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PubMed2003

Geriatric oncology: a clinical approach to the older patient with cancer.

Due to the ageing of the population and the sharp increase in life expectancy, cancer in the older person has become an increasingly common problem in the Western world. Although several authors have stressed that elderly cancer patients deserve special attention as a target group for research efforts, older aged patients are still less likely to be offered participation in clinical trials. The cellular and molecular mechanisms regulating the physiological process of ageing and senescence are far from understood, although inflammation is likely to play an important role, at least in some cancers. In addition, the relationship between ageing and cancer risk is also far from understood. One of the most intriguing aspects of ageing is how different the ageing process is from person to person; the basis for this variation is largely unknown. Population-based studies and longitudinal surveys have shown that comorbidity and physical and mental functioning are important risk factors; thus, a meaningful assessment of comorbidity and disability should be implemented in clinical practice. Modern geriatrics is targeted towards patients with multiple problems. Such patients are not simply old, but are geriatric patients because of interacting psychosocial and physical problems. As a consequence, the health status of old persons cannot be evaluated by merely describing the single disease, and/or by measuring the response, or survival after treatment. Conversely, it is necessary to conduct a more comprehensive investigation of the 'functional status' of the aged person. A geriatric consultation provides a variety of relevant information and enables the healthcare team to manage the complexity of health care in the elderly; this process is referred to as the Comprehensive Geriatric Assessment (CGA). The use of CGA is now being introduced into oncological practice. The definition of frailty is still controversial and represents a major issue of debate in clinical geriatrics. As the frail population increases, clinical trials in frail persons are needed. The usefulness of these trials requires a consensus as to the definition of frailty. Clearly, the management of older persons with cancer requires the acquisition of special skills in the evaluation of the older person and in the recognition and management of emergencies as well as experience in geriatric case management.

Age Factors↗

PubMed2000

The application of the principles of geriatrics to the management of the older person with cancer.

Is the patient going to die of cancer or with cancer? Is the patient going to suffer pain and disability due to cancer? Is the patient able to tolerate aggressive life-prolonging treatment? This paper tries to reply to the fundamentals of these questions by introducing the multidimensional assessment that evaluates areas where age-related changes are more likely. Chronologic age cannot be used to predict the degree of comorbidity and of functional deterioration of the single individual up to age 85 at least. Assessment of aging includes health, functional status, nutrition, cognition, socio-economic and emotion evaluations. This multidisciplinary assessment is referred to as comprehensive geriatric assessment (CGA). The risk of comorbid conditions increases with age and may result in underdiagnosis: in older patients, new symptoms may not be clearly recognized by the patient and may be dismissed by practitioners as manifestations of preexisting conditions. A meaningful assessment of comorbidity may be obtained with a comorbidity index. The Charlson scale and the Chronic Illness Rating Scale - Geriatric (CIRS-G), have enjoyed the widest acceptance. The Instrumental Activities of Daily Living (IADL) and the Activities of Daily Living (ADL) are the most sensitive assessment of function in older individuals. IADLs include shopping, managing finances, housekeeping, laundry, meal preparation, ability to use transportation and telephone and ability to take medications: in simple words, the IADLs are those skills a person needs to live independently. ADLs include feeding, grooming, transferring, toileting and are the skills necessary for basic living. Though a correlation exists among comorbidity, performance status, ADL and IADL, this correlation is not strong enough to be reflected in a single parameter. The Folstein Mini Mental Status (MMS), is the instrument of most frequent use to screen older individuals for dementia. The main problem with the MMS is lack of sensitivity to early stages of dementia. The Geriatric Depression Scale (GDS), a simple tool that can be completed by most patients at home, doubles the rate of detection of depression. The Mini Nutritional assessment is very sensitive to screen older persons for malnutrition. The risk of polypharmacy increases with age and partly results from the fact that older patients visit different practitioners. A CGA should also include evaluation of the so called Geriatric Syndromes like delirium, incontinence, osteoporosis, all of which represent a hallmark of frailty. The CGA may help the management of older individuals with cancer in at least three areas: detection of frailty, treatment of unsuspected conditions, removal of social barrier to treatment.

Aged↗

PubMed2006

Associations between somatic cell counts at calving or prior to drying-off and clinical mastitis in the remaining or subsequent lactation.

Data from 350 herds enrolled in the Norwegian Dairy Herd Recording System (NDHRS) were used to investigate the associations between the first two cow-milk somatic cell counts (SCC) test-days' results after calving or the three last SCC test-days prior to drying off in the first lactation and the hazard ratio (HR) of clinical mastitis (CM) during the remaining first or the subsequent second lactation respectively. Altogether, 9519 first lactations and 6046 second lactations were included. Cox regression analyses adjusted for herd frailty effect were used. In the first lactation, SCC>40000 cells/ml on the first or second test-day was significantly associated with an increased risk of a CM event in the remaining first lactation. HR, compared with 10000 cells/ml, increased from 1.6 (1.4) for SCC of 40000-60000 cells/ml to 6.9 (4.2) for SCC >800000 cells/ml, when using the first (second) SCC test-day in the first lactation. Cows with a geometric mean of the three last SCC test-days between 50000 and 100000 cells/ml and between 401000 and 800000 cells/ml in the first lactation had HR of CM during the second lactation of 1.3 and 2.8 respectively compared with a reference group of 10000-20000 cells/ml. If a CM episode in the first lactation occurred, the HR for having a CM event during the second lactation was 1.5. There was a significant frailty effect which disappeared if the incidence rate of CM at herd level was included in the model.

Animals↗

PubMed2026

Adolescent depression as a systemic multimorbidity catalyst: integrated genetic and metabolic pathway analysis.

BACKGROUND: Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied. METHODS: A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers. RESULTS: Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18-1.42]), diabetes (HR = 1.25 [1.13-1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50-2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03-2.05]), diabetes (OR = 1.01 [1.01-1.02]) and COPD (OR = 1.04 [1.02-1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions. CONCLUSIONS: Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.

Humans↗

PubMed2004

Estimating marginal effects in accelerated failure time models for serial sojourn times among repeated events.

Recurrent event data are commonly encountered in longitudinal studies when events occur repeatedly over time for each study subject. An accelerated failure time (AFT) model on the sojourn time between recurrent events is considered in this article. This model assumes that the covariate effect and the subject-specific frailty are additive on the logarithm of sojourn time, and the covariate effect maintains the same over distinct episodes, while the distributions of the frailty and the random error in the model are unspecified. With the ordinal nature of recurrent events, two scale transformations of the sojourn times are derived to construct semiparametric methods of log-rank type for estimating the marginal covariate effects in the model. The proposed estimation approaches/inference procedures also can be extended to the bivariate events, which alternate themselves over time. Examples and comparisons are presented to illustrate the performance of the proposed methods.

Age of Onset↗

PubMed2004

Modelling converging hazards in survival analysis.

The Cox proportional hazards model has become the standard model for survival analysis. It is often seen as the null model in that "... explicit excuses are now needed to use different models" (Keiding, Proceedings of the XIXth International Biometric Conference, Cape Town, 1998). However, converging hazards also occur frequently in survival analysis. The Burr model, which may be derived as the marginal from a gamma frailty model, is one commonly used tool to model converging hazards. We outline this approach and introduce a mixed model which extends the Burr model and allows for both proportional and converging hazards. Although a semi-parametric model in its own right, we demonstrate how the mixed model can be derived via a gamma frailty interpretation, suggesting an E-M fitting procedure. We illustrate the modelling techniques using data on survival of hospice patients.

Algorithms↗

PubMed2002

Caries risk analysis: considering caries as an individual time-dependent process.

AIM: To estimate the probability that a tooth does not develop a cavitated lesion (= end-stage caries) within time periods of interest. Additionally it was of interest to assess the heterogeneity between patients, in relation to the time periods required for their teeth to develop a cavitated lesion. DESIGN: A prospective study using patient data of a clinical pedodontic course. SAMPLE AND METHODS: Forty-one patients who had been followed for at least 3 years were selected. Before initiation of therapy, affiliation to a specific risk group was checked. Nine individuals who had belonged to a high-risk group on test were excluded. Of 1968 teeth, 1378 were eligible for data evaluation. The statistical techniques applied originate from time-to-event analysis methods, including a parametric frailty approach providing estimates of the relative caries risk for each individual to develop a cavitated lesion. RESULTS: In the selected group of patients the probability that a tooth remained free of a cavitated lesion within five years ranged from 0.89 to 0.95 applying a 95% confidence interval. In the present sample the true caries risk of the patients to develop a cavitated lesion varied considerably although such variation was not expected from the individual examinations at baseline. CONCLUSION: The frailty model accounts sufficiently for the heterogeneity of each patient. The applied time-to-event methods facilitated reliable estimation of both the probability that a tooth remains free of a cavitated lesion within a certain time and the relative caries risk of an individual to develop a cavitated lesion.

Child↗

PubMed2002

Profiles of older medicare decedents.

OBJECTIVES: To evaluate the usefulness of a clinical scheme to classify older decedents to better understand the issues associated with healthcare use and costs in the last year of life. DESIGN: We analyzed Medicare claims data for a random sample of 0.1% of all Medicare beneficiaries with expenditures between 1993 and 1998. This sample yielded 7,966 deaths. SETTING: Medicare claims data. PARTICIPANTS: Medicare beneficiaries. MEASUREMENTS: We classified decedents into groups representing four trajectories at the end of life: sudden death, terminal illness, organ failure, and frailty. RESULTS: Ninety-two percent of decedents were captured by the profiling strategy. The four trajectory groups had distinct patterns of demographics, care delivery, and Medicare expenditures. Frailty was a dominant pattern, with 47% of all decedents, whereas sudden death claimed only 7%; cancer claimed 22%, and organ system failure, 16%. CONCLUSIONS: The clinical scheme to classify decedents appears to fit most decedents and to form groups with substantial clinical differences. Acknowledging the differences among these groups may be a fruitful way to evaluate expenditures and develop strategies to improve care at the end of life.

Aged↗

PubMed2002

A program to prevent functional decline in physically frail, elderly persons who live at home.

BACKGROUND: Functional decline in physically frail, elderly persons is associated with substantial morbidity. It is uncertain whether such functional decline can be prevented. METHODS: We randomly assigned 188 persons 75 years of age or older who were physically frail and living at home to undergo a six-month, home-based intervention program that included physical therapy and that focused primarily on improving underlying impairments in physical abilities, including balance, muscle strength, ability to transfer from one position to another, and mobility, or to undergo an educational program (as a control). The primary outcome was the change between base line and 3, 7, and 12 months in the score on a disability scale based on eight activities of daily living: walking, bathing, upper- and lower-body dressing, transferring from a chair, using the toilet, eating, and grooming. Scores on the scale ranged from 0 to 16, with higher scores indicating more severe disability. RESULTS: Participants in the intervention group had less functional decline over time, according to their disability scores, than participants in the control group. The disability scores in the intervention and control groups were 2.3 and 2.8, respectively, at base line; 2.0 and 3.6 at 7 months (P=0.008 for the comparison between the groups in the change from base line); and 2.7 and 4.2 at 12 months (P=0.02). The benefit of the intervention was observed among participants with moderate frailty but not those with severe frailty. The frequency of admission to a nursing home did not differ significantly between the intervention group and the control group (14 percent and 19 percent, respectively; P=0.37). CONCLUSIONS: A home-based program targeting underlying impairments in physical abilities can reduce the progression of functional decline among physically frail, elderly persons who live at home.

Accidental Falls↗

PubMed2002

The aging baboon: comparative demography in a non-human primate.

Why do closely related primate genera vary in longevity, and what does this teach us about human aging? Life tables of female baboons (Papio hamadryas) in two wild populations of East Africa and in a large captive population in San Antonio, Texas, provide striking similarities and contrasts to human mortality patterns. For captive baboons at the Southwest Foundation for Biomedical Research, we estimate the doubling time of adult mortality rate as 4.8 years. Wild females in free-living populations in Tanzania and in Kenya showed doubling times of 3.5 and 3.8 years, respectively. Although these values are considerably faster than the estimates of 7-8 years for humans, these primates share a demographic feature of human aging: within each taxon populations primarily vary in the level of Gompertz mortality intercept (frailty) and vary little in the demographic rate of aging. Environmental and genetic factors within taxa appear to affect the level of frailty underlying senescence. In contrast, primate taxa are differentiated by rates of demographic aging, even if they cannot be characterized by species-specific lifespan.

Aging↗

PubMed1995

Speech technology in the year 2001.

This paper introduces the session "Technology in the Year 2001" and is the first of four papers dealing with the future of human-machine communication by voice. In looking to the future it is important to recognize both the difficulties of technological forecasting and the frailties of the technology as it exists today--frailties that are manifestations of our limited scientific understanding of human cognition. The technology to realize truly advanced applications does not yet exist and cannot be supported by our presently incomplete science of speech. To achieve this long-term goal, the authors advocate a fundamental research program using a cybernetic approach substantially different from more conventional synthetic approaches. In a cybernetic approach, feedback control systems will allow a machine to adapt to a linguistically rich environment using reinforcement learning.

Computers↗

PubMedDate not supplied

Individual aging and mortality rate: how are they related?

Many researchers working in the area of aging and longevity base their conclusions on the behavior of empirical age trajectories of mortality rates. In such analyses, changes in the slope of the logarithm of the mortality curve are often associated with changes in the rate of individual aging. We show that such interpretation may be incorrect: the changes in the slope of this curve do not necessarily correspond to the changes in the rate of individual aging. We use three models of mortality and aging to illustrate this statement. The first one is based on the idea of frailty. We show that changes in frailty distribution alone may be responsible for changes in the slope. The second model exploits the idea of saving lives. It evaluates changes in mortality rate after elimination of lethal stressful events. The third model uses the idea of Strehler and Mildvan (1960). It shows that changes in the rate of individual aging may take place without changes in the slope of the logarithm of the mortality curve.

Aging↗

PubMed2004

Lower levels of serum albumin and total cholesterol and future decline in functional performance in older persons: the Longitudinal Aging Study Amsterdam.

BACKGROUND: Both serum albumin and total cholesterol are potential markers of frailty. A decline in functional status is one of the key components of frailty. OBJECTIVE: The aim of this study was to investigate the association of serum albumin and total cholesterol, separately and combined, with future decline in functional performance. DESIGN: The Longitudinal Aging Study Amsterdam, an ongoing population-based longitudinal study, started in 1992/1993 with a follow-up every 3 years. PARTICIPANTS: 1,064 men and women aged 55-85 years with complete data on serum albumin and total cholesterol at baseline, and functional performance at baseline and 3-year follow-up. MEASUREMENTS: At baseline, serum albumin and total cholesterol were measured. At baseline and 3 years later, decline in functional status was measured with three performance tests (chair stand, 3-metre walk, putting on and taking off a cardigan). Associations were adjusted for age, life-style and health-related factors. RESULTS: Albumin concentration was not associated with decline in functional performance in men and women. Women with lower serum total cholesterol concentration (</=5.2 mmol/l) were more likely to decline in functional status compared to women with higher serum total cholesterol concentration (reference; OR = 2.50; 95% CI 1.07-5.84). Men with lower serum albumin (</=43 g/l) and lower serum total cholesterol concentration were three times more likely to decline in functional performance compared to men with higher levels (OR = 3.00; 95% CI 1.00-8.97). In women, a similar trend was found (OR = 1.73; 95% CI 0.34-8.94), although not statistically significant. CONCLUSIONS: A combination of low albumin and low cholesterol levels may increase the risk of future functional decline.

Activities of Daily Living↗

PubMed2006

Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission.

BACKGROUND: The prevalence of vitamin D deficiency in nursing home patients is high. OBJECTIVE: We aimed to ascertain whether lower serum 25-hydroxyvitamin D [25(OH)D] concentrations increase the risk of future nursing home admission and early death. DESIGN: We included 1260 independent, community-dwelling persons aged > or =65 y who were participating in the Longitudinal Aging Study Amsterdam (1995-1996). Study outcomes were time to nursing home admission during 6 y of follow-up and time to death until 1 April 2003. RESULTS: Vitamin D deficiency [25(OH)D < 25 nmol/L] and insufficiency [25(OH)D = 25-49.9 nmol/L] were present in 127 (10.1%) and 462 (36.7%) subjects, respectively. During follow-up, 138 subjects (11.0%) were admitted to nursing homes, and 380 subjects (30.2%) died. The risk of nursing home admission for participants with 25(OH)D deficiency was 53 cases per 1000 person-years higher than that for those with high 25(OH)D (> or =75 nmol/L) concentrations (58 compared with 5 cases). After adjustment for potential confounders, the hazard ratio (95% CI) of nursing home admission was 3.48 (1.39, 8.75) for vitamin D-deficient, 2.77 (1.17, 6.55) for vitamin D-insufficient, and 1.92 (0.79, 4.66) for vitamin D-borderline persons as compared with persons with high 25(OH)D (P for trend = 0.002). The results remained after additional adjustment for frailty indicators. Lower 25(OH)D was associated with higher mortality risk, but this association was not significant after adjustment for frailty indicators. CONCLUSION: Lower serum 25(OH)D concentrations in older persons are associated with a greater risk of future nursing home admission and may be associated with mortality.

Aged↗

PubMed2001

Assessment of deaths attributable to air pollution: should we use risk estimates based on time series or on cohort studies?

Epidemiologic studies are crucial to the estimation of numbers of deaths attributable to air pollution. In this paper, the authors present a framework for distinguishing estimates of attributable cases based on time-series studies from those based on cohort studies, the latter being 5-10 times larger. The authors distinguish four categories of death associated with air pollution: A) air pollution increases both the risk of underlying diseases leading to frailty and the short term risk of death among the frail; B) air pollution increases the risk of chronic diseases leading to frailty but is unrelated to timing of death; C) air pollution is unrelated to risk of chronic diseases but short term exposure increases mortality among persons who are frail; and D) neither underlying chronic disease nor the event of death is related to air pollution exposure. Time-series approaches capture deaths from categories A and C, whereas cohort studies assess cases from categories A, B, and C. In addition, years of life lost can only be derived from cohort studies, where time to death is the outcome, while in time-series studies, death is a once-only event (no dimension in time). The authors conclude that time-series analyses underestimate cases of death attributable to air pollution and that assessment of the impact of air pollution on mortality should be based on cohort studies.

Air Pollutants↗

PubMed2005

Risk factors for pelvis fracture in older persons.

From 1996 to 2001, the authors undertook a case-control study of 192 pelvis fracture cases (men and women) and 2,402 controls aged > or = 45 years at five Kaiser Permanente medical centers in Northern California. Most information on potential risk factors was obtained by means of an interviewer-administered questionnaire. Number of fractures since age 45 years and a maternal history of hip fracture were associated with increased risks. Several factors thought to protect against loss of bone mass, including recent use of menopausal hormone therapy (adjusted odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.33, 0.91) and high body mass index (weight (kg)/height (m)2; per 5-unit increase, adjusted OR = 0.65, 95% CI: 0.52, 0.81), were associated with decreased risks, while cigarette smoking (adjusted OR = 2.17, 95% CI: 1.34, 3.52) and hysterectomy (adjusted OR = 1.75, 95% CI: 1.15, 2.66) were associated with increased risks. Various conditions related to propensity to fall were associated with increased risks. Most indicators of frailty, including use of walking aids and needing help with or being unable to perform various activities of daily living, conferred increased risks. Thus, low bone mass, frailty, and probably a propensity to fall appear to be associated with increased risk of pelvis fracture.

Age Factors↗

PubMed2003

Exercise, aging, and muscle protein metabolism.

Age-associated alterations in muscle protein quantity and quality that adversely affect muscle structure, composition, and function have been referred to as sarcopenia. Muscle protein is metabolically active, and the age-associated loss of muscle protein mass is related to a loss of physical function and an inability to perform activities of daily living (physical frailty). It is important to maintain adequate reserves of muscle protein and amino acids as we age. As in all cachectic conditions, sarcopenia can be explained by an imbalance between the rates of muscle protein synthesis and muscle proteolysis, in which net muscle protein balance is negative. This review summarizes evidence that supports the notion that: (a). advancing age and physical frailty are associated with a reduction in the fasting rate of mixed and myosin heavy chain protein synthesis, which contributes to muscle protein wasting in advancing age; (b). this impairment can be corrected because resistance exercise acutely and dramatically increases the rate of muscle protein synthesis in men and women aged 76 years and older; and (c). resistance exercise training maintains a modest increment in the rate of muscle protein synthesis and contributes to muscle hypertrophy and improved muscle strength in frail elderly men and women. The cellular mechanisms responsible for these adaptations, as well as the role of nutrition and hormone replacement in reversing sarcopenia, require further investigation.

Aged↗

PubMed2005

The future (history) of socioeconomic measurement and implications for improving health outcomes among African Americans.

Socioeconomic status (SES) has powerful and complex impacts on health, and understanding the relationship between SES and health is essential for long-term improvements in the health of populations. In addition, in the United States, the impact of SES on health is inextricably intertwined with racial and ethnicity status and the historical development and maintenance of health disparities. Most of the literature documenting this relationship has focused on individual-level socioeconomic factors. There are sound theoretical reasons and some empirical support to suggest that socioeconomic resources at both individual and neighborhood levels have strong influences on health outcomes such as disease, disability, and mortality. However, these relationships have been inadequately examined to date. In this article, the term "ecological SES" will be used to denote SES at geographic group levels. As the United States attempts to achieve the goals of the Department of Health and Human Services' Healthy People 2010 program, understanding ecological SES and its impacts on health will be crucial. We review the theory, some of the empirical evidence, and likely future for the measurement and use of a broader approach to SES and offer a specific research paradigm for examining these issues. We focus in particular on one racial-ethnic group that experiences health disparity, that is, African Americans. We use our ongoing project investigating physical frailty in urban African Americans to illustrate the importance of a multilevel approach to understanding the impacts of socioeconomic resources on health and the potential implications for efforts to prevent or reverse frailty.

Black or African American↗