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Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial.

Med

December 2024

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address:

Background: The unmet needs of managing patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who progress after cyclin-dependent kinase (CDK)4/6 inhibitor (CDK4/6i) treatment remain unclarified.

Methods: This was a phase 1b/2, single-arm, open-label study that enrolled 29 patients with HR+/HER2- breast cancer who experienced first-line palbociclib treatment failure. The primary endpoint was the incidence of dose-limiting toxicity (DLT).

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Introduction: The aim of the observational SIMPLE study was to assess real-life effectiveness and safety of a single-pill combination (SPC) of perindopril arginine/amlodipine in a broad range of subjects with newly diagnosed mild-to-moderate hypertension treated in Canadian general practice.

Methods: Treatment-naïve participants aged 18-65 years with mild-to-moderate hypertension, whose physicians decided to initiate the perindopril/amlodipine SPC, were recruited from Canadian clinical practice from October 2017 to February 2019. Participants were followed at 3- (M3) and 6-month (M6) visits after treatment initiation.

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The complexity of the currently registered dosing schedules for bedaquiline and delamanid is a barrier to uptake in drug-resistant tuberculosis treatment across all ages. A simpler once-daily dosing schedule is critical to ensure patient-friendly regimens with good adherence. We assessed expected drug exposures with proposed once-daily doses for adults and compared novel model-informed once-daily dosing strategies for children with current World Health Organization (WHO) recommended dosing.

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Background: Huntington's disease (HD) is a rare neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in the huntingtin gene which encodes the mutant huntingtin protein (mHTT) that is associated with HD-related neuropathophysiology. Noninvasive visualization of mHTT aggregates in the brain, with positron emission tomography (PET), will allow to reliably evaluate the efficacy of therapeutic interventions in HD. This study aimed to assess the radiation burden of [F]CHDI-650, a novel fluorinated mHTT radioligand, in humans based on both in vivo and ex vivo biodistribution in mice and subsequent determination of dosimetry for dosing in humans.

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Rationale and Logistics of Continuous Infusion Cephalosporin Antibiotics.

Pharmacy (Basel)

December 2024

Department of Pharmacy, Prisma Health Richland, 5 Medical Park Drive, Columbia, SC 29203, USA.

Cephalosporins have traditionally been administered as an intermittent infusion. With the knowledge that cephalosporins demonstrate a time-dependent pharmacodynamic profile, administration via continuous infusion may provide more effective antibiotic exposure for successful therapy. Proposed benefits of administration via continuous infusion include less IV manipulation, decreased potential for antibiotic resistance, and potential cost savings.

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