Search

Background: Older patients with coronary artery disease (CAD) are particularly vulnerable to the efficacy and adverse drug reactions, and may therefore particularly benefit from personalized medication. Drug–gene interactions (DGIs) occur when an individual's genotype affects the pharmacokinetics and/or pharmacodynamics of a victim drug. Objectives: This study aimed to investigate the impact of cardiovascular-related DGIs on the clinical efficacy and safety outcomes in older patients with CAD. Methods: Hospitalized older patients (≥ 65 years old) with CAD were consecutively recruited from August 2018 to May 2022. Eligible patients were genotyped for the actionable pharmacogenetic variants of CYP2C9, CYP2C19, CYP2D6, CYP3A5, and SLCO1B1, which had clinical annotations or implementation guidelines for cardiovascular drugs. Allele frequencies and DGIs were determined in the cohort for the 5 actionable PGx genes and the prescribed cardiovascular drugs. All patients were followed up for at least 1 year. The influence of DGIs on the cardiovascular drug-related efficacy outcomes (all-cause mortality and/or major cardiovascular events, MACEs) and drug response phenotypes of "drug-stop" and "dose-decrease" were evaluated. Results: A total of 1,017 eligible older patients with CAD were included, among whom 63.2% were male, with an average age of 80.8 years old, and 87.6% were administrated with polypharmacy (≥ 5 medications). After genotyping, we found that 96.0% of the older patients with CAD patients had at least one allele of the 5 pharmacogenes associated with a therapeutic change, indicating a need for a therapeutic change in a mean of 1.32 drugs of the 19 cardiovascular-related drugs. We also identified that 79.5% of the patients had at least one DGI (range 0–6). The median follow-up interval was 39 months. Independent of age, negative association could be found between the number of DGIs and all-cause mortality (adjusted HR: 0.84, 95% CI: 0.73–0.96, P = 0.008), and MACEs (adjusted HR: 0.84, 95% CI: 0.72–0.98, P = 0.023), but positive association could be found between the number of DGIs and drug response phenotypes (adjusted OR: 1.24, 95% CI: 1.05–1.45, P = 0.011) in the elderly patients with CAD. Conclusions: The association between cardiovascular DGIs and the clinical outcomes emphasized the necessity for the integration of genetic and clinical data to enhance the optimization of cardiovascular polypharmacy in older patients with CAD. The causal relationship between DGIs and the clinical outcomes should be established in the large scale prospectively designed cohort study. [ABSTRACT FROM AUTHOR]

Clinical annotations for the actionable pharmacogenetic variants affecting the efficacy of cardiovascular drugs have been collected, yet their impacts on elderly patients with coronary artery disease (CAD) undergoing polypharmacy remain uncertain. We consecutively enrolled 892 elderly patients (mean age 80.7 ± 5.2) with CAD and polypharmacy. All the included patients underwent genotyping for 13 variants in 10 pharmacogenes (CYP2C19, CYP2C9, CYP4F2, CYP2D6, VKORC1, SLCO1B1, APOE, ACE, ADRB1, and MTHFR), which have the clinical annotations for 12 drugs that are commonly prescribed for patients with CAD. We found that 80.3% of the elderly CAD patients had at least one drug–gene pair associated with a therapeutical drug change. After adjusting for covariates, the number of drug–gene pairs was independently associated with a decreased risk of both major cardiovascular events (MACEs) (adjusted hazard ratio [HR]: 0.803, 95% confidence interval [CI]: 0.683–0.945, p = 0.008) and all-cause mortality (adjusted HR: 0.848, 95% CI: 0.722–0.996, p = 0.045), but also with an increased risk of adverse drug reactions (ADRs) (adjusted HR: 1.170, 95% CI: 1.030–1.329, p = 0.016). The Kaplan–Meier survival curves showed that compared to patients without a drug–gene pair, a significantly lower risk of MACEs could be observed in patients with a drug–gene pair during a 4-year follow-up (HR: 0.556, 95% CI: 0.325–0.951, p = 0.013). In conclusion, the carrier status of the actionable drug–gene pair is predictive for the clinical outcomes in elderly patients with CAD and polypharmacy. Implementing early or preemptive pharmacogenetic panel-guided polypharmacy holds the potential to enhance clinical outcomes for these patients. [ABSTRACT FROM AUTHOR]

Processing fine and ultrafine coal particles from primary resources is essential for sustainable development. As one of the most recently developed enrichment equipment, cyclonic microbubble flotation columns (FCMC) showed high efficiency in upgrading various fine minerals. However, understanding the effect of FCMC operating variables on coal upgrading process responses remains a black box and needs fundamental assessments. To fill the gap, this study examined the influence of circulating pump pressure and froth height on the recovery of different coal particle size ranges to assess and explore fundamental FCMC performance. The experimental results established that increased froth height would simultaneously reduce the collection and froth recovery. Coarse particles in the high froth height were detached due to bubble coalescence or rupture, while the liquid drainage reduced fine particle pollution of froth products. Increasing circulating pump pressure would increase the collection zone's turbulence, lead to coarse particle detachment, and reduce collection recovery. Meanwhile, increasing circulating pump pressure could promote froth stability and decrease froth detachment in the froth zone. The calculated first-order rate constant (kc) confirmed that the flotation rate constants of coarse (−0.5 + 0.25 mm) and fine (−0.074 mm) particles were low, while the intermediate particles (−0.125 + 0.074 mm) had faster flotation kinetics. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the combination of repetitive transcranial magnetic stimulation (rTMS) and auricular point pressure bean could effectively ameliorate postoperative affective disorder in elderly patients suffering from cerebral hemorrhage., Methods: From June 2020 to September 2023, 116 elderly patients with depression after cerebral hemorrhage, who underwent surgical procedures were divided into the exposure group and the control group. The division was determined based on whether received rTMS and traditional Chinese medicine auricular point pressure bean therapy. Hamilton anxiety scale (HAMA), Hamilton Depression scale (HAMD), National Institutes of Health Stroke scale (NIHSS), Montreal Cognitive Assessment scale (MoCA) and Mini Mental State examination scale (MMSE) were collected and compared between before intervention and after intervention., Results: In accordance with a 1 : 1 matching ratio, the patients in the study were paired using propensity score matching (PSM), with 53 patients in both the exposure group and the control group. There were no notable differences in baseline characteristics between the 2 groups ( P > .05). Following the intervention, the HAMA score and the NIHSS score of the exposure group were markedly lower than those of the control group ( P < .001). Additionally, theMoCA scores ( P = .001) and MMSE scores ( P < .001) in the exposure group were significantlyhigher. The difference score have a significant difference in HAMA score ( P = .001), NIHSS score ( P < .001), MoCA ( P < .001) and MMSE scores ( P < .001)., Conclusion: The combination of rTMS therapy and auricular point pressure bean therapy in traditional Chinese medicine demonstrates can effectively relieve the anxiety level, postoperative emotional and cognitive disorders of elderly patients after intracerebral hemorrhage, and provide certain ideas and support for clinical treatment., Competing Interests: Declaration of Interests: The authors have no conflicts of interest to declare., (2024 authors.)

Purpose: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist and lead to a much higher risk of mortality in the elderly population. The aim of this study was to investigate whether the CHA 2 DS 2 -VASc score could predict the risk of death in elderly patients with CAD and AF. Methods: Hospitalized patients aged ≥65 years with a diagnosis of CAD and AF were recruited consecutively. Patients were divided into 5 groups according to the CHA 2 DS 2 -VASc score (≤2, =3, =4, =5, and ≥6). At least a 1-year follow-up was carried out for the assessment of all-cause death. Results: A total of 1,579 eligible patients were recruited, with 582 all-cause deaths (6.86 per 100 patient-years) occurring during a follow-up of at least 1 year. With the increase in the CHA 2 DS 2 -VASc score, the 1-year and 5-year survival rate decreased (96.4% vs. 95.7% vs. 94.0% vs. 86.5% vs. 85.7%, respectively, P < 0.001; 78.4% vs. 68.9% vs. 64.6% vs. 55.5% vs. 50.0%, respectively, P < 0.001). Compared with the patients with CHA 2 DS 2 -VASc score <5, for patients with CHA 2 DS 2 -VASc score ≥5, the adjusted hazard ratio for death was 1.78 (95% CI: 1.45-2.18, P < 0.001). The predictive values of the CHA 2 DS 2 -VASc score ≥5 for in-hospital (C-index = 0.66, 95% CI: 0.62-0.69, P < 0.001), 1-year (C-index = 0.65, 95% CI: 0.63-0.67, P < 0.001) and 5-year (C-index = 0.60, 95% CI: 0.59-0.61, P < 0.001) death were in comparable. Conclusion: In elderly patients with concomitant CAD and AF, the CHA 2 DS 2 -VASc score can be used to predict death with moderate accuracy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Wang, Dong, Qin, Li, Yan, Guo, Feng, Zou, Wang, Du, Zhang, Ma and Yin.)