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OBJECTIVES: The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats. METHODS: Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines. RESULTS: Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation. CONCLUSIONS AND RELEVANCE: When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.

Abstract Background Stevens–Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky’s sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens–Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy. Case presentation An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky’s sign was positive. A diagnosis of Steven–Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission. Conclusion Stevens–Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted.

Background: Stevens–Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky's sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens–Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy. Case presentation: An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky's sign was positive. A diagnosis of Steven–Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission. Conclusion: Stevens–Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted. [ABSTRACT FROM AUTHOR]

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 ratio [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. Conclusions 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.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Womens Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

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).

Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H2 receptor antagonists (H2RA) compared with H2RA nonusers in relatively small studies. We evaluated the association of H2RA use and incident HF in postmenopausal women in the large-scale WHI (Women's Health Initiative) study. Methods and Results This study included postmenopausal women from the WHI without a history of HF at baseline. HF was defined as first incident hospitalization for HF and physician adjudicated. Multivariable Cox proportional hazards regression models evaluated the association of H2RA use as a time-varying exposure with HF risk, after adjustment for demographic, lifestyle, and medical history variables. Sensitivity analyses examined (1) risk of HF stratified by the ARIC (Atherosclerosis Risk in Communities) score, (2) propensity score matching on H2RA use, (3) use of proton pump inhibitors rather than H2RA nonuse as the referent, and (4) exclusion of those taking diuretics at baseline. The primary analysis included 158 854 women after exclusion criteria, of whom 9757 (6.1%) were H2RA users. During median 8.2 years of follow-up, 376 H2RA users (4.9 events/1000 person-years) and 3206 nonusers (2.7 events/1000 person-years) developed incident HF. After multivariable adjustment, there was no association between H2RA use and HF in the primary analysis (hazard ratio, 1.07; 95% CI, 0.94-1.22; P=0.31) or in any of the sensitivity analyses. Conclusions Clinical H2RA use was not associated with incident HF among postmenopausal women. Future studies are needed to evaluate potential effect modification by sex, HF severity, or patterns of use on H2RA exposure and HF risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000611.

Gastric acid-related disorders are commonly encountered in clinical practice. Acetylcholine, gastrin, and histamine are physiological agonists that stimulate acid secretion from parietal cells. Histamine plays a decisive role in the transformation of parietal cells into acid-secreting forms. The H+, K+- ATPase proton pump, which represents the final step of acid secretion, translocates from cytoplasmic tubulovesicles to secretory canaliculi upon parietal cell stimulation and facilitates exchange of intracellular H+ with extracellular K+ in a 1:1 ratio. Histamine-2 receptor antagonists and proton pump inhibitors (PPIs) are widely used in clinical practice, and potassium-competitive acid blockers (P-CABs) have gained attention in recent times. P-CABs address the unmet needs of patients who receive conventional PPIs and have broadened the spectrum of drug choices; however, further research is warranted to confirm long-term safety of these drugs. Comprehensive understanding of the mechanisms of actions, characteristics, advantages and disadvantages, and the adverse effect profile is essential for appropriate prescription of gastric acid-suppressive drugs. In this review, we provide a developing history and outline the pharmacological mechanisms underlying various gastric acid-suppressive drugs used in clinical settings.

Acid suppressants are widely-used classes of medications linked to increased risks of aerodigestive infections. Prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We aimed to determine the impact of chronic acid suppression use on COVID-19 infection risk while simultaneously evaluating the influence of social determinants of health to validate known and discover novel risk factors. We assessed the association of chronic acid suppression with incident COVID-19 in a 1:1 case-control study of 900 patients tested across three academic medical centers in California, USA. Medical comorbidities and history of chronic acid suppression use were manually extracted from health records by physicians following a pre-specified protocol. Socio-behavioral factors by geomapping publicly-available data to patient zip codes were incorporated. We identified no evidence to support an association between chronic acid suppression and COVID-19 (adjusted odds ratio 1.04, 95% CI 0.92-1.17, P = 0.515). However, several medical and social features were positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new infection. These findings demonstrate the value of integrating publicly-available databases with medical data to identify critical features of communicable diseases.

Background: Use of acid‐suppressive medications (ASMs), for example, proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs), has been rising along with the incidence of pediatric immune‐mediated diseases (IMDs). We conducted a scoping review to characterize the literature about prenatal or pediatric exposure to ASMs in relation to incident pediatric IMDs. Methods: Electronic searches were conducted to identify studies from 2001 to 2023 on (a) prenatal or pediatric exposure to PPIs and/or H2RAs and (b) the risk of developing chronic IMDs during childhood. Eligible studies after title/abstract and full‐text screening underwent data abstraction. Results: Of 26 eligible studies, 11 focused on prenatal ASM exposure and 16 on pediatric exposure. Asthma was the most commonly investigated outcome (16 studies), followed by other allergic diseases (8), eosinophilic esophagitis (3), inflammatory bowel disease (2), and other autoimmune diseases (2). Positive associations between ASM exposure and pediatric IMD outcomes emerged in all but two recent studies, which reported null or negative associations with allergic diseases. The strength of associations was similar across exposure times (prenatal/pediatric), medications (PPIs/H2RAs), and outcomes. Dose–response relationships were often present (7/11 studies). Reported effects by trimester and age of exposure varied. Commonly reported limitations were residual confounding, exposure misclassification, and outcome misclassification. Conclusion: In summary, prenatal or pediatric exposure to PPIs and/or H2RAs has frequently, but not exclusively, been associated with the development of asthma, other allergic diseases, and chronic gastrointestinal IMDs. However, concerns remain about confounding and other sources of bias. Prescribers and families should be aware of these possible risks of ASMs. [ABSTRACT FROM AUTHOR]

Background: Drug shortages are a complex global challenge, and few studies have analyzed quantitative data on their impacts. In September 2019, detection of a nitrosamine impurity in ranitidine led to recalls and shortages. Aims: We investigated the extent of the ranitidine shortage and its impacts on acid suppression drug utilization in Canada and the United States (US). Methods: We conducted an interrupted time series analysis of acid suppression drug purchases in Canada and the US from 2016 through 2021 using IQVIA's MIDAS database. We used autoregressive integrated moving average models to determine the impact of the shortage on purchasing rates for ranitidine, other histamine-2 receptor antagonists (H2RAs), and proton pump inhibitors (PPIs). Results: Prior to the recalls, 20,439,915 ranitidine units were purchased monthly in Canada and 189,038,496 in the US on average. After the recalls started in September 2019, purchasing rates decreased for ranitidine (Canada p = 0.0048, US p < 0.0001) and increased for non-ranitidine H2RAs (Canada p = 0.0192, US p = 0.0534). One month into the recalls, purchasing rates dropped by 99% (Canada) and 53% (US) for ranitidine and increased by 128.3% (Canada) and 37.3% (US) for non-ranitidine H2RAs. PPI purchasing rates did not change significantly in either country. Conclusions: The ranitidine shortage led to immediate and sustained shifts in H2RA utilization in both countries, potentially affecting hundreds of thousands of patients. Our results emphasize the need for future studies of the clinical and financial implications of the shortage, and the importance of ongoing work to mitigate and prevent drug shortages. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. OBJECTIVE: A systematic review and a meta-analysis was performed. METHODS: We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). RESULTS: From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98–11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37–22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12–2.34, I2 34.5%). CONCLUSIONS: In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the association between famotidine treatment and severity, as well as mortality, for patients with COVID-19. In addition, to investigate whether this association was changed in cases of concomitant treatment with corticosteroids, remdesivir, clarithromycin, low molecular weight heparin, or statin. Material and methods: This is a retrospective cohort study conducted by analyzing electronic medical records of 171 hospitalized patients into the Infectious DiseaseWard of a 2068-bed tertiary care medical center, with laboratory-confirmed COVID-19 between May 01, 2021 and August 31, 2021. Patients were classified as receiving famotidine if they were treated with oral drug, at any dose, within ± 7 days of COVID-19 screening and/or hospital admission. Famotidine use was extracted directly fromthe electronic medical record. Results: Current study failed to identify famotidine as a protective factor associated with a significant reduction in the risk of in-hospitalmortality (odds ratio 1.573, 95%confidence interval (CI) 0.464--5.325, p = 0.467) or a significant reduction in the risk of ICU admission (odds ratio 0.547, 95%confidence interval (CI) 0.286--1.045, p = 0.068).However, non-significant trend towards a lower rate of ICU admission in association with famotidine prescription was observed. Conclusions: The results of this study reflect the real-world use of famotidine does not reduce the risk of in-hospital-mortality or ICU admission of hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

BackgroundAbomasal ulceration is recognized in neonatal and adult cattle, but research regarding treatment is limited. Histamine-2 receptor antagonists (H2 RA), such as famotidine, are used clinically with little evidence-based research about efficacy in adult cattle.Hypothesis and objectivesIntravenous famotidine administered at 0.4 mg/kg will increase the pH of abomasal outflow digesta compared to saline control in adult cattle. The objectives were to assess the effect of famotidine, administered as a single dose and as multiple doses, on abomasal outflow fluid pH in adult cattle. A third objective was to describe the pharmacokinetic parameters of IV famotidine in cattle.AnimalsFour clinically healthy adult Angus-cross steers previously fitted with duodenal cannulae placed orad to the biliary and pancreatic ducts.MethodsRandomized, 2-way cross-over clinical trial. Steers received IV famotidine (0.4 mg/kg) as a single and 3-dose regimen (every 8 hours) versus saline control. Blood for analysis of serum famotidine concentration was collected intermittently for 12 hours, and abomasal outflow fluid pH was measured at intervals for a 24-hour period. After a 34-hour washout period, the opposite treatments were administered and the sampling repeated.ResultsAbomasal outflow fluid pH was higher in steers treated with famotidine for up to 4 hours after a single dose but the effect decreased with subsequent doses. The median (range) elimination half-life was 3.33 (3.21-3.54) hours.Conclusions and clinical importanceFamotidine may be useful for treatment or prevention of abomasal ulceration in adult cattle, but the duration of effect may decrease with time.

Purpose: The presence of the impurity N-nitrosodimethylamine (NDMA) has been a reason for recent drug product recalls in 2019–2020. Methods: This document reviews the timing of ranitidine and valsartan recalls due to NDMA; the numerical values reported in the available literature are compared, while the proposed mechanisms and influencing factors are discussed in detail. The liability of other histamine H2 receptor antagonists such as famotidine and cimetidine is also investigated according to the information available in the literature. Results: The presence of nitrate ions, acidity of the environment, and nitrate contamination of the pharmaceutical excipients and temperature are effective factors in the production of this impurity. The effect of excipients is also discussed. Special attention is necessary to select the proper type of analytical method in examining trace amounts of this impurity in drug samples. Conclusion: The available data builds a case for the evaluation of NDMA formation in all histamine H2 receptor antagonists especially famotidine as a liable agent at different conditions and in the presence or absence of nitrite ions and some pharmaceutical excipients in vitro and in vivo. Special pharmaceutical formulation and manufacturing designs may be able to prevent the formation of this impurity. [ABSTRACT FROM AUTHOR]

PurposeAcid-suppression therapy is known to decrease the systemic exposure of erlotinib. The erlotinib prescribing information recommends staggering dosing with a histamine-2 receptor antagonist (H2RA) and avoiding concurrent use of a proton pump inhibitor (PPI). This retrospective analysis evaluated the frequency of concurrent acid-suppression therapy in oncology patients receiving erlotinib and its association with outcomes.MethodsAll patients prescribed erlotinib within UC San Diego Health System between February 26, 2011, and February 28, 2014, were assessed for eligibility, survival outcomes and adverse events.ResultsOf the 76 patients in the analysis, 24 were prescribed both a PPI and an H2RA with erlotinib therapy (31.6 %). The two patient groups, with (n = 24) and without PPI/H2RA (n = 52), were similar in clinical characteristics and erlotinib dose. One patient received an H2RA therapy alone and was excluded from the analysis; no one received PPI therapy alone. Patients receiving erlotinib alone had a longer median progression-free survival (PFS) compared to patients with concurrent PPI/H2RA therapy (11.0 months vs. 5.3 months; P = 0.029). Overall survival (OS) and incidence of rash and/or diarrhea did not correlate with use of acid-suppression therapy.ConclusionNearly one-third of patients received acid-suppression therapy. Patients treated with erlotinib and PPI/H2RA therapy had shorter PFS, but similar OS and adverse event profile compared to those who did not receive acid-suppression.

Several key areas in gastroenterology pharmacotherapy are rapidly evolving, including the treatment of hepatitis C virus (HCV), irritable bowel syndrome, gastroesophageal reflux disease (GERD) and peptic ulcer disease. HCV treatment has radically changed in the past 2 years and now most patients are treatment candidates and have a high likelihood of permanent cure. Pharmacotherapy is now first-line treatment for patients with moderate to severe symptoms of irritable bowel syndrome. Proton pump inhibitors (PPIs) are the mainstay of therapy in gastric and duodenal ulcers and GERD, although long-term use carries the risk of several side effects that should be considered.

BackgroundPredictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeds (PUBs) are essential indicators because of significant morbidity and mortality rates of PUBs. However those have been infrequently reported since changes in medical therapy (PPI, proton pump inhibitors) and application of newer endoscopic haemostatic technique.AimsTo determine: (i) independent risk factors for 30-day rebleeding, surgery, and death and (ii) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB after successful endoscopic haemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists - H2RAs).MethodsA large prospectively followed population of patients hospitalised with severe PUBs between 1993 and 2011 at two US tertiary care academic medical centres, stratified by stigmata of recent haemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors for each outcome (rebleeding, surgery and death) up to 30 days were analysed. Effects for medical treatment (H2RA patients 1993-2005 vs. PPIs 2006-2011) were also analysed.ResultsA total of 1264 patients were included. For ulcers ≥10 mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95% CI 1.02-1.10, P = 0.0053). Other risk factors for 30-day rebleeding were major SRH, in-patient start of bleeding, and prior GI bleeding. Major SRH and ulcer size≥10 mm were predictors of 30-day surgery. Risk factors for 30-day death were major SRH, in-patient bleeding, and any initial platelet transfusion or fresh frozen plasma transfusion ≥2 units. Among patients with major SRH and out-patient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95% CI 1.02-1.14, P = 0.0095). Ulcer size was a significant independent variable for both time periods.ConclusionsUlcer size is a risk factor for worse outcomes after PUB and should be carefully recorded at initial endoscopy to improve patient triage and management.

Background: The purpose of this study was to investigate and predict ventilator-associated pneumonia (VAP) in the two groups of patients who received either proton pump inhibitors (Pantoprazole) or histamine H2 antagonist (Ranitidine). Methods: Patients in ICU received Pantoprazole or Ranitidine as stress-related mucosal injury and GI bleeding prophylaxis. The incidence rate of VAP and GI bleeding was estimated in each group during ICU stay. Chi-Square and Multivariate Logistic Regression Test were used for data analysis. P.value less than 0.05 was considered significant. Data analysis was performed through SPSS version 19.0. Results: The incidence rate of VAP in the Ranitidine and Pantoprazole groups was 44.7% and 37.3% respectively (p=0.3). According to the multivariable logistic regression analysis, length of mechanical ventilation ≥ 4 days was a predictive factor for VAP only in the Pantoprazole group (OR: 1.8, 95% CI: 1.56-1.90, p=0.006). No relationship between GI bleeding incidence and stress ulcer prophylaxis was found (p=0.4). Kaplan-Meier curve showed no significant difference between the two groups of Ranitidine and Pantoprazole (p=0.4) in survival time according to the length of ICU stay. Conclusion: According to the results, there was no difference between the two groups in terms of VAP, GI bleeding and stress ulcer. Due to the lower cost of Ranitidine, it may be a more appropriate choice for GI bleeding prophylaxis in ICU patients.

Objective: Approximately 1%–5% of critically ill patients experience clinically important gastrointestinal bleeding (CIGB). This study assessed the effectiveness and safety of proton pump inhibitors (PPIs) compared to histamine type 2 receptor antagonists (H2RAs) for prevention of CIGB in mechanically ventilated patients. Design: This is a retrospective, single‐center, pharmacoepidemiologic study. Setting: This study was carried out in six intensive care units (ICUs). Patients: Critically ill adults admitted between 9/1/14 and 9/1/19 who received PPIs or H2RAs within 24 h of intubation and for ≥48 h were included in this study. Intervention: PPIs or H2RAs for stress ulcer prophylaxis. Measurements and Main Results: Primary outcomes were CIGB occurring 48 h after ICU admission and hospital mortality. Secondary outcomes were pneumonia, Clostridioides difficile infection (CDI), acute kidney injury, myocardial infarction/ischemia, thrombocytopenia, and delirium. Outcomes were defined using International Classification of Diseases, Ninth Revision (ICD‐9) and Tenth Revision (ICD‐10)‐codes with manual cross‐reference for a hemoglobin drop, transfusion, or hemodynamic compromise to further define CIGB. Of 3873 patients, 2061 (53.2%) received PPIs. CIGB was rare but higher in the PPI group (0.34% vs. 0%, RR = 1, 95% CI, 1–1; p = 0.013); however, substantial group differences existed possibly predisposing the PPI group to CIGB. Hospital mortality was higher in the PPI group (42.1% vs. 29.1%, RR = 1.23, 95% CI, 1.17–1.29; p < 0.0001). PPIs remained an independent risk factor for mortality after multivariate adjustment (RR = 1.61, 95% CI, 1.39–1.88; p < 0.0001). Rates of secondary outcomes were similar between groups except thrombocytopenia (4.3% vs. 2.2%, RR = 1.02, 95% CI, 1.01–1.03; p = 0.0003) and delirium (83.7% vs. 78.1%, RR = 1.34, 95% CI, 1.18–1.53; p < 0.0001) that were higher in the PPI group. Conclusion: Proton pump inhibitors were associated with CIGB; however, the overall rate of CIGB was low. Compared to H2RAs, PPIs were associated with hospital mortality. Further identification of appropriate selection criteria for ulcer prophylaxis and comparisons of pharmacologic prevention strategies are warranted. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture; however, prior studies have not yielded consistent results, and many have suboptimal ascertainment of both PPI use and BMD. We used data from the Study of Women's Health Across the Nation (SWAN), a multicenter, multi-ethnic, community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, body mass index (BMI), lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone-replacement therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs, and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck, or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss.

Background and Aim: Concerns regarding adverse events associated with proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) for gastrointestinal bleeding (GIB) prophylaxis in the intensive care unit have increased in recent years. Few studies have focused on acid suppressant use in the cardiac care unit (CCU) setting exclusively. We performed a cohort study to determine the efficacy and safety of acid suppressants for GIB prophylaxis in CCU patients. Methods: This retrospective cohort study included adults who were admitted directly to the CCU for more than 2 days from January 1, 2014, to April 30, 2019. The Crusade score was calculated to evaluate the risk of GIB. The primary outcomes were clinically important gastrointestinal bleeding (CIGIB), hospital‐acquired pneumonia (HAP), and in‐hospital mortality. Results: Of the 3318 patients enrolled, 2284 (68.8%) patients received PPIs, 515 (15.5%) received H2RAs, and 519 (15.7%) received no acid suppressants. After adjusting for potential confounders, utilization of PPIs (2.69, 95% confidence interval [0.62–11.73]) and H2RAs (1.41, 95% confidence interval [0.19–10.36]) were not associated with a lower risk of CIGIB than the control. Sensitivity analyses revealed that PPI use was an independent risk factor for in‐hospital mortality in patients over 75 years old, with an adjusted odds ratio of 4.08 (1.14–14.63). PPIs increased the risk of HAP in patients over 75 years old and in those with heart failure, with adjusted odds ratios of 2.38 (1.06–5.34) and 2.88 (1.34–7.28), respectively. Conclusions: Proton pump inhibitors and H2RAs for GIB prophylaxis in CCU patients were not associated with a lower risk of CIGIB than the controls. PPI therapy is associated with increased risks of HAP and in‐hospital mortality in patients over 75 years old. PPIs may increase the risk of HAP in patients with heart failure. [ABSTRACT FROM AUTHOR]

Background: Long-term usage of acid suppression drugs like proton pump inhibitors (PPIs) or H2 receptor blockers in the elderly population has been found to result in vitamin B12 deficiency. However, the reports are equivocal. Objective: To determine the serum vitamin B12 levels in elderly patients under chronic acid suppression therapy. Methods: Patients aged above 60 years and on any of the PPIs or H2 blockers for at least 6 months were recruited. Out of 77 patients recruited, 60 patients were included for the final analysis. The serum vitamin B12 levels were measured using the AccuDiag™-Vitamin B12 ELISA system. Results: Out of 60 patients, pantoprazole (40%) and omeprazole (37%) were the commonly prescribed acid-suppressing drugs. Nearly 50% of the patients on prolonged acid suppression therapy were either "deficient" (less than 200 pg/ml) or "insufficient" (200 to 300 pg/ml) in serum vitamin B12 levels. Neither the average serum vitamin B12 levels (p = 0.994) nor the vitamin B12 status (p = 0.226) varied significantly across the drug groups of pantoprazole, omeprazole, and ranitidine. Conclusions: Prolonged acid suppression therapy with PPIs or H2 blockers may result in serum vitamin B12 deficiency. However, there was no class (PPIs vs. H2 receptor blockers)- or drug (pantoprazole vs. omeprazole vs. ranitidine)-based differences found in the vitamin B12 deficiency caused. [ABSTRACT FROM AUTHOR]

BackgroundAbnormal acid gastro-oesophageal reflux is common in patients with idiopathic pulmonary fibrosis (IPF) and is considered a risk factor for development of IPF. Retrospective studies have shown improved outcomes in patients given anti-acid treatment. The aim of this study was to investigate the association between anti-acid treatment and disease progression in IPF.MethodsIn an analysis of data from three randomised controlled trials, we identified patients with IPF assigned to receive placebo. Case report forms had been designed to prospectively obtain data about diagnosis and treatment of abnormal acid gastro-oesophageal reflux in each trial. The primary outcome was estimated change in forced vital capacity (FVC) at 30 weeks (mean follow-up) in patients who were and were not using a proton-pump inhibitor or histamine-receptor-2 (H2) blocker.FindingsOf the 242 patients randomly assigned to the placebo groups of the three trials, 124 (51%) were taking a proton-pump inhibitor or H2 blocker at enrolment. After adjustment for sex, baseline FVC as a percentage of predicted, and baseline diffusing capacity of the lung for carbon monoxide as a percentage of predicted, patients taking anti-acid treatment at baseline had a smaller decrease in FVC at 30 weeks (-0·06 L, 95% CI -0·11 to -0·01) than did those not taking anti-acid treatment (-0·12 L, -0·17 to -0·08; difference 0·07 L, 95% CI 0-0·14; p=0·05).InterpretationAnti-acid treatment could be beneficial in patients with IPF, and abnormal acid gastro-oesophageal reflux seems to contribute to disease progression. Controlled clinical trials of anti-acid treatments are now needed.FundingNational Institutes of Health.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

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.

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p

Background:The purpose of this study was to investigate and predict ventilator-associated pneumonia (VAP) in the two groups of patients who received either proton pump inhibitors (Pantoprazole) or histamine H2 antagonist (Ranitidine). Methods: Patients in ICU received Pantoprazole or Ranitidine as stress-related mucosal injury and GI bleeding prophylaxis. The incidence rate of VAP and GI bleeding was estimated in each group during ICU stay. Chi-Square and Multivariate Logistic Regression Test were used for data analysis. P.value less than 0.05 was considered significant. Data analysis was performed through SPSS version 19.0. Results: The incidence rate of VAP in the Ranitidine and Pantoprazole groups was 44.7% and 37.3% respectively (p=0.3). According to the multivariable logistic regression analysis, length of mechanical ventilation ≥ 4 days was a predictive factor for VAP only in the Pantoprazole group (OR: 1.8, 95% CI: 1.56-1.90, p=0.006). No relationship between GI bleeding incidence and stress ulcer prophylaxis was found (p=0.4). Kaplan-Meier curve showed no significant difference between the two groups of Ranitidine and Pantoprazole (p=0.4) in survival time according to the length of ICU stay. Conclusion: According to the results, there was no difference between the two groups in terms of VAP, GI bleeding and stress ulcer. Due to the lower cost of Ranitidine, it may be a more appropriate choice for GI bleeding prophylaxis in ICU patients. [ABSTRACT FROM AUTHOR]

Background: The growing reports regarding cardiac‐related adverse events of chronic proton‐pump inhibitors (PPI) treatment, a mainstay therapy of non‐cardiac chest pain (NCCP), have raised concerns about alteration of the natural course in NCCP patients using PPI. We aimed to determine if NCCP patients receiving PPI have a higher risk of developing ischemic heart disease (IHD) compared to those not receiving PPI therapy. Methods: Three groups of NCCP patients were included; PPI, histamine‐2 receptor antagonist (H2RA), and no antireflux treatment. Diagnosis of NCCP had to precede diagnosis of IHD by at least 30 days, and in those receiving antireflux treatment at 30 days after starting the medication. Data analysis was corrected for 6 known confounding factors for IHD including hyperlipidemia, hypertension, obesity, smoking status, male gender, and diabetes mellitus. Key Results: Of the patients on PPI or H2RA, 1280 and 250, respectively, developed IHD. Patients on PPI therapy displayed an increased odd of developing ischemic heart disease compared to patients never placed on therapy (OR 1.14, 95% CI 1.03‐1.25, P‐value.0093). Patients placed on H2RA therapy did not show a statistically significant change in risk compared to patients who were not placed on therapy (OR 0.90, 95% CI 0.77‐1.06, P‐value.2049). Number needed to harm in the PPI and H2RA groups was 17 and 45, respectively. Conclusions: PPIs confer a statistically significant, but marginal effect on the risk of IHD development in NCCP patients. Thus, PPI use in NCCP only minimally alters the overall benign natural course of the disease. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) have been widely used for multiple purposes. Recent studies have suggested an association between these medications and the risk of pancreatic cancer. However, the results have been inconclusive. Aim We, therefore, conducted a study to assess the risk of developing pancreatic cancer in patients who used PPI and H2RA. Design A systematic review and meta-analysis. Methods A literature search was performed using MEDLINE and EMBASE databases from inception through February 2019. Studies that reported risk ratio comparing the risk of pancreatic cancer in patients who received PPI or H2RA versus those who did not receive treatments were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect generic inverse variance method. Sensitivity analysis, excluding one study at a time, was performed. Results After screening abstracts from the searching methods, seven studies (six case–control studies and one cohort study) were included in the analysis with total 546 199 participants. Compared to patients who did not take medications, the pooled RR of developing pancreatic cancer in patients receiving PPI and H2RA were 1.73 (95% CI: 1.16–2.57) and 1.26 (95% CI: 1.02–1.57), respectively. However, the sensitivity analysis of PPI changed the pooled RR to 1.87 (95% CI: 1.00–3.51) after a study was dropped out. Likewise, H2RA sensitivity analysis also resulted in non-significant pooled RR. Conclusions This meta-analysis did not find the strong evidence for the associations between the use of PPI and H2RA and pancreatic cancer. [ABSTRACT FROM AUTHOR]

The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H+, K+-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H2RAs at night. The effectiveness of nighttime dose of H2RA suggests a major role of histamine in nocturnal acid secretion. H2RAs reduce secretion of gastric acid, and each H2RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H2RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.

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 H 2 receptor antagonists (H 2 RAs), 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., Competing Interests: The authors declared no potential conflicts of interest to the research, authorship, or publication of this article., (© 2024 Prayoga et al.)

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).

Study Objective: Because recent studies have challenged the efficacy of stress ulcer prophylaxis (SUP) in the critically ill patient, our objective was to evaluate the efficacy of SUP with proton pump inhibitors (PPIs) or histamine2‐receptor antagonists (H2RAs) against placebo, control, no therapy, or enteral nutrition alone in critically ill adults. Design: Meta‐analysis with trial sequential analysis (TSA) of 34 randomized controlled trials. Patients: A total of 3220 critically ill adults who received PPIs or H2RAs versus placebo, control, no therapy, or enteral nutrition. Measurements and Main Results: A systematic review was performed using a random effects meta‐analysis with TSA according to a predefined protocol. Randomized controlled trials comparing PPIs or H2RAs with either placebo, control, no therapy, or enteral nutrition alone were identified through a comprehensive search of the literature. Two blinded reviewers independently assessed studies for inclusion, risk of bias, and extracted data using Cochrane Collaborative methodology. The predefined primary outcomes were clinically important, overt, and any (clinically important plus overt) gastrointestinal bleeding. Secondary outcomes included pneumonia, Clostridium difficile–associated diarrhea (CDAD), and mortality. Subgroup analyses were conducted for the primary outcome by PPI or H2RA use, intensive care unit (ICU) subtype, studies published after early goal‐directed therapy (EGDT), the presence of risk factors for stress ulceration, and enteral nutrition use. Of the 34 trials included, 33 were judged as high risk of bias and 1 was judged as low risk. Use of SUP significantly reduced clinically important bleeding (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.37–0.76, p<0.001; I2 = 0%), overt bleeding (RR 0.55, 95% CI 0.39–0.76, p=0.0003; I2 = 53%), and any bleeding (RR 0.54, 95% CI 0.41–0.71, p<0.00001; I2 = 58%). TSA confirmed these findings. No significant differences in pneumonia, CDAD, or mortality were noted. Subgroup analyses revealed significant reductions in clinically important bleeding with SUP in neurosurgical patients (RR 0.37, p<0.05) but not in surgery/trauma or medical ICU patients with risk factors. SUP provided no benefit in studies published after EGDT. SUP significantly reduced clinically important bleeding regardless of the use of enteral nutrition (p<0.05). Conclusion: This meta‐analysis demonstrated that SUP use was associated with significant reductions in bleeding but not mortality. SUP should not be abandoned until large randomized trials demonstrate the futility of this intervention. [ABSTRACT FROM AUTHOR]

This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir ; registration number: IRCT20090117001556N138). • Post-COVID-19 complications persist in near 1/3 of the patients. • Cognitive impairment and neuropsychiatric disorders are the most common complications. • Few have assessed therapies for neuropsychiatric disorders caused by post-COVID-19 infection. • A short-term treatment with famotidine improved cognitive functioning in post-COVID-19 infection. [ABSTRACT FROM AUTHOR]