ABSTRACT
Background: Many patients with breast cancer receive therapies with the potential to cause cardiotoxicity. Echocardiography and multiple-gated acquisition (MUGA) scans are the most used modalities to assess cardiac function during treatment in high-risk patients; however, the optimal imaging strategy and the impact on outcome are unknown. Methods: Consecutive patients with stage 0-3 breast cancer undergoing pre-treatment echocardiography or MUGA were identified from a tertiary care cancer center from 2010-2019. Demographics, medical history, imaging data and clinical events were collected from hospital charts and administrative databases. The primary outcome is a composite of all-cause death or heart failure event. Clinical and imaging predictors of outcome were evaluated on univariable and multivariable analyses. Results: 1028 patients underwent pre-treatment MUGA and 1032 underwent echocardiography. The groups were well matched for most clinical characteristics except patients undergoing MUGA were younger, had more stage 3 breast cancer and more HER2 over-expressing and triple negative cases. Routine follow-up cardiac imaging scan was obtained in 39.3% of patients with MUGA and 38.0% with echocardiography. During a median follow-up of 2448 (1489, 3160) days, there were 194 deaths, including 7 cardiovascular deaths, and 28 heart failure events with no difference in events between the MUGA and echocardiography groups. There were no imaging predictors of the primary composite outcome or cardiac events. Patients without follow-up imaging had similar adjusted risk for the composite outcome compared to those with imaging follow-up, hazard ratio 0.8 (95% confidence interval 0.5,1.3), p=0.457. Conclusion: The selection of pretreatment echocardiography or MUGA did not influence the risk of death or heart failure in patients with early breast cancer. Many patients did not have any follow-up cardiac imaging and did not suffer worse outcomes. Cardiovascular deaths and heart failure event rates were low and the value of long-term cardiac imaging surveillance should be further evaluated.
ABSTRACT
Examining the effects of different cosolutes on in vitro enzyme kinetics yielded glimpses into their potential behavior when functioning in their natural, complex, in vivo milieu. Viewing cosolute in vitro influences on a model enzyme, calf intestinal alkaline phosphatase, as a combination of competitive and uncompetitive behaviors provided quantitative insights into their effects on catalysis. Observed decreases in the apparent specificity constant, K asp, caused by the presence of polyethylene glycols or betaine in the reaction solution, indicated interference with enzyme-substrate complex formation. This competitive inhibition appeared to be driven by osmotic stress. Dextran 6 K and sucrose strongly impeded the subsequent conversion of the bound substrate into a free product, which was marked by sharp reductions in V max, uncompetitive inhibition. For the same step, smaller noncarbohydrate cosolutes, triethylene glycol, polyethylene glycol 400, and betaine, also behaved as uncompetitive inhibitors but to a lesser extent. However, polyethylene glycol 8000 and 20,000 were uncompetitive activators, increasing V max. Polyethylene glycol of molecular weight 1000 displayed intermediate effects between these two groups of noncarbohydrate cosolutes. These results suggested that crowding has a strong influence on free product formation. The combination of competitive and uncompetitive effects and mixed behaviors, caused by the cosolutes on calf intestinal alkaline phosphatase kinetics, was consistent with the trends seen in similar enzyme-cosolute studies. It is proposed that the double-displacement mechanism of alkaline phosphatases, shared by many other enzymes, could be the root of this general observation.
ABSTRACT
BACKGROUND: The process of dying in intensive care units is complex as the technological environment shapes clinical decisions. Decisions at the end of life require the involvement of patient, families and healthcare professionals. The degree of involvement can vary depending on the professional and social culture of the unit. Nurses have an important role to play in caring for dying patients and their families; however, their knowledge is not always sought. OBJECTIVES: This study explored nurses' care practices at the end of life, with the objective of describing and identifying end of life care practices that nurses contribute to, with an emphasis on culture, religious experiences and professional identity. Research Design and context: Grounded theory was used. In all, 10 nurses from intensive care unit in two large hospitals in Bahrain were participated. Ethical Considerations: Approval to carry out the research was given by the Research Ethics Committee of the host institution, and the two hospitals. FINDINGS: A core category, Death Avoidance Talk, was emerged. This was supported by two major categories: (1) order-oriented care and (2) signalling death and care shifting. DISCUSSION: Death talk was avoided by the nurses, doctors and family members. When a decision was made by the medical team that a patient was not to be resuscitated, the nurses took this as a sign that death was imminent. This led to a process of signalling death to family and of shifting care to family members. CONCLUSION: Despite the avoidance of death talk and nurses' lack of professional autonomy, they created awareness that death was imminent to family members and ensured that end of life care was given in a culturally sensitive manner and aligned to Islamic values.
