The role of leukotriene modifying agent treatment in neuropsychiatric events of elderly asthma patients: a nested case control study.

BACKGROUND: In March 2020, the US Food and Drug Administration decided that the dangers related to neuropsychiatric events (NPEs) of montelukast, one of the leukotriene modifying agents (LTMAs), should be communicated through 'boxed warning'. In case of NPEs, the prevalence has been the highest in elderly people. Because the characteristics of the elderly such as old age itself can act as risk factors. Therefore, an investigation on safety of LTMAs related to NPEs in elderly using LTMAs is needed. METHOD: A nested case-control study using an elderly sample cohort from the Korean National Health Insurance Service database was used. The asthma cohort included asthma patients newly diagnosed between 2003 and 2013. Within the asthma cohort, the case group was defined as patients who were diagnosed with NPEs. Among patients who had never been diagnosed with NPEs, the control group was selected by matching 1:1 by propensity score. Patients who were prescribed LTMAs for 1 year prior to index date were defined as the exposure group. The logistic regression model was used to measure the effect of LTMAs on NPEs. RESULTS: We identified 141,165 patients with newly diagnosed asthma, and selected 31,992 patients per each case and control group. Exposure to LTMAs significantly increased the risk of overall NPEs about in comparison with the absence of exposure (crude odds ratio [OR] 1.58, 95% CI 1.50-1.68). After adjusting for confounding factors, the overall NPEs risk increased (adjusted OR, 1.67, 95% CI 1.58-1.78). CONCLUSION: This study suggests that elderly asthma patients prescribed LTMAs had a higher risk of NPEs than patients who were not treated with LTMAs. Therefore, clinicians should be aware of the potential risks of LTMAs.

Association Between Gout and Dementia in the Elderly: A Nationwide Population-Based Cohort Study.

OBJECTIVE: The data showing the association between gout and dementia are inconsistent. The objective of this study was to examine whether gout is associated with the risk of dementia in the elderly. METHODS: This retrospective cohort study used population-based representative claims data from the National Health Insurance Service in Korea. We used the Elderly Cohort database which represents 10% of the elderly Koreans over the age of 60, from 2002 to 2013. We assessed the association of gout with a new diagnosis of dementia with Cox proportional hazard models and adjusted the data for potential covariates such as demographics (age, sex) and comorbidities. RESULTS: We included 22,178 patients with gout and 113,590 without. In each group, 2,557 (11.53%) and 18,264 (16.08%) patients, respectively, had dementia. In multivariable analyses, gout was independently associated with a significantly lower hazard ratio of incident dementia, with an adjusted hazard ratio of 0.63 (95% CI, 0.60-0.66). A sub-group analysis conducted to find out the effects of gout medication showed that febuxostat use significantly decreased incident dementia. CONCLUSION: Gout was independently associated with a 37% lower risk of dementia in the elderly.

Factors Associated With Voriconazole Concentration in Pediatric Patients.

BACKGROUND: Serum concentrations of voriconazole are difficult to predict, especially in pediatric patients, because of its complex pharmacokinetic characteristics. This study aimed to identify the factors associated with the concentration of voriconazole in pediatric patients. METHODS: This cohort study was based on retrospective data collection and involved the administration of voriconazole to pediatric patients younger than 18 years, between January 2010 and August 2017. Electronic medical records of the patients were reviewed to collect demographic characteristics, voriconazole treatment regimen, and factors that could potentially influence voriconazole trough concentrations. A voriconazole trough serum concentration of less than 1.0 mcg/mL or greater than 5.5 mcg/mL was defined as outside the therapeutic range and was set as the outcome of this study. RESULTS: Among the 114 patients enrolled, 61 patients were included in the analysis. Oral administration of a maintenance dose of voriconazole and C-reactive protein (CRP) level were significantly and independently associated with a low initial trough concentration of voriconazole (<1.0 mcg/mL). Alanine aminotransferase levels were a significant factor associated with a high initial trough concentration of voriconazole (>5.5 mcg/mL) after adjusting for sex, age, weight, and serum creatinine (odds ratio 5.42; 95% confidence interval 1.34-21.97). CONCLUSIONS: Considering the variability of voriconazole concentrations in pediatric patients, monitoring certain parameters and considering the route of administration could help determine the therapeutic range of voriconazole and subsequently avoid unwanted effects.

ADAM17 Genetic Variants and the Response of TNF-α Inhibitor in Rheumatoid Arthritis Patients.

PURPOSE: TNF-α is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNF­α results in an increased inflammatory activity. We hypothesized that variants spanning the ADAM17 gene contribute towards the observed variation in patient response defined by the number of changes in TNF­α inhibitors. PATIENTS AND METHODS: Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-α inhibitors were analyzed: rs57467365, rs62117540, rs117645314, rs6432013, rs532704607, rs117179141, and rs12692386. Univariate and multivariate regression analysis were employed to investigate the independent predictable factors for changes in TNF-α inhibitors. RESULTS: ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-α inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-α inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-α inhibitor response. CONCLUSION: This study showed that the number of changes in TNF-α inhibitor is associated with ADAM17 SNPs.