scholarly journals Biomarker combinations for diagnosis and prognosis in multicenter studies: Principles and methods

2017 ◽  
Vol 28 (4) ◽  
pp. 969-985 ◽  
Author(s):  
Allison Meisner ◽  
Chirag R Parikh ◽  
Kathleen F Kerr

Many investigators are interested in combining biomarkers to predict a binary outcome or detect underlying disease. This endeavor is complicated by the fact that many biomarker studies involve data from multiple centers. Depending upon the relationship between center, the biomarkers, and the target of prediction, care must be taken when constructing and evaluating combinations of biomarkers. We introduce a taxonomy to describe the role of center and consider how a biomarker combination should be constructed and evaluated. We show that ignoring center, which is frequently done by clinical researchers, is often not appropriate. The limited statistical literature proposes using random intercept logistic regression models, an approach that we demonstrate is generally inadequate and may be misleading. We instead propose using fixed intercept logistic regression, which appropriately accounts for center without relying on untenable assumptions. After constructing the biomarker combination, we recommend using performance measures that account for the multicenter nature of the data, namely the center-adjusted area under the receiver operating characteristic curve. We apply these methods to data from a multicenter study of acute kidney injury after cardiac surgery. Appropriately accounting for center, both in construction and evaluation, may increase the likelihood of identifying clinically useful biomarker combinations.

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A305-A306
Author(s):  
Jesse Moore ◽  
Ellita Williams ◽  
Collin Popp ◽  
Anthony Briggs ◽  
Judite Blanc ◽  
...  

Abstract Introduction Literature shows that exercise moderates the relationship between sleep and emotional distress (ED.) However, it is unclear whether different types of exercise, such as aerobic and strengthening, affect this relationship differently. We investigated the moderating role of two types of exercise (aerobic and strengthening) regarding the relationship between ED and sleep. Methods Our analysis was based on data from 2018 National Health Interview Survey (NHIS), a nationally representative study in which 2,814 participants provided all data. Participants were asked 1) “how many days they woke up feeling rested over the past week”, 2) the Kessler 6 scale to determine ED (a score >13 indicates ED), and 3) the average frequency of strengthening or aerobic exercise per week. Logistic regression analyses were performed to determine if the reported days of waking up rested predicted level of ED. We then investigated whether strengthening or aerobic exercise differentially moderated this relationship. Covariates such as age and sex were adjusted in the logistic regression models. Logistic regression analyses were performed to determine if subjective reporting of restful sleep predicted level of ED. We investigated whether strengthening exercise or aerobic exercise differentially moderated this relationship. Covariates such as age and sex were adjusted in the logistic regression models. Results On average, participants reported 4.41 restful nights of sleep (SD =2.41), 3.43 strengthening activities (SD = 3.19,) and 8.47 aerobic activities a week (SD=5.91.) We found a significant association between days over the past week reporting waking up feeling rested and ED outcome according to K6, Χ2(1) = -741, p= <.001. The odds ratio signified a decrease of 52% in ED scores for each unit of restful sleep (OR = .48, (95% CI = .33, .65) p=<.001.) In the logistic regression model with moderation, aerobic exercise had a significant moderation effect, Χ2(1) = .03, p=.04, but strengthening exercise did not. Conclusion We found that restful sleep predicted reduction in ED scores. Aerobic exercise moderated this relationship, while strengthening exercise did not. Further research should investigate the longitudinal effects of exercise type on the relationship between restful sleep and ED. Support (if any) NIH (K07AG052685, R01MD007716, K01HL135452, R01HL152453)


2021 ◽  
pp. 1-10
Author(s):  
Guang Fu ◽  
Hai-chao Zhan ◽  
Hao-li Li ◽  
Jun-fu Lu ◽  
Yan-hong Chen ◽  
...  

Objective: The objective of this study was to assess the relationship between serum procalcitonin (PCT) and acute kidney injury (AKI) induced by bacterial septic shock. Methods: A retrospective study was designed which included patients who were admitted to the ICU from January 2015 to October 2018. Multiple logistic regression and receiver operating characteristic (ROC) as well as smooth curve fitting analysis were used to assess the relationship between the PCT level and AKI. Results: Of the 1,631 patients screened, 157 patients were included in the primary analysis in which 84 (53.5%) patients were with AKI. Multiple logistic regression results showed that PCT (odds ratio [OR] = 1.017, 95% confidence interval [CI] 1.009–1.025, p < 0.001) was associated with AKI induced by septic shock. The ROC analysis showed that the cutoff point for PCT to predict AKI development was 14 ng/mL, with a sensitivity of 63% and specificity 67%. Specifically, in multivariate piecewise linear regression, the occurrence of AKI decreased with the elevation of PCT when PCT was between 25 ng/mL and 120 ng/mL (OR 0.963, 95% CI 0.929–0.999; p = 0.042). The AKI increased with the elevation of PCT when PCT was either <25 ng/mL (OR 1.077, 95% CI 1.022–1.136; p = 0.006) or >120 ng/mL (OR 1.042, 95% CI 1.009–1.076; p = 0.013). Moreover, the PCT level was significantly higher in the AKI group only in female patients aged ≤75 years (p = 0.001). Conclusions: Our data revealed a nonlinear relationship between PCT and AKI in septic shock patients, and PCT could be used as a potential biomarker of AKI in female patients younger than 75 years with bacterial septic shock.


Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1790
Author(s):  
Lei Zhang ◽  
Ruohan Jia ◽  
Huizhen Li ◽  
Huarun Yu ◽  
Keke Ren ◽  
...  

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.


Author(s):  
Johanna B. Folk ◽  
Jeffrey B. Stuewig ◽  
Brandy L. Blasko ◽  
Michael Caudy ◽  
Andres G. Martinez ◽  
...  

Is the relationship between criminal thinking and recidivism the same for criminal justice–involved individuals from varying demographic backgrounds? Relying on two independent samples of offenders and two measures of criminal thinking, the current studies examined whether four demographic factors—gender, race, age, and education—moderated the relationship between criminal thinking and recidivism. Study 1 consisted of 226 drug-involved probationers enrolled in a randomized clinical trial. Study 2 consisted of 346 jail inmates from a longitudinal study. Logistic regression models suggested that the strength of the relationship between criminal thinking and subsequent recidivism did not vary based on participant demographics, regardless of justice system setting or measure of criminal thinking. Criminal thinking predicts recidivism similarly for people who are male, female, Black, White, older, younger, and more or less educated.


2015 ◽  
Vol 28 (2) ◽  
pp. 505-515 ◽  
Author(s):  
Teresa C. Silva ◽  
Håkan Stattin

AbstractWe aimed to analyze the impact of several parenting factors on the relationship between psychopathy and antisocial behavior. Nine hundred youths and their mothers reported on parent–youth interactions, and youth self-report measures of psychopathy, delinquency and violent behavior were taken. Multiple regression was used to test for the significance of interactions between parenting and psychopathy scores. In terms of delinquency, linear interactions between psychopathy and the level of conflict with parents and parents' knowledge of their youths' whereabouts/youths' willingness to disclose information were found based on the data reported by the youths. Data reported by mothers indicated a linear interaction between psychopathy and parents' knowledge/youth disclosure, and a quadratic interaction of conflict with parents. For violence, we used logistic regression models to analyze moderation. No interaction effects between psychopahy scores and parenting factors were found. Youths' reports of high conflict with parents and parents' knowledge/youth disclosure showed to have an impact on violence regardless of the level of psychopathic traits. Implications for the prevention and treatment are discussed.


2019 ◽  
pp. 119-125
Author(s):  
E. G. Nazarenko

The article emphasizes the role of magnesium in a woman’s body, the causes and symptoms of its deficiency. It also describes the role of estrogens, combined oral contraceptives and hormone replacement therapy in the development of magnesium-deficient states, and the relationship between these states and vitamin B6. The paper overviews multicenter studies on the treatment of magnesiumdeficient conditions from the standpoint of evidence-based medicine, which show the need to maintain an adequate level of magnesium  and pyridoxine in the treatment of estrogen-dependent diseases.


Author(s):  
Jia Guo ◽  
Wen-Hsuan W Lin ◽  
Jason E Zucker ◽  
Renu Nandakumar ◽  
Anne-Catrin Uhlemann ◽  
...  

Abstract Background The aim of this study was to determine the relationship of inflammation with mortality in COVID-19 hospitalized patients and to assess if the relationship differed by strata of type 2 diabetes status. We hypothesized that the association of inflammation with mortality was different by type 2 diabetes status. Methods A case-control (died-survived) study of 538 COVID-19 hospitalized patients, stratified by diabetes status, was conducted at Columbia University Irving Medical Center. We quantified the levels of eight cytokines and chemokines in serum, including interferon(IFN)-α2, IFN-γ, Interleukin(IL)-1α, IL-1β, IL-6, IL-8/CXCL8, IFNγ-induced protein 10 (IP10)/CXCL10 and tumor necrosis factor α (TNF-α) using immunoassays. Logistic regression models were used to model the relationships of log-transformed inflammatory markers (or their principal components) and mortality. Results In multiple logistic regression models, higher serum levels of IL-6 (adjusted odds ratio (aOR):1.74, 95% confidence intervals (CI): (1.48, 2.06)), IL-8 (aOR: 1.75 (1.41, 2.19)) and IP10 (aOR: 1.36 (1.24, 1.51)), were significantly associated with mortality. This association was also seen in second principal component (PC) with loadings reflecting similarities among these three markers (aOR: 1.88 (1.54-2.31)). Significant positive association of these same inflammatory markers with mortality was also observed within each strata of diabetes. Conclusions We show that mortality in COVID19 patients is associated with elevated serum levels of innate inflammatory cytokine IL-6 and inflammatory chemokines IL-8 and IP10. This relationship is consistent across strata of diabetes, suggesting interventions targeting these innate immune pathways could potentially also benefit patients with diabetes.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Yingying Wang

Abstract Background Obesity and homocysteine (Hcy) are two important risk factors for cardiovascular disease (CVD); however, there were conflicting results for the relationship between them. Our study is to explore the associations of general and central obesity with hyperhomocysteinemia (HHcy) in middle-aged women. Methods The current analysis was based on data from 11007 women aged 40-60 years. Height, weight, and waist circumference (WC) were measured and serum homocysteine was determined. Multiple logistic regression models were used to assess the associations of the risk of hyperhomocysteinemia (HHcy, Hcy&gt;15μmol/L) with BMI and WC. Results 13.71% women had HHcy. The prevalences of BMI-based general obesity and WC-based central obesity were 11.17% and 22.88%, respectively. Compared with non-obese women, the mean serum Hcy concentration was significantly higher in WC-based central obese women (P = 0.002), but not in BMI-based general obese women (P &gt; 0.05). In the multiple logistic regression models, central obesity was positively related to the risk of HHcy (OR = 1.30, 95%CI=1.10 to 1.52), while general obesity was inversely related to the risk of HHcy (OR = 0.82, 95%CI=0.72 to 0.93 and OR = 0.71,95% CI = 0.57 to 0.89). Conclusions Central obesity was positively, while general obesity was negatively related to the risk of HHcy. Menopause showed no effect modification on these associations. Key messages Homocysteine; Central obesity; Menopause; Cardiovascular Disease


2020 ◽  
Vol 26 ◽  
pp. 107602962094858
Author(s):  
Yan Bai ◽  
Ying-Ying Zheng ◽  
Jun-Nan Tang ◽  
Xu-Ming Yang ◽  
Qian-Qian Guo ◽  
...  

The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD.


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