Search

Objective: To investigate views, determinants and barriers to end-of-life discussions for doctors, nurses and members of the public (MoP) and their acceptability of risk prediction tools., Methods: Concurrent surveys of 360 doctors and nurses and 497 MoP., Results: Sixty per cent of clinicians reported high confidence in initiating end-of-life discussions, and 55.8% regularly engaged in them. Barriers to end-of-life communication reported by clinicians were uncertainty on the likely time to death (44.7%) and family requests to withhold information from patients (44.2%). By contrast, most (92.8%) MoP wanted information about life expectancy; 89.9% wanted involvement in treatment decisions if the likelihood of death was high; and 23.8% already had an advance care directive., Conclusions: A dissonance exists between doctor/nurses perception of older peoples' preference for receiving prognostic information and the public desire for involvement in decision-making at the end of life. As public attitudes change, strategies for greater involvement of patients in shared end-of-life planning are warranted., (© 2019 AJA Inc.)

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., (© 2019 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Nephrotoxicity is a serious side effect associated with ifosfamide use. It can affect up to 30% of children who are treated with this chemotherapeutic drug, and treatment may necessitate lifelong supplementations, renal dialysis, renal transplant, and in severe cases may result in death. The antioxidant n-acetylcysteine is a promising strategy for mitigating this renal toxicity. It is currently used in children for acetaminophen overdose in the 21-hour IV protocol, a dose which has also been suggested to provide renal protection against ifosfamide. Of significance, both in vitro and in vivo studies suggest n-acetylcysteine does not interfere with the antitumor actions of ifosfamide. Most importantly, n-acetylcysteine has successfully protected against ifosfamide-induced nephrotoxicity in both cell and rodent models, as well as in several paediatric cases, suggesting it should be evaluated as a treatment option for children on ifosfamide who present with renal dysfunction. The purpose of this paper is to outline strategies and recommendations for treating patients at risk or suffering from nephrotoxicity during ifosfamide therapy. These recommendations may be used when deciding who to treat, how and when to treat, as well as several considerations when exact recommendations cannot be met. They have been created to increase both the quality of care and quality of life of paediatric oncology patients.

Background/aim: Nephrotoxicity is observed in 30% of children treated with ifosfamide. We have shown that n-acetylcysteine (NAC) successfully mitigates nephrotoxicity of ifosfamide in cell and rodent models. However, before this treatment is evaluated clinically, it must be established that NAC does not interfere with the efficacy of ifosfamide., Materials and Methods: Mice implanted with Ewing's sarcoma tumours received the following treatments: saline, ifosfamide, ifosfamide + NAC concurrently, pre-treatment with NAC + ifosfamide, or NAC alone., Results: Median volumes of EW-7 tumour xenografts in mice treated with ifosfamide (n=8), ifosfamide with concurrent NAC therapy (n=7), and NAC pre-treatment (n=6) (p<0.05) were significantly reduced compared to median tumour volumes of control mice (n=6). None of the NAC treatments affected ifosfamide-mediated reduction in tumour volumes., Conclusion: NAC does not interfere with the efficacy of ifosfamide in a EW-7 xenograft model. These results support the clinical evaluation of NAC as a strategy against ifosfamide-induced nephrotoxicity in children.

Ifosfamide-induced nephrotoxicity is a serious adverse effect in children undergoing chemotherapy. Our previous cell and rodent models have shown that the antioxidant N-acetylcysteine (NAC), used extensively as an antidote for acetaminophen poisoning, protects renal tubular cells from ifosfamide-induced nephrotoxicity at a clinically relevant concentration. For the use of NAC to be clinically relevant in preventing ifosfamide nephrotoxicity, we must ensure there is no effect of NAC on the antitumor activity of ifosfamide. Common pediatric tumors that are sensitive to ifosfamide, human neuroblastoma SK-N-BE(2) and rhabdomyosarcoma RD114-B cells, received either no pretreatment or pretreatment with 400 µmol/L of NAC, followed by concurrent treatment with NAC and either ifosfamide or the active agent ifosfamide mustard. Ifosfamide mustard significantly decreased the growth of both cancer cell lines in a dose-dependent manner (p < 0.001). The different combined treatments of NAC alone, sodium 2-mercaptoethanesulfonate alone, or NAC plus sodium 2-mercaptoethanesulfonate did not significantly interfere with the tumor cytotoxic effect of ifosfamide mustard. These observations suggest that NAC may improve the risk/benefit ratio of ifosfamide by decreasing ifosfamide-induced nephrotoxicity without interfering with its antitumor effect in cancer cells clinically treated with ifosfamide.

The antineoplastic drug ifosfamide (IFO) in the treatment of solid tumors, particularly in children, is the cause of severe nephrotoxicity. Although it is a potent and effective chemotherapeutic agent, the associated nephrotoxicity has a serious impact on the health and the quality of life of exposed children. The toxic metabolite of IFO thought to be responsible for IFO-induced kidney damage is chloroacetaldehyde (CAA). Those suffering from nephrotoxicity typically develop tubular and glomerular toxicities, with the most severe form being Fanconi's syndrome. As the mode of toxicity of CAA seems to be primarily owing to oxidative stress, the use of antioxidants as a protective measure for the kidneys is a promising strategy. In this review, we highlight recent research that supports the local renal production of CAA as the proximate cause of IFO-induced nephrotoxicity with age as an important risk factor, those under the age of three being the most vulnerable. Most importantly, we focus on the potential advantages of the antioxidant N-acetylcysteine owing to both its antioxidant properties and its current use clinically in pediatrics.