Consultation-Based Deprescribing Service to Optimize Palliative Care for Terminal Cancer Patients.

(1) Background: A pharmacist-led deprescribing service previously developed within the Consultation-Based Palliative Care Team (CB-PCT) was implemented for terminal cancer patients. (2) Objective: To evaluate the clinical outcomes of the developed deprescribing service for terminal cancer patients in CB-PCT. (3) Methods: A retrospective analysis compared the active care (AC) group to the historical usual care (UC) group. The clinical outcomes included the deprescribing rate of preventive medications, the proportion of patients with one or more medication-related problems (MRPs) resolved upon discharge, and the clinical significance. The implementability of the service was also gauged by the acceptance rates of pharmacists' interventions. (4) Results: Preventive medications included lipid-lowering agents, gastroprotective agents, vitamins, antihypertensives, and antidiabetic agents. The AC group revealed a higher deprescribing rate (10.4% in the UC group vs. 29.6% in the AC group, p < 0.001). At discharge, more AC patients had one or more MRPs deprescribed (39.7% vs. 2.97% in UC, p < 0.001). The clinical significance consistently had a very significant rating (mean score of 2.96 out of 4). Acceptance rates were notably higher in the AC group (30.0% vs. 78.0%. p = 0.003). (5) Conclusions: The collaborative deprescribing service in CB-PCT effectively identified and deprescribed MRPs that are clinically significant and implementable in practice.

Drug repositioning prediction for psoriasis using the adverse event reporting database.

Introduction: Inverse signals produced from disproportional analyses using spontaneous drug adverse event reports can be used for drug repositioning purposes. The purpose of this study is to predict drug candidates using a computational method that integrates reported drug adverse event data, disease-specific gene expression profiles, and drug-induced gene expression profiles. Methods: Drug and adverse events from 2015 through 2020 were downloaded from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), information component (IC) and empirical Bayes geometric mean (EBGM) were used to calculate the inverse signals. Psoriasis was selected as the target disease. Disease specific gene expression profiles were obtained by the meta-analysis of the Gene Expression Omnibus (GEO). The reverse gene expression scores were calculated using the Library of Integrated Network-based Cellular Signatures (LINCS) and their correlations with the inverse signals were obtained. Results: Reversal genes and the candidate compounds were identified. Additionally, these correlations were validated using the relationship between the reverse gene expression scores and the half-maximal inhibitory concentration (IC50) values from the Chemical European Molecular Biology Laboratory (ChEMBL). Conclusion: Inverse signals produced from a disproportional analysis can be used for drug repositioning and to predict drug candidates against psoriasis.

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia.

Introduction: L-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN. Methods: The study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias. Results: The analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17-1.62) or the complete response rate (OR 0.86; 95% CI = 0.29-2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36-2.78 and OR 1.24; 95% CI, 0.50-3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups. Conclusion: There is no clear rationale for avoiding Asp-TPN in ASNase-treated patients.

Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

BACKGROUND: Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. METHODS: The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. RESULTS: The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%. CONCLUSIONS: The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

Meta-analysis of the impact of thioprine S-methyltransferase polymorphisms on the tolerable 6-mercaptopurine dose considering initial dose and ethnic difference.

A meta-analysis was conducted to decide whether to reduce an initial 6-mercaptopurine (6-MP) dose in TPMT heterozygote in the case of an initial 6-MP dose of <75 mg/m2/d and to compare the tolerable 6-MP dose among different ethnic groups. The study was undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The differences in mean values of the tolerable 6-MP dose were calculated by using Comprehensive Meta-Analysis version 3. The results of the meta-analysis indicated that the tolerable 6-MP dose was significantly lower in the TPMT heterozygote group (difference in mean values =11.729, 95% confidence interval =7.617-15.842, P<0.001) even when the initial 6-MP dose was <75 mg/m2/d. The TPMT*3C allele-dominant ethnic group (Asian) needed less reduction in mean 6-MP dose in comparison to the TPMT*3A allele-dominant ethnic group (Caucasian, Mediterranean, South American) (difference in mean values =8.884 vs 15.324). In conclusion, the initial 6-MP dose needs to be reduced in TPMT heterozygote when compared to the wild-type, and ethnic difference might influence the tolerable 6-MP dose in TPMT heterozygotes.