25 research outputs found

    Spironolactone and colitis: Increased mortality in rodents and in humans

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    Background: Crohn's disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an antifibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is antifibrotic in the context of intestinal inflammation. Methods: In vitro, spironolactone repressed fibrogenesis in transforming growth factor beta (TGF‐β)‐stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation‐induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since inflammatory bowel disease (IBD) patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Results: Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n = 390 deaths, P < 0.0001). In patients without liver disease, the adjusted odds ratio (OR) for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% confidence interval [CI]: 1.51–2.63) In contrast to the main effect of spironolactone mortality, multivariate modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted OR for mortality after CDI was 1.96 (95% CI: 1.50–2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82–2.00) for patients with liver disease on spironolactone when compared to a reference group without liver disease or spironolactone use. Conclusions: We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2‐fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the U.S. (Inflamm Bowel Dis 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92045/1/21929_ftp.pd

    Increasing ultraviolet light exposure is associated with reduced mortality from Clostridium difficile

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    BACKGROUND: Clostridium difficile infection (CDI) is an increasingly common cause of inpatient mortality. Vitamin D deficiency is associated with more aggressive CDI. We aimed to determine if average annual ultraviolet light (UV) exposure was associated with mortality in patients with CDI. METHODS: We used the US National Inpatient Sample (NIS) from 2004–2011 to assess the mortality risk in patients with a diagnosis of CDI (as per ICD-9CM 008.45). Annual average state UV exposure was assigned to each hospitalization. Logistic regression was used to determine the effects of UV exposure on mortality, controlling for age, gender, race and other comorbidities. RESULTS: During the study period, there were 2.61 million hospitalizations with a diagnosis of CDI. The mortality rate was 9.0%. In univariate analysis, the odds ratio (OR) of inpatient mortality for the UV index was 0.97 (95% CI 0.95–0.99; p = 0.008) per unit of UV exposure. In a multivariable model adjusting for age, gender, race, Charlson-Deyo index, season and coexisting inflammatory bowel disease, the UV index remained a protective predictor, with an OR of 0.94 (95% CI 0.92–0.96; p < 0.001). In the multivariate model, a seasonal effect was also present, with the highest risk of inpatient mortality in the period from January to March (OR 1.11; 95% CI 1.08–1.14) and the lowest risk, from July to September (OR 0.95; 95% CI 0.92–0.98). CONCLUSIONS: An increase in UV exposure index is associated with a reduced risk of inpatient mortality in patients with CDI. A seasonal effect is also present, with the highest risk of death during winter months. Further studies exploring the role of UV light in CDI are necessary
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