Background: Difficulties in prognostication are common deterrents to palliative care among dementia patients. This study aimed to evaluate the effectiveness of palliative care in reducing the extent of utilization of medical services and the potential risk factors of mortality among dementia patients receiving palliative care. Methods: We surveyed dementia patients involved in a palliative care program at a long-term care facility in Taipei, Taiwan. We enrolled 57 patients with advanced dementia (clinical dementia rating ≥ 5 or functional assessment staging test stage 7b). We then compared the extent of their utilization of medical services before and after the provision of palliative care. Based on multivariable logistic regression, we identified potential risk factors before and after the provision of palliative care associated with 6-month mortality. Results: The utilization of medical services was significantly lower among dementia patients after the provision of palliative care than before, including visits to medical departments (p < 0.001), medications prescribed (p < 0.001), frequency of hospitalization (p < 0.001), and visits to the emergency room (p < 0.001). Moreover, patients dying within 6 months after the palliative care program had a slightly but not significantly higher number of admissions before receiving hospice care (p = 0.058) on univariate analysis. However, no significant differences were observed in multivariate analysis. Conclusions: The provision of palliative care to dementia patients reduces the extent of utilization of medical services. However, further studies with larger patient cohorts are required to stratify the potential risk factors of mortality in this patient group.
Lurasidone is a second-generation antipsychotic agent indicated for schizophrenia and bipolar depression. Lurasidone is metabolized mainly by cytochrome P450 (CYP) 3A4, and drug-drug interaction needs to be considered. 1 Plasma concentrations (Cps) in 44 clinically stable patients (mean age, 47.8 AE 12.9 years, body weight [BW] 71.4 AE 14.8 kg) taking lurasidone for at least 1 month with informed consent were monitored after dosing for around 15 hours. Table 1 presents the mean Cps, Cps/daily dose (DD), and Cps/DD/BW among the patients and the breakdown by sex. Pearson correlation coefficient for Cps and DD/BW was 0.036, suggesting a wide interindividual range. Many factors contribute to this variation, such as genetic differences in the first-pass effect of the CYP system, sex, medication adherence, dosing time, and whether the medication is taken with meals. Because CYP3A4 plays a major role in the metabolism of lurasidone, this system exhibits remarkable interindividual activity variation as high as 20-fold 2 and racial genetic differences. 3 These differences may account for some of the Cps variations in the results.As most patients were in stable clinical condition, we assumed that their prescribed lurasidone dosage was suitable. Considering that the elimination half-life of lurasidone is approximately 18 hours, 4 and that our results were from approximately 15 hours after dosing, the trough mean Cps should be adjusted by 85% to 13.0 ng/mL and the median to 10.9 ng/mL. Using our preliminary results, we suggest that the therapeutic range of lurasidone in the maintenance phase be 10 to 15 ng/mL, which is slightly lower than the suggested range of 15 to 40 ng/mL by Hiemke et al. 5 In a study of 38 healthy Chinese men administered a 40-mg dose of lurasidone, 6 the area under the curve was 37% higher in Chinese than in Western participants. Findling et al. 7 conducted a pharmacokinetic study of lurasidone in children and adolescents and found it was similar to exposure observed at a steady state in adults. In the group receiving 80 mg/day, the 15 h Cps was approximately 9.5 ng/mL by extrapolation, which is approximately 40% lower than our results (15.7 AE 12.8 ng/mL, n = 35). From these two independent results, we infer that Chinese individuals might have a 30% to 40% higher Abbreviations: BW, body weight; Cps, plasma concentrations; DD, daily dose.
Cytochrome P450 2E1 (CYP2E1) gene is one of the candidate genes for alcohol dependence (AD). Four single nucleotide polymorphisms (SNPs) of CYP2E1 gene (CYP2E1*1D, *5B, *6 and *1B) have been associated with AD previously in other ethnic populations. To date, only CYP2E1*5B and *6 SNPs have been investigated in relation to AD in our population. The objective of the study was to examine the genetic associations of CYP2E1 covering the four above-noted SNPs conjointly with AD in Han Taiwanese population based on single SNP analysis and haplotype-based approach. We enrolled a total of 340 patients fulfilling DSM-IV-TR diagnostic criteria of AD and 319 healthy controls and genotyped them for the above four SNPs of CYP2E1 gene. By comparing the differences of genotype, allele, and pertinent haplotype frequencies, we did not support a genetic association between CYP2E1 and AD in Han Taiwanese either by single allele tests or haplotype-based analyses.
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