Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.

Prevalence and factors associated with inappropriate continuation of stress ulcer prophylaxis at discharge.

Stress ulcer prophylaxis is started in the critical care unit to decrease the risk of upper gastrointestinal ulcers in critically ill persons and to decrease mortality caused by stress ulcer complications. Unfortunately, the drugs are often continued after recovery through discharge, paving the way for unnecessary polypharmacy. STUDY DESIGN: We conducted a retrospective cross-sectional study including patients admitted to the adult critical care unit and started on the stress ulcer prophylaxis with a proton pump inhibitor (PPI) or histamine receptor 2 blocker (H2 blocker) with an aim to determine the prevalence of inappropriate continuation at discharge and associated factors. RESULT: 3200 people were initiated on stress ulcer prophylaxis, and the medication was continued in 1666 patients upon discharge. Indication for long-term use was not found in 744 of 1666, with a 44% prevalence of inappropriate continuation. A statistically significant association was found with the following risk factors: discharge disposition (home vs other medical facilities, p=0.002), overall length of stay (more than 10 days vs less than or equal to 10 days, p<0.0001), mechanical ventilator use (p<0.001), number of days on a mechanical ventilator (more than 2 days vs less than or equal to 2 days, p<0.001) and class of stress ulcer prophylaxis drug used (H2 blocker vs PPI, p<0.001). CONCLUSION: The prevalence of inappropriate continuation was found to be higher than prior studies. Given the risk of unnecessary medication intake and the associated healthcare cost, a web-based quality improvement initiative is being considered.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.

H2 antihistamines: May be useful for combination therapies in cancer?

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.

Effect of histamine-receptor antagonism on the circulating inflammatory cell and cytokine response to exercise: A pilot study.

The purpose of this study was to gain insight into histamine's role in the exercise inflammatory response and recovery from exercise. To explore this, young healthy participants (n = 12) performed 300 eccentric leg extensions under control (Placebo) versus histamine H1 and H2 receptor antagonism (Blockade) in a randomized cross-over study. Circulating leukocytes and cytokines were measured for 72 h after exercise. Circulating leukocytes were elevated at 6 and 12 h after exercise (p < 0.05) with the peak response being a 44.1 ± 11.7% increase with Blockade versus 13.7 ± 6.6% with Placebo (both p < 0.05 vs. baseline, but also p < 0.05 between Blockade and Placebo). Of the cytokines that were measured, only MCP-1 was elevated following exercise. The response at 6 h post-exercise was a 104.0 ± 72.5% increase with Blockade versus 93.1 ± 41.9% with Placebo (both p < 0.05 vs. baseline, p = 0.82 between Blockade and Placebo). The main findings of the present investigation were that taking combined histamine H1 and H2 receptor antagonists augmented the magnitude but not the duration of the increase of circulating immune cells following exercise. This suggests histamine is not only exerting a local influence within the skeletal muscle but that it may influence the systemic inflammatory patterns.

Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies.

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.

Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand.

Background: Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). Methods: We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. Results: A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). Conclusion: PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment.

PURPOSE: To describe the prescribing trends of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2 RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019. METHODS: We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H2 RAs. We also assessed rate ratios of PPIs and H2 RAs prescription rates to examine changes in prescribing over time. RESULTS: Our cohort included 177 477 children with a first ever diagnosis of gastroesophageal reflux during the study period. The median age was 13 years (IQR: 1, 17) among children prescribed PPIs and 0.2 years (IQR: 0.1, 0.6) among those prescribed H2 RAs. The total prescription rate of all GERD drugs was 1468 prescriptions per 1000 person-years (PYs) (95% CI 1463-1472). Overall, PPIs had a higher prescription rate (815 per 1000 PYs, 95% CI 812-818) than H2 RAs (653 per 1000 PYs 95% CI 650-655). Sex- and age-adjusted rate ratios of 2019 versus 1998 demonstrated a 10% increase and a 76% decrease in the prescription rates of PPIs and H2 RAs, respectively. CONCLUSIONS: Prescription rates for PPIs increased, especially during the first half of the study period, while prescription rates for H2 RA decreased over time.

Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication.

BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

The combined use of anti-peptic agents is associated with an increased risk of osteoporotic fracture: a nationwide case-control study.

BACKGROUND/AIMS: Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. METHODS: A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. RESULTS: The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of "PPI and H2RA" (HR, 1.58; p = 0.010) as well as "PPI, H2RA, and MPA" (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, "MPA and PPI or H2RA" was not associated with an increased risk of osteoporotic fracture. CONCLUSION: This study found that the combined use of "PPI and H2RA" was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

[Top 5 Research Studies of the month for Italian Primary Care Physicians: January 2024.] / La Top 5 di gennaio 2024. Gli studi clinici che vale la pena conoscere se lavori nelle cure primarie in Italia.

This monthly article provides a collection of summaries of the most relevant studies identified as POEMs (patient-oriented evidence that matters) for Italian primary care physicians. 1) A recent high-quality systematic review (SR) of 76 SRs found that, compared to all other lipid-lowering medications, for overall, primary, and secondary prevention the best balance of benefits, harms, and costs is provided by statins. 2) To our surprise, a network meta-analysis of 12 randomized controlled trials (RCTs) concluded that acetaminophen and ketorolac were more effective than morphine in alleviating pain from renal colic and were less likely than morphine to cause adverse effects and the need for rescue analgesia. 3) Proton pump inbibitors (PPI) use in children is associated with an increased risk of developing serious infections as compared with the use other acid-suppressing therapy. It seems prudent to use antacids and histamine 2 receptor antagonists first and reserve PPIs for nonresponders. 4) Overdiagnosis - the identification of, in this case, breast cancer, that would not have caused symptoms in a person's lifetime - seems to increase with age. In a study including more than 50.000 women aged above 70 who underwent mammography screening, the overdiagnosis rate was 31%, 47% and 51% for women aged 70 to 74 years, 75 to 84 years and over age 85, respectively. 5) An RCT among community-dwelling adults conducted in the US found that using a regular cuff on larger-than-average arms can falsely raise blood pressure readings by almost 5 mmHg, and a regular cuff on an especially thin arm can lower readings by 3.6 mmHg.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study.

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

Histamine H2-receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II-hypertensive mice.

Aldosterone through the mineralocorticoid receptor MR has detrimental effects on cardiovascular disease. It reduces the bioavailability of nitric oxide and impairs endothelium-dependent vasodilatation. In resistance arteries, aldosterone impairs the sensitivity of vascular smooth muscle cells to nitric oxide by promoting the local secretion of histamine which activates H2 receptors. The present experiments tested in vivo and ex vivo the hypothesis that systemic H2-receptor antagonism reduces arterial blood pressure and improves vasodilatation in angiotensin II-induced chronic hypertension. Hypertension was induced by intravenous infusion of angiotensin II (60 ng kg-1 min-1) in conscious, unrestrained mice infused concomitantly with the H2-receptor antagonist ranitidine (27.8 µg kg-1 min-1) or vehicle for 24 days. Heart rate and arterial blood pressure were recorded by indwelling arterial catheter. Resistance (mesenteric) and conductance (aortae) arteries were harvested for perfusion myography and isometric tension recordings by wire myography, respectively. Plasma was analyzed for aldosterone concentration. ANGII infusion resulted in elevated arterial blood pressure and while in vivo treatment with ranitidine reduced plasma aldosterone concentration, it did not reduce blood pressure. Ranitidine improved ex vivo endothelial function (acetylcholine 10-9 to 10-6 mol L-1) in mesenteric resistance arteries. This was abolished by ex vivo treatment with aldosterone (10-9 mol L-1, 1 h). In aortic segments, in vivo ranitidine treatment impaired relaxation. Activation of histamine H2 receptors promotes aldosterone secretion, does not affect arterial blood pressure, and protects endothelial function in conduit arteries but promotes endothelial dysfunction in resistance arteries during angiotensin II-mediated hypertension. Aldosterone contributes little to angiotensin II-induced hypertension in mice.

Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions: DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Impact of institutional interventions on the rate of paclitaxel hypersensitivity reactions.

PURPOSE: Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization. METHODS: Patients who received paclitaxel from 20 April 2018 to 8 December 2020 having an HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of the paclitaxel infusion. The incidences of all HSR prior to and post-standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed. RESULTS: There were 3499infusions in the pre-standardization group and 1159infusions in the post-standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p = 0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% of the post-standardization group (p = 0.55). CONCLUSIONS: This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA are safe premedication regimens for paclitaxel. No change in the severity of reactions was seen. Overall, better adherence to premedication administration was seen post-standardization.

Acid-suppressive drugs: A systematic review and network meta-analysis of their nocturnal acid-inhibitory effect.

BACKGROUND AND AIMS: Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs). METHODS: To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA). RESULTS: Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB. CONCLUSIONS: This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.