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Results for “Frailty”

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PubMed1997

Frailty modelling for the excess hazard.

Long-term excess hazards for cancer survival sometimes tend to zero or become negative even though we expect them to be positive. This may be explained by selection at diagnosis; individuals with certain cancers may have an increased risk of dying of other diseases in general. Then comparing with population mortality rates is not correct. Alternatively, we may have a continuous selection of the most robust individuals after diagnosis. When there are unobserved heterogeneity, and those with highest risk of dying of cancer also have the highest risk of dying of other diseases, this will cause selection after diagnosis. This may be modelled by multivariate frailty variables, and a corrected excess hazard may be estimated. In two examples, these corrected excess hazards give a better estimate when comparing to the cause-specific cancer mortality. Actually, this study questions the usefulness of long-term excess hazard rates.

Adult↗

PubMed2000

Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: apolipoprotein E gene is a "frailty gene," not a "longevity gene".

We developed a method to estimate genotype-specific average relative mortality risk, R, from genotype distributions in cross-sectional studies of people belonging to different age-groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40-year-old Danish men. Twenty-one percent of the centenarians were epsilon 2-carriers (genotypes epsilon 2 epsilon 2 and epsilon 3 epsilon 2) and 15% were epsilon 4-carriers (genotypes epsilon 4 epsilon 4 and epsilon 4 epsilon 3) compared to 13 and 29%, respectively, of the young men. The R-values were 0.95 (95% CI 0.88 to 1.02) for epsilon 2-carriers and 1.13 (95% CI 1.05 to 1.22) for epsilon 4-carriers, using epsilon 3 epsilon 3- and epsilon 4 epsilon 2 genotypes as reference. Corresponding values for epsilon 4-carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for epsilon 2-carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a "longevity gene".

Adult↗

PubMed2004

Frailty models for arbitrarily censored and truncated data.

In this paper, we propose a frailty model for statistical inference in the case where we are faced with arbitrarily censored and truncated data. Our results extend those of Alioum and Commenges (1996), who developed a method of fitting a proportional hazards model to data of this kind. We discuss the identifiability of the regression coefficients involved in the model which are the parameters of interest, as well as the identifiability of the baseline cumulative hazard function of the model which plays the role of the infinite dimensional nuisance parameter. We illustrate our method with the use of simulated data as well as with a set of real data on transfusion-related AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Tiredness in daily activities: a subjective measure for the identification of frailty among non-disabled community-living older adults.

The objective of this study was to determine whether the responses to questions about tiredness in daily activities is an early subjective sign of frailty indicating older community-living adults at increased risk for disability and mortality. Tiredness in daily activities as measured by the Mob-T Scale, maximal power in sustained work, and comorbid diseases were assessed together with sociodemographic variables in a sample of 705 non-disabled, 70-year old men and women surveyed in 1984. Vital status of members was determined prospectively over the next 15 years. Onset of disability was measured at 5-, 10-, and 15-year follow-up. Onset of disability among non-disabled 70-year old men and women was strongly related to tiredness in daily activities at 5- and 10-year follow-up. Scores on the Mob-T Scale were significantly associated with mortality during the aggregate 15-year follow-up period. Multiple stepwise regression analyses not only indicated that tiredness in daily activities is a strong independent predictor of both disability and mortality, but also that tiredness mediates the effects of comorbidity and maximal power in sustained work on disability/mortality. Self-reported tiredness in daily activities is suggested as a basis for identifying vulnerable frail subsets of older adults requiring targeted strategies for prevention.

Activities of Daily Living↗

PubMed2003

Frailty and the biochemical effects of recombinant human growth hormone in women after surgery for hip fracture.

We report a randomised double blind controlled trial investigating the short-term biochemical and adverse clinical responses to recombinant human growth hormone (r-hGH) after surgery for hip fracture. Hip fractures are common, dangerous and expensive, typically affecting frail women with osteoporosis and reduced muscle mass and strength, factors also associated with poor clinical outcomes. Growth hormone therapy increases IGF-I levels, promotes anabolism and increases muscle strength in well older people and selected patient groups and therefore has therapeutic potential to assist recovery of frail patients.Thirty-one women, mean age 86 years, received 14 nightly subcutaneous injections of r-hGH 0.05 mg/kg/day (high dose) or 0.025 mg/kg/day (low dose), or placebo from the 4th post-operative day. There were several serious adverse clinical events but no excess number of adverse events in the r-hGH treatment groups. The r-hGH treatment groups had similar serum IGF-I and IGFBP-3 responses, both significantly different from placebo. The large inter-individual variation of IGF-I responses were inversely correlated with pre-treatment indicators of frailty (body composition and functional abilities).

Aged↗

PubMed2005

Health system frailties in tuberculosis service provision in Russia: an analysis through the lens of formal nutritional support.

OBJECTIVE: The aim of this study was to describe health system challenges faced by tuberculosis (TB) treatment facilities in Russia through an analysis of formal institutional dietary provisions to patients in an inpatient facility that provides care for poor patients. METHODS: Analysis of formal dietary provisions by institutions and financing data from TB hospitals in Samara Oblast, Russia. RESULTS: Formal dietary provision for inpatients with TB has fallen substantially in recent years. In a hospital providing inpatient care for the poorest patients with fewest social support networks, this has been very pronounced. The likely reason for this is that financial support for other budget lines, principally salaries, has required protection. CONCLUSION: Formal institutional nutritional support in institutions providing care for the poorest patients with TB is unlikely to be enhancing the speed of recovery, or reducing the duration of infectiousness. Furthermore, the role that hospital may have played in the past in enabling patients to regain weight lost before admission may have been limited by reductions in formal financing. Reductions in state provision of food for patients may serve as an important illustration of wider TB control system frailties in the Russian Federation.

Budgets↗

PubMed2006

Inflammation markers predicting frailty and mortality in the elderly.

Greater numbers of individuals are living to older ages. A major concern at both individual and population levels is how to live these years at a high functional level. If we had physiological markers to identify those at risk for progressive functional decline and impeding death, therapies could be targeted towards these individuals to prevent adverse outcomes. Senescence is presently considered as the consequence of lifelong antigenic stress impinging upon the individual genetic background. We might consider inflammation markers as synthetic measures of lifelong attrition combined with genetic tendency to develop an inflammatory phenotype. Such biomarkers are the most powerful predictors of frailty and mortality in the elderly available today. The aim of this review is to translate results from the research on ageing into a practical view, suggesting new tools for the clinical approach to older people.

Aged↗

PubMed2003

State of the art in geriatric rehabilitation. Part I: review of frailty and comprehensive geriatric assessment.

OBJECTIVES: To increase recognition of geriatric rehabilitation and to provide recommendations for practice and future research. DATA SOURCES: A CINAHL and 2 MEDLINE searches were conducted for 1980 to 2001. A fourth search used the Cochrane database. STUDY SELECTION: One author reviewed the reference for relevance and another for quality. A total of 336 articles were selected. Excluded articles were unrelated to geriatric rehabilitation or were anecdotal or descriptive reports. DATA EXTRACTION: The following major geriatric rehabilitation subtopics were identified: frailty, comprehensive geriatric assessment, admission screening, assessment tools, interdisciplinary teams, hip fracture, stroke, nutrition, dementia, and depression. Part I describes the first 5 subtopics on concepts and processes in geriatric rehabilitation. Part II focuses on the latter 5 subtopics of common clinical problems in frail older persons. A level-of-evidence framework was used to review the literature. Level 1 evidence was a randomized controlled trial (RCT) or a meta-analysis or systematic review of RCTs. Level 2 evidence included controlled trials without randomization, cohort, or case-control studies. Level 3 evidence involved consensus statements from experts or descriptive studies. DATA SYNTHESIS: Of the 336 articles evaluated, 108 were level 1, 39 were level 2, and 189 were level 3. Recommendations were made for each subtopic. In cases in which several articles were written on the same topic and drew similar conclusions, the authors chose those articles with the strongest level of evidence, reducing the total number of references. CONCLUSIONS: Frail elderly patients should be screened for rehabilitation potential. Standardized tools are recommended to aid diagnosis, assessment, and outcome measurement. The team approach to geriatric rehabilitation should be interdisciplinary and use a comprehensive geriatric assessment. Medication reviews and self-medication programs may be beneficial. Future research should address cost effectiveness, consensus on outcome measures, which components of geriatric rehabilitation are most effective, screening, and what outcomes are sustainable.

Aged↗

PubMed2001

A study design to investigate the effect of intense Tai Chi in reducing falls among older adults transitioning to frailty.

This paper describes the study design, methodological considerations, and baseline characteristics of a clinical trial to determine if intense (48 weeks, twice per week) Tai Chi practice can reduce the frequency of falls among older adults transitioning to frailty compared to a wellness education program. Twenty facilities will be stratified on socioeconomic status and facility type and randomly assigned to one of the two interventions. Secondary outcome measurements include variables related to function, behavior, and the biomechanics of movement. This study is unique because it represents an effort to offer a novel physical intervention to a large sample of transitional frail adults, a population that has received few formal exercise interventions. In addition to bringing the interventions into facilities, a 1-year follow-up is also included to assess rates of change in outcome measurements.

Accidental Falls↗

PubMed2004

Temporal and spatial features of gait in older adults transitioning to frailty.

Examining gait characteristics in older adults who are transitioning to frailty enhances our understanding of movement control in this fall-prone population and helps to better target preventive interventions. This work presents data on temporal and spatial gait parameters of a group of older adults who have been operationally defined as "transitionally frail". Gait speed, cadence, stride length, stance, swing, double-support, and horizontal heel velocity at heel contact were measured in 50 transitionally frail older adults while walking at a self-selected pace. These data suggest that the temporal and spatial gait features of these older adults differ substantially from published results from other older adults.

Aged↗

PubMed2003

Sex hormones and male health: effects on components of the frailty syndrome.

Physicians are seeing an increasing number of older male patients with chronic diseases and conditions. However, the potential relevance of low levels of circulating endogenous androgens in connection with these diseases and conditions is generally poorly understood. Research findings have suggested that androgens play a distinct role in bone metabolism, body composition such as muscle and fat mass and fat distribution, cognitive functioning, mood and well being. The aim of this paper is to summarize the currently available data on the association between endogenous androgens and the intermediate or clinically manifest indicators of chronic conditions in men that might contribute to the phenomenon "frailty". The evidence that reductions in endogenous androgens play a role in age-related health problems is circumstantial. Therefore, large-scale randomized trials are needed to establish whether aging males with low serum androgen levels benefit from androgen supplementation.

Abdomen↗

PubMed1997

A nested frailty model for survival data, with an application to the study of child survival in northeast Brazil.

"This article presents a multivariate hazard model for survival data that are clustered at two hierarchical levels.... We apply the model to an analysis of the covariates of child survival using survey data from northeast Brazil collected via a hierarchically clustered sampling scheme. We find that family and community frailty effects are fairly small in magnitude but are of importance because they alter the results in a systematic pattern."

Americas↗

PubMedDate not supplied

Serum cholesterol levels as a measure of frailty in elderly patients.

The authors evaluated the association between serum cholesterol levels and social, clinical, and functional characteristics in 637 elderly hospitalized patients (mean age = 79.1 years, range = 65-97) from the Geriatric Evaluation and Rehabilitation Unit (GERU) at P. Richiedei Hospital in Gussago, Brescia (Italy). Patients consecutively admitted to the GERU during an 18-month period underwent a multidimensional evaluation including information on demographics, cognitive status, physical health (number of chronic diseases and administered drugs), functional disability, and nutritional status. Mean cholesterol levels were significantly lower in men; persons living with others; older individuals; and individuals with cognitive impairment, poorer somatic health, higher disability, and a higher level of malnutrition. Lower serum cholesterol levels may be considered an independent hematologic marker of frailty in elderly hospitalized patients.

Aged↗

PubMedDate not supplied

Caresharing: hiding frailty in a Florida retirement community.

This paper presents research findings generated from a study of the structure of a "caresharing system" for the elderly who reside in a Florida retirement community during the last decade of the twentieth century. A caresharing system is a combination of strategies employed in order to maximize pleasure and minimize losses that might otherwise be associated with communal and individual aging processes. In this instance, the caresharing system entailed a series of conscious efforts to hide frailty in the community. Consequences of such caresharing systems and implications for future retirement communities are discussed.

Activities of Daily Living↗

PubMed1995

Correlated individual frailty: an advantageous approach to survival analysis of bivariate data.

"We develop a new model of bivariate survival based on the notion of correlated individual frailty. We analyze the properties of this model and suggest a new approach to the analysis of bivariate data that does not require a parametric specification--but permits estimation--of the form of the hazard function for individuals. We empirically demonstrate the advantages of the model in the statistical analysis of bivariate data." (SUMMARY IN FRE)

Demography↗

PubMed1989

The effect of age and frailty upon acetanilide clearance in man.

Six healthy young subjects (aged 23-32 years), six healthy elderly subjects (over 60 years) and six hospitalized long-stay geriatric subjects over 60 years received single oral doses of acetanilide. Acetanilide clearance was similar in the fit and frail elderly subjects at 26.4 +/- 2.5 and 26.3 +/- 3.6 l/h and significantly lower (p less than 0.05) than in the young subjects at 39.0 +/- 1.9 l/h. Liver volumes, measured by ultrasound, were significantly less in the elderly than in the young subjects, whether expressed in absolute terms or per unit body weight (p less than 0.05). When acetanilide clearance was expressed per unit volume of liver, no change occurred with age or frailty. These results suggest that a reduced liver size may be an important contributor to the reduced elimination of capacity limited drugs in elderly man.

Acetanilides↗

PubMed2002

Multivariate survival models induced by genetic frailties, with application to linkage analysis.

We derive a multivariate survival model for age of onset data of a sibship from an additive genetic gamma frailty model constructed basing on the inheritance vectors, and investigate the properties of this model. Based on this model, we propose a retrospective likelihood approach for genetic linkage analysis using sibship data. This test is an allele-sharing-based test, and does not require specification of genetic models or the penetrance functions. This new approach can incorporate both affected and unaffected sibs, environmental covariates and age of onset or age at censoring information and, therefore, provides a practical solution for mapping genes for complex diseases with variable age of onset. Small simulation study indicates that the proposed method performs better than the commonly used allele-sharing-based methods for linkage analysis, especially when the population disease rate is high. We applied this method to a type 1 diabetes sib pair data set and a small breast cancer data set. Both simulated and real data sets also indicate that the method is relatively robust to the misspecification to the baseline hazard function.

Journal Article↗

PubMed2003

Frailty modeling for spatially correlated survival data, with application to infant mortality in Minnesota.

The use of survival models involving a random effect or 'frailty' term is becoming more common. Usually the random effects are assumed to represent different clusters, and clusters are assumed to be independent. In this paper, we consider random effects corresponding to clusters that are spatially arranged, such as clinical sites or geographical regions. That is, we might suspect that random effects corresponding to strata in closer proximity to each other might also be similar in magnitude. Such spatial arrangement of the strata can be modeled in several ways, but we group these ways into two general settings: geostatistical approaches, where we use the exact geographic locations (e.g. latitude and longitude) of the strata, and lattice approaches, where we use only the positions of the strata relative to each other (e.g. which counties neighbor which others). We compare our approaches in the context of a dataset on infant mortality in Minnesota counties between 1992 and 1996. Our main substantive goal here is to explain the pattern of infant mortality using important covariates (sex, race, birth weight, age of mother, etc.) while accounting for possible (spatially correlated) differences in hazard among the counties. We use the GIS ArcView to map resulting fitted hazard rates, to help search for possible lingering spatial correlation. The DIC criterion (Spiegelhalter et al., Journal of the Royal Statistical Society, Series B 2002, to appear) is used to choose among various competing models. We investigate the quality of fit of our chosen model, and compare its results when used to investigate neonatal versus post-neonatal mortality. We also compare use of our time-to-event outcome survival model with the simpler dichotomous outcome logistic model. Finally, we summarize our findings and suggest directions for future research.

Adult↗