Biomedical subjects

Arnold Mitnitski

Publications and source records attributed to Arnold Mitnitski.

14 recordsLinked to original sources

PubMed2006

A cross-national study of transitions in deficit counts in two birth cohorts: implications for modeling ageing.

Generally, health does not improve with age, and many physical and physiological functions are known to decline. These changes do not occur uniformly, however; for many reasons, some people experience significant improvement in their health over non-trivial time intervals. Earlier, we showed that 5-year transitions in health status in elderly people (age 65+ years) can be modeled as a stochastic process, using a modified Poisson distribution with four readily interpretable parameters. The original description was based on follow-up of a single cross-sectional study, thus mixing age and cohort effects. Here, we again used a multistate Markov chain to model 5-year deficit accumulation in relation to frailty in both a Swedish birth cohort (aged 70 years at inception) and, from the original cross-sectional study, a Canadian birth cohort, aged 69-71. In both datasets, we found again that a modified Poisson describes the transition in health status with high precision. The parameters of the model though different, are close to each other, even though the cohorts are from different countries, were assembled 20 years apart, and counted different deficits. The model suggests that all health transitions, including health improvement, worsening, and death, can be summarized in a unified stochastic model with a few interpretable parameters.

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PubMed2006

Going from bad to worse: a stochastic model of transitions in deficit accumulation, in relation to mortality.

As people age, they accumulate deficits. The more deficits they accumulate, the greater their vulnerability, which can be expressed as the probability to accumulate even more deficits, or to die. The probability of death is known to be exponentially related to the number of deficits. Using data from elderly (aged 65 + years) participants in the Canadian Study of Health and Aging (n = 9008), we investigated the relationship between the number of deficits and the change in the number of deficits over two successive 5 year intervals. We show that the probabilities of changes in the number of deficits, in relation to baseline, are well fitted (R(2) > 0.98) by a simple distribution, with two parameters. The model suggests a maximum to deficit accumulation, and illustrates no level of deficit accumulation at which there is a net gain in fitness. Age-related deficit accumulation is highly characteristic, and can be modeled as a stochastic process with readily interpretable parameters.

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PubMed2006

Limits to deficit accumulation in elderly people.

We evaluated limits to the accumulation of deficits (symptoms, diseases, disabilities) for 33,069 people aged 65+ years. We combined deficits in a frailty index (theoretical range 0-1) and found that the 99% limit varied little between samples, representing a frailty index value of about 0.65 +/- 0.05. This near-maximum shows no relationship with age. It is the same in community and institutional samples, even though the mean value is much higher in the latter. The data suggest a level of frailty beyond which, even in developed countries, further deficit accumulation is not sustainable.

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PubMed2006

Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70.

OBJECTIVES: To measure relative fitness and frailty in older people without specific frailty instruments and to relate that measurement to long-term health outcomes. DESIGN: Retrospective cohort studies. SETTING: Two population-based studies of people aged approximately 70 at baseline and followed up to 10 years (in the Canadian Study of Health and Aging (CSHA)) or 26 years in the Gothenburg H-70 cohort study. PARTICIPANTS: Nine hundred sixty-two men and 1,178 women. MEASUREMENTS: Deficit accumulation (the exposure) was counted using self-reported (CSHA) or clinically designated (H-70) symptoms, signs, diseases, and disabilities. Relative fitness and frailty were measured in relation to the degree of deficit accumulation evaluated in four quartiles, representing those most fit to those most frail. The items that made up the frailty index were selected randomly without replacement in 1,000 iterations. The outcomes were risks of death or residential long-term care. RESULTS: Worse frailty, however measured, was associated with worse survival; the Kaplan-Meier curves of random iterations of the frailty definition showed virtually no interquartile overlap for mortality. For any given level of frailty, men died younger than women. Worse frailty was also associated with a higher risk of institutionalization. CONCLUSION: Frailty appears to be a robust concept that is readily operationalized, with the risk of adverse outcomes being largely established by age 70.

Activities of Daily Living↗

PubMed2005

Decrease in the relative heterogeneity of health with age: a cross-national comparison.

Using data from seven studies from Canada, Australia and the United States we were able to evaluate the heterogeneity of health status for 34,095 people aged 60 years and older. We found that relative heterogeneity (measured by the coefficient of variation) decreased with age. The coefficient of variation also decreased as a function of deficit accumulation (i.e. was lower when people demonstrated more deficits) displaying a power-law relationship. The exponent was close to 0.5, and therefore belongs to the dynamic universality class, which is typical for complex dynamical networks. We interpret this as showing that decline in relative heterogeneity is a robust finding, and represents, at the group level, increased vulnerability amongst elderly people.

Age Distribution↗

PubMed2005

A global clinical measure of fitness and frailty in elderly people.

BACKGROUND: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. METHODS: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. RESULTS: The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%-30.6%) and entry into an institution (23.9%, 95% CI 8.8%-41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). INTERPRETATION: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

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PubMed2005

Index variables for studying outcomes in vascular cognitive impairment.

Multivariable modeling in dementia risk factor studies is limited by the number of factors that can be analyzed practicably. Index variables, which integrate exposures, can efficiently reduce dimensionality. The Consortium to Investigate Vascular Impairment of Cognition study, a Canadian memory-clinic-based 30-month cohort study of 1,347 patients, used a vascular risk factor index (from 20 exposures) and a vascular clinical profile index (17 items). Patients with vascular cognitive impairment had higher index counts compared to those without cognitive impairment (0.16 +/- 0.11 vs. 0.07 +/- 0.07 for the risk factor index and 0.21 +/- 0.16 vs. 0.09 +/- 0.07 for the clinical profile index; p < 0.05). Both the death rate and the rate of cognitive impairment increased exponentially with the index variable (r > 0.90 for each index). The risk ratio for death was 1.12 (95% CI 1.09-1.15) for each increment of the risk factor index and was 1.23 (95% CI 1.1-1.28) for each increment of the clinical profile index. With each index, the areas under the receiver operating characteristic curves for predicting death and institutionalization ranged from 0.73 +/- 0.01 to 0.75 +/- 0.01. Construction of index variables that integrate multidimensional factors is a promising approach to assessing risk in multi-determined states.

Adult↗

PubMed2005

Evaluation of a frailty index based on a comprehensive geriatric assessment in a population based study of elderly Canadians.

BACKGROUND AND AIMS: Objectives were to develop a frailty index (FI) based on a standard comprehensive geriatric assessment (CGA) derived from a clinical examination; to assess the validity of the FI-CGA and to compare its precision with other frailty measures. METHODS DESIGN: Secondary analysis of a prospective cohort study, with five-year follow-up data. SETTING: Second phase of the Canadian Study of Health and Aging (CSHA-2); clinical examinations were performed in clinics, nursing homes, and patients' homes. PARTICIPANTS: People selected (as either cognitively impaired cases or unimpaired controls) to receive the CSHA-2 clinical examination (n = 2305; women = 1431). MEASUREMENTS: Clinical and performance-based measures and diagnostic data were extracted to correspond to the 10 impairment domains and the single comorbidity domain of a CGA. The proportion of deficits accumulated in each domain was calculated to yield the FI-CGA. The FI-CGA was validated and its predictive ability compared with other frailty measures. RESULTS: Within the seven grades of fitness/frailty identified, subjects with greater frailty were older, less educated, and more likely to be women. The FI-CGA correlated highly with a previously validated, empirically-derived frailty index (r = 0.76). Frailty was associated with higher risk of death (for each increment in frailty, the hazard ratio, adjusted for age, sex and education, was 1.23 (95% CI 1.18-1.29) and institutionalization (HR 1.20; 1.10-1.32). CONCLUSIONS: In a population survey, the FI-CGA is a valid means of quantifying frailty from routinely collected data.

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PubMed2005

Relative fitness and frailty of elderly men and women in developed countries and their relationship with mortality.

OBJECTIVES: To investigate the relationship between accumulated health-related problems (deficits), which define a frailty index in older adults, and mortality in population-based and clinical/institutional-based samples. DESIGN: Cross-sectional and cohort studies. SETTING: Seven population-based and four clinical/institutional surveys in four developed countries. PARTICIPANTS: Thirty-six thousand four hundred twenty-four people (58.5% women) aged 65 and older. MEASUREMENTS: A frailty index was constructed as a proportion of all potential deficits (symptoms, signs, laboratory abnormalities, disabilities) expressed in a given individual. Relative frailty is defined as a proportion of deficits greater than average for age. Measures of deficits differed across the countries but included common elements. RESULTS: In each country, community-dwelling elderly people accumulated deficits at about 3% per year. By contrast, people from clinical/institutional samples showed no relationship between frailty and age. Relative fitness/frailty in both sexes was highly correlated (correlation coefficient >0.95, P<.001) with mortality, although women, at any given age, were frailer and had lower mortality. On average, each unit increase in deficits increased by 4% the hazard rate for mortality (95% confidence interval=0.02-0.06). CONCLUSION: Relative fitness and frailty can be defined in relation to deficit accumulation. In population studies from developed countries, deficit accumulation is robustly associated with mortality and with age. In samples (e.g., clinical/institutional) in which most people are frail, there is no relationship with age, suggesting that there are maximal values of deficit accumulation beyond which survival is unlikely.

Age Distribution↗

PubMed2004

Changes with age in the distribution of a frailty index.

Models of human mortality include a factor that summarises intrinsic differences in individual rates of ageing, commonly called frailty. Frailty also describes a clinical syndrome of apparent vulnerability. In a representative, cross-sectional, Canadian survey (n = 66,589) we calculated a frailty index as the mean accumulation of deficits and previously showed it to increase exponentially with age. Here, its density function exhibited a monotonic change in shape, being least skewed at the oldest ages. Although the shape gradually changed, the frailty index was well fitted by a gamma distribution. Of note, the variation coefficient, initially high, decreased from middle age on. Being able to quantify frailty means that health risks can be summarised at both the individual and group levels.

Adult↗

PubMed2004

Assessment of individual risk of death using self-report data: an artificial neural network compared with a frailty index.

OBJECTIVES: To evaluate the potential of an artificial neural network (ANN) in predicting survival in elderly Canadians, using self-report data. DESIGN: Cohort study with up to 72 months follow-up. SETTING: Forty self-reported characteristics were obtained from the community sample of the Canadian Study of Health and Aging. An individual frailty index score was calculated as the proportion of deficits experienced. For the ANN, randomly selected participants formed the training sample to derive relationships between the variables and survival and the validation sample to control overfitting. An ANN output was generated for each subject. A separate testing sample was used to evaluate the accuracy of prediction. PARTICIPANTS: A total of 8,547 Canadians aged 65 to 99, of whom 1,865 died during 72 months of follow-up. MEASUREMENTS: The output of an ANN model was compared with an unweighted frailty index in predicting survival patterns using receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve was 86% for the ANN and 62% for the frailty index. At the optimal ROC value, the accuracy of the frailty index was 70.0%. The ANN accuracy rate over 10 simulations in predicting the probability of individual survival mean+/-standard deviation was 79.2+/-0.8%. CONCLUSION: An ANN provided more accurate survival classification than an unweighted frailty index. The data suggest that the concept of biological redundancy might be operationalized from health survey data.

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PubMed2004

Comparison of machine learning techniques with classical statistical models in predicting health outcomes.

Several machine learning techniques (multilayer and single layer perceptron, logistic regression, least square linear separation and support vector machines) are applied to calculate the risk of death from two biomedical data sets, one from patient care records, and another from a population survey. Each dataset contained multiple sources of information: history of related symptoms and other illnesses, physical examination findings, laboratory tests, medications (patient records dataset), health attitudes, and disabilities in activities of daily living (survey dataset). Each technique showed very good mortality prediction in the acute patients data sample (AUC up to 0.89) and fair prediction accuracy for six year mortality (AUC from 0.70 to 0.76) in individuals from epidemiological database surveys. The results suggest that the nature of data is of primary importance rather than the learning technique. However, the consistently superior performance of the artificial neural network (multi-layer perceptron) indicates that nonlinear relationships (which cannot be discerned by linear separation techniques) can provide additional improvement in correctly predicting health outcomes.

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PubMed2003

Help available--phenomenological models for research on aging.

In "Help Wanted: Physiologists for Research on Aging," George Martin challenged the scientific community to find better means of tackling aging of the whole organism. Although initiatives such as those proposed by Martin would be most welcome, we propose an additional means by which scientists can take into account the integrative response of the organism and its changes over time. This method consists of systematizing facts that cannot necessarily be explained by considering those facts in isolation.

Aging↗

PubMed2002

Sequential control signals determine arm and trunk contributions to hand transport during reaching in humans.

When reaching towards objects placed outside the arm workspace, the trunk assumes an active role in transport of the hand by contributing to the extent of movement while simultaneously maintaining the direction of reach. We investigated the spatial-temporal aspects of the integration of the trunk motion into reaching. Specifically, we tested the hypothesis that the efficiency ('gain') of the arm-trunk co-ordination determining the contribution of the trunk to the extent of hand movement may vary substantially with the phase of reaching. Sitting subjects made fast pointing movements towards ipsi- and a contralateral targets placed beyond the reach of the right arm so that a forward trunk motion was required to assist in transporting the hand to the target. Sight of the arm and target was blocked before the movement onset. In randomly selected trials, the trunk motion was unexpectedly prevented by an electromagnet. Subjects were instructed to make stereotypical movements whether or not the trunk was arrested. In non-perturbed trials, most subjects began to move the hand and trunk simultaneously. In trunk-blocked trials, it was impossible for the hand to cover the whole pointing distance but the hand trajectory and velocity profile initially matched those from the trials in which the trunk motion was free, approximately until the hand reached its peak velocity. The arm inter-joint co-ordination substantially changed in response to the trunk arrest at a minimal latency of 40 ms after the perturbation onset. The results suggest that when the trunk was free, the influence of the trunk motion on the hand trajectory and velocity profile was initially neutralized by appropriate changes in the arm joint angles. Only after the hand had reached its peak velocity did the trunk contribute to the extent of pointing. Previous studies suggested that the central commands underlying the transport component of arm movements are completed when the hand reaches peak velocity. These studies, together with the present finding that the trunk only begins to contribute to the hand displacement at peak hand velocity, imply that the central commands that determine the contributions of the arm and the trunk to the transport of the hand are generated sequentially, even though the arm and trunk move in parallel.

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