Browsing by Subject "Mixed-effects models"

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    Increasing illness severity is associated with global myocardial dysfunction in the first 24 hours of sepsis admission
    (Springer, 2022-07-28) Ehrman, Robert R.; Bredell, Bryce X.; Harrison, Nicholas E.; Favot, Mark J.; Haber, Brian D.; Welch, Robert D.; Levy, Philip D.; Sherwin, Robert L.; Emergency Medicine, School of Medicine
    Background: Septic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission. Methods: This was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models. Results: We enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e' over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors. Conclusions: In the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.
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    Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer's disease
    (Nature Publishing Group, 2018-05-10) Sohn, Dongwha; Shpanskaya, Katie; Lucas, Joseph E.; Petrella, Jeffrey R.; Saykin, Andrew J.; Tanzi, Rudolph E.; Samatova, Nagiza F.; Doraiswamy, P. Murali; Radiology and Imaging Sciences, School of Medicine
    Sex differences in Alzheimer's disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer's and followed up to 10 years in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having "high" or "low" likelihood for MCI due to Alzheimer's. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer's Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer's was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer's disease progression.