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1.
Kayla Ann Andrews Joel S. Owen James McCarthy David Wesche Nathalie Gobeau Thaddeus H. Grasela Jrg J. Mhrle 《CTS Clinical and Translational Science》2021,14(2):712
Volunteer infection studies using the induced blood stage malaria (IBSM) model have been shown to facilitate antimalarial drug development. Such studies have traditionally been undertaken in single‐dose cohorts, as many as necessary to obtain the dose‐response relationship. To enhance ethical and logistic aspects of such studies, and to reduce the number of cohorts needed to establish the dose‐response relationship, we undertook a retrospective in silico analysis of previously accrued data to improve study design. A pharmacokinetic (PK)/pharmacodynamic (PD) model was developed from initial fictive‐cohort data for OZ439 (mixing the data of the three single‐dose cohorts as: n = 2 on 100 mg, 2 on 200 mg, and 4 on 500 mg). A three‐compartment model described OZ439 PKs. Net growth of parasites was modeled using a Gompertz function and drug‐induced parasite death using a Hill function. Parameter estimates for the PK and PD models were comparable for the multidose single‐cohort vs. the pooled analysis of all cohorts. Simulations based on the multidose single‐cohort design described the complete data from the original IBSM study. The novel design allows for the ascertainment of the PK/PD relationship early in the study, providing a basis for rational dose selection for subsequent cohorts and studies. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
2.
Elaine Owen 《Physical & occupational therapy in pediatrics》2019,39(3):254-258
3.
Jeffrey D. Hassebrock Michael G. Fox Mark J. Spangehl Matthew R. Neville Adam J. Schwartz 《The Journal of arthroplasty》2019,34(1):126-131
Background
The American Academy of Orthopedic Surgeons clinical practice guideline currently recommends repeat joint aspiration when workup of periprosthetic joint infection (PJI) reveals conflicting data. This guideline is based on a single study of 31 patients published 25 years ago. We sought to determine the correlation between first and second aspirations and factors that may play a role in variability between them.Methods
Sixty patients with less than 90 days between aspirations and no intervening surgery were identified at our institution and classified by Musculoskeletal Infection Society (MSIS) criteria as infected, not infected, or not able to determine after both aspirations. Culture results from both aspirations were recorded. The rates of change and correlation in clinical diagnosis and culture results between aspirations were determined.Results
Repeat aspiration changed the diagnosis in 26 cases (43.3%, 95% confidence interval 31.6-55.9, kappa coefficient 0.32, P < .001), and the culture results in 25 cases (41.7%, 95% confidence interval 30.1-54.3, kappa coefficient 0.27, P < .01). Among patients initially MSIS negative, the proportion who changed to MSIS positive was greater for those with a history of prior PJI compared to those without (66.7% vs 0%, P < .05), and the first aspiration mean volume was higher for those changed to MSIS positive compared to those that remained MSIS negative (12.0 vs 3.0 mL, P < .01). Among patients initially MSIS positive, the proportion of patients who changed to MSIS negative was greater for those with a history of adverse local tissue reaction (ALTR) to metal debris compared to patients without suspicion of ALTR (100% vs 7.7%, P < .05).Conclusion
Repeat aspiration is particularly useful in patients with conflicting clinical data and prior history of PJI, suspicion of ALTR, or with high clinical suspicion of infection. 相似文献4.
5.
Collin Mangenah Lawrence Mwenge Linda Sande Nurilign Ahmed Marc d'Elbe Progress Chiwawa Tariro Chigwenah Sarah Kanema Miriam N Mutseta Mutinta Nalubamba Richard Chilongosi Pitchaya Indravudh Euphemia L Sibanda Melissa Neuman Getrude Ncube Jason J Ong Owen Mugurungi Karin Hatzold Cheryl C Johnson Helen Ayles Elizabeth L Corbett Frances M Cowan Hendramoorthy Maheswaran Fern Terris‐Prestholt 《Journal of the International AIDS Society》2019,22(Z1)
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Marco A. De Jesús‐Tllez Dulce M. Snchez‐Cerrillo Patricia Quintana‐Owen Ulrich S. Schubert David Contreras‐Lpez Carlos Guerrero‐Snchez 《Macromolecular chemistry and physics.》2020,221(9)
Kinetic investigations of the quaternization reactions of poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) with alkyl halides (1‐iodobutane, 1‐iodoheptane, and 1‐iododecane) are carried out at different temperatures. For this purpose, a PDMAEMA (Mn = 17.8 kDa, Ð = 1.35) synthesized via reversible addition fragmentation chain transfer polymerization is utilized. The progress of the quaternization reactions is followed by proton nuclear magnetic resonance. As expected, the rate of quaternization is higher with increasing temperature. The experimental data are used to determine the following kinetic parameters: order of the reaction, Arrhenius' pre‐exponential factor, and activation energy. To the best of knowledge, this is the first contribution that provides detailed kinetic data of the quaternization reactions on PDMAEMA. 相似文献
9.
10.
Renuka V. Iyer MD Bhavana Konda MD MPH Christos Fountzilas MD Sarbajit Mukherjee MD MS Dwight Owen MD MS Kristopher Attwood PhD Chong Wang MA Orla Maguire PhD Hans Minderman PhD Sheryl-Ann Suffren BA Karen Hicks BS John Wilton PhD Robert Bies PhD Danielle Casucci BA Diane Reidy-Lagunes MD Manisha Shah MD 《Cancer》2020,126(16):3689-3697