Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort.
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SUBMITTER: Shah S
PROVIDER: S-EPMC9013721 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort.
Shah Shailja S Halvorson Alese A McBay Brandon B Dorn Chad C Wilson Otis O Tuteja Sony S Chang Kyong-Mi KM Cho Kelly K Hauger Richard R Suzuki Ayako A Hunt Christine C Siew Edward E Matheny Michael M Hung Adriana A Greevy Robert R Roumie Christianne C
Gut 20211018 7
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Project description:Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.
| S-EPMC9922884 | biostudies-literature
Project description:PurposeLymph node (LN) involvement in renal cell carcinoma (RCC) is associated with a poor prognosis. While lymph node dissection (LND) may provide diagnostic information, its therapeutic benefit remains controversial. Thus, the aim of our study is to analyze survival outcomes after LND for nonmetastatic RCC and to characterize contemporary practice patterns.Materials and methodsThe National Cancer Database was queried for patients with nonmetastatic RCC who underwent either partial or radical nephrectomy from 2010 to 2014. A total of 11,867 underwent surgery and LND. Chi-square tests were used to examine differences in patient demographics. To minimize selection bias, propensity score matching (PSM) was used to select one control for each LND case (n = 19,500). Cox regression analyses were conducted to examine overall survival (OS) in patients who received LND compared to those who did not.ResultsOf all patients undergoing LND for RCC (n = 11,867), 5%, 23%, 31%, 47% were performed for tumors of clinical T stage 1, 2, 3, and 4, respectively. Proportions of LND have not significantly changed from 2010 to 2014. No significant improvement in median OS for patients undergoing LND compared to no LND was shown (34.7 vs. 34.9 months, respectively; P = 0.98). Similarly, no significant improvement in median OS was found for clinically LN positive patients undergoing LND compared to no LND (P = 0.90). On Cox regression analysis, LND dissection was not associated with an OS benefit (hazard ratio: 1.00; 95% confidence interval 0.97 to 1.04).ConclusionsAmong all RCC patients, LNDs are often performed for low stage disease, suggesting a potential overutilization of LND. No OS benefit was seen in any subgroup of patients undergoing LND. Further investigation is needed to determine which patient populations may benefit most from LND.
| S-EPMC6295174 | biostudies-literature
Project description:ObjectiveTo examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction.DesignRetrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark.ParticipantsAll aspirin treated patients surviving 30 days after a first myocardial infarction from 1997 to 2006, with follow-up for one year. Patients treated with clopidogrel were excluded.Main outcome measuresThe risk of the combined end point of cardiovascular death, myocardial infarction, or stroke associated with use of proton pump inhibitors was analysed using Kaplan-Meier analysis, Cox proportional hazard models, and propensity score matched Cox proportional hazard models. Results 3366 of 19,925 (16.9%) aspirin treated patients experienced recurrent myocardial infarction, stroke, or cardiovascular death. The hazard ratio for the combined end point in patients receiving proton pump inhibitors based on the time dependent Cox proportional hazard model was 1.46 (1.33 to 1.61; P<0.001) and for the propensity score matched model based on 8318 patients it was 1.61 (1.45 to 1.79; P<0.001). A sensitivity analysis showed no increase in risk related to use of H(2) receptor blockers (1.04, 0.79 to 1.38; P=0.78). Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events.
| S-EPMC3092520 | biostudies-literature
Project description:BackgroundAlthough the National Comprehensive Cancer Network (NCCN) guidelines recommend use of lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) > 2 cm, there is limited evidence to support the association between use of LND and overall survival (OS).MethodsPatients with resected pNETs were identified in the National Cancer Database (2004-2014). The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups.ResultsA total of 2664 patients diagnosed met the study entry criteria. Of these, 2132 patients (80.6%) received LND, with a median of nine nodes removed. Positive nodes were identified in 28.0% of patients who underwent LND. IPTW-adjusted Kaplan-Meier analysis showed that median OS was similar between the LND and LND-omitted groups (152.8 vs. 147.3 months; p = 0.61). In IPTW-adjusted Cox proportional hazards regression analysis, LND was not associated with an OS benefit (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.94-1.42; p = 0.18). The results were consistent across subgroups stratified by clinical T and N stages. Among patients with lymph node metastasis, the number of removed nodes (NRN) above the median was not associated with an improved OS (HR 0.82, 95% CI 0.60-1.13; p = 0.22).ConclusionsLND had no additional therapeutic benefit among patients undergoing resection for pNETs. The present findings should be considered when managing patients with resectable pNETs.
| S-EPMC7436555 | biostudies-literature
Project description:BackgroundEsophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery.ObjectiveIn this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities.MethodsWe evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE.ResultsThe EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis (eotaxin 3, CCL26), barrier molecules (desmoglein 1, DSG1), tissue remodeling (periostin, POSTN), and mast cells (carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment.ConclusionThese findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.
| S-EPMC4289084 | biostudies-literature
Project description:BackgroundMethamphetamines are a common cause of systolic heart failure (HF). There are limited data on the prognosis associated with hospitalizations for decompensated HF in the setting of methamphetamine use. We aimed to evaluate patient characteristics and outcomes among patients admitted with decompensated HF who had positive drug screens for amphetamines as well as to determine whether any parameters from transthoracic echocardiogram (TTE) can predict outcomes in this population.MethodsThis was a retrospective cohort study of consecutive adult patients admitted to the Loma Linda Medical Center who had an active hospital problem of acute on chronic systolic (or systolic and diastolic) HF from 2013 to 2018. Electronic medical records were mined for relevant patient data. Methamphetamine-associated heart failure (MethHF) group was defined as those with an admission urine drug screen (UDS) that was positive for methamphetamines, whereas non-MethHF was defined by patients with negative methamphetamine on UDS or UDS was not done on physician's discretion. The primary outcomes of the study were 30-day composite outcome (defined as combined all-cause readmission and all-cause mortality), 365-day all-cause mortality, and length of stay (LOS). Propensity score weighting for these outcomes was performed using demographics, laboratory and clinical variables, and left ventricular ejection fraction (LVEF) as covariates. TTE parameters from presentation were also evaluated to determine if any had prognostic implications.ResultsA total of 1,655 patients were included (101 patients with positive urine methamphetamine and 1,554 patients without). Patients with MethHF were younger, more likely to be male, had fewer comorbidities, had lower LVEF, and were more likely to have right ventricular systolic dysfunction. In propensity-weighted analyses, there were no significant differences in LOS, 30-day composite outcome, or 365-day mortality between the MethHF and non-MethHF group in (P > 0.05 for all). Presence of at least moderate tricuspid valve regurgitation (TR) was the only TTE predictor of 30-day composite outcome (odds ratio (OR) = 4.67, 95% confidence interval (CI): 1.5 - 14.50, P < 0.01) and 365-day mortality (OR = 4.67, 95% CI: 1.5 - 14.50, P < 0.01) in the MethHF group.ConclusionPatients with MethHF admitted for decompensated HF had similar outcomes compared to non-MethHF after adjusting for baseline characteristics. TR is the only TTE value to predict outcomes in this population.
| S-EPMC8993440 | biostudies-literature
Project description:ObjectiveTo provide contemporary estimates of internists' perceptions of adverse effects associated with proton pump inhibitors (PPIs) and self-reported clinical use.MethodsWe invited 799 internists, including specialists and postgraduate trainees, to complete an online survey. Topics included perceptions of PPI adverse effects (AEs) and effectiveness for upper gastrointestinal bleeding (UGIB) prevention, changes in prescribing, and management recommendations for patients using PPIs for gastroesophageal reflux disease or UGIB prevention. We used logistic regression to identify factors associated with appropriate PPI continuation in the scenario of a patient at high risk for UGIB.ResultsAmong 437 respondents (55% response rate), 10% were trainees and 72% specialized in general medicine, 70% were somewhat/very concerned about PPI AEs, and 76% had somewhat/very much changed their prescribing. A majority believed PPIs increase the risk for 6 of 12 AEs queried. Fifty-two percent perceived PPIs to be somewhat/very effective for UGIB prevention. In a gastroesophageal reflux disease scenario in which PPI can be safely discontinued, 86% appropriately recommended PPI discontinuation. However, in a high-risk UGIB prevention scenario in which long-term PPI use is recommended, 79% inappropriately recommended discontinuation. In this latter scenario, perceived effectiveness for bleeding prevention was strongly associated with continuing PPI (odds ratio 7.68, P < 0.001 for moderately; odds ratio 17.3, P < 0.001 for very effective). Other covariates, including concern about PPI AEs, had no significant association.DiscussionMost internists believe PPIs cause multiple AEs and recommend discontinuation even in patients at high risk for UGIB. Future interventions should focus on ensuring that PPIs are prescribed appropriately according to individual risks and benefits.
| S-EPMC7196016 | biostudies-literature
Project description:BackgroundPrevious studies have reported that the suppression of acid secretion by using proton pump inhibitors (PPIs) results in dysbiosis of the small-bowel microbiota, leading to exacerbated small-bowel injuries, including erosions and ulcers. This study was designed to assess the association between PPI therapy and small-bowel lesions after adjustment for the differences in baseline characteristics between users and non-users of PPIs.MethodsWe retrospectively studied patients suspected to be suffering from small-bowel diseases, who underwent capsule endoscopy between 2010 and 2013. We used propensity matching to adjust for the differences in baseline characteristics between users and non-users of PPIs. The outcomes included the prevalence of small-bowel lesions: erosion, ulcer, angioectasia, varices, and tumor.ResultsWe selected 327 patient pairs for analysis after propensity matching, and found no significant differences in the prevalence of small-bowel injuries, including erosions and ulcers, between users and non-users of PPIs. Two subgroup analyses of the effect of the type of PPI and the effect of PPI therapy in users and non-users of nonsteroidal anti-inflammatory drugs indicated no significant differences in the prevalence of small-bowel injuries in these two groups.ConclusionPPI therapy did not increase the prevalence of small-bowel injury, regardless of the type of PPI used and the use of nonsteroidal anti-inflammatory drugs.
| S-EPMC5542471 | biostudies-literature
Project description:BackgroundProton pump inhibitors (PPIs) are recommended by the latest guidelines to reduce the risk of bleeding in acute myocardial infarction (AMI) patients treated with dual antiplatelet therapy (DAPT). However, previous pharmacodynamic and clinical studies have reported controversial results on the interaction between PPI and the P2Y12 inhibitor clopidogrel. We investigated the impact of PPIs use on in-hospital outcomes in AMI patients, aiming to provide a new insight on the value of PPIs.MethodsA total of 23, 380 consecutive AMI patients who received clopidogrel with or without PPIs in the China Acute Myocardial Infarction (CAMI) registry were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of in-hospital cardiac death, re-infarction and stroke. Propensity score matching (PSM) was used to control potential baseline confounders. Multivariate logistic regression analysis was performed to evaluate the effect of PPIs use on MACCE and gastrointestinal bleeding (GIB).ResultsAmong the whole AMI population, a large majority received DAPT and 67.5% were co-medicated with PPIs. PPIs use was associated with a decreased risk of MACCE (Before PSM OR: 0.857, 95% CI: 0.742-0.990, P = 0.0359; after PSM OR: 0.862, 95% CI: 0.768-0.949, P = 0.0245) after multivariate adjustment. Patients receiving PPIs also had a lower risk of cardiac death but a higher risk of complicating with stroke. When GIB occurred, an alleviating trend of GIB severity was observed in PPIs group.ConclusionsOur study is the first nation-wide large-scale study to show evidence on PPIs use in AMI patients treated with DAPT. We found that PPIs in combination with clopidogrel was associated with decreased risk for MACCE in AMI patients, and it might have a trend to mitigate GIB severity. Therefore, PPIs could become an available choice for AMI patients during hospitalization.
| S-EPMC7729183 | biostudies-literature
Project description:Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. Using data from Danish nationwide registries and Cox models regressing of both propensity scores and drug use, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer-specific and noncancer death among PPI users (≥2 prescriptions within six months after diagnosis; n = 36,066) compared with nonusers (<2 prescriptions, n = 311,853) or users of histamine H2 -receptor antagonists (H2 RA; n = 5,152). Adjusted HRs for cancer-specific mortality among postdiagnostic PPI users as compared with nonusers or H2 RA users were 1.29 (95% CI, 1.27-1.32) and 1.15 (95% CI, 1.10-1.20), respectively. HRs for cancer mortality associated with PPI use were highest for ovarian (1.35; 95% CI, 1.20-1.52) and lowest for esophageal cancer (0.91; 95% CI, 0.81-1.04). The associations were stronger among new PPI users after cancer diagnosis, indicating potential confounding. To test the effect of PPIs on tumor growth in a model system free for confounding factors, we investigated the effect of pantoprazole on tumor growth in mice. Pantoprazole (5 mg/kg/day) enhanced tumor growth (p = 0.033) and reduced the antitumor activity of gemcitabine (p = 0.008) in fibrosarcoma-bearing Balb/c mice, but not in immunodeficient Balb/c nude mice. In breast carcinoma-bearing FVB/N mice, pantoprazole had no effect on tumor growth alone but it reduced the life-prolonging effect of doxorubicin significantly (p = 0.007). Taken together, these data raise concerns about the increasing use of PPIs and calls for further studies addressing their safety among cancer patients.
| S-EPMC7611279 | biostudies-literature