Changes in Relatives' Perspectives on Quality of Death, Quality of Care, Pain Relief, and Caregiving Burden Before and After a Region-Based Palliative Care Intervention.

CONTEXT: A region-based palliative care intervention (Outreach Palliative Care Trial of Integrated Regional Model Study) increased home death, access to specialist palliative care, quality of care, and quality of death and dying. OBJECTIVES: The objective of this study was to examine changes in palliative care outcomes in different care settings (hospitals, palliative care units, and home) and obtain insights into how to improve region-level palliative care. METHODS: The intervention program was implemented from April 2008 to March 2011. Two bereavement surveys were conducted before and after intervention involving 4228 family caregivers of deceased cancer patients. Family-perceived quality of care (range 1-6), quality of death and dying (1-7), pain relief (1-7), and caregiver burden (1-7) were measured. RESULTS: Response rates were 69% (preintervention) and 66% (postintervention), respectively. Family-perceived quality of care (adjusted mean 4.89, 95% CI 4.54-5.23) and quality of death and dying (4.96, 4.72-5.20) at home were the highest and sustained throughout the study. Palliative care units were at the intermediate level between home and hospitals. In hospitals, both quality of care and quality of death and dying were low at baseline but significantly improved after intervention (quality of care: 4.24, 4.13-4.34 to 4.43, 4.31-4.54, P = 0.002; quality of death and dying: 4.22, 4.09-4.36 to 4.36, 4.22-4.50, P = 0.012). Caregiver burden did not significantly increase after intervention, regardless of place of death. CONCLUSIONS: The dual strategies of transition of place of death to home and improving quality of care in hospitals should be recognized as important targets for improving region-level palliative care.

Assessment of a twice dosing regimen both before and after partial hepatectomy in the rat liver micronucleus test.

The liver micronucleus test is an important method to detect in vivo genotoxicants, especially those that require metabolic activation for their genotoxicity. We have already reported that structural or numerical chromosome aberration inducers have to be given before or after partial hepatectomy, respectively, to detect their genotoxicity in the liver of rats. In the present study, we assessed a twice dosing regimen, in which the genotoxicant is dosed both before and after partial hepatectomy, using the four chromosome aberration inducers used in the previous study. Two structural chromosome aberration inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used. The genotoxicant was administered to 8-week old male F344 rats one day before and again one day after the partial hepatectomy and hepatocytes were isolated 3 days after second dosing (4 days after the partial hepatectomy). As a result, all genotoxicants (structural or numerical chromosome aberration inducers) caused a dose-dependent statistically significant increase in the incidence of micronucleated hepatocytes when given both before and after partial hepatectomy. No marked difference was observed in general toxicity, relative liver weight and cell classification between single dosing regimens and twice dosing regimen of the genotoxicants. These results confirm that the twice dosing regimen, in which the test compound is dosed both before and after partial hepatectomy, can detect in vivo induction of micronucleated hepatocytes by structural or numerical chromosome aberration inducers qualitatively similar to their appropriate regimen in which the test compound is administered either before or after partial hepatectomy.

Relationship between DNA damage and micronucleus in mouse liver.

To determine the optimum timing of partial hepatectomy (PH) in a previously developed mouse liver micronucleus test (Igarashi and Shimada, 1997), the relation between DNA damage and micronucleus was examined using the in vivo alkaline comet assay and the micronucleus test on the liver of the same individual mouse. Five genotoxic carcinogens, 1-nitropyrene (1-NP) (125 mg/kg), cyclophosphamide (CP) (50 mg/kg), methylmethan sulfonate (MMS) (80 mg/kg), mitomycin C (MMC) (2 mg/kg) and diethylnitrosamine (DEN) (50 mg/kg) were intraperitoneally dosed to each group consisting of 4 male ddY mice. The mice were subjected to PH 3, 8 or 24 hr after dosing of each carcinogen, and comet assay was performed using the removed liver. The regenerated hepatocyte was sampled five days after PH, and the incidence of micronucleus was measured. CP, MMS, MMC and DEN induced DNA damage at 8 and 24 hr after dosing, while 1-NP induced DNA damage only 8 hr after dosing. All five carcinogens induced micronuclei whenever PH was performed. In the case of CP, the peak of DNA damage was 24 hr after dosing and the timing of PH did not remarkably affect the incidence of micronuclei. The other 4 carcinogens showed peak DNA damage at 8 hr and the highest incidence of micronuclei when PH was operated 24 hr after dosing. In conclusion, we are the first to show the relation of induction between DNA damage and micronucleus in the liver from the same mouse, and tentatively showed the optimal timing of PH as 24 hr after dosing.

Optimum conditions for detecting hepatic micronuclei caused by numerical chromosome aberration inducers in mice.

To ascertain an optimum condition for detecting micronuclei in the liver caused by numerical aberration inducers, either carbendazim (125-1000mg/kg, p.o.), colchicine (0.375-1.5mg/kg, i.v.), cytochalasin B (2.5-20mg/kg, i.v.), diazepam (3.13-25mg/kg, i.v.), noscapine (7.8-62.5mg/kg, i.v.), paclitaxel (1-100mg/kg, i.v.) or trichlorfon (18.75-150mg/kg, i.v.) was administered once to male Slc:ddY mice 1 day before or after partial hepatectomy (PH, Day 1). Five days after PH (on Day 6), hepatic micronuclei were determined in conjunction with classifications of the main nuclei and relative liver weights as a proliferative indicator or a dysfunction marker of cell division. Additionally, hepatocyte proliferation index (HPI) was calculated by using mono-, bi- and multinucleated cell counts. Treatment of mice with six compounds, except for colchicine, after PH showed higher incidence of micronucleated hepatocytes (MNH) than that before PH, and also increases in binucleated and multinucleated cells. Especially for carbendazim, diazepam, noscapine and trichlorfon, the dosing after PH was essential for the detecting numerical aberration. Colchicine evidently increased HPI and decreased relative liver weights without MNH induction on Day 6. On Day 8 when HPI and relative liver weights almost returned to the basal range, a significant increase in MNH was noted. This implied that the strong inhibition of colchicine on hepatocyte proliferation may obstruct the induction of MNH on Day 6. In conclusion, to detect the potential numerical aberration, exposure of mice to test chemicals should be performed 1 day after PH, during which enhanced proliferation of hepatocytes was seen, and it would be better to analyze the liver specimens on Day 6 or more post-PH.