Journal of Clinical Pharmacy and Therapeutics最新文献

About one-third of the workers have irregular working hours, subsequently putting them at risk of sleep disorders. It also has negative impacts on employee performance. Sleep disorders and executive performance have been attributed to melatonin dysregulation due to long-term exposure to artificial light. This study investigates melatonin effects on sleep quality and cognitive performance in employees with sleep disorders following shift work. Seventy-two patients with sleep disorders following shift work were equally assigned to melatonin (5 mg before sleep at night after shifts) or matched placebo groups in a randomized, parallel-group, double-blind, placebo-controlled design. Patients were assessed using the short Pittsburgh Sleep Quality Index (shortPSQI), Occupational Cognitive Failure Questionnaire (OCFQ), and adverse events at baseline and weeks 1 and 4. Data from 65 patients were analyzed. Baseline characteristics were comparable between the groups (p values >0.05). The melatonin group showed a greater reduction in total shortPSQI score from baseline to the first (p value = 0.018) and fourth (p value = 0.001) weeks, as well as in total OCFQ score to the fourth week (p value <0.001). In addition, the time-treatment interaction effects on total scores of shortPSQI (p value = 0.004) and OCFQ (p value <0.001) were significant. The only different adverse event between the two groups was fatigue, which was higher in the placebo group (p value = 0.042). Melatonin was safely and tolerably superior to placebo in treating patients with sleep disorders following shift work in the short term. Evidence also shows its effects on improving occupational cognitive performance in the medium term. The study protocol was registered and published prospectively in the Iranian registry of clinical trials (registration number: IRCT20090117001556N153).

The escalating incidence of health issues linked to environmental pollutants, specifically endocrine-disrupting chemicals (EDCs), has emerged as a dire consequence of modern industrialization. Bisphenol A (BPA), a widespread EDC, is under scrutiny for its potential role in exacerbating bladder cancer via the modulation of cancer-associated fibroblasts (CAFs). CAFs are integral to the tumor microenvironment, influencing cancer progression through their interactions with immune cells and secretion of various factors and exosomes. By recognizing the critical role of CAFs, this study delves into their utility as therapeutic targets, focusing on the identification of reliable biomarkers within CAFs for bladder cancer. Through weighted correlation network analysis, genes associated with T cell activity were pinpointed, culminating in the creation of a CAFs-based, immune-related gene prognostic model. Central to this model is ANPEP, an enzyme whose expression level not only serves as an indicator of T cell infiltration but also implicates a substantial role in the CAF-mediated immunotherapy responses for bladder cancer. Our investigation posits ANPEP as a linchpin in regulating CAF functions, offering a novel perspective wherein targeting ANPEP may reduce the adverse side effects commonly associated with traditional immunotherapies. Furthermore, ANPEP-targeted strategies could lessen the tumor mutational burden in bladder cancer patients. Empirical evidence from our proliferation and invasion assays indicates that heightened ANPEP expression is correlated with diminished patient survival. These insights pave the way for tailored immunotherapeutic approaches in bladder cancer treatment, emphasizing the modulation of CAFs by ANPEP.

Context. Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. Objectives. Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. Materials and Methods. In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF-β1-induced EMT in HK-2 cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2 cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. Results. In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF-β1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2 cell epithelial-mesenchymal transition induced by HG combined with TGF-β1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF-β1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2 cells were weakened. Conclusions. The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF-β1/Smad7 signaling pathway.

B-cell chronic malignancies, including chronic lymphocytic leukemia and lymphomas, are among the most common blood malignancies. Conventional therapies for these lymphoproliferative diseases include chemotherapy and radiotherapy. However, treating these types of cancer is still challenging due to developing resistance to chemotherapy drugs and even novel agents like immunochemotherapy. Therefore, many studies are underway to clarify the mechanisms involved in this phenomenon. Recently, the role of noncoding RNAs in regulating gene expression has been well documented in the literature. microRNAs are small noncoding RNAs that regulate gene expression at transcriptional and posttranscriptional levels. Long noncoding RNAs are involved in cell differentiation and tissue development via transcriptional and posttranscriptional regulation. Several miRNAs regulate B-cell development and stimulate activation in normal or malignant B-cells. Molecular assessments revealed the relationship between the up/downregulation of different genes and the development of therapeutic resistance. Studies suggest that the dysregulation of these molecules could be the missing link in developing resistance to chemotherapy drugs. Serum levels of miRNAs can be employed as a predictive biomarker for diagnosis, prognosis, and response to treatment in B-cell malignancies. This study reviews the role of different microRNAs and long noncoding RNAs in regulating the expression of genes involved in drug resistance in B-cell chronic lymphocytic leukemia and lymphomas.

Objective. Intrahepatic cholestasis of pregnancy (ICP) significantly impacts the maternal and fetal safety. Research on the role of clinical pharmacists in guiding drug therapy for this condition remains limited. This study aimed to evaluate the effectiveness of graded pharmaceutical care for women with intrahepatic cholestasis of pregnancy and to provide a theoretical foundation for clinical pharmacist services. Study Design. This study comprises a pre-and-post analysis of women with intrahepatic cholestasis of pregnancy (ICP) treated between December 2019 and June 2023 at a tertiary hospital in Jiangsu province. Each group consisted of 102 participants. The control group received standard treatment, while the guardianship group received graded pharmacological care provided by a clinical pharmacist. The effectiveness of pharmacological monitoring by clinical pharmacists was assessed by comparing and analyzing clinical outcome indicators, quality management indicators, safety indicators, and economic factors. Results. The guardianship group exhibited a noteworthy 12.8% reduction in combined adverse pregnancy outcome and more effective management of total prenatal bile acids compared to the control group (16.05 µmol/L vs. 22.85 µmol/L, P < 0.05). The guardianship group displayed superior rationalization of therapeutic drugs and medication duration (P < 0.05). The cost-benefit analysis revealed a favorable economic impact concerning medication costs but did not indicate economic significance regarding total inpatient costs. Conclusion. The implementation of a graded pharmaceutical care model by a clinical pharmacist holds the potential to enhance outcomes for women experiencing intrahepatic cholestasis during pregnancy, mitigate adverse pregnancy results, optimize the rational utilization of therapeutic medications, and yield positive economic results.

Background. Take-up of the influenza (flu) vaccination in France is assessed every year by Santé publique France (SPF), a national health agency. In 2020, the pandemic of COVID-19 took place all over the world. With several symptoms known to be similar between flu and COVID-19, we expected to observe a positive association with people’s choice to also take the flu vaccine injection. Methods. Data regarding the flu vaccination for people aged 65 and over were extracted from the French National Health Data System (Système National des Données de Santé—SNDS). A noninterventional multicenter survey in the Department of Maine et Loire, an area in the west of France, was used for assessing the effect of COVID-19 on vaccination intention. Results. The flu vaccine take-up (Maine et Loire, France), among people aged 65 and over, improved since 2017 (54.36% in 2017–18 vs 58.12% in 2020–21). In 2020–21 (concomitant with the COVID-19 pandemic), people got vaccinated earlier than the previous year (peak in weeks 1–2 vs peak in weeks 5–6 in previous campaigns), before a shortage of doses interrupted the 2020–21 campaign. Of the 211 people who answered the survey among the 232 for whom it was proposed, 175 were vaccinated during the 2020–21 flu vaccine campaign. Among them, 29.12% declared they were aware of COVID-19 when receiving the flu vaccine. The most cited reason for taking the vaccination was the need to feel safe from the influenza virus; the second was “awareness of the fact that a virus can be contagious and deadly.” Conclusion. Our study highlights the COVID-19 association perceived by the elderly population (Maine et Loire) on flu vaccination rates. Despite having human consequences, the COVID-19 pandemic seems to be beneficial to flu vaccine take-up and may positively change people’s beliefs and behaviors towards flu vaccination.

Background. Few large-sample studies have examined the use of fecal management systems (FMSs) in intensive care units (ICUs) or evaluated the associated complications. This study aims to assess the effectiveness and safety of FMS for stool diversion in ICU patients with fecal incontinence (FI). Methods. We enrolled 381 FI patients, assigning them to either an FMS group (n = 134), which used a fecal management device, or a usual care (UC) group (n = 247) that received standard care including regular perianal cleaning. Results. The FMS group reported lower incidence and severity of incontinence-associated dermatitis (IAD) and higher Braden Scale scores (10.42 ± 2.77) compared to the UC group (9.71 ± 2.56), indicating reduced pressure ulcer risk. Notably, FMS-associated complications were minimal, with only 5 patients (3.73%) affected; one required surgical intervention for rectal mucosal bleeding. Conclusions. FMS significantly reduced stool-associated skin irritation, lowered the incidence of IAD and pressure injuries, and improved nurses’ convenience compared to UC.

What Is Known and Objective. Tocolytic agents are used to prolong gestational age and prevent immediate preterm birth (PTB). This study aims to provide an overview of the use of tocolytics among patients with PTB in China through retrospectively analyzing trends in application, influencing factors, and inappropriate prescriptions. Methods. The prescription data of five tocolytic agents from 2016 to 2021 were extracted from the database of the Hospital Prescription Analysis Cooperation Project. Drug consumption was expressed as number of prescriptions, cost of prescriptions, and DDDs (defined daily doses). Pearson correlation analysis was used to examine the association between DDDs and DDC (defined daily cost). The appropriateness of prescriptions was analyzed in terms of drug dosage form, administration, clinical diagnosis, and combined medication. Results. The total number of tocolytic prescriptions and the total cost of tocolytic agents increased by 6.12% and 387.58%, respectively, over the six-year duration of the study. From 2016 to 2021, the ranking of the number of prescriptions and DDDs of tocolytic agents was magnesium sulfate > ritodrine > nifedipine > indomethacin > atosiban. During the study period, the cost of tocolytic agents increased significantly, which was mainly related to the increased costs of magnesium sulfate in 2017 and atosiban in 2018 and 2019. The ranking of DDCs was atosiban > ritodrine > magnesium sulfate > nifedipine = indomethacin from 2016 to 2021. For atosiban, the DDC was negatively correlated with the DDDs. Inappropriate prescription, which accounted for 14.84% of all prescriptions, was mainly manifested in the inappropriate selection of nifedipine dosage form, low frequency of nifedipine and indomethacin, and overdosing of ritodrine. Furthermore, 22.87% of tocolytic prescriptions remained active after 34 weeks of gestation, and 7.24% of the prescriptions authorized the use of combination drugs, with magnesium sulfate and nifedipine being the most commonly prescribed combination. What Is New and Conclusion. Magnesium sulfate, ritodrine, and nifedipine were the top three tocolytic agents. As the inappropriate use of tocolytic agents continues to persist, it is important to intensify efforts to ensure the safety and the appropriateness of maternal medication.

Purpose. Catechol-O-methyltransferase (COMT) participates in the regulation of dopaminergic and adrenergic neurotransmission. COMT Val158Met polymorphism influences the efficacy and safety of opioids, but its association with oxycodone treatment in patients with cancer pain is yet to be elucidated. Hence, this study aimed to investigate the influence of COMT Val158Met polymorphism on oxycodone requirements, drug adverse effects, and pain sensitivity in patients with cancer. Methods. Patients with moderate to severe cancer pain treated with oxycodone were enrolled, of which 101 patients completed the study. All patients were genotyped for COMT Val158Met polymorphism using DNA from blood samples and were categorized into the wild-type group (n = 50) comprising individuals with the Val/Val genotype and the mutant group (n = 51) encompassing those with the Val/Met or Met/Met genotype. Numerical rating scale (NRS) scores, oxycodone requirements, and the incidence of oxycodone-related adverse drug reactions were compared between the two groups. Results. Patients in the mutant group exhibited higher NRS scores (6.18 ± 1.40) before the oxycodone treatment than those in the wild-type (5.48 ± 1.54) group (P = 0.017). Patients in the wild-type group required more oxycodone (96.00 ± 146.19 mg/24 h) than those in the mutant (77.25 ± 83.91 mg/24 h) group (P = 0.0365). The incidence rates of dysuria (2.0% vs. 16.0%, P = 0.016) and fatigue (0.0% vs. 12.0%, P = 0.013) were significantly lower in the mutant group than those in the wild-type group. Moreover, patients with at least one Met allele showed a lower risk of suffering from oxycodone-related side effects than those with the wild homozygote (41.2% vs. 68.0%, P = 0.007). Conclusion. Genetic variations in the COMT Val158Met gene may contribute to variability in the efficacy and safety of oxycodone in cancer pain treatment. The findings from this study emphasize the potential of pharmacogenetics in personalizing pain management. Furthermore, oxycodone therapeutic strategies can be designed based on genetic polymorphisms.

Background. Nasopharyngeal carcinoma (NPC), prevalent in East Asia and associated with EBV infection, poses unique challenges due to its complex immunological interactions. This study aims to dissect the molecular and immune mechanisms of NPC, providing a pathway to novel treatments. Methods. Through bioinformatics, we analyzed gene expression and immune cell infiltration in NPC tissues. Differential gene expression profiling, single-cell RNA sequencing, and gene set variation analysis (GSVA) were performed to understand the immune landscape and identify EBV-related molecular changes. Results. The differential gene expression analysis highlighted a diverse immune cell composition, suggesting an intricate immune evasion landscape. GSVA pinpointed pathways linked to tumor immunity and EBV pathogenesis. Notably, the expression of immune checkpoints, such as PD-L1, was significantly associated with NPC, offering a potential target for immunotherapy. Conclusions. Our findings underscore the potential of immunotherapeutic approaches in NPC, particularly those modulating the PD-1/PD-L1 axis. The integration of bioinformatics and immunology in NPC research provides a foundation for personalized medicine and warrants further exploration into combination therapies to enhance treatment efficacy.