Histamine Receptor Antagonists Research Articles

Association between acid-suppressive drugs and risk of psoriasis: retrospective study using Korean National Health Insurance Service-National Sample Cohort.

Psoriasis is a common inflammatory skin disorder following non-specific triggers. Involvement of immune system is widely accepted for pathogenesis studies have demonstrated importance of gut microbiota in pathogenesis of inflammatory skin diseases. Proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) are acid-suppressive drugs widely used for acid related gastrointestinal diseases, and prolonged use has been associated with altered gut microbiota. This study aimed to investigate association between psoriasis and acid suppressing drugs in Korean population. This study was conducted with 3,662 patients diagnosed with psoriasis between 2002 and 2013 in NHIS-NSC. A total of 14,648 controls were matched at 1:4 based on sex, age, and gastrointestinal disease. ORs were estimated to determine the association between acid suppressing drug use and psoriasis. Our study found a statistically significant association between the prolonged use of acid-suppressive drugs and the development of psoriasis in the Korean population. Specifically, patients with gastrointestinal diseases who used histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) for extended periods exhibited a higher risk of developing psoriasis. The adjusted odds ratio for psoriasis was 1.89 (95% CI, 1.66-2.17) with long-term use, indicating a clear dose-response relationship. Results from our study indicate that prolonged use of H2RA or PPI is associated with the risk of psoriasis among patients with gastrointestinal diseases in Korean population. The risk was increased in dose-response trend after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressing drugs.

Long-term use of proton pump inhibitors was associated with rapid progression to end stage kidney disease in a Korean nationwide study

Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. However, their influence on the progression of end-stage kidney disease (ESKD) in established chronic kidney disease (CKD) cases is unclear. Using the Korean Health Insurance Review and Assessment database encoded by the Observational Medical Outcomes Partnership–Common Data Model (OMOP-CDM), patients with stage 3 or 4 CKD initiating PPIs or histamine-2 receptor antagonists (H2RAs) for over 90 days were enrolled from 2012 through 2021. Incidence of ESKD events between the groups were compared using a cox proportional hazard model. A total of 34,656 eligible patients were included. Of the patients, 65.1% had CKD stage 3, 44.5% aged > 75 years, 59.8% were male individuals, and 68.3% had diabetes. After 1:1 propensity score matching, ESKD progression was observed in 2327 out of 19,438 patients and it was more frequent in PPI users (incidence rate, 10.5/100PYs) than that in H2RA users (incidence rate, 9.2/100PYs; IRR, 1.14 [1.07–1.12]). Using the subgroup analysis, IRR was significantly higher in patients with CKD stage 3 (IRR 1.40 [1.21–1.60]), whereas it was not in those with CKD stage 4 (IRR 1.04 [0.94–1.15]). A similar trend was observed in patients with CKD 3 or 4 with and without diabetes. In general, PPI use is associated with a 14% higher risk of ESKD progression in patients with CKD stage 3 or 4. However, the influence of PPIs differed according to the comorbidities and risks of adverse kidney outcomes.

Gastroprotection in Heart Failure and Outcomes: A Systematic Review of Proton Pump Inhibitors and Histamine-2 Receptor Antagonists.

The management of heart failure (HF) frequently includes gastroprotection via proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). This systematic review evaluates their impact on HF outcomes, including exacerbation, hospitalization, mortality, and major adverse cardiac events (MACE). In accordance with PRISMA guidelines, a complete search across databases such as PubMed/Medline, Scopus, and Web of Science was conducted until December 10, 2023. The inclusion criteria covered research on adult patients with HF that focused on the effects of PPI and H2RA usage. The risk of bias was determined via the Newcastle-Ottawa Scale (NOS), and data were synthesized quantitatively. Eleven studies encompassing 996,498 participants were analyzed. The data is not consistent across all research; however, some have suggested that PPI use may be linked to an increased risk of cardiovascular illnesses and heart failure aggravation. Conversely, H2RAs appeared to offer potential benefits in certain high-risk groups, potentially reducing all-cause and cardiovascular mortality. However, the limitations of the available studies should be taken into consideration when interpreting these findings. The review suggests that there may be differences in the impact of PPIs and H2RAs on HF outcomes. While some evidence indicates that PPIs may be linked to increased risks in HF patients, and H2RAs may offer potential benefits, these findings are not definitive and should be interpreted with caution. Further research is necessary to clarify these associations and guide clinical practice. PROSPERO CRD42023491752.

Prescriptions of anti-reflux drugs in neonatology and neonatal intensive care units: A large multicentre observational study (2014-2022).

Gastro-oesophageal reflux is common in newborns, especially in premature infants. Treatment by medication is controversial as the drugs prescribed have not been consistently proven to be effective and are known to have adverse effects. This study sought to identify trends in the prescription of anti-reflux medication in a large group of French neonatal units. Data on prescriptions of anti-reflux treatments-proton pump inhibitors (PPIs), antacids, histamine-2 receptor antagonists (H2RAs), and prokinetics-from 2014 to 2022 for infants with a corrected gestational age <45 weeks, were extracted from a prescription database (Logipren®) used by 63 French neonatal units, and then analysed. Of all infants recorded in the database during the study period (n =152 743), 10.2% (n = 15 650) were prescribed anti-reflux medication (95% confidence interval [CI] 10.0-10.4%), mainly as monotherapy (77.5%). The rate was higher in the subgroup of preterm infants born before 28 weeks of gestation (n = 9493) (20.6%, 95% CI 19.8-21.4%; n = 1956). PPIs were the most commonly prescribed anti-reflux medications (6.9% of infants, 95% CI 6.8-7.0), followed by antacids (5.2%, 95% CI 5.1-5.3%), while H2RAs and prokinetics were rarely prescribed. Over the period, the prescription rate remained stable for PPIs, decreased for H2RAs (τ = -0.86, P = .02), and, among preterm infants born at gestational ages of 28-31 or 32-36 weeks, increased for antacids. Anti-reflux medications were frequently prescribed by neonatal units, especially for extremely premature infants. Most of these prescriptions were for PPIs and antacids.

Association of acid-suppressive therapy and tuberculosis: A causal or coincidental link to the infection?

BackgroundAcid-suppressant proton-pump inhibitors (PPI) and histamine-2-receptor antagonists (H2RA) are associated with an increased risk of tuberculosis (TB). However, it remains unclear whether this association is causal or coincidental. MethodsPatients newly diagnosed with TB between 2000 and 2013 were identified from the Taiwan National Health Insurance Database. Each patient with TB was matched in a 1:10 ratio with patients without TB by age, sex, and index date. The time lags from the end of PPI or H2RA treatment to the index date, and respective cumulative doses in the 90 days before the index date, were analyzed for association with TB. ResultsThe age (mean [standard deviation] 60.8 [17.3] years) and sex ratio (69.4% males) were comparable between patients with TB (n = 6002) and patients without TB (n = 60,020). Previous PPI or H2RA treatment was more frequently observed in patients with TB (16.6% vs. 8.9%, p < 0.001). Concurrent antacid therapy posed the highest risk for TB (odds ratio [OR] 4.21 for PPI and 2.24 for H2RA, both p < 0.0001), and the closer to the end of the therapy, the more likely TB was detected (p for trend: 0.0077 for PPI and 0.0145 for H2RA). The cumulative doses of antacid in the 90 days before TB had an inverse relationship with TB risk. PPI, used either alone or in combination with H2RA, conferred a higher risk of TB than H2RA alone. ConclusionsTuberculosis should be considered in symptomatic patients receiving or recently ceased antacid therapy with PPI or H2RA in TB endemic areas.

Optimizing epidermal growth factor receptor-tyrosine kinase inhibitor treatment in lung cancer: a systematic review and meta-analysis of the influence of gastric acid suppressants.

The introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized advanced non-small cell lung cancer (NSCLC) treatment. However, their efficacy can be compromised by concurrent use of gastric acid suppressants (GASs), such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs). This study aimed to update the evidence on the impact of GASs on the overall survival (OS) and progression-free survival (PFS) in patients on EGFR-TKI treatment. A systematic review and meta-analysis were conducted using data from PubMed, Embase, Cochrane Library, Web of Science, Scopus, KoreaMed, and preprint repositories. Data from 13 retrospective studies, involving 10,814 patients, were analyzed. Overall, 34.6% of the patients used GASs, with most being Asian females and non-smokers. Most patients had EGFR-mutated adenocarcinoma, reflecting typical EGFR-TKI usage scenarios. Concurrent use of GASs was significantly associated with reduced OS [hazard ratio (HR) =1.34, 95% confidence interval (CI): 1.26-1.42], and PFS (HR =1.52, 95% CI: 1.25-1.86). In subgroup analysis, PPIs had a more negative impact on OS (HR =1.64, 95% CI: 1.51-1.79) than did H2RAs (HR =1.11, 95% CI: 0.95-1.31). Longer overlap times of GASs correlated with a higher trend in HRs for OS. However, the results for PFS were not significant in both subgroup analyses. Concurrent use of GASs with EGFR-TKIs is linked to poorer OS and PFS in patients with advanced NSCLC. Careful consideration is advised when prescribing GASs, including adjusting administration timing, minimizing overlap duration, or opting for H2RAs over PPIs. Further research is needed to optimize treatment protocols, specifically addressing the duration of overlap time, to improve patient outcomes.

Effects of famotidine use during pregnancy: an observational cohort study

BackgroundFamotidine, a histamine2-receptor antagonist (H2Ras), is widely used to treat and prevent gastrointestinal symptoms during pregnancy. Although several studies have reported the use of H2Ras during pregnancy, limited data on famotidine were included in these reports. Therefore, we analyzed pregnancy outcome data to evaluate the effects of famotidine use during pregnancy on the fetus.MethodsPregnancy outcome data were used for females enrolled in two Japanese facilities that provided counseling on drug use during pregnancy between April 1988 and December 2017. For the primary endpoint, the incidence of congenital malformations was calculated from the data of live birth to pregnant women who took famotidine (n = 330) or drugs considered to exert no teratogenic risk (control, n = 1,407) during the first trimester of pregnancy. Considering secondary endpoints, the incidence of obstetric outcomes, including preterm delivery, was calculated from data on the use of famotidine (n = 347) and controls (n = 1,476) during the entire pregnancy. The crude odds ratios (cORs) for the incidence of congenital malformations were calculated using univariate logistic regression analysis, with the control group used as the reference. Adjusted ORs (aORs) were calculated using multivariate logistic regression analysis adjusted for various other factors.ResultsThe incidences of congenital malformations in the famotidine and control groups were 3.9% and 2.8%, respectively. There was no significant difference between the famotidine and control groups (cOR: 1.40 [95% CI:0.68–2.71], aOR: 1.06 [95% CI:0.51–2.16]). Conversely, the preterm delivery rates were 8.1% and 3.8% in the famotidine and control groups, respectively, indicating a significant difference (cOR: 2.00 [95% CI:1.20–3.27]). However, the multivariate analysis eliminated famotidine use as a confounding factor.ConclusionsThis observational cohort study revealed that exposure to famotidine during the first trimester of pregnancy was not associated with an increased risk of congenital malformations in infants. Although a higher rate of preterm delivery was detected in famotidine users when compared with controls, this could be attributed to confounding factors, such as complications.

Association between gastroprotective agents and acute kidney injury in patients receiving non-steroidal anti-inflammatory drugs: Analysis of a Japanese hospital-based database.

The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs. The data analyzed were obtained from the JMDC hospital-based administrative claims database between April 2014 and August 2022. Histamine-2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin-angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log-rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time-varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates. After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92-3.63, p = 0.08). Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade-off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs.

Pitolisant 40 mg for excessive daytime sleepiness in obstructive sleep apnea patients treated or not by CPAP: Randomised phase 3 study.

Obstructive sleep apnea (OSA) syndrome commonly leads to excessive daytime sleepiness (EDS). Pitolisant, a selective histamine-3 receptor antagonist, is efficacious at doses up to 20 mg once daily in OSA treated or not with continuous positive airway pressure (CPAP). We assessed the efficacy and safety of pitolisant at doses up to 40 mg once daily in patients with moderate to severe OSA treated or not with CPAP therapy. In this phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trial, patients with OSA were assigned 2:1 to receive pitolisant (according to an individual up-titration scheme, 10, 20 or 40 mg once daily) or placebo for 12 weeks. The primary endpoint was a change in the Epworth Sleepiness Scale (ESS) score from baseline to week 12. Secondary endpoints included a change in reaction time using the Oxford Sleep Resistance test (OSleR), Clinical Global Impression of Change (CGI-C), and Patient's Global Opinion of the Effect (PGOE) of study treatment. Overall, 361 patients (mean age 52.4 years, 77.3% male; mean apnea-hypopnea index [AHI] 27.0 events/h) were randomised to receive pitolisant (n = 242; 50% received CPAP) or placebo (n = 119; 48.7% CPAP). After the dose-adjustment phase (week 3), 88.8% of patients received pitolisant 40 mg. Compared with placebo, pitolisant produced a significant reduction in the ESS score at week 12 (least square mean difference -2.6 (95% CI: -3.4; -1.8; p < 0.001)) irrespective of CPAP use; and improved the reaction time on OSleR, CGI-C, and PGOE at week 12. Pitolisant was well tolerated; no new safety signals were identified. In conclusion, pitolisant up to 40 mg once daily was an effective treatment for EDS in patients with moderate to severe OSA irrespective of CPAP use.

Hospitalized patients on proton pump inhibitors for stress ulcer prophylaxis have a higher risk of Clostridioides difficile infection compared with those on histamine-2 receptor antagonists

Previous studies on Clostridioides difficile infection (CDI) in proton pump inhibitor (PPI) users generally enrolled a heterogeneous population and did not include a control group of histamine H2 receptor antagonists (H2RAs) users or adjust for confounding variables, such as previous antibiotics. It is uncertain whether hospitalized patients using PPIs for stress ulcer prophylaxis (SUP) are at a higher risk of CDI compared with those using H2RAs. This study aimed to compare the association between CDI and the usage of antisecretory drugs (ASDs): PPIs and H2RAs, for SUP among hospitalized patients, and the impact of the duration of their use on CDI. In this nationwide population-based cohort study using the Taiwan National Health Insurance Database, hospitalized patients using ASDs for SUP were identified between 2017 and 2018. A total of 63,266 and 69,269 individuals were included in the PPI and H2RA groups, respectively. The primary endpoint was a 90-day monitoring of CDI occurrence. The incidences of CDI were 1.6/10,000 and 0.5/10,000 person-days in the PPIs and H2RAs groups, respectively. After adjusting for confounding factors, the risk of infection in the PPIs group remained significantly higher than in the H2RAs group (hazard ratio (HR), 2.49; 95% confidence interval (CI), 1.63-3.81). In the subgroup analysis, during hospitalization, the risk of CDI for patients using high-risk antibiotics or admitted to the intensive care unit (ICU), as well as patients with immunodeficiency, using PPIs for SUP, was higher than using H2RAs. Furthermore, the risk of CDI was higher in patients using ASDs for durations >14 days than in those using them for <7 days (adjusted HR, 3.66; 95% CI, 2.34-5.75). The risk of occurrence CDI for hospitalized patients using PPIs for SUP was higher than using H2RAs. It is recommended not to exceed 14 days of any gastric ASDs for SUP during hospitalization, especially for patients who have used high-risk antibiotics, have been admitted to the ICU, or have immunodeficiency.

No Impact of Concomitant Medications on Efficacy and Safety of Biologics and Small Molecules for Ulcerative Colitis

While participants with inflammatory bowel diseases (IBD) in clinical trials of biologics and small molecule drugs (henceforth, advanced therapies) frequently receive several medications concomitantly, it is unclear how they modify treatment effect. Through an individual patient data pooled analysis of ten clinical trials of advanced therapies for moderate-to-severe ulcerative colitis (UC), we assessed whether concomitant exposure to corticosteroids, immunomodulators, 5-aminosalicylates, proton pump inhibitors (PPIs), histamine receptor antagonists (H2RA), opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model. Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), 5-aminosalicylates (68%), PPIs (14%), H2RAs (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention vs. placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs. placebo with vs. without concomitant exposure: RRR, 0.81 [95% CI,0.63-1.06], 5-aminosalicylates (RRR, 1.04[0.78-1.39]), PPIs (RRR, 0.87 [0.61-1.22]), H2RAs (RRR, 1.72[0.97-14.29]), opiates (RRR, 0.90[0.54-1.49]), antidepressants (RRR, 1.02[0.57-1.83]), and antibiotics (RRR, 0.72[0.44-1.16]) on likelihood of clinical remission. Concomitant exposure to immunomodulators was associated with lower likelihood of achieving clinical remission (RRR, 0.73[0.55-0.97]), particularly with non-TNF antagonists. In clinical trials of advanced therapies for UC, baseline concomitant exposure to multiple commonly used class of medications does not impact treatment efficacy or safety. These findings directly inform design of regulatory clinical trials with respect to managing concomitant medications at baseline.

Novel insights into famotidine as a GSK-3β inhibitor: An explorative study in aluminium chloride-induced Alzheimer’s disease rat model

Alzheimer's disease (AD), a chronic neurodegenerative disease, presents a substantial global health challenge. This study explored the potential therapeutic role of famotidine, a histamine (H2) receptor antagonist, as a glycogen synthase kinase-3β (GSK-3β) inhibitor in the context of AD induced by aluminium chloride (AlCl3) in a rat model. The intricate relationship between GSK-3β dysregulation and AD pathogenesis, particularly in amyloid-β (Aβ) production, formed the basis for investigating famotidine's efficacy. Molecular modelling revealed famotidine's efficient binding to GSK-3β, suggesting inhibitory potential. In behavioural assessments, famotidine-treated groups exhibited dose-dependent improvements in Morris Water Maze, Novel Object Recognition, and Y-Maze tests, comparable to the standard Rivastigmine tartrate group. Biochemical analyses showed that famotidine inhibits acetylcholinesterase, decreases lipid peroxidation, increases antioxidant activity, and mitigates oxidative stress. Moreover, famotidine significantly lowered the levels of GSK-3β, IL-6, and Aβ(1−42). The neuroprotective effects of famotidine were further supported by histopathological analysis. This comprehensive investigation underscores famotidine's potential as a GSK-3β inhibitor, providing insights into its therapeutic impact on AD induced by AlCl3. The study offers a promising avenue for repurposing famotidine due to its established safety profile and widespread availability, highlighting its potential in addressing the formidable challenge of AD.

Effect of Switching the Histamine-1 Receptor Antagonist Clemastine to Cetirizine in Paclitaxel Premedication Regimens: The H1-Switch Study.

Premedication, including a histamine-1 receptor (H1) antagonist, is recommended to all patients treated with paclitaxel chemotherapy to reduce the incidence of hypersensitivity reactions (HSRs). However, the scientific basis for this premedication is not robust, which provides opportunities for optimization. Substitution of intravenously administered first-generation H1 antagonist for orally administered second-generation H1 antagonist could reduce side effects, and improve efficiency and sustainability. This study investigates the efficacy and safety of substituting intravenous clemastine for oral cetirizine as prophylaxis for paclitaxel-induced HSRs. This single-center, prospective, noninferiority study compares a historic cohort receiving a premedication regimen with intravenous clemastine to a prospective cohort receiving oral cetirizine. Primary end point of the study is HSR grade ≥3. The difference in incidence was calculated together with the 90% CI. We determined that the two-sided 90% CI of HSR grade ≥3 incidence in the oral cetirizine cohort should not be more than 4% higher (ie, the noninferiority margin) compared with the intravenous clemastine cohort. Two hundred and twelve patients were included in the oral cetirizine cohort (June 2022 and May 2023) and 183 in the intravenous clemastine cohort. HSR grade ≥3 incidence was 1.6% (n = 3) in the intravenous clemastine cohort and 0.5% (n = 1) in the oral cetirizine cohort, resulting in a difference of -1.2% (90% CI, -3.4 to 1.1). Premedication containing oral cetirizine is as safe as premedication containing intravenous clemastine in preventing paclitaxel-induced HSR grade ≥3. These findings could contribute to optimization of care for patients and improve efficiency and sustainability.

Does the Use of Gastric-Acid Suppressants Increase the Risk of Peritonitis in Patients Undergoing Peritoneal Dialysis? A Meta-Analysis.

Gastric-acid suppressants (GASs) are commonly prescribed to patients undergoing peritoneal dialysis for various gastrointestinal disorders. However, long-term GAS use has been linked with the risk of enteric peritonitis in this patient population. To assess the association between the enteric peritonitis risk and GAS use in patients undergoing peritoneal dialysis for end-stage renal disease, we conducted a systematic search for relevant articles published until December 2023 in PubMed, Embase, and the Cochrane Library databases. We included 11 articles on the association between GAS use and enteric peritonitis risk in patients undergoing peritoneal dialysis. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) using fixed and random-effects models to obtain overall effect estimates. We also explored potential sources of heterogeneity through subgroup analyses. We qualitatively analyzed data from 11 studies (n = 1993 participants), out of which, nine studies were included in meta-analysis. The overall results revealed a significant association between the enteric peritonitis risk and the use of GASs (OR, 1.61; 95% CI, 1.26-2.05; p < 0.00001). The analysis of study design subgroups showed a significant association in retrospective cohort studies (OR, 1.70; 95% CI, 1.42-2.03; p < 0.00001) but not in case-control studies. Histamine-2 receptor antagonist (H2RA) use was significantly associated with enteric peritonitis (OR, 1.49; 95% CI, 1.05-2.11, p = 0.03), whereas proton pump inhibitor use was not (OR, 1.13; 95% CI, 0.72-1.77, p = 0.28). Our findings suggest a significant association between the development of enteric peritonitis and GAS use in patients undergoing peritoneal dialysis. However, the observed heterogeneity in study characteristics warrants caution in interpreting the results.

Diagnostic yield of bidirectional endoscopy for iron deficiency anemia in young patients

BackgroundWhile bidirectional endoscopy is recognized as the standard approach for investigating iron deficiency anemia (IDA) in men older than 45 and postmenopausal women, evidence supporting the application of this approach in younger men and premenopausal women is scarce in the absence of symptoms. Our primary aim is to identify the diagnostic yield of bidirectional endoscopy in men younger than 45 and premenopausal women, and describe the clinical characteristics of those with significant endoscopic and pathology-proven findings.MethodsWe performed a retrospective chart review including patients younger than age 45 with IDA who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy at the Brooklyn VA Hospital between 2009 and 2023. Demographic, clinical, and endoscopic patient data was all collected, stratified, analyzed, and interpreted.ResultsIn 143 patients younger than age 45 with IDA, 28.6% were found to have positive upper gastrointestinal (GI) findings, of which 70.3% were pathology-proven H. pylori cases. 57.9% of patients reported upper GI symptoms, while 42.9% of patients were asymptomatic. In total, 18.2% of symptomatic patients were found to have clinically significant findings on EGD as compared with 42.9% of asymptomatic patients. Additionally, 9.1% of symptomatic patients were found to have biopsy proven H. pylori-associated gastritis or duodenitis as compared with 33.9% of asymptomatic patients. Of the patients who underwent colonoscopy, 8.3% were found to have lower GI lesions.ConclusionsWe found the diagnostic yield of EGD to be significantly higher than that of colonoscopy in younger IDA patients. Our findings suggest current guidelines are clinically relevant to the young patient cohort. Our study also found asymptomatic IDA patients below age 45 to have a significantly higher diagnostic yield of EGD as compared to symptomatic IDA patients within the same age cohort. The differences in diagnostic yields may be a result of symptomatic patients being more likely to have been prescribed proton pump inhibitors or histamine receptor antagonists prior to endoscopy.

Incidence of gastrointestinal bleeding with hydrocortisone use in neonates and infants less than three months of age in the neonatal intensive care unit.

The objective of this study was to determine the incidence of hydrocortisone-associated gastrointestinal bleeding (GIB) in infants <3 months and compare rates with or without stress ulcer prophylaxis. Retrospective cohort study of NICU patients <3 months who received hydrocortisone for hypotension. Three logistic regressions were conducted for adjusted associations between GIB, necrotizing enterocolitis (NEC), or infection and clinical characteristics. Of 233 patients included, 54 (23.2%) received SUP; the majority (96.3%) received histamine-2 receptor antagonists. Median postmenstrual and postnatal age at hydrocortisone initiation was 33.3 weeks and 2 days. GIB occurred in 22 patients (9.4%), with no difference in GIB (11.1% versus 8.9%, p = 0.632) or SUP-associated adverse effects (50.0% versus 52.0%, p = 0.80) with and without SUP. SUP was not associated with GIB, NEC, or infection when controlling for confounders. GIB occurred in 9.4% of patients. SUP did not provide benefit for GIB prevention and was not associated with increased risk of adverse effects.

Liposomal nanocarriers of preassembled glycocalyx restore normal venular permeability and shear stress sensitivity in sepsis: assessed quantitatively with a novel microchamber system.

The endothelial glycocalyx (EG), covering the luminal side of endothelial cells, regulates vascular permeability and senses wall shear stress. In sepsis, EG undergoes degradation leading to increased permeability and edema formation. We hypothesized that restoring EG integrity using liposomal nanocarriers of preassembled glycocalyx (LNPG) will restore normal venular permeability in lipopolysaccharide (LPS)-induced sepsis model of mice. To test this hypothesis, we designed a unique perfusion microchamber in which the permeability of isolated venules could be assessed by measuring the concentration of Evans blue dye (EBD) in microliter samples of extravascular solution (ES). Histamine-induced time- and dose-dependent increases in EBD in the ES could be measured, confirming the sensitivity of the microchamber system. Notably, the histamine-induced increase in permeability was significantly attenuated by histamine receptor (H1) antagonist, triprolidine hydrochloride. Subsequently, mice were treated with LPS or LPS + LNPG. When compared with control mice, venules from LPS-treated mice showed a significant increased permeability, which was significantly reduced by LNPG administration. Moreover, in the presence of wall shear stress, intraluminal administration of LNPG significantly reduced the permeability in isolated venules from LPS-treated mice. We have found no sex differences. In conclusion, our newly developed microchamber system allows us to quantitatively measure the permeability of isolated venules. LPS-induced sepsis increases permeability of mesenteric venules that is attenuated by in vivo LNPG administration, which also reestablished endothelial responses to shear stress. Thus, LNPG presents a promising therapeutic potential for restoring EG function and thereby mitigating vasogenic edema due to increased permeability in sepsis.NEW & NOTEWORTHY In sepsis, the degradation of the endothelial glycocalyx leads to increased venular permeability. In this study, we developed a potentially new therapeutic approach by in vivo administration of liposomal nanocarriers of preassembled glycocalyx to mice, which restored venular sensitivity to wall shear stress and permeability in lipopolysaccharide-induced sepsis, likely by restoring the integrity of the endothelial glycocalyx. Using a new microchamber system, the permeability of Evans blue dye could be quantitatively determined.

Pharmacodynamics Between a Dual Delayed-Release Formulation of Low-Dose Esomeprazole and Famotidine in Healthy Korean Subjects

PurposeGastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis. MethodsThis study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated. FindingsThe mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%. ImplicationsMultiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis.ClinicalTrials.gov identifier: NCT04967014.

Evaluating the efficacy of a premedication regimen including high-dose cetirizine in reduction of hypersensitivity reactions to paclitaxel: A retrospective cohort study.

Hypersensitivity reactions (HSR) are a known adverse effect of paclitaxel, occurring in approximately 10% of patients, typically during the first or second infusion of the medication. Corticosteroids, histamine-1 and histamine-2 receptor antagonists are given prior to paclitaxel infusions to reduce the incidence of HSR. There are limited data that suggest administration of cetirizine given prior to a platinum infusion as secondary prophylaxis may reduce HSR rates. The objective of this study was to assess the impact of a novel paclitaxel hypersensitivity prevention protocol including high-dose cetirizine administered 12 and 6 h prior to paclitaxel infusion on the rate of HSR compared to a historical control. The primary objective was the rate of HSR of any grade after the first cycle of paclitaxel. Secondary outcomes included grade of infusion reaction and incidence of severe HSR. A total of 104 patients were included for analysis in the cetirizine group and 124 in the control group. Hypersensitivity reactions occurred in 37 (16.2%) patients in the overall population, and no statistical difference was observed between groups. (13.46% vs 18.55%; p = 0.23). Numerically more grade 3-4 HSRs occurred in the control group than the treatment group (30.77% vs 69.23; p = 0.51). The addition of cetirizine to paclitaxel infusions resulted in numerically lower rates of HSR and a reduction in severity of grade 3-4 HSRs. Future studies with more robust compliance data and a larger patient population would be needed to appropriately assess the efficacy of our novel treatment regimen.

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study.

Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).