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PubMed2004

The interpretation of social comparison and its relation to life satisfaction among elderly people: does frailty make a difference?

We examined the interpretation of upward and downward social comparison and its effect on life satisfaction in a questionnaire study among 444 community-dwelling elderly persons with different levels of frailty. As we expected, elderly persons with higher levels of frailty were less inclined to contrast and more inclined to identify themselves with a downward comparison target. Furthermore, they were more inclined to contrast themselves with an upward comparison target, but contrary to our expectations, they were also more inclined to identify with this target. Upward identification and downward contrast related positively, whereas upward contrast and downward identification related negatively to life satisfaction. These effects existed independently of the negative effect of frailty on life satisfaction.

Aged↗

PubMed1997

Evaluation of a self-report screening instrument to predict frailty outcomes in aging populations.

The purpose of this study is to investigate the utility of a self-report screening instrument, the Health Status Form (HSF), to predict elderly members at risk of frailty in the subsequent year. The predictive ability of self-report HSF data was also compared to the predictive ability of inpatient discharges and pharmacy dispensings from administrative utilization databases. Four HSF variables best predicted elderly members at risk of frailty: (a) age, (b) indicating that health conditions interfered with daily activities, (c) needing or receiving assistance from another person for bathing, and (d) needing or receiving assistance from another person for taking medications. The predictive model yielded sensitivity 50.7%, specificity 97.8%, and correctly classified 90.9% of the population. Self-report population-based screening is a reliable method for predicting elderly members at risk of frailty in the coming year. Further studies should test a new brief instrument composed of portions of validated measures as a stand alone screener to select frail members for care management purposes.

Aged↗

PubMed2002

The use of frailty hazard models for unrecognized heterogeneity that interacts with treatment: considerations of efficiency and power.

Increasingly, genetic studies of tumors of the same histologic diagnosis are elucidating subtypes that are distinct with respect to clinical endpoints such as response to treatment and survival. This raises concerns about the efficiency of using the simple log-rank test for analysis of treatment effect on survival in studies of possibly heterogeneous tumors. Furthermore, such studies, designed under the assumption of homogeneity, may be severely underpowered. We derive analytic approximations for the asymptotic relative efficiency of the simple log-rank test relative to the optimally weighted log-rank test and for the power of the simple log-rank test when applied to subjects with unobserved heterogeneity, as reflected in a continuous frailty, that may interact with treatment. Numerical studies demonstrate that the simple log-rank test may be quite inefficient if the frailty interacts with treatment. Further, there may be a substantial loss of power in the presence of the frailty with or without an interaction with treatment.

Brain Neoplasms↗

PubMed2003

A bivariate frailty model with a cure fraction for modeling familial correlations in diseases.

We suggest a cure-mixture model to analyze bivariate time-to-event data, as motivated by the article of Chatterjee and Shih (2001, Biometrics 57, 779-786), but with a simpler estimation procedure and the correlated gamma-frailty model instead of the shared gamma-frailty model. This approach allows us to deal with left-truncated and right-censored lifetime data, and accounts for heterogeneity, as well as for an insusceptible (cure) fraction in the study population. We perform a simulation study to evaluate the properties of the estimates in the proposed model and apply it to breast cancer incidence data for 5857 Swedish female monozygotic and dizygotic twin pairs from the so-called old cohort of the Swedish Twin Registry. This model is used to estimate the size of the susceptible fraction and the correlation between the frailties of the twin partners. Possible extensions, advantages, and limitations of the proposed method are discussed.

Biometry↗

PubMed1991

Screening for frailty: criteria and predictors of outcomes.

OBJECTIVE: To determine the reliability of rapid screening by clinically derived geriatric criteria in predicting outcomes of elderly hospitalized patients. DESIGN: Prospective cohort study of 985 patients screened at the time of hospital admission and followed for 1 year with respect to the outcomes of mortality, hospital readmission, and nursing home utilization. SETTING: Palo Alto Veterans Affairs Medical Center, a tertiary care teaching hospital. SUBJECTS: Male patients 65 years of age and older admitted to the Medical and Surgical services during the period from October 1, 1985 through September 30, 1986. RESULTS: Patients were grouped by specific screening criteria into three groups of increasing frailty: Independent, Frail, and Severely Impaired. Each criterion focused on a geriatric condition and was designed to serve as a marker for frailty. Increasing frailty was significantly correlated with increasing length of hospital stay (P less than 0.0001), nursing home utilization (P less than 0.0001), and mortality (P less than 0.0001). Multivariate analyses revealed that the clinical groups were more predictive of mortality and nursing home utilization than were age or Diagnosis-Related Groups (DRGs). Rehospitalization was unrelated to age, clinical group, or DRG, suggesting that utilization may not be driven by the clinical factors measured in this study. CONCLUSIONS: Rapid clinical screening using specific geriatric criteria is effective in identifying frail older subjects at risk for mortality and nursing home utilization. Our findings suggest that geriatric syndromes are more predictive of adverse outcomes than diagnosis per se. This well operationalized screening process is inexpensive as well as effective and could easily be introduced into other hospital settings.

Activities of Daily Living↗

PubMed1993

Frailty and injuries in later life: the FICSIT trials.

Physical frailty and fall-related injuries present two of the biggest threats to older people's functioning and quality of life. The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) trials represent a set of eight different clinical trials concerning physical frailty and injuries in later life. This report documents the history and organization of the trials and provides an overview of the measures being collected at multiple sites and the analytic strategies to be used for multi-site investigations.

Accidental Falls↗

PubMed2004

Plasma hypertonicity: another marker of frailty?

OBJECTIVES: To determine whether plasma hypertonicity might be a marker of early frailty, this study tested the associations between plasma hypertonicity, incident disability, and mortality in nondisabled older adults. DESIGN: Longitudinal, observational study. SETTING: Community-based. PARTICIPANTS: Older adults (> or =70), who reported no disability and gave blood in the 1992 Duke Established Populations for Epidemiologic Studies of the Elderly survey (n=705), were re-interviewed in 1996 for functional status (n=561) and followed for all deaths up to January 1, 2000. MEASUREMENTS: Plasma tonicity was estimated from plasma glucose, sodium, and potassium measures and used to classify subjects as normo- (285-294 mOsm/L) or hypertonic (> or =300 mOsm/L). Disability was defined as any impairment on the Rosow-Breslau, activity of daily living (ADL), and instrumental activity of daily living (IADL) scales. The relative risk (RR) of any new disability and relative hazard of death associated with hypertonicity were estimated using logistic regression models and Cox proportional hazards models, respectively. All models were controlled for age, sex, race, weight status, current smoking, activity level, plasma blood urea nitrogen and creatinine, cognitive impairment, depression, and chronic disease status. To determine whether observed effects were attributable to plasma glucose alone, all models were repeated on a subsample of nondiabetic, normoglycemic subjects. RESULTS: Plasma hypertonicity (observed in 15% of subjects) was associated with increased risk of new Rosow-Breslau (RR=2.1, 95% confidence interval (CI)=1.2-3.6), IADL (RR=2.3, 95% CI=1.2-4.3), and ADL (RR=2.7 95% CI=1.3-5.6) disability by 1996 and mortality by 2000 (RR=1.4, 95% CI=1.0-1.9). Results were similar for the normoglycemic subgroup (ADL: RR=2.9, 95% CI=1.0-8.0; IADL: RR=2.5, 95% CI=1.0-6.3; Rosow-Breslau: RR=1.8, 95% CI=0.8-3.9; mortality: RR=1.5, 95% CI=0.9-2.3). CONCLUSION: Plasma hypertonicity may be a marker of early frailty. It was prevalent in this sample of nondisabled community-dwelling older adults and predicted incident disability and mortality. Further research to identify its determinants and consequences may help inform interventions against frailty.

Activities of Daily Living↗

PubMed2005

From bedside to bench: research agenda for frailty.

The American Geriatrics Society sponsored a working conference in January 2004, funded by the National Institute on Aging, to establish the state of the art in frailty research and to set a research agenda for the future. The invited participants included senior basic biologists, epidemiologists, geneticists, and clinical investigators who study aging-related issues. This article summarizes the central theoretical observations on frailty and research needs and opportunities presented and discussed at this conference, and lays out an agenda for future research on frailty.

Aged↗

PubMed2005

Fecal microbiota composition and frailty.

The relationship between fecal microbiota composition and frailty in the elderly was studied. Fecal samples from volunteers with high frailty scores showed a significant reduction in the number of lactobacilli (26-fold). At much higher population levels, both the Bacteroides/Prevotella (threefold) and the Faecalibacterium prausnitzii (fourfold) groups showed a significant reduction in percentage of total number of hybridizable bacteria in the elderly with high frailty scores. In contrast to this, the number of Enterobacteriaceae was significantly higher (sevenfold) in samples from very frail volunteers.

Aged↗

PubMed2002

Sarcopenia, weight loss, and nutritional frailty in the elderly.

The progression of the aging process leads to a decreased margin of homeostatic reserve and a reduced ability to accommodate metabolic challenges, including nutritional stress. Nutritional frailty refers to the disability that occurs in old age owing to rapid, unintentional loss of body weight and loss of lean body mass (sarcopenia). Sarcopenia, a loss of muscle mass and strength, contributes to functional impairment. Weight loss is commonly due to a reduction in food intake; its possible etiology includes a host of physiological and nonphysiological causes. The release of cytokines during chronic disease may also be an important determinant of frailty. In addition to being anorectic, cytokines also contribute to lipolysis, muscle protein breakdown, and nitrogen loss. Whereas the multiple causes of nutritional frailty are not completely understood, clinical interventions for weight loss, sarcopenia, and cytokine alterations have been used with modest success.

Aged↗

PubMed1994

Effects of frailty in survival analysis.

Unobserved individual heterogeneity, also called frailty, is a major concern in the application of survival analysis. Hazard rates do not give direct information on the change over time in the individual risk, but are strongly influenced by selection effects operating in the population. The individuals surviving up to a certain time will on average be less frail than the original population. Models are reviewed that account for this phenomenon, and some medical examples are discussed. It is emphasized that the frailty phenomenon may be modelled in many different ways, and a stochastic process approach is discussed as an alternative to the common proportional frailty model.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Analysis of rabbit doe longevity using a semiparametric log-Normal animal frailty model with time-dependent covariates.

Data on doe longevity in a rabbit population were analysed using a semiparametric log-Normal animal frailty model. Longevity was defined as the time from the first positive pregnancy test to death or culling due to pathological problems. Does culled for other reasons had right censored records of longevity. The model included time dependent covariates associated with year by season, the interaction between physiological state and the number of young born alive, and between order of positive pregnancy test and physiological state. The model also included an additive genetic effect and a residual in log frailty. Properties of marginal posterior distributions of specific parameters were inferred from a full Bayesian analysis using Gibbs sampling. All of the fully conditional posterior distributions defining a Gibbs sampler were easy to sample from, either directly or using adaptive rejection sampling. The marginal posterior mean estimates of the additive genetic variance and of the residual variance in log frailty were 0.247 and 0.690.

Animals↗

PubMed2002

Frailty and education in the Hispanic Health and Nutrition Examination Survey.

This study tests for the presence of education-frailty correlations among 1,176 Mexican Americans, 522 Cuban Americans, and 560 Puerto Ricans, 50 years and older, in the Hispanic Health and Nutrition Examination Survey. Hispanics with the least schooling (less than 7 years) were found to have the highest frailty rates, and those with the most (more than 12 years of schooling) were found to have the lowest frailty rates. Similar, but somewhat weaker, correlations were discovered after a measure of self-efficacy was accounted for.

Activities of Daily Living↗

PubMed2000

Frailty, family, and church support among urban African American elderly.

A community-based survey of 507 African Americans aged 60 and older from South Central Los Angeles was conducted to estimate the prevalence of frailty and describe the correlation between frailty, social support from family and church, and use of community services. Persons were considered frail if they met criteria for any of four conditions: functional impairment, depression, urinary incontinence, falls. Sixty-seven percent met criteria for frailty. Analyses revealed that frail elderly were significantly less likely to report feeling very close to family. Family contact, feeling that church was important, and receiving church support were similar for the frail and nonfrail. Frail elderly were more likely to use community services. These findings suggest that frail elderly in this population may not receive more support from family and church than nonfrail elderly. There is a need for caution when assuming families and churches in urban African American communities are able to support the most vulnerable elderly.

Activities of Daily Living↗

PubMed2004

The heritability of breast cancer: a Bayesian correlated frailty model applied to Swedish twins data.

The aim of this study was to investigate the role of genes and environment in susceptibility to breast cancer and to give an estimate of heritability in the propensity to develop the disease. To do this we applied an interdisciplinary approach, merging models developed in the field of demography and survival analysis - so-called frailty models - and models coming from quantitative genetics and epidemiology, namely genetic models. In our study, the inferential problem was solved in a Bayesian framework and the numerical work was carried out using MCMC methods. We used the special information coming from twin data, particularly breast cancer data, from the Swedish Twin Register. The application of a correlated log-normal frailty model leads to a very large estimate of the population heterogeneity (sigma = 6.7), and relatively small correlations between co-twins' frailties - around 0.3 for monozygotic and 0.1 for dizygotic twins. Comparing three different genetic models (an ACE, an AE and an ADE model), we furthermore concluded that genetic effects would explain globally almost 30% of the total variability of propensity to breast cancer. Environmental effects would be predominant in determining breast cancer susceptibility and these effects would be primarily individual-specific, that is, non-shared effects. Finally, a model which includes dominance genetic effects (ADE model) is preferred for genetic and statistical reasons.

Bayes Theorem↗

PubMed1999

[Methodology for analyzing censored correlated data: application of marginal and frailty approaches in human genetics. The European Community Alport Syndrome Concerted Action Group (ECASCA)].

BACKGROUND: Statistical analysis for correlated censored data allows to study censored events in clustered structure designs. Considering a possible correlation among failure times of the same group, standard methodology is no longer applicable. We investigated proposed models in this context to study familial data about a genetic disease, Alport syndrome. Alport syndrome is a severe hereditary disease due to abnormal collagenous chains. Renal failure is the main symptom of the disease. It progresses toward end-stage renal failure (IRT) according to a high time variability. As shown by genetic studies, mutations of COL4A5 gene are involved in the X-linked Alport Syndrome. Due to the large range of the mutation types, the aim of this study was to search for a possible genetic origin of the heterogeneity of the disease severity. METHODS: Marginal survival models and mixed effects survival models (so-called frailty models) were proposed to take into account the possible non independence of the observations. In this study, time until end-stage renal failure is a rightly censored end point. Possible intra-familial correlations due to shared environmental and/or genetic factors could induce dependence among familial failure times. In this paper, we fit marginal and frailty proportional hazards models to evaluate the effect of mutation type on the risk of IRT and an interfamilial heterogeneity of failure times. RESULTS: In this study, the use of these models allows to show the presence of an interfamilial heterogeneity of the failure times to IRT. Moreover, the results suggest that some mutation types are linked to a higher risk of fast evolution to IRT, which explains partially the interfamilial heterogeneity of the failure times. CONCLUSIONS: This paper shows the interest of marginal and frailty models to evaluate the heterogeneity of censored responses and to study relationships between a censored criterion and covariables. This study puts forward the importance of characterizing the mutation at a molecular level to understand the relationship between genotype and phenotype.

Data Interpretation, Statistical↗

PubMed2000

Frailty modelling for adult and old age mortality: the application of a modified DeMoivre hazard function to sex differentials in mortality.

Unobserved differences in individual's susceptibility to death are an important aspect in the analysis of contemporary mortality patterns. However, observed mortality rates at adult ages, which are usually well described by a Gompertz curve, are often perceived inconsistent with frailty models of mortality. The authors therefore propose a modified DeMoivre hazard function that is suitable for the application of frailty models to adult and old ages. The proposed hazard increases faster than exponential, and when combined with unobserved frailty it can capture a broad range of patterns encountered in the analysis of adult mortality. The authors' application to Bulgaria during 1992-93 suggests that the stronger selection process in the male population, caused by an overall higher level of mortality, may constitute a primary mechanism leading to the convergence of male and female mortality at higher ages. Hence, the convergence between male and female mortality is not necessarily caused by differential process of aging across sexes, but is merely a consequence of the different levels of mortality at adult ages.

Adult↗

PubMed2005

Assessing sealant retention using a Poisson frailty model.

OBJECTIVE: This paper utilises a Poisson frailty regression model with clustering to report on the failure rates of sealants placed and repaired during a three-year follow-up school-based comprehensive preventive programme. BASIC RESEARCH DESIGN: The programme included annual application/reapplication of light-cured fissure sealants in 210 12-year-old subjects over three years. Sealants placed at the commencement of each year of the programme were assessed for retention 12 months later and repair/reapplication was undertaken at that time for those surfaces judged to require it. An application of a Poisson regression model with random effects ("frailties") and clustering was used in this paper to allow for heterogeneity between subjects. Whilst it appears that the direct utilization of frailty models in determining fissure sealant failure rates has not been reported, it is clearly an appropriate use of this statistical method. A total of 1,544 sealants were placed during the study period. Of these, 1,038 (67.2%) were first placements at baseline and 506 (32.8%) were repairs/reapplications. Of these repairs/reapplications, 206 (40.7%) were performed at first year follow-up and 300 (59.3%) at second year follow-up. RESULTS: The Failure Rate Ratios were statistically significantly greater for second molars cf. first molars (FRR=1.33, p=0.008) and for lower molars cf upper molars (FRR=1.32, p<0.001). Failure rate ratios for sealants placed in the distal occlusal pit and fissures cf. mesial occlusal pit and fissures were significantly higher (FRR=1.33, p<0.001). A significant interaction was found for molar type versus pit and fissure site (p=0.009). There was no significant interaction between molar type and arch. CONCLUSIONS: Sealants placed on second molars, those placed on lower molars and those placed on the distal fissure sites have a higher failure rate. As individual tooth sites in the mouth are not independent, any statistical analysis should allow for these associations when assessing sealant retention.

Adolescent↗