Background: Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands.
Methods: We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands.
Background: Formal transition programs prepare pediatric patients with congenital heart disease (CHD) for successful lifelong management of their disease. Conducting transition program activities in pediatric cardiology clinics can be a challenge if there are limited resources. The purpose of this study was to test the effectiveness of a medical assistant (MA)-facilitated transition activity in increasing documentation of transition discussions and characterize staff acceptability of this intervention.
View Article and Find Full Text PDFBackground: Dolutegravir (DTG) is an antiviral agent used for the treatment of HIV, however, there is uncertainty over the influence of genetic variation on DTG exposure, and whether it has clinical implications for the efficacy or toxicity in different populations. This systematic review aims to create an overview of the impact of pharmacogenomics (PGx) on DTG exposure, efficacy, and toxicity.
Methods: Publications up to 14 November 2023 were searched and articles were selected on the following criteria: original research articles providing data on people with HIV, data on PGx and either PK or PD or both PD and PGx.
This study introduces a novel joint modeling framework integrating quantile regression for longitudinal continuous proportions data with Cox regression for time-to-event analysis, employing integrated nested Laplace approximation for Bayesian inference. Our approach facilitates an examination across the entire distribution of patient health metrics over time, including the occurrence of key health events and their impact on patient outcomes, particularly in the context of medication adherence and persistence. Integrated nested Laplace approximation's fast computational speed significantly enhances the efficiency of this process, making the model particularly suitable for applications requiring rapid data analysis and updates.
View Article and Find Full Text PDFBackground: Determining a therapeutic window for maintaining antiretroviral drug concentrations within an appropriate range is required for identifying effective dosing regimens. The limits of this window are typically calculated using predictive models. We propose that target concentrations should instead be calculated based on counterfactual probabilities of relevant outcomes and describe a counterfactual framework for this.
View Article and Find Full Text PDFExtracellular vesicles, small membrane-bound packages secreted by virtually all cells of the body, have become a focus of interest in nephrology over the recent years. After the first characterization of their proteomic and transcriptomic content, scientific attention shifted toward their potential as biomarkers for kidney diseases both as diagnostic and monitoring tools. More recently, researchers have begun exploring whether extracellular vesicles mediate intercellular signaling inside the nephron and between the kidney and other organs throughout the body.
View Article and Find Full Text PDFLetermovir and maribavir have demonstrated efficacy in the prevention and treatment, respectively, of immunosuppressed patients with cytomegalovirus (CMV) infection and disease. These patients often have polypharmacy making them at risk for drug-drug interactions. Both letermovir and maribavir can be perpetrators and victims of drug-drug interactions.
View Article and Find Full Text PDFIntroduction: Early diagnosis of acute kidney injury (AKI) is limited with current tools. MicroRNAs (miRNAs) are implicated in AKI pathogenesis in preclinical models, but less is known about their role in humans. We conducted a systematic review to identify dysregulated miRNAs in humans with AKI.
View Article and Find Full Text PDFCancer Chemother Pharmacol
December 2024
Introduction: For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal.
View Article and Find Full Text PDFPodocytes possess immune system components allowing for a variety of innate responses to endogenous and exogenous stimuli. Recently, several groups have linked inappropriate innate immune signaling to podocyte injury, particularly chronic, sustained injury; however, the immune capabilities of podocytes have not been fully elucidated. Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from damaged cells, including podocytes, and can elicit an inflammatory response and recruit immune cells to areas of injury.
View Article and Find Full Text PDFBackground: Darunavir is a potent HIV protease inhibitor with a high barrier to resistance. We conducted a nested pharmacokinetic sub-study within CHAPAS-4 to evaluate darunavir exposure in African children with HIV, taking once-daily darunavir/ritonavir for second-line treatment.
Methods: We used data from the CHAPAS-4 pharmacokinetic sub-study treating children with once-daily darunavir/ritonavir (600/100 mg if 14-24.
Context: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood.
Objective: To investigate the associations of aldosterone and renin with body composition according to sex in the general population.
Design: Population-based cohort study.
Small molecule inhibitors (SMIs) are increasingly being used in the treatment of non-small cell lung cancer. To support pharmacokinetic research and clinical treatment monitoring, our aim was to develop and validate an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay for quantification of eight SMIs: adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib. Development of the UPLC-MS/MS assay was done by trying different columns and eluents to optimize peak shape.
View Article and Find Full Text PDFJ Pediatric Infect Dis Soc
September 2024
We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to <20 kg) or 50 mg (>20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.
View Article and Find Full Text PDFNatural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro.
View Article and Find Full Text PDFBackground: Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction.
View Article and Find Full Text PDFAim: Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia-reperfusion (IR) injury in mice, although its long-term effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function.
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