Dataset Information

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients.

ABSTRACT: Although histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute stroke in a population controlled for confounding.We analyzed acute stroke patients admitted to a tertiary care hospital. To minimize confounding, we only included subjects who could not feed orally during 14 days of hospitalization. Exposure was defined as H2B or PPI, given in days; the outcome was development of pneumonia within this period. The incidence was calculated from the total number of pneumonias divided by the sum of person-days at risk. We additionally performed multivariate Poisson regression and propensity score analyses, although the restriction largely eliminated the need for multivariate adjustment.A total of 132 pneumonias occurred in 3582 person-days. The incidence was 3.69%/person-day (95% confidence interval (CI); 3.03-4.37%/day). All subjects had dysphagia. Stroke severity and consciousness disturbances were well-balanced between the groups exposed to H2B, PPI, or none. The relative risk (RR) compared with the unexposed was 1.22 in H2B (95%CI; 0.83-1.81) and 2.07 in PPI (95% CI; 1.13-3.62). The RR of PPI compared with H2B was 1.69 (95%CI; 0.95-2.89). In multivariate regression analysis, the RRs of H2B and PPI were 1.24 (95% CI; 0.85-1.81) and 2.00 (95% CI; 1.12-3.57), respectively; in propensity score analyses they were 1.17 (95% CI; 0.89-1.54) and 2.13 (95% CI; 1.60-2.84).The results of this study suggested that prophylactic acid-suppressive therapy with PPI may have to be avoided in acute stroke patients susceptible to pneumonia.

SUBMITTER: Arai N

PROVIDER: S-EPMC5234823 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients.

Arai Nobuhiko N Nakamizo Tomoki T Ihara Hikaru H Koide Takashi T Nakamura Akiyoshi A Tabuse Masanao M Miyazaki Hiromichi H

PloS one 20170113 1

<h4>Background</h4>Although histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute s ...[more]

PMID: 28085910

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Project description:Esophageal 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.In 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.We 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.The 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.These 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.

Project description:BackgroundUse of proton pump inhibitors (PPIs) is associated with community-acquired pneumonia (CAP), an association which may be confounded by unobserved patient and prescriber characteristics.ObjectiveWe assessed for confounding in the association between PPI use and CAP by using a 'falsification approach,' which estimated whether PPI use is also implausibly associated with other common medical conditions for which no known pathophysiologic link exists.DesignRetrospective claims-based cohort study.SettingSix private U.S. health plans.SubjectsIndividuals who filled at least one prescription for a PPI (N?=?26,436) and those who never did (N?=?28,054) over 11 years.InterventionsMultivariate linear regression of the association between a filled prescription for a PPI and a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested for implausible associations between PPI use in each quarter and rates of osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis (DVT), skin infection, and rheumatoid arthritis. Independent variables included an indicator for whether a prescription for a PPI was filled in a given quarter, and quarterly indicators for various co-morbidities, age, income, geographic location, and marital status.Key resultsCompared to nonusers, those ever using a PPI had higher adjusted rates of CAP in quarters in which no prescription was filled (68 vs. 61 cases per 10,000 persons, p?<?0.001). Similar associations were noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p?<?0.001; UTI, 151 vs. 139 cases, p?<?0.001). Among those ever using a PPI, quarters in which a prescription was filled were associated with higher adjusted rates of CAP (111 vs. 68 cases per 10,000, p?<?0.001) and all other conditions (e.g. chest pain, 597 vs. 336 cases, p?<?0.001; UTI, 186 vs. 151 cases, p?<?0.001), compared to quarters in which no prescription was filled.ConclusionPPI use is associated with CAP, but also implausibly associated with common medical conditions. Observed associations between PPI use and CAP may be confounded.

Project description:Histamine-2 receptor antagonists are commonly administered for stress ulcer prophylaxis in critically ill adults and may be associated with delirium development. We aimed to determine differential associations of histamine-2 receptor antagonist or proton-pump inhibitor administration with delirium development in patients admitted to a medical ICU.DesignRetrospective observational study using a deidentified database sourced from the University of North Carolina Health Care system. Participants were identified as having delirium utilizing an International Classification of Diseases-based algorithm. Associations among histamine-2 receptor antagonist, proton-pump inhibitor, or no medication administration and delirium were identified using relative risk. Multiple logistic regression was used to control for potential confounders including mechanical ventilation and age.SettingAcademic tertiary care medical ICU in the United States.PatientsAdults admitted to the University of North Carolina medical ICU from January 2015 to December 2019, excluding those on concurrent histamine-2 receptor antagonists and proton-pump inhibitors in the same encounter.InterventionsNone.Measurements and main resultsWe identified 6,645 critically ill patients, of whom 29% (n = 1,899) received mechanical ventilation, 45% (n = 3,022) were 65 or older, and 22% (n = 1,487) died during their medical ICU encounter. Of the 6,645 patients, 31% (n = 2,057) received an histamine-2 receptor antagonist and no proton-pump inhibitors, 40% (n = 2,648) received a proton-pump inhibitor and no histamine-2 receptor antagonists, and 46% (n = 3,076) had delirium. The histamine-2 receptor antagonist group had a greater association with delirium than the proton-pump inhibitor group compared with controls receiving neither medication, after controlling for mechanical ventilation and age (risk ratio, 1.36; 1.25-1.47; p < 0.001) and (risk ratio, 1.15; 1.07-1.24; p < 0.001, respectively).ConclusionsHistamine-2 receptor antagonists are more strongly associated with increased delirium than proton-pump inhibitors. Prospective studies are necessary to further elucidate this association and to determine if replacement of histamine-2 receptor antagonists with proton-pump inhibitors in ICUs decreases the burden of delirium in critically ill patients.

Dataset Information

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients.

Publications

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients.

Similar Datasets

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