Defining priorities for improving end-of-life care in Canada

Background

High-quality end-of-life care should be the right of every Canadian. The objective of this study was to identify aspects of end-of-life care that are high in priority as targets for improvement using feedback elicited from patients and their families.

Methods

We conducted a multicentre, cross-sectional survey involving patients with advanced, life-limiting illnesses and their family caregivers. We administered the Canadian Health Care Evaluation Project (CANHELP) questionnaire along with a global rating question to measure satisfaction with end-of-life care. We derived the relative importance of individual questions on the CANHELP questionnaire from their association with a global rating of satisfaction, as determined using Pearson correlation coefficients. To determine high-priority issues, we identified questions that had scores indicating high importance and low satisfaction.

Results

We approached 471 patients and 255 family members, of whom 363 patients and 193 family members participated, with response rates of 77% for patients and 76% for families. From the perspective of patients, high-priority areas needing improvement were related to feelings of peace, to assessment and treatment of emotional problems, to physician availability and to satisfaction that the physician took a personal interest in them, communicated clearly and consistently, and listened. From the perspective of family members, similar areas were identified as high in priority, along with the additional areas of timely information about the patient’s condition and discussions with the doctor about final location of care and use of end-of-life technology.

Interpretation

End-of-life care in Canada may be improved for patients and their families by providing better psychological and spiritual support, better planning of care and enhanced relationships with physicians, especially in aspects related to communication and decision-making.Although a “quality death” is an espoused right of Canadians,¹ for many dying patients and their families, it is not achieved. Recent reviews and observational studies describe considerable dissatisfaction with end-of-life care, indicating that there are still opportunities for improvement.^2–5Ideally, initiatives aimed at improving end-of-life care would be informed by the experiences and expectations of patients and their family members. However, such efforts are often hampered by inadequate definitions of quality of care and by suboptimal tools for measurement.^6–8 In a recent, large cross-sectional survey, the Canadian Researchers at the End of Life Network defined what matters most to seriously ill patients as they approach the end of life.⁹ Both patients and their family members reported that it was extremely important that they have trust and confidence in the physicians caring for them or their loved ones.⁹ Avoidance of unwanted life-support measures, effective communication, continuity of care, and feelings of life completion were also rated as highly important.⁹ We used these comprehensive ratings of importance to develop and validate a novel questionnaire to measure satisfaction with end-of-life care.¹⁰ Using this questionnaire, we formally evaluated the care received at the end of life in several Canadian centres.By targeting initiatives for change at gaps in quality, we can address the highest priorities for improving end-of-life care in Canada. Our objective was to identify high-priority areas for improvement in the care of patients with advanced, life-limiting diseases and in the perceived quality of that care by their families. We identified these areas by focusing on care-related issues that had been rated as important by patients and their family members but were rated low on the questionnaire measuring satisfaction with end-of-life care.     

Genetic and pharmacologic inhibition of β-catenin targets imatinib-resistant leukemia stem cells in CML

A key characteristic of hematopoietic stem cells (HSCs) is the ability to self-renew. Genetic deletion of β-catenin during fetal HSC development leads to impairment of self-renewal while β-catenin is dispensable in fully developed adult HSCs. Whether β-catenin is required for maintenance of fully developed CML leukemia stem cells (LSCs) is unknown. Here, we use a conditional mouse model to show that deletion of β-catenin after CML initiation does not lead to a significant increase in survival. However, deletion of β-catenin synergizes with imatinib (IM) to delay disease recurrence after imatinib discontinuation and to abrogate CML stem cells. These effects can be mimicked by pharmacologic inhibition of β-catenin via modulation of prostaglandin signaling. Treatment with the cyclooxygenase inhibitor indomethacin reduces β-catenin levels and leads to a reduction in LSCs. In conclusion, inhibiting β-catenin by genetic inactivation or pharmacologic modulation is an effective combination therapy with imatinib and targets CML stem cells.     

Angiopoietin-2 Primes Infection-Induced Preterm Delivery

Current knowledge on the participation of angiopoietin-2 (Ang-2) in the inflammatory process and on the importance of bacterial endotoxins (LPS) in the induction of preterm delivery (PTD) led us to investigate the role of Ang-2/LPS interplay in the pathogenesis of PTD. At a first stage, Ang-2 was measured at the end of the first trimester of pregnancy in the serum of 50 women who delivered prematurely; of 88 women well-matched for age and parity who delivered full-term; and of 20 non-pregnant healthy women. Ang-2 was greater in pregnant than in non-pregnant women. The time until delivery was shorter among those with Ang-2 greater than 4 ng/ml (odds ratio for delivery until week 34; p: 0.040). To further investigate the role of Ang-2 for PTD, an experimental model of PTD induced by the intraperitoneal injection of LPS in mice was used. Ang-2 was administered intraperitoneally before LPS on day 14 of pregnancy. When Ang-2 was administered before the LPS diluent, all mice delivered full-term. However, administration of Ang-2 prior LPS accelerated further the time until delivery. Sacrifice experiments showed that the effect of Ang-2 was accompanied by decrease of the penetration of Evans Blue in the embryos and by increase of its penetration in maternal tissues. In parallel, the concentration of tumour necrosis factor-alpha in the maternal circulation, in fetal tissues and in the placentas was significantly decreased. Results indicate that Ang-2 accelerated the phenomena of PTD induced by LPS. This is related with deprivation of fetal perfusion.     

Characterization of a novel herbicide and antibiotic-resistant Chlorella sp. with an extensive extracellular matrix

Photosynthesis Research - A herbicide and antibiotic-resistant microalgal strain, isolated from a eutrophic site at Giofyros river (Heraklion, Crete, Greece) was extensively characterized. In the...     

Kinetics of isotope incorporation into the desoxyribonucleic acid (DNA) of tissues: Life span and generation time of cells

The dynamics of cell multiplication and differentiation in tissues in asteady state and the kinetics of isotope incorporation into the DNA have been theoretically analyzed. Equations have been derived, with the aid of which thegeneration time, thelife span, and the distribution or rate of death of the cells can be obtained if the tissue is in asteady state, i.e., if the number of cells is maintained constant by constant, equal rates of cell division and cell death and if the mean DNA content per cell is also constant. An equation has also been derived which gives thegeneration time in the case of logarithmic multiplication of cells. Two special cases have been analyzed: InCase 1, the isotope is considered as being introduced into the metabolic system at zero time only; inCase 2, the specific activity of the DNA precursor is considered as being maintained constant. The use of the method has been illustrated by an example in which thegeneration time and themean, themedian, and themode life span, as well as the curve of the rate of death of leukocytes in a patient with chronic leukemic granulocytic leukemia, have been obtained from the rate of P³² incorporation into the DNA. The merits and the limitations of the method are discussed. Aided in part by grant C-2350 from the National Institutes of Health, U. S. Public Health Service, and contract AT(45-1)-581 from the U. S. Atomic Energy Commission.     

Biophysical characterization of V3-lipopeptide liposomes influencing HIV-1 infectivity

The V3-loop of the HIV-1 gp120 alters host cell immune function and modulates infectivity. We investigated biophysical parameters of liposome constructs with embedded lipopeptides from the principle neutralizing domain of the V3-loop and their influence on viral infectivity. Dynamic light scattering measurements showed liposome supramolecular structures with hydrodynamic radius of the order of 900 and 1300nm for plain and V3-lipopeptide liposomes. Electron paramagnetic resonance measurements showed almost identical local microenvironment. The difference in liposome hydrodynamic radius was attributed to the fluctuating ionic environment of the V3-lipopeptide liposomes. In vitro HIV-1 infectivity assays showed that plain liposomes reduced virus production in all cell cultures, probably due to the hydrophobic nature of the aggregates. Liposomes carrying V3-lipopeptides with different cationic potentials restored and even enhanced infectivity (p<0.05). These results highlight the need for elucidation of the involvement of lipid bilayers as dynamic components in supramolecular structures and in HIV-1 fusion mechanisms.