Journal of Clinical Pharmacy and Therapeutics最新文献

What Is Known and Objective. Given that autoantibodies are relatively abundant and easily measured, the detection of antibody biomarkers would be ideal for predicting therapeutic responses. Although anti-Ro60/SSA (anti-TROVE2) antibody has been identified as a useful predictor for the development of immunogenicity and therapeutic failure to adalimumab in RA patients, autoantibodies with similar predictive potentials are not yet sufficiently validated. Methods. We aimed to investigate the baseline autoantibodies, including rheumatoid factor (RF)-IgM, anti-citrullinated peptide antibodies (ACPA), antinuclear antibody (ANA), anti-Ro60/SSA antibody, and anti-La/SSB antibody, for their relationships with drug immunogenicity and therapeutic responses in RA patients assessed at week 48 of adalimumab therapy. We also compared adalimumab drug survival between participants with or without these autoantibodies. Results and Discussion. Our results showed that poor EULAR responders had significantly higher positive rates of baseline ANA, anti-Ro60/SSA antibody, and anti-La/SSB antibody than moderate or good responders. However, no significant differences in circulating levels of RF-IgM or ACPA were observed among groups with different responses. The multivariate logistic regression analysis revealed that ANA and anti-Ro60/SSA antibodies were significant predictors of developing immunogenicity to adalimumab (both p < 0.001). The presence of ANA, anti-Ro60/SSA, and anti-SSB antibodies could significantly predict poor EULAR response in adalimumab-treated RA patients (odds ratio, 4.98, 5.60, and 8.08, respectively, all p < 0.01). In Kaplan–Meier analysis, the adalimumab drug survival rate was significantly lower in RA patients with positivity for ANA, anti-Ro60/SSA, anti-SSB, and anti-drug antibodies than in the seronegative group. What Is New and Conclusion. Our results suggest that baseline ANA and anti-Ro60/SSA antibodies are potential predictive markers of drug immunogenicity and poor EULAR response in adalimumab-treated RA patients.

Background. Induction or augmentation of labor may cause more painful contractions compared to spontaneous labor and pose a challenge to the efficacy of analgesia provided by spinal opioids alone in the early phase of labor. Therefore, we studied the analgesic efficacy and maternal satisfaction during spontaneous and artificially induced or augmented delivery in parturients receiving neuraxial analgesia with intrathecal opioids. Methods. A forty-parturient cohort that received intrathecal opioid (sufentanil 5 µg or fentanyl 20 µg) by the combined spinal-epidural method at an early phase of labor (cervical dilatation ≤5 cm) was used for this post hoc study. Maternal satisfaction and pain during contractions were measured on 0–100 visual analog scale at 30 minutes after the initiation of labor analgesia. Obstetric parameters (methods used to advance labor, cervical dilatation, use of oxytocin, effective time of spinal opioids, and labor outcome) were also measured. Results. Of the 40 parturients, 18 had spontaneous labor and 22 had induced or augmented labor (prior cervical dilatation, artificial rupture of membranes, or oxytocin infusion at the time of neuraxial analgesia initiation). Spontaneous labor associated with lower mean pain scores (6.4 (±12.8) vs 29.6 (±30.6) mm, P = 0.005) and higher satisfaction scores (96.9 (±5.3) vs 81.1 (±28.0) mm, P = 0.024) compared to induced or oxytocin augmented labor at 30 minutes after the initiation of analgesia. The parturients were at a similar stage of labor, and their labor progressed at a similar rate. Conclusions. In parturients undergoing nonspontaneous labor, the initiation of labor analgesia by intrathecal opioids alone may not be sufficient for adequate analgesia and either intrathecal or epidural analgesia with a mixture of opioid and local anesthetic should be considered in this population. This trial is registered with NCT02885350.

Background. Succinylcholine and rocuronium are the predominant neuromuscular blocking agents (NMBAs) used for rapid sequence intubation (RSI) in the emergency department (ED). Prior studies have found reduced first-attempt intubation success (FAIS) with rocuronium compared to succinylcholine. Recent large registry data have shown no difference in intubating conditions or FAIS. Objectives. The objective of this study was to compare FAIS rates for rocuronium and succinylcholine when used for RSI in a high-acuity academic ED. Methods. This was a single-center retrospective study. Patients were included if they received either succinylcholine or rocuronium for RSI in the ED from January 2016 to August 2020. The primary endpoint was FAIS. Subgroup analyses were performed evaluating the impact of weight-based dosing on FAIS for each agent, and multivariate analysis was conducted to evaluate the impact of baseline characteristics on the primary outcome. Results. There were 448 patients who received rocuronium and 183 patients who received succinylcholine. No difference was observed in unadjusted FAIS between patients receiving rocuronium (median weight-based dose: 1.22 mg/kg) or succinylcholine (median weight-based dose: 1.43 mg/kg) (361 (80.6%) vs. 150 (82.0%), p = 0.69). There were no differences in FAIS between the weight-based dose categories for rocuronium and for succinylcholine. Conclusions. These findings were consistent with those from recent studies indicating no difference in FAIS between rocuronium and succinylcholine, although the median dose of rocuronium used in this study was higher than traditionally recommended. Larger prospective studies are warranted to further evaluate the effect of weight-based paralytic dosing on FAIS.

What is Known and Objective. Omalizumab is a humanized anti-IgE antibody, which is used in the treatment of chronic spontaneous urticaria (CSU). This study aims to investigate the trends in the efficacy of omalizumab for CSU, focusing on temporal aspects, drug dosages, and sample sizes. Methods. Cochrane, OVID MEDLINE, Embase, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) from 1900 to January 2023. The primary outcome was the percentage of complete responders (defined as the weekly urticaria activity score as 0, UAS7 = 0). Secondary outcomes included the percentage of patients with UAS7 ≤ 6, the percentage of patients achieving a minimally necessary difference in weekly itch severity score (defined as a reduction from baseline in ISS7 of ≥5 points, ISS7 MID), and adverse events (AEs). A cumulative meta-analysis was performed with pooled risk ratio (RR) and 95% confidence intervals (CI). Publication bias was assessed by the contour-enhanced funnel plots with the trim-and-fill method, alongside Begg’s and Egger’s tests. Results and Discussion. Twelve randomized, placebo-controlled studies encompassing 2166 patients were analyzed. Compared with the placebo group, the omalizumab group exhibited significant increases in the proportion of patients achieving UAS7 = 0 [RR 5.18, 95% CI (3.97, 6.75), I² = 14%], UAS7 ≤ 6 [RR 3.21, 95% CI (2.69, 3.83), I² = 30%], and ISS7 MID responders [RR 1.50, 95% CI (1.39, 1.63), I² = 33%]. AEs were similar between the omalizumab group and placebo group [RR 0.96, 95% CI (0.89, 1.03), I² = 4%]. What is New and Conclusion. The cumulative meta-analysis confirmed that the efficacy outcomes for omalizumab have remained consistent over time, across different drug doses and sample sizes, with improved precision from newer studies. Omalizumab is confirmed to be safe and effective for CSU. It is also suggested to minimize redundant RCTs to conserve scientific and medical resources efficiently.

Background. This study aims to assess and explore the different effects of national centralized drug procurement (NCDP) on three targeted antitumor drugs’ use in clinical practice. Materials and Methods. Clinical drug volume data were collected covering 18 months before, during, and after the seventh round of the NCDP in Inner Mongolia. The interrupted time-series method was employed to estimate the net effect of policy impact. Results. The volume of generic afatinib (30 mg) increased by 25.78 DDDs, the expenditures decreased by 3641.14 yuan (p = 0.001), and the DDDc decreased by 124.35 yuan (p < 0.001). The volume of generic afatinib (40 mg) increased by 65.19 DDDs (p < 0.001), the expenditures increased by 1304.93 yuan (p < 0.001), and the DDDc decreased by 120.2 yuan (p < 0.001). The volume of generic sunitinib increased by 75.79 DDDs (p < 0.001), the expenditures decreased by 15869.78 yuan (p < 0.001), and the DDDc decreased by 243.28 yuan. There was no significant change trend in volume, expenditures, and DDDc of the three original-targeted drugs after NCDP intervention. Conclusions. After the policy intervention, generic afatinib (40 mg) successfully aligned with the objectives of NCDP by reducing drug costs and enhancing patient affordability; however, the desired outcomes were not achieved for generic afatinib (30 mg) and generic sunitinib. This discrepancy may be attributed to the inherent clinical efficacy and safety profiles of these drugs. Therefore, in implementing NCDP, it is necessary to enhance the clinical efficacy and safety of generic-targeted antitumor drugs while considering economic efficiency.

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.