RATIONALE & OBJECTIVEThe potential effects of antenatal glucocorticoid exposure on the health of children are unclear. We examined the association of gestational exposure to maternal systemic glucocorticoids and the risk of developing chronic kidney disease (CKD) in childhood.STUDY DESIGNRetrospective cohort study.SETTING & PARTICIPANTSNewborns cared for at the largest health care delivery system in Taiwan between 2004 and 2018.EXPOSUREMaternal prescriptions for systemic glucocorticoids between the last menstrual period and birth as a proxy for gestational exposure.OUTCOMEIncidence of childhood CKD, including congenital anomalies of the kidney and urinary tract (CAKUT) and other kidney diseases (non-CAKUT), over 10 years.ANALYTICAL APPROACHCox proportional hazards models with stabilized inverse probability of treatment weighting and robust sandwich estimator were used to estimate the average association between systemic glucocorticoids and incident CKD after adjustment for offspring characteristics (adjusted HR: AHR).RESULTSAmong 23,363 singleton-born children, gestational systemic glucocorticoid exposure was significantly associated with a higher risk of childhood CKD (AHR, 1.69 [95% CI, 1.01-2.84]). Stratified analyses showed stronger associations between systemic glucocorticoids and childhood CKD within the strata of birth<37 weeks' gestational age (AHR, 2.38 [95% CI, 1.19-4.78]), male sex (AHR, 1.89 [95% CI, 1.00-3.55]), gestational exposure in the second trimester (AHR, 6.70 [95% CI, 2.17-20.64]), and total dose of>24mg hydrocortisone equivalent (AHR, 1.91 [95% CI, 1.05-3.47]).LIMITATIONSStudy was limited to the Taiwan health care delivery system and childhood CKD events through the age of 10 years.CONCLUSIONSThe findings of this study suggest that gestational exposure to systemic glucocorticoids is associated with the occurrence of kidney disease in childhood. If these findings are confirmed, they may inform clinicians who are considering prescribing systemic glucocorticoids during pregnancy.PLAIN-LANGUAGE SUMMARYIn a singleton-born cohort of neonates, maternal exposure to antenatal systemic glucocorticoids was significantly associated with a 1.7-fold increased risk of the children developing chronic kidney disease over the first 10 years of life. Children of mothers who received>24mg of hydrocortisone equivalent, systemic glucocorticoid treatment in second trimester of gestation, and children born at<37 weeks of gestational age had a higher risk of childhood kidney disease after gestational systemic glucocorticoid exposure. If these findings are confirmed, they may inform clinicians who are considering prescribing systemic glucocorticoids during pregnancy.

2024-05-20·Journal of Clinical Oncology

Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression

Article

作者: Oliveira, Mafalda ; Piccart-Gebhart, Martine ; Carey, Lisa A ; Gianni, Luca ; Bardia, Aditya ; Hurvitz, Sara A ; Hofsess, Scott ; Rugo, Hope S ; Tolaney, Sara M ; Phan, See-Chun ; Shaughnessy, Joyce O' ; Diéras, Véronique ; Kalinsky, Kevin ; Loirat, Delphine ; Cortés, Javier ; Punie, Kevin ; Loibl, Sibylle ; Pan, Yang ; Yoon, Oh Kyu ; Brufsky, Adam

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Sacituzumab govitecan (SG), a first-in-class anti–trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physician's choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study. Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression. Final efficacy secondary end point analyses and post hoc analyses of outcomes stratified by Trop-2 expression and human epidermal growth factor receptor 2 status are reported. Updated safety analyses are provided. In this final analysis, SG (n = 267) improved median progression-free survival (PFS; 4.8 v 1.7 months; hazard ratio (HR), 0.41 [95% CI, 0.33 to 0.52]) and median overall survival (OS; 11.8 v 6.9 months; HR, 0.51 [95% CI, 0.42 to 0.63]) over TPC (n = 262). SG improved PFS over TPC in each Trop-2 expression quartile (n = 168); a trend was observed for improved OS across quartiles. Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups. These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.

2024-04-02·Drug Development and Industrial Pharmacy

Enhanced dissolution rates of glibenclamide through solid dispersions on microcrystalline cellulose and mannitol, combined with phosphatidylcholine

Article

作者: Lee, Robert J. ; Weecharangsan, Wanlop

OBJECTIVEThis study aimed to investigate the impact of physical solid dispersions of spray-dried glibenclamide (SG) on the surface of microcrystalline cellulose (MC) and mannitol (M) surfaces, as well as their combination with phosphatidylcholine (P), on enhancing the dissolution rate of glibenclamide (G).METHODSSolid dispersions were prepared using varying proportions of 1:1, 1:4, and 1:10 for SG on the surface of MC (SGA) and M (SGM), and then combined with P, in a proportion of 1:4:0.02 using spray drying. The particle size, specific surface area, scanning electron microscopy (SEM), X-ray diffraction (XRD), and dissolution rate of SGA and SGM were characterized.RESULTSSEM analysis revealed successful adhesion of SG onto the surface of the carrier surfaces. XRD showed reduced crystalline characteristic peaks for SGA, while SGM exhibited a sharp peaks pattern. Both SGA and SGM demonstrated higher dissolution rates compared to SG and G alone. Furthermore, the dissolution rates of the solid dispersions of SG, MC and P (SGAP), and SG, M, and P (SGMP) were sequentially higher than that of SGA and SGM.CONCLUSIONSThe study suggests that physical solid dispersions of SG on MC and M, along with their combination with P, can effectively enhance the dissolution rate of G. These findings may be valuable in developing of oral solid drug dosage forms utilizing SGA, SGM, SGAP, and SGMP.

100 项与异丙基安替比林/对乙酰氨基酚/烯丙基乙酰脲/无水咖啡因相关的药物交易

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