Doses Of Proton Pump Inhibitors Research Articles

Proton Pump Inhibitors Worsen Colorectal Cancer Outcomes in Patients Treated with Bevacizumab

Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab.

Postoperative ileus in obstetric and gynecological practice: a prospective solution to the problem

Proton pump inhibitors (PPIs) are the undisputed leaders in the treatment of acid-related diseases. In actual clinical practice, the use of PPIs has been growing exponentially in recent decades. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines and reviews and meta-analyses of the current decade on the safety of PPI use note that when prescribing PPIs in large doses for a long period, the possibility of developing numerous side effects should be taken into account. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to 12/01/2023. The review addresses issues of drug interactions between PPIs and chemotherapeutic drugs, which should certainly be taken into account in real clinical practice. In addition, recent reviews and meta-analyses have examined side effects of long-term PPI use, such as increased risk of infection (Clostridium difficile infection, community-acquired pneumonia), electrolyte disturbances, kidney damage, increased risk of hip, wrist and spine fractures; increased cardiovascular risk and a number of others, which can also have an adverse effect on the prognosis of cancer patients. The risk of developing gastric cancer with long-term PPI therapy can be considered as a likely side effect, since their association with PPI use is not denied or questioned in recent reviews and meta-analyses. There is still uncertainty regarding the increased risk of other cancers, since there are publications that do not confirm their association with PPI use. However, the presented review, despite a number of contradictions, allows us to conclude that the increased cancer risk with long-term use of PPIs is real and must be taken into account when prescribing PPIs for a long term.

Current status and influencing factors of prophylactic use of proton pump inhibitors in internal medicine inpatients receiving glucocorticoid therapy.

The actual situation and influencing factors of prophylactic use of proton pump inhibitors (PPIs) in internal medicine inpatients receiving glucocorticoid therapy are rarely reported. This study aimed to investigate the current status and influencing factors of prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy to provide a basis for rational prophylactic use of PPIs. Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Information on the prophylactic use of PPIs was collected and analyzed by clinical pharmacists. Associated factors with prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. 980 inpatients were finally included in our study, of which 271 (27.7%) inpatients received prophylactic use of PPIs. Among the inpatients prescribed PPIs, 90 inpatients received a standard dose of PPIs twice a day. Multiple logistic regression analysis showed that age ≥80years [OR = 7.009, 95% CI (1.424, 34.495), p = 0.017], history of gastroesophageal reflux disease (GERD) [OR = 2.047, 95% CI (1.338, 3.133), p = 0.001], low platelet count [OR = 0.997, 95% CI (0.994, 0.999), p = 0.004], number of concomitant diseases [OR = 1.104, 95% CI (1.056, 1.153), p < 0.001], junior doctors [OR = 1.755, 95% CI (1.248, 2.468), p = 0.001], glucocorticoid dose (higher than 50mg, measured by methylprednisolone) [OR = 2.455, 95% CI (1.371, 4.395), p = 0.003], antiplatelet agents [OR = 2.567, 95% CI (1.456, 4.524), p = 0.001], immunosuppressants [OR = 1.477, 95% CI (1.014, 2.153), p = 0.042], and betahistine [OR = 5.503, 95% CI (1.124, 26.950), p = 0.035] were associated with more prophylactic use of PPIs. The prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy is common in China. Clinical pharmacists will take targeted measures to promote the rational use of PPIs according to the results of this study.

Significance of serological atrophic gastritis on proton pump inhibitor prescriptions and referrals to gastroscopy in the general population.

We aimed to investigate whether individuals with low pepsinogen I levels differed from those with normal pepsinogen I levels in terms of proton pump inhibitors (PPIs) use, referral to gastroscopy, and findings on gastroscopy. Serum pepsinogen I was measured in 518 persons (mean age 51.6, SD 8.8; 49% women). A medical chart review focused on PPI prescriptions and gastroscopic findings in the follow-up period. Patients with serological atrophic gastritis (pepsinogen I < 28 μg/L) had higher body mass index (27.5 vs 26.2 kg/m2; P = 0.007), were less likely to be current smokers (8% vs 17%; P = 0.025), and had higher prevalence of Helicobacter pylori seropositivity (57% vs 36%; P < 0.001) compared with those without. During follow-up (mean 21.4 years, SD 6.5 years), the patients with serological atrophic gastritis had more often findings of atrophic gastritis or gastric polyps on gastroscopy (20% vs 8%; P < 0.001), despite no differences in the mean number of gastroscopies per 1000 person-years (33 vs 23; P = 0.19) and the mean prescribed PPI dose (omeprazole equivalents) per year (1064 mg vs 1046 mg; P = 0.95). Persons with serological atrophic gastritis had lower odds of being prescribed PPIs at least once (odds ratio [95% confidence interval]: 0.58 [0.35-0.96]), but there was no significant difference in the chance of being referred to gastroscopy at least once (1.15 [0.70-1.96]). Persons with serological atrophic gastritis were less likely to be prescribed PPIs. Persons with serological atrophic gastritis had more often gastric polyps and atrophic gastritis when referred to gastroscopy.

First-line Helicobacter pylori empirical treatment in the Czech Republic (2019–2024) – initial insights from the European registry on H. pylori management (Hp-EuReg)

Summary: Background and Aim: Helicobacter pylori (H. pylori) infection remains a significant public health concern worldwide, including in the Czech Republic. The study aims to provide an overview of the current first-line treatment approaches for H. pylori infection in the Czech Republic based on data from the European Registry on H. pylori Management (Hp-EuReg), and to evaluate the most effective treatment regimens. Methods: Hp--EuReg is an international multicentric registry on the management of H. pylori, from which we extracted data from the Czech Republic from 2019 to January 2024. This registry collects demographic information, diagnostic procedures, treatment prescriptions, and outcomes for H. pylori infection management by gastroenterologists. A modified intention-to-treat (mITT) analysis was performed to evaluate the effectiveness of the treatments. Results: A total of 546 patients from 14 centres in the Czech Republic who receive first-line treatment were analysed. Low-dose (i.e.; 20 mg omeprazole equivalent twice daily) proton pump inhibitors (PPIs) were administered in 89% of patients, and the most common length of treatments was 14 days (40%). The overall mITT effectiveness of first-line treatment was 85%, obtaining 86% when prescriptions were combined either with low-dose (20 mg omeprazole equivalent twice daily), and high dose (80 mg omeprazole equivalent twice daily) PPIs, and 82.5% with standard-dose (40 mg omeprazole equivalent twice daily) PPIs. The effectiveness of 7-day prescriptions was reported to be 83%, lower than that of 10- and 14-day, both of which achieved effectiveness of 86%. The most frequently used treatment scheme was triple therapy with PPI, amoxicillin and clarithromycin, which was used in 67% of patients, reaching 87% effectiveness both with 7- and 14-day prescriptions. Optimal (&gt;90% mITT) effectiveness was obtained with both 10-day, sequential therapy and with 14-day non-bismuth quadruple concomitant therapy including both PPI, amoxicillin, clarithromycin and metronidazole, providing 96% (48/50 patients) and 97% (34/35 patients) cure rates, respectively. The remaining therapies provided all an effectiveness lower than 90%, the lowest one obtained with PPI, clarithromycin and metronidazole (66%; 35/53 patients). Conclusions: In the Czech Republic, the first-line empirical treatment overall effectiveness was suboptimal (&lt;90%); however, 10-day non-bismuth quadruple sequential and 14-day concomitant therapies, both composed of PPI, amoxicillin, clarithromycin and metronidazole, achieved over 90% cure rates. Key-words: Helicobacter pylori – first-line treatment – proton pump inhibitors – Czech Republic

The Impact of a Twice-daily Versus Once-daily Proton Pump Inhibitor Dosing Regimen on Laryngopharyngeal Reflux Symptoms: A Prospective Randomized Controlled Trial.

Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19 to 79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16- week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups. Each dosing regimen demonstrated significant decreases in RSI and RFS. Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

Common laryngopharyngeal reflux: A review

Abstract Clinically, gastroesophageal reflux disease (GERD) or gastroesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease characterized by persistent and regular flow of stomach content up into the esophagus, resulting in symptoms and/or complications. Further, if acid reflux symptoms are more apparent in the larynx or pharynx, then the disorder may be called laryngopharyngeal reflux disorder (LPRD). The reflux of such acid to soft tissues beyond the esophagus will cause damage, which may turn into a relatively serious condition, especially for those with laryngeal reflux. Traditionally, obesity has been known as a primary risk factor for GERD or LPRD and related complications. Many studies have reported the association between obesity, hiatus hernia, and various motility dysfunctions of the upper gastrointestinal tract in patients with LPRD. Somehow obesity predisposes to these conditions, or whether they merely coexist with LPRD remains to be elucidated and dissents exist. Previous studies often recommend longer treatment and higher doses of proton pump inhibitors (PPI) for general gastroesophageal reflux because the presence of gastric acid in the pharynx and larynx can damage the vocal cords. Patients with laryngopharyngeal reflux can feel the symptoms while sitting at rest, and those with GERD feel the symptoms when lying down. The stomach contents, including pepsin and gastric acid, are the culprits that cause major damage to the tissues. Bile salts from the gallbladder further worsen the injury. A high-risk population includes people with obesity and/or obstructive sleep apnea.

Proton pump inhibitor use and bone fractures in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing. We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors. In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures (OR 1.68; 95% CI 1.55-1.83). This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 with a PPI prescription for longer than two years (OR 6.85, 95% CI 1.85-25.38). The same was true, when analyzing cumulative PPI doses. Here, patients below the age of 60 with a cumulative PPI dose above 16000mg (highest quartile) had the highest risk for fractures (OR 4.62, 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures. This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.

The association between proton-pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy.

The association between long-term proton-pump inhibitors (PPIs) use and malignancies had long been discussed, but it still lacks consensus. Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery. We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non-users: <28 cumulative defined daily dose [cDDD]; short-term users: 28-89 cDDD; mid-term users: 90-179 cDDD, and long-term users: ≥180 cDDD, respectively). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazard models. Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10years, interquartile range [IQR] 1.49-5.01) compared with non-users (2.73years, IQR 1.20-4.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44-0.74, P<0.001). When considering the cumulative dosage of PPI, only long-term PPI users had significant lower risk of HCC recurrence than non-PPI group (adj-HR: 0.50; 95% CI: 0.35-0.70; P<0.001). Moreover, the impact of long-term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non-cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non-users (4.23years, IQR 2.73-5.86 vs 4.04years, IQR 2.51-5.82, P=0.369). Long-term PPI use (≥180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70–145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient’s age, and patients’ origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.What is Known:• Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness.What is New:• Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy.• PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density.

Aim: Although Proton pump inhibitors (PPIs) are well-tolerated, their long-term use may be associated with decreased bone mass. Methods: This is a case-control study including patients treated with PPIs (>1year) and control subjects who have not received PPIs treatment. Results: A total of 90 patients and 90 matched controls were included. PPIs use was associated with hypocalcemia and hypomagnesemia. Vitamin D3 deficiency and hyperparathyroidism were associated with PPIs use. Long-term PPIs use was significantly associated with decreased bone density. Risk factors of decreased bone mineral density (BMD) included age >50years, menopause, lack of sun exposure, double PPIs dose, daily intake, post-meal intake and association with a mucoprotective agent. Conclusion: Our results highlight the risk of decreased BMD in patients on long-term PPIs treatment.

#2824 Use of proton pump inhibitors is not associated with post-dialysis fatigue and time of recovery after dialysis in patients on chronic hemodialysis

Abstract Background and Aims Chronic hemodialysis is often associated with post-dialysis fatigue (PDF), a condition characterized by extreme tiredness and lack of energy. PDF is a debilitating symptom that significantly impairs quality of life of hemodialysis patients. Furthermore, PDF is independently associated with the time to recover after dialysis (TIRD), which can be used as an indirect measure of PDF. Recent studies have shown that the use of proton pump inhibitors (PPI) is independently associated with the prevalence and severity of fatigue in kidney transplant recipients. The aim of this study is to determine whether the use of PPIs in patients undergoing chronic hemodialysis is associated with PDF prevalence and characteristics, as well as the TIRD. Method For this retrospective study, we recruited patients undergoing chronic hemodialysis and asked open-ended questions about their post-dialysis fatigue and time of recovery. Each patient was asked to rate the intensity, duration and frequency of their PDF on a scale of 1 to 5. We defined whether patients used a PPI (no PPI use or PPI use), the type of PPI used, the dose of PPI used, and the duration of the PPI use (&amp;lt;1 year or ≥1year). Results The study analysed 346 patients, of whom 259 used PPIs (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Among the patients, 232 reported suffering from PDF, while 114 did not. The median [min-max] TIRD was 210 minutes [0-1440]. The prevalence of PDF in PPI users and non-users was 67% and 68%, respectively (p= 0.878). There was no significant difference in the median [min-max] TIRD between PPI users and non-users (180 [0-1440] and 240 [0-1440], respectively; p=0.871). Additionally, there was no significant difference in the median PDF intensity, duration, frequency, and severity PPI users and non-users. The prevalence of PDF was similar among the different types of PPI used and did not differ with respect to PPI non-users. Duration of PPI exposure was &amp;lt;1 year in 42 patients and ≥1 year in 224 patients. There was no difference in prevalence of PDF between the two exposures. The correlation matrix showed no statistical significance between PPI equivalent dose, treatment duration, PDF frequency, PDF characteristics, and TIRD. Conclusion There is no association between the use of PPIs and PDF or time of recovery after dialysis in patients on chronic hemodialysis.

Proton pump inhibitor therapy after transcatheter angiography in refractory nonvariceal acute upper gastrointestinal bleeding patients: a cohort study.

Transcatheter angiography (TA) could help to diagnose and treat refractory nonvariceal upper gastrointestinal bleeding (NVUGIB). Proton pump inhibitors (PPIs) are the key medication for reducing the rebleeding rate and mortality and are usually continued after TA. It is unknown whether high-dose PPIs after TA are more effective than the standard regimen. We retrospectively collected data from patients who received TA because of refractory NVUGIB from 2010 to 2020 at West China Hospital. 244 patients were included and divided into two groups based on the first 3 days of PPIs treatment. All baseline characteristics were balanced using the inverse probability of treatment weighting method. The 30-day all-cause mortality, rebleeding rate and other outcomes were compared. The propensity score matching method was also used to verify the results. There were 86 patients in the high-dose group and 158 in the standard group. The average daily doses of PPI were 192.1 ± 17.9mg and 77.8 ± 32.0mg, respectively. Cox regression analysis showed no difference in the 30-day all-cause mortality (aHR 1.464, 95% CI 0.829 to 2.584) or rebleeding rate (aHR 1.020, 95% CI 0.693 to 1.501). There were no differences found in red blood cell transfusion, hospital stay length and further interventions, including endoscopy, repeating TA, surgery and ICU admission. The results were consistent in the subgroup analysis of patients with transcatheter arterial embolization. In refractory NVUGIB patients who received TA, regardless of whether embolization was performed, high-dose PPI treatment did not provide additional benefits compared with the standard regimen.

Awareness of Proton Pump Inhibitor Adverse Events and Treatment Pattern Change According to Physician Practice: A National Questionnaire Study in Korea.

Although adverse events of proton pump inhibitors (PPIs) have been reported, there are few studies on physicians' perceptions. We aimed to investigate physicians' awareness of PPI-related adverse events and changes in treatment patterns according to their practice. We conducted an online survey of physicians using a 15-item questionnaire. The survey queried respondents' demographic information, PPI prescription patterns, perceptions, and concerns on the reported PPI-related adverse events. Concerns regarding the adverse events of PPI were assessed by dividing them into possibilities and medical causality. Of the 450 respondents, 430 were specialists, and 232 were gastroenterologists. A total of 87.8% of the respondents were generally or well aware of the adverse effects of PPI, 29.1% considered side effects when prescribing PPI, and 14.6% explained them to patients. Specialists were more aware of the side effects of PPI than general practitioners (p = 0.005), and gastroenterologists were more aware of the side effects of PPI than non-gastroenterologists (p < 0.001). However, gastroenterologists explained less to patients (p = 0.001) and preferred to reduce the dose of PPI rather than discontinue it. The adverse events that were recognized as having the highest probability of occurrence and strongest association with PPI use were bone diseases, Clostridium difficile infection, gastrointestinal infection, pneumonia, and interactions with anti-thrombotic drugs. Physicians' awareness of PPI-related adverse events and treatment patterns differed significantly according to their positions and practice. Although a number of adverse events of PPIs were reported, physicians seem to accept their significance differently according to their specialty and practice patterns.

Impact of medication dosage on Helicobacter pylori eradication rates among pediatric patients.

Helicobacter pylori rates of eradication to common first-line regimens continue to decline globally. Prescription of the appropriate medication dosage is an important consideration, particularly in the pediatric population due to medication weight-based dosing. Limited data is available on the impact of guideline-recommended weight-based dosing on the successful eradication of H. pylori in children. Retrospective study of patients with histologic evidence of H. pylori from two pediatric tertiary care centers in New England. We excluded patients who were not treated or those missing eradication data. We compared the eradication rates of patients prescribed recommended weight-based dosages, duration, and frequency of treatment with those who were not. One hundred forty-four patients were included. The overall eradication rate was 73.6% (106/144). All treatment regimens were properly prescribed for 14 days. There was a high rate of improper weight-based dosing: proton pump inhibitor (PPI) 31.2% (45/144), amoxicillin 31.7% (39/123), metronidazole (MET) 19.4% (12/62), clarithromycin (CLA) 23.9% (22/70), tetracycline 50% (6/12), bismuth 26.1% (6/23). When PPIs were properly weight-dosed, there was a 78.8% eradication rate that dropped to 62.2% with suboptimal dosing (p = 0.036, OR: 2.26, CI: 1.04-4.87). When amoxicillin was properly weight-dosed, successful eradication was achieved in 81% versus only 53.8% when improperly dosed (p = 0.002; OR: 3.64, CI: 1.58-8.37). There was no statistically significant impact on eradication rates with improper weight-based dosing of MET, CLA, tetracycline, or bismuth. Proper weight-based dosing of amoxicillin and PPI is important for the successful eradication of H. pylori among children in the New England area.

Side effects of proton pump inhibitors with long-term use: focus on the urinary system

Proton pump inhibitors (PPIs) are the most effective drugs for treating acid-related diseases. In recent decades, the use of PPIs has increased exponentially. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the associations between PPIs and a number of diseases/conditions. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to January 30, 2024. In this review, we examined the effect of long-term use of PPIs on the urinary system. This review demonstrates possible changes in the urinary system and an increased risk of developing nephrolithiasis, acute interstitial nephritis, acute kidney injury, chronic kidney disease, end-stage renal failure with long-term use of PPIs, which should certainly be taken into account when prescribing them for a long period, especially in patients with comorbid pathology.

Cardiovascular risk with long-term use of proton pump inhibitors: myth or reality. A review

Proton pump inhibitors (PPIs) are the most effective drugs for treating acid-related diseases. In recent decades, the use of PPIs has increased exponentially. From gastroenterological practice, PPIs are being actively introduced into other specialties, in particular in cardiology and rheumatology, where they are used to protect the mucous membrane of the gastrointestinal tract and prevent gastrointestinal bleeding during long-term antithrombotic therapy and long-term use of non-steroidal anti-inflammatory drugs. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the relationship between PPIs and a number of diseases/conditions, including the question of a possible association of PPI use with an increased risk of cardiovascular complications, but note the inconsistency of these data. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to 12/01/2023. In this review, we examined the possible cardiovascular risk of long-term use of PPIs. Analysis of publications, despite a number of contradictions, allows us to conclude that the cardiovascular risk with long-term use of PPIs is real and must be taken into account when prescribing PPIs for a long period and to comorbid/multimorbid patients.

Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics.

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies-the only accurate method of assessing PPI response-efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.

Influence of novel CYP2C-haplotype on proton pump inhibitor pharmacokinetics in children.

In this brief report, we provide an analysis of the influence of a novel CYP2C haplotype (CYP2C:TG) on proton pump inhibitor (PPI) pharmacokinetics (PK) in children. The CYP2C:TG haplotype has been proposed to be associated with increased CYP2C19 activity. We sought to determine if this CYP2C:TG haplotype resulted in similar alterations in metabolism for proton pump inhibitors, which are primarily metabolized by CYP2C19. In a cohort of 41 children aged 6-21 participating in a PPI pharmacokinetic study, effects of the CYP2C:TG allele were assessed by fitting two linear regression models for each of the six PK outcomes assessed, the second of which accounted for the presence of the CYP2C:TG allele. The difference in R2 values between the two models was computed to quantify the variability in the outcome that could be accounted for by the CYP2C:TG allele after adjustment for the CYP2C19 genotype. We found the CYP2C:TG haplotype to have no measurable additive impact on CYP2C19-mediated metabolism of PPIs invivo in older children and adolescents. The findings of this study do not support the clinical utility of routine testing for the CYP2C:TG haplotype to guide PPI dose adjustments in children.

Relationship between CYP2C19 genotypes and proton pump inhibitorsʹs pharmacokinetics and pharmacodynamics: review

The purpose of this review is to provide clinicians with information and a concise interpretation of the results of pharmacogenetic testing for the cytochrome P450 2C19 (CYP2C19) genotype when choosing a proton pump inhibitor (PPI) dosage. PPIs are widely used for the treatment and prevention of common gastrointestinal diseases, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, and other hypersecretory conditions. Most PPIs are metabolized predominantly by cytochrome P450 2C19 (CYP2C19) to form inactive metabolites, and the CYP2C19 genotype determines the action of PPIs, their efficacy and possible side effects. In clinical practice, a gastroenterologist or therapist is faced with problems of insufficient effectiveness or the development of adverse reactions when prescribing PPIs. Thus, consideration of CYP2C19 genotype appears to be necessary to determine the optimal PPI dosing regimen. The above served as a reason for generalizing in the presented review of literature data on the prescription of PPIs depending on the CYP2C19 genotype.