Construction and application of medication reminder system: intelligent generation of universal medication schedule.

BACKGROUND: Patients with chronic conditions need multiple medications daily to manage their condition. However, most patients have poor compliance, which affects the effectiveness of treatment. To address these challenges, we establish a medication reminder system for the intelligent generation of universal medication schedule (UMS) to remind patients with chronic diseases to take medication accurately and to improve safety of home medication. METHODS: To design medication time constraint with one drug (MTCOD) for each drug and medication time constraint with multi-drug (MTCMD) for each two drugs in order to better regulate the interval and time of patients' medication. Establishment of a medication reminder system consisting of a cloud database of drug information, an operator terminal for medical staff and a patient terminal. RESULTS: The cloud database has a total of 153,916 pharmaceutical products, 496,708 drug interaction data, and 153,390 pharmaceutical product-ingredient pairs. The MTCOD data was 153,916, and the MTCMD data was 8,552,712. An intelligent UMS medication reminder system was constructed. The system can read the prescription information of patients and provide personalized medication guidance with medication timeline for chronic patients. At the same time, patients can query medication information and get remote pharmacy guidance in real time. CONCLUSIONS: Overall, the medication reminder system provides intelligent medication reminders, automatic drug interaction identification, and monitoring system, which is helpful to monitor the entire process of treatment in patients with chronic diseases.

Analysis of hemorrhagic drug-drug interactions between P-gp inhibitors and direct oral anticoagulants from the FDA Adverse Event Reporting System.

BACKGROUND: Limited understanding exists regarding the hemorrhagic risk resulting from potential interactions between P-glycoprotein (P-gp) inhibitors and direct oral anticoagulants (DOACs). Utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) data, we analyzed hemorrhagic adverse events (AEs) linked with the co-administration of P-gp inhibitors and DOACs, aiming to offer guidance for their safe and rational use. METHODS: Hemorrhagic events associated with P-gp inhibitors in combination with DOACs were scrutinized from the FAERS database. Hemorrhagic signals mining was performed by estimating the reported odds ratios (RORs), corroborated by additive and multiplicative models and a combination risk ratio (PRR) model. RESULTS: Our analysis covered 4,417,195 cases, revealing 11,967 bleeding events associated with P-gp inhibitors. We observed a significantly higher risk of bleeding with the combination of apixaban and felodipine (ROR 118.84, 95% CI 78.12-180.79, additive model 0.545, multiplicative model 1.253, PRR 22.896 (2450.141)). Moreover, consistent associations were found in the co-administration analyzes of rivaroxaban with dronedarone and diltiazem, and apixaban with losartan, telmisartan, and simvastatin. CONCLUSION: Our FAERS data analysis unveils varying degrees of bleeding risk associated with the co-administration of P-gp inhibitors and DOACs, underscoring the importance of vigilance about them in clinical practice.

S-Allyl-L-cysteine (SAC) inhibits copper-induced apoptosis and cuproptosis to alleviate cardiomyocyte injury.

Cardiomyocyte injury is closely related to various myocardial diseases, and S-Allyl-L-cysteine (SAC) has been found to have myocardial protective effects, but its mechanism is currently unclear. Meanwhile, copper also has various physiological functions, and this study found that copper inhibited cell viability in a concentration and time-dependent manner, and was associated with multiple modes of death. Elesclomol plus CuCl2 (ES + Cu) significantly inhibited cell viability, and this effect could only be blocked by copper chelator TTM, indicating that "ES + Cu" induced cuproptosis in cardiomyocytes. SAC reduced the inhibitory effects of high concentration copper and "ES + Cu" on cell viability in a concentration and time-dependent manner, indicating that SAC plays a cardioprotective role under stress. Further mechanism study showed that high concentration of copper significantly induced cardiomyocyte apoptosis and increased the levels of LDH, MDA and ROS, while SAC inhibited the apoptosis and injury of cardiomyocytes induced by copper. "ES + Cu" significantly increased intracellular copper levels and decreased the expression of FDX1, LIAS, Lip-DLST and Lip-DLAT; FDX1 siRNA did not affect the expression of LIAS, but further reduced the expression of Lip-DLST and Lip-DLAT; SAC did not affect the expression of these genes, but enhanced the effect of "ES + Cu" in down-regulating these gene expression and restored intracellular copper levels. In addition, "ES + Cu" reduced ATP production, weakened the activity of mitochondrial complex I and III, inhibited cell viability, and increased the contents of injury markers LDH, MDA, CK-MB and cTnI, while SAC significantly improved mitochondrial function injury and cardiomyocyte injury induced by "ES + Cu". Therefore, SAC can inhibit apoptosis and cuproptosis to play a cardioprotective role.

Optimizing medication guidance support for patients with cancer pain: development and evaluation of a pharmaceutical care system for healthcare professionals.

BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Decreased FGF19 and FGF21: possible underlying common pathogenic mechanism of metabolic and cognitive dysregulation in depression.

Background: Accumulating studies suggested that major depressive disorder (MDD) was closely related to metabolic syndrome (MetS). Important endogenous regulators fibroblast growth factors (FGFs) 19 and 21 were also reported to participate in psychiatric disorders. This study aimed to investigate the role of FGF19 and FGF21 in MDD and to explore the possible pathogenic mechanism of metabolic and cognitive dysregulation in depression. Methods: A total of 59 MDD patients and 55 healthy control participants were recruited. The serum levels of FGF19 and FGF21 and lipid profiles were measured by means of enzymatic methods. Cognitive function was measured by repeatable battery for the assessment of neuropsychological status (RBANS) scores. The gene expression of PGC-1α and FNDC5 was determined by quantitative polymerase chain reaction (PCR). Results: We found that plasma FGF19 and FGF21 levels were significantly decreased in patients with MDD. Meanwhile, triglyceride (TG) was significantly elevated and PGC-1α was significantly downregulated in MDD patients. Correlation analyses showed negative associations between TG and FGF19 levels. As for cognitive performance, both FGF19 and FGF21 levels were positively correlated with immediate memory. However, FGF19 levels were negatively correlated with language, and FGF21 levels were also negatively correlated with attention and delayed memory. Additionally, negative associations were found between FGF19 levels and PGC-1α. FGF21 levels were positively associated with PGC-1α and negatively associated with FNDC5. Conclusion: This study elucidated the role of FGF19 and FGF21 in MDD. MDD patients were confirmed to have metabolic and cognitive dysregulation, and this abnormality was linked to the decreased concentrations of FGF19 and FGF21 through the PGC-1α/FNDC5 pathway. Our results showed that the alterations of FGF19 and FGF21 levels may be a common pathogenic mechanism of metabolic and cognitive disturbances in patients with MDD.

Effects of antifungal drugs on the plasma concentrations and dosage of tacrolimus in kidney transplant patients.

OBJECTIVES: Tacrolimus is one of the three basic immunosuppressants used following kidney transplantation, and its plasma concentration is susceptible to antifungal drugs. Abnormal tacrolimus concentrations may lead to adverse outcomes for patients. Adjustment of the tacrolimus dose after administering antifungal drugs to patients with fungal infection after transplantations therefore has important clinical significance. Our objective is to measure the impact of antifungal drugs on the plasma concentration of tacrolimus in kidney transplant patients. METHODS: A retrospective study was carried out in 109 kidney transplant recipients treated with a tacrolimus-based regimen and antifungal drugs simultaneously. Tacrolimus levels and dosage requirements were compared before and during antifungal therapy. RESULTS: The plasma levels of tacrolimus were significantly increased after the combination with voriconazole and fluconazole (p<0.05). Consequently, the daily dose of tacrolimus was significantly reduced after the combination (p<0.05). However, although the tacrolimus concentration was significantly decreased after the administration of caspofungin (p<0.05), no apparent change in the daily dose of tacrolimus was found. Moreover, there were no significant changes in the tacrolimus levels and the daily dose after the combination with micafungin (p>0.05). CONCLUSIONS: Our results suggest that there is considerable variability in the interaction between tacrolimus and different antifungal drugs. The dose of tacrolimus should be reduced by two-thirds and one-third before the combination with voriconazole and fluconazole, respectively. It is not recommended that the dose should be adjusted before combination with other antifungal drugs, and the dose should be adjusted under the guidance of therapeutic drug monitoring.

Atezolizumab compared to chemotherapy for first-line treatment in non-small cell lung cancer with high PD-L1 expression: a cost-effectiveness analysis from US and Chinese perspectives.

BACKGROUND: The IMpower110 trial revealed that atezolizumab treatment had significantly longer overall survival (OS) than chemotherapy in non-small cell lung cancer (NSCLC) patients with high-programmed death ligand 1 (PD-L1) expression. The purpose of the present study was to estimate the cost-effectiveness of atezolizumab versus platinum-based chemotherapy for first-line treatment in metastatic NSCLC with high PD-L1 expression, from the perspective of US and Chinese payers. METHODS: A partitioned survival model was constructed based on information from the IMpower110 clinical trial to estimate cost-effectiveness of atezolizumab versus chemotherapy as first-line treatment of metastatic NSCLC. Costs were estimated from US and Chinese payer perspectives. The impact of uncertainty was explored by performing one-way and probabilistic sensitivity analyses. RESULTS: In the United States, treatment with atezolizumab was estimated to increase 0.87 quality adjusted life years (QALYs) at a cost of $123,424/QALY. In China, the use of atezolizumab cost an additional $68,489 compared with chemotherapy, yielding an incremental cost-effectiveness ratio (ICER) of $78,936/QALY. Sensitivity analysis indicated that the cost of atezolizumab was the most influential factor in both countries. CONCLUSIONS: In the United States, which had a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY, atezolizumab was a cost-effective strategy for first-line treatment in metastatic NSCLC patients with high PD-L1 expression when compared to chemotherapy. For China, with a WTP threshold of $33,210 per QALY, atezolizumab was not considered good-value treatment for NSCLC, and a price reduction of 52% appeared to be justified.

A rapid, simple and sensitive method for the determination and bioequivalence study of transdermal fentanyl in human plasma using liquid chromatography-electrospray ionization tandem mass spectrometry.

OBJECTIVE: Since the 1960s, fentanyl has been used to replace morphine nd other opioids due to its higher potency in the treatment of acute pain; since the 1990s, it has also been administrated to control chronic pain by using transdermal fentanyl device system. It is crucial and of utmost importance and crucial to validate a sensitive method for the quantification of transdermal fentanyl in human plasma. MATERIALS AND METHODS: A rapid, simple and sensitive high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method has been established and validated for the determination of transdermal fentanyl in human plasma using fentanyl-D5 as an internal standard (IS). Following liquid-liquid extraction (LLE) with n-hexane, the extracts were separated on a Thermo Hypersil ODS(C18) column (2.1 × 150 mm i.d., 5 µm) interfaced with a triple-quadrupole tandem mass spectrometer using positive electrospray ionization. RESULTS AND CONCLUSIONS: Quantification of fentanyl was carried out by multiple reaction monitoring (MRM) of the transitions at m/z 337.1→188.0 for fentanyl and 341.9→187.9 for IS. The lower limit of quantification was 9.75 pg×mL-1, and the test showed a linear range of 9.75 - 10,000 pg×mL-1. The validated method was subsequently applied to a bioequivalence (BE) study in 24 healthy Chinese volunteers by using transdermal fentanyl patches.