Browsing by Author "Akushevich, I"

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Open Access
Adjuvant radiotherapy in the treatment of invasive intraductal papillary mucinous neoplasm of the pancreas: an analysis of the surveillance, epidemiology, and end results registry.
(Ann Surg Oncol, 2012-04) Worni, M; Akushevich, I; Gloor, B; Scarborough, J; Chino, JP; Jacobs, DO; Hahn, SM; Clary, BM; Pietrobon, R; Shah, A
BACKGROUND: Management and outcomes of patients with invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas are not well established. We investigated whether adjuvant radiotherapy (RT) improved cancer-specific survival (CSS) and overall survival (OS) among patients undergoing surgical resection for invasive IPMN. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was used in this retrospective cohort study. All adult patients with resection of invasive IPMN from 1988 to 2007 were included. CSS and OS were analyzed using Kaplan-Meier curves. Unadjusted and propensity-score-adjusted Cox proportional-hazards modeling were used for subgroup analyses. RESULTS: 972 patients were included. Adjuvant RT was administered to 31.8% (n=309) of patients. There was no difference in overall median CSS or OS in patients who received adjuvant RT (5-year CSS: 26.5 months; 5-year OS: 23.5 months) versus those who did not (CSS: 28.5 months, P=0.17; OS: 23.5 months, P=0.23). Univariate predictors of survival were lymph node (LN) involvement, T4-classified tumors, and poorly differentiated tumor grade (all P<0.05). In the propensity-score-adjusted analysis, adjuvant RT was associated with improved 5-year CSS [hazard ratio (HR): 0.67, P=0.004] and 5-year OS (HR: 0.73, P=0.014) among all patients with LN involvement, though further analysis by T-classification demonstrated no survival differences among patients with T1/T2 disease; patients with T3/T4-classified tumors had improved CSS (HR: 0.71, P=0.022) but no difference in OS (HR: 0.76, P=0.06). CONCLUSION: On propensity-score-adjusted analysis, adjuvant RT was associated with improved survival in selected subsets of patients with invasive IPMN, particularly those with T3/T4 tumors and LN involvement.
Open Access
Age-Associated Disorders As A Proxy Measure Of Biological Age: Findings From the NLTCS Data
(2017-06-07) Kulminski, A; Yashin, A; Ukraintseva, S; Akushevich, I; Arbeev, K; Land, K; Manton, K
Background: The relative contribution of different aging-associated processes to the age phenotype may differ among individuals, creating variability in aging manifestations among age-peers. Capturing this variability can significantly advance understanding the aging and mortality. An index of age-associated health disorders (deficits), called a "frailty index" (FI), appears to be a promising characteristic of such processes. In this study we address the connections of the FI with age focusing on disabled individuals who might be at excessive risk of frailty. Methods: The National Long Term Care Survey (NLTCS) assessed health and functioning of the U.S. elderly in 1982, 1984, 1989, 1994, and 1999. Detailed information for our sample was assessed from about 26,700 interviews. The individual FI is defined as a proportion of deficits for a given person. We perform cross-sectional empirical analysis of the FI age-patterns. Results: FI in the NLTCS exhibits accelerated (quadratic) increase with age. Deficits might accumulate faster among the elderly who, at younger ages, had a low mean FI ("healthy" group) than a high FI ("disabled" group). Age-patterns for "healthy" and "disabled" groups converge at advanced ages. The rate of deficit accumulation is sex-sensitive. Convergence of the (sex-specific) FI for "healthy" and "disabled" groups in later ages determines biological age limits, associated with given levels of health-maintenance in the society, which correspond to 109.4 years for females and 92.5 years for males. Conclusions: The FI can be employed as a measure of biological age and population heterogeneity for modeling aging processes and mortality in elderly individuals.
Open Access
CARDIOVASCULAR COMORBIDITIES IN LUNG CANCER PATIENTS: TREATMENT-SPECIFIC EFFECTS ON SURVIVAL
(GERONTOLOGIST, 2014-11) Kravchenko, J; Berry, MF; Arbeev, KG; Akushevich, I
Open Access
Frailty Index as a Major Indicator of Aging Processes and Mortality in Elderly: Results From Analyses of the National Long Term Care Survey Data
(2017-06-07) Kulminski, A; Yashin, A; Akushevich, I; Ukraintseva, S; Land, K; Arbeev, K; Manton, K
To better understand mortality change with age capturing the variability in individuals' rates of aging, we performed comprehensive analysis of statistical properties of a cumulative index of age-associated disorders (deficits), called a "frailty index" (FI). This index is calculated as the proportion of the health deficits in an individual. It is found, first, that frequency, time-to-death, mortality-rate, and relative-risk-of-death exhibit remarkably similar FI- and age- patterns. Second, the FI, on the one hand, and mortality rate and relative risk, on the other hand, also exhibit similar age patterns with accelerated increase up to oldest-old ages and with subsequent deceleration and even decline. Third, distribution of the FI with time-to-death is sharper than that of age with time-to-death. These and related findings support the conclusion that the FI can describe aging processes and population heterogeneity. We also discuss the ability of the FI to capture physiological processes underlying aging both on individual and population levels.
Open Access
IMPACTS OF CEREBROVASCULAR AND NEURODEGENERATIVE DISEASES ON SURVIVAL OF LUNG CANCER PATIENTS
(GERONTOLOGIST, 2015-11) Kravchenko, J; Berry, MF; Arbeev, KG; Lyerly, H; Yashin, AI; Akushevich, I
Open Access
Joint analysis of health histories, physiological state, and survival
(Mathematical Population Studies, 2011-12-01) Yashin, AI; Akushevich, I; Arbeev, KG; Kulminski, A; Ukraintseva, S
Data on individual health histories, age trajectories of physiological or biological variables, and mortality allow for the study of the joint evolution of health and physiological states and their effects on mortality. Individual health and physiological trajectories are described using a stochastic process with two mutuallydependent continuous and jumping components. The parameters of this process and mortality rate are identified from the data in which the continuous component is measured in discrete times, and transitions of jumping process are observed. © Taylor & Francis Group, LLC.
Open Access
Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.
(Int J Chron Obstruct Pulmon Dis, 2014) Kravchenko, J; Akushevich, I; Abernathy, AP; Holman, S; Ross, WG; Lyerly, HK
BACKGROUND: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. MATERIALS AND METHODS: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. RESULTS: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. CONCLUSION: Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.
Open Access
MEDICARE-BASED MULTIMORBIDITY INDEX FOR PROJECTING MORBIDITY AND MORTALITY AMONG OLDER ADULTS IN THE U.S
(GERONTOLOGIST, 2012-11) Akushevich, I; Kravchenko, J; Whitson, H; Cohen, HJ; Ukraintseva, SV; Arbeev, KG; Yashin, AI
Open Access
Modeling longitudinal data on health aging and life span
(Physics of Life Reviews, 2012-06-01) Yashin, AI; Arbeev, KG; Akushevich, I; Kulminski, A; Ukraintseva, SV; Stallard, E; Land, KC
We address comments from the three discussants of our paper, paying particular attention to the properties of our model likely to be of interest in new applications to complex dynamic systems. © 2012 Elsevier B.V.
Open Access
Monte Carlo generator ELRADGEN 2.0 for simulation of radiative events in elastic ep-scattering of polarized particles
(Computer Physics Communications, 2012-07-01) Akushevich, I; Filoti, OF; Ilyichev, A; Shumeiko, N
The structure and algorithms of the Monte Carlo generator ELRADGEN 2.0 designed to simulate radiative events in polarized ep-scattering are presented. The full set of analytical expressions for the QED radiative corrections is presented and discussed in detail. Algorithmic improvements implemented to provide faster simulation of hard real photon events are described. Numerical tests show high quality of generation of photonic variables and radiatively corrected cross section. The comparison of the elastic radiative tail simulated within the kinematical conditions of the BLAST experiment at MIT BATES shows a good agreement with experimental data. © 2012 Elsevier B.V. All rights reserved.
Open Access
Patterns of Aging-Related changes on the way to 100: An Approach to studying aging, mortality, and longevity from longitudinal data
(North American Actuarial Journal, 2012-12-01) Yashin, AI; Arbeev, KG; Ukraintseva, SV; Akushevich, I; Kulminski, A
The objective of this paper is to investigate dynamic properties of age trajectories of physiological indices and their effects on mortality risk and longevity using longitudinal data on more than 5,000 individuals collected in biennial examinations of the Framingham Heart Study (FHS) original cohort during about 50 subsequent years of follow-up. We first performed empirical analyses of the FHS longitudinal data. We evaluated average age trajectories of indices describing physiological states for different groups of individuals and established their connections with mortality risk. These indices include body mass index, diastolic blood pressure, pulse pressure, pulse rate, level of blood glucose, hematocrit, and serum cholesterol. To be able to investigate dynamic mechanisms responsible for changes in the aging human organisms using available longitudinal data, we further developed a stochastic process model of human mortality and aging, by including in it the notions of "physiological norms," "allostatic adaptation and allostatic load," "stress resistance," and other characteristics associated with the internal process of aging and the effects of external disturbances. In this model, the persistent deviation of physiological indices from their normal values contributes to an increase in morbidity and mortality risks. We used the stochastic process model in the statistical analyses of longitudinal FHS data. We found that different indices have different average age patterns and different dynamic properties. We also found that age trajectories of long-lived individuals differ from those of the shorter-lived members of the FHS original cohort for both sexes. Using methods of statistical modeling, we evaluated "normal" age trajectories of physiological indices and the dynamic effects of allostatic adaptation. The model allows for evaluating average patterns of aging-related decline in stress resistance. This effect is captured by the narrowing of the U-shaped mortality risk (considered a function of physiological state) with age. We showed that individual indices and their rates of change with age, as well as other measures of individual variability, manifested during the life course are important contributors to mortality risks. The advantages and limitations of the approach are discussed.
Open Access
PATTERNS OF AGING-RELATED DISEASES INCIDENCE AND RECOVERY IN US ELDERLY
(GERONTOLOGIST, 2011-11) Akushevich, I; Kravchenko, J; Ukraintseva, SV; Arbeev, KG; Yashin, AI
Open Access
Predictive model of the treatment effect for patients with major depressive disorder
(2013 ACM Conference on Bioinformatics, Computational Biology and Biomedical Informatics, ACM-BCB 2013, 2013-11-28) Akushevich, I; Kravchenko, J; Gersing, K; Mane, KK
The model to evaluate and predict the effectiveness of treatment of the Major Depressive Disorder (MDD) was developed and estimated using MindLinc data. The clinical global impression (CGI) scale with seven categories was used to measure the patient's state. The proportional odds model was selected because of ordinal nature of the outcome. The set of predictors included i) CGI score measured at preceded visit, ii) three groups of medications (antidepressants, atypical medicine, and augmentation medicine), all categorized for appropriate number of strata (from six to nine) and their daily doses, iii) psychiatric comorbidities, iv) type of the therapy used (talk vs. medications), v) demographic variables (e.g., age group, sex), and vi) the history of the efficiency of prior treatment. More than a half of a million records with measured CGI scores and their predictors were identified in the MindLinc database and used for model estimation. The predicted model of future CGI scales was developed and evaluated for single and recurrent episodes of MDD. Significant estimates were obtained for demographic factors, history of previous SGI scales, and for comorbidity and treatment indices. The methods of causal inferences based on the inverse probability weighting approach were applied to evaluate the treatment effects. The model extensions allowing for addressing the limitations of the proportional odds model are discussed. Copyright © 2007 by the Association for Computing Machinery.
Open Access
QED radiative effects in the processes of exclusive photon electroproduction from polarized protons with the next-to-leading accuracy
(Physical Review D - Particles, Fields, Gravitation and Cosmology, 2014-08-01) Akushevich, I; Ilyichev, A; Shumeiko, NM
Radiative effects in the electroproduction of photons in polarized ep scattering are calculated with next-to-leading-order accuracy. The contributions of loops and two-photon emission are presented in analytical form. The covariant approach of Bardin and Shumeiko is used to extract the infrared divergence. All contributions to the radiative correction are presented in the form of the correction to the leptonic tensor thus allowing for further applications in other experiments, e.g., deep inelastic scattering. The radiative corrections to the cross sections and polarization asymmetries are analyzed numerically for the kinematical conditions of the current measurement at Jefferson Lab. Specific attention is paid to analyzing kinematical conditions for the process with a large radiative effect when the momenta of two photons in the final state are collinear with the momenta of the initial and final electrons, respectively. © 2014 American Physical Society.
Open Access
Radiative corrections beyond the ultra relativistic limit in unpolarized ep elastic and Møller scatterings for the PRad Experiment at Jefferson Laboratory
(European Physical Journal A, 2015-01-01) Akushevich, I; Gao, H; Ilyichev, A; Meziane, M
© 2015, SIF, Springer-Verlag Berlin Heidelberg.The clear 7σ discrepancy between measurements of the proton charge radius from muonic hydrogen Lamb shifts and those from hydrogen Lamb shift and electron scattering lead to both intense theoretical and experimental efforts to understand and explain this difference. In this regard, a new experiment (PRad) based on unpolarized ep elastic scattering cross section measurements normalized to Møller scattering is underway at Jefferson Laboratory to extract the proton charge radius based on new proton electric form factor down to values of momentum transfer squared Q2, as low as 10−4 GeV/c)2. To reach the precision of the experiment in such a small Q2 region requires reliable knowledge of radiative corrections. In this paper, we present a complete calculation of radiative corrections for unpolarized elastic ep and Møller scatterings performed within a covariant formalism resulting in the set of explicit formulas beyond the ultra relativistic approximation (me2 ≪ Q2), and numerical results for the kinematics of the PRad experiment.
Open Access
Radiative effects in the processes of exclusive photon electroproduction from polarized protons
(Physical Review D - Particles, Fields, Gravitation and Cosmology, 2012-03-28) Akushevich, I; Ilyichev, A
Radiative effects in the electroproduction of photons in polarized ep scattering are calculated in the leading log approximation and analyzed numerically for kinematical conditions of current measurement at Jefferson Lab. Radiative corrections to the cross sections, their azimuthal distributions, and Fourier coefficients are in particular focus. Kinematical regions where the radiative corrections are considerable are identified. © 2012 American Physical Society.
Open Access
Resistance to stresses and reliability of biological systems: Insights for genetic studies of human aging, health, and longevity
(Proceedings - 2nd International Symposium on Stochastic Models in Reliability Engineering, Life Science, and Operations Management, SMRLO 2016, 2016-03-11) Yashin, AI; Arbeev, KG; Arbeeva, LS; Wu, D; Akushevich, I; Kulminski, A; Kovtun, M; Zhbannikov, I; Ukraintseva, SV
© 2016 IEEE.Connection between stress resistance and longevity in biological organisms is widely discussed and confirmed experimentally. Much less is known about the roles of genetic and non-genetic factors in regulation of such connection. Earlier studies emphasized that mechanism that realizes such connection involves interplay between processes of individual aging and external challenges. As a result of such interplay the parameters of the Gompertz mortality curve are negatively correlated. Such correlation has been also observed in the process of survival improvement in developed part of the world during the first part of the last century. The mortality decline was mainly due to favorable changes in external and living conditions as well as progress in health care. Surprisingly, similar pattern of survival changes is observed in the groups of individuals ranked with respect to the number of «longevity» alleles carried by individuals. We showed that this phenomenon can be interpreted as an increase in resistance to stresses and showed that similar effect is observed in reliability of technical systems when redundancy of their components increases. The availability of longitudinal data for genotyped individuals opens unique opportunity to address more sophisticated questions about roles of genetic and non-genetic factors in connection between aging, stress resistance and longevity in humans. For this purpose the dynamic model of human mortality and aging is used. We show how such model can be used in genetic analyses of fundamental processes of interaction between genetic and non-genetic factors to influence human longevity.
Open Access
The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span.
(Phys Life Rev, 2012-06) Yashin, AI; Arbeev, KG; Akushevich, I; Kulminski, A; Ukraintseva, SV; Stallard, E; Land, KC
A better understanding of processes and mechanisms linking human aging with changes in health status and survival requires methods capable of analyzing new data that take into account knowledge about these processes accumulated in the field. In this paper, we describe an approach to analyses of longitudinal data based on the use of stochastic process models of human aging, health, and longevity which allows for incorporating state of the art advances in aging research into the model structure. In particular, the model incorporates the notions of resistance to stresses, adaptive capacity, and "optimal" (normal) physiological states. To capture the effects of exposure to persistent external disturbances, the notions of allostatic adaptation and allostatic load are introduced. These notions facilitate the description and explanation of deviations of individuals' physiological indices from their normal states, which increase the chances of disease development and death. The model provides a convenient conceptual framework for comprehensive systemic analyses of aging-related changes in humans using longitudinal data and linking these changes with genotyping profiles, morbidity, and mortality risks. The model is used for developing new statistical methods for analyzing longitudinal data on aging, health, and longevity.
Open Access
Theory of partitioning of disease prevalence and mortality in observational data.
(Theor Popul Biol, 2017-04) Akushevich, I; Yashkin, AP; Kravchenko, J; Fang, F; Arbeev, K; Sloan, F; Yashin, AI
In this study, we present a new theory of partitioning of disease prevalence and incidence-based mortality and demonstrate how this theory practically works for analyses of Medicare data. In the theory, the prevalence of a disease and incidence-based mortality are modeled in terms of disease incidence and survival after diagnosis supplemented by information on disease prevalence at the initial age and year available in a dataset. Partitioning of the trends of prevalence and mortality is calculated with minimal assumptions. The resulting expressions for the components of the trends are given by continuous functions of data. The estimator is consistent and stable. The developed methodology is applied for data on type 2 diabetes using individual records from a nationally representative 5% sample of Medicare beneficiaries age 65+. Numerical estimates show excellent concordance between empirical estimates and theoretical predictions. Evaluated partitioning model showed that both prevalence and mortality increase with time. The primary driving factors of the observed prevalence increase are improved survival and increased prevalence at age 65. The increase in diabetes-related mortality is driven by increased prevalence and unobserved trends in time-periods and age-groups outside of the range of the data used in the study. Finally, the properties of the new estimator, possible statistical and systematical uncertainties, and future practical applications of this methodology in epidemiology, demography, public health and health forecasting are discussed.
Open Access
Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: A propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008
(Diseases of the Esophagus, 2014-01-01) Worni, M; Castleberry, AW; Gloor, B; Pietrobon, R; Haney, JC; D'Amico, TA; Akushevich, I; Berry, MF
We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Browsing by Author "Akushevich, I"

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