Proton Pump Inhibitors Research Articles

Pharmacological management of osteoarthritis: judicious use of nonsteroidal anti-inflammatory drugs

Background: Osteoarthritis (OA) is a chronic disease characterized by persistent pain and joint deformation. Effective pain management in patients with OA necessitates accurate diagnosis and appropriate treatment planning, considering the prolonged therapy required for OA. Although non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management in patients with OA, their long-term use can lead to various adverse effects that warrant careful consideration.Current Concepts: NSAIDs inhibit cyclo-oxygenase (COX) enzymes and produce an anti-inflammatory and analgesic effect. However, this mechanism of action can produce adverse gastrointestinal, cardiovascular, and renal effects. The relative risk of gastrointestinal and cardiovascular adverse events depends on the COX selectivity of NSAIDs. Consequently, selective COX-2 inhibitor or concomitant proton pump inhibitor administration is recommended in patients at a high risk of gastrointestinal complications. Minimizing NSAID use is advised in patients at a high risk of cardiovascular adverse events; however, if this is unavoidable, short-term administration of naproxen or low-dose celecoxib should be considered. COX selectivity is not associated with adverse renal events. Therefore, acetaminophen is preferred in patients with impaired renal function, and short-term use of NSAID patches or topical formulations may be useful.Discussion and Conclusion: The choice of NSAIDs for OA should be tailored to patients’ needs, considering their risk factors, potential drug interactions, and other relevant factors. Additionally, incorporation of nonpharmacological interventions can minimize the NSAID dosage and reduce the risk of adverse effects, and regular monitoring is essential to identify adverse effects.

Hibiscus sabdariffa as a Novel Alternative Strategy Against Helicobacter pylori Infection Development to Gastric Cancer.

Most gastric cancers (95%) are related to an initial Helicobacter pylori infection worldwide. Treatments against this pathogen include a mix of antibiotics, antimicrobials, and proton-pump inhibitors. Over time, H. pylori mutated, generating resistance to treatments and making it hard to combat its infection. The purpose of this review is Hibiscus sabdariffa, commonly known as hibiscus, as a potential agent for anti-H. pylori activity. Scientific interest has increased toward plant-derived bioactive compounds, which have the ability to enhance the antibiotic effect and can lead to the development of new drugs, such is the case for H. sabdariffa. In general, studies show that natural products, such as plant-derived bioactive compounds, can be used as alternative treatments from natural origin against the pathogen. The specific action mechanism of these bioactive compounds is still controversial, but it is suggested that they have an anti-inflammatory effect, and they also act as antibiotic coadjutants. Research has been conducted regarding different bioactive compounds such as polyphenols, epicatechins, alkaloids, and caryophyllenes. H. sabdariffa contains several of these compounds; therefore, more studies are needed to establish its effect against H. pylori.

Design of a phase 3, randomized, double-blind, placebo-controlled, 48-week study to evaluate the efficacy and safety of cendakimab in adult and adolescent patients with eosinophilic esophagitis

BackgroundEosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory condition that interferes with normal food ingestion, negatively impacting quality of life (QoL). Treatment options include proton pump inhibitors, corticosteroids, biologics, or dietary elimination; however, ∼1/3 of patients remain insufficiently controlled. The pathogenesis of EoE involves interleukin-13 (IL-13); therefore, targeted IL-13 inhibition may be beneficial. In a phase 2 study, cendakimab, a recombinant, humanized anti–IL-13 monoclonal antibody, significantly reduced mean esophageal eosinophil counts and improved other inflammatory parameters in patients with EoE. These findings prompted further investigation of the efficacy and safety of cendakimab in adults and adolescents with EoE in a phase 3 registrational study (NCT04753697), the design of which is presented here. MethodsThis multicenter, multinational, randomized, double-blind, placebo-controlled, 48-week, treat-through study plans to enroll 399 adults and adolescents. Randomized patients (1:1:1) will receive subcutaneous administration of 1) cendakimab 360 mg once weekly (QW) for 48 weeks, 2) cendakimab 360 mg QW for 24 weeks followed by cendakimab 360 mg every other week (with matching placebo on alternative weeks to maintain the blind) for 24 weeks, or 3) placebo QW for 48 weeks. Co-primary endpoints are mean change from baseline in dysphagia days and proportion of patients with eosinophil histologic response, defined as peak esophageal eosinophil count ≤6 per high-power field, at 24 weeks. Secondary and exploratory endpoints will address endoscopic and histologic features, QoL, safety, and pharmacokinetic assessments. ConclusionThis phase 3 pivotal study will determine whether cendakimab provides an effective, safe, targeted treatment for patients with EoE.

Salivary microbiota composition before and after use of proton pump inhibitors in patients with laryngopharyngeal reflux: a self-control study

BackgroundIssues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study.MethodsThirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results.ResultsThe alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R2 = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter_gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples ( P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050).ConclusionsThese findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients.Chinese clinical trial registryNo. ChiCTR2300067507. Registered on January 10,2023 retrospectively.Level of evidence4.

Awareness, knowledge, and behaviour of Jordanian public regarding misuse and overuse of proton pump inhibitors

Awareness, knowledge, and behaviour of Jordanian public regarding misuse and overuse of proton pump inhibitors

Assessment of proton pump inhibitors utilization in intensivecare units patients of a tertiary care hospital in the United ArabEmirates

Assessment of proton pump inhibitors utilization in intensivecare units patients of a tertiary care hospital in the United ArabEmirates

Proton Pump Inhibitors and Oral-Gut Microbiota: From Mechanism to Clinical Significance.

Proton pump inhibitors (PPIs) are some of the most commonly prescribed drugs worldwide, but there are increasing concerns about digestive complications linked to PPIs. Next-generation sequencing studies have suggested that PPIs can significantly affect the composition of the gut microbiota, which in turn may substantially contribute to the development of these complications. Recently, emerging evidence has suggested that the translocation of oral microbes into the gut may be the primary mechanism underlying the alterations in the gut microbiota induced by PPIs in the presence of gastric acid suppression and impaired oral-gut barrier function. Moreover, the significance of oral-gut microbial translocation in health and disease conditions has gained increasing recognition. Consequently, it is imperative to enhance our understanding of the functions of the oral-gut microbiota axis in digestive disorders associated with PPI therapies. This review aims to summarize current research findings and further elucidate the contribution of the oral-gut microbiota to the pathogenesis of PPI-related digestive diseases. We aim to provide a theoretical foundation for future therapeutic and preventive strategies targeting PPI-related digestive complications through modulation of the oral-gut microbiota.

Deprescribing of proton pump inhibitors in older patients: A cost-effectiveness analysis.

Over-prescribing of proton-pump inhibitors (PPIs) is widely observed in older patients. Clinical findings have showed that deprescribing service significantly decreased inappropriate PPIs utilization. We aimed to examine the cost-effectiveness of PPI deprescribing service from the perspective of Hong Kong public healthcare provider. A decision-analytic model was constructed to examine the clinical and economic outcomes of PPI deprescribing service (deprescribing group) and usual care (UC group) in a hypothetical cohort of older PPI-users aged ≥65 years in the ambulatory care setting. The model inputs were retrieved from literature and public data. The model time-frame was one-year. Base-case analysis and sensitivity analysis were performed. Primary model outcomes were direct medical cost and quality-adjusted life-years (QALYs) loss. In base-case analysis, the deprescribing service (versus UC) reduced total direct medical cost by USD235 and saved 0.0249 QALY per PPI user evaluated. The base-case results were robust to variation of all model inputs in one-way sensitivity analysis. In probabilistic sensitivity analysis, the deprescribing group was accepted as cost-effective (versus the UC group) in 100% of the 10,000 Monte Carlo simulations. In conclusion, the PPI deprescribing service saved QALYs and reduced total direct medical cost in older PPIs users, and showed a high probability to be accepted as the cost-effective option from the perspective of public healthcare provider in Hong Kong.

8079 PPI Breaks a Leg! An Unusual Case of Atypical Femur Fracture

Abstract Disclosure: M. Sedghian: None. M. Flanagan: None. D. Pinkhasova: None. K. Selk: None. G. Moloney: None. Background: Atypical femur fractures (AFF) occur along the shaft of the femur extending from the subtrochanteric region proximally to the distal femoral metaphysis. These fractures have an increased incidence in patients taking bisphosphonates and denosumab for osteoporosis and develop as stress reactions in the lateral cortex of the femoral shaft (beaking). However, few cases that meet the characteristics of these fractures have occurred in patients who have never used antiresorptive drugs. We present a case with a history of long-term proton pump inhibitor (PPI) use and possible association with AFF. Clinical Case: The patient is a 68-year-old female with a past medical history of hypothyroidism who presented to the emergency department (ED) after an atraumatic femur fracture and consequently ground level fall. The patient reported experiencing a distinctive cracking sound in her femur while leaning over to wash her feet, resulting in a fall that prompted her to seek immediate care in the ED. Upon initial evaluation, radiographic imaging was significant for displaced left mid-femoral diaphyseal fracture and right femur lateral cortex thickening consistent with AFF. Labs were consistent with elevated PTH to 100.7 [18.4-80.1], Vit D2 1,25 (OH)2 &amp;lt;8 pg/mL, Vit D 25OH 34 ng/ml [30-100], and Calcium level of 9.5. Upon further history taking, the patient stated that she has been taking PPIs intermittently for more than 10 years. She denied a history of bisphosphonate and denosumab exposure, non-Hodgkin's lymphoma, rheumatoid arthritis, and COL1A2 variant mutations as main predisposing factors for atypical femur fractures. She had potential steroid exposure for less than a year before hospitalization as she was on "adrenal complex" from her functional medicine provider. The patient underwent open reduction and internal fixation of the left femur with placement of intramedullary nail and prophylactic fixation with placement of intramedullary nail of the right femur as there was radiographic evidence of beaking. Discussion/Conclusion: Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. Overall, PPIs are positively associated with elevated fracture risk in multiple studies. Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, decreasing bone turnover, impairing calcium absorption, and altering homocysteine levels through impairment of folate and vitamin B12 absorption.This case supports a potential association between long-term PPI use and atypical femur fractures. There have been other case reports that also highlight this potential risk of PPI use. This shows the importance of more comprehensive research on this topic as the number of patients on long-term PPIs is growing in outpatient settings. Presentation: 6/2/2024

Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease.

Breakthrough symptoms are thought to occur in roughly half of all gastroesophageal reflux disease (GERD) patients despite maximal acid suppression (proton pump inhibitor, PPI) therapy. Topical alginates have recently been shown to enhance mucosal defense against acid-pepsin insult during GERD. We aimed to examine potential alginate protection of transcriptomic changes in a cell culture model of PPI-recalcitrant GERD. Immortalized normal-derived human esophageal epithelial cells underwent pretreatment with commercial alginate-based anti-reflux medications (Gaviscon Advance or Gaviscon Double Action), a matched-viscosity placebo control, or pH 7.4 buffer (sham) alone for 1 min, followed by exposure to pH 6.0 + pepsin or buffer alone for 3 min. RNA sequencing was conducted, and Ingenuity Pathway Analysis was performed with a false discovery rate of ≤0.01 and absolute fold-change of ≥1.3. Pepsin-acid exposure disrupted gene expressions associated with epithelial barrier function, chromatin structure, carcinogenesis, and inflammation. Alginate formulations demonstrated protection by mitigating these changes and promoting extracellular matrix repair, downregulating proto-oncogenes, and enhancing tumor suppressor expression. These data suggest molecular mechanisms by which alginates provide topical protection against injury during weakly acidic reflux and support a potential role for alginates in the prevention of GERD-related carcinogenesis.

7686 A Case Of A 66-Year-Old Male With Systemic Macrocytosis Complicated By Osteoporosis

Abstract Disclosure: J.M. Gri: None. M. Hillhouse: None. P. madhavan: None. Background: Osteoporosis in men is underestimated and warrants investigation for secondary causes of osteoporosis. Systemic mastocytosis is a rare secondary cause of osteoporosis. Clinical Case: This is a 66-year-old male with a past medical history of severe persistent asthma, eczema, hypertension, GERD with esophagitis, basal cell carcinoma, and systemic mastocytosis (diagnosed in 2010). Family history was significant for lung cancer in both of his parents. Patient was first noted to have hyperpigmented skin lesions on his legs, trunk and upper extremities in the early 1990s. The spots were biopsied and he was diagnosed with urticaria pigmentosa in 1998. Due to persistent symptoms of facial flushing and soft stool, he was referred to Hematology and was started on antihistamines. He later underwent a bone marrow biopsy in 2010 which showed multifocal mast cell aggregates but normal trilineage hematopoiesis. He endorsed back pain shortly after his diagnosis and a DXA scan was completed. The DXA scan showed osteopenia of the spine T score of -1.8, BMD 0.999 mg/mm3 and normal bone density in bilateral hips. He had no history of fractures. He was started on alendronate and remained on the medication from 2012 to 2015. It was stopped due to intolerable symptoms of acid reflux and he required proton pump inhibitors. DXA scan in 2017 showed normal bone density of the hips and osteopenia of the lumbar spine (T score -1.2). DXA scan in 2022 showed a decrease in spine BMD by 6% (T score -1.8) from 2017 to 2022 but unchanged from 2010. Hip bone mineral density was normal but decreased by 10% since 2010 and by 6% since 2017. Labs obtained in May 2022 showed normal serum electrophoresis, normal urine calcium and creatinine ratio, calcium and vitamin D level and urine NTX of 41 nM BCE/mM (21-83) and bone specific alkaline phosphatase level of 31.5 U/L (15-41.3). After discussion with the patient, conservative management with calcium, vitamin D and exercise has been implemented along with close follow up. Should the patient’s bone turnover markers increase or fracture risk increase, additional antiresorptive therapy will be initiated. Conclusion: This case study highlights the importance of screening for osteoporosis in patients with systemic macrocytosis. As this patient was diagnosed with osteopenia at age 53, this case also emphasizes the importance of early screening in both women and men with this rare condition. Presentation: 6/3/2024

Proton pump inhibitor-induced hypomagnesemia, a rare cause of reversible delirium: A case report with literature review.

Hypomagnesemia is associated with multiple electrolyte disturbances such as hypokalemia, hypocalcemia and hypoparathyroidism. Proton pump inhibitors (PPIs) are widely used in gastrointestinal disorders and are generally considered safe by clinicians. However, it is unusual side effect of hypomagnesemia is potentially under-recognized. Delirium is usually thought to be a clue of cerebrovascular disease, and the association between delirium and hypomagnesemia is unexpected. We describe a patient used PPI with hypomagnesemia showed normal parathyroid hormone (PTH) despite hypocalcemia and reversible delirium. To enhance clinicians' vigilance, we performed a literature review on cerebellar syndromes due to hypomagnesemia. A 74-year-old woman was admitted to our hospital with intermittent nausea, vomiting, hand tremors, and delirium. Laboratory analysis showed hypokalemia, hypomagnesemia, and normal parathyroid hormone despite hypocalcemia, physical examination showed horizontal nystagmus and the brain MRI was negative. Surprising, detailed medical history revealed that the etiology was the usage of omeprazole. Omeprazole was discontinued and oral supplementation with magnesium, calcium, and potassium was administered. Delirium quickly disappeared and the serum potassium, magnesium, and calcium levels gradually normalized; at discharge, nystagmus gradually disappeared, and plasma electrolyte levels were stable at follow-up. Hypomagnesemia is associated with a variety of neurological symptoms up to life-threatening conditions if left untreated; as Mg is not present in routine electrolyte panels, hypoparathyroidism, hypokalemia, and delirium may be a clue, and physicians must be alert to consider PPI as a potential cause of unexplained hypomagnesemia, and timely treatment to avoid sequelae.

Spontaneous esophageal submucosal hematoma.

A 57-year-old woman presented to our hospital with chest distension, sore throat and back discomfort beginning the previous day after taking 5 panax notoginseng capsules. She had a history of hypertension for more than 2 years. Physical examination was unremarkable. Blood tests revealed results: A red blood cell count of4.27T/L, a platelet count of 296G/L, a hemoglobin count of 130 g/L (130-175 g/L), and a D-dimer count of0.252 mg/L. Endoscopy showed a longitudinal dark red submucosal hematoma (SH) extending from 20 cm down to 36 cm, with no active bleeding. The next day an enhanced CT of the chest showed uneven thickening of esophageal wall suggestive of intramural esophageal hematoma. A second endoscopy was performed 6 days later, and it showed an esophageal ulcer where the hematoma had been seen at the previous part. The patient was treated with a proton pump inhibitor (PPI) and nutritional support while oral intake was completely prohibited. Her symptoms gradually improved and disappeared. She was discharged one week after the second Upper GI endoscopy when she was able to eat liquid diet. After discharge, she continued the PPI and Kang Fuxin for 2 months. During the 4-month follow up, the symptoms did not recur.

The Effects of Omeprazole on the Neuron-like Spiking of the Electrical Potential of Proteinoid Microspheres.

This study examines a new approach to hybrid neuromorphic devices by studying the impact of omeprazole-proteinoid complexes on Izhikevich neuron models. We investigate the influence of these metabolic structures on five specific patterns of neuronal firing: accommodation, chattering, triggered spiking, phasic spiking, and tonic spiking. By combining omeprazole, a proton pump inhibitor, with proteinoids, we create a unique substrate that interfaces with neuromorphic models. The Izhikevich neuron model is used because it is computationally efficient and can accurately simulate the various behaviours of cortical neurons. The results of our simulations show that omeprazole-proteinoid complexes have the ability to affect neuronal dynamics in different ways. This suggests that they could be used as adjustable components in bio-inspired computer systems. We noticed a notable alteration in the frequency of spikes, patterns of bursts, and rates of adaptation, especially in chattering and triggered spiking behaviours. The findings indicate that omeprazole-proteinoid complexes have the potential to serve as adaptable elements in neuromorphic systems, presenting novel opportunities for information processing and computation that have origins in neurobiological principles. This study makes a valuable contribution to the expanding field of biochemical neuromorphic devices and establishes a basis for the development of hybrid bio-synthetic computational systems.

Prescribing patterns in older people with advanced chronic kidney disease towards the end of life

ABSTRACT Background Advancing age and chronic kidney disease (CKD) are risk factors for polypharmacy. Polypharmacy is associated with negative healthcare outcomes. Deprescribing, the systematic rationalization of potentially inappropriate medications, is a proposed way of addressing polypharmacy. The aim of this study was to describe longitudinal prescribing patterns of oral medications in a cohort of older people with advanced CKD in their last years of life. Methods The European QUALity (EQUAL) study is a European, prospective cohort study of people ≥65 years with an incident estimated glomerular filtration rate (eGFR) of ≤20 mL/min/1.73 m2. We analysed a decedent subcohort, using generalized additive models to explore trends in the number and types of prescribed oral medications over the years preceding death. Results Data from 563 participants were analysed (comprising 2793 study visits) with a median follow-up time of 2.2 years (interquartile range 1.1–3.8) pre-death. Participants’ numbers of prescribed oral medications increased steadily over the years approaching death—7.3 (95% confidence interval 6.9–7.7) 5 years pre-death and 8.7 (95% confidence interval 8.4–9.0) at death. Over the years pre-death, the proportion of people prescribed (i) proton-pump inhibitors and opiates increased and (ii) statins, calcium-channel blockers and renin–angiotensin–aldosterone system inhibitors decreased, whilst (iii) beta-blockers, diuretics and gabapentinoids remained stable. At their final visits pre-death 14.6% and 5.1% were prescribed opiates and gabapentinoids, respectively. Conclusion Elderly people with advanced CKD experienced persistent and increasing levels of polypharmacy as they approached the end of life. There was evidence of cessation of certain classes of medications, but at a population level this was outweighed by new prescriptions. This work highlights the potential for improved medication review in this setting to reduce the risks associated with polypharmacy. Future work should focus at the individual patient–clinician level to better understand the decision-making process underlying the observed prescribing patterns.

Proton Pump Inhibitors Worsen Colorectal Cancer Outcomes in 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.

B-320 Understanding CA 72-4: Exploring False Positives in Clinical Context

Abstract Background CA 72-4, initially identified in 1981 as an antigen reactive to murine antibodies, is a glycoprotein expressed on the cell surface of certain carcinoma cells. Its production is elevated in various cancers, including ovarian, pancreatic, colorectal, and gastric cancer. However, CA 72-4 serum concentration may rise in non-cancerous conditions, leading to potential misdiagnosis and a low positive predictive value (PPV), particularly in asymptomatic patients. Our aim in this study was to describe CA 72-4 false positive values and assess the pathological conditions and pharmacological treatments associated with this. We also intended to compare other tumour markers status in false and true positive results of CA 72-4. Methods A retrospective analysis form pseudo-anonymized database was conducted using data from 1290 laboratory analysis from different patients taking a blood test at our laboratory hospital from 2017 to 2019. CA 72-4 and other tumour markers were analysed by ECLIA (Roche Diagnostics Gmbh. Mannheim, Germany). Results Among 1290 CA 72-4 laboratory tests in different patients, 204 were considered positive because they were above the reference interval (&amp;lt;7 U/mL). Within this subgroup, 44 of the 204 were clearly classified as false positives, as patients were not diagnosed with any form of neoplastic process. 45% of cases were between 7-14 U/mL (group 1), 30% were between 14-28 U/mL (group 2), and finally 25% of patients were above 28 U/mL ranging from 35.1 to 240.4 U/mL (group 3). Interestingly, CA19-9, CA 125 and CEA were measured in 37 of the false positive cases and it was found that 59.5% had at least another tumour marker above the reference range. In 103 true positive cases it was found that 88% of patients had at least one tumour marker above the normal range. Patients exhibiting false positive results for CA 72-4 demonstrated a wide spectrum of pathological conditions, with pulmonary disease, inflammation, infection, and heart and kidney disease emerging as the most prevalent. Group 1 patients most common underlying pathologies were pulmonary disease in 25%, heart disease in 25% and either viral or bacterial infection in 60% of patients. Group 2 patients most common pathologies were heart disease in 42%, pulmonary disease in 33% and infection in 25% of patients. In group 3 patients, renal disease was present in 45% of patients, heart disease was found in 45% of patients and inflammation/sepsis was found in 36% of patients. When looking into pharmacological treatment, 86.3% of patients were taking at least one of previously described treatments increasing CA 72-4 in serum; proton pump inhibitors, corticosteroids, antiplatelet drugs and colchicine. Drug treatment proportion was very similar across the different groups. Conclusions CA72-4 false positive cases are sometimes in conjunction with other false positive tumour markers but not in the same proportion as true positives. In addition, most false positive patients can be explained by pharmacological treatments. This research may help in the understanding and identification of potential factors influencing tumor marker levels and thus contribute to the interpretation of results.

Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis: A Meta-analysis Based on Randomized Controlled Trials.

This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.

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

Previous studies on Clostridioides difficile infection (CDI) in proton pump inhibitor (PPIs) users generally enrolled a heterogeneous population and did not include a control group of histamine H2 receptor antagonists (H2RAs) users or adjust for confounding variables, such as previous antibiotics. It is uncertain whether hospitalized patients using PPIs for stress ulcer prophylaxis (SUP) are at a higher risk of CDI compared to those using H2RAs. This study aimed to compare the association between CDI and the usage of antisecretory drugs (ASDs): PPIs and H2RAs, for stress ulcer prophylaxis (SUP) among hospitalized patients, and the impact of the duration of their use on CDI. In this nationwide population-based cohort study using the Taiwan National Health Insurance Database, hospitalized patients using ASDs for SUP were identified between 2017-2018. A total of 63,266 and 69,269 individuals were included in the PPI and H2RA groups, respectively. The primary endpoint was a 90-day monitoring of CDI occurrence. The incidences of CDI were 1·6/10,000 and 0·5/10,000 person-days in the PPIs and H2RAs groups, respectively. After adjusting for confounding factors, the risk of infection in the PPIs group remained significantly higher than in the H2RAs group (Hazard ratio [HR], 2·49; 95% Confidence Interval [CI], 1·63-3·81). In the subgroup analysis, during hospitalization, the risk of CDI for patients using high-risk antibiotics or admitted intensive care unit (ICU), as well as patients with immunodeficiency, using PPIs for SUP, was higher than using H2RAs. Furthermore, the risk of CDI was higher in patients using ASDs for durations > 14 days than in those using them for < 7 days (adjusted HR, 3·66; 95% CI, 2·34-5·75). The risk of occurrence CDI for hospitalized patients using PPIs for SUP was higher than using H2RAs. It is recommended not to exceed 14 days of any gastric ASDs for SUP during hospitalization, especially for patients who have used high-risk antibiotics, been admitted to the ICU, or have immunodeficiency.

Relationship between proton pump inhibitor prescription and asthma exacerbation among adult patients: a self-controlled case series study.

Proton-pump inhibitors (PPI) are empirically used to treat asthma symptoms such as cough; however, the effectiveness of PPI on asthma exacerbation has not been well studied. We aimed to evaluate the relationship between PPI use and asthma exacerbation using a large administrative claims database in Japan. We conducted a self-controlled case series using the JMDC Claims Database (JMDC, Inc., Tokyo, Japan). The cases included adult patients with asthma who were prescribed PPI and experienced at least one outcome event between January 2015 and December 2019. The primary outcome was the composite outcome of hospital admissions and unscheduled outpatient clinic visits due to asthma exacerbation. We also conducted stratified analyses based on PPI generation, the presence of gastroesophageal reflux disease (GERD), asthma severity, and the number of allergic comorbidities. A total of 7379 eligible patients were included in the study. PPI prescription was associated with a decrease in the composite outcomes (incidence rate ratio, 0.90; 95% confidence interval, 0.87-0.93). However, PPI prescriptions did not affect the outcomes of hospital admissions (incidence rate ratio, 1.34; 95% confidence interval, 0.86-2.10). Stratified analyses based on PPI generation, the presence of GERD, asthma severity (except for severe asthma), and the number of allergic comorbidities yielded consistent results. PPI use was associated with a moderate decrease in asthma exacerbation, regardless of the patient profile. However, this effect was not as strong as the prevention of hospital admissions, and outcome events were not prevented in patients with severe asthma.