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Hepatocellular carcinoma (HCC) is a global health concern with high prevalence and mortality. A marine alkaloid, AP‐427, has been reported to show potential for HCC treatment. However, its use is limited by low solubility and high toxicity. We aimed to investigate the preformulation parameters and develop AP‐427 liposomes to improve its clinical suitability. A stability‐indicating HPLC assay was established, and the physicochemical properties of AP‐427 were analyzed. Afterward, AP‐427 liposomes were prepared and characterized, and their cytotoxicity was evaluated. AP‐427 had a low solubility at physiological pH, a LogD of 2.56 ± 0.03, and a basic pKa of 3.24 ± 0.12. An entrapment efficiency of 52.71 ± 3.2% was achieved after optimization. The resulting AP‐427 liposomes were 147.2 ± 3.4 nm and stable up to three months when stored in a pellet form at 4°C. The crystallization of AP‐427 in liposomes became less ordered, and AP‐427 liposomes exhibited a controlled release fitted in Korsmeyer–Peppas model, indicating the release was driven by diffusion. Furthermore, AP‐427 liposomes showed a 3.6 times reduced cytotoxicity against HepG2 cells compared with free AP‐427, potentially enhancing its antitumor efficacy. In conclusion, the precise preformulation parameters advanced the AP‐427 liposomal formulation development, which showed potential for HCC treatment. Practical Applications: The aaptamine derivative AP‐427 has shown cytotoxic effects against hepatocellular carcinoma. However, the low solubility and high toxicity limit its clinical application. The present study aims to prepare liposomal formulation to solve the current problems. Results obtained from this study shed light on challenges related to drug solubility and have paved the way for the development of an effective AP‐427 liposomal formulation with promising application in hepatocellular carcinoma therapy. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Aim: As the direct oral anticoagulant most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multicentre registry of patients treated in real‐world clinical practice. Methods: This real‐world, prospective, multicentre and non‐interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. Results: The median patient age was 70.0 years (interquartile range 61.0‐78.0 years) and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low dosage (183, 18.2%) or wrong drug selection (109, 10.8%), high dosage (73, 7.3%), unreasonable off‐label use (49, 4.9%), contraindicated medication combinations (27, 2.7%) and incorrect administration timing (16, 1.6%). Several factors, such as age ≥75 years (odds ratio [OR] = 1.921, 95% confidence interval [CI] 1.355‐2.723, P < 0.001), weight >60 kg (OR = 2.657, 95%CI 1.970‐3.583, P < 0.001), severe renal insufficiency (OR = 1.988, 95% CI 1.043‐3.790, P = 0.037), current anaemia (OR = 1.556, 95% CI 1.151‐2.102, P = 0.004) and history of bleeding (OR = 2.931, 95% CI 1.605‐5.351, P < 0.001) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties, such as admission to a cardiovascular department (OR = 0.637, 95% CI 0.464‐0.873, P = 0.005), dronedarone use (OR = 0.065, 95% CI 0.026‐0.165, P < 0.001) and amiodarone use (OR = 0.365, 95% CI 0.209‐0.637, P < 0.001) decreased this risk. Conclusion: In this real‐world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban. [ABSTRACT FROM AUTHOR]

Patients in ICU were often administered with many kinds of drugs simultaneously. The drug-drug interactions can either affect therapeutic efficacy or increase toxicity of the drugs. Pharmaceutical care based on drug interaction filter application can efficiently screen out potential drug interaction, thus enabling clinical pharmacists to intervene in a faster and more effective manner and at the same time increasing clinical medication safety [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the influence of aging on the effectiveness and tolerance of sacubitril/valsartan (sac/val) among hypertensive patients complicated with heart failure in a real-world setting., Methods: This multicenter, retrospective study included patients (≥18 years old) admitted with a diagnosis of hypertension and heart failure, starting sac/val therapy between January 2020 and December 2021 from 3 medical centers. Patients were grouped by the cutoff age of 65 years. Outcomes were collected 31-365 days after the initiation of sac/val and were compared in a matched cohort after 1: 1 propensity score matching (PSM)., Results: A total of 794 patients were finally analyzed. Blood pressure and cardiac functions improved significantly compared with values at baseline. There were 269 patients in each cohort (<65 years and ≥65 years) after PSM. After PSM, the incidence of hyperuricemia and hypotension in the elderly patients (≥65 years) was significantly higher than in those <65 years of age. Kaplan-Meier estimate suggested that the cumulative incidence of new or recurrent cardiovascular events increased significantly at the age of ≥65 years after the point of 3 months (log-rank P =.00087)., Conclusion: Sac/val benefited patients in both cohorts by improving blood pressure and cardiac function. Elderly patients (≥65 years) were susceptible to hypotension, low diastolic blood pressure, hyperuricemia, and underwent cardiac-related readmissions more frequently.

Background: The pharmaceutical services based on therapeutic care pathway for kidney transplantation from infants and young children (age <3 years, weight <15 kg) to pediatric recipients can detect and resolve medication-related problems. In this paper, we report our experience on pharmaceutical services based on therapeutic care pathway to evaluate the therapeutic effects and assess the feasibility of perioperative treatment protocols., Methods: We performed a retrospective study of 12 recipients who received their graft from infants and young children, between September 2011 and December 2013 at our institution. As providers of pharmaceutical services, the clinical pharmacists collected and reviewed the clinical data from all patients, including the clinical characteristics, outcome indices, and follow-up dates. A three-step-protocol of pharmaceutical services including clinician's application, pharmacist consultation, and ongoing direct pharmaceutical care and follow-up was used through the entire length of patient's admission, hospitalization, and discharge. This protocol was developed and refined based on the guidelines for transplant perioperative treatment and experiences of the clinical pharmacists to standardize the workflow, and improve the medical treatment and quality of life of patients., Results: There was no acute rejection, graft loss, or death in 10 recipients after transplantation, and another 2 received nephrectomy due to dysfunction. Postoperative follow-up of the patients who received the pharmaceutical services from the clinical pharmacist showed an effectiveness in managing medication-related complications, patient-related factors, and an improvement of the outcomes., Conclusions: The three-step protocol of pharmaceutical services for pharmaceutical care and individual dosing regimen sponsored by pharmacists facilitated access to personalized therapies for children undergoing kidney transplantation in our hospital., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-21-515/coif). The authors have no conflicts of interest to declare., (2022 Translational Pediatrics. All rights reserved.)

Background: Invasive pulmonary aspergillosis (IPA) is a rapidly progressive and fatal disease for those with autoimmune diseases. The performance of existing diagnostic tools is unsatisfactory, and a novel algorithm based on pentraxin 3 (PTX3) gene polymorphisms with adjusted PTX3 and galactomannan (GM) values is urgently needed., Methods: Levels of PTX3 and GM were measured in the bronchoalveolar lavage fluid (BALF) and blood samples of patients who had autoimmune diseases with IPA between June 2017 and June 2021. Urea dilution was applied internally to correct the real BALF PTX3 and GM values. Three single-nucleotide polymorphisms (SNPs; rs1840680, rs2305619, and rs3816527) in the PTX3 gene were detected by polymerase chain reaction direct sequencing, and their associations with IPA were evaluated. Receiver operating characteristic (ROC) curves based on different variables were generated to determine the best algorithm for IPA diagnosis., Results: This study enrolled 50 patients with IPA and 100 without IPA in the control groups (comprising 50 patients with Aspergillus airway colonization and 50 patients with bacterial pneumonia). The levels of adjusted BALF PTX3 and GM were higher in the IPA group than in the control groups (P<0.05, respectively). For diagnosing IPA, the best adjusted cutoff value for PTX in BALF was 14.5 ng/mL and the best adjusted cutoff value for GM in BALF was 2.5 optical density index (ODI). The SNP rs1840680 AA homozygote was associated with a higher risk of IPA [odds ratio (OR) 18.86, 95% confidence interval (CI): 7.96-44.69; P<0.01], while no genotypic distribution differences were observed for the other 2 SNPs (rs2305619 and rs3816527). Six algorithms were established based on PTX3 gene polymorphisms. The algorithm consisting of PTX3 gene polymorphisms with adjusted BALF PTX3 and BALF GM values demonstrated the best diagnostic performance (sensitivity 90.03%; specificity 97.09%; area under the curve 0.94)., Conclusions: It was revealed that our new algorithm based on PTX3 gene polymorphisms combined with adjusted BALF GM and BALF PTX3 values performed well in diagnosing IPA., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4017). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)