Proton Pump Research Articles

Agreement of Different Drug-Drug Interaction Checkers for Proton Pump Inhibitors

ImportanceProton pump inhibitors (PPIs) are a widely prescribed class of drugs, potentially interacting with a large number of medicines, especially among older patients with multimorbidity and polypharmacy. Beyond summary of product characteristics (SPCs), interaction checkers (ICs) are routinely used tools to help clinicians in medication review interventions.ObjectiveTo assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs.Design, Setting, and ParticipantsThis cross-sectional study was conducted using data from SPCs for 5 PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) and 5 ICs (ie, INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com). Information from the SPCs and the ICs were extracted between July 15 and 30, 2023.Main Outcomes and MeasuresThe main outcome was the level of agreement among SPCs and the 5 ICs in identifying drugs potentially interacting with PPIs and attributing drug-drug interaction (DDI) severity categories. The level of agreement was computed using Gwet AC1 statistic on the 5 ICs and by comparing 4-sets and 2-sets of ICs. As a sensitivity analysis, the level of agreement in listing PPI-related DDIs was evaluated using Cohen κ and Fleiss κ coefficients.ResultsConsidering SPCs and the 5 ICs, a total of 518 potentially interacting drugs with omeprazole were reported, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. As compared with the ICs, the SPCs reported a much smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% (11 potentially interacting drugs) for rabeprazole to 7.6% (33 potentially interacting drugs) for lansoprazole of the total identified drugs at risk of interaction with a PPI. The overall level of agreement among the 5 ICs for identifying potential interactions was poor (from 0.23 [95% CI, 0.21-0.25] for omeprazole to 0.27 [95% CI, 0.24-0.29] for pantoprazole and 0.27 [95% CI, 0.25-0.29] for rabeprazole). Similarly, the level of agreement was low in 4-set and 2-set analyses as well as when restricting the analysis to the potential DDIs identified as severe (range, 0.30-0.32).Conclusions and RelevanceThis cross-sectional study found significant disagreement among different ICs and SPCs, highlighting the need to focus on standardizing DDI databases. Therefore, to ensure evaluation and prevention of clinically relevant DDIs, it is recommended to revise multiple ICs and consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions.

Prognostic Impact of the Administration of Antibiotics and Proton Pump Inhibitors in Immune Checkpoint Inhibitor Combination Therapy for Advanced Renal Cell Carcinoma.

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. 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. 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). 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.

Greenness and practicability assessment of a new HPLC-DAD method for simultaneous determination of three drugs used for a triple-therapy regimen for helicobacter pylori and application to a pharmacokinetic study

Improving the environmental friendliness of laboratory procedures has become very strongly recommended. In this research, several metric tools evaluating the analytical methods, including eco-scale, analytical greenness calculator (AGREE), green analytical procedure index (GAPI), red–green–blue software (RGB) and blue applicability grade index (BAGI) have been used to assess the greenness, performance and practicality of a new useful HPLC-DAD method. The main cause of peptic ulcers and the problems that follow is Helicobacter pylori. Due to the bacteria’s high resistance, different medications are co-administered to overcome the resistance and manage the symptoms. Two antibiotics are mostly used to decrease bacterial resistance in addition to proton pump inhibitors. Pantoprazole, Levofloxacin, and Amoxicillin are co-administered in a triple therapy regimen for suppressing Helicobacter pylori. In this work, the first-time simultaneous estimation of the three medications in rat plasma has been designed and utilized to investigate pharmacokinetics using a new HPLC method with outstanding greenness and practicability. The method involved using a C18 analytical column with an eluent of acetonitrile: 0.03 M Na2HPO4 buffer (20: 80, v/v) of 1.5 mL min−1 flow rate. Oxytetracycline was used as an internal standard and the drugs were determined at 230 nm. The validation protocol was adopted according to FDA instructions, and the results proved the ability of the new method to estimate the three medications in rat plasma.

Drug-Associated Acute Kidney Disease: Data From a World Pharmacovigilance Database.

Background Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS)developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.

The V-ATPase/ATG16L1 axis is controlled by the V1H subunit

Defects in organellar acidification indicate compromised or infected compartments. Recruitment of the autophagy-related ATG16L1 complex to pathologically neutralized organelles targets ubiquitin-like ATG8 molecules to perturbed membranes. How this process is coupled to proton gradient disruption is unclear. Here, we reveal that the V1H subunit of the vacuolar ATPase (V-ATPase) proton pump binds directly to ATG16L1. The V1H/ATG16L1 interaction only occurs within fully assembled V-ATPases, allowing ATG16L1 recruitment to be coupled to increased V-ATPase assembly following organelle neutralization. Cells lacking V1H fail to target ATG8s during influenza infection or after activation of the immune receptor stimulator of interferon genes (STING). We identify a loop within V1H that mediates ATG16L1 binding. A neuronal V1H isoform lacks this loop and is associated with attenuated ATG8 targeting in response to ionophores in primary murine and human iPSC-derived neurons. Thus, V1H controls ATG16L1 recruitment following proton gradient dissipation, suggesting that the V-ATPase acts as a cell-intrinsic damage sensor.

Enhanced interlayer interaction in sulfonated CONs membrane by amino-rich CONs enabling ultrafast proton transport

Covalent organic framework nanosheets (CONs) with porous crystalline features and ultrathin thickness are ideal candidates as membrane building blocks to form well-defined transfer nanochannels. The formidable challenge behind self-supporting CONs membrane lies in weak non-covalent interlayer interactions and thus loose stacking, insufficient strength and structure stabilities. Herein, we propose the fabrication of interlayer force-strengthened freestanding CONs membrane through the electrostatic attraction bridge effect of positively-charged amino-rich CONs (CON–NH2) to negatively-charged sulfonated CONs (CON–SO3H). Ultrathin and large lateral sized CON–SO3H and CON–NH2 are synthesized, followed by restacking to prepare freestanding CONs membrane with CON–SO3H as the membrane bulk. Benefiting from effective interlayer interconnection due to strong electrostatic interaction, the obtained CON–SO3H/CON–NH2 membrane displays features of ultrahigh integrity, dense stacking, eminent water/acid/base/organic solvents stabilities and mechanical strength (109 MPa). The shortened –SO3H distance contributes to construct site-continuous transfer pathways, and the deprotonated –SO3H and protonated –NH2 form acid–base pairs to decrease interfacial resistance, which impart membrane superior proton conductivity of 486 mS cm−1 (80 °C, 100% RH). This interlayer force enhancement strategy offers a promising perspective on achieving densely-stacked CONs membrane with ultrahigh mechanical property and conduction performance for fuel cell application.

Ethylenediamine tetramethylenephosphonic acid boosting the electrocatalytic interface construct and proton transfer for high-temperature polymer electrolyte membrane fuel cells

High-temperature polymer electrolyte membrane fuel cells (HT-PEMFCs) show excellent application prospects due to its enhanced tolerance of hydrogen impurity. However, the sluggish electrode kinetics caused by its inefficient electrocatalytic interface and proton transfer severely restricts its performance. To overcome the sluggish electrode kinetics, the ethylenediamine tetramethylenephosphonic acid (EDTMPA) was successfully incorporated into the catalysts layer to regulate the phosphoric acid (PA) distribution to boost the electrocatalytic reaction interface and proton transfer, thus increasing the output power and stability of HT-PEMFCs. The hydrophilic H2PO4− and electron donor N atom of EDTMPA could efficiently decrease the absorption of PA on the catalyst surface and facilitate proton transportation in the membrane electrode, as demonstrated by our experiments. The fuel cell assembled with the prepared membrane electrode shows a high reactivity of 1175 mW cm−2 and excellent stability, which is much better than the past reference report. The results of this work provide new insights into the utilization of small molecules with phosphate groups to enhance phosphate tolerance and proton conduction, and there is also a further improvement in the reactivity, durability, and utilization of the electrocatalysts in HT-PEMFCs.

Electrical properties and transport numbers of yttrium and gadolinium co-doped BaCe0.5Zr0.3Y0.2-xGdxO3-δ proton-conducting electrolyte

BaCe0.5Zr0.3Y0.2-xGdxO3-δ (x = 0, 0.05, 0.1) proton-conducting electrolyte materials co-doped with Y (yttrium) and Gd (gadolinium) were successfully synthesized by solid-state reaction method. The influence of Gd concentration on the phase composition, chemical stability, and electrical conductivity of BaCe0.5Zr0.3Y0.2-xGdxO3-δ (BCZYGx, x = 0, 5, and 10) materials were systematically investigated under different atmospheres within the temperature range of 500-800 ºC. The BCZYG5 material presents enhanced chemical stability and conductivity in comparison to the pristine BZCY. Electrochemical impedance spectra analysis using the distribution of relaxation times (DRT) and equivalent circuit scheme (ECS) methods revealed that BCZYG5 demonstrates a maximum electrical conductivity of 8.90×10-3 S·cm-1 at 800 °C under 20% O2 and 4.51 kPa H2O. The defect equilibrium model was employed to calculate the partial conductivity and transport numbers. The results indicate a decrease in proton transport numbers with rising temperature, while oxygen ion and electron-hole transport numbers increase. The doping of Gd inhibits electron conduction in both the BCZYG5 and BCZYG10, as illustrated by the map of the dominant region of each carrier. This study will serve as a reference for future research.

Evaluation of first hospital entry and hospitalization related prescription polypharmacy targeting patients of fifty years old and more at a general hospital, Duhok, Iraq

Background: Polypharmacy is the intake of ≥ 5 medications. This study evaluates the prevalence of polypharmacy among elderly patients hospitalized during October 2023 at Azadi Hospital in Duhok, Iraq. Methods: This was a retrospective cross-sectional study. The files of 373 patients aged ≥ 50 years were reviewed for the occurrence of polypharmacy (5 medications), major polypharmacy (6-9 medications) and excessive polypharmacy (≥ 10 medications) as well as their disease conditions. Results: The 373 patients received 5 to 10 medications at first hospital entry, and during hospitalization (1-29 days), 220 (58.98%) of them received 5 to 12 medications. Cardiovascular disorders (44.04%) were the most encountered conditions in the hospitalized patients, followed by endocrine disorders (26.4%) and gastrointestinal disorders (8.14%). Polypharmacy occurred in 63 (16.89%) patients on the first day of hospital entry and in 73 (19.57%) during the hospitalization period. Major and excessive polypharmacy occurred among 90 (24.13%) and 2 (0.54%) of patients at the first entry and among 129 (34.58%) and 18 (4.83%) patients during the hospitalization, respectively. During hospitalization, polypharmacy significantly (Chi squared=22.655; df=1; p=1.9387˟10-6) increased by 17.43% when compared to that of the first hospital entry. The most commonly used medications at the first hospital entry were paracetamol (17.18%) followed by antibiotics (11.8%). During hospitalization the most commonly used medications were antibiotics (13.52%) followed by proton pump inhibitors (11.43%). Conclusion: The prevalence of polypharmacy was high among elderly hospitalized patients. This condition might increase the risk of potential drug-drug interaction and the intake of inappropriate medications. Alerting clinicians about the significance of polypharmacy is necessary in prescribing and deprescribing medications to hospitalized elderly patients.

Genetic Markers of Helicobacter pylori Resistance to Clarithromycin and Levofloxacin in Moscow, Russia.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To address the need to develop test systems for personalized drug selection, this study was designed to analyze the molecular resistance of H. pylori using a newly developed Sanger sequencing test platform. The characteristics of the test system were determined on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100% and those to levofloxacin were 93% and 92%, respectively. The test system has been tested in real clinical practice on 112 H. pylori-positive patients who had not previously received proton pump inhibitors (PPIs) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples and those indicating resistance to levofloxacin were found in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G and to levofloxacin resistance-261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help to avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

Proton Transport through Ice Nanoribbons

Proton Transport through Ice Nanoribbons

Clinical case of funicular myelosis in combination with a concomitant genetic predisposition to folate cycle disorder

Funicular myelosis (sub­acute combined degeneration) is a disease characterized by the development of degeneration of the posterior and lateral cords of the spinal cord. Funicular myelosis is a neurological complication of vitamin B12 deficiency, which occurs as a result of reduced intake of vitamin B12 with food, malabsorption, in connection with taking some drugs (metformin, proton pump inhibitors, and nitrous oxide), with invasion by Diphyllobothrium latum. The disease is usually characterized by the presence of paresthesias, the development of sensitive ataxia, and impaired gait. The aim of the work was to demon­strate a clinical case of funicular myelosis in a young patient in order to improve the diagnostic process, paying attention to the genetic profile and identifying a concomitant predisposition to folate cycle disorder. A clinical case of funicular myelosis in a 39-year-old woman is described. The patient came to the neurology department with complaints of numbness in the upper and lower limbs, periodic shooting pains along the spine when the head is tilted forward. During the neurological examination, the following was observed: a decrease in vibrational, muscle-joint, discrimination sensitivity in the upper limbs, paresthesias in the distal parts of the limbs, and sensitive ataxia. According to the results of the magnetic resonance imaging (MRI) of the spinal cord, a lesion of the posterior cords on the long segment (C2-Th1) was found, which corresponds to the subacute degeneration of the spinal cord, which arose due to the deficiency of holotranscobalamin (active B12). The patient received appropriate treatment and was discharged home. Subsequently, the patient was found to have a concomitant genetic predisposition to folate cycle disorder and the development of thrombophilia. A year later, the woman again came to the neurological department. We carried out a repeated examination, evaluation of the results of the MRI of the cervical spine and other examinations in dynamics. According to the results of the literature analysis, additional markers for the diagnosis of funicular myelosis (in particular, homocysteine), the causes of hyper­homocysteinemia and its effects on the body were described. Timely detection and treatment of vitamin B12 deficiency is quite important, since in severe cases the development of spastic paraplegia is possible. Recovery of lost functions depends on the extent of spinal cord damage and the duration of the disease. If anemia is observed together with neurological symptoms, it is necessary to be especially attentive to possible funicular myelosis and to carry out appropriate diagnostic searches. And when detecting hyperhomocysteinemia, it is advisable to take into account other factors that can cause an increase in the level of homocysteine, in addition to a deficiency of vitamins B6, B12 and folic acid.

Elderly Care: Commonly Prescribed Gastrointestinal Drugs Associate With Cognitive Decline

Background — Gastrointestinal (GI) medications are among the most common drugs used in old age. Recent studies reported heterogeneous association between proton pump inhibitors (PPIs) with neurological complications such as memory impairment. Objective — This research was conducted to assess the effect of different categories of GI drugs on cognitive function of older adults. Methods — This case-control study was carried-out on adults 60 or more years of age and over living in Amirkola, northern Iran, where health-related data were available in the database of the second phase of the Amirkola Health and Ageing Cohort Project (AHAP). Cognitive function of the elderly was examined with the Mini-Mental State Examination (MMSE) screening test. Results — Among 900 examined individuals, total intake of GI medications exhibited no significant effect on cognitive function of older adults [adjusted OR:1.049 (95% CI: 0.757-1.452); p=0.775]; however, a statistically significant effects of PPIs [adjusted OR=1.571 (1.001-2.467); p=0.050) and medicinal drugs affecting GI tract movements [adjusted OR=2.202 (1.180-4.111); p=0.013) on cognitive function were observed. Conclusion — Although total intake of GI medications did not cause a statistically significant impact on cognitive function of older adults, PPIs and medicinal drugs affecting GI tract movements had a significant effect.

Proton Pump Inhibitors and Risk of COVID-19 Infection in Children

To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children. This retrospective, case-control study included all children ≤21years undergoing COVID-19 polymerase chain reaction testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes. 116 209 patients age 8.5±6.2years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P=.002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P=.77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P=.26]. We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.

Molecular transport enhancement in pure metallic carbon nanotube porins.

Nanofluidic channels impose extreme confinement on water and ions, giving rise to unusual transport phenomena strongly dependent on the interactions at the channel-wall interface. Yet how the electronic properties of the nanofluidic channels influence transport efficiency remains largely unexplored. Here we measure transport through the inner pores of sub-1 nm metallic and semiconducting carbon nanotube porins. We find that water and proton transport are enhanced in metallic nanotubes over semiconducting nanotubes, whereas ion transport is largely insensitive to the nanotube bandgap value. Molecular simulations using polarizable force fields highlight the contributions of the anisotropic polarizability tensor of the carbon nanotubes to the ion-nanotube interactions and the water friction coefficient. We also describe the origin of the proton transport enhancement in metallic nanotubes using deep neural network molecular dynamics simulations. These results emphasize the complex role of the electronic properties of nanofluidic channels in modulating transport under extreme nanoscale confinement.

Single-Arm, Prospective, Interventional Study of Helicobacter pylori Eradication Rescue Therapy with Rifabutin, Metronidazole, and Vonoprazan.

Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%-86.0%) and 72.2% (95% CI: 50.2%-88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%-100%) and 100% (90% CI: 65.2%-100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%-88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

Physicians' perceptions and awareness of adverse effects of proton pump inhibitors and impact on prescribing patterns.

Background: Heightened scrutiny surrounds the inappropriate use of proton pump inhibitors (PPIs) due to concerns regarding potential serious adverse effects (AEs). Understanding the impact of these AEs on real-world practice is crucial. This study aimed to assess physicians' perceptions, experiences, awareness, and beliefs regarding published data on potential AEs associated with PPIs. Additionally, it sought to determine alterations in PPI prescribing patterns resulting from these AEs, explore attitudes towards PPI use, and ascertain recommendations for PPI use in clinical scenarios with varying levels of risk for upper gastrointestinal bleeding (UGIB). Method: A quantitative, cross-sectional study utilized a self-administered questionnaire, inviting 282 physicians from 55 primary healthcare centers and 334 internal medicine physicians from seven governmental hospitals to participate. Results: With a response rate of 87.8% (541/616), 74% (95% CI: 70.2-77.7) of respondents were somewhat or very familiar with published data on PPI AEs. Among the familiar, 69.5% (CI: 65.2-73.5) had somewhat or very much changed their PPI prescribing patterns. General concerns about AEs when prescribing PPIs were reported by 62% (CI: 56.7-65.1). Respondents displayed awareness of a median (IQR) of 15 (9) different AEs associated with long-term PPI use, including osteoporosis or osteopenia (90.2%), hypomagnesemia (81.5%), vitamin B12 deficiency (80.6%), and bone fracture (80.0%). Respondents believed that PPIs elevate the risk for a median (IQR) of 7 (6) different AEs, with osteoporosis or osteopenia (81.8%) being the most common, followed by hypomagnesemia (67.1%), and vitamin B12 deficiency (62.3%). The most common strategies for PPI de-escalation were PPI discontinuation (61%) and using PPI on-demand/as-needed (57.9%). The majority (87.4%) agreed or strongly agreed that PPI overuse is prevalent in Kuwait and 78.2% emphasized the necessity for large-scale education on rational PPI use for medical staff and the public. In the UGIB prevention scenarios, 43.6% recommended appropriately the PPI discontinuation in the minimal-risk scenario, while 56% recommended appropriately the PPI continuation in the high-risk scenario. Associations and comparative analyses revealed predictors influencing physicians' practices and attitudes toward PPI usage. Conclusion: These findings lay the foundation for future research and targeted interventions aimed at optimizing PPI prescribing practices and ensuring patient safety.

Interconnection between injectable omeprazole and clopidogrel tablet: a comprehensive analysis of clinical and pharmacological implications

Therapeutic synergy is a sought-after goal in contemporary medical practice, aiming to maximize therapeutic benefits while minimizing pharmacological adverse effects (Chowdhury et al., 2020). However, the drug interaction between injectable omeprazole and clopidogrel tablet emerges as a crucial clinical and pharmacological concern. Clopidogrel, a widely used antiplatelet agent in cardiovascular event prevention, and omeprazole, a proton pump inhibitor often prescribed for gastrointestinal disorders, are frequently co-administered in patients with elevated cardiovascular risk (Bhurke et al., 2018). Nevertheless, recent studies suggest that this combination might compromise the antiplatelet efficacy of clopidogrel due to potential pharmacokinetic and pharmacodynamic interactions.

Role of prescribed medication in the development of iron deficiency anaemia in adults—a case–control study

ObjectiveTo estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA), specifically considering oral anticoagulants (OACs), antidepressants, antiplatelet...

Cobra Venom Cytotoxins as a Tool for Probing Mechanisms of Mitochondrial Energetics and Understanding Mitochondrial Membrane Structure.

In this paper, we provide an overview of mitochondrial bioenergetics and specific conditions that lead to the formation of non-bilayer structures in mitochondria. Secondly, we provide a brief overview on the structure/function of cytotoxins and how snake venom cytotoxins have contributed to increasing our understanding of ATP synthesis via oxidative phosphorylation in mitochondria, to reconcile some controversial aspects of the chemiosmotic theory. Specifically, we provide an emphasis on the biochemical contribution of delocalized and localized proton movement, involving direct transport of protons though the Fo unit of ATP synthase or via the hydrophobic environment at the center of the inner mitochondrial membrane (proton circuit) on oxidative phosphorylation, and how this influences the rate of ATP synthesis. Importantly, we provide new insights on the molecular mechanisms through which cobra venom cytotoxins affect mitochondrial ATP synthesis, mitochondrial structure, and dynamics. Finally, we provide a perspective for the use of cytotoxins as novel pharmacological tools to study membrane bioenergetics and mitochondrial biology, how they can be used in translational research, and their potential therapeutic applications.