Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

End-of-life priorities of older adults with terminal illness and caregivers: A qualitative consultation

Abstract Background As older adults approach the end‐of‐life (EOL), many are faced with complex decisions including whether to use medical advances to prolong life. Limited information exists on the priorities of older adults at the EOL. Objective This study aimed to explore patient and family experiences and identify factors deemed important to quality EOL care. Method A descriptive qualitative study involving three focus group discussions (n = 18) and six in‐depth interviews with older adults suffering from either a terminal condition and/or caregivers were conducted in NSW, Australia. Data were analysed thematically. Results Seven major themes were identified as follows: quality as a priority, sense of control, life on hold, need for health system support, being at home, talking about death and competent and caring health professionals. An underpinning priority throughout the seven themes was knowing and adhering to patient's wishes. Conclusion Our study highlights that to better adhere to EOL patient's wishes a reorganization of care needs is required. The readiness of the health system to cater for this expectation is questionable as real choices may not be available in acute hospital settings. With an ageing population, a reorganization of care which influences the way we manage terminal patients is required

The Time Trade-Off Method: An Exploratory Study

In a pilot study we investigate whether the inferences we draw about people's preferences towards health care treatments are altered if we vary the procedure that is used to elicit these preferences. In a conventional Time Trade-Off question, respondents express their preferences towards treatment by comparing a period of ill-health with a shorter period in a higher quality of life. In our less conventional TTO question, we vary the procedure by asking respondents their preferences towards treatment by comparing a period of ill-health with a longer period in a lower quality of life. The quantitative data is equivocal about whether preferences for treatment differ between the conventional and unconventional questions. The qualitative data support the notion of contrasting issues in questions that involve prolonging time in a more severe quality of life and appear to account for a failure to find quantitative differences in all of the questions.Time Trade-Off, Procedural invariance

Metronomic chemotherapy preserves quality of life ensuring efficacy in elderly advanced non small cell lung cancer patients

Metastatic non small cell lung cancers (NSCLC) are diseases with poor prognosis and platinum-based doublet chemotherapy still remains their standard cure. Elderly patients often present comorbidities that limit the utilization of this chemotherapy; therefore these patients should have a first-line treatment with low toxicity and capable to preserve the quality of life (QoL) but, at the same time, to ensure the best possible response. Furthermore, a first-line treatment allows patients to be fit for further treatments, prolonging overall survival. At this regard, metronomic chemotherapy can be an optimal choice for elderly, able to improve QoL and to obtain an optimal palliation. We retrospectively studied a cohort of 41 elderly advanced NSCLC patients with different histotypes, treated with metronomic chemotherapy (weekly carbo-paclitaxel or vinorelbine as single agent) as first choice and we analyzed the tolerability, the impact on QoL and the efficacy of these schedules: no toxicity of 3 and 4 grade was observed, together to a clinical benefit of 43%. We administered FACT-L test to evaluate QoL at baseline and after 4 months and found a significant improvement in all FACT-L parameters: physical, social, emotional and functional, confirming a QoL improvement. At a median follow-up of 20.2 months the progression free survival was of 6 months and the overall survival was of 15 months. These results suggest that metronomic chemotherapy can be an effective choice of treatment for elderly NSCLC patients and further trials with more patients are needed to confirm this proposal

Role of splenectomy in human liver transplantation under modern-day immunosuppression

Between January 1987 and October 1991, 1466 patients underwent consecutive Orthotopic Liver Transplantation (OLTx) at the University of Pittsburgh. Forty of these patient's had concomitant splenectomy with OLTx. These patients were compared to 147 randomly selected OLTx patients without splenectomy within the same time period. One-year patient and graft survival (PS and GS) were lower in splenectomized (Splx) patients compared to nonsplenectomized (non-Splx) patients (59% vs 86% PS, 55% vs 80% GS, respectively). One-month and one-year patient mortality in the Splx group was higher than in the non-splx patients (20% vs 3.4% P < 0.001 for one month; 40% vs 14.3%, P = 0.003 for one year, respectively). One-month and one-year sepsis-related mortality was also high in Splx patients (17.5% vs 2.7%, P = 0.0022, for one month, and 30% vs 11.5%, P = 0.0043, for one year, respectively). We conclude that concomitant splenectomy with OLTx has a significantly higher patient mortality mainly due to its septic complications and, at present, unless there is a specific indication for a splenectomy, the routine addition of this procedure to liver allograft surgery would not be recommended

Extending life for people with a terminal illness: a moral right and an expensive death? Exploring societal perspectives

BACKGROUND: Many publicly-funded health systems apply cost-benefit frameworks in response to the moral dilemma of how best to allocate scarce healthcare resources. However, implementation of recommendations based on costs and benefit calculations and subsequent challenges have led to ‘special cases’ with certain types of health benefits considered more valuable than others. Recent debate and research has focused on the relative value of life extensions for people with terminal illnesses. This research investigates societal perspectives in relation to this issue, in the UK. METHODS: Q methodology was used to elicit societal perspectives from a purposively selected sample of data-rich respondents. Participants ranked 49 statements of opinion (developed for this study), onto a grid, according to level of agreement. These ‘Q sorts’ were followed by brief interviews. Factor analysis was used to identify shared points of view (patterns of similarity between individuals’ Q sorts). RESULTS: Analysis produced a three factor solution. These rich, shared accounts can be broadly summarised as: i) ‘A population perspective – value for money, no special cases’, ii) ‘Life is precious – valuing life-extension and patient choice’, iii) ‘Valuing wider benefits and opportunity cost - the quality of life and death’. From the factor descriptions it is clear that the main philosophical positions that have long dominated debates on the just allocation of resources have a basis in public opinion. CONCLUSIONS: The existence of certain moral positions in the views of society does not ethically imply, and pragmatically cannot mean, that all are translated into policy. Our findings highlight normative tensions and the importance of critically engaging with these normative issues (in addition to the current focus on a procedural justice approach to health policy). Future research should focus on i) the extent to which these perspectives are supported in society, ii) how respondents' perspectives relate to specific resource allocation questions, and iii) the characteristics of respondents associated with each perspective

Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease

Energy Efficient Ant Colony Algorithms for Data Aggregation in Wireless Sensor Networks

In this paper, a family of ant colony algorithms called DAACA for data aggregation has been presented which contains three phases: the initialization, packet transmission and operations on pheromones. After initialization, each node estimates the remaining energy and the amount of pheromones to compute the probabilities used for dynamically selecting the next hop. After certain rounds of transmissions, the pheromones adjustment is performed periodically, which combines the advantages of both global and local pheromones adjustment for evaporating or depositing pheromones. Four different pheromones adjustment strategies are designed to achieve the global optimal network lifetime, namely Basic-DAACA, ES-DAACA, MM-DAACA and ACS-DAACA. Compared with some other data aggregation algorithms, DAACA shows higher superiority on average degree of nodes, energy efficiency, prolonging the network lifetime, computation complexity and success ratio of one hop transmission. At last we analyze the characteristic of DAACA in the aspects of robustness, fault tolerance and scalability.Comment: To appear in Journal of Computer and System Science