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Objective: Periodontal disease is caused by subgingival bacteria that adversely affect the host immune system and create and maintain unmitigated inflammation in gingival and periodontal tissues. The condition is also linked to systemic conditions including cardiovascular disease, diabetes, and arthritis. Periodontitis elevates the bacterial load and spreads systemic inflammation through infection and inflammation. The main radiographic sign of periodontitis is marginal bone loss. Risk factors, including medications, smoking, age, and sex, are known to influence periodontal health. However, there is little information about the impact of systemic conditions and medications on tooth wear. The aim of the present study was to assess the association between systemic conditions and medications and radiographic signs of tooth wear and marginal bone loss. Method and materials: This retrospective analysis was conducted on a group of 2,223 consecutive patients who came for dental treatment in the clinics of a large Health Maintenance Organization in Israel. Data available for the study included details of concomitant systemic diseases and medication and fullmouth radiographic surveys. Odds ratio and logistic regression analysis were used to detect associations between systemic conditions and medication, and marginal bone loss and tooth wear. Results: The results indicated an elevated odds ratio for tooth wear associated with age, sex, and smoking across all age groups. Among young patients, those using proton pump inhibitors and psychiatric medications had an elevated risk of tooth wear. Age, smoking, and diabetes conditions were associated with an increased odds ratio for marginal bone loss in all age groups. Psychiatric medications and sex elevated the odds ratio for marginal bone loss only among older patients. Conclusion: The results highlight the significant impact of age, sex, and smoking on tooth wear, and extend these risks to alveolar bone loss when combined with diabetes and psychiatric conditions. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Half of patients with gastroesophageal reflux disease (GERD) experience persistent symptoms while on proton pump inhibitors (PPIs), thus driving efforts to develop novel adjunctive therapies for PPI-refractory GERD. An economic analysis was performed to establish at what cost and efficacy such potential medications are likely to become cost effective in clinical practice. METHODS: A Markov decision model was used to examine a hypothetical cohort of patients being evaluated for PPI-refractory GERD in the USA. The model compared 3 strategies: (1) usual care (i.e., upfront diagnostic testing with upper endoscopy ± ambulatory pH testing); (2) use of a PPI-adjunctive therapy after positive ambulatory pH testing; and (3) empiric use of a PPI-adjunctive therapy (i.e., diagnostic testing only after failing empiric treatment). The primary outcome was incremental cost per quality-adjusted life year (QALY) gained (third-party payer perspective) over a 10-year time horizon using a willingness to pay threshold of $100,000/QALY. RESULTS: In two-way sensitivity analyses varying the cost and effectiveness of the PPI-adjunctive therapy, most combinations revealed that use of the medication after positive pH testing was the most cost-effective approach. Empiric treatment was the preferred strategy only when the therapy was highly efficacious (≥ 87.5% response rate) and low cost (≤ $109/month). Use of PPI-adjunctive treatments were not cost effective when the cost exceeded $1150/month. CONCLUSION: Use of PPI-adjunctive therapies in those with persistent GERD symptoms may become cost effective when guided by ambulatory pH tests. These data can guide investigators, industry, and payers as they develop, validate, and price new treatments for PPI-refractory GERD.

Extracellular vesicles (EVs) are involved in the progression of various diseases. Tumor cell-derived EVs (TEVs) are a particular concern, as they can induce fatty liver by promoting liver macrophages to secrete tumor necrosis factor (TNF), thus enhancing the toxicity of chemotherapy. Therefore, reducing pathogenic EV production is a potential strategy for treating EV-related diseases. However, there are currently no effective clinical reagents to obtain this purpose. In addition, EVs are also natural and ideal drug-delivery vehicles. Improving the delivery efficiency of EVs remains a challenge. Proton pump inhibitors (PPIs) have been demonstrated to promote cell uptake of EVs by inducing micropinocytosis. Here, we show that PPIs can accelerate TEV clearance, reduce TEV uptake by liver macrophages and decrease the mRNA expression of TNF in liver macrophages of tumor-bearing mice. Correspondingly, the fatty liver phenotypes are alleviated, and the tolerance to chemotherapy is improved in these mice. Furthermore, our findings indicate that PPIs facilitate the uptake of red blood cell-derived EVs (RBC-EVs) loaded with antisense oligonucleotides of Trim21 (Trim21-ASOs) by the liver macrophages of obesity. Consequently, the inhibition of macrophage inflammatory responses in obese mice mediated by RBC-EVs/Trim21-ASOs was further enhanced by PPIs, resulting in a more profound improvement in obesity and related metabolic disorders. In conclusion, our findings demonstrated that PPIs can effectively clear pathogenic EVs and enhance the delivery efficacy of EV vehicles, making them a highly promising clinical prospect. [ABSTRACT FROM AUTHOR]

Purpose Minimally invasive surgery (MIS) with integrated enhanced recovery pathways (ERPs) helps reduce length of stay and improve surgical outcomes. As these procedures have become more prevalent over time, pharmacists are in key positions to manage medications in the perioperative space to help optimize transitions of care and reduce safety events. Here we identify several clinical areas across phases of care for these procedures in which the knowledge and guidance of pharmacists, as members of the interprofessional team, are paramount. Summary Perioperative pharmacy expertise is often required for MIS procedures in the areas of acid suppression, antithrombotic management, blood glucose control, drug formulation, immunosuppressant optimization, pain mitigation, and postoperative nausea and vomiting prevention and treatment. For each MIS procedure, pharmacists should identify and consider diet and anatomical changes as well as patient- and surgery-specific risk factors. Pharmacists can then utilize their knowledge of the pharmacokinetics and pharmacodynamics of individual medications along with evidence-based medicine to recommend selection of appropriate agents. Conclusion Pharmacist contributions to perioperative medication management for MIS procedures can improve care as surgical patients navigate transitions through the perioperative setting. Pharmacists can further incorporate medication expertise through development and implementation of institutional MIS protocols within the context of ERPs. As such, any pharmacist should feel empowered to aid in the care of surgical patients. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion Clostridioides difficile infection (CDI) is a leading cause of nosocomial infection and is associated with both higher morbidity and mortality. Cirrhotic patients are more susceptible to CDI because of impaired gut immune response, use of proton pump inhibitor, and frequent hospitalization. We aim to investigate the impact of CDI on cirrhotic patients' in‐hospital and 30‐day mortality, length of stay, and hospital cost.Potentially eligible studies were identified from Embase, Medline, and Web of Sciences databases.A total of 2320 articles were identified. After reviewing, nine studies reporting in‐hospital mortality and three reporting 30‐day mortality of cirrhotic patients with CDI versus those without CDI were included. The meta‐analysis of nine studies, consisting of 7 746 126 patients, revealed a significant association between CDI and in‐hospital mortality in cirrhotic patients with the pooled OR of 1.68 (95% CI 1.29–1.85, I2 94%). Length of stay and hospital cost were also higher in the CDI group (pooled MD of 6.56 days [95% CI 5.75–7.36, I2 94%] and 27.85 (×$1000) [95% CI 10.41–45.29, I2 100%], respectively). The funnel plots for the meta‐analysis of the association between CDI and in‐hospital mortality, length of stay, and hospitalization cost were not suggestive of publication bias. From three studies consisting of 3694 patients, we found that CDI was not associated with 30‐day mortality in cirrhotic patients (pooled OR 1.20, 95% CI 0.75–2.24, I2 74%).CDI is associated with increased in‐hospital mortality, length of stay, and hospital costs, but not with 30‐day mortality in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Introduction: The prevalent overprescribing of proton pump inhibitors (PPIs) poses health risks from prolonged use. GPs play a key role in initiating deprescribing PPIs, so understanding their decision-making factors and strategies to improve feasibility is crucial. This study aimed to investigate the perspectives of GPs on deprescribing PPIs with a focus on identifying facilitators, barriers, and strategies to enhance feasibility in clinical settings. Methods: A qualitative study involving semi-structured interviews was conducted with nine GPs or trainees. The thematic analysis of the interviews was conducted using NVivo R1 (2020). Results: Four main categories were identified: 1) Inappropriate prescribing of PPIs, 2) Facilitators for deprescribing PPIs, 3) Barriers to deprescribing PPIs, 4) Feasibility of deprescribing PPIs. GPs acknowledged excessive and often inappropriate PPI prescribing, with a lack of deprescribing efforts mainly due to time constraints. Other key barriers included patient reluctance, fear of symptom recurrence, and unawareness of long-term risks. Patient-initiated request is key facilitator for deprescribing PPIs. GPs emphasized the need for collaboration with healthcare professionals, clear guidelines, improved digital support, increased physician availability, and raising awareness among providers and patients to enhance deprescribing feasibility. Discussion: GPs are calling for a multifaceted approach to improve the feasibility of deprescribing PPIs, involving patient-centered approaches, systemic optimizations, support from other healthcare professionals, and provider-centered strategies to emphasize the importance of deprescribing PPIs. [ABSTRACT FROM AUTHOR]

Background: Appropriate prescription of Proton pump inhibitors (PPIs) remains an important concern amid the rising overuse. A gap exists in the literature regarding the benefit of PPI prophylaxis and the consequences of underprescription in patients at risk for upper gastrointestinal bleeding (UGIB). Aims: This study aims to describe the characteristics of hemorrhage in relation to PPI use in patients experiencing UGIB, with a focus on high-risk individuals requiring gastroprotection. Methods: Data from a French multicentric cohort of patients experiencing UGIB were analyzed. Patients using PPI were compared to those without PPI considering bleeding etiologies and outcomes of peptic ulcer disease (PUD)-related hemorrhage. The rate of PPI use and its effect on bleeding characteristics in high-risk populations, defined based on international guidelines, were also assessed. Results: Among 2497 included patients, 31.1% were on PPI at bleeding onset. PPI users exhibited a significantly lower rate of PUD-related bleeding in comparison with those without PPI (24.7 vs 40.8%, respectively, p < 0.0001). Similar difference was observed in high-risk populations, of whom, only 40.3% had gastroprotection with PPI before bleeding onset. PPI prophylaxis, however, did not influence the severity of bleeding in the general study population or in high-risk groups. Multivariate analysis identified age, comorbidities, and having more than two anti-thrombotic agents as predictors of severe bleeding. Conclusions: PPI users appear to have a lower rate of bleeding ulcers compared to non-users. However, underprescription in high-risk groups raises the need for standardized care to ensure appropriate PPI use. [ABSTRACT FROM AUTHOR]

Background/Aims: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract. [ABSTRACT FROM AUTHOR]

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

Background and Objective: Serum markers such as gastrin and pepsinogen are useful for stratifying gastric cancer risk. However, their utility in predicting metachronous gastric cancer after endoscopic submucosal dissection (ESD) in patients with gastric cancer after Helicobacter pylori eradication (GCAE) is unclear. This study aimed to clarify predictive factors for metachronous gastric cancer after ESD with a focus on serum markers. Methods: A retrospective analysis was conducted on 197 patients with 224 GCAE lesions who underwent ESD at Hiroshima University Hospital between April 2010 and December 2019. In total, 63 patients with 74 differentiated-type lesions were classified into metachronous gastric cancer (MG) and non-metachronous gastric cancer (NMG) groups, excluding proton pump inhibitor (PPI) users, female patients, and undifferentiated-type cases. The predictive value of serum markers was assessed using ROC curve analysis, and their association with carcinogenesis was evaluated using multiple logistic regression. Furthermore, the incidence of MG was compared between long-term PPI users and non-users. Results: ROC analysis revealed that serum gastrin had the highest discriminative ability for MG (AUC 0.77, cut-off 99 pg/mL, sensitivity 61.6%, and specificity 80.0%). Severe mucosal atrophy and high gastrin levels were significantly more common in the MG group and were independent predictors (p < 0.01). Although serum gastrin levels were significantly elevated in PPI users, no increased risk of MG was observed. Conclusions: In addition to severe mucosal atrophy, PPI-independent elevated serum gastrin levels may be associated with an increased risk of MG after ESD. Serum gastrin may serve as a valuable marker for post-ESD cancer surveillance in GCAE patients. [ABSTRACT FROM AUTHOR]

Background: Potentially inappropriate medications (PIMs) are medications whereby the harms may outweigh the benefits for a given individual. Although overprescribed to older adults, their direct costs on the healthcare system are poorly described. Methods: This was a cross‐sectional study of the cost of PIMs for Canadians aged 65 and older, using adapted criteria from the American Geriatrics Society. We examined prescription claims information from the National Prescription Drug Utilization Information System in 2021 and compared these with 2013. The overall levels of inflation‐adjusted total annual expenditure on PIMs, average cost per quarterly exposure, and average quarterly exposures to PIMs were calculated in CAD$. Results: Exposure to most categories of PIMs decreased, aside from gabapentinoids, proton pump inhibitors, and antipsychotics, all of which increased. Canadians spent $1 billion on PIMs in 2021, a 33.6% reduction compared with 2013 ($1.5 billion). In 2021, the largest annual expenditures were on proton pump inhibitors ($211 million) and gabapentinoids ($126 million). The quarterly amount spent on PIMs per person exposed decreased from $95 to $57. In terms of mean cost per person, opioids and antipsychotics were highest ($138 and $118 per exposure). Some cost savings may have occurred secondary to an observed decline of 16.4% in the quarterly rate of exposure to PIMs (from 7301 per 10,000 in 2013 to 6106 per 10,000 in 2021). Conclusions: While expenditures on PIMs have declined in Canada, the overall cost remains high. Prescribing of some seriously harmful classes of PIMs has increased and so directed, scalable interventions are needed. [ABSTRACT FROM AUTHOR]

Objectives: We compared the efficacy and safety of transoral incisionless fundoplication (TIF) with the EsophyX2.0 and MUSE systems for treatment of gastroesophageal reflux disease (GERD). Methods: TIF outcomes from prospective protocols (Esophy2.0X: 2007–2012; MUSE: 2015–2019) were retrospectively compared regarding technical success, moderate/severe adverse events, morpho‐functional findings up to 1 year, and clinical outcomes up to 3 years. Inclusion criteria were: (i) at least 6‐month symptomatic GERD, full/partial response to proton pump inhibitors (PPI), esophagitis, and nonerosive reflux disease/hypersensitive esophagus (both protocols); (ii) hiatal hernia <3 cm (Esophy2.0X) and ≤2.5 cm (MUSE); and (iii) Barrett's esophagus <3 cm (MUSE). Results: In the 50 EsophyX2.0 and 46 MUSE procedures, technical success and adverse event rates were similar, but MUSE‐related adverse events (4.4%) were life‐threatening. At 12 months, hiatal hernia recurred more frequently after EsophyX2.0 (P = 0.008). At 6 months, significantly fewer total and acid refluxes were reported after both TIF, but not more significantly at 1 year. Symptoms improved after both TIF up to 1 year (P < 0.0001), but to a greater extent in MUSE patients up to 3 years (P < 0.0001 vs. P < 0.01 for EsophyX2.0). The rates of 3‐year off‐PPI therapy patients were 73.5% in the MUSE and 53.3% in the EsophyX2.0 series (P = 0.069). Conclusion: Although no conclusion could be drawn from this limited study, the MUSE technique seemed more effective in the long term in patients with hiatal hernia; however, there were more severe adverse events than with EsophyX2.0. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are the most commonly used medication for stomach secretion disorders. However, when it comes to safe, discreet pharmaceutical practice, widely recognized preparational and analytical method(s) for PPIs with sensitivity, selectivity, speed and high accuracy still remains underdeveloped. For this reason, this paper sets out to make a comprehensive review of the preparation and determination methods for PPIs based on multiple matrices since 2010. We have integrated newly-developed techniques (such as solid phase extraction, liquid phase micro-extraction, and solid phase micro-extraction) into conventional sample preparational methods. On the other hand, our analytical techniques include liquid chromatography, supercritical fluid chromatography, capillary electrophoresis, and employment of sensors. In addition, we have identified the pros and cons of each technique and have forecast their future developmental trends. HIGHLIGHTS: Development of preparational and analytical methods for PPIs has been documented. The pros and cons of different pretreatment techniques have been specifically identified with comparison. The evolution of different microextraction methods for PPIs has been presented. The future trends of pretreatment and analytical methods for PPIs have been discussed. [ABSTRACT FROM AUTHOR]

Background: Historically, DeMeester score over 14.7 has been used to diagnose GERD. The 2022 American Gastroenterological Association clinical guidelines define GERD based on acid exposure time (AET) instead of DeMeester score. We aim to compare outcomes after laparoscopic Nissen fundoplication (LNF) in patients based on differing GERD diagnostic criteria. Methods: Patients who underwent first-time LNF between 2009 and 2017 were identified. Demographics, objective GERD evaluation, and outcomes were maintained in an IRB-approved database. Disease-specific quality of life was assessed with a survey (GERD-HRQL) with higher values representing more symptomatic disease. Descriptive statistics, Fischer's exact test and logistic regression were used to analyze the data, p-value < 0.05. Results: 225 patients were stratified into two groups: borderline GERD (AET 4–6%, n = 25.11%) and GERD (AET ≥ 6%, n = 200.89%). The mean age was 50.1 ± 13.4 years and 169 (75%) were female. Baseline GERD-HRQL was lower in the borderline group (24.3 vs 30.0, p = 0.031). Short-term (5 weeks [IQR 4, 8]), medium-term (14 months [IQR 7.25, 31]) and long-term (6.75 years [IQR 5.5, 8]) follow-up was performed. GERD-HRQL scores did not differ between borderline and GERD patients at short-(6.0 vs 7.1, p = 0.630), medium-(12.0 vs 12.1, p = 0.818), or long-term follow-up (10.0 vs 9.0, p = 0.757). The absolute long-term improvement in GERD-HRQL was −12.3 (p = 0.022) vs. −21.3 (p < 0.001). At long-term follow-up there was no difference in PPI use (50% vs 47%, p = 0.852), satisfaction (58% vs 76%, p = 0.187), willingness to repeat the procedure given the benefit of hindsight (75% vs 85%, p = 0.386), or need for reoperation (14% vs 13%, p = 0.910). Conclusion: Both patients with borderline GERD and GERD achieve GERD-HRQL improvements at 7 years following laparoscopic Nissen fundoplication and demonstrate similar long-term PPI usage and satisfaction with surgical results. Borderline GERD patients have lower GERD-HRQL at baseline, and thus have smaller improvements in their QOL scores. Anti-reflux surgery should be considered for patients with a diagnosis of borderline GERD refractory to medical therapy. [ABSTRACT FROM AUTHOR]

In most older patients with Helicobacter pylori infection, the risks of eradication therapy (ET) are outweighed by the benefits, which include decreases in the incidences of gastric cancer, ulcer-related bleeding, hospitalisation and death. ET involves proton pump inhibitors or potassium-competitive acid blockers, antibiotics and/or bismuth, with quadruple therapy as front-line therapy. Prescribing complexity is increased by age-related comorbidities and polypharmacy, but overall, ET is effective and well tolerated in older people. To ensure successful eradication and prevent the emergence of drug-resistant H. pylori, performing antibiotic-resistance testing, adhering to guideline-recommended treatment durations, switching antibiotics after treatment failure, and performing post-therapy examinations is recommended. [ABSTRACT FROM AUTHOR]

Objective: To explore a link between the use of proton pump inhibitor (PPI) and the risk of stroke. Methods: Comprehensive literature search in PubMed, EMBASE, and Cochrane CENTRAL Library databases was carried out for observational studies establishing the link between PPI and a risk of stroke. Data extraction and quality assessment were performed by two reviewers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) using random-effects models were plotted. Subgroup analyses were conducted based on age, gender, PPI type, duration of follow-up, and propensity score matching (PSM). Results: The analysis included 12 studies, with considerable heterogeneity (I2 = 95%). PPI use did not affect the incidence of ischemic stroke (HR: 1.11, 95% CI: 0.98-1.26). Subgroup analyses revealed that PPI use correlated with the risk of ischemic stroke, in particular in patients<65 years old (HR: 1.25, 95% CI: 1.07-1.45), both males (HR: 1.12, 95% CI: 1.02-1.24) and females (HR: 1.21, 95% CI: 1.10-1.33). The correlation varied depending on the PPI type, with pantoprazole showing elevated risk (HR: 1.66, 95% CI: 1.43-1.93). Duration of follow-up or propensity score matching (PSM) did not impact the association. Conclusion: PPI use may be linked with ischemic stroke, particularly in individuals <65 years old and of all genders. The specific PPI type may also influence the risk. However, the cumulative analysis did not find any statistically significant association, and heterogeneity among studies was substantial. [ABSTRACT FROM AUTHOR]

Background Aims/Methods Results Conclusions Gastro‐esophageal reflux disease (GERD) is the most common cause for noncardiac chest pain (NCCP), with an estimated prevalence rate ranging between 30% and 60%. Heartburn and NCCP may share common mechanisms.To assess whether particular patterns of impedance‐pH variables characterize patients with dominant heartburn, regurgitation, or NCCP and their ability to predict proton pump inhibitor (PPI) response for each symptom, GERD patients, evaluated with high‐resolution manometry (HRM) and impedance‐pH, were included.In total, 109 NCCP, 68 heartburn, and 64 regurgitation patients were included. Pathological reflux episodes were observed in 28%, 19%, and 56% (p < 0.001). Pathological mean nocturnal baseline impedance (MNBI) values were observed in 55%, 53%, and 34% (p < 0.05). Hypomotility was more frequent in NCCP compared to heartburn patients (p < 0.05). When comparing NCCP with heartburn, hypomotility was associated with NCCP perception (OR: 2.34, 95% CI: 1.23–4.43; p < 0.01). When comparing NCCP with regurgitation, >80 refluxes and type 2/3 esophagogastric junction (EGJ) were associated with regurgitation perception (OR: 0.31, 95% CI: 0.16–0.59; p < 0.001, and OR: 0.5, 95% CI: 0.27–0.93; p < 0.05), while pathological MNBI was associated with NCCP perception (OR: 2.34, 95% CI: 1.23–4.43; p < 0.01). 45.5% NCCP patients, 45.6% with heartburn, and 36% with regurgitation responded to PPIs (p < 0.05). At multivariate analysis, pathological MNBI or PSPW index were associated with PPI responsiveness in patients with NCCP or heartburn, while in patients with regurgitation, pathological MNBI was associated with PPI responsiveness and a reflux number >80 to PPI refractoriness.We highlight the usefulness of an accurate clinical and functional evaluation of GERD patients, allowing to discriminate particular characteristics in patients with dominant heartburn, NCCP, or regurgitation, which may benefit of distinct therapeutic strategies. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) disorders range from intermittent heartburn to life-threatening GI hemorrhage. One of the most common GI disorders is gastroesophageal reflux disease (GERD), which affects an estimated 19% of adults in North America. This article discusses the advantages and disadvantages of acidsuppressive therapy for patients with GERD as well as relevant nursing considerations. [ABSTRACT FROM AUTHOR]

Distal esophageal spasm (DES) is a rare motility disorder presenting with dysphagia or chest pain. Although studies suggest a link between DES and gastroesophageal reflux disease (GERD), data supporting a distinct GERD-related phenotype are limited. This study aims to investigate demographic, symptomatic, and physiologic differences between DES subjects with and without GERD. A retrospective cohort analysis of DES patients determined by high resolution manometry (HRM) was conducted between February 2020 and January 2023. Demographics, medications, symptoms, and quantitative reflux testing data were collected. DES subjects with reflux (R-DES) were defined by presence of Los Angeles Grade B/C/D esophagitis, Barrett's metaplasia, or abnormal pH testing. DES subjects without reflux (NR-DES) had normal parameters. Statistical analysis employed two-sided or Wilcoxon Rank-Sum, Chi-squared, or Fisher's exact tests, and multivariate logistic regression. Of 69 DES subjects, 32 (46.3%) had GERD. R-DES and NR-DES patients had similar demographic variables except for higher BMI in R-DES (30.41 vs. 26.88, P  = 0.01). R-DES and NR-DES shared similar symptom profiles (heartburn P  = 0.67, dysphagia P  = 0.448, chest pain P  = 0.32). Proton pump inhibitor use was similar between groups (78.1% vs. 91.9%, P  = 0.202). HRM metrics were comparable except for basal LES tone (20.7 mmHg vs. 32.99 mmHg, P  = 0.03) and median IRP 11.82 mmHg versus 17.20 mmHg, P  = 0.017). This study found no distinguishing clinical or physiologic differences between DES patients with and without GERD, challenging the historical emphasis of GERD in DES pathogenesis. The impact of GERD management on the natural history of DES remains uncertain. [ABSTRACT FROM AUTHOR]

Gastroparesis (Gp) patients often have gastroesophageal reflux disease (GERD). Management of GERD in Gp patients is a challenge. Many studies have shown that gastric peroral endoscopic pyloromyotomy (G-POEM or POP) is moderately effective in reducing nausea and vomiting in patients with Gp. This study aims to determine whether G-POEM can improve GERD in Gp Patients. Patients who underwent G-POEM from July 2021 to October 2022 were enrolled in the study. GERD Health-Related Quality of Life (GERD HRQL) and Reflux Symptom Index (RSI) were used to assess patients' GERD before and after G-POEM. The use of proton pump inhibitors (PPIs) before and after G-POEM were also documented. The Gastroparesis Cardinal Symptom Index (GCSI) was used to assess the severity of Gp before and after G-POEM. A 'Welch two-sample t -test' was used to find differences in GERD HRQL (health-related quality of life) and RSI scores before and after the procedure. Pearson's chi-square test was used to find differences for use of PPI before and after G-POEM. Twenty-three consecutive refractory Gp patients with 30% male (average age 63.2) and 70% female patients (average age 53.9) were enrolled. Of these, 14 had diabetes, 3 had a history of surgery, and 6 had idiopathic Gp. The mean follow-up was 41 days (range 7–61 days). There was a significant decrease in the mean GERD HRQL score from 16.5 to 6.5 after G POEM with a P -value <0.0001 (95% level of significance) and a significant decrease in mean RSI score from 15.3 to 5.2 after G-POEM with P -value <0.0001 (95% level of significance). The proportion of use of PPI before GPOEM was 0.91, and the proportion of PPI use after GPOEM was 0.43 (P  = 0.0008). The mean GCSI pre- and post-GPOEM were 3.53 and 1.59, respectively. Eighteen had clinical success in Gp as defined by decreased mean GCSI score greater than 1. In this short-term outcome study, 87% of patients' GERD HRQL scores and RSI scores decreased after G-POEM. These findings indicate that GPOEM not only effectively reduces Gp symptoms but also improves GERD symptoms leading to decreased or more effective use of PPI in these patients. To our knowledge, this is the first study to comprehensively show G-POEM significantly improves GERD. Further studies with a larger patient population and long-term outcomes are needed. [ABSTRACT FROM AUTHOR]

Purpose: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. Methods: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. Results: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p =.036 and.045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. Conclusion: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. Trial registration: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100. [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]

Purpose: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). Methods: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. Results: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020–1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. Conclusion: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients. [ABSTRACT FROM AUTHOR]

Objectives: Vocal process granuloma (VPG) is a chronic condition resulting from a mucoperichondrial injury of vocal process. Initial conservative treatment typically involves vocal hygiene education and antireflux medication. Treatment challenges arise with refractory cases. Outcomes of second‐line treatments such as surgical excision and botulinum toxin injections remain inconsistent. Thus, we propose this study to investigate the effectiveness of intralesional steroid injections for refractory VPG. Methods: We conducted a retrospective review of 23 patients with VPG who showed no improvement after 3 months of proton pump inhibitors. These patients underwent one to three courses of monthly in‐office intralesional steroid injections as a second‐line therapy. Treatment outcomes were evaluated by measuring the size of the VPG relative to the length of the vocal folds before and after the final injection procedure. Results: Results showed a significant reduction in VPG size from baseline of 27.74 ± 15.06 to 5.48 ± 8.95 (p <.001). 15 out of 23 patients were responsive (size reduction ≥ 75%) to intralesional steroid injection. Alcohol consumption and longer symptom duration were associated with a poor response (size reduction <75%), whereas prior intubation was associated with better response. Conclusions: For refractory VPG not responding to conservative treatment, intralesional steroid injection appears to be a promising alternative option without significant adverse effects. [ABSTRACT FROM AUTHOR]

Background: Post-endoscopic variceal ligation (EVL) ulcers represent a complication following EVL, with potential implications for mortality in cirrhotic patients. Prophylaxis against this complication typically involves either a proton pump inhibitor (PPI) or sucralfate. Limited studies have explored the combination of PPI with sucralfate suspension in the prevention of post-EVL ulcers. Objective: The present study aimed to assess the efficacy of the combination of omeprazole and sucralfate suspension in comparison to omeprazole alone for preventing post-EVL ulcers in cirrhotic patients classified as Child-Turcotte-Pugh (CTP) A or B. Materials and Methods: Conducted from March 2019 to December 2022, this prospective, single-center, randomized controlled trial enrolled patients diagnosed liver cirrhosis CTP A or B with esophageal varices. Systematic randomization assigned patients to either the omeprazole plus sucralfate suspension group or the omeprazole alone group. Subsequent esophagogastroduodenoscopy (EGD) was performed two weeks later to evaluate EVL ulceration using Jamwal's classification and complications. Results: Out of the 84 initially enrolled patients, 2 in the omeprazole group were lost to follow-up. Intention-to-treat analysis (82 patients) revealed no significant differences between the combination of omeprazole plus sucralfate suspension and omeprazole alone groups in terms of EVL ulcer type (1 (2.4%) vs. 3 (7.5%) in type C, 40 (95.2%) vs. 35 (87.5%) in type D ulcer; p=0.41), EVL ulcer numbers (4.4±2.0 vs. 4±2.1; p=0.43), and percent decreasing of EVL ulcer numbers (33.3±35.8 vs. 35.7±28.8: p=0.47). No statistically significant variations in post-EVL complications were observed between the two treatment groups. Conclusion: The present study indicates no discernible differences in post-EVL ulcer type, EVL ulcer numbers, percentage reduction in EVL ulcer numbers, and complications between the combination of omeprazole plus sucralfate suspension and omeprazole alone. [ABSTRACT FROM AUTHOR]

Introduction: Gastroesophageal reflux disease (GERD) is a common ailment associated with troublesome symptoms. The standard of care in Italy involves initial treatment with proton pump inhibitor (PPI)-based medical management or laparoscopic Nissen fundoplication (LNF) for patients unwilling to continue or intolerant of long-term PPI therapy. RefluxStop is a novel medical device, intended for laparoscopic implantation, that has recently proven to be an efficacious and cost-effective treatment option for patients with GERD. This analysis aims to describe the short-term budget impact of introducing RefluxStop as a GERD treatment option within the Italian National Health Service (SSN). Methods: A model adherent to international best practice recommendations was developed to estimate the budget impact of introducing RefluxStop over a 5-year time horizon. Two scenarios were considered: one without RefluxStop (i.e., comprising PPI therapy, LNF, and magnetic sphincter augmentation using the LINX system); and one with RefluxStop (i.e., addition of RefluxStop to the three treatment options previously mentioned). Clinical benefits and costs associated with each intervention were included in the analysis. Results: Over 5 years, the introduction of RefluxStop resulted in avoidance of 95 surgical failures, 11 reoperations, and 64 endoscopic esophageal dilations. Introduction of RefluxStop resulted in an almost neutral impact on the existing budget with a 0.316% increase in the annual Italian SSN spending on GERD treatment. Conclusion: Introduction of RefluxStop as a GERD treatment option in Italy is likely to be associated with substantial clinical benefits and a marginal budget impact. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal cancer type. PDAC is characterized by fibrotic, hypoxic, and presumably acidic tumor microenvironment (TME). Acidic TME is an important player in tumor development, progression, aggressiveness, and chemoresistance. The dysregulation of ductal ion transporters/channels might contribute to extracellular pH (pHe) acidification and PDAC progression. Our aim was to test whether H+/K+‐ATPases and pH‐sensitive K+ channels contribute to these processes and could be targeted by clinically approved drugs. We used human pancreatic cancer cells adapted to various pHe conditions and grown in monolayers and spheroids. First, we created cells expressing pHoran4 at the outer plasma membrane and showed that pantoprazole, the H+/K+‐ATPase inhibitor, alkalinized pHe. Second, we used FluoVolt to monitor the membrane voltage (Vm) and showed that riluzole hyperpolarized Vm, most likely by opening of pH‐sensitive K+ channels such as TREK‐1. Third, we show that pantoprazole and riluzole inhibited cell proliferation and viability of monolayers and spheroids of cancer cells adapted to various pHe conditions. Most importantly, combination of the two drugs had significantly larger inhibitory effects on PDAC cell survival. We propose that co‐targeting H+/K+‐ATPases and pH‐sensitive K+ channels by re‐purposing of pantoprazole and riluzole could provide novel acidosis‐targeted therapies of PDAC. [ABSTRACT FROM AUTHOR]

Context Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). Objective To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined. Methods This population-based case-cohort study utilized data from the Danish National Healthcare system, including longitudinal records of medication use, healthcare utilization, and x-ray images. Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010 and 2015 (n = 4973) were identified and compared to a random sample (n = 37 021). Bisphosphonate use was collected from 1995-2015. Fracture radiographs (n = 4769) were reviewed by blinded study radiologists to identify AFFs (n = 189) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10. Results Compared to <1 year of BP use, 5 to 7 years of use was associated with a 7-fold increase in AFF (adjusted HR = 7.29 [CI: 3.07, 17.30]); the risk of AFF fell quickly after discontinuation. The 5-year number needed to harm for one AFF was 1424, while the 5-year number needed to treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure. Conclusion The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Esomeprazole use is increasing in dogs, but the gastrointestinal adverse events associated with q12h dosing necessitate pharmacodynamic evaluation of a reduced dose and frequency of administration.To compare the efficacy of 2 doses of (q24h) esomeprazole in raising intragastric pH in dogs.Nine healthy, client‐owned dogs, >20 kg.Prospective, randomized, double blinded, crossover study. Esomeprazole (0.5 or 1 mg/kg q24h) was orally administered for up to 5 days per treatment arm, and the mean percentage time intragastric pH was ≥3 (MPT3) and ≥4 (MPT4) for 24 hours periods were compared to pretreatment pH using a continuous pH monitoring system. Dogs failing to reach pH goals (MPT3 ≥75%, MPT4 ≥66%) with once daily dosing received esomeprazole 1 mg/kg PO q12h to determine if a higher dose would improve acid suppression.No significant difference in the MPT3 or MPT4 was identified between treatments for any time point (P > .05). Both doses increased the MPT pH ≥3 and 4 median [range] (0.5 mg/kg, 1 mg/kg) on days 1 (MPT3: 76.8% [44‐100], 69.2% [28.2‐100]; MPT4: 65.6% [16.7‐99.3], 54.9% [14.9‐93.3]; P = .0009) and 2 (MPT3:77.2% [27.4‐100], 75.4% [49.4‐89.5]; MPT4: 66.3% [15.5‐100], 59.7% [33.8‐81.2]; P = .0005) of PPI treatment compared to pretreatment (MPT3: 58.3% [0.02‐93.9], 52.6% [6.1‐94.7]; MPT4: 25.2% [0‐86.8], 32.4% [1.8‐89.3]). Six dogs (66%, [0.36, 0.97]) reached pH goals established in humans with q24h dosing.Both q24h PO esomeprazole doses were effective in raising intragastric pH, despite high intersubject variability, but 33% of dogs required q12h dosing to reach pH goals. [ABSTRACT FROM AUTHOR]

Background/Aims: Long‐term acid suppression with proton pump inhibitors (PPI) leads to hypochlorhydria and facilitates the growth of bacterial flora in the small intestine. Novel acid‐suppressants called potassium‐competitive acid blockers (P‐CABs) seem to be superior to PPIs. However, data on the risk of small intestinal bacterial overgrowth (SIBO) in patients taking P‐CABs are limited. Method: We retrospectively analyzed a consecutive series of patients with long‐term acid‐suppressant (PPIs or P‐CABs) use for gastroesophageal reflux disease or nonsteroidal anti‐inflammatory drug (NSAID)‐induced gastropathy. All of them underwent endoscopic examinations and Helicobacter pylori testing and took PPIs or P‐CABs for at least 3 months. Glucose hydrogen breath tests (GBT) were performed to check for SIBO, and newly developed SIBO‐related symptoms including bloating, postprandial discomfort, diarrheas, and constipation, were evaluated. Results: A total of 142 patients were enrolled. Six patients were excluded due to equivocal Helicobacter pylori infection results. The frequency of positive GBTs was 31.7% (25/79) for PPI and 22.8% (13/57) for P‐CAB use (p = 0.15). Regarding GBT positivity, age‐related factor was found to be significant in multivariate analysis (p = 0.02). The results of multivariate analysis in cases of SIBO‐related symptoms showed that GBT positivity and PPI use were significant (p < 0.01). Conclusion: Long‐term use of gastric acid suppressants resulted in positive GBT in approximately 30% of patients, and the risk was particularly high in elderly patients. The occurrence of SIBO‐related symptoms was significant in long‐term use of PPIs and in patients with positive GBT. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMaterial and methodsResultsConclusionsEosinophilic esophagitis (EoE) is a chronic immune-mediated disease. The budesonide orodispersible tablet (BOT) is recommended as second-line treatment according to the Danish guideline. This study aimed to compare potential treatment disparities before BOT initiation, follow-up practices, clinico-histologic remission rates during BOT treatment, and adherence to the national guideline between the highly specialized EoE-Cph cohort and the population-based DanEoE cohort.This cohort study compared 65 adult patients from the EoE-Cph cohort with 65 patients from the DanEoE cohort. All patients were diagnosed between 2015-2021. The diagnosis of EoE was defined according to the AGREE consensus. Data were extracted manually from medical records and registries.In the EoE-Cph cohort, 88% were prescribed proton pump inhibitors (PPIs) before started on BOT compared to 100% in the DanEoE cohort (p = 0.0035). Symptomatic follow-up occurred in 89% of EoE-Cph patients compared to 97% of DanEoE patients after BOT treatment (p = 0.0841). No difference was found between patients who underwent histologic follow-up after topical steroid treatment (83% versus 82%, p = 0.8162). Complete clinico-histologic remission was frequently observed, and no significant difference was observed between the two cohorts (67% versus 80%, p =0.1789). One out of four patients had conflicting symptomatic and histological responses.This study did not provide conclusive evidence favoring the treatment of EoE patients exclusively at highly specialized EoE centers. However, the authors acknowledge that further evidence is necessary before considering changes in clinical practice. Conflicting treatment responses, and discontinuation of treatment due to side effects remains a notable concern. [ABSTRACT FROM AUTHOR]

ABSTRACT Abomasal ulcers are a challenge in animal farming, affecting health, welfare, and productivity. Omeprazole's (OPZ) efficacy in treating these ulcers is known, but data on its pharmacokinetics (PK) in adult goats and sheep are lacking. The purpose of this research was to investigate and contrast OPZ's PK in these animals following a single intravenous (IV, 1 mg/kg) and subcutaneous (SC, 2 mg/kg) doses. Sheep and goats had similar exposure levels for all administration routes, with no significant AUC(0‐∞)D variations. Half‐life was short in both species (sheep: 0.20 h; goats: 0.31 h). Goats had a higher volume of distribution after IV administration. Clearance was rapid, and extraction ratio values were high for both goats and sheep (43% and 30%, respectively). SC administration showed similarities in Cmax and Tmax values between species. Both goats and sheep had high bioavailability (about 80%) levels and comparable mean absorption times (MAT). Despite some PK parameters' variances, systemic exposure to OPZ is similar in sheep and goats. SC administration's high bioavailability suggests it as a convenient field application route. Further investigations are needed to understand OPZ's effectiveness in small ruminants with abomasal ulcers and improve dosing regimens for clinical use. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) versus controls in different segments of the gastrointestinal tract, as well as the links between the MAM, gastrointestinal symptoms, and use of proton pump inhibitors (PPI). Methods: We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms), 44 patients with ulcerative colitis (UC) and 31 with Crohn's disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardised nutrient challenge (SNC). Results: Microbial communities of the MAM in the upper and lower gastrointestinal tract differed. IBD patients were characterised by relative and absolute depletion of numerous genera known to produce butyrate and/or propionate, with the largest differentiation being the depletion of Faecalibacterium in the lower gastrointestinal tract of CD patients. Notably, PPI users exhibited an enrichment of Faecalibacterium in the lower gastrointestinal tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the gastrointestinal tract. Conclusion: The absolute and relative composition of the MAM is variable across different segments of the gastrointestinal tract. These quantitative changes indicates that MAM can be targeted in specific segments of the GI tract to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Despite being cornerstone medications for managing gastrointestinal disorders, proton pump inhibitors (PPI) have raised concerns due to inappropriate prescribing and overutilization, their potential side effects, and interactions with other medications. General practitioners (GPs) provide long-term patient follow-up and are targets to promote PPI deprescribing to reach the widest possible population. GPs practicing in rural settings encounter unique challenges as their numbers dwindle and their workload increases. Hence, targeted educational interventions are crucial to promote appropriate prescribing practices in such underserved areas. Methods: We developed a continuing medical education (CME) program focused on PPI deprescribing for GPs in rural settings. The program comprised of an interactive training session featuring clinical cases, an open discussion, and distribution of educational materials. We assessed the program's effectiveness using a two-level Kirkpatrick model, evaluating participant satisfaction and knowledge levels through pre- and post-course questionnaires. Results: Thirty-three GPs participated, with 61.9% working in semi-rural and 38.1% in rural areas (21 responded to the 1st questionnaire, 14 to the 2nd). Median medical experience was 6 years, with 61.9% serving as internship supervisors. Despite 95.2% acknowledging PPI overprescription, none had previously participated in dedicated PPI CME programs. The open discussion session provided valuable insights into various topics related to PPI use and gastrointestinal health. Participants expressed high satisfaction with the program (average rating of 9.1/10) and 92.9% reported changes in practice, including increased awareness of inappropriate PPI prescriptions. Indeed, 92.9% of GPs identified inappropriate PPI use following the course. 57.1% of participants utilized the provided educational materials. The main practice changes observed included an increased reassessment rate of PPI indications (71.4% at each renewal after vs. 19% before, 28.6% non-systematically after vs. 66.8% before, 0% rarely after vs. 14.3% before; p = 0.006), the necessity for more than one consultation to deprescribe (64.3% after vs. 23.8% before; p = 0.021), systematic utilization of gradual cessation of PPI (100% vs. 61.9%; p = 0.039) and more frequent use of additional medication (92.9% vs. 57.1%; p = 0.022), primarily antiacids (92.3%). Conclusions: Our study underscores the effectiveness of targeted CME programs in promoting appropriate prescribing practices and enhancing knowledge among GPs in rural settings. Despite the challenges encountered in deprescribing PPI, the program facilitated proactive approaches in managing treatment discontinuation failures. Tailored educational interventions are essential for mitigating medication prescribing challenges and improving patient outcomes in rural primary care settings. Trial registrations: Not applicable. [ABSTRACT FROM AUTHOR]

Acute upper gastrointestinal bleeding (UGIB) is a medical emergency with most common cause being peptic ulcer disease (PUD) or variceal bleeding. However, cancers that cause UGIB by invading the small intestine are uncommon, and the invasion of renal cell carcinoma (RCC) into the duodenum is an even rarer occurrence. A 55‐year‐old male presented with melena and right flank pain. Esophagogastroduodenoscopy (EGD) revealed an active bleeding source in the duodenum, later identified on contrast‐enhanced computed tomography (CECT) as a duodenorenal fistula (DRF) caused by direct extension of the RCC. The imaging confirmed the presence of a malignant renal mass infiltrating adjacent organs. This atypical presentation of RCC with DRF manifesting as UGIB underscores the importance of comprehensive evaluations in cases of gastrointestinal bleeding to identify rare underlying causes. [ABSTRACT FROM AUTHOR]

Background: This study aims to explore the relationship between magnesium depletion score (MDS) and periodontitis in US adults using data from the National Health and Nutritional Examination Survey (NHANES) 2009–2014. Methods: This cross-sectional study's outcome was periodontitis, defined by the CDC/AAP using clinical periodontal parameters. The exposure of this study was MDS, which was calculated according to four parameters (diuretic use, proton pump inhibitor use, renal function and alcohol consumption). Weighted univariable and multivariable logistic regression analyses were performed to explore the association between MDS intake and periodontitis. Confounding factors included in the adjusted model were age, sex, race, income, smoking status, dietary magnesium, obesity, diabetes, hypertension, education level, recreational activity, and work activity. Results: A total of 8,628 participants over the age 30 were included in our study. Individuals with high level of magnesium deficiency were more likely referred to poorer periodontal health in both crude model (OR = 2.01, 95% CI: 1.54–2.61, p < 0.0001) and fully adjusted model (OR = 1.35, 95% CI: 1.03–1.77, p = 0.03). Conclusions: MDS is positively associated with moderate/severe periodontitis. Further longitudinal studies are needed to understand the impact of MDS on periodontitis. [ABSTRACT FROM AUTHOR]

The relationship between magnesium deficiency and metabolic dysfunction associated steatotic liver disease (MASLD) remains unclear. This study aimed to examine the association between the magnesium depletion score (MDS) and the risk of MASLD, as well as explore potential underlying mechanisms. Data from 12,024 participants from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 were analyzed. MDS was calculated based on the use of diuretics and proton pump inhibitors, kidney function, and alcohol consumption. MASLD was defined using the fatty liver index. Logistic regression, restricted cubic spline analysis, and mediation analyses were conducted to evaluate the association between MDS and MASLD and to identify potential mediators. A higher MDS was significantly associated with an increased risk of MASLD (OR = 2.00, 95% CI [1.47, 2.74] for MDS 3 vs. 0). A dose-response relationship between MDS and MASLD risk was observed. Neutrophils, albumin, and white blood cells partially were identified as partial mediators of the association, with albumin exhibiting the highest mediating effect (14.05%). Elevated MDS is significantly associated with an increased risk of MASLD in U.S. adults. Inflammation and albumin may serve as potential mediators of this relationship. These findings underscore the importance of addressing magnesium deficiency in the prevention and management of MASLD. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are some of the most frequently prescribed medications, but they are often used inappropriately, either being prescribed without a clear indication or continued for longer than necessary. In such cases, deprescribing is recommended. However, despite its proven effectiveness, the implementation of deprescribing in clinical practice remains inconsistent and varied, making it challenging to identify the most effective strategies. The goal is to provide a comprehensive outline of deprescribing interventions for PPI therapy implemented across various settings and by different healthcare professionals. Methods: The study is designed to be a systematic review of the published literature. PubMed, Embase, and Web of Science databases were searched from 1 January 1989 (the first PPI on the market) to 30 September 2024 for articles assessing PPI deprescribing in adult patients, focusing on the implementation rate (primary outcome) or effects on symptoms (secondary outcome). Results: After screening, 66 studies were included, predominantly pragmatic trials (N = 32) or randomized controlled trials (N = 25). We found a variety of interventions promoting PPI deprescription. Collaborative efforts involving multiple healthcare professionals, the use of algorithms for clinical decision-making, and patient involvement have proven to be key elements in the most effective strategies. Discontinuing therapy may not be advisable in cases of recurrent symptoms, suggesting that on-demand therapy could be a recommended approach. Deprescribing is particularly relevant for individuals with mild illnesses and symptoms, where tapering can effectively mitigate the rebound symptoms often associated with abrupt discontinuation. Conclusions: Given the current prevalence of inappropriate PPI prescribing, it is imperative to raise awareness among both physicians and patients about the importance of the deprescribing process, which should be tailored to the specific needs of each patient, considering his/her medical history, current health status, and personal preferences. [ABSTRACT FROM AUTHOR]

Background/Objectives: Proton pump inhibitors (PPIs) are amongst the most commonly prescribed classes of medication. However, inappropriate PPI use can lead to several adverse drug reactions (ADRs). Limited data exist on factors contributing to the risk of ADRs associated with PPI prescribing patterns in the Eastern Region of Saudi Arabia. This retrospective, cross-sectional study aimed to assess the prevalence and the pattern of PPI use and to identify factors contributing to the risk of ADRs. Methods: Data were collected from electronic medical records of patients at Al-Qateef Central Hospital from January 2020 to December 2021. The inclusion criteria included patients aged ≥40 years attending an outpatient medical care clinic. PPI prescribing patterns were categorized based on their dosage intensity into low-dose, medium-dose (MD), and high-dose (HD) categories. Binary and multinominal logistic regression models were used to determine the relationship between PPI prescribing patterns and use, categorized by MD or HD, and patient characteristics, adjusted for significant covariates. Results are presented as adjusted odds ratio (OR) with corresponding 95% confidence intervals (95% CI). Results: The study included 41,084 patients. The prevalence of PPI prescribing was 31%. PPI users were more frequently found to be females than males (52% vs. 50%, p = 0.013); they were also likely to be prescribed more medications (7 vs. 6, p < 0.001), but less likely to have gastritis-related diseases (34% vs. 32%, p < 0.001) compared to non-users. PPI HD users were more likely male (56% vs. 43%, p < 0.001), older (53 vs. 52 years, p < 0.001), and prescribed more medications (11.8 vs. 2.8, p < 0.001) compared to MD users. PPI usage was associated with concurrent use of antiplatelet drugs (OR = 1.08, 95% CI 1.01–1.15). An increasing number of prescribed medications was associated with HD usage (OR = 1.13, 95% CI 1.12–1.14), but negatively associated with MD usage (OR = 0.7 95% CI 0.69–0.71). Female gender was negatively associated with HD usage (OR = 0.85, 95% CI 0.79–0.91). Conclusions: Our findings indicate that 31% of the included cohort were prescribed PPI. Inappropriate PPI prescribing related to the drug's omission is a concern as PPI non-users presented with valid indications such as gastritis. Male gender and increasing NPM were the common factors contributing to increased risk of PPI ADR. This study points to the importance of re-evaluating PPI use to ensure effective therapy with minimum risks of ADR. [ABSTRACT FROM AUTHOR]

Objective To investigate the use of proton pump inhibitors (PPIs) for preventing non-steroidal anti-inflammatory drug (NSAID) related gastric mucosal injury in orthopedic patients and to evaluate its rationality, providing a reference for the proper use of PPIs. Methods A retrospective survey was conducted, collecting data from January 1,2022, to December 31,2022, on orthopedic patients who used PPIs to prevent NSAID-related gastric mucosal injury. The study assessed whether patients had indications for prophylactic use of PPIs and then evaluated the appropriateness of drug selection, timing of administration, dosage, and duration of treatment in cases with indications. Results Out of 307 patients, 62(20.20%) did not have indications for prophylactic use of PPIs. Among the 245 instances where there were indications, 83 instances (33.88%) involved inappropriate medication use, primarily due to unsuitable drug selection, inappropriate timing of administration, inappropriate frequency of administration, and excessively long treatment duration. Conclusion The inappropriate use of PPIs to prevent NSAID-related gastric mucosal injury in the orthopedics department is notable. Physicians should strictly control the indications for medication use, and pharmacists should enhance prescription review to jointly promote the rational use of drugs. [ABSTRACT FROM AUTHOR]

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

Introduction: Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma. Areas covered: Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients. Expert opinion: PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD. [ABSTRACT FROM AUTHOR]

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]

Medication can affect the gut microbiota composition and function. The aim of this study was to investigate connections between use of common non-antibiotic medicines and the gut microbiota composition and function in a large Swedish cohort (N = 2223). Use of 67 medications and polypharmacy (≥ 5 medications), based on self-reported and prescription registry data, were associated with the relative abundance of 881 gut metagenomic species (> 5% prevalence) and 103 gut metabolic modules (GMMs). Altogether, 97 associations of 26 medications with 40 species and of four medications with five GMMs were observed (false discovery rate < 5%). Several earlier findings were replicated like the positive associations of proton pump inhibitors (PPIs) with numerous oral species, and those of metformin with Escherichia species and with lactate consumption I and arginine degradation II. Several new associations were observed between, among others, use of antidepressants, beta-blockers, nonsteroidal anti-inflammatory drugs and calcium channel blockers, and specific species. Polypharmacy was positively associated with Enterococcus faecalis, Bacteroides uniformis, Rothia mucilaginosa, Escherichia coli and Limosilactobacillus vaginalis, and with 13 GMMs. We confirmed several previous findings and identified numerous new associations between use of medications/polypharmacy and the gut microbiota composition and functional potential. Further studies are needed to confirm the new findings. [ABSTRACT FROM AUTHOR]