Life-shortening Effect Research Articles

Measurement of anisotropic fatigue life in micrometre-scale single-crystal silicon specimens

The fatigue life of micrometre-scale single-crystal silicon specimens was measured using the resonant vibration of a micromachined resonator device. Two kinds of identically shaped specimens oriented to 〈110〉 and 〈100〉 crystal directions on the (001) plane were tested. On the deflection–life relationship, the deflection amplitudes of the 〈100〉 oriented specimens were approximately 1.56 times higher than that of 〈110〉 oriented ones at the same fatigue life. Observation by scanning electron microscope showed that the fracture surfaces differed depending on the specimen orientation and deflection amplitude. The life-shortening effect of the surface roughness was also demonstrated.

Continuous Deep Sedation Until Death: Palliation or Physician-Assisted Death?

Published literature has not discerned end-of-life palliative versus life-shortening effects of pharmacologically maintaining continuous deep sedation until death (i.e., dying in deep sleep) compared with common sedation practices relieving distress in the final conscious phase of dying. Continuous deep sedation predictably suppresses brainstem vital centers and shortens life. Continuous deep sedation remains controversial as palliation for existential suffering and in elective death requests by discontinuation of chronic ventilation or circulatory support with mechanical devices. Continuous deep sedation contravenes the double-effect principle because: (1) it induces permanent coma (intent of action) for the contingency relief of suffering and for social isolation (desired outcomes) and (2) because of its predictable and proportional life-shortening effect. Continuous deep sedation should be distinguished from common sedation practices for palliation and characterized instead as physician-assisted death.

Policies to improve end-of-life decisions in Flemish hospitals: communication, training of health care providers and use of quality assessments

BackgroundThe prevalence and implementation of institutional end-of-life policies has been comprehensively studied in Flanders, Belgium, a country where euthanasia was legalised in 2002. Developing end-of-life policies in hospitals is a first step towards improving the quality of medical decision-making at the end-of-life. Implementation of policies through quality assessments, communication and the training and education of health care providers is equally important in improving actual end-of-life practice. The aim of the present study is to report on the existence and nature of end-of-life policy implementation activities in Flemish acute hospitals.MethodsA cross-sectional mail survey was sent to all acute hospitals (67 main campuses) in Flanders (Belgium). The questionnaire asked about hospital characteristics, the prevalence of policies on five types of end-of-life decisions: euthanasia, palliative sedation, alleviation of symptoms with possible life-shortening effect, do-not-resuscitate decision, and withdrawing or withholding of treatment, the internal and external communication of these policies, training and education on aspects of end-of-life care, and quality assessments of end-of-life care on patient and family level.ResultsThe response rate was 55%. Results show that in 2007 written policies on most types of end-of-life decisions were widespread in acute hospitals (euthanasia: 97%, do-not-resuscitate decisions: 98%, palliative sedation: 79%). While standard communication of these policies to health care providers was between 71% and 91%, it was much lower to patients and/or family (between 17% and 50%). More than 60% of institutions trained and educated their caregivers in different aspects on end-of-life care. Assessment of the quality of these different aspects at patient and family level occurred in 25% to 61% of these hospitals.ConclusionsMost Flemish acute hospitals have developed a policy on end-of-life practices. However, communication, training and the education of health care providers about these policies is not always provided, and quality assessment tools are used in less than half of the hospitals.

C. elegans as Model for the Study of High Glucose– Mediated Life Span Reduction

OBJECTIVEEstablishing Caenorhabditis elegans as a model for glucose toxicity–mediated life span reduction.RESEARCH DESIGN AND METHODSC. elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high glucose on life span, glyoxalase-1 activity, advanced glycation end products (AGEs), and reactive oxygen species (ROS) formation and on mitochondrial function were studied.RESULTSHigh glucose conditions reduced mean life span from 18.5 ± 0.4 to 16.5 ± 0.6 days and maximum life span from 25.9 ± 0.4 to 23.2 ± 0.4 days, independent of glucose effects on cuticle or bacterial metabolization of glucose. The formation of methylglyoxal-modified mitochondrial proteins and ROS was significantly increased by high glucose conditions and reduced by mitochondrial uncoupling and complex IIIQo inhibition. Overexpression of the methylglyoxal–detoxifying enzyme glyoxalase-1 attenuated the life-shortening effect of glucose by reducing AGE accumulation (by 65%) and ROS formation (by 50%) and restored mean (16.5 ± 0.6 to 20.6 ± 0.4 days) and maximum life span (23.2 ± 0.4 to 27.7 ± 2.3 days). In contrast, inhibition of glyoxalase-1 by RNAi further reduced mean (16.5 ± 0.6 to 13.9 ± 0.7 days) and maximum life span (23.2 ± 0.4 to 20.3 ± 1.1 days). The life span reduction by glyoxalase-1 inhibition was independent from the insulin signaling pathway because high glucose conditions also affected daf-2 knockdown animals in a similar manner.CONCLUSIONSC. elegans is a suitable model organism to study glucose toxicity, in which high glucose conditions limit the life span by increasing ROS formation and AGE modification of mitochondrial proteins in a daf-2 independent manner. Most importantly, glucose toxicity can be prevented by improving glyoxalase-1–dependent methylglyoxal detoxification or preventing mitochondrial dysfunction.

Palliative Care – schwierige Entscheidungen am Lebensende

Palliative care comprises the complete treatment and care of patients suffering from incurable, life-threatening or chronically progressive disease. The aim is to provide the patients with the best possible quality of life and support them through the course of their illness until their death, to alleviate their suffering as much as possible and in consideration of the social, spiritual and religious aspects according to the patient's wishes. Palliative care is most important when the dying process and the patient's impending death do seem to be inevitable. Shared decision-making at an early stage of illness is mandatory. Respect for a person's dignity means focusing on their autonomy, their personal preferences and their right to live according to their own values and convictions. A person's autonomy is based on the level of information that he or she is given, the pertinent situation, and the patient's readiness and ability to take responsibility for their own life and end-of-life decisions. Decisions about life-prolonging measures, treatment of pain, dyspnea and palliative sedation require balancing the burden against the benefits. Decision-making must rest with the patient - as far as possible and as long as possible. The potential life-shortening effect of palliative therapy will need to be considered and discussed.

Attitudes of Flemish secondary school students towards euthanasia and other end‐of‐life decisions in minors

The aim of the study was to investigate attitudes of secondary school students towards acceptability of requests by minors for end-of-life decisions (ELDs) with a possible life-shortening effect: non-treatment decisions, potentially life-shortening alleviation of pain and symptoms (APS) and euthanasia. A cross-sectional survey was conducted among second and fourth grades students in 20 secondary schools in Flanders, Belgium. An anonymous structured questionnaire was administered to measure attitudes towards acceptability of requests for euthanasia and other ELDs, towards the right to be informed about terminal prognosis and their own desire to be informed. In total, 1769 students participated. In case of a terminal patient, 61% found a request for euthanasia acceptable, 60% a request for APS and 69% a request for non-treatment decision, compared with 18% (euthanasia) and 50% (APS) in case of a non-terminal patient. Acceptance was highest among: boys, participants older than 14 years and participants from general as opposed to technical and vocational education. Sixty-six per cent said the parents' opinion not being asked was a circumstance that should hold back a physician from administering a lethal drug. Ninety per cent of participants thought a minor has the right to be informed about terminal prognosis of a disease while 78% would like to be informed themselves. Attitudes towards ELD requests varied with case and participant characteristics and type of ELD. The studied adolescents have a clear wish to be informed about terminal prognosis. Physicians and caregivers should adequately involve adolescents in decision making and tailor prognosis-related information to their needs and level of competency.

Euthanasia and other end-of-life decisions: a mortality follow-back study in Belgium

BackgroundThis study compares prevalence and types of medical end-of-life decisions between the Dutch-speaking and French-speaking communities of Belgium. This is the first nationwide study that can make these comparisons and the first measurement after implementation of the euthanasia law (2002).MethodsWe performed a mortality follow-back study in 2005–2006. Data were collected via the nationwide Sentinel Network of General Practitioners, an epidemiological surveillance system representative of all Belgian GPs.Weekly, all GPs reported the medical end-of-life decisions among all non-sudden deaths of patients in their practice. We compared the northern Dutch-speaking (60%) and southern French-speaking communities (40%) controlling for population differences.ResultsWe analysed 1690 non-sudden deaths. An end-of-life decision with possible life-shortening effect was made in 50% of patients in the Dutch-speaking community and 41% of patients in the French-speaking community (OR 1.4; 95%CI, 1.2 to 1.8). Continuous deep sedation until death occurred in 8% and 15% respectively (OR 0.5; 95%CI, 0.4 to 0.7). Community differences regarding the prevalence of euthanasia or physician-assisted suicide were not significant.Community differences were more present among home/care home than among hospital deaths: non-treatment decisions with explicit life-shortening intention were made more often in the Dutch-speaking than in the French-speaking community settings (OR 2.2; 95%CI, 1.2 to 3.9); while continuous deep sedation occurred less often in the Dutch-speaking community settings (OR 0.5; 95%CI, 0.3 to 0.9).ConclusionEven though legal and general healthcare systems are the same for the whole country, there are considerable variations between the communities in type and prevalence of certain end-of-life decisions, even after controlling for population differences.

Expression of human uncoupling protein-3 in Drosophila insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan

Uncoupling proteins (UCPs) can dissipate mitochondrial protonmotive force by increasing the proton conductance of the inner membrane and through this effect could decrease ROS production, ameliorate oxidative stress and extend lifespan. We investigated whether ubiquitous, pan-neuronal or neurosecretory cell-specific expression of human UCP3 (hUCP3) in adult Drosophila melanogaster affected lifespan. Low, ubiquitous expression of hUCP3 at levels found in rodent skeletal muscle mitochondria did not affect proton conductance in mitochondria isolated from whole flies, but high pan-neuronal expression of hUCP3 increased the proton conductance of mitochondria isolated from fly heads. Expression of hUCP3 at moderate levels in adult neurons led to a marginal lifespan-extension in males. However, high expression of hUCP3 in neuronal tissue shortened lifespan. The life-shortening effect was replicated when hUCP3 was expressed specifically in median neurosecretory cells (mNSC), which express three of the Drosophila insulin-like peptides (DILPs). Expression of hUCP3 in the mNSC did not alter expression of dilp2, dilp3 or dilp5 mRNA, but led to increased amounts of DILP2 in fly heads. These data suggest that lowering mitochondrial coupling by high expression of hUCP3 alters mNSC function in a way that appears to increase DILP-levels in fly heads and lead to a concomitant decrease in lifespan.

Mosquitoes Cut Short

Can the life-shortening effect of a bacterium on mosquitoes control the transmission of dengue?

End-of-Life Decision-Making and Terminal Sedation among Very Old Patients

Background: About half of the persons who die in developed countries are very old (aged 80 years or older) and this proportion is still rising. In general, there is little information available concerning the circumstances and quality of the end of life of this group. Objective: This study aims (1) to describe the incidence and characteristics of medical end-of-life decisions with a possible or certain life-shortening effect (ELDs) and terminal sedation among very old patients who died nonsuddenly, (2) to describe the characteristics of the preceding decision-making process, and (3) to compare this with the deaths of younger patients. Methods: A sample of 5,005 death certificates was selected from all deaths in Flanders (Belgium) in the second half of 2001 (before euthanasia was legalized). Questionnaires were mailed to the certifying physicians. Results: Response rate was 58.9%. An ELD was made for 53.6% very old (aged 80+) patients who died nonsuddenly (vs. 63.3% for the younger patients). Use of life-ending drugs occurred among 1.1% (six times less frequently than in younger patients), with no euthanasia cases, pain and symptom alleviation with a possible life-shortening effect among 27.3% (two times less frequently), and withholding or withdrawing life-prolonging treatments among 25.2% (slightly more frequently). Terminal sedation occurred among 6.9% of the cases, two times less frequently than for the younger patients. ELDs were not often discussed with very old patients. Among competent patients this was less than compared with younger patients. Conclusion: ELDs are less common for very old than for younger patients. Physicians seem to have a more reluctant attitude towards the use of lethal drugs, terminal sedation and participation in decision-making when dealing with very old patients. Advance care planning should increase the involvement of very old competent and noncompetent patients in end-of-life decision-making.

A comparison of physicians' end-of-life decision making for non-western migrants and Dutch natives in the Netherlands

Non-western migrants have a different cultural background that influences their attitudes towards healthcare. As the first wave of this relatively young group is growing older, we investigated, for the first time, whether end-of-life decision-making practices for non-western migrants differ from Dutch natives. In 2005, we sent questionnaires to physicians who attended deaths identified from the central death registry of Statistics Netherlands (n = 9651; non-western migrants: n = 627, total response: 78%). We performed multivariate logistic regression analyses adjusted for age, sex and cause of death. Of all deaths of non-western origin, 54% were non-sudden, whereas 67% of all deaths with a Dutch origin were non-sudden (P = 0.00). A relatively large number of non-suddenly deceased persons of non-western origin had died under the age of 65 (53%) as compared to Dutch natives (15%). Euthanasia was performed in 2.4% of all non-suddenly deceased persons in the non-western migrant group as compared to 2.7% in the native Dutch group (adjusted odds ratio = 0.82, P = 0.63). Alleviation of symptoms with a potential life-shortening effect was somewhat lower for non-western migrants (30% vs. 38%; adjusted odds ratio = 0.78, P = 0.07). Physicians decided to forgo potentially life-prolonging treatment in comparable rates (26% vs. 23%; adjusted odds ratio = 1.1, P = 0.73). Yet, the type of treatments forgone and underlying reasons differed. Euthanasia was not less common among non-suddenly deceased non-western migrants as compared to Dutch natives. However, intensive symptom alleviation was used less frequently and forgoing potentially life-prolonging treatment involved different characteristics. These findings suggest that cultural factors may affect end-of-life decision making.

A post-mortem survey on end-of-life decisions using a representative sample of death certificates in Flanders, Belgium: research protocol

BackgroundReliable studies of the incidence and characteristics of medical end-of-life decisions with a certain or possible life shortening effect (ELDs) are indispensable for an evidence-based medical and societal debate on this issue. This article presents the protocol drafted for the 2007 ELD Study in Flanders, Belgium, and outlines how the main aims and challenges of the study (i.e. making reliable incidence estimates of end-of-life decisions, even rare ones, and describing their characteristics; allowing comparability with past ELD studies; guaranteeing strict anonymity given the sensitive nature of the research topic; and attaining a sufficient response rate) are addressed in a post-mortem survey using a representative sample of death certificates.Study designReliable incidence estimates are achievable by using large at random samples of death certificates of deceased persons in Flanders (aged one year or older). This entails the cooperation of the appropriate administrative authorities. To further ensure the reliability of the estimates and descriptions, especially of less prevalent end-of-life decisions (e.g. euthanasia), a stratified sample is drawn. A questionnaire is sent out to the certifying physician of each death sampled. The questionnaire, tested thoroughly and avoiding emotionally charged terms is based largely on questions that have been validated in previous national and European ELD studies. Anonymity of both patient and physician is guaranteed through a rigorous procedure, involving a lawyer as intermediary between responding physicians and researchers. To increase response we follow the Total Design Method (TDM) with a maximum of three follow-up mailings. Also, a non-response survey is conducted to gain insight into the reasons for lack of response.DiscussionThe protocol of the 2007 ELD Study in Flanders, Belgium, is appropriate for achieving the objectives of the study; as past studies in Belgium, the Netherlands, and other European countries have shown, strictly anonymous and thorough surveys among physicians using a large, stratified, and representative death certificate sample are most suitable in nationwide studies of incidence and characteristics of end-of-life decisions. There are however also some limitations to the study design.

The role of polyamines in protein-dependent hypoxic tolerance of Drosophila

BackgroundChronic hypoxia is a major component of ischemic diseases such as stroke or myocardial infarction. Drosophila is more tolerant to hypoxia than most mammalian species. It is considered as a useful model organism to identify new mechanisms of hypoxic tolerance. The hypoxic tolerance of flies has previously been reported to be enhanced by low protein diets. This study analyses the mechanisms involved.ResultsFeeding adult Drosophila on a yeast diet dramatically reduced their longevities under chronic hypoxic conditions (5% O2). Mean and maximum longevities became close to the values observed for starving flies. The action of dietary yeast was mimicked by a whole casein hydrolysate and by anyone of the 20 natural amino acids that compose proteins. It was mimicked by amino acid intermediates of the urea cycle such as L-citrulline and L-ornithine, and by polyamines (putrescine, spermidine and spermine). α-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, partially protected hypoxic flies from amino acid toxicity but not from polyamine toxicity. N1-guanyl-1,7 diaminoheptane, a specific inhibitor of eIF5A hypusination, partially relieved the toxicities of both amino acids and polyamines.ConclusionDietary amino acids reduced the longevity of chronically hypoxic flies fed on a sucrose diet. Pharmacological evidence suggests that the synthesis of polyamines and the hypusination of eIF5A contributed to the life-shortening effect of dietary amino acids.

End-of-life decision-making in Belgium, Denmark, Sweden and Switzerland: does place of death make a difference?

Objective:To examine differences in end-of-life decision-making in patients dying at home, in a hospital or in a care home.Design:A death certificate study: certifying physicians from representative samples of death certificates,...

Having a difficult time leaving: experiences and attitudes of nurses with palliative sedation

Background: Palliative sedation is an important topic of medical and ethical debates. Although nurses often participate in its use, little is known about their attitudes and experiences. Methods: In a qualitative study, we explored nurses' attitudes and experiences with palliative sedation. In semi-structured interviews with 16 nurses, we collected data about their most memorable cases of palliative sedation. Interviews were transcribed, coded and analysed using constant comparative analysis. Results: In all of the described cases, palliative sedation was used primarily to address physical suffering in severely ill patients. Concomitant reasons for the use of palliative sedation were nonphysical suffering, the patient's wish and the family's distress about the patient's suffering. The use of palliative sedation for the patient's nonphysical suffering was often difficult for many of the nurses. Nurses had different perspectives on whether palliative sedation may have had a life-shortening effect on the patient. Some thought that it had not accelerated death; others thought that it may have accelerated death but that this was justified when there was no other way of relieving discomfort. A third group thought that palliative sedation was close to the practice of euthanasia and they often found it difficult to be involved in its use. Nevertheless, palliative sedation was considered by all the nurses to positively contribute to the patient's quality of dying in all discussed cases. Conclusions: The struggles that nurses in this study cohort experienced indicate the need for further study and may suggest the need for more nursing education and discussion about ethical aspects of palliative sedation. Palliative Medicine 2007; 21 : 643—649

Factors related to the involvement of nurses in medical end-of-life decisions in Belgium: A death certificate study

Background Although nurses play an important role in end-of-life care for patients, they are not systematically involved in end-of-life decisions with a possible or certain life-shortening effect (ELDs). Until now we know little about factors relating to the involvement of nurses in these decisions. Objective To explore which patient- and decision-characteristics are related to the consultation of nurses and to the administering of life-ending drugs by nurses in actual ELDs in institutions and home care, as reported by physicians. Method We sampled at random 5005 of all registered deaths in the second half of 2001 – before euthanasia was legalized – in Flanders, Belgium. We mailed anonymous questionnaires to physicians who signed the death certificates and asked them to report on ELDs, including nurses’ involvement. Results Response rate was 59% ( n=2950). Physicians reported nurses involved in decision making more often in institutions than at home, and more often in care homes for the elderly than in hospitals (OR 1.70, 95% CI 1.15, 2.52). This involvement was more frequently when physicians intended to hasten the patient's death than when they had no such intention (institutions: OR 2.05, 95% CI 1.41, 2.99; home: OR 2.04, 95% CI 1.19, 3.49). In institutions, this involvement was also more likely where patients were of lower rather than higher education (OR 2.95, 95% CI 1.49, 5.84). The administering of life-ending drugs by nurses, as reported by physicians was also found more frequently in institutions than at home, and in institutions more frequently with lower rather than higher educated patients ( p=.037). Conclusions These findings raise questions about physicians’ perception of the nurse's role in ELDs, but also about physicians’ skills in interacting with all patients. Education and guidelines for physicians and nurses are needed to optimize good communication and to promote a clearer assignment of responsibilities concerning the execution of those decisions.

Changes in medical end-of-life practices during the legalization process of euthanasia in Belgium

Changes in medical practices during transitions in regulating healthcare are rarely investigated. In this study, we investigated changes in medical end-of-life decisions with a possible or certain life-shortening effect (ELDs) that occurred during the legalization process of euthanasia in Belgium. We took representative random samples from deaths reported to registries in Flanders, Belgium in 1998 ( n=3999) at the beginning of the process and in 2001 ( N=5005), at the end of the process. The reporting physicians received an anonymous mail questionnaire about possible ELDs preceding the death involved. We found no significant shifts in the epidemiology of diseases between 1998 and 2001. The overall incidence of ELDs did not change. The incidence decreased for euthanasia, administering life-ending drugs without patient's explicit request, and alleviation of pain and symptoms with life-shortening co-intention. Incidence increased for alleviation of pain and symptom without life-shortening intention, and remained stable for non-treatment decisions. All decisions in 2001 were more often discussed with patients, their relatives and nurses. In 2001, continuous deep sedation was reported in 8.3% of deaths. We can conclude that physicians’ end-of-life practices have substantially changed during the short but tumultuous legalization process of euthanasia in Belgium. Although follow-up research is needed to investigate the continuance of these changes, it is important for policy makers to keep in mind that social factors related to transitions in healthcare regulation may play an important role in the physicians’ actual behaviour.

Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity

The neurotransmitter serotonin has been implicated in affecting the variation of longevity in natural Drosophila populations and age-related diseases in mammals. Based on these observations, it has been predicted that serotonin signal, perhaps at levels of serotonin biosynthesis, may control lifespan. Here, we investigated a variety of mutations in serotonin-signal genes, including serotonin biosynthesis genes, a serotonin transporter gene, and serotonin receptor genes. Despite this prediction, mutations in the serotonin biosynthesis genes had little or modest effects on lifespan, while the mod-5 mutation with increased availability of serotonin caused a modest life-shortening effect. In contrast, a deletion mutation of the ser-1 serotonin receptor gene increased longevity by up to 46%, likely through the insulin/insulin-like growth factor 1 pathway. This result suggests an interaction between the serotonin pathway and the insulin/insulin-like growth factor 1 pathway. A deletion mutation of another serotonin receptor gene, ser-4, shortened early to mid lifespan. The results suggest that serotonin signal antagonistically modulates longevity through different serotonin receptors. This study may indicate serotonin receptors as a potential target for antigeric interventions.

END‐OF‐LIFE DECISIONS AND OLD‐AGE MORTALITY: A CROSS‐COUNTRY ANALYSIS

END‐OF‐LIFE DECISIONS AND OLD‐AGE MORTALITY: A CROSS‐COUNTRY ANALYSIS

Comment on “End-of-life care: is euthanasia the answer?”by Truog

In an recent editorial published in Intensive Care Medicine Truog [1] commented upon the article by Provoost and colleagues [2] concerning the use of drugs with a life-shortening effect in end-of-life pediatric care, and he concluded that following the “doctrine of double effect” (DDE) is a preferable alternative to euthanasia. Although the DDE is morally acceptable in order to relieve the patient’s suffering and not directly to cause death when no alternatives are not available, we disagree with Truog’s use of the term euthanasia. The author uses euthanasia to describe unilateral decisions to avoid unnecessary suffering, decisions made without taking the patient’s opinion into account, on the basis of quality-of-life criteria as judged by physicians or parents. However, the patient’s explicit request for euthanasia as an option for end-of-life care is an essential condition in Dutch law for the use of this term. Obviously the term cannot be applied to infants who are not competent to make decisions of this kind. Therefore we believe that it is highly relevant to use the proper word, for the moral consequences involved in the concept are very important: euthanasia consists of putting an end to life when the patient is experiencing terminal suffering only if this is the expressed will of the patient. References