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91.
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?
92.
Girish B Nair Craig J Galban Sayf Al-Katib Robert Podolsky Maarten van den Berge Craig Stevens Edward Castillo 《The British journal of radiology》2021,94(1118)
Objective:To evaluate CT-ventilation imaging (CTVI) within a well-characterized, healthy cohort with no respiratory symptoms and examine the correlation between CTVI and concurrent pulmonary function test (PFT).Methods:CT scans and PFTs from 77 Caucasian participants in the NORM dataset (clinicaltrials.gov ) were analyzed. CTVI was generated using the robust Integrated Jacobian Formulation (IJF) method. IJF estimated total lung capacity (TLC) was computed from CTVI. Bias-adjusted Pearson’s correlation between PFT and IJF-based TLC was computed.Results:IJF- and PFT-measured TLC showed a good correlation for both males and females [males: 0.657, 95% CI (0.438–0.797); females: 0.667, 95% CI (0.416–0.817)]. When adjusting for age, height, smoking, and abnormal CT scan, correlation moderated [males: 0.432, 95% CI (0.129–0.655); females: 0.540, 95% CI (0.207–0.753)]. Visual inspection of CTVI revealed participants who had functional defects, despite the fact that all participant had normal high-resolution CT scan.Conclusion:In this study, we demonstrate that IJF computed CTVI has good correlation with concurrent PFT in a well-validated patient cohort with no respiratory symptoms.Advances in knowledge:IJF-computed CTVI’s overall numerical robustness and consistency with PFT support its potential as a method for providing spatiotemporal assessment of high and low function areas on volumetric non-contrast CT scan. NCT00848406相似文献
93.
G.R. Iball D. Tolan G.R. Avery L.H. Cope T. Hoare H. Lambie A. Lowe R.J. de Noronha C.L. Roberts M.E. Wilkinson P. Woolfall 《Clinical radiology》2021,76(8):626.e13-626.e21
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96.
B.R. Mussmann S.D. Mørup P.M. Skov S. Foley A.S. Brenøe F. Eldahl G.M. Jørgensen H. Precht 《Radiography》2021,27(1):1-7
IntroductionOrgan-based tube current modulation (OBTCM) is designed for anterior dose reduction in Computed Tomography (CT). The purpose was to assess dose reduction capability in chest CT using three organ dose modulation systems at different kVp settings. Furthermore, noise, diagnostic image quality and tumour detection was assessed.MethodsA Lungman phantom was scanned with and without OBTCM at 80–135/140 kVp using three CT scanners; Canon Aquillion Prime, GE Revolution CT and Siemens Somatom Flash. Thermo-luminescent dosimeters were attached to the phantom surface and all scans were repeated five times. Image noise was measured in three ROIs at the level of the carina. Three observers visually scored the images using a fivestep scale. A Wilcoxon Signed-Rank test was used for statistical analysis of differences.ResultsUsing the GE revolution CT scanner, dose reductions between 1.10 mSv (12%) and 1.56 mSv (24%) (p < 0.01) were found in the anterior segment and no differences posteriorly and laterally. Total dose reductions between 0.64 (8%) and 0.91 mSv (13%) were found across kVp levels (p < 0.00001). Maximum noise increase with OBTCM was 0.8 HU. With the Canon system, anterior dose reductions of 6–10% and total dose reduction of 0.74–0.76 mSv across kVp levels (p < 0.001) were found with a maximum noise increase of 1.1 HU. For the Siemens system, dose increased by 22–51% anteriorly; except at 100 kVp where no dose difference was found. Noise decreased by 1 to 1.5 HU.ConclusionOrgan based tube current modulation is capable of anterior and total dose reduction with minimal loss of image quality in vendors that do not increase posterior dose.Implications for practiceThis research highlights the importance of being familiar with dose reduction technologies. 相似文献
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BACKGROUND AND PURPOSE:Although multishot EPI (readout-segmented EPI) has been touted as a robust DWI sequence for cholesteatoma evaluation, its efficacy in disease detection compared with a non-EPI (eg, HASTE) technique is unknown. This study sought to compare the accuracy of readout-segmented EPI with that of HASTE DWI in cholesteatoma detection.MATERIALS AND METHODS:A retrospective review was completed of consecutive patients who underwent MR imaging for the evaluation of suspected primary or recurrent/residual cholesteatomas. Included patients had MR imaging examinations that included both HASTE and readout-segmented EPI sequences and confirmed cholesteatomas on a subsequent operation. Two neuroradiologist reviewers assessed all images, with discrepancies resolved by consensus. The ratio of signal intensity between the cerebellum and any observed lesion was noted.RESULTS:Of 23 included patients, 12 (52.2%) were women (average age, 47.8 [SD, 25.2] years). All patients had surgically confirmed cholesteatomas: Six (26.1%) were primary and 17 (73.9%) were recidivistic. HASTE images correctly identified cholesteatomas in 100.0% of patients. On readout-segmented EPI sequences, 16 (69.6%) were positive, 5 (21.7%) were equivocal, and 2 (8.7%) were falsely negative. Excellent interobserver agreement was noted between reviews on both HASTE (κ = 1.0) and readout-segmented EPI (κ = 0.9) sequences. The average signal intensity ratio was significantly higher on HASTE than in readout-segmented EPI, facilitating enhanced detection (mean difference 0.5; 95% CI, 0.3–0.8; P = .003).CONCLUSIONS:HASTE outperforms readout-segmented EPI in the detection of primary cholesteatoma and disease recidivism.Middle ear cholesteatomas are ectopic, keratinizing squamous epithelium, which may be acquired or, much less commonly, congenital.1,2 Although not considered a true neoplasm, cholesteatomas are locally destructive and have a high propensity for recurrence following surgical removal. As they gradually expand, cholesteatomas erode the osseous structures within and adjacent to the middle ear cavity, including the ossicles, labyrinth, fallopian canal, and middle fossa bone plate.3 Current mainstay therapy includes microsurgical extirpation, with the chief goal of complete disease removal and prevention of intratemporal and intracranial complications.4 The most common microsurgical approach for cholesteatoma is an canal wall up tympanomastoidectomy, in which the posterior bony ear canal is left intact and the tympanic membrane is reconstructed. Depending on the extent of disease at surgery, a planned second-look procedure may be performed approximately 1 year after the initial operation to evaluate residual disease and potentially reconstruct the ossicular chain when indicated. Nevertheless, residual and/or recurrent (ie, recidivism) disease occurs in up to 30% of cases. Imaging is crucial in cholesteatoma management; it aids in the initial diagnosis and may obviate the need for second-look surgery.5,6During the past decade, DWI has emerged as a powerful diagnostic tool for detection of both primary and residual or recurrent cholesteatomas.7-9 Cholesteatomas demonstrate marked hyperintensity on DWI , likely related to either T2 shinethrough or intralesional restricted diffusion related to keratin debris.10 Across the years, there have been many iterations of DWI optimization for cholesteatoma identification. The EPI trajectory used by conventional DWI makes such sequences prone to substantial susceptibility artifacts, and single-shot EPI sequences were found to be poor at identifying lesions of <4–5 mm.11-13 Consequently, non-EPI DWI techniques began to be favored; such algorithms minimize susceptibility artifacts and geometric distortion related to the skull base and are able to detect lesions as small as 2 mm.14,15 BLADE (Siemens) and other such PROPELLER sequences are subtypes of non-EPI techniques that minimize susceptibility artifacts and geometric distortions by sampling k-space in a rotating fashion.16,17More recently, HASTE DWI (Siemens) has emerged as a particularly effective sequence, which is relatively insensitive to motion and has been shown in prior studies to detect cholesteatomas with promising accuracy.18,19 Although traditional EPI techniques have been largely abandoned in the setting of cholesteatoma detection, readout-segmented EPI (RESOLVE; Siemens) DWI is a relatively new technique that has been promoted as a possible alternative diffusion sequence. RESOLVE is a multishot (MS) EPI sequence that is able to reduce geometric distortions at the expense of longer imaging time. Recent reports have indicated that RESOLVE may be a useful sequence in cases of suspected cholesteatoma.7,20Despite its proposed efficacy in cholesteatoma imaging, the diagnostic utility of RESOLVE sequences has yet to be robustly evaluated against non-EPI DWI, the current criterion standard. Thus, this study was conceived with the chief goal of assessing the accuracy of RESOLVE in the detection of cholesteatomas and comparing the ability of RESOLVE with that of HASTE sequences in this context. 相似文献
99.
The population is ageing, but while average life expectancy continues to increase, healthy life expectancy has not necessarily matched this and negative ageing stereotypes remain prevalent. Self-directed ageing stereotypes are hypothesised to play an important role in older adults’ health and well-being; however, a wide variety of terms and measures are used to explore this construct meaning there is a lack of clarity within the literature. A review was conducted to identify tools used to measure self-directed ageing stereotype in older adults and evaluate their quality. Searches identified 109 papers incorporating 40 different measures. Most common were the Philadelphia Geriatric Centre Morale Scale Attitude Towards Own Ageing (ATOA) subscale, Ageing Perceptions Questionnaire (APQ) and Attitudes to Ageing Questionnaire. Despite being most frequently used, the ATOA was developed to measure morale in older adults rather than self-directed ageing stereotypes. Over 25 terms were used to describe the concept, and it is suggested that for consistency the term “self-directed ageing stereotype” be adopted universally. Across measures, poor reporting of psychometric properties made it difficult to assess scale quality and more research is needed to fully assess measures before conclusions can be drawn as to the best tool; however, the Brief-APQ appears to hold most promise. Future research must address this issue before interventions to reduce negative self-directed ageing stereotypes can be developed and fully evaluated.Electronic supplementary materialThe online version of this article (10.1007/s10433-020-00574-7) contains supplementary material, which is available to authorized users. 相似文献