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Helicobacter pylori infection is an important causative factor in a variety of gastrointestinal diseases, such as atrophic gastritis, peptic ulcer disease, and gastric cancer. Timely eradication treatment is conducive to maintaining the health of patients. With the increase of drug resistance in Helicobacter pylori, dual therapy with proton pump inhibitors combined with high-dose amoxicillin has gradually gained attention. Potassium- competitive acid blockers are new types of antacids that have a faster onset of action and a longer lasting acid suppression effect than traditional proton pump inhibitors, making it more suitable for dual therapy. In recent years, scholars have carried out a lot of exploration, improvement and verification of potassium-competitive acid blockers dual therapy, and this article reviews its research progress. [ABSTRACT FROM AUTHOR]

This document is a summary of a Cochrane review that examines the effectiveness of various medications in treating gastroesophageal reflux disease (GORD) in infants and older children. The review found very low-certainty evidence regarding the benefits of medications for symptom improvement in infants. For older children, there was also very low-certainty evidence that proton pump inhibitors (PPIs) may or may not improve GORD outcomes. The review calls for further research with longer follow-up periods and improved trial design. It also highlights the potential side effects and conflicts of interest associated with these medications. [Extracted from the article]

Simple Summary: Proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) are commonly used for acid reduction in patients with peptic ulcer disease or esophageal reflux. Previous studies have shown that acid-reducing agents (ARAs) might affect bevacizumab treatment. This study found that PPI use worsened the oncological outcomes in patients with metastatic colorectal cancer (mCRC) undergoing bevacizumab treatment. There was a negative dose–response relationship when compared to H2RA use. Physicians should consider the benefits and risks of long-term use of ARAs, especially PPIs, in mCRC patients treated with bevacizumab. Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab. [ABSTRACT FROM AUTHOR]

Background: Children with IgA Vasculitis (IgAV) may develop renal complications, which can impact their long-term prognosis. This study aimed to build a machine learning model to predict renal damage in children with IgAV and analyze risk factors for IgA Vasculitis with Nephritis (IgAVN). Methods: 50 clinical indicators were collected from 217 inpatients at our hospital. Six machine learning algorithms—Logistic Regression, Linear Discriminant Analysis, K-Nearest Neighbor, Support Vector Machine, Decision Trees, and Random Forest—were utilized to select the model with the highest predictive performance. A simplified model was developed through feature importance ranking and validated by an additional cohort with 46 patients. Results: The random forest model had the highest accuracy, precision, recall, F1 score, and area under the curve, with values of 0.91, 0.98, 0.70, 0.79 and 0.94, respectively. The top 11 features according to the importance ranking were anti-streptolysin O, corticosteroids therapy, antihistamine therapy, absolute eosinophil count, immunoglobulin E, anticoagulant therapy, C-reactive protein, prothrombin time, age at onset, D-dimer, recurrence of rash ≥ 3 times. A simplified model using these features demonstrated optimal performance with an accuracy of 84.2%, a sensitivity of 89.4%, and a specificity of 82.5% in external validation. Finally, we provided a web tool based on the simplified model, whose code was published on https://github.com/mulanruo/IgAVN%5fPrediction. Conclusion: The model based on the random forest algorithm demonstrates good performance in predicting renal damage in children with IgAV, providing a basis for early clinical diagnosis and decision-making. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid (TXA) is commonly considered a safe drug to mitigate bleeding during and after various surgical settings among adults and children. In recent decades, anaphylaxis induced by TXA has been increasingly reported in adults. However, among pediatrics, there are fewer reported cases. Case presentation: We report a case of a 6-year-old female who experienced anaphylaxis after receiving intravenous TXA following unilateral cleft lip and palate repair surgery. She exhibited clinical symptoms involving the cardiovascular system, respiratory system, and skin. Following the administration of epinephrine, corticosteroid, and anti-histamine, the patient's symptoms were relieved. A few months after discharge, an intradermal test, yielded a positive result, confirming TXA as the culprit drug. Conclusion: Our report emphasizes the importance of considering anaphylaxis as a potential adverse reaction to TXA in pediatric patients, showing the criticality of rapid diagnosis and appropriate management for a successful outcome. [ABSTRACT FROM AUTHOR]

Background: The actual situation and influencing factors of prophylactic use of proton pump inhibitors (PPIs) in internal medicine inpatients receiving glucocorticoid therapy are rarely reported. This study aimed to investigate the current status and influencing factors of prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy to provide a basis for rational prophylactic use of PPIs. Methods: Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Information on the prophylactic use of PPIs was collected and analyzed by clinical pharmacists. Associated factors with prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. Results: 980 inpatients were finally included in our study, of which 271 (27.7%) inpatients received prophylactic use of PPIs. Among the inpatients prescribed PPIs, 90 inpatients received a standard dose of PPIs twice a day. Multiple logistic regression analysis showed that age ≥80 years [OR = 7.009, 95% CI (1.424, 34.495), p = 0.017], history of gastroesophageal reflux disease (GERD) [OR = 2.047, 95% CI (1.338, 3.133), p = 0.001], low platelet count [OR = 0.997, 95% CI (0.994, 0.999), p = 0.004], number of concomitant diseases [OR = 1.104, 95% CI (1.056, 1.153), p < 0.001], junior doctors [OR = 1.755, 95% CI (1.248, 2.468), p = 0.001], glucocorticoid dose (higher than 50 mg, measured by methylprednisolone) [OR = 2.455, 95% CI (1.371, 4.395), p = 0.003], antiplatelet agents [OR = 2.567, 95% CI (1.456, 4.524), p = 0.001], immunosuppressants [OR = 1.477, 95% CI (1.014, 2.153), p = 0.042], and betahistine [OR = 5.503, 95% CI (1.124, 26.950), p = 0.035] were associated with more prophylactic use of PPIs. Conclusion: The prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy is common in China. Clinical pharmacists will take targeted measures to promote the rational use of PPIs according to the results of this study. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. Methods: This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient‐level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5–9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6‐month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. Results: Age and gender distribution was similar across the six countries (mean age 75–76 years; 54–56% female). The prevalence of polypharmacy of 5–9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. Conclusions: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe. [ABSTRACT FROM AUTHOR]

Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all‐cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non‐H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan–Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all‐cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30‐day, 90‐day, and 1‐year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696‐0.882 for 30‐day; HR = 0.860, 95% CI: 0.778‐0.950 for 90‐day; and HR = 0.883, 95% CI: 0.811‐0.961 for 1‐year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients. [ABSTRACT FROM AUTHOR]

Introduction: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy. Areas covered: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization. Expert opinion: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim: Helicobacter pylori plays an important role in causing digestive diseases. The purpose of this study is to investigate Helicobacter pylori in COVID‐19 patients with and without gastrointestinal symptoms. Methods: In this case–control study, all patients with COVID‐19 admitted to Imam Khomeini Hospital in Jiroft city in 2021 were convenience sampled and divided into two homogeneous groups. Ninety‐five patients with COVID‐19, who presented with gastrointestinal symptoms, were included in the case group, while 95 patients with COVID‐19 without gastrointestinal symptoms were included in the control group. Noninvasive diagnostic methods, including serology and stool antigen tests, were used to identify Helicobacter pylori in the studied patients. Results: Fifty‐three people (55.8%) from the case group had Helicobacter pylori, and 48 (50.5%) from the control group had Helicobacter pylori. Among the 53 people from the case group, 27 (50.9%) were men and 26 (49.1%) were women. Nineteen people (35.8%) were taking pantoprazole, 10 people (18.8%) were taking nonsteroidal anti‐inflammatory drugs, 20 people (37.7%) were taking narcotics, and 7 people (13.2%) had peptic ulcer. Seven people (13.2%) had an H2 blocker, and 21 people had an underlying disease. A significant relationship between infection with Helicobacter pylori and the use of pantoprazole, nonsteroidal anti‐inflammatory drugs, narcotics, peptic ulcer, underlying disease, and H2 blocker in COVID‐19 patients with gastrointestinal symptoms and without gastrointestinal symptoms was present (P‐value < 0.05). Conclusion: The prevalence of Helicobacter pylori infection in patients with COVID‐19, who have gastrointestinal symptoms, is high and should be considered as a treatment criterion for people infected with COVID‐19. [ABSTRACT FROM AUTHOR]

Texture and color enhancement imaging (TXI) may improve the visibility of gastric tumors and allow their early detection. However, few reports have examined the utility of TXI. Between June 2021 and October 2022, 56 gastric tumors in 51 patients undergoing endoscopic submucosal dissection at Fukuchiyama City Hospital were evaluated preoperatively using conventional white light imaging (WLI), narrow-band imaging (NBI), and TXI modes 1 and 2. The color differences of the tumors and surrounding mucosae were evaluated using the CIE 1976 L*a*b color space, Additionally, the visibility scores were scaled. Of the 56 gastric tumors, 45 were early gastric cancers, and 11 were adenomas. Overall, the color difference in TXI mode 1 was considerably higher compared to WLI (16.36 ± 7.05 vs. 10.84 ± 4.05; p < 0.01). Moreover, the color difference in early gastric cancers was considerably higher in TXI mode 1 compared to WLI, whereas no significant difference was found in adenomas. The visibility score in TXI mode 1 was the highest, and it was significantly higher compared to WLI. Regarding adenomas, the visibility score in TXI mode 1 was also significantly higher compared to that in WLI. TXI may provide improved gastric tumor visibility. [ABSTRACT FROM AUTHOR]

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280–6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions 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. [ABSTRACT FROM AUTHOR]

This article explores the potential misdiagnosis of diarrhea-predominant irritable bowel syndrome (IBS) as systemic mastocytosis (SM), a hematological condition characterized by abnormal mast cell proliferation. It provides an overview of SM and its diagnostic criteria, as well as the clinical features and histology of the disease. The article includes a case report of a patient initially diagnosed with refractory IBS-D who was later found to have SM, highlighting the challenges in diagnosing SM and the importance of awareness among healthcare professionals. The document also discusses the role of serum biomarkers in the diagnosis, treatment, and monitoring of SM, including well-known markers like serum tryptase and other biomarkers that are still being investigated. Treatment for SM is individualized and may involve medications to control symptoms and tyrosine kinase inhibitors. Early diagnosis is crucial and can be achieved through a high clinical index of suspicion. [Extracted from the article]

Aim: The use of vitamin K antagonists (VKAs) may increase the risk of peripheral arterial disease (PAD) because vitamin K is a strong inhibitor of medial arterial calcification. Type 2 diabetes (T2D) exposes patients to an increased risk of PAD. We examined how the use of VKAs modulates the risk of incident PAD in people with T2D. Materials and Methods: SURDIAGENE is a French cohort including 1468 patients with T2D with a prospective follow‐up from 2002 to 2015. The primary outcome of the current analysis was the first occurrence of PAD, a composite of lower‐limb amputation (LLA) or lower‐limb revascularization. LLA and lower‐limb revascularization were considered individually as secondary outcomes. Results: During a 7‐year median follow‐up, PAD occurred in 147 (10%) of the 1468 participants. The use of VKAs was not significantly associated with the risk of PAD [multivariable adjusted hazard ratio (HR) 1.42, 95% confidence interval (CI), 0.88‐2.31]. During the study period, LLA and lower‐limb revascularization occurred in 82 (6%) and 105 (7%) participants, respectively. The use of VKAs was significantly associated with increased risk of LLA [multivariable adjusted HR 1.90 (95% CI, 1.04‐3.47)], but not lower‐limb revascularization [multivariable adjusted HR 1.08 (95% CI, 0.59‐1.97)]. Conclusions: In this prospective study, we did not observe any excess risk of PAD requiring lower‐limb revascularization in people with type 2 diabetes using VKAs. However, our data suggest a high risk of LLA in VKA users. Further studies are required to confirm this observation. [ABSTRACT FROM AUTHOR]

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of "adequate" prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18–1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians' consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a microvascular complication that frequently affects numerous patients diagnosed with diabetes. For the diagnosis of CKD, the guidelines recommend the identification of the urinary albumin/creatinine ratio and the determination of serum creatinine, based on which the estimated rate of glomerular filtration (eGFR) is calculated. Serum creatinine is routinely measured in clinical practice and reported as creatinine-based estimated glomerular filtration rate (eGFRcr). It has enormous importance in numerous clinical decisions, including the detection and management of CKD, the interpretation of symptoms potentially related to this pathology and the determination of drug dosage. The equations based on cystatin C involve smaller differences between race groups compared to GFR estimates based solely on creatinine. The cystatin C-based estimated glomerular filtration rate (eGFRcys) or its combination with creatinine (eGFRcr-cys) are suggested as confirmatory tests in cases where creatinine is known to be less precise or where a more valid GFR estimate is necessary for medical decisions. Serum creatinine is influenced by numerous factors: age, gender, race, muscle mass, high-protein diet, including protein supplements, and the use of medications that decrease tubular creatinine excretion (H2 blockers, trimethoprim, fenofibrate, ritonavir, and other HIV drugs). The low levels of creatinine stemming from a vegetarian diet, limb amputation, and conditions associated with sarcopenia such as cirrhosis, malnutrition, and malignancies may lead to inaccurately lower eGFRcr values. Therefore, determining the GFR based on serum creatinine is not very precise. This review aims to identify a new perspective in monitoring renal function, considering the disadvantages of determining the GFR based exclusively on serum creatinine. [ABSTRACT FROM AUTHOR]

The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity for human H3R (Ki = 24 nM) and selectivity towards histamine H1 and H4 receptors (Ki > 2500 nM), and showed anti-inflammatory activity in a model of lipopolysaccharide-induced inflammation in BV-2 cells. The presented tests confirmed its antagonist/inverse agonist activity profile and good metabolic stability while docking studies showed the binding mode to histamine H1, H3, and H4 receptors. In in vitro tests, cytotoxicity was evaluated at three cell lines (neuroblastoma, astrocytes, and human peripheral blood mononuclear cells), and a neuroprotective effect was observed in rotenone-induced toxicity. In vivo experiments in a mouse neuropathic pain model demonstrated the highest analgesic effects of AR71 at the dose of 20 mg/kg body weight. Additionally, AR71 showed antiproliferative activity in higher concentrations. These findings suggest the need for further evaluation of AR71's therapeutic potential in treating ND and CNS cancer using animal experimental models. [ABSTRACT FROM AUTHOR]

Summary: Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk–benefit ratios). This represents an important gap for informing clinician decision‐making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep‐promoting medications. Adverse event data values were extracted from the most recent FDA‐approved package inserts and converted to an integer before being placebo‐adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre‐to‐post self‐reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta‐analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk–benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non‐benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre‐to‐post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk–benefit, histamine antagonist had the most favourable profile (risk–benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk–benefit = 395.7). Overall, the combined metric for risk–benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first‐line therapy for the medical management of insomnia. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents. To assess the risk of TB relapse in patients (re-)started on TNF antagonists or JAK inhibitors. Systematic review. PubMed and Cochrane Library databases until 11 December 2023. Randomized control trials, prospective and retrospective cohort studies, case reports and case series. Patients with current or previous TB who were (re-)started on TNF antagonists or JAK inhibitors. (Re-)introduction of TNF antagonists and JAK inhibitors. All studies meeting entry criteria were included regardless of quality. Categorical data are presented as frequencies and percentages. For non-normally distributed aggregated data, we calculated the pooled weighted median with 95% CI. For individual patient data, the median and interquartile range (IQR) were calculated. Of 5018 articles screened for eligibility, 67 publications reporting on 368 TB patients who (re-)initiated treatment with TNF antagonists for underlying diseases were included. The median age was 42.5 years (95% CI: 40.4–42.5) and the proportion of female patients was 36.6% (n = 74) of patients whose sex was reported. A total of 14 patients (3.8%, 95% CI: 2.1–6.3%) developed TB relapse after a median of 8.5 months (interquartile range, 6.8–14.8 months) following (re-)initiation of anti-TNF treatment. Furthermore, among 251 articles screened for eligibility, 11 reports on TB patients who were (re-)started on JAK inhibitors for underlying diseases were identified. The median age was 62 years (interquartile range, 48.5–68.5 years) and 45.5% (n = 5) were female. Only one patient (9.1%; 95% CI: 0.2–41.3%) had TB reactivation 10 months after starting treatment with ruxolitinib. In addition, 94 patients who were treated with TNF antagonists and two patients temporarily treated with JAK inhibitors for the prevention or treatment of paradoxical reactions were analysed. None of the publications reported microbiological failure or worsening of TB-related symptoms. (Re-)initiation of TNF antagonists and JAK inhibitors may be relatively safe in patients with current or previous TB and the need for further treatment of underlying diseases. [ABSTRACT FROM AUTHOR]

A physiologically‐based pharmacokinetic (PBPK) model for tipifarnib, which included mechanistic absorption, was built and verified by integrating in vitro data and several clinical data in healthy subjects and cancer patients. The final PBPK model was able to recover the clinically observed single and multiple‐dose plasma concentrations of tipifarnib in healthy subjects and cancer patients under several dosing conditions, such as co‐administration with a strong CYP3A4 inhibitor and inducer, an acid‐reducing agent (proton pump inhibitor and H2 receptor antagonist), and with a high‐fat meal. In addition, the model was able to accurately predict the effect of mild or moderate hepatic impairment on tipifarnib exposure. The appropriately verified model was applied to prospectively simulate the liability of tipifarnib as a victim of CYP3A4 enzyme‐based drug–drug interactions (DDIs) with a moderate inhibitor and inducer as well as tipifarnib as a perpetrator of DDIs with sensitive substrates of CYP3A4, CYP2B6, CYP2D6, CYP2C9, and CYP2C19 in healthy subjects and cancer patients. The effect of a high‐fat meal, acid‐reducing agent, and formulation change at the therapeutic dose was simulated. Finally, the model was used to predict the effect of mild, moderate, or severe hepatic, and renal impairment on tipifarnib PK. This multipronged approach of combining the available clinical data with PBPK modeling‐guided dosing recommendations for tipifarnib under several conditions. This example showcases the totality of the data approach to gain a more thorough understanding of clinical pharmacology and biopharmaceutic properties of oncology drugs in development. [ABSTRACT FROM AUTHOR]

Background: Famotidine is a competitive histamine H-receptor antagonist that reduces the formation of stomach acid and is used to treat gastrointestinal disorders associated with acid reflux, gastroesophageal reflux disease, duodenal ulcer, gastric ulcer, and pathological hypersecretory disorders. This study is designed to investigate the possible neuroprotective effects of the ranolazine scopolamine-induced Alzheimer's disease-like feature in a mouse model. Methods: Mice were divided equally into five groups (ten mice per group), including control group and induction group. The mice in the induction group were administered scopolamine 1 mg/kg i.p., once daily for 7 days, to induce features similar to Alzheimer's disease. The mice in the remaining three treatment groups were given tested medications prophylactically for 14 days. After that the induction was carried out with scopolamine 1 mg/kg i.p., once daily, while the tested medication dosages were continued for an additional 7 days. These treatment groups included: the donepezil group (5 mg/kg/day), the famotidine group (40 mg/kg/day) and the combined group with donepezil (5 mg/kg/day) and famotidine (40 mg/kg/day); all were administrated i.p., once daily. Behavioral parameters were assessed, among others with the Y-maze test and novel object recognition test, and the inflammatory cytokines and oxidative stress parameters were assessed as well. Results: Famotidine exhibits significant improvements in behavior and memory, level of oxidative stress parameter, and inflammatory cytokines. Conclusions: Famotidine and its combination at prescribed doses in the current study improved learning and memory impairments in mice model of Alzheimer's disease probably via their antioxidant and anti-inflammatory properties confirmed by a significant increase in antioxidant mediator and a significant decrease in oxidative stress marker and inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Objective The ductus arteriosus normally closes after birth. Histamine 2 receptor antagonist (H 2 RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids—proton pump inhibitors (PPIs) and H 2 RA. Study Design This was a population-based matched case–control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001 and 2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the postdelivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H 2 RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC). Results PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H 2 RA (odds ratio [OR] 4.18) and PPIs (OR 3.50; all p < 0.001). PDA association with exposure window was similar in each trimester (1.5–2%) for both H 2 RA and PPI. Conclusion PDA incidence in term infants in our population was greater than previously reported. PPI and H 2 RA are both antiacids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias. Key Points Term newborns with PDA have different characteristics than newborns without PDA. Prenatal exposure to PPIs or H 2 RA is associated with greater risk of PDA in term newborns. The possible effect mechanism of PPIs on the ductus is unclear and understudied. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 1 (TRPV1) was reported to be a putative target for recovery from chronic pain, producing analgesic effects after its inhibition. A series of drug candidates were previously developed, without the ability to ameliorate the therapeutic outcome. Starting from previously designed compounds, derived from the hybridization of antagonist SB-705498 and partial agonist MDR-652, we performed a virtual screening on a pharmacophore model built by exploiting the Cryo-EM 3D structure of a nanomolar antagonist in complex with the human TRPV1 channel. The pharmacophore model was described by three pharmacophoric features, taking advantage of both the bioactive pose of the antagonist and the receptor exclusion spheres. The results of the screening were implemented inside a 3D-QSAR model, correlating with the negative decadic logarithm of the inhibition rate of the ligands. After the validation of the obtained 3D-QSAR model, we designed a new series of compounds by introducing key modifications on the original scaffold. Again, we determined the compounds' binding poses after alignment to the pharmacophoric model, and we predicted their inhibition rates with the validated 3D-QSAR model. The obtained values resulted in being even more promising than parent compounds, demonstrating that ongoing research still leaves much room for improvement. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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). Results: 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. Conclusions: 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 COVID19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. Funding: 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). [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of non-steroid mineralocorticoid receptor antagonists (ns-MRAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with diabetic kidney disease (DKD). Methods: Systematic literature searches were performed using PubMed, Embase and Web of Science encompassing inception until January 20, 2024. Randomized control trials (RCTs) comparing ns-MRAs and SGLT2is in DKD were selected. The efficacy outcomes of interest included kidney-specific composite outcome, cardiovascular (CV)-specific composite outcome, end-stage kidney disease (ESKD), and overall mortality. We also investigated safety outcomes, including acute kidney injury (AKI) and hyperkalemia. Results: A total of 10 randomized clinical trials with 35,786 patients applying various treatments were included. SGLT2is (SUCRA 99.84%) have potential superiority in kidney protection. SGLT2is (RR 1.41, 95%CI 1.26 to 1.57) and ns-MRAs (RR 1.17, 95% CI 1.08 to 1.27) were associated with significantly lower kidney-specific composite outcome than the placebo. Regarding the reduction in CV-specific composite outcome and ESKD, SGLT2is (SUCRA 91.61%; 91.38%) have potential superiority in playing cardiorenal protection. Concerning the CV-specific composite outcome (RR 1.27, 95%CI 1.09 to 1.43) and ESKD (RR 1.43, 95% CI 1.20 to 1.72), SGLT2is significantly reduced the risks compared to placebo. Regarding the reduction in overall mortality, SGLT2is (SUCRA 83.03%) have potential superiority in postponing mortality. Concerning the overall mortality, SGLT2is have comparable effects (RR 1.27, 95%CI 1.09 to 1.43) with placebo to reduce the risk of overall mortality compared to placebo. For AKI reduction, ns-MRAs (SUCRA 63.58%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. For hyperkalemia reduction, SGLT2is (SUCRA 93.12%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. Concerning hyperkalemia reduction, nsMRAs (RR 1.24 95% CI 0.39 to 3.72) and SGLT2is (RR 1.01 95%CI 0.40 to 3.02) did not show significant benefit compared to placebo. Conclusion: Concerning the efficacy and safety outcomes, SGLT2is may be recommended as a treatment regimen for maximizing kidney and cardiovascular protection, with a minimal risk of hyperkalemia in DKD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023458613. [ABSTRACT FROM AUTHOR]

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 mIU/ml] in these patients. Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22 +/-0.27 mg/kg/die, in the L-LT4 group 1.36+/-0.22 µg/kg/die (p>0.05). Results: At the basal evaluation the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 mIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up. [ABSTRACT FROM AUTHOR]

H. pylori infection is gaining increasing attention, but detailed investigations into its impact on gastric microbiota remain limited. We collected gastric mucosa samples from 47 individuals divided into three groups: 1. Group HP: patients with initial positive H. pylori infection (25 cases); 2. Group ck: H. pylori-negative patients (14 cases); 3. Group DiffHP: patients with refractory H. pylori infection (8 cases). The samples were analyzed using 16S rDNA sequencing and functional prediction with PICRUSt. Group HP showed differences in flora distribution and function compared to Group ck, while Group DiffHP overlapped with Group HP. The abundances of Aeromonas piscicola, Shewanella algae, Vibrio plantisponsor, Aeromonas caviae, Serratia marcescens, Vibrio parahaemolyticus, Microbacterium lacticum, and Prevotella nigrescens were significantly reduced in both Group DiffHP and Group HP compared to Group ck. Vibrio shilonii was reduced only in Group DiffHP compared to Group ck, while Clostridium perfringens and Paracoccus marinus were increased only in Group DiffHP. LEfSe analysis revealed that Clostridium perfringens and Paracoccus marinus were enriched, whereas Vibrio shilonii was reduced in Group DiffHP compared to Group ck at the species level. In individuals with refractory H. pylori infection, the gastric microbiota exhibited enrichment in various human diseases, organic systems, and metabolic pathways (amino acid metabolism, carbohydrate metabolism, transcription, replication and repair, cell cycle pathways, and apoptosis). Patients with multiple failed H. pylori eradication exhibited significant changes in the gastric microbiota. An increase in Clostridium perfringens and Paracoccus marinus and a decrease in Vibrio shilonii appears to be characteristic of refractory H. pylori infection. [ABSTRACT FROM AUTHOR]

Background: Although several small cohort studies have shown the utility of argon plasma coagulation (APC) in the treatment of gastric dysplasia, its clinical significance has not been established. This study aims to assess the efficacy of APC as a first line treatment for gastric dysplasia, and identify risk factors for residual dysplasia. Methods: A total of 179 cases of gastric dysplasia were treated with APC and have been followed-up with upper endoscopy within 1 year. The overall incidence and the characteristics of lesions with residual dysplasia in follow-up endoscopy were analyzed by logistic regression. Results: Among 179 lesions treated with APC, 171 (95.5%) lesions have achieved complete ablation in the follow-up endoscopy. Additional APC was applied for residual dysplasia, achieving complete ablation in 97.77% (175/179). The upper third location of the gastric dysplasia was significantly associated with residual dysplasia, while tumor size, horizontal location, macroscopic morphology and grade of dysplasia showed no significant associations with residual dysplasia following the initial APC. Conclusions: APC with meticulous follow-up can be recommended as a first line treatment in patients with gastric dysplasia. [ABSTRACT FROM AUTHOR]

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Key content: The perinatal period confers an elevated risk of both relapses and new onset of mental illness. Suboptimal treatment can have a profound impact on maternal mortality and morbidity, neonatal outcomes and longer term child development.Most psychotropic medication can be used safely in pregnancy, with some notable exceptions.While decisions on the use of psychotropic medications in pregnancy are often complex and should be multidisciplinary, it is imperative that obstetricians and gynaecologists familiarise themselves with current literature to provide evidence‐based counselling and care.Existing guidelines on the use of psychotropic medication are largely aimed at psychiatrists, and to date there has been a lack of concise, digestible information with a focus on core knowledge for obstetricians and gynaecologists.We summarise existing evidence on the use of antidepressants, antipsychotics, mood stabilisers and sedatives in the perinatal period. For each drug class we describe the teratogenicity, impact on pregnancy, breastfeeding and the newborn. Learning objectives: To be familiar with common psychotropic medication used in pregnancy and the postpartum period.To understand key evidence on the safety profile of psychiatric medication in the perinatal period and apply this to individualised counselling. [ABSTRACT FROM AUTHOR]

Background: To compare the effects of proton pump inhibitor (PPI) and histamine‐2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. Methods: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high‐risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis‐associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO‐3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. Results: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO‐3 rate was higher in the PPI group than in the H2RA group (log‐rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11–1.58, p = 0.002] was associated with incident KDIGO‐3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). Conclusions: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO‐3 AKI compared with H2RA use. [ABSTRACT FROM AUTHOR]

This article explores the benefits and challenges of conducting pragmatic trials using electronic health records (EHRs). Pragmatic trials are crucial for informing clinical practice when there is limited data available. EHRs offer advantages such as accessibility and the ability to enroll large numbers of patients quickly. However, there are unique challenges in conducting EHR-enabled trials, including potential biases and contamination of treatment groups. Real-time monitoring of enrollment and safety events is also difficult. Despite these challenges, EHR-enabled trials have shown promising results in various fields. The article emphasizes the importance of careful planning, monitoring, and validation of data in EHR-enabled trials to ensure accurate and reliable results. It also discusses the potential benefits and limitations of EHR-enabled trials in improving patient care. [Extracted from the article]

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal‐regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine‐induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p‐ERK in the spinal cord in a dry skin mouse model induced by acetone–ether–water (AEW). q‐PCR, Western blot, pharmacology and immunofluorescence were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c‐Fos and p‐ERK expression in the spinal cord neurons were increased and co‐labelled with GRPR‐positive neurons in AEW mice. Furthermore, H4R agonist 4‐methyhistamine dihydrochloride (4‐MH)induced itch. Both 4‐MH‐induced itch and the spontaneous itch in AEW mice were blocked by p‐ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p‐ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW‐induced dry skin mice. [ABSTRACT FROM AUTHOR]

Esophageal and gastric varices (EGV) bleeding is a dangerous side effect of liver cirrhosis. Ascites may affect the effectiveness of carvedilol in preventing EGV rebleeding. A retrospective analysis was done on patients with EGV bleeding who visited our gastroenterology department between January 1, 2015, and October 29, 2020, and were given carvedilol therapy again. Patients were classified based on whether they had ascites. The primary outcome was EGV rebleeding. A total of 286 patients were included, with a median follow‐up of 24.0 (19.0–42.0) months, comprising those without ascites (N = 155) and those with ascites (N = 131). The mean age of the patients was 55.15 ± 12.44 years, and 177 (61.9%) of them were men. There were 162 (56.6%) Child‐Pugh A grades. The etiology of cirrhosis included 135 (47.2%) cases of hepatitis B. After carvedilol therapy, the patient's portal vein diameter (DPV) was widened (p < 0.05), velocity of portal vein (VPV) was slowed (p = 0.001). During the 1‐year follow‐up, patients with ascites had a substantially higher rebleeding rate than patients without ascites, with 24 (18.3%) versus 13 (8.4%), respectively (p = 0.013). On univariate analysis, ascites was a risk factor for rebleeding (p = 0.015). The multivariate analysis remained significant after adjusting for age, gender, etiology of cirrhosis, and previous endoscopic treatment, with OR of 2.37 (95% CI: 1.12–5.04; p = 0.025). Ascites was a risk factor for EGV rebleeding in patients undergoing carvedilol therapy. After carvedilol therapy, the patient's DPV was widened and VPV was slowed. [ABSTRACT FROM AUTHOR]

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

Background/Aim: The prognostic impact of the administration of antibiotics and proton pump inhibitors (PPIs) in immune checkpoint inhibitor (ICI) therapy for advanced cancer has recently been documented. However, how these drugs affect the outcomes of first-line ICI combination therapy for advanced renal cell carcinoma (RCC) remains unclear. Patients and Methods: We retrospectively evaluated the data of 128 patients with RCC who received first-line ICI combination therapy. The patients were grouped according to their history of antibiotics and PPIs use one month before the initiation of ICI combination therapy. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after ICI combination therapy were compared between patients treated with and without antibiotics or PPIs. Results: Of the 128 patients, 30 (23%) and 44 (34%) received antibiotics and PPIs, respectively. Patients treated with antibiotics exhibited shorter PFS and OS compared to those who did not receive antibiotics (median PFS: 4.9 vs. 16.1 months, p<0.0001; OS: 20.8 vs. 49.0 months, p=0.0034). Multivariate analyses showed that antibiotic administration was an independent predictor of shorter PFS (hazard ratio: 2.54: p=0.0002) and OS (hazard ratio: 2.56: p=0.0067) after adjusting for other covariates. In contrast, there were no significant differences in either PFS or OS between patients who received PPIs and those who did not. (PFS: p=0.828; OS: p=0.105). Conclusion: Antibiotics administration before ICI combination therapy was negatively associated with outcomes of first-line ICI combination therapy for advanced RCC. Therefore, careful monitoring is required for potentially high-risk patients undergoing ICI combination therapy. [ABSTRACT FROM AUTHOR]

Background: Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. Objectives: This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. Design: A systematic review and network meta-analysis. Data sources and methods: Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. Results: In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. Conclusion: This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. Trial registration: The study protocol was registered with INPLASY (registration number INPLASY2023120053). Plain language summary: A review and network meta-analysis of different medications for treating erosive esophagitis: potassium-competitive acid blockers and proton-pump inhibitors Why was the study done? Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are commonly used to treat Erosive esophagitis (EE) due to their good safety and tolerance. This study aimed to compare the effectiveness of P-CABs and PPIs in healing EE patients. We wanted to determine the best treatment choice in terms of the duration of treatment (4 or 8 weeks) and the dosage (standard or double-dose). What did the researchers do? The researchers searched relevant databases for randomized controlled trials that studied the use of PPIs and P-CABs in treating EE up until May 31, 2023. They included studies that evaluated the healing effects of standard or double-dose PPIs or P-CABs over a period of 4 or 8 weeks. A network meta-analysis was performed to compare the effectiveness of these treatments. They also conducted sensitivity analysis and subgroup analysis to examine the effects on patients with different levels of EE. What did the researchers find? The results showed that the healing rate after 4 weeks of treatment was significantly lower than the healing rate after 8 weeks for most treatments. Additionally, the higher healing rate observed with double-dose treatment compared to standard-dose treatment was not seen in the initial treatment of most drugs. In the main analysis, which included studies with patients both with and without severe EE at the beginning, Keverprazan 20mg qd was ranked as the most effective treatment with a healing rate of 84.7, followed by Ilaprazole 10mg qd with a healing rate of 82.0 at 8 weeks. The results were robust in sensitivity analysis. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, especially for patients with severe EE. What do the findings mean? Treating EE patients for 8 weeks was more effective than treating them for 4 weeks. Keverprazan (20mg once a day) with the 8-week treatment is the optimal method. [ABSTRACT FROM AUTHOR]

The plant health status is determined by the interplay of plant-pathogen-microbiota in the rhizosphere. Here, we investigate this tripartite system focusing on the pathogen Fusarium oxysporum f. sp. lycopersici (FOL) and tomato plants as a model system. First, we explore differences in tomato genotype resistance to FOL potentially associated with the differential recruitment of plant-protective rhizosphere taxa. Second, we show the production of fusaric acid by FOL to trigger systemic changes in the rhizosphere microbiota. Specifically, we show this molecule to have opposite effects on the recruitment of rhizosphere disease-suppressive taxa in the resistant and susceptible genotypes. Last, we elucidate that FOL and fusaric acid induce changes in the tomato root exudation with direct effects on the recruitment of specific disease-suppressive taxa. Our study unravels a mechanism mediating plant rhizosphere assembly and disease suppression by integrating plant physiological responses to microbial-mediated mechanisms in the rhizosphere. The phytotoxin fusaric acid produced by the phytopathogen Fusarium oxysporum f. sp. lycopersici results in a differential assembly of the rhizosphere microbiota of resistant and susceptible genotypes with implication for disease suppression. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to estimate the prevalence of potentially inappropriate prescriptions (PIPs) in patients starting their first noninsulin antidiabetic treatment (NIAD) using two explicit process measures of the appropriateness of prescribing in UK primary care, stratified by age and polypharmacy status. Methods: A descriptive cohort study between 2016 and 2019 was conducted to assess PIPs in patients aged ≥45 years at the start of their first NIAD, stratified by age and polypharmacy status. The American Geriatrics Society Beers criteria 2015 was used for older (≥65 years) patients and the Prescribing Optimally in Middle‐age People's Treatments criteria was used for middle‐aged (45‐64 years) patients. Prevalence of overall PIPs and individual PIPs criteria was reported using the IQVIA Medical Research Data incorporating THIN, a Cegedim Database of anonymized electronic health records in the UK. Results: Among 28 604 patients initiating NIADs, 18 494 (64.7%) received polypharmacy. In older and middle‐aged patients with polypharmacy, 39.6% and 22.7%, respectively, received ≥1 PIP. At the individual PIP level, long‐term proton pump inhibitors (PPI) use was the most frequent PIP among older adults, and strong opioid without laxatives was the most frequent PIP in middle‐aged patients with polypharmacy (11.1% and 4.1%, respectively). Conclusions: This study revealed that patients starting NIAD treatment receiving polypharmacy have the potential for pharmacotherapy optimization. [ABSTRACT FROM AUTHOR]

Purpose: Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. Methods: Four types of SSTR antagonists were utilized, including [68Ga]Ga-NODAGA-LM3, [68Ga]Ga-DOTA-LM3, [68Ga]Ga-NODAGA-JR11, and [68Ga]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [68Ga]Ga-DOTATATE. Results: A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [68Ga]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [68Ga]Ga-DOTATATE (40.1 ± 32.5 vs. 39.4 ± 23.8, p = 0.772). While [68Ga]Ga-NODAGA-LM3 showed significantly higher uptake than [68Ga]Ga-DOTATATE (57.4 ± 38.5 vs. 40.0 ± 22.8, p<0.001), [68Ga]Ga-NODAGA-JR11 (39.7 ± 26.5 vs. 34.3 ± 23.9, p = 0.108) and [68Ga]Ga-DOTA-LM3 (38.9 ± 32.1 vs. 37.2 ± 22.1, p = 0.858) showed comparable uptake to [68Ga]Ga-DOTATATE, and [68Ga]Ga-DOTA-JR11 showed lower uptake (28.9 ± 26.1 vs. 44.0 ± 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [68Ga]Ga-DOTATATE (12.1 ± 10.8 vs. 5.2 ± 4.5, p<0.001). Conclusion: Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [68Ga]Ga-NODAGA-LM3 seems to have the best imaging profile. [ABSTRACT FROM AUTHOR]

Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs. [ABSTRACT FROM AUTHOR]

Background Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via transient receptor potential melastatin 8 (TRPM8) agonism have shown potential in itch management. However, animal studies on itch have limitations, as animals cannot communicate subjective events and their fur-coated skin differs from that of humans. Human studies offer more direct and reliable information. Objectives To investigate the effects of a specific TRPM8 agonist gel (cryosim-1) on itch induced by various pruritogens in human skin. Methods Calcium imaging experiments determined the binding of cryosim-1 and histamine to their respective receptors. Thirty healthy volunteers underwent skin prick tests with pruritogens and a control vehicle. Itch and pain intensity were measured using a numerical rating scale (NRS) across 10 min. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated at a later date, and skin moisture, transepidermal water loss and mechanical sensitivity were measured. Results The in vitro study confirmed that histamine is not a TRPM8 agonist and cryosim-1 does not act as an agonist or antagonist on the human histamine 1 receptor. The TRPM8 agonist gel significantly reduced the itch intensity for all pruritogens compared with the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced. Conclusions The specific TRPM8 agonist gel effectively suppressed human skin itch induced by various pruritogens. These versatile actions suggest that cooling agents may be promising treatments for multiple forms of itch stimuli. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. : We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. : Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. : Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant Campylobacter jejuni and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID. [ABSTRACT FROM AUTHOR]

Background: The coccoid form of Helicobacter pylori (H. pylori) is resistant to antibiotics. There are only a few studies that have analyzed the frequency of coccoid H. pylori in patients with gastritis. The aim of this work was to examine the correlation between the H. pylori form and the pathohistological characteristics of the stomach in patients with gastritis. Materials and methods: This research was cross-sectional and focused on the gastric mucosa samples of 397 patients from one general hospital in Croatia. Two independent pathologists analyzed the samples regarding the pathohistological characteristics and the form of H. pylori. Results: There was a statistically significant difference in the gender of patients with H. pylori gastritis. Only the coccoid form of H. pylori was present in 9.6% of patients. There was a statistically significant difference in the frequency of a certain form of the bacterium depending on its localization in the stomach. The intensity of the bacterium was low in the samples where only the coccoid or spiral form was described. In cases of infection in the antrum, premalignant lesions and the coccoid form of H. pylori were more often present. Conclusion: In the diagnosis of H. pylori infection, the determination of the form of the bacterium via immunohistochemistry should be included to increase the rate of eradication therapy and reduce the incidence of gastric malignancy. [ABSTRACT FROM AUTHOR]

BACKGROUND: National guidelines no longer recommend adults 60 years of age and older to begin treatment with low-dose daily aspirin for primary prevention of atherosclerotic cardiovascular disease (CVD) due to a lack of proven net benefit and a higher risk of bleeding. OBJECTIVE: The objective of this cross-sectional retrospective analysis was to evaluate the appropriateness of low-dose aspirin prescribing and subsequent gastrointestinal bleeding in older persons receiving primary care in a large academic health system. SETTING: Large, academic health system within Colorado. PATIENTS: Patients with an active order for daily low-dose aspirin as of July 1, 2021, were assessed for appropriateness based on indication (primary vs secondary prevention) and use of a concomitant proton-pump inhibitor (PPI). Incident gastrointestinal bleeds (GIBs) in the subsequent 12 months and GIB risk factors were also evaluated. RESULTS: A total of 19,525 patients were included in the analysis. Eighty-nine percent of patients identified as White and 54% identified as male. Of the total cohort, 44% had CVD and 19% were co-prescribed a PPI. GIB occurred in 247 patients (1.27%) within the subsequent year. Risk factors significantly associated with a GIB within 1 year included: history of GIB, history of peptic ulcer disease, other esophageal issue (esophagitis, Barrett's esophagus, Mallory Weiss tears, etc.), 75 years of age or older, and history of gastroesophageal reflux disease. CONCLUSION: This evaluation found that many older persons at this institution may be inappropriately prescribed aspirin, providing opportunities for pharmacists to improve medication safety by deprescribing aspirin among primary prevention patients or potentially co-prescribing a PPI in secondary prevention patients. [ABSTRACT FROM AUTHOR]

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