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The Journal of the Association of... Oct 2023: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of...
: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of gastroesophageal reflux disease (GERD). : In this multicenter retrospective study, electronic medical records (EMRs) of GERD patients prescribed with PPIs at two Indian clinics/hospitals were reviewed (2016-2020). Rabeprazole's effectiveness was assessed at different follow-up visits and compared with other PPIs. : Overall, 269 patients (moderate and severe GERD: 84.39%) were included in three groups, rabeprazole, pantoprazole, and esomeprazole groups. A significant proportion of patients experienced quick and complete symptomatic relief at visit 1 with rabeprazole compared to the baseline visit, which gradually increased till visit 4 for both daytime [ heartburn (38.78-93.88%; < 0.001)] and nocturnal symptoms [ sleep disturbances (62.92-97.75%; < 0.001)]. Rabeprazole provided quick relief at visit 1 when compared with pantoprazole for daytime heartburn (38.78 vs 5.56%; = 0.01), daytime epigastric pain (66.04 vs 12.12%; = 0.049), and nocturnal water brash (60.71 vs 16.13%; = 0.015), and when compared with esomeprazole for nocturnal nausea (82.61 vs 20.00%; = 0.013). Further, the proportion of patients exhibiting complete treatment response was relatively higher in the rabeprazole group (83.33%) than in the pantoprazole (62.07%) and esomeprazole (65.67%) groups at visit 4. : Rabeprazole was effective in providing quick and sustained relief for both daytime and nocturnal GERD symptoms in patients with moderate and severe GERD. Rabeprazole also demonstrated greater effectiveness when compared with pantoprazole and esomeprazole in reducing the severity of multiple GERD symptoms. : Lawate P, Jilawar N, Vyas K, Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study). J Assoc Physicians India 2023;71(10):37-44.
Topics: Humans; Proton Pump Inhibitors; Gastroesophageal Reflux; Rabeprazole; Retrospective Studies; Male; Female; Middle Aged; Severity of Illness Index; Adult; Pantoprazole; Esomeprazole; Treatment Outcome; Electronic Health Records
PubMed: 38716522
DOI: 10.59556/japi.71.0366 -
Pharmacological Research Jun 2024Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6... (Review)
Review
Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
Topics: Humans; Low Density Lipoprotein Receptor-Related Protein-6; Neoplasms; Animals; Antineoplastic Agents; Molecular Targeted Therapy; Wnt Signaling Pathway
PubMed: 38710241
DOI: 10.1016/j.phrs.2024.107200 -
Pharmacotherapy Feb 2024Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs).
METHODS
To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA).
RESULTS
Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB.
CONCLUSIONS
This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.
Topics: Humans; Adult; Pharmaceutical Preparations; Network Meta-Analysis; Proton Pump Inhibitors; Rabeprazole; Histamine H2 Antagonists; Benzene Derivatives; Imidazoles; Pyrroles; Sulfonamides
PubMed: 38049205
DOI: 10.1002/phar.2899 -
Trials Aug 2023Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use...
Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial.
BACKGROUND
Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection.
METHODS
The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.
DISCUSSION
Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.
TRIAL REGISTRATION
REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].
Topics: Humans; Proton Pump Inhibitors; Pantoprazole; Respiration, Artificial; Cohort Studies; Critical Illness; Venous Thromboembolism; COVID-19; Gastrointestinal Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37644556
DOI: 10.1186/s13063-023-07589-2 -
Medical Oncology (Northwood, London,... Dec 2023Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to... (Randomized Controlled Trial)
Randomized Controlled Trial
Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.
Topics: Adult; Male; Humans; Middle Aged; Female; Squamous Cell Carcinoma of Head and Neck; Pantoprazole; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 38129716
DOI: 10.1007/s12032-023-02234-z -
Acta Anaesthesiologica Scandinavica Jun 2024Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological...
BACKGROUND
Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole.
METHODS
Extended Cox models with time-varying co-variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed.
RESULTS
Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause-specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19-0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14-1.82, p = .003), and lower risk of all-cause mortality (HR: 0.22, 95% CI: 0.18-0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21-0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13-0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63-1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all-cause mortality (HR: 1.27, 95% CI: 0.99-1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all-cause mortality was statistically significant (p = .024).
CONCLUSIONS
Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study.
PubMed: 38867404
DOI: 10.1111/aas.14471 -
BioMed Research International 2023Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the...
BACKGROUND
Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion.
METHODS
Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation.
RESULTS
The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups.
CONCLUSION
Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.
Topics: Male; Animals; Rats; Pantoprazole; Gastrins; Alkaline Phosphatase; Octreotide; Bone Diseases, Metabolic; Parathyroid Hormone
PubMed: 37711876
DOI: 10.1155/2023/2594664 -
Arquivos de Gastroenterologia 2023•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse...
•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.
Topics: Humans; Gemifloxacin; Helicobacter pylori; Bismuth; Pantoprazole; Retrospective Studies; Drug Therapy, Combination; Helicobacter Infections; Amoxicillin; Metronidazole; Treatment Outcome; Gastritis; Anti-Bacterial Agents; Proton Pump Inhibitors
PubMed: 37792765
DOI: 10.1590/S0004-2803.230302-23-51 -
Drugs & Aging Jul 2023Cumulative evidence of dementia risk in patients taking proton pump inhibitors (PPIs) is still inconclusive, probably due to a variety of study designs.
BACKGROUND
Cumulative evidence of dementia risk in patients taking proton pump inhibitors (PPIs) is still inconclusive, probably due to a variety of study designs.
OBJECTIVE
This study aimed to compare how the association between dementia risk and use of PPIs differs by different outcome and exposure definitions.
METHODS
We conceptualized a target trial using claims data with 7,696,127 individuals aged 40 years or older without previous dementia or mild cognitive impairment (MCI) from the Association of Statutory Health Insurance Physicians in Bavaria. Dementia was defined as either including or excluding MCI to compare how the results alter by different outcome definitions. We used weighted Cox models to estimate the PPI initiation effect on dementia risk and weighted pooled logistic regression to assess the effect of time-varying use versus non-use during 9 years of study period, including 1 year of wash-out period (2009-2018). The median follow-up time of PPI initiators and non-initiators was 5.4 and 5.8 years, respectively. We also evaluated the association between each PPI agent (omeprazole, pantoprazole, lansoprazole, esomeprazole, and combined use) and dementia risk.
RESULTS
A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk. A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.
CONCLUSION
Our large study supports existing evidence that PPI use is related to an increased risk of dementia.
Topics: Humans; Proton Pump Inhibitors; Pantoprazole; Omeprazole; Cognitive Dysfunction; Dementia
PubMed: 37178361
DOI: 10.1007/s40266-023-01031-7 -
Geriatrics (Basel, Switzerland) Aug 2023Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of...
Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential.
BACKGROUND
Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of 290 older adults and analysed the prevalence of gene polymorphisms that can increase their interacting potential. We also pinpointed clinical decision support systems (CDSSs) that incorporate pharmacogenomic factors in DDI risk evaluation.
METHODS
Perpetrator drugs were identified using the Drug Interactions Flockhart Table, the DRUGBANK website, and the Mayo Clinic Pharmacogenomics Association Table. Allelic variants affecting their activity were identified with the PharmVar, PharmGKB, dbSNP, ensembl and 1000 genome databases.
RESULTS
Amiodarone, amlodipine, atorvastatin, digoxin, esomperazole, omeprazole, pantoprazole, simvastatin and rosuvastatin were perpetrator drugs prescribed to >5% of our patients. Few allelic variants affecting their perpetrator activity showed a prevalence >2% in the European population: CYP3A4/5*22, *1G, *3, CYP2C9*2 and *3, CYP2C19*17 and *2, CYP2D6*4, *41, *5, *10 and *9 and SLC1B1*15 and *5. Few commercial CDSS include pharmacogenomic factors in DDI-risk evaluation and none of them was designed for use in older adults.
CONCLUSIONS
We provided a list of the allelic variants influencing the activity of drug perpetrators in older adults which should be included in pharmacogenomics-oriented CDSSs to be used in geriatric medicine.
PubMed: 37736884
DOI: 10.3390/geriatrics8050084