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PubMed2005

Association between somatic cell count in early lactation and culling of dairy heifers using cox frailty models.

The association between somatic cell count (SCC) of dairy heifers in early lactation [SCCel; measured between 5 and 14 d in milk (DIM)] and the culling hazard during the first lactation was studied using Cox frailty models. Udder health problems were the culling reason for 10% of the culled heifers in this study. For each unit increase in the log-transformed SCCel (LnSCCel), the culling hazard increased by 11% [Hazard ratio (HR) = 1.11]. The strength of the association depended on 5 factors. Firstly, the association was stronger when SCCel was recorded after 10 DIM than at an earlier DIM. Secondly, the association was stronger if only culling events for udder disorders were considered (HR = 1.32) instead of all culling events (HR = 1.11). Furthermore, for each unit increase of test-day LnSCC after 14 DIM, modeled as a time-varying covariate, the culling hazard in the first lactation increased by 26% (HR = 1.26). Including LnSCC in the model already containing LnSCCel, reduced the estimate of LnSCCel slightly. Fourth, a higher test-day milk yield, modeled as a time-varying covariate, protected against culling and reduced the magnitude of the effect of LnSCCel as well when taken into account. Finally, the association between LnSCCel and culling was still present, although smaller, in the group of heifers with a second test-day SCC </=50,000 cells/mL.

Animals↗
PubMed2005

Frailty in older adults: insights and interventions.

Frailty is a state of vulnerability that carries an increased risk of poor outcomes in older adults. Common signs and symptoms are fatigue, weight loss, muscle weakness, and progressive decline in function. Frail older adults are among the most challenging for medical management. However, awareness of this syndrome and its risks can help us care for these patients more confidently and decrease their risk for adverse outcomes.

Activities of Daily Living↗
PubMedDate not supplied

Determinants of musculoskeletal frailty and the risk of falls in old age.

Neuromuscular parameters that describe locomotion are indispensable variables for the diagnosis and treatment of frailty, fall risk and osteoporosis. A scientifically-based standardized locomotor assessment should be an essential part of medical examinations in research and clinical practice. There has been no previous consensus regarding which test procedures should be included in a locomotor assessment. The goal of this article is to provide a rationale for the selection of appropriate locomotor tests in a comprehensive locomotor assessment for elderly patients. We propose that a locomotor assessment should comprise the parameters that have been proven predictive for both falls and impending disability. The parameters should be measured in the standard units of physics. Therefore, we propose the following tests for a standardized locomotor assessment: (1) Self-selected gait velocity as the single best measure of general locomotor status and a good predictor of age-related adverse events; (2) Chair rise test (timed 5 chair rises) which measures power on vertical movement and the hip surrounding muscles as the most important neuromuscular risk factor for falls and fall-related fractures; (3) Tandem standing and tandem walking to measure postural capacity (balance) to the side; (4) Timed up and go test as a global screening procedure; (5) Clinical gait analysis with special focus on regularity; and (6) At least on a research level, movement must be measured referring to the terms of physics by mechanography. Mechanography (Leonardo force plate system, Novotec Pforzheim, Germany) records the time course of ground reaction forces, velocity of the vertical movements of the center of mass and power during unrestricted physiological movements. In the mechanogram the eccentric and concentric phases of movements can be differentiated and the storage of energy in the elastic elements of the body can be examined. The kinetics of human movement is explained by mechanograms of a two-legged jump. The ground reaction forces resulting from a jump down from a height of 0,46 m are demonstrated as a performance that is representative for human coordination. One goal of this text is to underline the insights that arise if the rules of physics are applied to human movement. A deeper understanding enables us to create more effective treatments for disorders of the muscle-bone unit. Bringing physics and cybernetics into the field of osteoporosis is a great heritage of Harold Frost.

Accidental Falls↗
PubMed1991

A Monte Carlo method for Bayesian inference in frailty models.

Many analyses in epidemiological and prognostic studies and in studies of event history data require methods that allow for unobserved covariates or "frailties." Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-117) proposed a generalization of the proportional hazards model that implemented such random effects, but the proof of the asymptotic properties of the method remains elusive, and practical experience suggests that the likelihoods may be markedly nonquadratic. This paper sets out a Bayesian representation of the model in the spirit of Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221) and discusses inference using Monte Carlo methods.

Algorithms↗
PubMed1990

Age-specific death rates with tobacco smoking and occupational activity: sensitivity to sample length, functional form, and unobserved frailty.

In this article, we estimate accelerated time-to-failure and proportional-hazard functions with about 100,000 members of the Dorn sample, finding greater hazards associated with smoking and some dependence on occupational variables that measure risk and physical activity. We answer three questions: (1) How sensitive are the estimates to sample length, using monthly data for the periods 1954-1969 and 1954-1980? The results differ somewhat between these sample periods. (2) How sensitive are the estimates to alternative functions for the hazard? Within a given time period, the estimates are fairly robust to specification changes in the distribution of the hazard in the accelerated time-to-failure models. (3) How sensitive are the estimates to alternative controls for unobserved frailty? Within a given sample period, the estimates are fairly robust to the allowance for parametric or nonparametric heterogeneity in the proportional-hazard models.

Adult↗
PubMed1993

REML estimation for survival models with frailty.

A method of estimation for generalised mixed models is applied to the estimation of regression parameters in proportional hazards models for failure times when there are repeated observations of failure on each subject. The subject effect is incorporated into the model as a random frailty term. Best linear unbiased predictors are used as an initial step in the computation of maximum likelihood and residual maximum likelihood estimates.

Bias↗
PubMed1997

How frailty models can be used for evaluating longevity limits: taking advantage of an interdisciplinary approach.

In this paper we discuss an approach to the analysis of mortality and longevity limits when survival data on related individuals with and without observed covariates are available. The approach combines the ideas of demography and survival analysis with methods of quantitative genetics and genetic epidemiology. It allows us to analyze the genetic structure of frailty in the Cox-type hazard model with random effects. We demonstrate the implementation of this strategy to survival data on Danish twins. We then evaluate the resulting lower bounds for biological limits of human longevity. Finally, we discuss the limitations of this approach and directions of further research.

Aged↗
PubMed1997

Testosterone and frailty.

Although estrogen replacement therapy has become well established in the management of postmenopausal women, most physicians pay much less attention to the testosterone status of their older male patients. There is now increasing evidence that testosterone deficiency-Low Testosterone Syndrome-occurs in older men and is associated with decreased muscle strength and bone density, as well as memory problems. This article reviews the evidence for the existence of Low Testosterone Syndrome, often characterized as the male menopause or viropause, and the emerging evidence that testosterone therapy may ameliorate some of the symptoms and signs of frailty in men beyond 50 years of age.

Aged↗
PubMed1998

[Changes in the energy needs of the elderly: an often encountered cause of nutritional deficiencies and frailty].

Changes in the body composition of elderly people and diminished physical activity reduce the energy requirement and the daily energy intake. It is especially frail elderly people who run an increased risk of a poor nutritional condition which further enhances fragility. Frailty is often defined as the state of reduced physiologic reserve associated with increased susceptibility to disability. In frail elderly people energy requirement is often reduced. Studies have shown that when energy intake falls below a level of about 6.3 MJ, it is hard to obtain a diet with a sufficient supply of minerals and water soluble vitamins. It is especially the daily intake of vitamins of the B complex and of vitamin C that then prove insufficient. In addition, immobile elderly and elderly of 75 years and older are at risk for an inadequate vitamin D status. An adequate diet is one of the factors that may prevent frail health. Screening lists have been developed to quickly obtain information about the nutritional status of older adults. However, these lists still have to be adapted to the Dutch dietary pattern. Currently, a change of the body weight is the best warning of insufficient nutrition.

Aged↗
PubMedDate not supplied

Estimating surgical volume--outcome relationships applying survival models: accounting for frailty and hospital fixed effects.

This paper investigates the surgical volume-outcome relationship for patients undergoing hip fracture surgery in Quebec between 1991 and 1993. Using a duration model with multiple destinations which accounts for observed and unobserved (by the researcher) patient characteristics, our initial estimates show that higher surgical volume is associated with a higher conditional probability of live discharge from the hospital. However, these results reflect differences between hospitals rather than differences within hospitals over time: when we also control for differences between hospitals that are fixed over time, hospitals performing more surgeries in period t + 1 than in period t experience no significant change in outcomes, as would be predicted by the 'practice makes perfect' hypothesis. The volume-outcome relationship for hip fracture patients thus appears to reflect quality differences between high and low volume hospitals.

Aged↗
PubMed1996

Influence of age, frailty and liver function on the pharmacokinetics of brofaromine.

OBJECTIVE: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y). METHODS: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). RESULTS: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001). CONCLUSION: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.

Administration, Oral↗
PubMed2006

Dynamic survival models with spatial frailty.

In many survival studies, covariates effects are time-varying and there is presence of spatial effects. Dynamic models can be used to cope with the variations of the effects and spatial components are introduced to handle spatial variation. This paper proposes a methodology to simultaneously introduce these components into the model. A number of specifications for the spatial components are considered. Estimation is performed via a Bayesian approach through Markov chain Monte Carlo methods. Models are compared to assess relevance of their components. Analysis of a real data set is performed, showing the relevance of both time-varying covariate effects and spatial components. Extensions to the methodology are proposed along with concluding remarks.

Bayes Theorem↗