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The Use of Proton Pump Inhibitors and COVID-19: A Systematic Review and Meta-Analysis.

ABSTRACT: COVID-19 has proved to be a serious, and consequential disease that has affected millions of people globally. Previously, the adverse effects of proton pump inhibitors (PPI) have been observed with increasing the risk of pneumonia and COVID-19. This meta-analysis aims to address the relationship between the use of PPI and the severity of COVID-19 infection. We conducted a systemic literature search from PUBMED, Science Direct, and Cinahl from December 2019 to January 2022. Published and unpublished randomized control trials and cohort studies were included. Review Manager was used for all statistical analyses. In total, 14 studies were included in this systemic review and meta-analysis. Outcomes of interest include: (1) susceptibility of COVID-19 infection and (2) severity of COVID-19 (defined as the composite of poor outcomes: ICU admission, need for oxygen therapy, need for a ventilator, or death), and (3) mortality due to COVID-19. PPI use was marginally associated with a nominal but statistically significant increase in the risk of COVID-19 infection (OR 1.05 [1.01, 1.09]; I2 97%, p = 0.007). PPI use also increased the risk of the composite poor outcome (OR 1.84 [1.71, 1.99]; I2 98%, p < 0.00001) and mortality (OR 1.12 [1.00, 1.25]; I2 84%, p = 0.05) in patients with COVID-19.

SUBMITTER: Fatima K

PROVIDER: S-EPMC8950138 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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The Use of Proton Pump Inhibitors and COVID-19: A Systematic Review and Meta-Analysis.

Fatima Kaneez K Almas Talal T Lakhani Shan S Jahangir Arshia A Ahmed Abdullah A Siddiqui Ayra A Rahim Aiman A Qureshi Saleha Ahmed SA Arshad Zukhruf Z Golani Shilpa S Musheer Adeena A

Tropical medicine and infectious disease 20220228 3

COVID-19 has proved to be a serious, and consequential disease that has affected millions of people globally. Previously, the adverse effects of proton pump inhibitors (PPI) have been observed with increasing the risk of pneumonia and COVID-19. This meta-analysis aims to address the relationship between the use of PPI and the severity of COVID-19 infection. We conducted a systemic literature search from PUBMED, Science Direct, and Cinahl from December 2019 to January 2022. Published and unpublis ...[more]

PMID: 35324584

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Project description:Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model. Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71). Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).

Project description:(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.

Dataset Information

The Use of Proton Pump Inhibitors and COVID-19: A Systematic Review and Meta-Analysis.

Publications

The Use of Proton Pump Inhibitors and COVID-19: A Systematic Review and Meta-Analysis.

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