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BACKGROUND: Intraoperative fluoroscopy is increasingly common in orthopaedics, although recent guidelines have reduced the maximum recommended exposure to 20 mSv annually. A systematic review of the literature was conducted to comprehensively assess current adherence to exposure guidelines, identify practice settings at increased risk for exposure, and determine the best practices and personal protective equipment for ocular radiation risk mitigation. QUESTIONS/PURPOSES: In this systematic review we asked: (1) Is the annual amount of eye irradiation received by orthopaedic surgeons below the recommended limit of 20 mSv? (2) What is the effectiveness of leaded glasses in reducing the eye's exposure to radiation? (3) Which imaging setups and operative techniques reduce ocular irradiation? METHODS: PubMed, Medline, EBSCOhost, and Google Scholar were queried on September 28, 2023, to identify studies assessing intraoperative ocular radiation exposure among orthopaedic surgeons. Studies that measured radiation in or around the eye (such as the bridge of the nose or eyebrows) during orthopaedic procedures were included. Exclusion criteria were duplicate studies, studies that only estimated eye radiation based on the radiation dose recorded at parts of the body distant from the eyes, nonoriginal research, case reports, and articles without full-text English versions available. A total of 393 unique articles were retrieved, and after title, abstract, and full-text screening, 23 dosimetry studies were included, comprising 12 prospective observational studies, 7 phantom models, 1 cadaver model, 2 observational studies, and 1 randomized control trial. Risk of bias was determined via the Methodological Index for Nonrandomized Studies (MINORS) tool. Study quality was generally good to excellent, with noncomparative studies having a mean MINORS score of 14 ± 0 of 16 and comparative studies achieving a mean score of 19 ± 1 of 24, with higher scores representing better study quality. Due to extensive heterogeneity in study design, a meta-analysis was not conducted, with the results rather presented as a narrative summary of key findings. RESULTS: The vast majority of surgeons conducting a variety of orthopaedic and traumatologic procedures were not exposed to a hazardous level of eye irradiation annually, but surgeons who perform a high volume of fluoroscopy-intensive procedures may exceed guidelines. Leaded eyeglasses reduced eye radiation by about 90%, with sport wrap-around glasses offering better shielding than alternatives, although leaded glasses overall were largely underutilized. Positioning mini C-arms in the standard vertical configuration was shown to provide up to a 13-fold decrease in radiation exposure compared with inverted configuration, while standing perpendicular to the fluoroscope further reduced eye irradiation. CONCLUSION: We found that orthopaedic surgeons who perform a high volume of fluoroscopy-intensive procedures may be at risk of exceeding recommendations on annual radiation exposure, although exposure can be mitigated through various simple strategies. In particular, this analysis found that the use of sport wrap-around leaded glasses, positioning of mini-C arms in the standard vertical configuration, and standing perpendicular to the fluoroscope provide the most effective means of limiting ocular radiation exposure. As ophthalmic radiation exposure presents a potentially important occupational health hazard to orthopaedic surgeons, further investigations of radiation exposure specific to high-volume, fluoroscopy-intensive orthopaedic practices and long-term ophthalmic outcomes will help determine the extent of the potential harm posed by frequent exposure to intraoperative radiation over the span of a career. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Lipid nanoparticles have proved an attractive approach for drug delivery; however, the challenges of optimising formulation stability and increasing drug loading have limited progression. In this work, we investigate the role of unpegylated lipid surfactants (helper lipids) in nanoparticle formation and the effect of blending helper lipids with pegylated lipid surfactants on the formation and stability of lipid-based nanoparticles by nanoprecipitation. Furthermore, blends of unpegylated/pegylated lipid surfactants were examined for ability to accommodate higher drug loading formulations by means of a higher weight percentage (wt%) of drug relative to total mass of formulation components (i.e. drug, surfactants and lipids). Characterisation included evaluation of particle diameter, size distribution, drug loading and nanoformulation stability. Our findings demonstrate that the addition of unpegylated lipid surfactant (Lipoid S100) to pegylated lipid surfactant (Brij S20) enhances stability, particularly at higher weight percentages of the core material. This blending approach enables drug loading capacities exceeding 10% in the lipid nanoparticles. Notably, Lipoid S100 exhibited nucleating properties that aided in the formation and stabilisation of the nanoparticles. Furthermore, we examined the incorporation of a model drug into the lipid nanoparticle formulations. Blending the model drug with the core material disrupted the crystallinity of the core, offering additional potential benefits in terms of drug release and stability. This comprehensive investigation provides valuable insights into the interplay between surfactant properties, core material composition, and nanoparticle behaviour. The study enhances our understanding of lipid materials and offers guidance for the design and optimisation of lipid nanoparticle formulations.
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A significant number of new chemical entities in the drug development pipeline are poorly soluble, therefore routes that facilitate effective administration is of considerable value. Lipid nanoparticles have proved an attractive approach for drug delivery; however, challenges that include optimising drug loading and understanding the impact of drug physiochemical parameters on nanoparticle properties have limited progression. In this work, we investigate the effect of modifying the log P of a model drug on the formation and stability of lipid-based nanoparticles. A range of model drug analogues with systematically varying alkyl chains were produced using a lamivudine (nucleoside analog reverse transcriptase inhibitor) scaffold and processed into lipid nanoparticles by nanoprecipitation. Characterisation included evaluation of particle diameter, size distribution, drug loading and nanoformulation stability. A distinct correlation with the LaMer model of nucleation was observed and log P appeared to strongly influence rates of nucleation. Model drugs with high log P were uniform in particle size and distribution and offered enhanced stability. In addition, various model drug/lipid blends were produced and their physical properties were investigated using dynamic light scattering (DLS) and differential scanning calorimetry (DSC). Complex mixtures of lipids were shown to influence formulation crystallinity and strategies to form uniform and stable lipid based nanoparticles of high drug loading- through manipulation of log P are discussed.
Assuntos
Fármacos Anti-HIV/química , Lamivudina/química , Lipossomos/química , Nanopartículas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Modelos Moleculares , Estrutura Molecular , Tamanho da PartículaRESUMO
Thomas Campbell Butler, at 63 years of age, is completing the first year of a 2-year sentence in federal prison, following an investigation and trial that was initiated after he voluntarily reported that he believed vials containing Yersinia pestis were missing from his laboratory at Texas Tech University. We take this opportunity to remind the infectious diseases community of the plight of our esteemed colleague, whose career and family have, as a result of his efforts to protect us from infection by this organism, paid a price from which they will never recover.