Journal of Clinical Pharmacy and Therapeutics最新文献

Background: The rise of drug-resistant bacteria poses a significant challenge to global healthcare, underscoring the urgent need for new therapeutic interventions. In this study, ethanolic extracts of Datura stramonium and Prosopis farcta, sourced from Northern Iran, were examined for their antibacterial properties against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Methods: The antibacterial activities of the medicinal extracts were examined in this study using disc diffusion, microbroth dilution, and agar well diffusion methods against both Gram-positive and Gram-negative microorganisms. In addition, the extracts were assessed for toxicity using the MTT assay on HT29 cells. The biofilm-inhibitory effects of the extracts were also investigated.

Results: The results showed that the ethanolic extracts from D. stramonium and P. farcta have strong antibacterial activity against S. aureus. However, their activity against P. aeruginosa and A. baumannii is less pronounced. The extracts showed significant antibiofilm capabilities against the tested bacteria at both MIC and 2× MIC concentrations (p < 0.05). The MTT test showed HT29 cells were more sensitive to P. farcta extract than D. stramonium, especially at 200 μg/mL concentration.

Conclusion: The findings demonstrate that ethanolic extracts of P. farcta and D. stramonium exhibit significant antibacterial activity, particularly against S. aureus, while also effectively disrupting bacterial biofilms. These results suggest that these extracts possess considerable potential as alternative therapeutic agents against drug-resistant bacterial infections. Further investigation is warranted to elucidate the specific mechanisms of action and to explore their efficacy in clinical applications.

Background: Pharmacological sedation during neonatal magnetic resonance imaging (MRI) is crucial for procedure success and minimizing artifacts. Hence, it is vital to evaluate the effectiveness and safety of conventional sedatives in this population. In this study, we aim to evaluate the effectiveness of oral chloral hydrate combined with intranasal dexmedetomidine in neonatal MRI.

Methods: Neonates aged 0 to 28 days undergoing MRI were enrolled and received intranasal dexmedetomidine followed by oral chloral hydrate. Subsequently, sedation scores, onset time, and overall time of sedation, as well as any potential adverse reactions, were recorded.

Results: All neonates completed the MRI without notable adverse reactions. 128 neonates (90.1%) completed the MRI study with a single dose, while 14 neonates (9.9%) required additional medications. In the neonates with a single dose, no statistically significant differences in onset time were observed across postnatal days, gender, and weight. And no statistically significant differences in total time were observed across postnatal days and gender. However, the total time was significantly extended in the neonates with a weight under 3 kg. Furthermore, compared to the neonates with a single dose, the total time was significantly extended in the neonates with additional medications.

Conclusion: Oral chloral hydrate combined with intranasal dexmedetomidine is effective and safe for neonatal MRI, but extra attention is needed for neonates under 3 kg.

To overcome TRAIL resistance, we tested the antidepressant drug citalopram (CTL) in combination with TRAIL. The resistance of several types of cancer cells to TRAIL impedes TRAIL-induced cancer cell death. In this study, we investigated the role of, and molecular mechanism by which, the antidepressant CTL-induced cell death in TRAIL-resistant lung cancer cells. We found that CTL increased death receptor 5 (DR5) expression levels by impairing autophagic flux and protecting against lysosomal degradation, thereby increasing the TRAIL-induced apoptosis of TRAIL-resistant A549 lung cancer cells. We also found that CTL impaired autophagic flux and promoted the conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, thereby inducing autophagosome accumulation. Our hypothesis that impaired autophagic flux plays an important role in the upregulation of DR5 being confirmed when we determined that DR5 upregulation by CTL was markedly decreased in the presence of rapamycin, an autophagy inducer. Further verification of our theory was achieved through experiments pairing CTL with the early-stage autophagy inhibitor 3-methyladenine (3-MA) and the late-stage autophagy inhibitor chloroquine (CQ). CQ inhibits autophagy by impairing autophagosome–lysosome fusion. Both CTL and CQ markedly increased DR5 expression levels and increase TRAIL-induced apoptosis, whereas 3-MA marginally enhanced TRAIL-induced apoptosis and resulted in minimal DR5 expression. In summary, our findings indicate that CTL impairs autophagic flux, resulting in autophagosome accumulation and augmentation of DR5 to potentiate TRAIL-induced apoptosis, suggesting that CTL may act as a therapeutic agent that sensitizes TRAIL-resistant cancer cells to TRAIL-mediated cancer therapy.

What Is Known and Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve renal and cardiovascular outcomes and have been reported to have a positive impact on anemia, a common and challenging condition in patients with chronic kidney disease (CKD). The aim of this study is to evaluate the effects of SGLT2 inhibitors on anemia in patients with CKD.

Methods: We performed a systematic review and meta-analysis of randomized controlled trials. Changes in hemoglobin (Hb) and hematocrit (Hct) levels were assessed in participants treated with SGLT2 inhibitors—empagliflozin, dapagliflozin, or canagliflozin—and compared with those receiving control treatments. Statistical analyses were performed using a fixed-effects model or a random-effects model, depending on the heterogeneity. Sensitivity analyses were also conducted to evaluate the impact of each study on the meta-analysis. Publication bias was examined using Begg’s and Egger’s tests.

Results and Discussion: Five studies assessing Hb levels were included. SGLT2 inhibitors significantly increased Hb levels compared with controls (standard difference in means [SE] = −0.350; 95% confidence interval [CI] −0.401–−0.299). Similarly, in three studies evaluating Hct levels, SGLT2 inhibitors significantly increased Hct levels compared with controls (SE = −0.453; 95% CI −0.829–0.077).

What Is New and the Conclusions: This systematic review confirms that SGLT2 inhibitors effectively improve anemia in patients with CKD. We recommend considering SGLT2 inhibitors as a treatment option for CKD patients, not only for their renal and cardiovascular benefits but also for their reliability in addressing anemia.

Objective: The primary objective of this study revolves around the development of a population pharmacokinetic (PPK) model for vancomycin in neonatal subjects, with the objective of providing a theoretical basis for judicious therapeutic interventions.

Methods: In this study, a retrospective collection encompassed 75 neonatal patients, contributing to a total of 89 vancomycin blood concentration monitoring datasets. The establishment of the PPK model is carried out utilizing the nonlinear mixed effects model methodology. The PPK model was constructed employing a one-compartment model with proportional residual error, and the influence of covariates on pharmacokinetic parameters was systematically assessed through forward stepwise addition and backward elimination methods. The stability and predictive accuracy of the final model were assessed using goodness-of-fit plots, nonparametric bootstrap validation, visual predictive checks, and normalized prediction distribution errors. Furthermore, Monte Carlo simulations were employed to predict vancomycin concentrations in neonatal patients with typical characteristics.

Results: The final PPK model yielded population-typical values of 0.24 L/h for vancomycin clearance (CL). Noteworthy contributors to vancomycin CL were identified as body weight, gestational age, creatinine clearance rate (CLcr), and sex. Internal validation results of the model indicate that it possesses stability, efficacy, and demonstrates a favorable predictive capacity. Monte Carlo simulations indicate that for a male neonatal patient characterized by a gestational age of 37 weeks, a body weight of 2.5 kg, and a CLcr of 60 mL/min, the recommended dosing regimen is 25.5 to 41.5 mg every 8 h.

Conclusion: This investigation has successfully formulated a PPK model for vancomycin in neonatal patients, offering the capacity to estimate individual CL. The dosing regimen for neonates should take into account factors such as body weight, gestational age, CLcr, and sex.

Background: Asthma is a prevalent chronic respiratory condition marked by airway inflammation and hyperresponsiveness, significantly impacting quality of life. Emerging evidence suggests a potential association between proton pump inhibitor (PPI) use and an increased risk of asthma. This systematic review and meta-analysis assessed the relationship between PPI use and the development or exacerbation of asthma.

Methods: A systematic search of PubMed, Web of Science, and Embase databases was conducted, covering studies published from the inception of the database to July 12, 2024. Observational studies examining the association between PPI use and asthma risk were included. Two reviewers independently extracted data using Nested Knowledge software, with study quality assessed via the Newcastle–Ottawa Scale. A random-effects meta-analysis was performed, pooling odds ratios (ORs) and hazard ratios (HRs) to assess the association, with heterogeneity evaluated via the I² statistic.

Results: Fourteen studies, conducted between 2009 and 2024 and involving over 1.7 million participants, met the inclusion criteria. The pooled HR showed a 38% increased risk of asthma among PPI users compared to nonusers (HR, 1.38; 95% CI, 1.14–1.62). OR analysis indicated a 29% higher risk (OR, 1.29; 95% CI, 1.23–1.35). PPI users had an 81% higher risk compared to histamine H₂ receptor antagonist (H₂RA) users (HR, 1.81; 95% CI, 1.09–2.53), and asthma patients using PPIs were 61% more likely to experience exacerbations (OR, 1.61; 95% CI, 1.42–1.80).

Conclusion: PPI use is associated with an increased risk of asthma. These findings underscore the need for cautious prescribing and further investigation into underlying mechanisms.

Background: Remimazolam is a good option for anesthesia in elderly patients undergoing gastrointestinal (GI) endoscopy procedures because of its rapid onset, short metabolic duration, and extensively documented safety profile. However, the accurate clinical dosage of these agents has yet to be determined. The objective of this research was to examine the efficacy of the 90% effective dose (ED90) of remimazolam in suppressing the responses of elderly patients during the insertion phase of upper GI endoscopy.

Methods: We enrolled 53 individuals aged 65– 85 years who underwent upper GI endoscopy and were anesthetized with an intravenous bolus of remimazolam. After initiating an initial dose of 0.35 mg/kg remimazolam, subsequent adjustments were made on the basis of the patient’s response, employing an up-and-down sequential allocation using a biased coin design. The primary outcome was the ED90 of the remimazolam infusion for inhibiting the response to upper GI endoscope insertion. Adverse reactions during the perioperative period were observed and recorded.

Results: The ED90 of remimazolam for upper GI endoscope insertion in elderly patients was 0.400 mg/kg (95% CI = 0.348–0.524). Stable circulation was maintained in all patients, and no serious adverse events were observed during sedation. Satisfaction levels were high among the participants: Patients reported a satisfaction score of 4.98 ± 0.14 points, anesthesiologists rated their satisfaction at 4.91 ± 0.35 points, and endoscopists expressed a satisfaction level of 4.89 ± 0.38 points (based on a total score of 5 points, with a minimum of 1 point).

Conclusion: Administration of remimazolam for upper GI endoscopy in elderly patients was found to be both safe and effective. A single intravenous bolus at an ED90 dose of 0.556 mg/kg effectively suppressed the response to the procedure.

Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2200062535

Purpose: Inappropriate use of antibiotics contributes to the increase in antimicrobial resistance with negative health safety implications. Global health organizations have promoted projects to improve proper and rational use of antibiotics. Recent studies show how antibiotics can also influence the efficacy of immune checkpoint inhibitors (ICIs) treatment in cancer patients. This work analyzes the impact of concomitant antibiotic therapy in patients affected by skin, lung, and kidney cancer, who started immunotherapy in 2020-2021 at Veneto Institute of Oncology IRCCS. The aim of this study is to evaluate clinical outcomes, treatment efficacy, discontinuation causes, and occurrence of adverse drug reactions in cancer patients treated with ICIs.

Methods: Data from the real-world retrospective study were extracted from Territorial Pharmaceutical Care databases, medical records, and the AIFA registry. A descriptive analysis of the study population was performed, as well as of patient outcomes in terms of progression-free survival (PFS) and overall survival (OS).

Results: A total of 239 subjects affected by kidney (8%), lung (48%), and skin (44%) cancer were enrolled; of these, 50%, 32%, 9%, and 9% were treated with single-agent nivolumab, pembrolizumab, atezolizumab, and cemiplimab, respectively. A total of 119 patients received concomitant antibiotic therapy. Median OS was 8.8 months (95% CI: 5.02–11.8) and 31.05 months (95% CI: 24.81–NA) in subjects with high and low antibiotic exposure, respectively. Multivariate subgroup analysis confirmed that high antibiotic exposure is an unfavorable factor also for median PFS.

Conclusion: A prolonged exposure to antibiotics correlates with unfavorable outcomes in cancer patients undergoing concomitant immunotherapy. Thus, managing antibiotic exposure is fundamental for optimizing ICI treatment.

Aim: This study aimed to investigate post-marketing adverse events (AEs) of interleukin-6 (IL-6) inhibitors, and to explore risk factors for death.

Method: Disproportionality analyses were conducted on adverse event cases of IL-6 inhibitors reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the time of drug launch until the fourth quarter of 2023. Univariate and multivariate logistic regression analyses were carried out utilizing patient-related clinical information, and prediction models for IL-6 inhibitor-related mortality risk were developed by incorporating patient age and weight factors.

Results: A total of 63,445 reports were retrieved, with the majority of known age groups falling between 18 and 64 years. Most reports were submitted by consumers and physicians, predominantly from the United States. Tocilizumab was associated with AEs such as drug intolerance and infection, while sarilumab showed symptoms of pain and condition aggravated. Siltuximab was linked to disease progression and thrombocytopenia. The median time to AEs with IL-6 inhibitors was 74 days (interquartile range [IQR] 10-311), mostly occurring within 1 month. Factors such as age, propionic acid derivative, infections and infestations, nervous system disorders, and immune system disorders were independent risk factors for deaths related to IL-6 inhibitor use (p < 0.05). The mortality risk prediction model demonstrated good discriminatory power and clinical applicability in both the training set (AUC 0.6968) and the validation set (AUC 0.7502).

Conclusion: Our postmarketing pharmacovigilance analysis revealed the types and incidence of AEs related to IL-6 inhibitors. Column line diagrams may be useful for clinical assessment of the occurrence of death and have high clinical utility.

Renal clear cell carcinoma (ccRCC) presents a unique landscape of genetic and epigenetic modifications, the understanding of which is crucial for the development of targeted therapies and improved prognostication. This study explores the differential expression of histone-related genes (HRGs) in ccRCC and correlates these findings with patient clinical outcomes. By leveraging the Cancer Genome Atlas (TCGA) data, we performed a robust multidimensional analysis of HRG expression profiles in ccRCC versus adjacent normal tissues. Our results demonstrate a significant upregulation of several key epigenetic regulators, including UHRF1, KDM5A, EZH2, PRDM6, and TWIST1, in tumor samples, with statistical significance suggesting their involvement in tumorigenesis and progression. Paired expression analysis within patient-matched samples confirmed the consistency of overexpression in tumors. The prognostic relevance of these genes was underscored through survival analyses, which revealed a clear stratification of patients into distinct risk categories based on their expression profiles. The integration of these genetic markers with clinical parameters facilitated the development of a predictive nomogram, yielding a quantifiable tool for survival prediction. Our comprehensive analysis elucidates the profound impact of epigenetic dysregulation in ccRCC and proposes a novel set of biomarkers for disease diagnosis, prognostic stratification, and potential therapeutic targeting, marking a significant stride toward precision oncology in renal cancer.