Proton Pump Inhibitors Non-users Research Articles

Proton pump Inhibitors and Risk of Enteric Infection in Inflammatory Bowel Disease: A Self-controlled Case Series.

We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD), after adequately accounting for baseline differences between PPI users and nonusers. This was a self-controlled case series, with each patient serving as their own control. Ambulatory patients with IBD were included if they were tested for enteric infection by multiplex polymerase chain reaction testing panel (GIPCR) and/or Clostridoides difficile toxin PCR from 2015 to 2019 and received PPIs for some but not all of this period. Rates of enteric infections were compared between the PPI-exposed period vs pre- and post-PPI periods identical in duration to the exposed period. Conditional Poisson regression was used to adjust for time-varying factors. Two hundred twenty-one IBD patients were included (49% ulcerative colitis, 46% Crohn's disease, and 5% indeterminate colitis). The median PPI duration was 7 months (interquartile range 4 to 11 months). A total of 25 (11%) patients had a positive GIPCR or C. difficile test in the PPI period, 9 (4%) in the pre-PPI period, and 8 (4%) in the post-PPI period. Observed incidence rates for enteric infections were 2.5, 7.4, and 2.2 per 100 person years for the pre-PPI, PPI, and post-PPI periods, respectively (adjusted incidence rate ratios, 2.8; 95% confidence interval [CI] 1.3-6.0) for PPI vs pre-PPI and 2.9 (95% CI, 1.3-6.4) for PPI vs post-PPI). The adjusted absolute excess risk associated with PPIs was 4.9 infections per 100 person years. Proton pump inhibitors were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.

Bone microstructure in proton pump inhibitor users.

We assessed skeletal microstructure and stiffness in proton pump inhibitor (PPI) users compared to non-users with high resolution peripheral quantitative computed tomography (HRpQCT) and microfinite element analysis (μFEA) and other modalities. Relationships between PPI dose/frequency and bone parameters were evaluated. We cross-sectionally assessed skeletal health in 601 older (≥age 65years) adults (130 PPI users and 471 non-users) participating in a multi-ethnic population-based study of aging. PPI users tended to have more comorbidities and take more medications than non-users. Female PPI users (n=100) were more likely to be non-Caucasian, shorter with higher BMI, and more likely to have diabetes, lower physical activity and be using anti-depressants and thiazide diuretics compared to non-users (n=302). Male PPI users (n=30) were more likely to have liver disease than non-users (n=169). In women, historical fractures (53.0% vs. 43.4%, p=0.05) and falls (38% vs. 26.8%, p=0.04) tended to be more frequent in PPI users compared to non-users. Number of falls was higher in women reporting daily rather than intermittent PPI use (1.8/year vs. 1.0/year, p<0.001). In women, there were no differences in any HRpQCT or μFEA parameter. By HRpQCT, covariate-adjusted cortical volumetric bone density (Ct.vBMD) was 4.2% lower in male PPI users vs. non-users at the tibia (p=0.04), but this did not result in reduced stiffness. There were no other differences by HRpQCT at the tibia or radius. PPI use was not associated with altered skeletal microstructure or stiffness in elderly men and women. The results do not support a relationship between PPI use and microstructure.

The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis.

(1) Although emerging evidence suggests that proton pump inhibitor (PPI)-induced dysbiosis negatively alters treatment response to immune checkpoint inhibitors (ICIs) in cancer patients, no study systematically investigates the association between PPIs, ICIs, and chemotherapy; (2) Cochrane Library, Embase, Medline, and PubMed were searched from inception to 20 May 2022, to identify relevant studies involving patients receiving ICIs or chemotherapy and reporting survival outcome between PPI users and non-users. Survival outcomes included overall survival (OS) and progression-free survival (PFS). Network meta-analyses were performed using random-effects models. p-scores, with a value between 0 and 1, were calculated to quantify the treatment ranking, with a higher score suggesting a higher probability of greater effectiveness. We also conducted pairwise meta-analyses of observational studies to complement our network meta-analysis; (3) We identified 62 studies involving 26,484 patients (PPI = 8834; non-PPI = 17,650), including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and squamous cell carcinoma (SCC) of the neck and head. Eight post-hoc analyses from 18 randomized-controlled trials were included in our network, which demonstrated that, in advanced NSCLC and UC, patients under ICI treatment with concomitant PPI (p-score: 0.2016) are associated with both poorer OS (HR, 1.49; 95% CI, 1.37 to 1.67) and poorer PFS (HR, 1.41; 95% CI, 1.25 to 1.61) than those without PPIs (p-score: 1.000). Patients under ICI treatment with concomitant PPI also had poorer OS (HR, 1.18; 95% CI, 1.07 to 1.31) and poorer PFS (HR, 1.30; 95% CI, 1.14 to 1.48) in comparison with those receiving chemotherapy (p-score: 0.6664), implying that PPIs may compromise ICI's effectiveness, making it less effective than chemotherapy. Our pairwise meta-analyses also supported this association. Conversely, PPI has little effect on patients with advanced melanoma, RCC, HCC, and SCC of the neck and head who were treated with ICIs; (4) "PPI-induced dysbiosis" serves as a significant modifier of treatment response in both advanced NSCLC and UC that are treated with ICIs, compromising the effectiveness of ICIs to be less than that of chemotherapy. Thus, clinicians should avoid unnecessary PPI prescription in these patients. "PPI-induced dysbiosis", on the other hand, does not alter the treatment response to ICIs in advanced melanoma, RCC, HCC, and SCC of the head and neck.

Monitoring of serum magnesium levels during long-term use of proton pump inhibitors in elderly japanese patients: is it really necessary or not?

BackgroundLong-term use of proton pump inhibitors (PPIs) has been found to significantly lower serum magnesium levels in patients in the USA and Europe. The package inserts of PPIs in these countries clearly state that healthcare professionals should consider monitoring magnesium levels prior to initiation of PPI treatment and periodically thereafter. However, the package inserts of PPIs in Japan do not clearly mention the monitoring of magnesium levels. In this study, we evaluated the relationship between long-term use of PPIs and the lower serum magnesium concentrations in elderly Japanese patients.MethodsUsing a retrospective observational approach, a total of 264 Japanese outpatients were included in the study. Patients over the age of 75 years were considered elderly. Serum magnesium levels of the patients were measured in units of 0.1 mg/dL between January 2016 and June 2022 at the Higo Internal Medicine Clinic and Ai Pharmacy in Kyoto, Japan.ResultsFour of the 264 eligible patients were diagnosed with hypomagnesemia. Three were PPI non-users, and one was a PPI user. Serum magnesium concentrations were significantly lower in PPI users (n = 47) than in non-users (n = 85; 2.1 ± 0.2 vs. 2.2 ± 0.3 mg/dL, p < 0.05) in the 132 elderly patients. Comorbidity included diabetes mellitus in both PPI users (23.4%) and non-users (57.6%) and hyperlipidemia in both PPI users (61.7%) and non-users (41.2%).ConclusionPPIs are commonly used oral drugs for elderly patients. There was an association between the long-term use of PPIs and lower serum magnesium concentrations in elderly patients. Although the difference in the decrease in serum magnesium concentrations was within the normal range of serum magnesium levels, health care professionals should consider monitoring serum magnesium levels periodically in elderly patients receiving long-term PPIs.

Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality

The use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised. We conducted a prospective cohort study using data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias). Among 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13-1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17-1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02-1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12-1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10-2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97-1.11; cancer: HR, 1.07; 95% CI, 0.89-1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81-1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95-1.50; digestive diseases: HR, 1.38; 95% CI, 0.88-2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality. After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.

Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors

The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial.We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models.Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28-3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23-2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36-1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93-1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10-8.05, P[interaction] = 0.032).PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.

The association between chronic rhinosinusitis and proton pump inhibitor use: a nested case–control study using a health screening cohort

This study aimed to evaluate the relationship between chronic rhinosinusitis (CRS) and proton pump inhibitor (PPI) use in a Korean population. The Korea National Health Insurance Service-National Sample Cohort was assessed from 2002 to 2013. Patients with CRS (n = 7194) and control participants (n = 28,776) were matched by random order at a 1:4 ratio for age, sex, income group, region of residence, and index date. We analyzed PPI use by patients with and without CRS. ICD-10 codes defined CRS, and claim codes defined previous PPI use. Conditional logistic regression analyzed the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CI). Subgroup analyses were performed according to age and sex. There was a difference in PPI prescription history and prescription duration between the CRS and control groups. The rate of CRS was higher in current (33.8% [263/778]) and past (26.3% [713/2708]) PPI users than PPI non-users (19.1% [6218/32,484], P < 0.001). The adjusted OR (aOR) of CRS with/without nasal polyps was 1.71 (95% CI 1.46–2.02, P < 0.001) and 1.28 (95% CI 1.16–1.41, P < 0.001) in current and past PPI users, respectively. Irrespective of PPI prescription days, PPI use was associated with higher CRS occurrence (aOR 1.46; 95% CI 1.26–1.69, P < 0.001) in the 30–89-day PPI user group. The subgroup analyses results were consistent. The ORs of CRS were higher in PPI users than in the controls, and consistently so in all age and sex groups.

MP03-12 ASSOCIATION OF USE OF POTASSIUM COMPETITIVE ACID BLOCKERS AND EFFECTIVENESS OF PEMBROLIZUMAB IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 May 2022MP03-12 ASSOCIATION OF USE OF POTASSIUM COMPETITIVE ACID BLOCKERS AND EFFECTIVENESS OF PEMBROLIZUMAB IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA Wataru Fukuokaya, Takahiro Kimura, Kazumasa Komura, Taizo Uchimoto, Kazuki Nishimura, Yu Oyama, Hirokazu Abe, Haruhito Azuma, Jun Miki, and Shin Egawa Wataru FukuokayaWataru Fukuokaya More articles by this author , Takahiro KimuraTakahiro Kimura More articles by this author , Kazumasa KomuraKazumasa Komura More articles by this author , Taizo UchimotoTaizo Uchimoto More articles by this author , Kazuki NishimuraKazuki Nishimura More articles by this author , Yu OyamaYu Oyama More articles by this author , Hirokazu AbeHirokazu Abe More articles by this author , Haruhito AzumaHaruhito Azuma More articles by this author , Jun MikiJun Miki More articles by this author , and Shin EgawaShin Egawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002515.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Evidence showed that proton pump inhibitor use was associated with worse survival of patients with metastatic urothelial carcinoma (UC) treated with pembrolizumab. Potassium competitive acid blocker (P-CAB) is a new class of acid blockers which has distinct advantages compared to other conventional proton pump inhibitors (PPI) in terms of the effectiveness for acid suppression. However, the impact of its use on the effectiveness of pembrolizumab in these patients is still unclear. We investigated the impact of P-CAB use on the effectiveness of pembrolizumab in patients with metastatic UC. METHODS: We retrospectively analyzed the records of 227 patients with metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) per immune response evaluation criteria in solid tumors were also compared. Multivariable Cox regression models were performed to evaluate the association between P-CAB use and these outcomes. RESULTS: Overall, 30 (13.2%) and 56 (24.7%) patients used P-CABs and PPIs, respectively. Median follow-up period of was 12.8 months (95% CI: 10.6 to 19.3). There were significant differences in baseline platelet count (median; P-CAB users vs. PPI users vs. non-users: 292.5 vs. 271 vs. 249 *1000/uL; P=0.047) and the use of concomitant analgesics (P-CAB users vs. PPI users vs. non-users: 22 [73.3%] vs. 28 [50.0%] vs. 38 [27.0%]; P <0.001). Multivariable Cox regression models showed that both P-CAB and PPI use were associated with worse OS (P-CAB, hazard ratio [HR]: 2.51, 95% confidence interval [CI]: 1.44 to 4.38, P=0.001; PPI, HR: 1.58, 95% CI: 0.96 to 2.61, P=0.072) and iPFS (P-CAB, HR: 1.79, 95% CI: 1.12 to 2.86, P=0.015; PPI, HR: 1.56, 95% CI: 1.07 to 2.28, P=0.021). CONCLUSIONS: Similar to PPI, P-CAB use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e24 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wataru Fukuokaya More articles by this author Takahiro Kimura More articles by this author Kazumasa Komura More articles by this author Taizo Uchimoto More articles by this author Kazuki Nishimura More articles by this author Yu Oyama More articles by this author Hirokazu Abe More articles by this author Haruhito Azuma More articles by this author Jun Miki More articles by this author Shin Egawa More articles by this author Expand All Advertisement PDF DownloadLoading ...

Effects of Proton Pump Inhibitors on Survival Outcomes in Patients with Metastatic or Unresectable Urothelial Carcinoma Treated with Pembrolizumab.

The gut microbiome influences tumor response to immune checkpoint inhibitors (ICIs). The proton pump inhibitors (PPI) significantly impair diversity of the gut microbiota and can affect the efficacy of ICIs. Therefore, the present study aimed to evaluate the influence of PPI on survival in patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. We conducted a retrospective cohort study of patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. The use of PPI was defined as any administration for ≥30 d within 60 d prior and/or 30 d after treatment initiation. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and Cox proportional hazards regression analysis was performed to investigate prognostic factors based on patient characteristics. Seventy-nine patients were included in the analysis, and 34 patients (43.0%) received PPI. There were no significant differences in OS and PFS between PPI users and nonusers (median OS: 8.2 months vs. 11.2 months, hazard ratio (HR): 1.36, 95% confidence interval (CI): 0.75-2.42, p = 0.296; median PFS: 3.5 months vs. 5.1 months, HR: 1.63, 95% CI: 0.95-2.80, p = 0.069). In the multivariable analysis, PPI use was not associated with OS (HR 0.80, 95% CI 0.40-1.56, p = 0.526) or PFS (HR 1.44, 95% CI 0.79-2.60, p = 0.233). In conclusion, the estimated effect size of PPI use on survival in Japanese patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab was not reproducible.

259 Proton pump inhibitor use is not significantly associated with severe COVID-19 related outcomes after extensive covariate adjustment

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

Association between Proton Pump Inhibitor Use and Parkinson's Disease in a Korean Population.

Few studies have shown an increased risk of Parkinson’s disease (PD) with the use of proton pump inhibitors (PPIs), and the pathophysiological mechanism for this association has not been unveiled. This study examined the relationship between PPI use and PD in a Korean population. We investigated 3026 PD patients and 12,104 controls who were matched by age, sex, income, and region of residence at a ratio of 1:4 in the Korean National Health Insurance Service, National Sample Cohort between 2002 and 2015. We estimated the associations between current and past use of PPIs and PD using odds ratios (ORs) and 95% confidence intervals (CIs) in a conditional/unconditional logistic regression after adjusting for probable confounders. Compared with PPI nonusers, both current users and past users had significantly greater odds of having PD, with ORs of 1.63 (95% CI = 1.44–1.84) and 1.12 (95% CI = 1.01–1.25), respectively. A significant association with PD was observed in individuals who used PPIs for 30–90 days and ≥90 days (OR = 1.26 and 1.64, 95% CI = 1.12–1.43 and 1.43–1.89) but not among those who used PPIs for <30 days. Both current and past use of PPIs associated with a higher probability of PD in the Korean population. Our study provides evidence regarding the association between PPI exposure and PD, but further investigation and possible explanations are warranted.

Efficacy of Atezolizumab in Patients With Advanced NSCLC Receiving Concomitant Antibiotic or Proton Pump Inhibitor Treatment: Pooled Analysis of Five Randomized Control Trials

IntroductionGut dysbiosis may reduce immune checkpoint inhibitor (ICI) efficacy. Antibiotics and proton pump inhibitors (PPIs) are commonly used drugs causing gut dysbiosis. There is limited randomized controlled trial (RCT) evidence on whether antibiotics or PPIs impact ICI benefit versus comparator treatments. MethodsThis study pooled five RCTs (IMpower130, IMpower131, IMpower150, OAK, and POPLAR) evaluating atezolizumab in advanced NSCLC. Atezolizumab efficacy (hazard ratio with 95% confidence intervals) was assessed for subgroups on the basis of antibiotic and PPI use at randomization. The association between antibiotic and PPI use with pretreatment peripheral blood immunophenotype was also explored. ResultsOf 4458 participants, 285 received an antibiotic in the 30-day pretreatment and 1225 were using a PPI at treatment initiation. Overall survival efficacy of atezolizumab was similar (p[interaction] = 0.35) for antibiotic users (hazard ratio 95% confidence interval: 0.73 [0.53–0.99]) and antibiotic nonusers (0.82 [0.74–0.91]). Nevertheless, efficacy was reduced (p[interaction] = 0.003) for PPI users (1.00 [0.85–1.17]) compared with PPI nonusers (0.76 [0.69–0.83]). Findings were consistent across RCTs and for progression-free survival. PPI use was associated with 9%, 18%, and 9% lower counts of lymphocytes, CD19+, and CD16+CD56+ immune cells, respectively (p < 0·01). ConclusionsReassuringly, atezolizumab efficacy did not differ for antibiotic users. Opposingly, PPI use was consistently associated with decreased atezolizumab efficacy and lower pretreatment counts of lymphocytes, CD19+, and CD16+CD56+ immune cells. Given that approximately 30% of patients with cancer use PPIs, there is an urgent need for evidence on the impacts of PPIs on other ICIs and for the development of guidelines on nonessential PPI use with ICIs.

Proton pump inhibitor use and hearing loss in patients with type 2 diabetes: Evidence from a hospital-based case-control study and a population-based cohort study.

This study aimed to investigate the association between proton pump inhibitor (PPI) use and risk of sensorineural hearing loss (SNHL) or tinnitus in patients with type 2 diabetes using hospital- and population-based data. For the case-control study using the Asan Biomedical Research Environment database, the characteristics between cases and sex-, age- and index-year-matched controls were compared by the chi-squared test. Conditional logistic regression was used to estimate the odds ratios (ORs). For the cohort study using the Korean National Health Insurance Service - National Sample Cohort, the hazard ratios (HRs) for SNHL or tinnitus associated with PPI use were analysed by the Cox proportional hazard regression model. The case-control study included 1379 cases and 5512 matched controls. After adjustment, PPI use was associated with an increased risk of SNHL or tinnitus (OR 1.61, 95% confidence interval [CI] 1.30-1.99). The ORs were higher for current or recent use of PPI and high average daily dose. In the cohort study including 17 233 pairs of PPI users and nonusers after propensity score matching, the risk of SNHL or tinnitus increased in PPI users compared with nonusers (HR 1.50, 95% CI 1.40-1.61). In the stratified analyses, risks remained significant and the magnitude of association was relatively high in those of younger age, patients without gastroesophageal reflux disease and patients not receiving histamine 2 receptor blockers. Our study suggests that PPI use is associated with an increased risk of SNHL or tinnitus. Given the widespread use of PPIs, the potential ototoxic effects of PPIs remain an important concern.

Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B-12 status, and the impact of fortified foods, in older adults

ABSTRACTBackgroundAtrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking.ObjectivesTo investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults.MethodsEligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008–2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < −0.5. A pepsinogen I:II ratio <3 was considered indicative of AG.ResultsAG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0–4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG.ConclusionsOlder adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG.

S369 Pre-admission Proton Pump Inhibitors Use Associated With Increasing Secondary Infection in Hospitalized COVID-19 Patients: A New Finding From a Single Center Experience

Introduction: Despite advances in treatment and vaccination, COVID-19 continues to have a significant toll on healthcare services. Identifying more modifiable risk factors for severe infection is of utmost importance to guide effective health care delivery. Recent studies show conflicting results regarding the association of gastric acid suppression with the risk of developing severe COVID-19 infection. Considering that acid-suppressive medications are among the most commonly consumed drugs in the United States, an understanding of the impact of these agents on COVID-19 outcomes is of significant importance and inconclusive. We aimed to investigate if pre-admission exposure to proton pump inhibitors (PPIs) is associated with worse outcomes among patients hospitalized with COVID-19. Methods: We retrospectively identified COVID-19 patients admitted to Ochsner LSU Health, Shreveport, from July 2020 to November 2020. Information on baseline demographics, comorbidities, presenting symptoms, PPI use and clinical course was abstracted. We compared outcomes for PPI users and non-users using univariate and multivariate logistic regression. Results: 1370 patients were included in this study, with 14 (22.9%) PPI users, and 1056 (77.1%) non-users. Baseline characteristics are shown in Table 1. PPI users were older (66.00 vs 61.24, p< .0001) and had a lower BMI (31.54 vs 32.39, p< .0085) compared to non-users. Both groups received similar treatment: steroids, antibiotics, remdesivir, convalescent plasma, and supplemental oxygen. There was no significant difference in the length of stay between these 2 groups. On univariate analysis, PPI users were significantly associated with developing secondary infection (OR 1.45, P= 0.049) and acute kidney injury (AKI) (OR 1.45, P=0.015). The rate of developing other complications like deep venous thrombosis, pulmonary embolism, stroke, encephalopathy, shock, need for renal replacement therapy was similar in both groups. After adjusting for age, gender, race, BMI, comorbidities, PPI use was not associated with worse outcomes like ICU admission, ventilation requirement, mortality, or more complications (Figure 1). Conclusion: An interesting finding in this study was that PPI users were significantly associated with developing secondary infection but not with worse clinical outcomes or mortality. We recommend continuing PPI use when clinically indicated and educating users regarding their safety.Table 1.: Baseline Characteristics of Patients.Figure 1.: Outcomes of PPI users vs non-users. Line with blue dot is based on univariate model and with red dot is adjusted for age, gender, race, BMI and co-morbidities.

Proton Pump Inhibitors Are Associated with Increased Risk of Psoriasis: A Nationwide Nested Case-Control Study

Background: Proton pump inhibitors (PPIs) are among the most widely used drugs. Little is known about the association between PPI use and risk of psoriasis. Objective: To investigate the association between PPI use and subsequent psoriasis risk. Methods: We included participants from the Taiwan National Health Insurance Research Database. Patients with PPI use and an incidence of psoriasis (n = 5,756) were assigned to the case cohort and 1:1 matched to controls. PPI use was defined as >30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as ≤30 cDDDs. Logistic regression was used for the analyses. Results: There was a significant association between PPI use and psoriasis risk. The confounder-adjusted odd ratios (95% confidence interval [CI]) were 1.52 (1.31–1.76) and 1.54 (1.22–1.93) for patients with 120–365 cDDDs and >365 cDDDs, respectively, compared with PPI nonusers. Stratified analyses based on PPI type showed that exposure to lansoprazole (OR, 1.25; 95% CI, 1.11–1.41) was associated with subsequent psoriasis risk. Conclusions: PPI use might be associated with an increased risk of developing psoriasis or as an epiphenomenon. Further prospective studies are needed to elucidate the association and underlying mechanisms.

Association between proton pump inhibitors after percutaneous coronary intervention and risk of gastric cancer

BackgroundPrevious studies showing an association between chronic use of proton pump inhibitor (PPI) and gastric cancer are limited by confounding by indication. This relationship has not been studied in patients...

Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study.

Proton pump inhibitors (PPIs) are associated with microbiome changes of the gut, which in turn may affect the progression of colorectal cancer (CRC). This study aims to assess the associations between PPI use and all-cause and CRC-specific mortality. We selected all patients registered in the Swedish Prescribed Drug Registry who were diagnosed with CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through register linkage to the Swedish Causes of Death Registry until December 2013. PPI users were patients with ≥1 post-diagnosis PPI dispensation. Time-dependent Cox-regression models were performed with PPI use as time-varying exposure. Overall 4746 (14.0%) patients died, with an aHR of 1.38 (95% CI 1.32-1.44) for all-cause mortality comparing PPI users with PPI nonusers. Higher-magnitude associations were observed among male, cancer stage 0-I, rectal cancer and patients receiving CRC surgery. The PPI-all-cause mortality association was also more pronounced comparing new users to non-users (aHR = 1.47, 95%CI 1.40-1.55) than comparing continuous users to non-users (aHR = 1.32, 95%CI 1.24-1.39). The risk estimates for CRC-specific mortality comparing PPI users to PPI nonusers were similar to those for all-cause mortality. PPI use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.

Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy.

Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The underlying mechanism(s) for this association are unclear. We performed a prospective study of hospitalized coronavirus disease 2019 (COVID-19) patients and COVID-negative controls to understand how PPI use may affect angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, 2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors of in-hospital mortality. Control PPI users had higher salivary ACE2 mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 (P = 0.02), respectively. Salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In 694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors of mortality by logistic regression were PPI use (adjusted odds ratio [aOR] = 2.72, P < 0.001), age (aOR = 1.66 per decade, P < 0.001), race (aOR = 3.03, P = 0.002), cancer (aOR = 2.22, P = 0.008), and diabetes (aOR = 1.95, P = 0.003). The PPI-associated mortality risk was higher in black patients (aOR = 4.16, 95% confidence interval: 2.28-7.59) than others (aOR = 1.62, 95% confidence interval: 0.82-3.19, P = 0.04 for interaction). COVID-negative PPI users had higher salivary ACE2 expression. PPI use was associated with increased mortality risk in patients with COVID-19, particularly African Americans.

Proton Pump Inhibitors and Survival in Patients With Colorectal Cancer Receiving Fluoropyrimidine-Based Chemotherapy.

Concomitant use of proton pump inhibitors (PPIs) may negatively affect the efficacy of anticancer drugs such as fluoropyrimidines in patients with colorectal cancer (CRC). The primary objective of this study was to assess whether there is an association between concomitant PPI use and survival outcomes in patients with CRC treated with a fluoropyrimidine-based chemotherapy. A secondary analysis of 6 randomized controlled clinical trials in patients with advanced CRC was conducted using individual patient data through data-sharing platforms. The outcome measures were progression-free survival and overall survival in PPI users and nonusers. Subgroup analysis included the type of chemotherapy, capecitabine versus 5-FU, line of therapy, and addition of a vascular endothelial growth factor receptor inhibitor. Overall pooled hazard ratios (HRs) with 95% confidence intervals were calculated using a random effects model. A total of 5,594 patients with advanced CRC across 6 trials and 11 trial arms were included; 902 patients were receiving a PPI at trial entry and initiation of chemotherapy. PPI use was significantly associated with worse overall survival (pooled HR, 1.20; 95% CI, 1.03-1.40; P=.02; I2 for heterogeneity = 69%) and progression-free survival (overall pooled HR, 1.20; 95% CI, 1.05-1.37; P=.009; I2 = 65%) after adjusting for clinical covariates. Furthermore, the association between concomitant PPI use and survival outcomes was similar across most treatment subgroups. We speculate that alterations in the gut microbiome, altered immune milieu within the tumor, and interactions through transporters are potential mechanisms behind this association between PPI use and chemotherapy in patients with CRC, which warrant further study. Concomitant use of PPIs is associated with worse survival outcomes in patients with CRC treated with fluoropyrimidine-based chemotherapy. Clinicians should cautiously consider the concomitant use of PPIs in such patients.