Remaining Life Span Research Articles

Markers and mechanisms of death in Drosophila.

Parameters correlated with age and mortality in Drosophila melanogaster include decreased negative geotaxis and centrophobism behaviors, decreased climbing and walking speed, and darkened pigments in oenocytes and eye. Cessation of egg laying predicts death within approximately 5days. Endogenous green fluorescence in eye and body increases hours prior to death. Many flies exhibit erratic movement hours before death, often leading to falls. Loss of intestinal barrier integrity (IBI) is assayed by feeding blue dye ("Smurf" phenotype), and Smurf flies typically die within 0-48h. Some studies report most flies exhibit Smurf, whereas multiple groups report most flies die without exhibiting Smurf. Transgenic reporters containing heat shock gene promoters and innate immune response gene promoters progressively increase expression with age, and partly predict remaining life span. Innate immune reporters increase with age in every fly, prior to any Smurf phenotype, in presence or absence of antibiotics. Many flies die on their side or supine (on their back) position. The data suggest three mechanisms for death of Drosophila. One is loss of IBI, as revealed by Smurf assay. The second is nervous system malfunction, leading to erratic behavior, locomotor malfunction, and falls. The aged fly is often unable to right itself after a fall to a side-ways or supine position, leading to inability to access the food and subsequent dehydration/starvation. Finally, some flies die upright without Smurf phenotype, suggesting a possible third mechanism. The frequency of these mechanisms varies between strains and culture conditions, which may affect efficacy of life span interventions.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects

ObjectiveThe authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. MethodSingle-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. ResultsAmong 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007. Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. ConclusionsNew morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

Prediction of the Remaining Useful Life of a Switch Machine, Based on Multi-Source Data

Aimed at the shortcomings of a single feature to characterize the health status and accurately predict the remaining life span of the equipment, a prediction method for a switch machine, based on the weighted Mahalanobis distance (WDMD), is proposed. The method consists of two parts: the construction of a health indicator, based on the weighted Markov distance and the prediction of the remaining useful life, based on the hidden Markov model (HMM). Firstly, a kernel principal component analysis (KPCA) is used to extract the characteristics of the power curve data of the switch machine, and the characteristics with a high correlation with the degradation process are screened, according to the trend indicators. Secondly, the resulting features are combined with multi-source information, as the input, and a comprehensive health indicator (HI) is constructed by the weighted fusion of the WDMD algorithm, to characterize the degradation process of the switch machine. The degradation model of this HI is established and trained by the HMM, so as to predict the remaining life span of the equipment. Finally, the actual operation data of the railway field is selected to verify the prediction method proposed in the paper. The results show that the state recognition and the life prediction accuracy of the proposed method is higher, which can provide effective opinions for the predictive maintenance of the switch machine equipment.

PB1886: LONG-TERM TRENDS IN THE LOSS OF LIFE EXPECTANCY AFTER A DIAGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA: A POPULATION-BASED STUDY IN THE NETHERLANDS, 1989-2018

Background: The introduction of chemoimmunotherapy heralded a new era for chronic lymphocytic leukemia (CLL) management. More recently, the chemoimmunotherapy paradigm has shifted towards more novel targeted agents that can further improve progression-free survival and overall survival. Population-based studies have shown that the five-year relative survival in CLL increased markedly since the introduction of chemoimmunotherapy, approximating 90% for patients up to age 70. Seeing the comparatively favorable prognosis of CLL patients in modern times, other survival estimates may be more informative because relative survival does not inform on patient survival across the entire remaining life span. Aims: Studies estimating the life expectancy of CLL patients are hitherto lacking. Therefore, we assessed trends in the life expectancy of CLL patients from a historical and contemporary perspective. Methods: We selected all CLL patients diagnosed in the Netherlands between 1989 and 2018—with follow-up for survival up to December 31, 2020—from the Netherlands Cancer Registry. We estimated the loss in expectation of life (LEL)—quantifying the difference between the life expectancy of CLL patients and the general population, the latter being matched to patients by age, sex, and calendar year—using flexible parametric relative survival models. The LEL is interpreted as the average number of life years lost due to a CLL diagnosis. The LEL can vary markedly across ages because life expectancy is age-dependent. Therefore, the proportional LEL (PLEL) was estimated (calculated as the LEL divided by the population life expectancy). These survival measures were presented by year of diagnosis for four age categories at diagnosis (i.e., 50, 60, 70, and 80 years), stratified by sex. Results: Our cohort included 23,692 CLL patients (median age, 69 years, interquartile range 61-77 years; 61% males) diagnosed in the Netherlands between 1989-2018. The life expectancy of CLL patients increased gradually across all ages between 1989-2018, with a most pronounced increase in patients aged 50 and 60 years at diagnosis (Fig 1A). CLL patients diagnosed in 1990 and 2018 lost 3.1-19.0 and 1.7-8.2 life-years depending on age and sex, respectively (Fig 1A). The increase in the life expectancy of CLL patients was greater than in the general population. Consequently, the LEL (Fig 1B) and PLEL (Fig 1C) of CLL patients across all four age categories decreased over time. Despite the decrease in LEL over time, all studied age groups diagnosed in 2018 had excess mortality, reflected in a LEL ranging from 1.7 to 8.2 life-years, depending on age and sex (Fig 1B). The PLEL estimates showed that the age differential in survival became less pronounced over time and eventually disappeared for female patients, of which the former indicates that older patients (i.e. 70 and 80 years), who generally have fewer life-years left, experience the same improvement in life expectancy as younger patients. Image:Summary/Conclusion: The life expectancy of CLL patients diagnosed in the Netherlands between 1989-2018 has steadily increased over time. This increase is likely attributed to the broader application of more efficacious therapies over time. Notwithstanding, continuous population-based surveillance is essential to assess the impact of the rapidly evolving management of CLL on survival since excess mortality is still a threat in contemporary diagnosed and managed patients.

Ayahuasca on Trial

In 1986, American scientist and entrepreneur Loren Miller received Plant Patent No. 5, 751 on a “novel” strain of the ayahuasca plant, which he named “Da Vine.” Indigenous tribes and healers had been using ayahuasca for hundreds of years before it was brought into Western culture. Miller’s accepted claim to novelty, however, was founded on this particular strain’s color and medicinal properties. Several years after his “discovery,” Indigenous peoples of Ecuador learned that their sacred plant had been patented and demanded that Miller’s patent be revoked for not meeting the novelty requirements of the US Plant Patent Act. In 1999, the US Patent and Trademark Office revoked Miller’s patent based on evidence of the strain’s existence in US botanical museums prior to Miller’s licensing. Subsequent to this decision, however, Miller filed for an appeal, and his “Da Vine” patent was reinstated for its remaining life span. This case demonstrates how international patent law reinscribes asymmetrical power relations between the “West and the rest” by deferring to a legal structure that remains inherently colonial in nature and practice. Beginning with a history of patent law, this paper examines Miller’s case as it disregards Indigenous existence, legitimizes property theft, and commodifies a sacred plant.

Considering Computational Mathematics IGHG3 as Malignant Melanoma Is Associated with Immune Infiltration of Malignant Melanoma.

Malignant melanoma is one of the most threatening cancers to human health. Only 14% of patients with malignant melanoma have a remaining life span of 5 years. At present, there have been some studies looking for potential prognostic indicators of esophageal cancer from the level of genes and infiltrating immune cells, but there are still some problems that need to be resolved urgently. This paper proposes IGHG3 as the immune infiltration of malignant melanoma, which takes into account the computational mathematics. It aims to deduce the characteristics of immune cell infiltration in malignant melanoma and study the relationship between different immune cell infiltration characteristics and prognosis. The method in this article is to establish a computational mathematical model for the immunotherapy of melanoma, then study the method of identification of the affinity of the IGHG3 reagent, and finally obtain the gene expression of immune infiltration. The functions of these methods are, respectively, to predict the dynamic behavior of T cells with two different specificities through mathematical models and to test the matching degree of different concentrations of IGHG3 reagent with the human body. Then use the ssGSEA algorithm to obtain immune infiltration related data and calculate the difference between the weighted empirical cumulative distribution function of all genes in the effect of IGHG3 on melanoma that was carried out. The experimental results showed the computational mathematical method genome and all the remaining genes. In this study, a computational mathematical method to detect the IGHG3 gene expression had a significant inhibitory effect on A375 cells in the experimental group, and the knockdown efficiency reached 85.6%.

Prescribing Smartphone Apps for Physical Activity Promotion in Primary Care: Modeling Study of Health Gain and Cost Savings.

BackgroundInadequate physical activity is a substantial cause of health loss worldwide, and this loss is attributable to diseases such as coronary heart disease, diabetes, stroke, and certain forms of cancer.ObjectiveThis study aims to assess the potential impact of the prescription of smartphone apps in primary care settings on physical activity levels, health gains (in quality-adjusted life years [QALYs]), and health system costs in New Zealand (NZ).MethodsA proportional multistate lifetable model was used to estimate the change in physical activity levels and predict the resultant health gains in QALYs and health system costs over the remaining life span of the NZ population alive in 2011 at a 3% discount rate.ResultsThe modeled intervention resulted in an estimated 430 QALYs gained (95% uncertainty interval 320-550), with net cost savings of 2011 NZ $2.2 million (2011 US $1.5 million) over the remaining life span of the 2011 NZ population. On a per capita basis, QALY gains were generally larger in women than in men and larger in Māori than in non-Māori. The health impact and cost-effectiveness of the intervention were highly sensitive to assumptions on intervention uptake and decay. For example, the scenario analysis with the largest benefits, which assumed a 5-year maintenance of additional physical activity levels, delivered 1750 QALYs and 2011 NZ $22.5 million (2011 US $15.1 million) in cost savings.ConclusionsThe prescription of smartphone apps for promoting physical activity in primary care settings is likely to generate modest health gains and cost savings at the population level in this high-income country. Such gains may increase with ongoing improvements in app design and increased health worker promotion of the apps to patients.

Концептуальные основы качества жизни как важнейшего индикатора продуктивности лечебно-диагностического процесса

We consider the main conceptual basic principles of the theory of assessing the quality of life (QoL) and the quality of life associated with health (HRQoL). We reveal the essence and socio-economic significance of the concept of “quality of life”, its semantic and operational fullness. We present the analysis of the essence of the “health-related quality of life” concept, its significance for evaluating the effectiveness of the therapeutic and diagnostic process, important aspects of the use of HRQoL tools in real clinical conditions, differences and orientation of non-specific and specific questionnaires used in medicine. It is noted that measuring the quality of life is an important component of interviewing a patient, involving him in treatment, making decisions about medical interventions and limiting the possibilities of modern medicine by suspending or stopping treatment, so as not to prolong life at any cost, but to improve subjective perceptions during the remaining life span. Making the quality of life measurable is a methodological task, since it cannot be directly displayed; the development of objective and subjective indicators is indicative here, but they should also be sensitive enough to changes to correctly assess the quality of life. At the same time, the development of questionnaires for measuring the quality of life is subject to quality assurance criteria that must be met in the research process. In conclusion, an example of comprehensive studies of the quality of life conducted at the Public Health and Healthcare Department of Medical Institute in Derzhavin Tambov State University, where a regional center for the study of the quality of life of various population groups, as well as the quality of life of patients suffering from various diseases, has been successfully operating in the last few years.

Secondary malignancy risk for patients with localized prostate cancer after intensity-modulated radiotherapy with and without flattening filter.

Men treated for localized prostate cancer by radiotherapy have often a remaining life span of 10 yr or more. Therefore, the risk for secondary malignancies should be taken into account. Plans for ten patients were evaluated which had been performed on an Oncentra® treatment planning system for a treatment with an Elekta Synergy™ linac with Agility™ head. The investigated techniques involved IMRT and VMTA with and without flattening filter. Different dose response models were applied for secondary carcinoma and sarcoma risk in the treated region and also in the periphery. As organs at risk we regarded for carcinoma risk urinary bladder, rectum, colon, esophagus, thyroid, and for sarcoma risk bone and soft tissue. The excess absolute risk (EAR) was found very similar in the treated region for both techniques (IMRT and VMAT) and also for both with and without flattening filter. The secondary sarcoma risk resulted about one magnitude smaller than the secondary carcinoma risk. The EAR to the peripheral organs was statistically significant reduced by application of the flattening filter free mode concerning the flattening filter as main source of scattered dose. Application of flattening filter free mode can thus support to reduce second malignancy risk for patients with localized prostate cancer.

Landslide‐dammed lake sediment volume calculation using waterborne ERT and SONAR profiling

AbstractLake sediment volume calculation is a challenging task, namely in cases when detailed drilling is complicated, expensive, or impossible, information on the pre‐sedimentation surface unavailable, and record of siltation rate non‐existent or too short. This study shows how waterborne, non‐invasive geophysical survey, such as electrical resistivity tomography (ERT) can be very effective in acquiring the missing data, namely when combined with sound navigation ranging (SONAR) water depth measurements and supported by information from auxiliary sources. However, ERT surveying in water environment requires specific approaches, as we illustrate on the case of the Mladotice lake study. The lake was created after a landslide in May 1872, and since its formation, the depth has gradually decreased due to sedimentation. We have reconstructed the original surface, calculated the sediment volume, and compiled information on sedimentation to estimate its remaining life span. To achieve this, we measured nine waterborne ERT profiles across the lake. To reach the necessary depth, all ERT profiles were extended on land and crossed the lake using custom‐built flotation pads. ERT profiling was combined with SONAR depth measurements, historical bathymetric surveys, borehole core analysis, sediment flux measurements, volumetric calculations, and water conductivity probing. The study has achieved three main results. First, practical applicability and advantages of stationary waterborne ERT profiling in combination with bathymetric sounding were demonstrated. Second, the original lake volume and accumulated sediment was calculated. We estimate that the volume of lake sediment is 187 000 m3, two‐thirds of the original lake volume (over 275 000 m3). Finally, based on three volumetric data sets from 1972, 2003, and 2017, and recent monitoring of the sediment inflow, we propose scenarios of lake filling and its future development. Most interestingly, the sedimentation rate has decreased significantly in the last 20 years, suggesting that the lake may survive much longer than hitherto expected. © 2020 John Wiley &amp; Sons, Ltd.

Short-term Psychological Outcomes of Disclosing Amyloid Imaging Results to Research Participants Who Do Not Have Cognitive Impairment

The goal of preclinical Alzheimer disease (AD) clinical trials is to move diagnosis and treatment to presymptomatic stages, which will require biomarker testing and disclosure. To assess the short-term psychological outcomes of disclosing amyloid positron emission tomography results to older adults who did not have cognitive impairment. This observational study included participants who were screening for a multisite randomized clinical trial that began on February 28, 2014, and is anticipated to be completed in 2022. Participants aged 65 to 85 years who had no known cognitive impairments underwent an amyloid positron emission tomography scan and learned their result from an investigator who used a protocol-specified process that included prescan education and psychological assessments. This report compares participants with elevated amyloid levels with at least 1 available outcome measure with participants who did not have elevated amyloid levels who enrolled in an observational cohort study and received further evaluations. Data were collected from April 2014 to December 2017 and analyzed from March 2019 to October 2019. A personal biomarker result described as either an elevated or not elevated amyloid level. To assess the immediate and short-term psychological outcome of disclosure, the following validated measures were used: the Geriatric Depression Scale, the state items from the State-Trait Anxiety Inventory, and the Columbia Suicide Severity Rating Scale, as well as the Concerns About AD Scale and the Future Time Perspective Scale to assess changes in participants' perceived risk for AD and perceived remaining life span, respectively. A total of 1167 participants with elevated amyloid levels and 538 participants with not elevated amyloid levels were included. Participants had a mean (SD) age of 71.5 (4.7) years, 1025 (60.1%) were women, and most were white (1611 [94.5%]) and non-Latino (1638 [96.1%]). Compared with participants who learned that they had a not elevated amyloid result, individuals who learned of an elevated amyloid result were no more likely to experience short-term increases in depression (mean [SD] change in the Geriatric Depression Scale score, 0.02 [1.3] vs 0.04 [1.3]; P = .90), anxiety (mean [SD] change in State-Trait Anxiety Inventory score, -0.02 [3.2] vs -0.15 [3.0]; P = .65), or suicidality (mean [SD] change in the Columbia Suicide Severity Rating Scale score, 0.0 [0.4] vs -0.01 [0.5]; P = .67). Participants with elevated amyloid levels had increased Concern About AD scores (raw change in scores: elevated amyloid group, 0.8 [3.9]; not elevated amyloid group, -0.4 [3.8]; P < .001). Participants with not elevated amyloid levels experienced a slight increase in Future Time Perspective score(mean [SD] score, 1.15 [7.4] points; P < .001); there was no change in time perspective among those receiving an elevated amyloid result (mean [SD] score, 0.33 [7.8] points). In this observational preclinical AD study, participants who learned they had elevated amyloid levels did not experience short-term negative psychological sequelae compared with persons who learned they did not have elevated amyloid levels.

Redefining Palliative Care—A New Consensus-Based Definition

ContextThe International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. ObjectiveThe main objective of this article is to present the research behind the new definition. MethodsThe three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. ResultsThe consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. ConclusionParticipants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.

A Device to Drive CFL Bulbs with Busted Electronic Ballast: A Prototype Development and Evaluation

CFLs are one of the most commonly used lighting fixtures in the modern era. Studies regarding its life cycle assessment (LCA) indicated that in the disposal stage CFLs have more hazardous potential to impact human health and ecosystem than the incandescent bulbs due to their higher metal-containing components. Thus, possible recycling of CFL bulbs with busted electronic ballast but still has its remaining life span should considered. By using experimental-developmental method, the study aimed to develop a prototype device to drive CFL bulbs with busted electronic ballast. The prototype was tested and evaluated regarding its efficiency as compared to original electronic ballast of CFLs. Results indicated that the developed prototype had efficiencies ranging from 75.6% to 90.8% respectively. Statistical tests also indicated that though found out to have numerical difference between the illuminations emitted by the lamp when driven by its original electronic ballast to the illumination it emits when driven by the prototype device, this numerical difference would not translate into a significant statistical difference.

Repair vs. replacement: Selection of the best end-of-life scenario for small household electric and electronic equipment based on life cycle assessment

This study presents a methodology designed for selecting, from an environmental point of view, the best end-of-life scenario for electric and electronic equipment which breaks before the end of its life span. To this end, the environmental impact of the life cycle of the equipment is evaluated for two different end-of-life scenarios: repair & reuse vs. replacement. As a case study, the proposed methodology is applied to a representative sample of nine categories of small household electric and electronic equipment (120 appliances). Repair & reuse scenarios consider the life span and the typical failures and repairs associated with each electric and electronic equipment category and the use of the repaired equipment until the remaining life span after its breakage. Replacement scenarios also consider the life span associated to each electric and electronic equipment category and the replacement of the broken equipment by an equivalent during the remaining life span after its breakage. The environmental impact obtained for both scenarios for each small household electric and electronic equipment category is compared in order to identify the best end-of-life scenario. To do so, the life cycle assessment methodology is applied, using CML and ReCiPe as midpoint- and endpoint-impact assessment methods, respectively. The results indicate that for all the analysed categories, the repair & reuse scenarios generally prove environmentally better than replacement scenarios, as Directive 2012/19/EU promotes. However, for some types of failure, e.g. those related to motors or printed circuit boards, if the failure occurs at the end of its life span, replacement is a better option than repair & reuse, since the environmental impact of the repair activities is not offset by the environmental benefits of extending the useful life until the end of the life span.

Individual Risk Evaluation for Local Recurrence and Distant Metastasis in Ewing Sarcoma: A Multistate Model

Background: This study aims to investigate the effect of surgical margins, histological response and radiotherapy, on local recurrence (LR), distant metastasis (DM) and survival in Ewing sarcoma patients. Methods: We performed a retrospective analysis of 982 Ewing sarcoma patients who underwent surgery after induction chemotherapy. To study disease evolution a multistate model with initial state surgery, intermediate states LR, pulmonary metastasis (DMpulm), other DM±LR (DMother) and final state death was estimated. The effect of risk factors on different disease states was estimated using Cox proportional hazard models. Hazard ratios (HRs) along with 95% confidence interval (95%CI) are provided. Overall survival (OS) from surgery was calculated using Kaplan-Meier's estimates. Findings: The median follow-up was 7·6 years (95%CI 7·2-8·0). 5-year OS was 74% (71-77) for localized disease, 56% (47-55) for pulmonary metastasis, 43% (33-53%) for extrapulmonary metastasis. Risk factors for LR are pelvic location, HR 2·04(95%CI 1·10-3·80), and marginal/intralesional resection, HR 2·28(1·25-4·16), administration of radiotherapy is protective, HR 0·52(0·28-0·95), for all tumor sites combined; risk factors for DMpulm are <90% necrosis, HR 2·13(1·13-4·00), and previous pulmonary metastasis, HR 4·90(2·28-8·52). Risk factors for DMother are 90-99% necrosis, HR 1·56(1·09-2·23), <90% necrosis, HR 2·66 (1·87-3·79), and previous bone/other metastasis, HR 3·08(2·03-4·70). Risk factors for death without LR/DM are pulmonary metastasis, HR 8·08(4·01-16·29), bone/other metastasis, HR 10·23(4·90-21·36) and <90% necrosis. Early LR (0-24 months) negatively influences survival, HR 3·79(1·34-10·76). Once DMpulm/DMother arise only previous bone/other metastasis remain prognostic for death, HR 1·74(1·10-2·75). Interpretation: Disease extent at diagnosis and histological response are the main risk factors for progression to distant metastasis or death. Tumor site and surgical margins are important risk factors for LR. In case disease progression occurs, previous risk factors lose their relevance, and the balance between toxicity of intensive salvage treatments and quality of life in the remaining life span of these patients should be carefully considered. In case of isolated LR, time to recurrence is important for decision-making, since early LR (0-24 months) negatively influences survival. Radiotherapy seems to be protective for LR especially in pelvic/axial locations. The low percentage of LR in extremity tumors and associated toxicity questions the need for radiotherapy in extremity Ewing sarcoma. Funding Statement: This study was supported by a donation from the Team Westland Foundation (to PDSD), a German Cancer Aid grant 108128 to UD; ERA-Net-TRANSCAN consortium, project number 01KT1310, and Euro Ewing Consortium EEC, project number EU-FP7 602856, both funded under the European Commission Seventh Framework Program FP7-HEALTH (to UD); and by David Dressler+ (to UD). Declaration of Interests: The authors have no conflict of interest. Ethics Approval Statement: This retrospective study was reviewed and approved by the institutional review board of Leiden University Medical Center (Leiden, The Netherlands) and a waiver for informed consent was granted.

Process of Decline in Activities of Daily Living of Older Chinese People Prior to Death: Evidence From Three Cohorts.

The study analyzes the decline in activities of daily living (ADL) prior to death among three cohorts of older Chinese. With data from the Chinese Longitudinal Healthy Longevity Survey, the process of decline in ADL in older people born during the periods 1899-1908, 1909-1918, and 1919-1928 is analyzed using the hierarchical linear model with mixed effects. The remaining survival time has a stronger effect on changes in ADL than chronological age, and there is significant heterogeneity among the older adults in ADL. Decline in ADL is delayed by extending life span. Older people with healthy behaviors, good living conditions in childhood, and age-friendly living environment have long-lasting good ADL during their remaining life span; socioeconomic resources help the older adults with ADL disabilities to survive. Selective effects of mortality and protective effects of socioeconomic resources explain the heterogeneity in ADL and its changes over time.

Expectation and Preferences with Palliative Systemic Therapy in Recurrent Gliomas

Background: Expectation and preferences of recurrent glioma patients are rarely captured and hence are ill reported in literature. To overcome the above-mentioned deficiency, we undertook a study to capture the expectation and preferences of recurrent glioma patients. Methods: This was cross-sectional study, with the expectation and preferences, of 40 recurrent glioma patients were captured at a single visit post counseling about the disease prognosis and treatment options. SPSS version 16 and RStudio version 3.4.2 was used for analysis and descriptive statistics was performed. Results: Prolongation of life as alone or in combination with symptom control was the primary expectation in 90% of patients (n=36, 95% CI 76.2-96.5). The median time patients preferred to devote out of the remaining life span for home, work and hospital were 60% (IQR 60-90), 32.5% (IQR 1.25-50) and 0% (IQR 0-10) respectively. The adverse event most feared by patients and hence not preferred were skin rash (7, 17.5%), numbness (7, 17.5%) and vomiting (6, 15%). Majority of patients (67.5%, 27) were willing to trade off a survival of >4 months for a cheaper regimen if necessitated. Ninety-five (38) percent of patients were willing to participate in the research protocols if they are available. Conclusion: Prolongation of life either alone or along with symptom control is the primary expectation from systemic therapy of recurrent glioma patients.

Abiraterone acetate, enzalutamide and their sequence for castration-resistant prostate cancer : Adherence, survival and hospitalization analysis of amedical claims database.

To analyze drug adherence, overall survival (OS) and hospitalization rates of patients with castration-resistant prostate cancer (CRPC) treated with arbiraterone acetate (AA), enzalutamide (ENZ) and their sequence in areal-life setting. The database of the largest public insurance company in Austria was analyzed. All CRPC patients with at least one prescription of AA and/or ENZ between September 2013 and August 2016 in the pre-chemotherapy and post-chemotherapy setting were extracted and matched to the Austrian death and hospital admission statistics. Drug adherence was estimated by the medication possession ratio (MPR). Data of 457 patients (mean age: 74.4 ± 8.5years) were analyzed. The mean MPR was 90% for AA, 85% for ENZ and 88% for the sequence therapy cohort. The median overall survival (OS) of the entire cohort was 21months: 15months for AA, 24months for ENZ, 26months for the sequence group, and 10months for the sequence group after switching. In the post-chemotherapy setting, the median OS was 14months in AA treatment (mean: 15.8 ± 0.9months), 19months in the ENZ treatment (mean: 17.2 ± 1.4months) and 25months in the sequence group (mean: 22.7 ± 0.8months). Median OS in the pre-chemotherapy setting was 25months (mean: 21.5 ± 1.1months), 18months in AA treatment group (mean: 18.9 ± 1.5months) and 17months in ENZ treatment group (mean: 18.2 ± 1.9months). Only 43 (9.4%) patients were not hospitalized during the course of the study. On average patients spent 13% of their remaining life span in hospital care (median 8%, range: 1-34%). This Austrian prescription database allows some insights into the outcome of CRPC patients treated with AA and ENZ and their sequence in areal-life setting. Drug adherence was satisfactory, OS was shorter for AA and ENZ as compared to the pivotal phase III trials.

Chronological and Biological Age Predict Seasonal Reproductive Timing: An Investigation of Clutch Initiation and Telomeres in Birds of Known Age.

Female vertebrates that breed earlier in the season generally have greater reproductive success. However, evidence suggests that breeding early may be costly, thus leading to the prediction that females with fewer future reproductive events will breed earlier in the season. While chronological age is a good indicator of remaining life span, telomere lengths may also be good biomarkers of longevity as they potentially reflect lifetime wear and tear (i.e., biological age). We examined whether variation in the timing of the first seasonal clutch was related to age and telomere length in female dark-eyed juncos (Junco hyemalis), predicting that older females and those with shorter telomeres would breed earlier. Both predictions held true and were independent of each other, as telomere length did not significantly vary with age. These results suggest that females may adjust their reproductive effort based on both chronological and biological age.

Lifetime cost for type 2 diabetes mellitus in Singapore.

The mean annual direct medical cost of type 2 diabetes mellitus (T2DM) in Singapore has been found to be SGD 2034 using the prevalence-based approach, but the lifetime direct medical cost of T2DM in Singapore remains largely unknown. The aim of the present study was to determine the lifetime direct medical cost attributable to T2DM and provide estimates of potential savings if T2DM can be prevented or delayed. The incidence-based approach was used for the cost-of-illness analysis. Yearly medical expenses were obtained from a regional health system database in Singapore to estimate the lifetime medical cost of T2DM patients. Then, the lifetime medical cost of non-T2DM subjects was predicted using a regression model. From the database, gender- and age-specific annual survival rates of T2DM and non-T2DM subjects were obtained and survival-adjusted yearly expenses over the estimated remaining life span were added to obtain lifetime medical costs. The difference between T2DM and non-T2DM subjects was attributed to excess direct medical costs of T2DM. The excess lifetime medical expenses for T2DM patients were SGD 132 506, 108 589, 83 326 and 70 110 when the age of T2DM diagnosis was 40, 50, 60, and 65 years, respectively. Even though T2DM patients have a lower life expectancy, T2DM is associated with substantially higher lifetime medical costs. Delaying the onset of T2DM, especially in the young, may lead to lower lifetime medical expenses. If prevention costs can be kept sufficiently low, effective T2DM prevention efforts would likely lead to a reduction in long-term medical costs.