the depletion of the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Taken together, the gastroprotective action of encapsulated MMEO may be multi-factorial, and ascribable, at least in parts, to its anti-inflammatory and antioxidant properties.

Night-time gastric acid suppression by tegoprazan compared to vonoprazan or esomeprazole.

AimsNocturnal acid breakthrough has been considered an unmet need of proton‐pump inhibitors. Tegoprazan, a novel potassium‐competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night‐time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid‐suppressive effects.MethodsA randomized, open‐label, 3‐period, 6‐sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing.ResultsSixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night‐time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night‐time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes.ConclusionTegoprazan produced more rapid, potent and well sustained night‐time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.

The potential for deprescribing in a palliative oncology patient population: a cross-sectional study

ObjectivesThe use of preventive medication in palliative oncology patients may be inappropriate due to limited life expectancy. Deprescribing tools are available but time-consuming and not always tailored to this specific...

A Narrative Review on Efficacy and Safety of Proton Pump Inhibitors in Children.

Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use in pediatrics is approved for children older than 1 year, for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD), healing of erosive esophagitis, treatment of peptic ulcer disease, and eradication of Helicobacter pylori. PPIs are also considered the standard of care for pediatric eosinophilic esophagitis. Despite the strict range of indications, the use of this class of molecules has increased in all pediatric age ranges. The long-term gastric acid suppression in children has been linked to increased risks of gastrointestinal and lower respiratory tract infections, bone fractures, and allergy. This study aims to provide a comprehensive overview of the mechanism of actions, use (and misuse) in infants and children, and safety of PPIs.

The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial.

Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI. In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n=15) or placebo (n=15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2-6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6. Short term PPI treatment increased the microbial abundance of Streptococcaceae (p=0.004), Leuconostacaceae (p=0.001), and Pasteurellaceae (p=0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p=0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p<0.05) along with other species present in the multi-strain probiotic. Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. CLINICAL TRIALS. NCT03327051.

Gastric Acid Suppression and Penicillin Allergy Label

Penicillin allergy status has an overall negative impact on patient health. Active de-labeling has been shown to improve healthcare outcomes. We assessed the risk of developing penicillin allergy among patients using proton pump inhibitors (PPI)s or histamine-2 receptor antagonists (HR2A)s as examples of potentially modifiable risk factors.

Concomitant Gastric Acid Suppressants on the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Meta-Analysis.

Background The influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. We performed a meta-analysis to evaluate the effect of additional AS in patients with NSCLC taking TKIs. Methods Relevant observational studies were identified by a search of Medline, Embase, and Web of Science databases. Only studies with multivariate analyses were included. A random-effect model was used to combine the results. Results Thirteen retrospective studies with 12259 patients were included. Pooled results showed that concomitant use of AS was associated with worse progression-free survival (PFS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.31 to 1.89, P < 0.001; I2 = 65%) and overall survival (OS, adjusted HR: 1.38, 95% CI: 1.19 to 1.61, P < 0.001; I2 = 70%) in NSCLC patients taking TKIs. Sensitivity analysis limited to studies including NSCLC with EGFR mutation showed consistent results (HR for PFS: 1.53, P=0.003; HR for OS: 1.43, P=0.001). Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, P for subgroup analysis all >0.05). Conclusions Concomitant use of AS in patients with NSCLC taking TKIs may be associated with poor survival outcomes.

Efficacy of acotiamide on postprandial distress syndrome and epigastric pain syndrome depending on the estimated gastric acid secretion level.

Background/AimsGastric acid secretion is suspected to be a pivotal contributor to the pathogenesis of functional dyspepsia. The present study investigates the potential association of the gastric acid secretion estimated by measuring serum pepsinogen with therapeutic responsiveness to the prokinetic drug acotiamide.MethodsDyspeptic patients consulting participating clinics from October 2017 to March 2019 were prospectively enrolled in the study. The dyspeptic symptoms were classified into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Gastric acid secretion levels were estimated by the Helicobacter pylori infection status and serum pepsinogen using established criteria and classified into hypo-, normo-, and hyper-secretion. Each patient was then administered 100 mg acotiamide thrice daily for 4 weeks, and the response rate to the treatment was evaluated using the overall treatment efficacy scale.ResultsOf the 86 enrolled patients, 56 (65.1%) and 26 (30.2%) were classified into PDS and EPS, respectively. The estimated gastric acid secretion was not significantly different between PDS and EPS. The response rates were 66.0% for PDS and 73.1% for EPS, showing no significant difference. While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among subjects with PDF, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among subjects with EPS (42.0% vs 83.0%, P = 0.046).ConclusionAlthough acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hyper-secretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable.

Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants.

Background: Gastric acid suppressants have a major impact on gut microbiome which in turn, may increase the risk of cholelithiasis, but epidemiological evidence remains unclear. We undertook this research to evaluate the association between regular use of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) with risk of cholelithiasis. Methods: Prospective cohort study included 477,293 UK residents aged 37–73 years from the UK Biobank. We included the participants reported PPI or H2RA use, and were free of cholelithiasis or cancer. We evaluated hazard ratios (HRs) of regular use of PPIs or H2RAs and risk of cholelithiasis adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications, and clinical indications. Results: We identified 12,870 cases of cholelithiasis over a median follow-up of 8.1 years. Regular use of PPIs (HR 1.22 95% CI 1.16–1.29) or H2RAs (HR 1.16, 95% CI 1.05–1.28) was associated with an increased risk of cholelithiasis after confounding adjustment. There were no major differences among individual PPIs/H2RAs. The absolute risk of PPI-associated cholelithiasis was increased with the baseline predicted risk evaluated by known environmental and genetic risk factors (Risk differences in the lowest vs. the highest quartile: 1.37 vs. 4.29 per 1,000 person-years). Conclusion: Regular use of PPIs and H2RAs was associated with increased risk of cholelithiasis. Future prospective studies are required to confirm whether the observed associations are casual.

PPI ADMINISTRATION CAUSES COLONIC TIGHT JUNCTION BARRIER DYSFUNCTION VIA INCREASE INENETROCOCCUS FECALIS

Abstract BACKGROUND Proton pump inhibitors (PPIs) are highly effective antagonists of gastric acid secretion and are widely used to treat a number of gastroesophageal disorders, including peptic ulcer disease, GERD, Barrett’s esophagus. PPI-induced elevation in intra-gastric pH and subsequent alterations of gastrointestinal physiology are known to cause undesired effects on the entire GI tract. Gastric acid suppression can change the composition of the intestinal microbiota causing intestinal dysbiosis and increased risk for intestinal inflammation. The intrinsic intestinal barrier is composed of a single layer of columnar epithelial cells and inter-epithelial tight junctions (TJ) residing at the apical-most region of the intercellular space. Defective intestinal TJ barrier is an important pathogenic factor for intestinal inflammation. The role of PPI on Intestinal TJ barrier is not known. AIM The aim of the present study was to study the effect of PPI on intestinal dysbiosis and mouse colonic TJ permeability. METHODS 8 to 12-week-old male C57BL/6N mice were divided into two groups (Controls and PPI treatments (Omeprazole 20mg/kg B.W.) and were fed a nutritionally adequate feed for 30 days. Fecal samples were collected from both treated and untreated mice after 30 days. Fecal DNA was isolated using the Qiagen kit according to the manufactures Instructions. 16s amplicon DNA was sequenced by Genewiz (South Plainfield, NJ). Degenerate primers that amplify the V3-V4 region of bacterial rDNA genes were used (F341-806R pair).The amplicon pool sequenced on Illumina MiSeq generated paired-end 301 bp reads was multiplexed using Illumina’s fastq. At the end of the experiments, the colonic permeability was measured on Ussing chambers. Western blot (WB) and Immunofluorescence (IF) was used to study myosin light chain kinase (MLCK, a key regulator of TJ barrier) protein expression in mice colon. RESULTS The microbiome changes identified by 16S rRNA sequencing showed a significant increased proportion of Firmucutis in the fecal samples of PPI treated mice compared with untreated mice. Also, PPI group showed prominent increase in enterococcus spp which was identified as Enterococcus fecalis (EF). In Ussing chambers studies, PPI administration caused a decrease in transepithelial resistance (TER), and increase in urea and inulin flux when compared to untreated colonic tissues. Immunofluorescence and Western blot analysis showed that PPI administration also caused an increase in MLCK and phospho- MLC protein expression in mice colonic tissues. Also, PPI treatment caused increased focal sloughing of colonic surface epithelium with focal to diffuse lymphocytic infiltration in the colonic lamina propria in mice colon. CONCLUSION Our results suggest that the PPI causes overgrowth of a pathobiont EF associated increase in mouse colonic TJ barrier permeability.

PPI ADMINISTRATION CAUSES COLONIC TIGHT JUNCTION BARRIER DYSFUNCTION VIA INCREASE IN ENETROCOCCUS FECALIS

Proton pump inhibitors (PPIs) are highly effective antagonists of gastric acid secretion and are widely used to treat a number of gastroesophageal disorders, including peptic ulcer disease, GERD, Barrett’s esophagus. PPI-induced elevation in intra-gastric pH and subsequent alterations of gastrointestinal physiology are known to cause undesired effects on the entire GI tract. Gastric acid suppression can change the composition of the intestinal microbiota causing intestinal dysbiosis and increased risk for intestinal inflammation.

Gastric acid suppressants and cognitive decline in people with or without cognitive impairment.

IntroductionStudies suggest associations between proton pump inhibitors (PPIs) and dementia risk; however, many neither considered histamine‐2 receptor antagonists (H2RAs) nor baseline cognitive status.MethodsParticipants (National Alzheimer's Coordinating Center Database; 2005–2021) using a PPI or H2RA were compared. Covariate‐adjusted Cox regression was used to estimate hazard ratios (HR) for progression from normal cognition to mild cognitive impairment (MCI), and from MCI to dementia over 5 years. In a propensity‐score–matched subsample of mild–moderate Alzheimer's disease (AD), mixed‐effects negative binomial regression was used to estimate decline in delayed recall memory.ResultsCompared to PPI, H2RA use was associated with earlier progression from MCI to dementia (HR = 1.40 [1.09–1.81]; n = 1701), and with faster memory decline in AD over time (rate ratio = 0.76 [0.64–0.92]; n = 628), but not with progression from normal cognition to MCI (HR = 0.94 [0.71–1.24]; n = 2784).DiscussionCompared to PPIs, H2RAs were associated with cognitive decline, specifically among people with pre‐existing cognitive impairment.

Association between the Co-administration of Histamine H2 Receptor Antagonists and the Effectiveness of Capecitabine in Patients with Colorectal Cancer: Propensity Score Analysis.

Background: The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H2 receptor antagonists (H2RAs) in early-stage colorectal cancer (CRC) patients using real-world data.Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed.Results: In total, 552 patients were included in this study, of which 30 were co-administered H2RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H2RA and non-H2RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H2RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 95% CI: 0.86-4.70 and HR, 1.81; 95% CI: 0.77-4.22, respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen.Conclusions: The study findings suggest that the co-administration of H2RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed.

745. Evaluation of a Pharmacist-driven Risk Factor Tool for the Prevention of Hospital-onset Clostridium difficile Infection in a Community Hospital

Abstract Background Clostridium difficile infection (CDI) is the most frequently reported nosocomial infection and is the major cause of healthcare and antibiotic associated diarrhea. Guideline recommended preventative strategies include antibiotic stewardship, hand hygiene, barrier precautions, and disinfection of environmental spaces to reduce the risk of hospital onset CDI (HO-CDI); however, there is no standardized scoring method to tactically detect high-risk patients in order to prevent HO-CDI. The objective of this study was to implement a risk stratification procedure for a pharmacist to prospectively identify high-risk patients and make early interventions to prevent the incidence of HO-CDI. Methods In this single center, ambidirectional cohort study, patients who acquired HO-CDI from January 2019 to June 2020 were identified and evaluated to determine which modifiable risk factors were most prominent. A pharmacist prospectively screened patients who were admitted from October 2020 to February 2021 using a web-based screening tool to detect high-risk patients based on the previously identified risk factors. An interdisciplinary approach was used to make early interventions for high-risk patients such as discontinuation or de-escalation of antibiotics, discontinuation of gastric acid suppression, and early CDI testing before 72 hours of admission. The primary outcome was incidence of HO-CDI per 10,000 patient days and secondary outcomes were length of hospital stay and duration of non-CDI antibiotic therapy. Appropriate statistical tests were used to measure significance. Results The primary outcome of HO-CDI cases per 10,000 patient days occurred at a median rate of 3.95 (IQR 3.38 – 6.30) in the retrospective cohort versus 2.15 (IQR 1.68 – 3.04) in the prospective cohort [p &amp;lt; 0.0125]. There were no significant differences in length of non-CDI antibiotic therapy or length of hospital stay. Baseline Characteristics Primary Outcome Secondary Outcomes Conclusion In patients at high-risk of developing HO-CDI, pharmacist intervention resulted in a reduced rate of HO-CDI cases per 10,000 patient days. Disclosures All Authors: No reported disclosures

98. Outcomes of Clinical Decision Support for Outpatient Management of Clostridioides difficile Infection

BackgroundOur antimicrobial stewardship program identified high rates of suboptimal metronidazole prescribing for Clostridioides difficile infection (CDI) within ambulatory clinics. An outpatient best practice advisory (BPA) was implemented to notify prescribers “Vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI. MethodsWe conducted an IRB approved quasi-experiment before and after implementation of the BPA on June 3, 2020. Inclusion: Adult patients diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between 11/1/2019 and 11/30/2020. Exclusion: fulminant CDI. Primary endpoint: guideline-concordant CDI therapy, defined as oral vancomycin or fidaxomicin. Oral metronidazole was considered guideline-concordant if prescribed due to cost barrier. Secondary endpoints: reasons for alternative CDI therapy, patient outcomes, prescriber response to the BPA. Descriptive and bivariate analyses were completed.Results189 patients were included in the study, 92 before and 97 after the BPA. Median age: 59 years, 31% male, 75% Caucasian, 30% with CDI-related comorbidities, 35% with healthcare exposure, 65% with antibiotic exposure, 44% with gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 out of 26 times and optimized the therapy of 16 patients in six months. Guideline-concordant therapy increased after implementation of the BPA (72% vs. 91%, p=0.001) (Figure 1). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA (Figure 2). Reasons for alternative CDI therapy included medication cost, lack of insurance coverage, and non-CDI infection. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs. 7%, p< 0.001). Figure 1. Guideline-concordant CDI therapy Figure 2. Specific CDI therapy ConclusionClinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.Disclosures Susan L. Davis, PharmD, Nothing to disclose Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

Utilization trend of gastric acid-suppressing agents in relation to analgesics.

Controversies exist about excessive use of gastric acid-suppressing agents or lack of adequate indications, especially when co-prescribed with analgesics for gastroprotection. We aimed to analyze the nationwide trend of gastric acid-suppressing agents and analgesics. We obtained nationwide consumption data of analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, others) and gastric acid-suppressing agents (proton pump inhibitors [PPI] and histamine-2 receptor antagonists [H2RAs]) between years of 2014-2018 from IQVIA Turkey. Drug utilization was measured by defined daily dose (DDD)/1000 inhabitants/day (DID) unit. Drug sales data were further used to test the correlation of PPIs and H2RAs to analgesics. During the study period, analgesic utilization increased from 65.7 to 67.4 DID. NSAIDs constituted 82.7%-84.9% of all analgesic utilization. The consumption of NSAIDs increased by 3.1%, and the most commonly consumed analgesic was diclofenac (18.5 ± 1.5 DID), constituting 25.4%-29.0% of all analgesics. PPI utilization was found to regularly raise from 52.1 DID in 2014 to 72.0 DID in 2018 with an overall increment of 38.2%. Use of H2RAs was found to increase from 11.4 DID in 2014 to 14.0 DID in 2018. The physician visit-adjusted utilization of both antirheumatic NSAIDs and non-antirheumatic analgesics showed significantly moderate-strong positive correlations with PPIs (r: 0.63, 0.48-0.76 and r: 0.63, 0.47-0.75, respectively) and H2RAs (r: 0.61, 0.44-0.73 and r: 0.57, 0.41-0.71, respectively). The utilization trend exhibited a dramatic increase of the gastric acid-suppressing agents -more pronounced for PPIs, with a modest increase in analgesics. Excessive utilization of PPIs does not seem to imply a tendency toward only NSAID-related gastroprotection.

Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis.

IntroductionFamotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.MethodsFive databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.ResultsFour studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death—HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.ConclusionBased on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

How We Approach Difficult to Eradicate Helicobacter pylori

How We Approach Difficult to Eradicate Helicobacter pylori

Risk of Enteric Infection in Patients with Gastric Acid Supressive Drugs: A Population-Based Case-Control Study.

: BackgroundLong-term use of gastric-acid-suppressive drugs is known to be associated with several adverse effects. However, the association between enteric infection and acid suppression therapy is still uncertain. This study aimed to evaluate the association between gastric acid suppression and the risk of enteric infection. Materials and Methods: We conducted a population-based case-control study using the data from Chang Gung Research Database (CGRD) in Taiwan. Between January 2008 and December 2017, a total of 154,590 adult inpatients (age > 18) were identified. A pool of potential eligible controls according to four propensity scores matching by sex, age, and index year were extracted (n = 89,925). Subjects with missing data or who received less than 7 days of proton pump inhibitors (PPIs) and/or H2-receptor antagonists (H2RAs) were excluded. Finally, 17,186 cases and 69,708 corresponding controls were selected for analysis. The use of PPIs and H2RAs, the result of microbiological samples, and co-morbidity conditions have been analyzed. Confounders were controlled by conditional logistic regression. Results: 32.84% of patients in the case group used PPIs, compared with 7.48% in the control group. Of patients in the case group, 9.9% used H2RAs, compared with 6.9% in the control group. Of patients in the case group, 8.3% used a combination of PPIs and H2RAs, compared with 2.7% in the control group. The most common etiological pathogens were Enterococcus (44.8%), Clostridioides difficile (34.5%), and Salmonella spp. (10.2%). The adjusted odds ratio (OR) for PPI use with enteric infection was 5.526 (95% confidence interval [CI], 5.274–5.791). For H2RAs, the adjusted odds ratio was 1.339 (95% confidence interval [CI], 1.261–1.424). Compared to the control group, persons with enteric infection had more frequent acid-suppressive agent usage. Conclusions: This study demonstrates that gastric-acid-suppressive drug use is associated with an increased risk of enteric infection after adjusting for potential biases and confounders.