Background: Posaconazole (PCZ) has been used to prevent and treat invasive fungal infections in immunocompromised patients with hematological malignancies. There is a significant correlation between plasma drug concentration and the efficacy of posaconazole.
Objective: sThis study aimed to investigate the effects of glucocorticoid on PCZ Cmin and on the outcome of PCZ prevention/treatment of invasive fungal infections.
Methods: We conducted a retrospective study at a tertiary hospital, examining patients who were administered posaconazole oral suspension between September 2021 and September 2023, to assess the effect of glucocorticoid on the plasma drug concentration and antifungal effect of posaconazole.
Results: (Ⅰ) The concomitant usage of glucocorticoid reduced PCZ Cmin from 1310.00 (648.48，2550.00) ng/mL to 1085.00 (529.79，1767.50) ng/mL (p = 0.032), and the Cmin/Dose (C/D) decreased from 2.14 (0.98, 4.10) ng/mL/mg to 1.66 (0.86, 2.73) ng/mL/mg (p = 0.038). (Ⅱ) There was a significant difference in PCZ Cmin between patients on low-dose glucocorticoids and those on medium & high-dose glucocorticoids (1271.14 vs 720.19 ng/mL, p < 0.001). (Ⅲ) PCZ Cmin was significantly lower in patients with longer glucocorticoid duration than with shorter (p = 0.013). (Ⅳ) Compared with PCZ alone, the concomitant usage of PPIs, glucocorticoids, and PPIs & glucocorticoids significantly reduced PCZ Cmin (p < 0.001, p= 0.001, p= 0.001).
Conclusions: The concomitant usage of glucocorticoid can significantly reduce PCZ Cmin, and this decrease has a correlation with the dose and duration of glucocorticoid. However, glucocorticoid may not affect the clinical outcome of posaconazole in the prevention/treatment of invasive fungal infections.
Objective: To investigate the effects of Lianggu Decoction combined with clomiphene on insulin resistance, ovarian hemodynamics, and pregnancy outcomes in infertile patients with obese polycystic ovary syndrome (PCOS).
Methods: A total of 127 infertile patients with obese PCOS admitted between February 2022 and December 2023 were enrolled in the study. Patients were randomly assigned into a control group (n = 64, clomiphene alone) and an observation group (n = 63, clomiphene + Lianggu Decoction). Clinical efficacy, insulin resistance indices, blood glucose, blood lipids, body mass index (BMI), ovarian hemodynamics, serum sex hormone levels, ovulation rate, pregnancy outcomes, and adverse reactions were compared between the two groups.
Results: The total effective rate was significantly higher in the observation group (P < 0.05). After treatment, fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and BMI were significantly lower in the observation group (P < 0.05). Fasting insulin (FINS) and the homeostasis model assessment of insulin resistance (HOMA-IR) were also lower in the observation group, while the HOMA of β-cell function (HOMA-β) was higher (P < 0.05). In terms of ovarian hemodynamics, pulsatility velocity spectrum (PVS) and pulsatility index (PI) were higher, whereas the resistance index (RI) was lower in the observation group (P < 0.05). Additionally, serum estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were lower in the observation group (P < 0.05). The ovulation rate and clinical pregnancy rate were significantly higher, while the miscarriage rate was lower in the observation group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05).
Conclusion: Lianggu Decoction combined with clomiphene is effective in treating infertility in obese PCOS patients. It can significantly improve insulin resistance, glucose and lipid metabolism, sex hormone levels, and ovarian hemodynamics, thereby enhancing pregnancy outcomes.
There are currently six ALK inhibitors available for the first-line treatment of patients diagnosed with ALK-positive advanced non-small cell lung cancer (NSCLC). However, clinicians face challenges in selecting the most appropriate drug for treatment. We have collated pertinent evaluative evidence and undertaken a multifaceted assessment of the enrolled medications across five critical dimensions: safety, efficacy, pharmaceutical properties, drug economy, and other properties. This comprehensive analysis aims to furnish a robust foundation for the selection and clinical deployment of pharmaceuticals, thereby advocating for the judicious and rational utilization of medications in clinical practice. Upon conducting an exhaustive evaluation, we determined that the aggregate scores for all ALK inhibitors under review surpassed the threshold of 75 points, with brigatinib distinguishing itself as the top performer in terms of overall scoring. Considering that safety, efficacy, and pharmacological properties are paramount in the comprehensive clinical appraisal of pharmaceuticals, lorlatinib emerged with the highest score when evaluated solely on these three critical criteria. Through an extensive evaluation of ALK inhibitors, it has been determined that each ALK inhibitor possesses unique strengths across a spectrum of five distinct dimensions. Notably, when evaluating both the comprehensive scores across all five dimensions and the focused scores for the top three dimensions, third-generation inhibitors consistently ranked as the optimal choice. Healthcare organizations can leverage these findings to assess and select ALK inhibitors that align with their specific requirements, utilizing the comparative rankings and scores across various dimensions to inform their selection process.
Objective: To determine the optimal timing, dosage, and efficacy of combination NSAID therapy in preventing post-ERCP pancreatitis.
Methods: A total of 866 patients undergoing ERCP between December 2021 and December 2023 were enrolled and randomly assigned to an observation group or a control group, with further subgrouping into combination therapy or monotherapy groups. The observation group received NSAIDs such as indomethacin suppositories and/or diclofenac sodium before ERCP, while the control group received NSAIDs postoperatively. The combination therapy group received both diclofenac sodium and indomethacin suppositories, whereas the monotherapy group received only diclofenac sodium. Primary endpoints included the incidence and severity of pancreatitis, as well as the occurrence of post-procedural complications such as perforation, bleeding, cholangitis, and pain scores. These outcomes were compared between groups to evaluate differences in the incidence and severity of PEP.
Results: The group receiving pre-procedural NSAIDs had a significantly lower risk of adverse reactions compared with the post-procedural group. Combination therapy showed superior PEP risk reduction compared to monotherapy. Independent risk factors for PEP included female sex, age > 60 years, a history of gallstones or pancreatitis, hypertension, five cannulation attempts > 5, and non-dilated extrahepatic bile ducts.
Conclusion: Prophylactic combination therapy with indomethacin suppositories and diclofenac sodium before ERCP significantly reduces PEP incidence and severity, while concurrently decreasing risks of perforation, hemorrhage, cholangitis, and postoperative pain scores.
Objective: To investigate the factors influencing venlafaxine blood concentration exceeding the alert threshold in patients with depression and to develop a risk prediction model for elevated venlafaxine concentrations, providing a reference for individualized VEN therapy.
Methods: A retrospective analysis was conducted on 590 hospitalized patients who received venlafaxine treatment and underwent TDM at the First Hospital of Hebei Medical University between January 2021 and August 2024. Patients were categorized into a target concentration group (100-400 ng/mL) and an above-alert group (> 800 ng/mL) based on their VEN plasma concentrations. Demographic and clinical variables, including sex, age, body mass index (BMI), average daily dose, plasma albumin level, concomitant medications, liver and kidney function, were collected and compared between groups. Logistic regression analysis was performed to identify independent risk factors associated with VEN concentrations exceeding the alert threshold. A nomogram prediction model was constructed based on the identified factors and was subsequently validated.
Results: Among the 590 patients, 516 were in the target concentration group and 74 were in the above-alert group. The proportion of females, patients with BMI < 24, average daily dose ≥ 225 mg, renal impairment, and concomitant use of CYP2D6 inhibitors was significantly higher in the above-alert group than in the target group (P < 0.05). Logistic regression analysis revealed that average daily dose ≥ 225 mg (OR = 26.628, 95 % CI: 12.912-54.916), renal impairment (OR = 2.429, 95 % CI: 1.215-4.854), and concomitant use of CYP2D6 inhibitors (OR = 5.232, 95 % CI: 2.781-9.844) were independent risk factors for VEN concentrations exceeding the alert threshold (P < 0.05). The nomogram model showed an AUC of 0.899 (95 % CI: 0.864-0.935), sensitivity of 48.65 %, specificity of 95.74 %, positive predictive value of 62.07 %, and negative predictive value of 92.86 %. Bootstrap validation demonstrated good consistency (Brier score = 0.072), and the Hosmer-Lemeshow test indicated good calibration (χ2 = 3.16, P = 0.531). Decision curve analysis demonstrated clinical utility for threshold probabilities of 0.05-0.80.
Conclusions: Average daily dose ≥ 225 mg, renal impairment, and concomitant use of CYP2D6 inhibitors are independent risk factors for VEN plasma concentrations exceeding the alert threshold. The constructed nomogram model effectively predicts the risk of venlafaxine concentration exceeding the alert range and has significant clinical application value.