Proton Pump Inhibitors Exposure Research Articles

The impact of proton pump inhibitors on the course of ulcerative colitis: a cohort study of over 10,000 newly diagnosed patients in Norway

Background and Aims Proton pump inhibitors (PPI) affect the gastrointestinal microbiota, which is thought to play a role in the pathogenesis of ulcerative colitis (UC). Previous studies suggest an association between PPI use and risk of incident UC as well as disease course. The aim of the study was to examine if PPI exposure is associated with disease course in UC patients. Methods A national cohort consisting of all newly diagnosed UC patients from 2010 to 2020 was defined combining data from Norwegian registries. PPI exposure was included as a time dependent variable with a 30 day time lag from starting the drug. Outcomes were starting advanced therapies including anti-TNF, systemic glucocorticoids, any additional systemic anti-inflammatory medication and undergoing colectomy during follow-up. Time-dependent Cox regressions included the variables PPI use, first systemic glucocorticoid prescription, first UC hospitalization, age-groups and sex. Results The study cohort consisted of 10,149 patients with median age 40 years (IQR 27–56) and 56% males. PPI use independently increased the risk of starting advanced therapies (HR 1.54, 95% CI 1.36–1.73, p < 0.005), starting systemic glucocorticoids (HR 1.20, 95% CI 1.07–1.34, p < 0.005), starting any additional anti-inflammatory treatment (HR 1.18, 95%CI 1.05–1.32, p < 0.01) and undergoing colectomy (HR 1.52, 95%CI 1.17–1.98, p < 0.005). Conclusions PPI use was associated with unfavorable outcomes including advanced therapy initiation, additional anti-inflammatory medications and undergoing colectomy. Although further studies are needed, the evidence suggests that PPIs could affect the course of UC and should be used cautiously in UC patients.

CYP2C19 genotypes and osteoporotic fractures in long-term users of proton pump inhibitors: A hospital-based study.

Proton pump inhibitors (PPIs) are commonly prescribed medications. The existing data suggest that individuals at a high risk of fractures have been exposed to high doses of PPIs for prolonged durations. CYP2C19 plays a pivotal role in metabolism of PPIs and thereby influences their pharmacokinetic profile. Hence, we hypothesize that CYP2C19 genotypes may be associated with fragility fracture among PPIs users due to PPI exposure. This study aimed to investigate the association between CYP2C19 genotypes, bone mineral density (BMD), and osteoporotic fracture in a hospital-based population. This retrospective cohort study enrolled patients who were prescribed long-term PPIs at Taichung Veterans General Hospital using data extracted from the Taiwan Precision Medicine Initiative between January 2010 and April 2021. Associations between CYP2C19 phenotypes, comorbidities, and fractures in PPI users were analyzed. We enrolled 1518 long-term PPI users; 571 (38%), 727 (48%), and 220 (14%) CYP2C19 normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs), respectively. Among them, 49 (3.2%) patients developed fractures within the 1-year follow-up period; 20 (3.5%) fractures in NMs, 24 (3.3%) in IMs, and 5 (2.3%) in PMs, respectively. No significant difference was observed among CYP2C19 genotypes and fracture. Additionally, BMD measurements during the 1-year follow-up period were made available among 75 participants. No significant difference in BMD between CYP2C19 PMs and non-PMs was found. This real-world, hospital-based study concludes that CYP2C19 PMs/IMs are not associated with an increased risk for fractures or reduced BMD in individuals on long-term PPI therapy.

Transcriptional analysis of Helicobacter pylori cytotoxic-associated gene-pathogenicity islandin response to different pH levels and proton pump inhibitor exposure.

Long-term use of proton pump inhibitors (PPIs) can increase therisk of gastric cancer in Helicobacter pylori-infected patients; nevertheless, there is no data about their impact on the pathogenicity of H. pylori. This study aimed at investigating thetranscriptional alteration of key gene mediators of cytotoxin-associated gene-pathogenicity island (cag-PAI) among clinical H. pylori isolates in response to omeprazole at different pH levels. Accordingly, H. pylori isolates with the same virulence genotypes selected from the gastric biopsies of patients and transcriptional alteration in the cag-PAI genes studied in the presence or absence of omeprazole (2mg/mL) at pH 2.0, 4.0 and 7.0 after 30 and 90minutes of the treatment. Relative changes in the transcriptional levels were recorded in each assay, separately. Of 18 H. pylori isolates, the cag-PAI empty site was detected in four strains, while the presence of cagA, cagL and cagY was characterized in 77.7%, 83.3% and 83.3% of the cag-PAI-positive strains, respectively. Transcriptional analysis of the selected strains showed up-regulation of cagA and cagL, mainly at pH 2.0 and 4.0 after 30 and 90-minute exposure. A diversity in the expression levels of cag-PAI genes was seen among the strains at the extent and time of induction. Our results showed that omeprazole could increase the expression of H. pylori cagA and cagL at acidic pH. Heterogeneity among the strains probably has an impact on the extent of their interplay with PPIs. Further studies are needed to establish this correlation.

P10 Think zinc: nutritional deficiency in a breastfed infant associated with antenatal proton-pump inhibitor exposure

Abstract A 5-month-old infant presented with a 3-month history of a dramatic periorofacial and acral dermatitis associated with recurrent infections, increasing lethargy and poor feeding. He was born at full term, breastfed exclusively, and had no family history of skin disease. Serum alkaline phosphatase was 41 (range 82–383) and zinc levels were undetectably low (&amp;lt; 3 mg mol–1; normal 10–25). Maternal breastmilk zinc levels were low (3.15, control mean 12.7), and maternal serum zinc was normal. A rapid improvement was noted within days of zinc sulfate supplementation. Zinc supplementation was stopped after 3 months, with normal follow-up zinc levels. The mother had taken omeprazole from 30 weeks’ gestation to birth. In her previous pregnancy there was no proton-pump inhibitor (PPI) ingestion, and no manifestation of zinc deficiency in the older sibling, who had also been breastfed exclusively. Maternal genetic testing for defects in SLC30A2, a zinc transporter in mammary tissue, was negative. Acrodermatitis enteropathica involves recessive mutations in the SLC39A4 gene, and secondary transient infantile zinc deficiency can be due to prematurity, low zinc intake, or malabsorptive processes such as cystic fibrosis. It is rare in breastfed infants due to enhanced bioavailability of zinc. PPIs can decrease serum zinc due to intestinal chelation, although little is known regarding their effect on transplacental or transmammary zinc transmission. To our knowledge this is the first report of zinc deficiency in a breastfed infant associated with maternal PPI use, potentially due to diminished transmammary and/or transplacental zinc transmission.

Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children

Proton pump inhibitor (PPI) use may lead to infections through alteration of the microbiota or direct action on the immune system. However, only a few studies were conducted in children, with conflicting results. To assess the associations between PPI use and serious infections in children, overall and by infection site and pathogen. This nationwide cohort study was based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS). We included all children born between January 1, 2010, and December 31, 2018, who received a treatment for gastroesophageal reflux disease or other gastric acid-related disorders, namely PPIs, histamine 2 receptor antagonists, or antacids/alginate. The index date was defined as the first date any of these medications was dispensed. Children were followed up until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019. PPI exposure over time. Associations between serious infections and PPI use were estimated by adjusted hazard ratios (aHRs) and 95% CIs using Cox models. PPI use was introduced as time-varying. A 30-day lag was applied to minimize reverse causality. Models were adjusted for sociodemographic data, pregnancy characteristics, child comorbidities, and health care utilization. The study population comprised 1 262 424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including 606 645 who received PPI (323 852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655 779 who did not receive PPI (342 454 male [52.2%]; median [IQR] age, 82 [44-172] days). PPI exposure was associated with an increased risk of serious infections overall (aHR, 1.34; 95% CI, 1.32-1.36). Increased risks were also observed for infections in the digestive tract (aHR, 1.52; 95% CI, 1.48-1.55); ear, nose, and throat sphere (aHR, 1.47; 95% CI, 1.41-1.52); lower respiratory tract (aHR, 1.22; 95% CI, 1.19-1.25); kidneys or urinary tract (aHR, 1.20; 95% CI, 1.15-1.25); and nervous system (aHR, 1.31; 95% CI, 1.11-1.54) and for both bacterial (aHR, 1.56; 95% CI, 1.50-1.63) and viral infections (aHR, 1.30; 95% CI, 1.28-1.33). In this study, PPI use was associated with increased risks of serious infections in young children. Proton pump inhibitors should not be used without a clear indication in this population.

Use of proton pump inhibitors during pregnancy: A systematic review and meta-analysis of congenital malformations

Use of proton pump inhibitors (PPI) are common among pregnant women to relieve gastrointestinal symptoms. The number of exposed pregnancies is therefore considerable, and a recent meta-analysis (MA) from 2020 raised concern about their teratogenicity. The aim of the study was to provide a MA of the risk of major congenital malformations (MCM) after PPI exposure during the first trimester of pregnancy. A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva). The primary outcome was the incidence of overall MCM. The secondary outcomes of interest were specific MCM reported by at least three studies. All comparative studies assessing these outcomes in PPI exposed pregnancies were searched from inception to April 2022. From the 211 initially identified studies, 11 were included in the MA. The pooled odds ratio (OR) for the primary outcome showed no significant results based on 5 618 exposed pregnancies (OR 1.10, 95% CI [0.95;1.26]; I²=0%). Similarly, no result was significant for the secondary outcomes. The total exposed sample size ranged from 3 161–5 085; OR ranged between 0.60 and 1.92; heterogeneity was between 0% and 23%. Based on the results of the present MA, first trimester PPI exposure was not associated with a significantly increased risk of overall or specific MCM. However, this MA included only observational studies which are prone to bias and there were insufficient data to evaluate PPI at a substance level. Future studies are needed to address this concern.

Use of proton pump inhibitors (PPI) in glioblastoma (GBM) and relationship to overall survival in a national real-world evidence (RWE) database.

e14027 Background: Aldehyde dehydrogenase-1A1 ( ALDH1A1) mediates therapy resistance and poor prognosis in multiple cancers. In GBM, ALDH1A1 expression above vs. below the mean is associated with a significant reduction in survival.1 ALDH enzymes activate transcriptional programs that induce the cancer stem cell phenotype, detoxify anticancer drugs, and function as antioxidants by reversing lipid peroxidation and etheno-DNA adducts, thus conferring chemotherapy and radiation resistance. PPI have been shown to increase enzyme activity of ALDH1A1 up to 6-fold, suggesting a potentially hazardous effect on tumor biology and survival. However, no prospective randomized data are available to address these concerns. Thus, we turned to XCELSIOR, an observational database that prospectively collects medical records including medication usage. Methods: Patients with GBM were e-consented to XCELSIOR ( NCT03793088 ), a nationwide observational research protocol that leverages patient consent to permit gathering of medical records from all sites of care. Clinical data were abstracted from medical documents into a central EDC system, source-verified, and standardized to generate comprehensive longitudinal histories for aggregate analysis. Identified patient records permitted the definitive identification of dates of diagnosis and death. Overall survival (OS) was calculated and stratified based for PPI exposure, extent of surgical resection (EOR), and MGMT methylation status. Results: XCELSIOR contained 320 GBM patients from 222 treatment sites. We stratified patients based on exposure to PPI and assessed median OS (mOS). For the entire population, mOS was substantially better for patients not receiving PPI. (TABLE) The 5-yr survival was 29.9% [21.0 – 42] and 6.6% [1.4 – 32.0] for patients not receiving vs. receiving PPI. In a multivariate analysis considering EOR and MGMT methylation, PPI exposure yielded a hazard ratio (HR) of 1.57 (p=0.009). For the interaction of m-MGMT and PPI exposure together, the HR is 2.63 (p=0.043), significant as the HR of m-MGMT alone is 0.40 (p=0.0028). Conclusions: In this RWE dataset, PPI use in GBM appeared detrimental to survival. This is strongly consistent with the hypothesis that PPI antagonizes chemotherapy. Additionally, use of PPI appeared to completely abrogate the survival benefit of chemotherapy associated with methylated-MGMT. While we recognize the utility of PPI in managing acute UGI bleeding, these data suggest avoiding PPIs in GBM patients. 1) Schmidt-Graf F, et al. Neuro Oncol. 2012;14(12):1452–1464. [Table: see text]

Association Between Proton Pump Inhibitor Use and Extended-Spectrum Beta-Lactamase Urinary Tract Infection in Adults: A Retrospective Study.

To study the association between proton pump inhibitor (PPI) use and the risk of urinary tract infection (UTI) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL). A retrospective cross-sectional study was conducted between October 2018 and September 2019. Adults with ESBL-UTIs were compared to adults with UTIs caused by gram-negative bacteria (GNB) and those with UTIs caused by miscellaneous organisms. The association between ESBL infection and PPI use was assessed. A total of 117 of 277 ESBL cases, 229 of 679 non-ESBL GNB controls, and 57 of 144 non-ESBL miscellaneous controls were exposed to PPIs within 3 months prior to admission. The univariate analysis indicated unadjusted odds ratio for PPI exposure with ESBL infection versus the GNB controls was 1.43 (95% CI 1.07-1.90, P = 0.015) while the odds ratio for PPI exposure with ESBL infection versus miscellaneous organisms was 1.10 (95% CI 0.73-1.67, P = 0.633) indicating positive association (PPI exposure increases risk of ESBL infection). Multivariate analysis revealed a positive association between ESBL infection and PPI use versus the GNB controls with an odds ratio of 1.74 (95% CI 0.91-3.31). While Esomeprazole was positively associated with ESBL infection, particularly compared with the miscellaneous group (adjusted OR 1.35, 95% CI 0.47-3.88), Lansoprazole was inversely associated (adjusted OR 0.48, 95% CI 0.18-1.24 and adjusted OR 0.40, 95% CI 0.11-1.41 for ESBL versus GNB controls and ESBL versus miscellaneous organisms, respectively). Exposure to PPIs in the preceding 3 months showed an association with increased risk of ESBL-UTI. While Esomeprazole showed a positive association, Lansoprazole had an inverse association for ESBL-UTI. Restricting the use of PPIs may be beneficial in the fight against antimicrobial resistance.

The Effect of Proton Pump Inhibitor Use on Survival of Patients With Colorectal Cancer: A Study of a Racially Diverse Population.

Introduction Proton pump inhibitor (PPI) use is increasing in the general population. Chronic PPI use can lead to hypergastrinemia, which has been purported to increase the risk of developing colorectal cancer (CRC). Several studies have failed to report any association between PPI use and the risk of CRC. However, little is known about the effect of PPI use on CRC survival. In this retrospective analysis, we studied the effect of PPI use on CRC survival in a racially diverse population. Methods Data were abstracted for 1050 consecutive patients diagnosed with CRC from January 2007 to December 2020. The Kaplan-Meier curve was created to study the effect of PPI exposure compared to no exposure on overall survival (OS). Univariate and multivariate analyses were performed to investigate predictors of survival. Results Complete data were available for 750 patients with CRC, 52.5% were males, 22.7% were Whites, 60.1% were Asians, and 17.2% were Pacific Islanders. A total of 25.6% of patients had a history of PPI use. Moreover, 79.2% had hypertension, 68.8% had hyperlipidemia, 38.0% had diabetes mellitus, and 30.2% had kidney disease. There was no difference in median OS among PPI users compared to non-users, p value=0.4. Age, grade, and stage were predictors of inferior OS. No significant association was noticed with gender, race, comorbidities, or treatment with chemotherapy. Conclusion In this retrospective analysis of a racially diverse population of CRC patients, we found that PPI use was not associated with worse OS. Until high-quality prospective data are available, physicians should not stop PPIs that are clinically indicated.

The Impact of Concomitant Proton Pump Inhibitors Therapy on Clinical Outcome of Cancer Patients Treated With Immune Checkpoint Inhibitors: A Meta-analysis.

In patients with advanced cancer receiving immune checkpoint inhibitors (ICIs) therapy, there are conflict perspectives about the influence of concomitant use of proton pump inhibitors (PPIs). We are aimed at exploring the influence of concomitant PPIs exposure on clinical outcome among cancer patients receiving ICIs treatment. We searched relevant literatures in PubMed, EMBASE, and the Cochrane Library without language restrictions. We extracted the data from selected studies and calculated the pooled hazard ratios (HRs) with 95% CIs through professional software for overall survival and progression-free survival among cancer patients undergoing ICIs therapy exposed to PPIs. Fourteen studies including 6716 advanced cancer patients receiving ICIs treatment were appropriate for analysis judging by pre-set inclusion and exclusion criteria. The result indicated that concomitant PPIs exposure was significantly related to shorter overall survival (HR=1.388; 95% CI: 1.278-1.498, P <0.001) and progression-free survival (HR=1.285; 95% CI: 1.193-1.384, P <0.001) among multiple cancer patients receiving ICIs therapy. Our meta-analysis showed that concomitant PPIs exposure had an adverse impact on clinical outcome among patients receiving ICIs therapy. Clinical oncologists must be cautious of PPIs delivery during ICIs treatment.

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients: Results From the TransplantLines Biobank and Cohort Study

Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Cross-sectional study. Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. PPI use, PPI type, PPI dosage, and duration of PPI use. Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Logistic and linear regression. We included 937 kidney transplant recipients (mean age 56±13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P<0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P<0.001), lower physical HRQoL (regression coefficient-8.54, 95% CI,-11.54 to-5.54, P<0.001), and lower mental HRQoL (regression coefficient-4.66, 95% CI,-7.15 to-2.17, P<0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Residual confounding and inability to assess causal relationships. PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted.

Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review.

(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have assessed the pathological characteristics and outcomes of biopsy-proven kidney IRAEs. (2) Methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane for case reports, case series, and cohort studies for patients with biopsy-proven kidney IRAEs. All data were used to describe pathological characteristics and outcomes, and individual-level data from case reports and case series were pooled to analyze risk factors associated with different pathologies and prognoses. (3) Results: In total, 384 patients from 127 studies were enrolled. Most patients were treated with PD-1/PD-L1 inhibitors (76%), and 95% presented with acute kidney disease (AKD). Acute tubulointerstitial nephritis/acute interstitial nephritis (ATIN/AIN) was the most common pathologic type (72%). Most patients (89%) received steroid therapy, and 14% (42/292) required RRT. Among AKD patients, 17% (48/287) had no kidney recovery. Analyses of pooled individual-level data from 221 patients revealed that male sex, older age, and proton pump inhibitor (PPI) exposure were associated with ICI-associated ATIN/AIN. Patients with glomerular injury had an increased risk of tumor progression (OR 2.975; 95% CI, 1.176, 7.527; p = 0.021), and ATIN/AIN posed a decreased risk of death (OR 0.164; 95% CI, 0.057, 0.473; p = 0.001). (4) Conclusions: We provide the first systematic review of biopsy-proven ICI-kidney IRAEs of interest to clinicians. Oncologists and nephrologists should consider obtaining a kidney biopsy when clinically indicated.

Association Between Proton Pump Inhibitor Exposure and Acute Kidney Injury After Cardiac Surgery

ObjectiveTo evaluate the association of preoperative proton pump inhibitor (PPI) exposure with incident acute kidney injury (AKI) after cardiac surgery. Patients and MethodsThe Severance cardiac surgery cohort included 9860 cardiac surgery patients aged 18 years or older. The National Health Insurance Service-senior cohort included 2933 patients aged 60 years or older who underwent cardiac surgery. Preoperative PPI exposure was defined as a PPI prescription within 3 weeks prior to cardiac surgery. Primary outcomes were postoperative AKI and AKI requiring dialysis (AKI-dialysis). ResultsIn the Severance cardiac surgery cohort after propensity score matching for PPI exposure, incident AKI (44.0% [472 of 1073] vs 40.5% [1304 of 3219]) and AKI-dialysis (5.8% [62 of 1073] vs 3.7% [119 of 3219]) were more common in patients exposed to PPI than in those who were not. Hospital and intensive care unit stay durations were longer among PPI-exposed than PPI-nonexposed patients. Multivariable conditional logistic analyses revealed that PPI exposure was significantly associated with incident AKI (adjusted odds ratio [AOR], 1.21; 95% CI, 1.03 to 1.42; P=.02) and AKI-dialysis (AOR, 1.74; 95% CI, 1.15 to 2.63; P=.009). The National Health Insurance Service–Senior cohort had similar results, revealing a significant association between PPI exposure and incident AKI-dialysis (AOR, 1.87; 95% CI, 1.25 to 2.81; P=.003). Discontinuation of PPI prior to operation was associated with a lower odds of AKI development in both cohorts. ConclusionPreoperative PPI exposure may be a modifiable risk factor for AKI among patients undergoing cardiac surgery.

P325 Proton pump inhibitors are associated with a disabling course of Crohn’s disease

Abstract Background The impact of proton pump inhibitors (PPIs) on the evolution of inflammatory bowel disease (IBD) remains debated with only sparse data available. The primary objective of this study was to analyze the impact of PPIs on the course of IBD. Methods This was a single-center, retrospective cohort study. We included consecutive adult patients diagnosed with Crohn disease (CD) or ulcerative colitis (UC) who were followed prospectively in our day hospital over a 4-month period (from May to August 2022). PPI exposure was defined as PPI use for a cumulative duration of more than seven days from the date of IBD diagnosis until the end of follow-up. We performed a time to event analysis to investigate the association of PPI exposure with treatment failure defined as an IBD-related surgery or hospitalization and/or failure for more than four biologic treatment (Anti TNF, Vedolizumab, Ustekinumab). Results Among the 281 patients identified, 244 patients were eligible for analysis of the primary objective (152 with CD, mean age 45 years, sex ratio 1:1). 113 (46%) patients had been previously exposed to a PPI. PPI-exposed patients were significantly older (p=0.013), more often women (p=0.029), with more frequent active smoking (p=0.001). A total of 152 patients (62%) had treatment failure. Using Cox regression analysis, (Table 1), PPI use identified as an independent factor associated with treatment failure (HR = 1.920; 95% CI [1.084-3.403]; p0.025). In a subgroup analysis by IBD type, this remained statistically significant only for CD (HR = 3.190; 95% CI (1.412-7.206); p 0.005) but not for UC (HR = 0.981; 95% CI (0.384-2.504); p0.968). Survival without treatment failure (Figure 1) was significantly higher in patients without PPI exposure compared to patients with PPI exposure, (325 months vs. 228 months, respectively, p=0.022 (Log-Rank). In a subgroup analysis of infliximab-treated patients, PPI use was not associated with risk of immunogenicity (HR = 1.071; 95% CI (0.515-2.226); p0.854). Conclusion This study demonstrates the negative impact of PPIs on the disease course in patients with CD. The use PPIs should better be discussed on a case-by-case basis.

Association between Proton Pump Inhibitor Use and the Risk of Female Cancers: A Nested Case-Control Study of 23 Million Individuals.

Firm conclusions about whether long-term proton pump inhibitor (PPI) drug use impacts female cancer risk remain controversial. We aimed to investigate the associations between PPI use and female cancer risks. A nationwide population-based, nested case-control study was conducted within Taiwan's Health and Welfare Data Science Center's databases (2000-2016) and linked to pathologically confirmed cancer data from the Taiwan Cancer Registry (1979-2016). Individuals without any cancer diagnosis during the 17 years of the study served as controls. Case and control patients were matched 1:4 based on age, gender, and visit date. Conditional logistic regression with 95% confidence intervals (CIs) was applied to investigate the association between PPI exposure and female cancer risks by adjusting for potential confounders such as the Charlson comorbidity index and medication usage (metformin, aspirin, and statins). A total of 233,173 female cancer cases were identified, consisting of 135,437 diagnosed with breast cancer, 64,382 with cervical cancer, 19,580 with endometrial cancer, and 13,774 with ovarian cancer. After matching each case with four controls, we included 932,692 control female patients. The number of controls for patients with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer was 541,748, 257,528, 78,320, and 55,096, respectively. The use of PPIs was significantly associated with reduced risk of breast cancer and ovarian cancer in groups aged 20-39 years (adjusted odds ratio (aOR): 0.69, 95%CI: 0.56-0.84; p &lt; 0.001 and aOR: 0.58, 95%CI: 0.34-0.99; p &lt; 0.05, respectively) and 40-64 years (aOR: 0.89, 95%CI: 0.86-0.94; p &lt; 0.0001 and aOR: 0.87, 95%CI: 0.75-0.99; p &lt; 0.05, respectively). PPI exposure was associated with a significant decrease in cervical and endometrial cancer risks in the group aged 40-64 years (with aOR: 0.79, 95%CI: 0.73-0.86; p &lt; 0.0001 and aOR: 0.72, 95%CI: 0.65-0.81; p &lt; 0.0001, respectively). In contrast, in elderly women, PPI use was found to be insignificantly associated with female cancers among users. Our findings, based on real-world big data, can depict a comprehensive overview of PPI usage and female cancer risk. Further clinical studies are needed to elucidate the effects of PPIs on female cancers.

Time-dependent association between omeprazole and esomeprazole and hospitalization due to hyponatremia

PurposeThe aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole.MethodsIn this register-based case–control study, we compared patients hospitalized with a main diagnosis of hyponatremia (n = 11,213) to matched controls (n = 44,801). We used multiple regression to investigate time-related associations between omeprazole and esomeprazole and hospitalization because of hyponatremia.ResultsThe overall adjusted OR (aOR) between proton pump inhibitor (PPI) exposure, regardless of treatment duration and hospitalization with a main diagnosis of hyponatremia, was 1.23 (95% confidence interval CI 1.15–1.32). Exposure to PPIs was associated with a prompt increase in risk of hospitalization for hyponatremia from the first week (aOR 6.87; 95% CI 4.83–9.86). The risk then gradually declined, reaching an aOR of 1.64 (0.96–2.75) the fifth week. The aOR of ongoing PPI treatment was 1.10 (1.03–1.18).ConclusionThe present study shows a marked association between omeprazole and esomeprazole and hyponatremia related to recently initiated treatment. Consequently, newly initiated PPIs should be considered a potential culprit in any patient suffering from hyponatremia. However, if the patient has had this treatment for a longer time, the PPI should be considered a less likely cause.

Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?

The association between proton pump inhibitor (PPI) use and dementia remains controversial. This cohort study re-examines this issue, addressing shortcomings identified in previous publications using a population-based and a high-dimension propensity-score matched cohort to follow patients for up to 22 years. Cox regression models using baseline characteristics, a lag period, and time-varying variables were used to examine the risk of dementia by cumulative PPI exposure. High-dose PPI users (> 180 days of use) had significantly higher risk of dementia in crude Cox models. After adjustment for medical diagnoses and prescription drug use, these associations disappeared. Among high-dose users starting PPI therapy between 46 and 55 years old, the unadjusted hazard ratio (HR) was 1.55 (95% confidence interval (CI) 1.14, 2.10); the adjusted hazard ratio (aHR) was 1.10 (95% CI 0.80, 1.51). For high-dose users starting therapy between 56 and 65 years, HR=1.22 (95% CI1.03, 1.44); aHR=0.99 (95% CI 0.83, 1.17). High-dose users between the ages of 66 and 75 years had no association with the risk of dementia. The use of lag models or time-varying parameters similarly found some association with dementia in crude, but not multivariable Cox models. Although high-dose PPI users were more likely to develop dementia, they were more likely to be diagnosed with dementia risk factors, such as diabetes and cardiovascular disease, which are risk factors for dementia. Controlling for these conditions using multivariable models or a propensity-score matched cohort eliminated this association.

Proton pump inhibitors-related subacute cutaneous lupus erythematosus: Clinical characteristics, management, and outcome.

Previous knowledge about the association between proton pump inhibitors (PPIs) exposure and subacute cutaneous lupus erythematosus (SCLE) was mainly based on limited case reports or few review studies. We aim to evaluate the clinical characteristics, management, and outcome in patients with PPIs-induced SCLE. Case reports and case series from 2000 to December 31, 2021, on SCLE induced by PPIs were collected and retrospectively analyzed. A total of 29 patients (6 male and 23 female) were included from 19 studies, the median age was 61 years (range 19-85), and 65.5% of patients were ≥60 years old. 37.9% of patients had the history of autoimmune diseases. The incubation period of PPIs intro to SCLE was 6 weeks for PPI-naive patients and 2 weeks for those re-administration of PPIs. The most common symptoms were annular and polycyclic erythematous (74.1%), rash or maculopapular (48.1%), and scaly plaques (40.7%). Trunk (69.2%), extremities (69.2%), face (26.9%), chest (26.9%), and back (26.9%) were common involved locations. Antinuclear antibodies, anti-Ro/SSA antibodies, and anti-La/SSB antibodies were positive in 24 patients (82.8%), 24 patients (82.8%), and 6 patients (20.7%), respectively. Direct immunofluorescence was positive in 50% of cases. Complete clinical remission (92.6%) was observed (median time: 4 weeks) with discontinuation of PPIs and treatment of oral corticosteroids (61.1%), hydroxychloroquine (44.4%), or topical steroids (16.7%). PPIs-related SCLE is a rare adverse reaction based on clinical manifestations associated with immunological abnormalities and suggestive histological findings. PPIs should be suspected when considering possible culprits for drug-related SCLE.

Proton pump inhibitors use and risk of inflammatory bowel diseases: a meta-analysis of observational studies.

Proton Pump Inhibitors (PPIs) reduce gastric acid production and they are indicated for myriad gastrointestinal conditions. Prolonged use of PPI has been linked to the risk of inflammatory bowel disease (IBD) though this fact is not well established. We aimed to conduct a systematic review and meta-analysis to estimate the risk of IBD occurrence with PPI use. The databases such as PubMed, Scopus, and Cochrane Library were accessed from inception to December 2020. Additionally, the bibliographic search and a random search in Google, Google Scholar, and ResearchGate were performed to find additional sources. The observational studies estimating the risk of IBD following the use of PPI, published in the English language were considered for this review. The methodological quality of included studies was assessed using the Modified Downs and Black checklist. Eight out of 2038 studies with 157,758 participants were included in this meta-analysis. A significantly higher risk of IBD (adjusted odds ratio [aOR] 2.43; 95% Confidence Interval [CI] 1.18-5.02; P=0.02; n=6) was observed in participants taking PPIs for any indication. Moreover, a significant association was observed between PPI exposure on the different types of IBD such as ulcerative colitis and Crohn's disease together (aOR: 3.60; 95% CI: 1.10-11.74), collagenous colitis (OR: 4.73; 95% CI: 1.99-11.22) and lymphocytic Colitis (OR: 3.77; 95% CI: 2.91-4.87), but not with ulcerative colitis (P=0.47) and microscopic colitis (P=0.07) alone. Similarly, a significant association was observed among Europeans (aOR: 3.98; 95% CI: 2.36-6.71), but not with North American (aOR: 0.48; 95% CI: 0.01-26.71) studies. Overall the study quality was good. The current evidence indicates that exposure to PPI is significantly associated with increased risk of IBD. Further, adequately powered studies from various parts of the world are needed for better quantification and generalizability of our findings. CRD42020209674.

PROTON PUMP INHIBITORS AND RISK OF PLEURAL EMPYEMA AND LUNG ABSCESS

PROTON PUMP INHIBITORS AND RISK OF PLEURAL EMPYEMA AND LUNG ABSCESS