Use Of Proton Pump Inhibitors Research Articles

Proton pump inhibitors associated with severe COVID-19 among two-dose but not three-dose vaccine recipients.

Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among vaccine recipients. This was a territory-wide cohort study of 3272286 vaccine recipients (aged ≥18years) of ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use. Among 439154 PS-matched two-dose vaccine recipients (mean age: 65.3years; male: 45.7%) with a median follow-up of 6.8months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188360 PS-matched three-dose vaccine recipients (mean age: 62.5years; male: 49.0%; median follow-up: 9.1months [interquartile range: 8.0-10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes. Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.

Abstract PO1-01-08: The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study

Abstract Background: Data suggest that concomitant intake of proton pump inhibitors (PPI) may create drug-drug interactions, potentially impacting efficacy of agents including palbociclib, which is widely used in the treatment of metastatic hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer. In the open label, randomized, phase 3 PALLAS trial, the addition of palbociclib for two years to standard adjuvant endocrine therapy (ET) in patients with HR+/HER2- early breast cancer (EBC) did not improve invasive disease-free survival (IDFS) compared to adjuvant ET alone. We explored whether concomitant use of PPIs could have affected clinical outcomes in patients treated with palbociclib in PALLAS. Methods: This is an exploratory, unplanned analysis of the PALLAS trial (AFT-05/ABCSG-42/PrE0109/BIG-14-13, NCT02513394), which enrolled 5796 patients with stage II-III HR+/HER2- EBC. Patients were randomized to receive either 2 years of palbociclib (125 mg oral capsules once daily on days 1-21 of a 28-day cycle) with adjuvant ET or ET alone. Primary endpoint was IDFS in the intention-to-treat population. The present exploratory analysis included patients who received at least one dose of palbociclib. Definitions of IDFS, distant relapse-free survival (DRFS) and overall survival (OS) were according to the PALLAS protocol (STEEP criteria), using first day of palbociclib intake as start date. Only PPI concomitant intake during palbociclib treatment was considered. To determine the association of concomitant PPI use with IDFS, DRFS, and OS, uni- and multivariable Cox models with time-dependent PPI (the latter adjusted for age, prior chemotherapy, progesterone receptor, grade, tumor stage, nodal stage, body mass index (BMI)) were used. Also, the association between PPI use and neutropenia was investigated in patients initiating PPI prior to randomization vs never. Odds ratios (OR) unadjusted and adjusted for age and BMI estimated with logistic regression models are reported. Results: Of 2840 patients treated with palbociclib + ET, 533 (18.8%) had concomitant PPI and palbociclib intake. Median duration of PPI intake was 10.8 months (interquartile range 2.3-22.3). Most patients received omeprazole as PPI (n=265, 49.7%). PPI intake was significantly associated with older age, post-menopausal status, use of aromatase inhibitors as ET, higher BMI, and worse ECOG status (all p< 0.001). Concomitant PPI intake was not significantly associated with survival outcomes (Table 1). Unadjusted all grade neutropenia rates were slightly lower in patients who initiated PPI prior study start vs patients never initiating (79% vs 85%, unadjusted OR 0.66, 95%CI 0.50-0.88). After adjustment for BMI and age, the difference between the groups decreased (adjusted OR = 0.77, 95%CI 0.57-1.04). Similar effect sizes were found for grade 3/4 neutropenia rates (54% vs 64%, unadjusted OR 0.66, 95%CI 0.52-0.83, adjusted OR 0.81, 95%CI 0.64-1.03). Conclusions: Our exploratory analysis did not demonstrate a statistically significant relationship between concomitant use of PPIs and palbociclib and survival outcomes of patients in the PALLAS trial. Nonetheless, careful consideration of concomitant medications and of drug-drug interactions is important when studying novel agents in the adjuvant breast cancer setting. Support: AFT, Pfizer; https://acknowledgments.alliancefound.org Table 1. Association between PPI intake and survival outcomes. Citation Format: Elisa Agostinetto, Georg Pfeiler, Dominik Hlauschek, Erica Mayer, Matteo Lambertini, Evandro de Azambuja, Meritxell Bellet- Ezquerra, Jane Meisel, Gabor Rubovszky, Nicholas Zdenkowski, Yelena Novik, Manuel Ruíz - Borrego, Karen Gelmon, Eleftherios Mamounas, Hiroji Iwata, Dongrui Lu, Lidija Sölkner, Christian Fesl, Michael Gnant, Angela DeMichele. The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-08.

Efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease: A protocol for meta-analysis and systematic review.

The incidence of gastroesophageal reflux disease (GERD) is increasing year by year, the clinical manifestations are complex and diverse, and the adverse effects of long-term use of proton pump inhibitors and gastrointestinal motility drugs have been of great concern in recent years. The effectiveness of tegoprazan in the treatment of GERD is still controversial. This protocol describes a systematic review and meta-analysis to evaluate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease. PubMed, Embase, Cochrane Library and Web of Science will be searched from the database inception to 1 March 2023. All randomized controlled trials related to tegoprazan for GERD will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be complete resolution of major symptoms, complete resolution of heartburn, proportion of heartburn-free days, chronic cough, hoarseness, and adverse events. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The results of this study will provide reliable evidence to evaluate the efficacy and safety of tegoprazan in the treatment of GERD and help patients, physicians and clinical investigators choose the most appropriate treatment.

Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007–2018

BackgroundProton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones.MethodsWe performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders.ResultsThe multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10–1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15–1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09–1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13–1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06–1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02–1.54, P = 0.033) in Model 3.ConclusionsOur study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.

Analysis of the Consumption of Medicinal Products Associated with a High Risk of Drug-Induced Liver Injury in Patients with COVID-19

INTRODUCTION. The risk of liver damage correlates with the severity of COVID-19. However, a growing number of studies have shown an association between liver function impairment and combinations of medicinal products used to treat COVID-19.AIM. The study aimed to analyse the annual consumption of medicinal products associated with a high risk of drug-induced liver injury (DILI) used as part of combination therapy in COVID-19 patients and to review a number of medication administration records in order to develop measures to prevent DILI.MATERIALS AND METHODS. The study used the ATC/DDD methodology to study consumption data for 2020, 2021, and 2022 and analysed a sample of 1250 inpatient medical records and medication administration records of COVID-19 patients treated in a Volgograd region hospital converted into a COVID-19 care centre. For genetically engineered biologicals and cyclophosphamide, which were lacking DDDs, the authors calculated the volume of consumption using the average dose per treatment course. The authors identified medicines capable of causing clinically apparent liver damage (according to the LiverTox database and Russian clinical practice guidelines) and/or elevated liver enzymes in ≥1% of patients (according to safety reports).RESULTS. The study found that 28% of the medicinal products used in combination for inpatient treatment of COVID-19 were associated with a high risk of DILI. In 2020, 2021, and 2022, the total consumption of medicinal products associated with a high risk of DILI was 342.3, 425.3, and 402.3 DDDs per 100 bed days, and the total consumption of genetically engineered biologicals (administered as a single dose) and cyclophosphamide was 3.5, 16.9, and 29.7 average course doses per 100 patients, respectively. According to the selective analysis of medical records, 19.8% (247/1250) reported concomitant use of 5 or more medicinal products associated with a high risk of DILI, which increased the risk of adverse drug interactions leading to DILI. In 2022, the most prescribed medicinal products with a high risk of DILI were omeprazole (188.7 DDDs per 100 bed days), non-steroidal anti-inflammatory drugs and paracetamol (54.4 DDDs per 100 bed days), atorvastatin (46.2 DDDs per 100 bed days), levofloxacin (26.4 DDDs per 100 bed days), ceftriaxone (20.5 DDDs per 100 bed days), favipiravir (17.3 DDDs per 100 bed days), and genetically engineered biologicals (24.0 DDDs per 100 bed days).CONCLUSIONS. To reduce the risk of DILI in COVID-19 patients admitted to infectious disease units, including the risk of DILI due to drug interactions, it is necessary to limit the use of hepatotoxic antibacterial agents, proton-pump inhibitors, and non-steroidal anti-inflammatory drugs, or consider alternative medicinal products with a lower risk of hepatotoxicity.

Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

Risk Factors and Prognosis Analysis of Upper Gastrointestinal Bleeding in Patients With Acute Severe Cerebral Stroke.

We aim to explore the relationship between the use of proton pump inhibitors (PPIs) and upper gastrointestinal bleeding (UGIB). We develop a nomogram model to predict mortality in critically ill stroke patients. This is a retrospective study based on the MIMIC IV database. We extracted clinical information including demographic data, comorbidities, and laboratory indicators. Univariate and multivariable logistic regressions were used to assess and identify risk factors for the occurrence of UGIB and for the in-hospital mortality of critically ill stroke patients. The resulting model was used to construct a nomogram for predicting in-hospital mortality. Five thousand seven hundred sixteen patients from the MIMIC-IV database were included in our analysis. UGIB occurred in 109 patients (1.9%), whereas the PPI use rate was as high as 60.6%. Chronic liver disease, sepsis, shock, anemia, and increased level of urea nitrogen were independent risk factors for the occurrence of UGIB in severe stroke patients. We identified age, heart failure, shock, coagulopathy, mechanical ventilation, continuous renal replacement therapy, antiplatelet drugs, anticoagulation, simplified acute physiology score-II, and Glasgow coma score as independent risk factors for in-hospital mortality in severe stroke patients. The C-index for the final nomograms was 0.852 (95% confidence interval: 0.840, 0.864). We found that the overall rate of UGIB in severe stroke patients is low, whereas the rate of PPI usage is high. In our study, PPI was not identified as a risk factor for the occurrence of UGIB and UGIB was not associated with all-cause mortality. More clinical trials are needed to evaluate the benefits of using PPI in critically ill stroke patients.

Effects of comorbid conditions and prescribed chronic medications on the treatment plan for chronic hepatitis C infection: A cross-sectional retrospective study.

Chronic hepatitis C (CHC) infection is a potentially life-threatening condition characterized by various complications, including end-stage liver disease and cirrhosis. The mortality rate associated with CHC has been increasing due to the presence of comorbidities and the use of chronic medications. Therefore, the objective of this study was to investigate the impact of these comorbidities and chronic medications on the treatment plan for CHC. To achieve this objective, a cross-sectional retrospective study was conducted at a tertiary hospital in Jeddah, Saudi Arabia. The study population included patients aged 12 years and above who were diagnosed with CHC between 2016 and 2021. Patients below the age of 12 were excluded from the study. A total of 170 patients with CHC were included in the analysis. The study aimed to evaluate the relationship between CHC complications and the treatment approach. The mean age of the study participants was 66.78 years, with a higher proportion of female patients. The findings revealed a significant association between hypertension (p = 0.042) and cirrhosis (p = 0.007) with changes in the treatment plan for CHC. Moreover, the presence of diabetes mellitus (p = 0.045), renal diseases (p < 0.001), and hypothyroidism (p = 0.004) were significantly associated with HCV clearance after the initiation of therapy. Additionally, the use of proton pump inhibitors (p = 0.033) and levothyroxine (p = 0.025) was found to be associated with a higher rate of CHC clearance. In conclusion, this study highlights the prevalence of comorbid conditions and the use of chronic medications among patients with CHC. The findings emphasize the importance of considering the effects of comorbidities and chronic medications when developing treatment plans for CHC infections. By taking these factors into account, healthcare professionals can optimize the management of CHC and improve patient outcomes.

Individualized prevention of proton pump inhibitor related adverse events by risk stratification

Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.

E060 A multinational survey investigating the unmet needs and patient perspectives concerning proton pump inhibitors in systemic sclerosis

Abstract Background/Aims The gastrointestinal (GI) tract is largely (&amp;gt;95%) affected in systemic sclerosis (SSc) and its involvement is associated with significant morbidity, mortality and huge impact on the quality of life. Upper GI tract dysfunction, often presenting with gastroesophageal reflux disease (GERD) is one of the principal complaints. Proton pump inhibitors (PPIs) are widely used to treat GERD in SSc. However, not all patients respond to this therapy, and many remain on long-term treatment. Significant concerns about PPI long-term safety have been raised. Our aim was to identify perspectives and unmet needs of SSc patients on PPIs. Methods An online English survey, targeting SSc patients on PPIs was developed and distributed through social media and international patient associations. The survey was launched on 4th November 2022 and kept open for 4 weeks. Results 301 respondents from 14 countries completed the survey (UK 19.3% and US 70.4%). Most respondents were between 30-70 years and the majority were female (95%). The most frequently reported symptoms were acid reflux (97%), dysphagia (60%), and trouble swallowing or food got stuck in the chest (32%). Multiple PPIs use (two: 30% and three: 21%; in series) was common and the majority (89%) reported improvement in GI symptoms with PPIs. Even though only 19% experienced side effects on PPIs, most respondents (79%) were concerned (Table 1). Half (47%) experienced a flare of symptoms after initial improvement with PPIs and 58% received lifestyle information, while most (85%) searched online for information about PPIs. A minority (12%) reported that a surgical approach was discussed, and 46% indicated that they would be willing to undergo surgery, despite having significant concerns. Conclusion Our survey highlights the importance of upper GI symptoms in SSc patients and the frequent use of PPIs. There is significant heterogeneity in use, and treatment is often not fully effective. Patients have concerns about side effects related to long-term PPI use. There is a clear unmet need regarding patients’ education about PPIs. A surgical approach is rarely discussed, although patients would potentially consider this approach. Further research is needed to optimize the therapeutic strategy concerning PPIs in SSc. Disclosure G. Bandini: None. A. Alunno: None. F. Oliveira Pinheiro: None. C. Campochiaro: None. I. Galetti: None. P. Matucci Cerinic: None. B. Ruaro: None. K. El Aoufy: None. M. Melis: None. A. Moggi Pignone: None. L. Dagna: None. M. Matucci Cerinic: None. Z. McMahan: None. M. Hughes: None.

Small intestinal bacterial overgrowth in diabetic gastroenteropathy.

Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.

Efficacy and safety of proton pump inhibitors on cardiovascular events and inflammatory factors in patients with upper gastrointestinal bleeding undergoing dual antiplatelet therapy.

This work evaluated the effects of proton pump inhibitors (PPIs) on cardiovascular events (CVEs) and inflammatory factors in patients with upper gastrointestinal bleeding (UGIB) undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Clinical data from these patients were analysis, intending to provide relevant theoretical evidence for clinical practice. Data of 166 patients who underwent percutaneous coronary intervention and developed UGIB while on DAPT at The First People' Hospital of Linping District from April 2021 to April 2023 were retrospectively analyzed. The patients were rolled into two groups: those who received PPI treatment and those who did not, namely, PPI and non-PPI group, respectively. Furthermore, occurrence of CVEs and the levels of inflammatory factors of patients in all groups were statistically analyzed. In patients with UGIB, melena is a common presentation. The incidence of CVE in the PPI group showed no statistically significant difference compared to the control group, and there was no significant variance observed in the distribution of CVE incidence among different PPIs. However, levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were significantly lower in the PPI group compared to the non-PPI group (P < 0.05). Melena was the most frequent clinical manifestation in UGIB patients. The use of PPIs did not increase the risk of CVEs, and different PPI drugs did not affect the occurrence of CVEs. Furthermore, PPIs lowered CRP and TNF-α levels in serum of these patients.

Long-Term Intake of Proton-Pump Inhibitors Could Be Associated with an Increased Incidence of Liver Cancer in Women.

Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06-1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09-1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09-1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21-3.26). Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication.

Longitudinal microbiome changes in children exposed to proton pump inhibitors.

Proton pump inhibitor (PPI) use has been associated with an increased risk of gastrointestinal and upper respiratory infections in children. There are limited longitudinal data on the effect of PPI in children. The goal of this prospective observational study was to compare the stool and oropharyngeal microbiome of children before and after starting PPIs. We prospectively recruited participants from a gastroenterology clinic. Consented pariticpants provided stool samples and oropharyngeal swabs at baseline and after eight weeks of PPI therapy. Microbiome changes were measured by analyzing 16S sequencing from both body sites at both timepoints. Thirty-four participants completed the study and provided samples both at baseline and after eight weeks on PPI therapy. Of those, 24 participants had sufficient sequencing from both stool and oropharyngeal samples at both time points. There were no differences between the pre- vs post-PPI samples using beta-diversity metrics in either the oropharynx or stool. There were, however, significant changes in specific taxa. There was an enrichment of Streptococcus in the stool in after PPI-use and a reduction in the relative abundance of Bifidobacterium, Peptostreptococcus and Turicibacter (p-values < 0.01). Furthermore, there was an increase in the relative abundance of oropharyngeal bacteria in the stool after PPI therapy. This enrichment of oropharyngeal bacteria in the stool was most prominent in younger participants. Further investigation is needed to determine the clinical and microbial factors that predispose or protect against microbiome changes due to PPI-use, and why young children are more susceptible to this PPI effect.

Impact of concurrent medications on the outcome of immunotherapy in non-small cell lung carcinoma.

There have been reports on the impact of concurrent drugs on the outcome of immunotherapy for non-small cell lung carcinoma (NSCLC). However, the effect of some drugs, such as antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), has not been clarified in patients with NSCLC. In the present study, we aimed to assess the association between concurrent drugs and the outcomes of immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy for patients with advanced NSCLC. We retrospectively assessed patients with advanced NSCLC who underwent ICI treatment between September 2017 and December 2021 at Kobe University Hospital. We evaluated the data regarding the use of antibiotics within 30 days before ICI initiation, as well as the use of proton pump inhibitors (PPIs) and NSAIDs during ICI initiation. A total of 127 patients were assessed, among whom 28 (22.0%) patients received antibiotics, 39 (30.7%) PPIs, and 36 (28.3%) NSAIDs. No significant differences were observed between the patients with and without antibiotic use. However, patients using NSAIDs had significantly worse objective response rates (ORR) and progression-free survival (PFS) with ICI alone or in combination with chemotherapy compared to those who did not (ORR, 47.2% vs. 67.0%; p = 0.045. PFS, 6.3 months vs. 10.8 months; p = 0.02). Patients using PPIs demonstrated a worse ORR of ICI in combination with chemotherapy compared to those who did not (ORR, 45.2% vs. 72.6%; p = 0.013). The unnecessary use of NSAIDs along with immunotherapy should be discouraged.

Side effects of proton pump inhibitors: how real are they in clinical practice?

The presented article discusses the risk of side eff ects when using proton pump inhibitors (PPI): infectious complications (small intestinal bacterial overgrowth, Clostridium difficile-associated disease, community-acquired pneumonia, spontaneous bacterial peritonitis), stomach cancer, myocardial infarction, hypomagnesemia, iron and vitamin B12 deficiency, kidney damage, bone fractures, dementia, Alzheimer’s disease. An analysis of the literature indicates a weak causal relationship between the occurrence of these diseases and the use of PPI. Nevertheless, it is necessary to strive for the appointment of these drugs in the minimum effective dose and for as short a time as possible.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study

ObjectiveTo determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes.DesignDifference-in-difference study.SettingUS Veterans Affairs Healthcare System,...

The Effects of Pantoprazole on Kidney Outcomes.

Observational studies have found an association between proton pump inhibitor (PPI) use and worsening kidney function. It is unclear whether these associations are causal.We conducted post-hoc analyses to determine the effect of pantoprazole on kidney function using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, a 17,598 participant randomized trial comparing pantoprazole (8,791) to placebo (8,807). The primary outcome was the rate of change of estimated glomerular filtration rate (eGFR). Rate of eGFR change was based on the two eGFR measures available, the eGFR at randomization and at the open label extension study that enrolled at trial conclusion. Secondary outcomes included incident chronic kidney disease (CKD) (defined by eGFR <60 ml/min/1.73 m2 at open label extension or case report forms) as well as acute kidney injury (AKI), acute nephritis, and nephrotic syndrome. 8,991 of the 17,598 participants randomized to pantoprazole/placebo (51%) had eGFR recorded at baseline and open label extension enrollment and were included in the rate of eGFR change population (mean age 67 [SD 8] years, 22% female, mean baseline eGFR 75 [SD 17.5] ml/min/1.73 m2). The mean duration between randomization and open label extension eGFR was 3.3 years. The placebo rate of eGFR change was -1.41 (SD 4.45) ml/min/1.73 m2 per year. The pantoprazole rate of eGFR change was -1.64 (SD 4.47) ml/min/1.73 m2 per year. In adjusted analyses pantoprazole had a 0.27 ml/min/1.73 m2 per year greater decline in eGFR (95% CI 0.11 to 0.43). The odds ratio for the effect of pantoprazole on incident CKD was 1.11 (95% CI 0.98 to 1.25) and on AKI was 0.89 (95% CI 0.65 to 1.21). There were 5 nephrotic syndrome outcomes recorded and 1 event of acute nephritis. In this post-hoc analysis of the COMPASS trial pantoprazole resulted in a statistically significant greater rate of eGFR decline as compared to placebo. The clinical importance of this is uncertain.

Oral-to-rectum microbial transmission in orthopedic patients without a history of intestinal disorders.

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.

Proton Pump Inhibitors and Kidney Disease: Fact or Fiction?

Proton pump inhibitors (PPI) are commonly prescribed medications for dyspepsia and gastroesophageal reflux. There are concerns about their use in the development of chronic kidney disease (CKD). The available published literature fails to support an association with PPI and the development of CKD. Placebo-controlled trials demonstrate no difference on the incidence of CKD between placebo and PPI. If one examines the data according to the Bradford Hill perspective incorporating temporal relationship, strength of association, dose response relationship, replacement of findings, cessation of exposure, specificity of the association and consistency with other knowledge, one can only conclude that there is no consistent relationship between PPI use and the development of CKD, or its progression. There is insufficient evidence to link PPI exposure with the development or progression of CKD.