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PubMed2001

Utilitarianism and the measurement and aggregation of quality--adjusted life years.

It is widely accepted that one of the main objectives of government expenditure on health care is to generate health. Since health is a function of both length of life and quality of life, the quality-adjusted life-year (QALY) has been developed in an attempt to combine the value of these attributes into a single index number. The QALY approach--and particularly the decision rule that health care resources should be allocated so as to maximise the number of QALYs generated--has often been equated with the utilitarian philosophy of maximising 'the greatest happiness of the greatest number'. This paper considers the extent to which the measurement and aggregation of QALYs really is utilitarian by developing a new taxonomy in order to classify utilitarianism and the different aspects of the QALY approach. It is shown that the measurement of QALYs is consistent with a number of different moral positions and that QALYs do not have to be aggregated according to the maximisation rule. Therefore it is inappropriate to necessarily equate QALYs with utilitarianism. It is shown that much turns on what in principle the QALY represents and how in practice it can be operationalised. The paper highlights the category confusion that is often present here and suggests possible avenues for future theoretical and empirical research.

Classification↗
PubMed2005

Maximum longevities of chemically protected and non-protected fishes, reptiles, and amphibians support evolutionary hypotheses of aging.

Evolutionary hypotheses of aging predict that species with low rates of mortality from extrinsic sources, such as predation, should senesce more slowly and have longer maximum life spans than related species with higher rates of extrinsic mortality. We tested this prediction by synthesizing information on maximum body lengths and life spans in captivity of 1193 species of chemically protected (venomous or poisonous) and non-chemically protected fishes, snakes, caudatans (salamanders and newts), and anurans (frogs and toads). In every phylogenetic group maximum longevity was positively correlated with body size and, when size was controlled for statistically, chemically protected species and genera usually had longer maximum life spans than non-protected species. These results reemphasize the importance of life history traits, particularly protection from predation, in the evolution of senescence.

Animals↗
PubMed2000

Longevity and aging of mice from lines divergently selected for body weight for over 90 generations.

We have analysed the differences between longevity and aging process in two lines of mice selected divergently for body weight. As a result of long-term selection, the mice from two lines varied significantly in body weight during their life span. The differences regarded maturation rate, the length of the life time, reproduction performance, and fertility. Females from the light line (L) were fertile for a longer period of time than those from the heavy line (C), while the process of spermatogenesis disappearance started earlier in the light males than in the heavy ones. There were also differences in the relative weight of adrenal glands and histopathological changes connected with the hyperplasia of their spindle cells. The adrenal glands in females from both lines were heavier than in males. A significantly higher percentage of the cortex cell hyperplasia was observed in adrenals of mice from the C line than the L line. The differences were also scored between mice from the selection lines in relation to the length of their life. On average, the L mice lived 30 days longer than the heavy ones. Body weight loss was observed earlier in the old heavy males than the L ones and this was correlated with the earlier mortality in this group of animals.

Adipose Tissue↗
PubMed1995

Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period.

Myotonic dystrophy (DM) is associated with an underlying CTG trinucleotide repeat expansion at a locus on chromosome 19q13.3. We have determined the repeat length in 23 DM patients with varying clinical severity of symptoms and various sizes of repeat amplification. We confirm that as in previous studies there is no strong correlation between repeat length and clinical symptoms but find that the repeat length in peripheral blood cells of patients increases over a time span of five years indicating continuing mitotic instability of the repeat throughout life. Repeat length progression does not appear to be indicative of clinical progression but age probably is. The degree of expansion correlates with the initial repeat size and 50% of the patients with continuing expansions showed clinical progression of their disease symptoms over the five year study period.

Adolescent↗
PubMed1982

Life span study of SPF Fischer 344 male rats fed ad libitum or restricted diets: longevity, growth, lean body mass and disease.

A life-span study was carried out on longevity, pathologic lesions, growth, lean body mass and selected aspects of muscle of barrier-maintained SPF Fischer 344 rats fed either ad libitum (Group A) or 60% of the ad libitum intake (Group R). Food restriction was as effective in prolonging the life of already long-lived SPF rats as previously shown for rats maintained in conventional facilities. Food restriction not only increased the mean length of life but also acted to extend life span since more than 60% of the Group R rats lived longer than the longest lived Group A rat. Renal lesions occurred at an earlier age in Group A rats than in Group R rats and progressed more rapidly. Death of most Group A rats was associated with severe renal lesions while few Group R rats showed such lesions at death. Food restriction was also found to delay or prevent interstitial cell tumors of the testes, bile duct hyperplasia, myocardial fibrosis and myocardial degeneration. Gastrocnemius muscle mass declined in advanced age and food restriction delayed this decline. Interestingly, however, lean body mass did not progressively decline with increasing age but rather decline occurred only after the onset of the terminal disease process.

Aging↗
PubMed2006

[The combination of "Careworks" insurance plan integrated with medical and long-term care insurance].

The social security system in Japan was greatly revolutionized when the long-term care insurance plan began in April 2000. Thus, Japan began the 21st century with two great social insurance plans, that is, medical care insurance and long-term care insurance. Each delivery system is divided: the medical care insurance plan is for the acute stage, and the long-term care is for the chronic stage. Both systems can be intended to cooperate to provide continuous care throughout life. The public health and welfare system has been trying hard to efficiently integrate the medical and long-term care insurance plans. However, it is necessary to establish a new insurance plan for ensuring the integrated adequacy of both insurance systems. One's life is destined to shift from medical care to long-term care at some point. As one ages or becomes disabled, it becomes difficult to lead an independent life with self-decision, and social support become necessary from third parties, instead of from the family or from one's own means. The society imposes the responsibility of payment of the medical and long-term care plan premiums on the individual throughout life. However, the structure of these insurance foundations should be combined under an integrated system, "Careworks", in order to also combine the concepts of length of life from the medicine and the respect of living from the long-term case to improve the social security of the life.

Aged↗
PubMed1979

Quantitative analysis of mating behavior in aging male Drosophila melanogaster.

Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.

Aging↗
PubMed1999

The concept of quality of life of dying persons in the context of health care.

Considerable research has addressed quality of life and quality of care; however, it has not addressed adequately the experiences of patients and their families at the end of life. Health care may have a greater effect on quality of life during the dying process than it normally does. Building on research and expert review, a conceptual framework is presented that specifies and integrates quality of life and quality of health care indicators. Five main concepts include patient/family context, structure of care, process of care, satisfaction with care, and quality and length of life. Patient and family perspectives are considered. The framework emphasizes quality of life, thus detailed definitions of each quality of life domain are provided. The goal is to facilitate development of a comprehensive set of measures to describe the quality of life of dying persons and evaluate the care they receive, to be used to improve end-of-life care.

Attitude to Death↗
PubMed1986

Physical activity, all-cause mortality, and longevity of college alumni.

We examined the physical activity and other life-style characteristics of 16,936 Harvard alumni, aged 35 to 74, for relations to rates of mortality from all causes and for influences on length of life. A total of 1413 alumni died during 12 to 16 years of follow-up (1962 to 1978). Exercise reported as walking, stair climbing, and sports play related inversely to total mortality, primarily to death due to cardiovascular or respiratory causes. Death rates declined steadily as energy expended on such activity increased from less than 500 to 3500 kcal per week, beyond which rates increased slightly. Rates were one quarter to one third lower among alumni expending 2000 or more kcal during exercise per week than among less active men. With or without consideration of hypertension, cigarette smoking, extremes or gains in body weight, or early parental death, alumni mortality rates were significantly lower among the physically active. Relative risks of death for individuals were highest among cigarette smokers and men with hypertension, and attributable risks in the community were highest among smokers and sedentary men. By the age of 80, the amount of additional life attributable to adequate exercise, as compared with sedentariness, was one to more than two years.

Adult↗
PubMed1985

Dietary habits and the prediction of life span of rats: a prospective test.

A multivariable statistical model for predicting the duration of life of rats permitted to select their own diets was evaluated prospectively. With information relating to pre-adult dietary habits and growth responses, the predicted length of life for an individual closely matched the observed life span; the average absolute error was 11%. This suggests that, even under normal feeding conditions, the diet/growth history is an important factor bearing on death rate. In general, an early adult death age is associated with a high food intake prior to adulthood particularly when coupled with a high efficiency of food utilization during the post-puberty period, a rapid growth rate and early attainment of mature weight. Deviations from this pattern serve to increase the duration of life of the individual.

Animals↗
PubMed2001

C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p.

An important quest in modern biology is to identify genes involved in aging. Model organisms such as the nematode Caenorhabditis elegans are particularly useful in this regard. The C. elegans genome has been sequenced [1], and single gene mutations that extend adult life span have been identified [2]. Among these longevity-controlling loci are four apparently unrelated genes that belong to the clk family. In mammals, telomere length and structure can influence cellular, and possibly organismal, aging. Here, we show that clk-2 encodes a regulator of telomere length in C. elegans.

Aging↗
PubMed2005

Does ICU length of stay influence quality of life?

BACKGROUND: Patients with prolonged stay in the intensive care unit (ICU) use a disproportionate share of resources. However, it is not known if such treatment results in impaired quality of life (QOL) as compared to patients with a short length of stay (LOS) when taking into account the initial severity of illness. METHODS: Prospective, observational case-control study in a university hospital surgical and trauma adult ICU. All patients admitted to the ICU during a 1-year period were included. Patients with a cumulative LOS in the ICU > 7 days, surviving up to 1 year after ICU admission and consenting were identified (group L, n = 75) and matched to individuals with a shorter stay (group S). Matching criteria were diagnostic group and severity of illness. Health-related quality of life (HRQOL) was assessed 1 year after admission using the short-form 36 (SF-36) and was compared between groups and to the general population. Further, overall QOL was estimated using a visual analogue scale (VAS) and willingness to consent to future intensive care, and was compared between groups L and S. RESULTS: Based on ANCOVA, a significant difference between groups L and S was noted for two out of eight scales: role physical (P = 0.033) and vitality (P = 0.041). No differences were found for the physical component summary (P = 0.065), the mental component summary (P = 0.267) or the VAS (P = 0.316). Further, there was no difference in expectation to consent to future intensive care (P = 0.149). As compared to the general population, we found similar scores for the mental component summary and for three of eight scales in group L and five of eight scales in group S. CONCLUSIONS: When taking into account severity of illness, HRQOL 1 year after intensive care is comparable between patients with a short and a long LOS in the ICU. Thus, prolonged stay in the ICU per se must not be taken as an indicator of future poorer HRQOL. However, as compared to the general population, significant differences, mostly in physical aspects of QOL, were found for both groups of patients.

Aged↗
PubMed2003

Comparative physical and pharmacologic characteristics of iodine-131 and yttrium-90: implications for radioimmunotherapy for patients with non-Hodgkin's lymphoma.

Radioimmunotherapy (RIT) is a promising new treatment option for patients with relapsed/refractory non-Hodgkin's lymphoma. Clinical trials have demonstrated that both iodine-131 (131I) and yttrium-90 (90Y) are suitable radionuclides for RIT. Iodine-131 and 90Y differ markedly in their physical properties including half-life, path length, type of energy emissions, intracellular stability, and the organs targeted by the free radionuclide. Both radionuclides can be safely administered in the outpatient setting under current Nuclear Regulatory Commission guidelines. Potential advantages of 131I for RIT include availability, stable chemistry, longer half-life, and an emission spectrum that allows for dosimetric studies and therapy with the same immunoconjugate. By contrast, 90Y has a longer path length and superior intracellular stability compared with 131I. Yttrium-90 may therefore be preferable to 131I for patients with bulky disease, poorly vascularized solid tumors, or when targeting internalized antigens. Although 90Y emits no gamma photon, dosimetry studies for 90Y RIT can be performed using a surrogate radionuclide such as indium-111. Both 131I- and 90Y-labeled anti-CD20 antibodies have demonstrated efficacy in treating relapsed/refractory non-Hodgkin's lymphoma. Further studies are needed, however, to determine if the differences in the pharmacology of 131I and 90Y are clinically relevant.

Biological Availability↗
PubMed2002

Assessment of patient preferences: integrating treatments and outcomes.

OBJECTIVES: The purpose of this study was to develop a patient-centered measure of treatment preference applicable across a range of diseases and treatment decisions. METHODS: Instrument development was based on previous research supplemented by open-ended interviews and focus groups. Psychometric properties of the instrument were determined by administration to 125 persons aged 60 or older with a limited life expectancy secondary to congestive heart failure, chronic obstructive pulmonary disease, or cancer. Test-retest and inter-rater reliability were established using intraclass correlation coefficients. Construct validity was established by examining associations of the measure with a single-item question regarding treatment goals and with age, ethnicity, and functional impairment, characteristics known to be associated with preferences. The Willingness to Accept Life-Sustaining Treatment instrument (WALT) consists of 6 scenarios in which respondents weigh treatment burden against treatment outcomes expressed in terms of the likelihood of different health states and length of life following treatment. RESULTS: Inter-rater reliability ranged from .73 to .95 and test-retest reliability from .49 to .93. WALT scores were significantly associated with a simpler measure of preference and with age, ethnicity, and functional impairment. CONCLUSIONS: The WALT measures patients' treatment preferences, assessed in the context of treatment burden and multiple aspects of treatment outcome with sound psychometric properties.

Aged↗
PubMed1996

Differentials in active life expectancy in the older population of the United States.

This study clarifies the process by which mortality and disability interact to determine differences in active life expectancy by age, sex, race, and education for the U.S. population 70 years of age and over. The analysis is performed using data from the Longitudinal Study of Aging and multistate life tables constructed using the results of hazard models. Women spend more years than men both active and inactive at every age; however, the proportion of life that is expected to be active is smaller for women. These differences are largely due to mortality differences favoring women. Persons with less than a high school education have shorter total and active life expectancies but similar expected lengths of inactive life compared to those with more than a high school education. There are no significant race differences in total life expectancy for race-education groups of the older population; but Blacks have lower expected active life than non-Blacks because of worse functioning.

Age Factors↗
PubMed1998

Arch length changes from 6 weeks to 45 years.

The purpose of this study was to evaluate, on a longitudinal basis, changes in maxillary and mandibular arch length over a 45-year period. Subjects were drawn from two pools of normal individuals. Twenty-eight male and 33 female infants were evaluated longitudinally at 6 weeks, 1 year, and 2 years (before the eruption of the deciduous dentition). Fifteen males and 15 females from the Iowa Facial Growth Study were evaluated at 3, 5, 8, 13, 26, and 45 years. Arch length measurements were obtained independently by two investigators. Intra- and interexaminer reliabilities were predetermined at 0.25 and 0.5 mm, respectively. The greatest incremental increases occurred during the first two years of life. Arch length continued to increase until 13 years in the maxillary arch, and until 8 in the mandibular. Then significant and consistent decreases occurred in both arches mesial to the permanent first molars.

Adolescent↗
PubMed1985

Survival in trisomy 18. Life tables for use in genetic counselling and clinical paediatrics.

Clinical management of neonates with Trisomy 18 depends on a knowledge of life expectancy. True estimates of potential life span are required for genetic counselling purposes when parents interpret the genetic threat, not only in terms of the mathematical odds involved, but also in terms of the quality and length of life of an affected infant, should such be born. This paper reports the findings from a study to generate life tables for Trisomy 18. This study is a total population study over 10 years based on a primary population of 2.2 million. Forty-eight cases of Trisomy 18 were identified, five at amniocentesis. Four of the 43 clinical cases (9%) were mosaics. The median life expectancy for live-born infants was five days (range one hour to 18 months). Mean age at death was 48 days. Life tables, by sex and by sub-types (associated congenital abnormalities) are presented. The annual incidence is 14 per 100,000 total births, with a prevalence estimate of 0.06 per 100,000 total population.

Chromosomes, Human, 4-5↗
PubMed2003

[Analysis of growth model in vestibular aqueduct during human fetal development].

OBJECTIVE: To characterize the growth of the developing vestibular aqueduct in order to gain a better understanding of the possible origins of enlarged vestibular aqueduct. METHODS: Serial sections from 32 temporal bones for every other week from human embryos ranging in age from 6 to 38 weeks were studied with 3DMed medical image analysis software. The internal, external aperture, midpoint diameter and length vestibular aqueduct were analyzed with regression analysis to obtain a growth curve. RESULTS: The internal aperture of vestibular aqueduct was began to form at 6 weeks' gestation. It grew to reach the posterior surface of the petrous bone in the posterior cranial fossa by 10 weeks' gestation. All width parameter mean value in our embryos nerve reached the maximum average width in the adult. Statistical analysis showed that the vestibular aqueduct grew in a nonlinear continuous fashion and instability trend throughout embryonic life, except length parameter. CONCLUSION: The vestibular aqueduct grows in a nonlinear fashion throughout embryonic life. The widest aqueduct measured in embryonic life does not reach the maximum average width in the adult. These results suggest that it would be possible for vestibular aqueduct to develop postnatally.

Anthropometry↗