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Reducing off-target expression of mRNA therapeutics and vaccines in the liver with microRNA binding sites.
Mol Ther Methods Clin Dev
March 2025
Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA.
Lipid nanoparticles (LNPs) are often liver tropic, presenting challenges for LNP-delivered mRNA therapeutics intended for other tissues, as off-target expression in the liver may increase side effects and modulate immune responses. To avoid off-target expression in the liver, miR-122 binding sites have been used by others in viral and non-viral therapeutics. Here, we use a luciferase reporter system to compare different copy numbers and insertion locations of miR-122 binding sequences to restrict liver expression.
View Article and Find Full Text PDFDrug-Induced Myoclonus: A Systematic Review.
Medicina (Kaunas)
January 2025
Neurology Department, Cooper University Hospital, Camden, NJ 08103, USA.
: Myoclonus is already associated with a wide variety of drugs and systemic conditions. As new components are discovered, more drugs are suspected of causing this disabling abnormal involuntary movement. This systematic review aims to assess the medications associated with drug-induced myoclonus (DIM).
View Article and Find Full Text PDFLonger disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis.
J Comp Eff Res
January 2025
Mitsubishi Tanabe Pharma America, Inc., Health Economics and Outcomes Research (HEOR), Medical Affairs, Jersey City, NJ, 07310 USA.
To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava IV, Mitsubishi Tanabe Pharma America [MTPA], hereafter "IV edaravone") in a real-world setting. IV edaravone is US FDA approved for the treatment of ALS and was shown in clinical trials to slow the rate of physical functional decline. This retrospective observational analysis included PALS continuously enrolled in Optum's Clinformatics Data Mart between 8 August 2017 and 31 December 2021.
View Article and Find Full Text PDFComparative risks and clinical outcomes of midazolam versus other intravenous sedatives in critically ill mechanically ventilated patients: A systematic review and meta-analysis of randomized trials.
Intensive Crit Care Nurs
January 2025
School of Nursing, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region. Electronic address:
Objectives: This systematic review synthesized literature evidence and compared midazolam's risks and clinical outcomes with other sedatives in critically ill mechanically ventilated patients.
Methods: We included randomized controlled trials (RCTs) from databases of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL without language restrictions. We used relative risk (RR) for binary outcomes and standardized mean difference (SMD) for continuous outcomes, with corresponding 95% confidence interval (CI).
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