Search Results (12)

Background and objectives: Life expectancies have increased globally, including in Romania, leading to an aging population and thus increasing the burden of chronic diseases. Over 80% of individuals over 65 have more than three chronic conditions, with many exceeding ten and often requiring multiple medications and supplements. This widespread polypharmacy raises concerns about drug interactions, side effects, and inappropriate prescribing. This review examines the impact of polypharmacy in older adult patients, focusing on the physiological changes affecting drug metabolism and the potential risks associated with excessive medication use. Special attention is given to proton pump inhibitors (PPIs), a commonly prescribed drug class with significant benefits but also risks when misused. The aging process alters drug absorption and metabolism, necessitating careful prescription evaluation. Methods: We conducted literature research on polypharmacy and PPIs usage in the older adult population and the risk associated with this practice, synthesizing 217 articles within this narrative review. Results: The overuse of medications, including PPIs, may lead to adverse effects and increased health risks. Clinical tools such as the Beers criteria, the STOPP/START Criteria, and the FORTA list offer structured guidance for optimizing pharmacological treatments while minimizing harm. Despite PPIs’ well-documented safety and efficacy, inappropriate long-term use has raised concerns in the medical community. Efforts are being made internationally to regulate their consumption and reduce the associated risks. Conclusions: Physicians across all specialties must assess the risk–benefit balance when prescribing medications to older adult patients. A personalized treatment approach, supported by evidence-based prescribing tools, is essential to ensure safe and effective pharmacotherapy. Addressing inappropriate PPI use is a priority to prevent potential health complications. Full article

Background and Objectives: Perforated peptic ulcers are a common surgical emergency and rank among the leading causes of acute peritonitis worldwide. Previous studies have suggested a seasonal pattern in the occurrence of symptomatic perforated peptic ulcers. With the advancement of modern medicine, including the widespread use of proton pump inhibitors, and the effects of climate change, this study aimed to assess potential seasonal variations in the incidence of peptic ulcer perforation in our region. Methods: This retrospective analysis included 104 adult patients (mean age: 61.5 ± 14.7 years) who underwent surgical treatment for peptic ulcer perforation between January 2021 and April 2024. Patients were analyzed by gender, age, risk factors (smoking and alcohol consumption), the location of the perforation (gastric or duodenal), and discharge outcome (survived or deceased). Additionally, cases were categorized by the month and season of the ulcer perforation. Results: Among the 104 patients (mean age 61.5 ± 14.7 years), 68 (65.4%) were male. Gastric and duodenal perforations were nearly equally observed (51% vs. 49%). A statistically significant difference in overall perforation rates by gender was observed (p = 0.009), though not between ulcer sites (p = 0.628 and p = 0.739). The highest number of perforations occurred in July (n = 12), while the lowest occurred in November (n = 4); however, no significant variation was found by month (p = 0.916) or season (p = 0.891), despite a predominance in spring. Comorbidities were present in 60% of patients. Smoking (33.6%) and alcohol use (22.1%) were common. Alcohol abuse was noted in 22.1% of patients and was significantly associated with both gastric (p < 0.001) and duodenal (p < 0.001) perforations, though not with the overall incidence (p = 0.284). Smoking, reported in 33.6% of patients, showed no significant association with the perforation site or overall incidence (p = 0.946). The combination of smoking and alcohol use favored gastric perforations, but without statistical significance (p = 0.157). Conclusions: Alcohol consumption appeared to increase the risk of ulcer perforation, while smoking did not demonstrate a statistically significant association. Although spring exhibited the highest observed incidence of peptic ulcer perforation, seasonal variation did not show a statistically significant difference overall. Full article

Background: Exposure to antimicrobials and Proton Pump Inhibitors (PPIs) are modifiable risk factors for nosocomial Clostridiodes difficile infection (CDI). We investigated the association between these agents and nosocomial CDI over five years. Methods: Nosocomial CDI from January 2017 to December 2021 were included. Consumption trends were analyzed using a simple linear regression model. A correlation analysis was performed using Spearman’s test in two ways: without a time interval and with 1-month interval matching. An interrupted time-series method to evaluate the impact of three key temporal breakpoints on CDI incidence rate was performed using the Poisson regression model. Results: A downward trend for cephalexin, ceftriaxone, clindamycin, gentamicin, macrolides, metronidazole, and penicillin sodium was identified. In contrast, an upward trend was recognized for amoxicillin, ceftazidime/avibactam, ertapenem, fluconazole, ketoconazole, levofloxacin, and tigecycline. Among the antimicrobials that showed a positive association between consumption and the incidence of CDI are clindamycin and cephalosporins after immediate consumption. Moreover, macrolides and metronidazole presented a positive correlation, in both immediate and delayed consumption. PPIs consumption did not show changes and was not associated with nosocomial CDI incidence. The interrupted time series analysis showed no changes at the breakpoints selected. Conclusions: Consumption of clindamycin, cephalosporins, and macrolides showed positive association with CDI, despite having a downtrend in consumption. Specific events, such as the COVID-19 pandemic and the implementation of ASP, have had no correlation with CDI. Further analysis is required in Latin America to advance our understanding of risk factors associated with CDI. Full article

Background/Objectives: Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders, but their potential association with lung cancer risk and mortality remains underexplored and debated. This study sought to investigate the association between PPI use and lung cancer likelihood and mortality, focusing on the impact of PPI exposure history and duration. Methods: This study utilized data from 6795 lung cancer patients, 27,180 matched controls, and 4257 deceased and 2538 surviving lung cancer patients from the Korean National Health Insurance Service’s Health Screening Cohort (2002–2019). Propensity score overlap weighting and logistic regression models were applied to assess the correlations between PPI usage history and duration with lung cancer risk and mortality, while standardized differences ensured balanced baseline characteristics. Results: Overall, PPI use was modestly associated, with a 19% increased likelihood of lung cancer occurrence (95% confidence intervals (CI): 1.12–1.26). Interestingly, prolonged PPI use (≥30 days) was linked to a 13% reduction in lung cancer incidence (95% CI: 0.80–0.94), particularly in subgroups such as older adults (≥70 years), individuals with gastroesophageal reflux disease (GERD) or hypertension, and those with low alcohol consumption. Conversely, overall PPI usage was linked with a 36% increased mortality likelihood among lung cancer patients (95% CI: 1.20–1.55), with prolonged use further correlating with a 27% higher mortality risk (95% CI: 1.05–1.53), especially in high-risk subgroups, including smokers, underweight individuals, and those with hypercholesterolemia or GERD. Conclusions: These findings may suggest a complex and context-dependent relationship between PPI use and lung cancer outcomes, emphasizing the need for individualized risk assessments and careful prescribing practices. Full article

Background: In the absence of Helicobacter pylori (HP) infection, a characteristic gastric mucus adhesion may appear during the use of vonoprazan. We named this novel characteristic mucus “web-like mucus” (WLM). This study aimed to determine the incidence and risk factors for WLM. Methods: Between January 2017 and January 2022, 5665 patients were enrolled in this study. The patients were divided into a proton-pump inhibitor (PPI)-prescribed group (n = 2000), a vonoprazan-prescribed group (n = 268), and a no-PPI/vonoprazan-prescribed (n = 3397) group, and the presence of WLM was examined. After excluding four patients with autoimmune gastritis, the remaining 264 patients in the vonoprazan group were divided into WLM and non-WLM groups, and their clinical features were analyzed. Results: A total of 55 (21%) patients had WLM, all in the vonoprazan-prescribed group. There were no significant differences in factors such as, sex, age, chronic kidney disease, diabetes mellitus, HP eradication history, smoking, or alcohol consumption between the WLM and non-WLM groups. The median duration from the start of vonoprazan administration to the endoscopic detection of WLM was 2 (1–24) months. Conclusions: WLM appears to be a characteristic feature in patients treated with vonoprazan. Full article

Hybrid therapy is a recommended first-line anti-H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori-infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9–95.1%), 94.4% (95% CI: 93.8–97.2%) and 95.5%% (95% CI: 93.8–97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy. Full article

Proton pump inhibitors (PPIs) are among the most controversially prescribed drugs in polypharmacy. This observational prospective study assessed the PPI prescriptive trend during hospitalization before and after implementation of a prescribing/deprescribing algorithm in a real-life hospital setting and the related clinical–economic benefit at discharge. PPI prescriptive trends were compared between three quarters of 2019 (9 months) and the same period of 2018 by a chi-square test with a Yate’s correction. The proportions of treated patients in the two years (1120 discharged patients in 2018 and 1107 in 2019) were compared by the Cochran–Armitage trend test. DDDs (defined daily doses) were compared between 2018 and 2019 by the non-parametric Mann–Whitney test and normalizing DDD/DOT (days of therapy) and DDD/100 bd (bed days) for each patient. Multivariate logistic regression was performed on PPI prescriptions at discharge. The distribution of patients with PPIs at discharge was significantly different in the two years (p = 0.0121). There was a downward trend in the number of PPI prescriptions (29.9%) in the third trimester of 2019 compared to the others of the same year (first trimester: 34.1%, second trimester: 36.0%) and by contrast with the same periods of 2018 (29.4, 36.0, and 34.7%) (p = 0.0124). DDDs/patient did not differ between 2018 and 2019 nor across the three trimesters. However, both DDD/DOT and DDD/100 bd showed a decrease in the third trimester of 2019, with a marked difference for DDD/DOT (p = 0.0107). The reduction in consumption detected in the last phase of 2019 in terms of DDD/DOT was 0.09 with a consequent containment of pharmaceutical spending. The development and implementation of multidisciplinary prescribing/deprescribing protocols in both hospital and community settings could lead to a reduction in the misuse of PPIs, with significant savings in healthcare resources. Full article

Clopidogrel, an antiplatelet agent used for secondary prevention of cerebrovascular diseases, is often taken with proton pump inhibitors (PPIs). Generally, the combined use of clopidogrel and PPIs causes adverse drug–drug interactions. VerifyNow is a quick and convenient method to confirm clopidogrel resistance (CR), which compromises adequate antithrombotic effects. We aimed to confirm CR, identify its factors, and determine the influence of the combination of ilaprazole and clopidogrel on clopidogrel using VerifyNow. In this retrospective study, we examined patients who were receiving clopidogrel after three months, starting within one week from the onset of cerebral infarction symptoms. Clinical records, imaging records, and diagnostic laboratory results, including P2Y12 reaction units (PRU), were compared and analyzed to check for CR. Additionally, the groups treated with either both ilaprazole and clopidogrel or with medications other than ilaprazole were comparatively analyzed. CR was defined as a PRU ≥240 after clopidogrel for three months. Among factors influencing CR by affecting clopidogrel metabolism, positive statistical correlations with age and alcohol consumption were confirmed. The diagnostic tests revealed a lower glomerular filtration rate and platelet count of the CR-positive group. This finding proved that the combination therapy of ilaprazole and clopidogrel is safe, as it does not interfere with the metabolism of clopidogrel. Full article

The oxidation of proline to pyrroline-5-carboxylate (P5C) leads to the transfer of electrons to ubiquinone in mitochondria that express proline dehydrogenase (ProDH). This electron transfer supports Complexes CIII and CIV, thus generating the protonmotive force. Further catabolism of P5C forms glutamate, which fuels the citric acid cycle that yields the reducing equivalents that sustain oxidative phosphorylation. However, P5C and glutamate catabolism depend on CI activity due to NAD⁺ requirements. NextGen-O2k (Oroboros Instruments) was used to measure proline oxidation in isolated mitochondria of various mouse tissues. Simultaneous measurements of oxygen consumption, membrane potential, NADH, and the ubiquinone redox state were correlated to ProDH activity and F₁F_O-ATPase directionality. Proline catabolism generated a sufficiently high membrane potential that was able to maintain the F₁F_O-ATPase operation in the forward mode. This was observed in CI-inhibited mouse liver and kidney mitochondria that exhibited high levels of proline oxidation and ProDH activity. This action was not observed under anoxia or when either CIII or CIV were inhibited. The duroquinone fueling of CIII and CIV partially reproduced the effects of proline. Excess glutamate, however, could not reproduce the proline effect, suggesting that processes upstream of the glutamate conversion from proline were involved. The ProDH inhibitors tetrahydro-2-furoic acid and, to a lesser extent, S-5-oxo-2-tetrahydrofurancarboxylic acid abolished all proline effects. The data show that ProDH-directed proline catabolism could generate sufficient CIII and CIV proton pumping, thus supporting ATP production by the F₁F_O-ATPase even under CI inhibition. Full article

Background: Clopidogrel and proton pump inhibitors (PPIs) are among the most used drugs in Denmark for which there exists pharmacogenomics (PGx)-based dosing guidelines and FDA annotations. In this study, we further scrutinized the use of clopidogrel and PPIs when prescriptions were redeemed from Danish Pharmacies alone or in combination in the Danish population and among persons with diabetes in Denmark. The focus deals with the potential of applying PGx-guided antiplatelet therapy taking both drug–drug interactions (DDI) and drug–gene interactions (DGI) into account. Methods: The Danish Register of Medicinal Product Statistics was the source to retrieve consumption data. Results: The consumption of PPIs and clopidogrel in terms of prevalence (users/1000 inhabitants) increased over a five-year period by 6.3% to 103.1 (PPIs) and by 41.7% to 22.1 (clopidogrel), respectively. The prevalence of the use of clopidogrel and PPIs in persons with diabetes are 3.8 and 2.1–2.8 times higher compared to the general population. When redeemed in combination, the prevalence increased to 4.7. The most used combination was clopidogrel and pantoprazole. Conclusions: The use of clopidogrel and PPIs either alone or in combination is quite widespread, in particular among the elderly and persons with diabetes. This further supports the emerging need of accessing and accounting for not only DDI but also for applying PGx-guided drug therapy in clinical decision making for antiplatelet therapy with clopidogrel having a particular focus on persons with diabetes and the elderly. Full article

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis. Full article

Background: This study describes the prevalence of non-steroidal anti-inflammatory drug (NSAID) use, and analyses prescribing patterns of NSAIDs and associated gastroprotection. Methods: The study population consisted of 5650 workers at the General Motors automobile assembly plant in Zaragoza, Spain. NSAID prescription data for 2014 were obtained from the prescription database of Aragon (Spain). NSAID consumption was determined based on the number of defined daily doses purchased per year. Heavy NSAIDs users were identified using Lorenz curves. Results: NSAID use in the cohort was high (40.7% of workers, 95% CI 39.4–41.9). The prescription of proton pump inhibitors increased with age. Gastrointestinal protection was lacking in some participants who were being treated with drugs associated with a high risk of gastrointestinal bleeding. Heavy NSAID users (defined as those above the 95th percentile of consumption), accounted for 26% of total DDDs, and consumed a greater proportion of coxibs than non-heavy users. Conclusions: The rate of NSAID consumption in the cohort was high. To reduce the risk of gastrointestinal complications, monitoring and adequate gastroprotection are essential in patients who are prescribed NSAIDs for long periods of time or who are treated concomitantly with drugs that increase the risk of gastrointestinal bleeding. Full article