The Prevalence and Features of Medications With Actionable Pharmacogenomic Biomarkers Prescribed to Kidney Transplant Recipients.

BACKGROUND: Genetic variants are associated with pharmacokinetic and pharmacodynamic changes, leading to variability in drug effects and safety profiles in the clinical response. The role of genetic variants in kidney transplant recipients (KTRs) has not been extensively studied. Here, we explored the potential of incorporating pharmacogenomic (PGx) gene biomarkers into prescription practices for KTRs. METHODS: This study analyzed 490 KTRs participating in the Taiwan Precision Medicine Initiative program and used medications with actionable PGx biomarkers. The analysis included prescriptions issued between January 2000 and December 2021 with 206 CPIC-recommended level A or B gene-drug pairs, encompassing 363 single or combination drug products. RESULTS: All KTRs had the potential to receive at least one prescription that could be adjusted based on their genetic profiles after the day of surgery. The top 5 medications prescribed within the first 3 months after transplantation were mycophenolic acid, tacrolimus, pantoprazole, labetalol, and tramadol. These findings highlight the significant potential of PGx-guided prescriptions for KTRs. Additionally, some drug-gene pairs, such as tramadol/CYP2D6, pantoprazole/CYP2C19, and atorvastatin/SLCO1B1, were considered high-quality evidence by the Clinical Pharmacogenetics Implementation Consortium and were included in the Food and Drug Administration's drug labels, indicating that they have the potential for clinical application. CONCLUSIONS: Overall, this study demonstrated the potential of incorporating PGx gene biomarkers into prescribing practices for KTRs, which could improve personalized pharmacotherapy for these patients.

Effect of an automated dispensing cabinet system on drug distribution effectiveness in a surgical unit.

The use of the automated dispensing cabinet (ADC) for drug distribution in hospitals has become increasingly common and has numerous benefits. This retrospective study assessed the effectiveness of an ADC that uses integrated information technology in the drug distribution process in a surgical unit as part of a smart medical process improvement project at Taichung Veterans General Hospital in 2019. The outcomes include medicine delivery time, working time of healthcare professionals, transportation manpower, dispensing errors, and satisfaction of nursing staff with the medication distribution process. After ADC implementation, the average waiting time of standing orders decreased significantly for both on and off duty periods (40.0 ± 27.6 to 3.0 ± 3.9 min, P < 0.001; 45.2 ± 25.8 to 2.9 ± 2.9 min, P < 0.001; respectively). Similar results were observed with immediate or temporary medication orders (54.4 ± 31.5 to 2.0 ± 3.0 min, P < 0.001; 64.0 ± 47.5 to 1.5 ± 1.8 min, P < 0.001; respectively). The average time spent by operation room and post-operation room (OR/POR) nurses on communicating with ward nurses for medication delivery to OR/POR was shortened by 46.9 ± 4.4 h per month, and the average time pharmacists spent on dispensing immediate or temporary medication orders was shortened by 5.6 ± 0.2 h per month. The satisfaction of nursing staff with the OR/POR drug delivery process was significantly improved after ADC implementation (3.2 ± 0.8 vs 4.2 ± 0.7, P < 0.001). Our results showed that ADC implementation in surgical units simplified drug delivery processes, shortened drug delivery time, improved drug delivery timeliness for surgical patients, decreased dispensing errors, and increased nursing staff satisfaction. In conclusion, the implementation of ADC was beneficial for surgical units. To the best of our knowledge, there have been no studies on a similar ADC system.

CYP2C19 genotypes and osteoporotic fractures in long-term users of proton pump inhibitors: A hospital-based study.

Proton pump inhibitors (PPIs) are commonly prescribed medications. The existing data suggest that individuals at a high risk of fractures have been exposed to high doses of PPIs for prolonged durations. CYP2C19 plays a pivotal role in metabolism of PPIs and thereby influences their pharmacokinetic profile. Hence, we hypothesize that CYP2C19 genotypes may be associated with fragility fracture among PPIs users due to PPI exposure. This study aimed to investigate the association between CYP2C19 genotypes, bone mineral density (BMD), and osteoporotic fracture in a hospital-based population. This retrospective cohort study enrolled patients who were prescribed long-term PPIs at Taichung Veterans General Hospital using data extracted from the Taiwan Precision Medicine Initiative between January 2010 and April 2021. Associations between CYP2C19 phenotypes, comorbidities, and fractures in PPI users were analyzed. We enrolled 1518 long-term PPI users; 571 (38%), 727 (48%), and 220 (14%) CYP2C19 normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs), respectively. Among them, 49 (3.2%) patients developed fractures within the 1-year follow-up period; 20 (3.5%) fractures in NMs, 24 (3.3%) in IMs, and 5 (2.3%) in PMs, respectively. No significant difference was observed among CYP2C19 genotypes and fracture. Additionally, BMD measurements during the 1-year follow-up period were made available among 75 participants. No significant difference in BMD between CYP2C19 PMs and non-PMs was found. This real-world, hospital-based study concludes that CYP2C19 PMs/IMs are not associated with an increased risk for fractures or reduced BMD in individuals on long-term PPI therapy.

Glycemic control was associated with nonprostate cancer and overall mortalities in diabetic patients with prostate cancer.

BACKGROUND: Diabetes mellitus (DM) can worsen the prognosis or survival in prostate cancer (PC) patients. We investigated whether glycemic control impacts mortality in PC patients with existing diabetes. METHODS: All PC patients with or without preexisting DM were enrolled from 2006 to 2017. Mean hemoglobin A1c (HbA1c) values (<7%, 7%-9%, ≥9%) were used to represent glycemic control. Major outcomes included all-cause, PC-specific, and non-PC mortalities. Statistical analyses were performed using Cox regression models with adjusted mean HbA1c and other related confounders. RESULTS: A total of 831 PC patients were enrolled (non-DM group, n = 690; DM group with a record of mean HbA1c values, n = 141). Results showed that the DM group with mean HbA1c level ≥ 9% (n = 14) had significantly increased risk for all-cause and non-PC mortality (hazard ratio [HR], 3.09; 95% CIs, 1.15-8.32; p=0.025 and HR, 5.49; 95% CIs, 1.66-18.16; p = 0.005, respectively), but not for PC-specific mortality (HR, 1.03; 95% CIs, 0.13-8.44; p = 0.975), compared with the non-DM group. CONCLUSION: Our findings indicate that PC patients with DM who had a mean HbA1c level ≥ 9% had higher risks of all-cause and non-PC mortality compared with non-DM subjects. Further large and long-term studies are needed to verify the effect of glycemic control in PC patients with DM.

Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study.

PURPOSE: Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population. PATIENTS AND METHODS: This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed. RESULTS: From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is *2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19-8.22). CONCLUSION: In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.

The effects of a pharmacist-led medication review in a nursing home: A randomized controlled trial.

BACKGROUND: In this study, an intensive review of pharmaceutical care for elderly patients was conducted in a Veterans Administration nursing home in Taiwan and its effects were evaluated. METHODS: One hundred participants were enrolled in this randomized controlled study with even distribution. The inclusion criteria were age 65 years or older, prescriptions for at least 5 oral medicines daily, and ≥2 chronic diseases, for the period May 2013 to October 2014. Subjects were excluded if they had previously been included in an intensive medication review conducted by a pharmacist. The primary outcomes were numbers of drugs prescribed, potential inappropriate medications, and numbers of drug-related problems. The secondary outcomes were self-reported medical usages, measurements of quality of life, results of a satisfaction survey, and health status. RESULTS: A total of 80 cases (42 in the intervention group with medication reconciliation and 38 in the control group without medication reconciliation) completed the study. Baseline characteristics were not statistically different between the 2 groups. The overall prevalence of potential inappropriate medication was 74.3%. There were no differences between the 2 groups, with the exception of "medical problems," which showed a significantly higher prevalence in the intervention group (P < .05). The intervention group reported greater satisfaction regarding pharmacist visits and medication compliance (P < .01). The mean number of drug-related problems was significantly lower after the intervention (P < .01). CONCLUSION: In this study, the intensive review of the elderly patients' medications revealed that the only significant effect of pharmaceutical care was on "all outcomes." A possible reason for this is the rather advanced ages of some patients who needed a considerable number of medications to treat several chronic diseases. Another reason may be the small sample size. However, participants who received the pharmacist intervention did have higher satisfaction with medication reconciliation and fewer drug-related problems.

Preventing epilepsy after traumatic brain injury: A propensity score analysis.

BACKGROUND: Due to the potential consequences of post-traumatic epilepsy (PTE) exacerbating secondary injury following traumatic brain injury (TBI), the use of antiepileptic drugs (AEDs) is an accepted option for seizure prophylaxis. However, there is only a paucity of data that can be found regarding outcomes surrounding the use of AEDs. The purpose of this retrospective study is to evaluate whether the prophylactic administration of AEDs significantly decreased the incidence of PTE, when considering the severity of TBI. METHODS: All trauma patients who had been newly diagnosed with TBI from January 1, 2010 to December 31, 2017 were retrospectively analyzed. Statistical comparisons were made using the chi-square test, Mann-Whitney U test, and Cox regression modeling. After excluding any exposed subjects with no appropriate match, patients who had received AED prophylaxis were matched by propensity score with those who did not receive AEDs. All of the TBI populations were followed up until June 30, 2018. RESULTS: We identified 1316 patients who met the inclusion and exclusion criteria in our matched cohort through their propensity scores, where 138 patients had been receiving prophylactic AEDs and 138 patients had not. Baseline characteristics were similar in gender, age, Glasgow Coma Scale (GCS) scores, and risk factors of PTE including skull fracture, chronic alcoholism, subdural hematoma, epidural hematoma, and intracerebral hematoma. After adjusting for those risk factors, the relative incidence of seizure was not statistically significant in either of the groups (p = 0.566). CONCLUSION: In our cohort analysis, AED prophylaxis was ineffective in preventing seizures, as the rate of seizures was similar whether patients had been receiving the drugs or not. We therefore concluded that the benefits of routine prophylactic anticonvulsant therapy in patients with TBI need to be re-evaluated.

Risk Factors in and Long-Term Survival of Patients with Post-Transplantation Diabetes Mellitus: A Retrospective Cohort Study.

Post-transplant diabetes mellitus (PTDM) is associated with infection, cardiovascular morbidity, and mortality. A retrospective cohort study involving patients who underwent renal transplantation in a transplantation center in Taiwan from January 2000 to December 2018 was conducted to investigate the incidence and risk factors of PTDM and long-term patient and graft survival rates. High age (45-65 vs. <45 years, adjusted odds ratio (aOR) = 2.90, 95% confidence interval (CI) = 1.64-5.13, p < 0.001), high body mass index (>27 vs. <24 kg/m2, aOR = 5.35, 95% CI = 2.75-10.42, p < 0.001), and deceased organ donor (cadaveric vs. living, aOR = 2.01, 95% CI = 1.03-3.93, p = 0.04) were the three most important risk factors for the development of PTDM. The cumulative survival rate of patients and allografts was higher in patients without PTDM than in those with PTDM (p = 0.007 and 0.041, respectively). Concurrent use of calcineurin inhibitors and mammalian target of rapamycin inhibitors (mTORis) decreased the risk of PTDM (tacrolimus vs. tacrolimus with mTORi, aOR = 0.28, 95% CI = 0.14-0.55, p < 0.001). Investigating PTDM risk factors before and modifying immunosuppressant regimens after transplantation may effectively prevent PTDM development.

Efficacy of second-line regimens for Helicobacter pylori eradication treatment: a systemic review and network meta-analysis.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy (BQT) and quinolone-containing therapy after failure of first-line Helicobacter pylori eradication therapy. However, the optimum regimen of second-line eradication therapy remains elusive. We conducted a network meta-analysis to compare the relative efficacy of 16 second-line H. pylori eradication regimens. METHODS: Three major bibliographic databases were reviewed to enrol relevant randomised controlled trials between January 2000 and September 2018. Network meta-analysis was conducted by STATA software and we performed subgroup analysis in countries with high clarithromycin resistance and high levofloxacin resistance, and in patients with documented failure of first-line triple therapy. RESULTS: Fifty-four studies totalling 8752 participants who received 16 regimens were eligible for analysis. Compared with a 7-day BQT, use of probiotic add-on therapy during, before, and after second-line antibiotic regimens, quinolone-based sequential therapy for 10-14 days, quinolone-based bismuth quadruple therapy for 10-14 days, bismuth quadruple therapy for 10-14 days, and quinolone-based triple therapy for 10-14 days were significantly superior to the other regimens. Subgroup analysis of countries with high clarithromycin resistance and high levofloxacin resistance revealed that the ranking of second-line eradication regimens was distributed similarly in each group, as well as in patients with failure of first-line triple therapy. CONCLUSION: We conducted a detailed comparison of second-line H. pylori regimens according to different antibiotic resistance rates and the results suggest alternative treatment choices with potential benefits beyond those that could be achieved using salvage therapies recommended by guidelines.

Improving medication safety by cloud technology: Progression and value-added applications in Taiwan.

OBJECTIVES: To develop and implement an integrated cloud technology with the aim of ensuring medication reconciliation during transitions of care and improve medication safety in aged societies. METHODS: PharmaCloud is a new technical platform adopted by the National Health Insurance Administration of Taiwan to collect patients' medication information via cloud technology. Using this platform, healthcare providers can access patients' medication-related information with patient consent. Our hospital applied this technology and developed several approaches to collect and detect medication-related information and alert physicians for the purpose of enhancing patients' medication safety. In addition, pharmacists were involved in the admission process to access medication data and provide optimal suggestions to physicians. Several indicators, including a reduction in the number of drug items in each prescription and medication expenditure, were employed to evaluate the overall effects of the cloud inquiry. RESULTS: After the application of PharmaCloud, the average number of prescribed drug items significantly decreased (change of 0.04 to -0.35 per prescription, p < 0.05), and the median medication expenditure significantly decreased by an average of 3.55 USD, (p < 0.05) per prescription. Intra-hospital medication duplication rates also showed a downward trend. CONCLUSIONS: The use of the cloud technology and value-added applications significantly improved patient medication safety. Further long-term beneficial effects in terms of medication safety and medical cost savings are expected.

Prescription-filling process reengineering of an outpatient pharmacy.

Shortening waiting times is the most obvious and effective method of increasing service quality. As the workforce is limited, it is necessary to reform current systems of medical care and improve the efficiency of medical care. After process reengineering was proposed in 1990s, however, this concept has not yet been commonly applied to medical centers. The subject of this study was an outpatient pharmacy in a medical center. This study applied the methods of a time study to measure field observations and as an analytic tool in process reengineering. The results show that the pharmacists were hindered in filling prescriptions for the following reasons: the preparation of certain prescription units, the menial sorting of medicines and also storage issues related to medicines. Improving the process will decrease time wasted by 10.41% and enhance service by 8.95%. The reengineering process resulted not only in a reduction in outpatients' waiting time but also enhanced the quality and competitiveness of the Hospital's medical treatment.

Construction, expression and functional characterization of the ß-lactamase with αv integrin ligands.

Antibody-directed enzyme prodrug therapy (ADEPT) delivers chemotherapeutic agents at high concentration to tumor tissues while minimizing systemic drug exposure. ß-Lactamases are particularly useful enzymes for ADEPT systems due to their unique substrate specificity, which allows the activation of a variety of lactam-based prodrugs with minimal interference from mammalian enzymes. This study used integrin α(v)ß(3) as a target for tumor-specific delivery of ß-Lactamase. ß-Lactamase was fused with ACDCRGDCFCG peptide (RGD4C) by recombinant DNA technology. Likewise, this study cloned a fused cDNA and successfully expressed active recombinant protein in E. coli purified with Ni-NTA resin. After purification, ß-Lactamase moiety showed the expected size of 42 kDa on Tricine-SDS-PAGE, and was further confirmed by Western blotting. Based on flow cytometric analysis, the purified protein was found to be active for specificity in breast cancer cell line, MCF-7, which supports the utility of the protein as an agent for ADEPT.