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PubMed1998

Relationship between pharmacokinetic half-life and pharmacodynamic half-life in effect-time modeling.

A pharmacodynamic parameter relating time-dependent changes of the effect with time-dependent changes of concentrations has yet to be developed. In pharmacokinetics, half-lives (T1/2kin) are used to describe the relation between concentration (C) and time (t). In pharmacodynamics, often the sigmoid Emax model and the Hill equation are used (E = Emax CH/(EC50H + CH)) to describe the relation between effect (E) and concentration (C). To describe the correlation between effect (E) and time (t), a pharmacodynamic half-life (T1/2dyn) could be estimated if the use of the term half-life is not restricted only to log-linear first order processes. To bisect the drug effect a variable time (t1-2 = t2-t1) will be required for this nonlinear process. The bisection of the effect (E2 = 1/2 E1) is associated with a decrease in concentrations (C2 = C1 exp(-0.693 t1-2/T1/2kin)). A mathematical relationship can be derived between pharmacodynamic half-life (T1/2dyn = t1-2) and pharmacokinetic half-life (T1/2dyn = T1/2kin (ln (1 + ln(a)/ln(2))/H ) with (a = (EC50H + C1H)/(EC50H + C2H)). For concentrations in the range of the EC50 value with the Hill coefficient (H = 1), the pharmacodynamic half-life will be 1.6-2.0 times the kinetic half-life (T1/2dyn < or = 2.0 T1/2kin). For high concentrations (C1 > EC50), the dynamic half-life will grow much longer than the kinetic half-life, consequently the effect of a drug will not increase but it will last longer. The pharmacodynamic half-life turns out to be a specific estimate for the effect time relation, being a concentration-dependent function of the kinetic half-life.

Dose-Response Relationship, Drug↗
PubMed2006

The value of life and the value of life extension.

Recent developments in aging research have added new urgency to the bioethical debate concerning life and death issues, the value of life, and the reasonable limits of medicine. This paper analyzes the basic structures of the liberal and conservative components of this debate, showing that there has hitherto been inadequate analysis on both sides concerning the nature and implications of the value of life, as well as, and as distinct from the value of life extension. Classic concepts of the intrinsic or extrinsic value of life are argued to be tangential or actually irrelevant to the value of life's continuance and so to the value of life extension. An analysis of personhood is proposed which focuses explicitly upon the value of life extension to persons. This analysis shows that persons may only intelligibly be understood as processes, for whom life extension is an inalienable and fundamental value. It is further proposed that, properly understood, such an analysis may significantly narrow the liberal/conservative divide in bioethics.

Aging↗
PubMed1988

Hypertension, quality of life and functional status: the concept of active life expectancy.

Mortality rates and measures of life expectancy are widely used to compare and monitor health within populations. However, there is a need to add dimensions of population health other than survival. An alternative measure, 'active life expectancy', is a way of quantifying the functional health of older adult populations and, in part, measuring quality of life. Life-table techniques are used to define the expected duration of well-being. Instead of death, the end-point of active life expectancy is loss of independence in activities of daily living. Initial studies showed that active life expectancy decreased with age, from 10 years to 4.7 years and 2.9 years, respectively, for people entering the age intervals 65-69, 80-84 and 85 years and over. Since cardiovascular disease is the major cause of disability in the older adult population, measures of active life expectancy can provide improved information about functional independence and dependence. Life tables with estimates of active life expectancy can be used as a basis for determining the needs of age cohorts of people with hypertension and other conditions.

Activities of Daily Living↗
PubMed1999

A prospective study on quality of life and traumatic events in early life--a 30-year follow-up.

AIM: To investigate the connection between early life trauma and the quality of life some 30 years later in Denmark. DESIGN: Prospective, longitudinal study with questionnaire-based follow-up survey. METHODS: In 'The Quality of Life Research Study of 10,000 Danes', a newly designed questionnaire was mailed in February 1993 to 7222 persons from the Prospective Paediatric Cohort of persons born at the State University Hospital in Copenhagen (Rigshospitalet) between 1959 and 1961. Response rate was 64% (4626 people between the ages 31-33). VARIABLES: Mother's attitude towards her pregnancy, child being placed in a children's home, mother using antipsychotic drugs indicating acute, mental illness, child adopted in the first year of life and quality of life of the child 31-33 years later. RESULTS: Of the early life traumas studied, only relatively weak connections to the quality of life in later life were found. CONCLUSIONS: These relatively weak findings suggest that the children that survive to adulthood are resilient to many adverse events in early life.

Adoption↗
PubMed2005

Socioeconomic status differentials in life and active life expectancy among older adults in Beijing.

PURPOSE: The study compares life and active life expectancy estimates across indicators of socioeconomic status (SES) for a cohort of older adults in the Beijing municipality. Our aim is to determine if associations found are consistent across indicators and with those typically observed in the Western industrialized countries. METHOD: A multistate life table method is used to estimate expected years of total and active life, defined as life spent without limitation in functions necessary for performing daily tasks. RESULTS: We find that men of higher status experience advantages with respect to life and active life expectancies. Among women, only active life expectancy is significantly higher for those of higher status, but the difference by income is not statistically significant. With respect to the proportion of life spent in an active state, both men and women of higher status benefit in comparison to their lower status counterparts. Finally, we find that disparities by SES generally increase with age. CONCLUSIONS: Despite several inconsistencies across SES indicators by gender, findings generally confirm inequalities within a society that is organized very differently socially, economically, and politically from the West.

Activities of Daily Living↗
PubMed2005

The life mission theory VII. Theory of existential (Antonovsky) coherence: a theory of quality of life, health, and ability for use in holistic medicine.

A theoretical framework of existential coherence is presented, explaining how health, quality of life (QOL), and the ability to function were originally created and developed to rehabilitate human life from an existential perspective. The theory is inspired by the work of Aaron Antonovsky and explains our surprising recent empirical findings -- that QOL, health, and ability primarily are determined by our consciousness. The theory is a matrix of nine key elements in five layers: (1) coherence; (2) purpose and talent; (3) consciousness, love, and physicality/sexuality; (4) light and joy; and (5) QOL/meaning of life. The layer above causes the layer below, with the layer of QOL again feeding the fundamental layer of coherence. The model holds the person responsible for his or her own degree of reality, happiness, and being present. The model implies that when a person takes responsibility in all nine "dimensions" of life, he or she can improve and develop health, the ability to function, all aspects of QOL, and the meaning of life. The theory of existential coherence integrates a wide range of QOL theories from Jung and Maslow to Frankl and Wilber. It is a nine-ray theory in accordance with Gurjieff's enneagram and the old Indian chakra system. It can be used in the holistic medical clinic and in existential coaching. Love is in the center of the model and rehabilitation of love in its broadest sense is, accordingly, the essence of holistic medicine. To know yourself, your purpose of life (life mission) and talents, and taking these into full use and becoming coherent with life inside and reality outside is what human life is essentially about. The new model has been developed to integrate the existing knowledge in the complex field of holistic medicine. Its strength is that it empowers the holistic physician to treat the patient with even severe diseases and can also be used for existential rehabilitation, holistic psychiatry, and sexology. Its major weakness is that it turns holistic medicine more into an art than into a science because the physician must master intent, which is a poorly understood dimension of existence.

Consciousness↗
PubMed1998

Coevolutionary interactions between host life histories and parasite life cycles.

Several recent studies have discussed the interaction of host life-history traits and parasite life cycles. It has been observed that the life-history of a host often changes after infection by a parasite. In some cases, changes of host life-history traits reduce the costs of parasitism and can be interpreted as a form of resistance against the parasite. In other cases, changes of host life-history traits increase the parasite's transmission and can be interpreted as manipulation by the parasite. Alternatively, changes of host's life-history traits can also induce responses in the parasite's life cycle traits. After a brief review of recent studies, we treat in more detail the interaction between the microsporidian parasite Edhazardia aedis and its host, the mosquito Aedes aegypti. We consider the interactions between the host's life-history and parasite's life cycle that help shape the evolutionary ecology of their relationship. In particular, these interactions determine whether the parasite is benign and transmits vertically or is virulent and transmits horizontally.

Aedes↗
PubMed1995

Suicide, life course, and life story.

This article explores how a life-course perspective and narrative methodology can be used to study risk factors for late-life suicide. A life-course approach to aging and suicide requires consideration of age as both social and personal construction. "On-" and "off-time" events and their impact on adjustment are used to illustrate these social and personal constructions. Cohort, period, and historical events have potentially profound effects on risk for suicide, yet the study of these effects is difficult because they are so often confounded in longitudinal study. Lifelong personality characteristics that are not life-threatening in earlier life may be of greater risk in later life depending on life circumstances such as physical dependencies. A life-story or narrative approach offers an alternative method for incorporating these complicated factors when studying late-life suicide. The psychological autopsy can be considered a type of "narrative" used by various individuals to gain understanding about a suicide.

Age Factors↗
PubMed2004

Measuring quality of life at the end of life: validation of the QUAL-E.

OBJECTIVES: To validate the QUAL-E, a new measure of quality of life at the end of life. METHODS: We conducted a cross-sectional study to assess the instrument's psychometric properties, including the QUAL-E's associations with existing measures, evaluation of robustness across diverse sample groups, and stability over time. The study was conducted at the VA and Duke University Medical Centers, Durham, North Carolina, in 248 patients with stage IV cancer, congestive heart failure with ejection fraction < or = 20%, chronic obstructive pulmonary disease with FEV1 < or = 1.0 1, or dialysis-dependent end stage renal disease. The main outcome measures included QUAL-E and five comparison measures: FACIT quality of life measure, Missoula-VITAS Quality of Life Index, FACIT-SP spirituality measures, Participatory Decision Making Scale (MOS), and Duke EPESE social support scales. RESULTS: QUAL-E analyses confirmed a four-domain structure (25 items): life completion (alpha = 0.80), symptoms impact (alpha = 0.87), relationship with health care provider (alpha = 0.71), and preparation for end of life (alpha = 0.68). Convergent and discriminant validity were demonstrated with multiple comparison measures. Test-retest reliability assessment showed stable scores over a 1-week period. SIGNIFICANCE OF RESULTS: The QUAL-E, a brief measure of quality of life at the end of life, demonstrates acceptable validity and reliability, is easy to administer, performs consistently across diverse demographic and disease groups, and is acceptable to seriously ill patients. It is offered as a new instrument to assist in the evaluation of the quality and effectiveness of interventions targeting improved care at the end of life.

Adult↗
PubMed2000

Can life be evaluated? The Jewish Halachic approach vs. the quality of life approach in medical ethics: a critical view.

In recent years there has been an increase in the number of requests for "mercy killings" by patients and their relatives. Under certain conditions, the patient may prefer death to a life devoid of quality. In contrast to those who uphold this "quality of life" approach, those who hold the "sanctity of life" approach claim that life has intrinsic value and must be preserved regardless of its quality. This essay describes these two approaches, examines their flaws, and offers a "golden path" between the two extreme positions. We discuss the halachic and the secular views, arguing for a balance between the sanctity of life and the quality of life. We argue that, indeed, such a balance exists in practice, and that life is important, but it is not sacred. Life can be evaluated, but quality of life is not the sole criterion.

Euthanasia↗
PubMed2004

Quality of life in the general Norwegian population, measured by the Quality of Life Scale (QOLS-N).

The main aim of the present study was to derive norms or reference values from the general Norwegian population for the Norwegian version of the Quality of Life Scale (QOLS-N). In addition, associations between socio-demographic and health variables on the level of quality of life were examined. The sample consisted of 1893 subjects from a total of 4000 randomly selected Norwegian citizens representative of the entire Norwegian population, aged 19-81. The subjects received a mailed questionnaire containing the QOLS-N. Results show that the mean quality of life score was 84.1 (SD 12.5). Women reported a higher quality of life than men. People with higher levels of education reported a higher quality of life. Those who were married or cohabitating reported the highest quality of life and those who were unemployed reported a lower quality of life than those who worked. In addition, people reporting long-term diseases or health problems scored significantly lower on quality of life. These results could serve as reference values for the level of quality of life, as measured by the QOLS-N in the Norwegian population.

Adult↗
PubMed2001

Is good 'quality of life' possible at the end of life? An explorative study of the experiences of a group of cancer patients in two different care cultures.

The purpose of this paper was to explore how a group of gravely ill patients, cared for in different care cultures, assessed their quality of life during their last month of life. The study material comprised quality of life assessments from 47 cancer patients, completed during their last month of life. Two quality of life questionnaires, the EORTC QLQ-C30 and a psychosocial well-being questionnaire, were used. The data were treated in accordance with instructions for the respective questionnaires, and the results are presented primarily as means, mostly at the group level. Assessments from patients in two different care cultures, care-orientated and cure-orientated, were compared. The results show that despite having an assessed lower quality of life in many dimensions than people in general, several patients experienced happiness and satisfaction during their last month of life. 'Cognitive functioning' and 'emotional functioning' were the dimensions that differed least from those of the general population, and 'physical functioning', 'role functioning' and 'global health status/quality of life' differed the most. 'Fatigue' showed the highest mean for the symptom scales/items. There was a tendency for those cared for in the cure-orientated care culture to report more symptoms than those in the care-orientated care culture. An exception to this was 'pain', which was reported more often by those in the care-orientated care culture. The implications of the results are discussed from different angles. The significance of knowledge concerning how patients experience their quality of life is also discussed with respect to the care and the planning of care for dying patients.

Activities of Daily Living↗
PubMed2000

A prospective and randomized study, "SVEA," comparing effects of three methods for delayed breast reconstruction on quality of life, patient-defined problem areas of life, and cosmetic result.

During the last 30 years, many methods for delayed breast reconstruction have been described. There is a lack of prospective randomized trials comparing reconstruction methods. The present study (SVEA), conducted 1995 to 1996, describes the impacts of three methods: the lateral thoracodorsal flap, the latissimus dorsi flap, and the pedicled transverse rectus abdominis muscle flap (TRAM), on important areas of life, patients' perception of cosmetic result, and quality of life. Questionnaires were completed before randomization and at 6 and 12 months postoperatively. The preoperative questionnaire concerned the impact of breast loss and expectations on reconstruction. Follow-up questionnaires dealt with satisfaction with cosmetic result and impact on important areas of life. A health-related quality-of-life questionnaire (SF-36) was completed at all points of assessment. A total of 75 of 87 randomized patients underwent breast reconstruction: 16 patients with the lateral thoracodorsal flap, 30 with the latissimus dorsi flap, and 29 with the TRAM flap. The majority were very satisfied with the cosmetic result. Most women reported improvements in important areas of life, and quality of life in terms of "social functioning" and "mental health" increased significantly after the reconstruction. The latissimus dorsi flap and TRAM flap scored significantly higher as compared with the lateral thoracodorsal flap for similarity with the contralateral breast and reduced problems in social situations. No differences between irradiated and nonirradiated patients were found. All methods were considered to produce good cosmetic results and improvements in patient-defined problem areas of life and quality of life. No negative effects were recorded. Thus, irrespective of method, breast reconstruction is a valuable tool for the mastectomized woman to cope with problems in everyday life.

Activities of Daily Living↗
PubMed2004

Quality of life as medicine III. A qualitative analysis of the effect of a five-day intervention with existential holistic group therapy or a quality of life course as a modern rite of passage.

Existential group therapy seems to be a very efficient way of inducing the holistic state of healing, described in the holistic process theory of healing. We have designed a series of four quality of life (QOL) and health courses of 5-days duration called "Philosophy of Life that Heals--Courses in QOL and Personal Development". The four courses are meant to be taken over four consecutive years. They contain training in philosophy of life and existential theory as well as exercises in holding: awareness, respect, care, acknowledgment, and acceptance. The courses teach the participants respect, love, and intimacy; help them to draw on their seemingly unlimited hidden resources; and inspire them to take more responsibility for their own life. Exercises are accomplished with a partner chosen at the course as: (1) a person you like, (2) a person you do not know already, or (3) a person to whom you want to give help, support, and holding more than you want to get help from him or her. Pilot studies with 5-day quality of life interventions that combine training in quality of life philosophy with psychotherapy and bodywork have proved effective on patients with chronic pain and alcoholism. The present design aims to take this a step further and engage the patients in a process of personal growth that will last for years. The aim is to lead them to a stabile state of quality of life, health, and ability, from where they will not again fall into sickness and unhappiness. The focus of these courses is as much on prevention as is it on healing. The existential group therapy induces spontaneous healing of body, mind, and soul that seems to be highly efficient with hopefully lasting results. Every course is intended to give an immediate improvement in the quality of life, so its efficiency can be measured with the square curve paradigm. We have studied the participant"s accounts from their experience with the courses and have analyzed the remarkably large, qualitative changes in the state of being, quality of life, health, and consciousness, which many participants experience during the course. The long-term and preventative effects of the courses have yet to be documented.

Existentialism↗
PubMed2004

The life mission theory VI. A theory for the human character: healing with holistic medicine through recovery of character and purpose of life.

The human character can be understood as an extension of the life mission or purpose of life, and explained as the primary tool of a person to impact others and express the purpose of life. Repression of the human character makes it impossible for a person to realize his personal mission in life and, therefore, is one of the primary causes of self-repression resulting in poor quality of life, health, and ability. From Hippocrates to Hahnemann, repression of physical, mental, and spiritual character can be seen as the prime cause of disease, while recovery of character has been the primary intention of the treatment. In this paper, human character is explained as an intersubjective aspect of consciousness with the ability to influence the consciousness of another person directly. To understand consciousness, we reintroduce the seven-ray theory of consciousness explaining consciousness in accordance with a fractal ontology with a bifurcation number of seven (the numbers four to ten work almost as well). A case report on a female, aged 35 years, with severe hormonal disturbances, diagnosed with extremely early menopause, is presented and treated according to the theory of holistic existential healing (the holistic process theory of healing). After recovery of her character and purpose of life, her quality of life dramatically improved and hormonal status normalized. We believe that the recovery of human character and purpose of life was the central intention of Hippocrates and thus the original essence of western medicine. Interestingly, there are strong parallels to the peyote medicine of the Native Americans, the African Sangomas, the Australian Aboriginal healers, and the old Nordic medicine. The recovery of human character was also the intention of Hahnemann''s homeopathy. We believe that we are at the core of consciousness-based medicine, as recovery of purpose of life and human character has been practiced as medicine in most human cultures throughout time. We believe that such recovery can help some (motivated) patients to survive, even with severe disease.

Adult↗
PubMed1990

Early natural menopause and the duration of postmenopausal life. Findings from a mathematical model of life expectancy.

Menopause marks the beginning of a stage of life characterized by an increased susceptibility to diseases such as coronary heart disease and osteoporosis. It was therefore hypothesized that early age at natural menopause would lengthen the duration of the postmenopausal stage of life and thereby result in an earlier age at death. This study investigated the relations between age at natural menopause, duration of postmenopausal life (ie, life expectancy at menopause), and age at death (ie, age at menopause plus life expectancy at menopause). Data were derived from a study of 5,287 naturally postmenopausal Seventh-day Adventists observed during 1976-1982. Life expectancy was estimated by a mathematical model that used mortality ratios from the study and mortality rates from the US general population. For natural menopause before the age of 47 years, each one-year decrease in age at menopause was associated with a 0.53-year increase in postmenopausal life (P = .04) and a 0.47-year decrease in the age at death (P = .04). For natural menopause at the age of 47 years and older, however, each one-year decrease in age at menopause was associated with a 0.99-year increase in postmenopausal life (P = .03) and only a 0.01-year decrease in the age at death (P = .85). Overall, these findings argue against the possibility that the association between age at menopause and age at death in this study was due to the relation of age at menopause to the duration of postmenopausal life.

Aged↗
PubMed1997

Chronic obstructive pulmonary disease stage and health-related quality of life. The Quality of Life of Chronic Obstructive Pulmonary Disease Study Group.

BACKGROUND: The American Thoracic Society recently recommended that chronic obstructive pulmonary disease be staged on the basis of the percentage of predicted FEV1. OBJECTIVE: To examine 1) the relation between the american Thoracic Society system for staging chronic obstructive pulmonary disease and health-related quality of life and 2) the effect of self-reported comorbid conditions on health-related quality of life. DESIGN: Cross-sectional study. SETTING: Outpatient clinics of respiratory departments of four hospitals and one primary health care center in spain. PATIENTS: 321 consecutive male patients with chronic obstructive pulmonary disease. MEASUREMENTS: Functional respiratory impairment, FEV1, respiratory symptoms, and health-related quality of life. Respiratory symptoms and health-related quality of life were measured by using the Spanish version of the St. George's Respiratory Questionnaire and the Nottingham Health Profile. RESULTS: Patient scores on the St. George's Respiratory Questionnaire were moderately to strongly associated with disease staging (r = 0.27 to 0.51). Compared with reference values, values for health-related quality of life for patients with stage I disease were substantially higher on the St. George's Respiratory Questionnaire (6 and 34; p < 0.001) and values for impairment were significantly greater in stage 1 patients with comorbid conditions (19 and 36; P = 0.001). At least one concomitant chronic condition was found in 84% of study patients. Comorbid conditions only partly influenced the observed pattern of deterioration of health-related quality of life with worsening stages of disease. CONCLUSION: Staging criteria for chronic obstructive pulmonary disease based on percentage of predicted FEV1 separated groups of patients with varying degrees of impairment in health-related quality of life. Contrary to expectations, even patients with mild disease showed substantially compromised health-related quality of life. Comorbid conditions influenced the relation between chronic obstructive pulmonary disease and health-related quality of life.

Comorbidity↗
PubMedDate not supplied

[The life form concept and the use in the analysis of life cycle evolutionary strategies].

The life form is a generalized morphoecological characteristic of an animal giving an idea of the organism as a whole, its position and function and functional role in the ecosystem. This characteristic is inherent to a species or to a group of congeneric species (for applied goal it is better to use a genus, not species) considered in the framework of higher taxon (from family to type). The principal contradiction of life form concept is determined by the existence of ontogenetic stages and changes of life forms during the whole life of individual. It is usually assumed that the concept of life form should be applied only to the adult stage, thus ignoring the integral character of the life cycle as indivisible unit of selection, evolution and functioning in ecosystem. We propose that a morphologically specific ontogenetic of a given species should be used as an elementary lowest unit in the classification of life forms. Thus it can be considered as integrated internally structured morphoecological unit in time and multidimensional space of abiotic and biotic environmental factors. As an example we describe the types of reproductive strategies and classification of elementary (ontogenetic) life forms in cephalopods. We present characteristics of the life cycle of some typical cephalopod species inhabiting different biotopes and having different models of locomotion, feeding, reproduction and development.

Animals↗