Browsing by Author "Ukraintseva, Svetlana"
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Item Open Access Age patterns of incidence of geriatric disease in the U.S. elderly population: Medicare-based analysis.(J Am Geriatr Soc, 2012-02) Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Yashin, Anatoliy IOBJECTIVES: To use the Medicare Files of Service Use (MFSU) to evaluate patterns in the incidence of aging-related diseases in the U.S. elderly population. DESIGN: Age-specific incidence rates of 19 aging-related diseases were evaluated using the National Long Term Care Survey (NLTCS) and the Surveillance, Epidemiology, and End Results (SEER) Registry data, both linked to MFSU (NLTCS-M and SEER-M, respectively), using an algorithm developed for individual date at onset evaluation. SETTING: A random sample from the entire U.S. elderly population (Medicare beneficiaries) was used in NLTCS, and the SEER Registry data covers 26% of the U.S. population. PARTICIPANTS: Thirty-four thousand seventy-seven individuals from NLTCS-M and 2,154,598 from SEER-M. MEASUREMENTS: Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services and procedures, and Medicare enrollment and disenrollment. RESULTS: The majority of diseases (e.g., prostate cancer, asthma, and diabetes mellitus) had a monotonic decline (or decline after a short period of increase) in incidence with age. A monotonic increase in incidence with age with a subsequent leveling off and decline was observed for myocardial infarction, stroke, heart failure, ulcer, and Alzheimer's disease. An inverted U-shaped age pattern was detected for lung and colon carcinomas, Parkinson's disease, and renal failure. The results obtained from the NLTCS-M and SEER-M were in agreement (excluding an excess for circulatory diseases in the NLTCS-M). A sensitivity analysis proved the stability of the incidence rates evaluated. CONCLUSION: The developed computational approaches applied to the nationally representative Medicare-based data sets allow reconstruction of age patterns of disease incidence in the U.S. elderly population at the national level with unprecedented statistical accuracy and stability with respect to systematic biases.Item Open Access Cancer Risk and Behavioral Factors, Comorbidities, and Functional Status in the US Elderly Population.(ISRN Oncol, 2011) Akushevich, Igor; Kravchenko, Julia; Akushevich, Lucy; Ukraintseva, Svetlana; Arbeev, Konstantin; Yashin, AnatoliyAbout 80% of all cancers are diagnosed in the elderly and up to 75% of cancers are associated with behavioral factors. An approach to estimate the contribution of various measurable factors, including behavior/lifestyle, to cancer risk in the US elderly population is presented. The nationally representative National Long-Term Care Survey (NLTCS) data were used for measuring functional status and behavioral factors in the US elderly population (65+), and Medicare Claims files linked to each person from the NLTCS were used for estimating cancer incidence. The associations (i.e., relative risks) of selected factors with risks of breast, prostate, lung and colon cancers were evaluated and discussed. Behavioral risk factors significantly affected cancer risks in the US elderly. The most influential of potentially preventable risk factors can be detected with this approach using NLTCS-Medicare linked dataset and for further deeper analyses employing other datasets with detailed risk factors description.Item Open Access Circulatory Diseases in the U.S. Elderly in the Linked National Long-Term Care Survey-Medicare Database: Population-Based Analysis of Incidence, Comorbidity, and Disability.(Res Aging, 2013-07) Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Yashin, Anatoli IIncidence rates of acute coronary heart disease (ACHD; including myocardial infarction and angina pectoris), stroke, and heart failure (HF) were studied for their age, disability, and comorbidity patterns in the U.S. elderly population using the National Long Term Care Survey (NLTCS) data linked to Medicare records for 1991-2005. Incidence rates increased with age with a decrease in the oldest old (stroke and HF) or were stable at all ages (ACHD). For all diseases, incidence rates were lower among institutionalized individuals and higher in individuals with higher comorbidity indices. The results could be used for understanding currently debated effects of biomedical research, screening, and therapeutic innovations on changes in disease incidence with advancing age as well as for projecting future Medicare costs.Item Open Access Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps.(Int J Cancer, 2012-07-15) Soubry, Adelheid; Il'yasova, Dora; Sedjo, Rebecca; Wang, Frances; Byers, Tim; Rosen, Clifford; Yashin, Anatoli; Ukraintseva, Svetlana; Haffner, Steven; D'Agostino, RalphHigh levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risk of several cancers. Regarding colorectal cancer, these associations are generally weak. We hypothesized that an increase in IGF-1 over time would be a stronger risk factor for cancer-related outcomes than the actual levels. In this analysis we utilized existing data from the Insulin Resistance and Atherosclerosis Study (IRAS). Circulating IGF-1 levels and molar ratios of IGF-1 to IGF binding protein 3 (IGFBP-3) were measured at three time points, within a 10-year follow-up period. We examined the associations of increase of the two variables with the presence of colorectal adenoma at the end of follow-up among participants with normal glucose tolerance at baseline. This included 143 individuals, from which 24 were diagnosed with adenomatous polyps. Although the mean levels of IGF-1 and IGF-1/IGFBP-3 decline with age, ~ 30% of the participants showed an increase of at least fifteen percent ("ever increase") in one or both of these variables, compared to baseline. We found a positive association between "ever increase" in IGF-1 or IGF-1/IGFBP-3 and the presence of colorectal adenoma: ORs were 3.81 (95% CI: 1.30-10.8) and 2.83 (95% CI: 1.00-8.22), respectively. No association was found when analyzing the actual levels of both variables at any time point. Our data suggest that an increase in circulating IGF-1 or IGF-1/IGFBP-3 may represent a disturbed GH/IGF1 homeostasis, which could favor the development of precancerous lesions such as colorectal adenoma.Item Open Access Intra-individual changes in circulating IGF-1 and IGF-1/IGFBP-3 molar ratio are associated with colorectal adenomatous polyps presence(CANCER RESEARCH, 2011-04-15) Soubry, Adelheid; Sedjo, Rebecca; Wang, Frances; Byers, Tim; Rosen, Clifford; Yashin, Anatoli; Ukraintseva, Svetlana; Haffner, Steve; D'Agostino, Ralph; Il'yasova, DoraItem Open Access Medical cost trajectories and onsets of cancer and noncancer diseases in US elderly population.(Comput Math Methods Med, 2011) Akushevich, Igor; Kravchenko, Julia; Akushevich, Lucy; Ukraintseva, Svetlana; Arbeev, Konstantin; Yashin, Anatoliy ITime trajectories of medical costs-associated with onset of twelve aging-related cancer and chronic noncancer diseases were analyzed using the National Long-Term Care Survey data linked to Medicare Service Use files. A special procedure for selecting individuals with onset of each disease was developed and used for identification of the date at disease onset. Medical cost trajectories were found to be represented by a parametric model with four easily interpretable parameters reflecting: (i) prediagnosis cost (associated with initial comorbidity), (ii) cost of the disease onset, (iii) population recovery representing reduction of the medical expenses associated with a disease since diagnosis was made, and (iv) acquired comorbidity representing the difference between post- and pre diagnosis medical cost levels. These parameters were evaluated for the entire US population as well as for the subpopulation conditional on age, disability and comorbidity states, and survival (2.5 years after the date of onset). The developed approach results in a family of new forecasting models with covariates.Item Open Access Morbidity risks among older adults with pre-existing age-related diseases.(Exp Gerontol, 2013-12) Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Kulminski, Alexander; Yashin, Anatoliy IMulti-morbidity is common among older adults; however, for many aging-related diseases there is no information for U.S. elderly population on how earlier-manifested disease affects the risk of another disease manifested later during patient's lifetime. Quantitative evaluation of risks of cancer and non-cancer diseases for older adults with pre-existing conditions is performed using the Surveillance, Epidemiology, and End Results (SEER) Registry data linked to the Medicare Files of Service Use (MFSU). Using the SEER-Medicare data containing individual records for 2,154,598 individuals, we empirically evaluated age patterns of incidence of age-associated diseases diagnosed after the onset of earlier manifested disease and compared these patterns with those in general population. Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services/procedures, and Medicare enrollment/disenrollment. More than threefold increase of subsequent diseases risk was observed for 15 disease pairs, majority of them were i) diseases of the same organ and/or system (e.g., Parkinson disease for patients with Alzheimer disease, HR=3.77, kidney cancer for patients with renal failure, HR=3.28) or ii) disease pairs with primary diseases being fast-progressive cancers (i.e., lung, kidney, and pancreas), e.g., ulcer (HR=4.68) and melanoma (HR=4.15) for patients with pancreatic cancer. Lower risk of subsequent disease was registered for 20 disease pairs, mostly among patients with Alzheimer's or Parkinson's disease, e.g., decreased lung cancer risk among patients with Alzheimer's (HR=0.64) and Parkinson's (HR=0.60) disease. Synergistic and antagonistic dependences in geriatric disease risks were observed among US elderly confirming known and detecting new associations of wide spectrum of age-associated diseases. The results can be used in optimization of screening, prevention and treatment strategies of chronic diseases among U.S. elderly population.Item Open Access New stochastic carcinogenesis model with covariates: an approach involving intracellular barrier mechanisms.(Math Biosci, 2012-03) Akushevich, Igor; Veremeyeva, Galina; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Akleyev, Alexander V; Yashin, Anatoly IIn this paper we present a new multiple-pathway stochastic model of carcinogenesis with potential of predicting individual incidence risks on the basis of biomedical measurements. The model incorporates the concept of intracellular barrier mechanisms in which cell malignization occurs due to an inefficient operation of barrier cell mechanisms, such as antioxidant defense, repair systems, and apoptosis. Mathematical formalism combines methodological innovations of mechanistic carcinogenesis models and stochastic process models widely used in studying biodemography of aging and longevity. An advantage of the modeling approach is in the natural combining of two types of measures expressed in terms of model parameters: age-specific hazard rate and means of barrier states. Results of simulation studies allow us to conclude that the model parameters can be estimated in joint analyses of epidemiological data and newly collected data on individual biomolecular measurements of barrier states. Respective experimental designs for such measurements are suggested and discussed. An analytical solution is obtained for the simplest design when only age-specific incidence rates are observed. Detailed comparison with TSCE model reveals advantages of the approach such as the possibility to describe decline in risk at advanced ages, possibilities to describe heterogeneous system of intermediate cells, and perspectives for individual prognoses of cancer risks. Application of the results to fit the SEER data on cancer risks demonstrates a strong predictive power of the model. Further generalizations of the model, opportunities to measure barrier systems, biomedical and mathematical aspects of the new model are discussed.Item Open Access Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper Interpretation of Research Findings in GWAS of Populations with Different Genetic Structures.(Front Genet, 2016) Yashin, Anatoliy I; Zhbannikov, Ilya; Arbeeva, Liubov; Arbeev, Konstantin G; Wu, Deqing; Akushevich, Igor; Yashkin, Arseniy; Kovtun, Mikhail; Kulminski, Alexander M; Stallard, Eric; Kulminskaya, Irina; Ukraintseva, SvetlanaThis paper shows that the effects of causal SNPs on lifespan, estimated through GWAS, may be confounded and the genetic structure of the study population may be responsible for this effect. Simulation experiments show that levels of linkage disequilibrium (LD) and other parameters of the population structure describing connections between two causal SNPs may substantially influence separate estimates of the effect of the causal SNPs on lifespan. This study suggests that differences in LD levels between two causal SNP loci within two study populations may contribute to the failure to replicate previous GWAS findings. The results of this paper also show that successful replication of the results of genetic association studies does not necessarily guarantee proper interpretation of the effect of a causal SNP on lifespan.Item Open Access Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.(Biogerontology, 2016-02) Ukraintseva, Svetlana; Yashin, Anatoliy; Arbeev, Konstantin; Kulminski, Alexander; Akushevich, Igor; Wu, Deqing; Joshi, Gaurang; Land, Kenneth C; Stallard, EricComplex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.Item Open Access Recovery and survival from aging-associated diseases.(Exp Gerontol, 2013-08) Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Yashin, Anatoliy IOBJECTIVES: Considering disease incidence to be a main contributor to healthy lifespan of the US elderly population may lead to erroneous conclusions when recovery/long-term remission factors are underestimated. Using two Medicare-based population datasets, we investigated the properties of recovery from eleven age-related diseases. METHODS: Cohorts of patients who stopped visiting doctors during a five-year follow-up since disease onset were analyzed non-parametrically and using the Cox proportional hazard model resulted in estimated recovery and survival rates and evaluated the health state of recovered individuals by comparing their survival with non-recovered patients and the general population. RESULTS: Recovered individuals had lower death rates than non-recovered patients, therefore, patients who stopped visiting doctors are a healthier subcohort. However, they had higher death rates than in general population for all considered diseases, therefore the complete recovery does not occur. CONCLUSION: Properties of recovery/long-term remission among the US population of older adults with chronic diseases were uncovered and evaluated. The results allow for a better quantifiable contribution of age-related diseases to healthy life expectancy and improving forecasts of health and mortality.Item Open Access Resilience Versus Robustness in Aging.(J Gerontol A Biol Sci Med Sci, 2016-11) Ukraintseva, Svetlana; Yashin, Anatoliy I; Arbeev, Konstantin GItem Open Access Time trends of incidence of age-associated diseases in the US elderly population: Medicare-based analysis.(Age Ageing, 2013-07) Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Yashin, Anatoly IOBJECTIVES: time trends of age-adjusted incidence rates of 19 ageing-related diseases were evaluated for 1992-2005 period with the National Long Term Care Survey and the Surveillance, Epidemiology and End RESULTS Registry data both linked to Medicare data (NLTCS-Medicare and SEER-Medicare, respectively). METHODS: the rates were calculated using individual medical histories (34,077 individuals from NLTCS-Medicare and 199,418 from SEER-Medicare) reconstructed using information on diagnoses coded in Medicare data, dates of medical services/procedures and Medicare enrolment/disenrolment. RESULTS: increases of incidence rates were dramatic for renal disease [the average annual percent change (APC) is 8.56%, 95% CI = 7.62, 9.50%], goiter (APC = 6.67%, 95% CI = 5, 90, 7, 44%), melanoma (APC = 6.15%, 95% CI = 4.31, 8.02%) and Alzheimer's disease (APC = 3.96%, 95% CI = 2.67, 5.26%), and less prominent for diabetes and lung cancer. Decreases of incidence rates were remarkable for angina pectoris (APC = -6.17%, 95% CI = -6.96, -5.38%); chronic obstructive pulmonary disease (APC = -5.14%, 95% CI = -6.78,-3.47%), and ulcer (APC = -5.82%, 95% CI = -6.77,-4.86%) and less dramatic for carcinomas of colon and prostate, stroke, hip fracture and asthma. Incidence rates of female breast carcinoma, myocardial infarction, Parkinson's disease and rheumatoid arthritis were almost stable. For most diseases, an excellent agreement was observed for incidence rates between NLTCS-Medicare and SEER-Medicare. A sensitivity analysis proved the stability of the evaluated time trends. CONCLUSION: time trends of the incidence of diseases common in the US elderly population were evaluated. The results show dramatic increase in incidence rates of melanoma, goiter, chronic renal and Alzheimer's disease in 1992-2005. Besides specifying widely recognised time trends on age-associated diseases, new information was obtained for trends of asthma, ulcer and goiter among the older adults in the USA.