336 results on '"Moore, Caroline"'
Search Results
2. Prostate magnetic resonance imaging utilization and its relationship with advanced prostate cancer detection.
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Qian Z, Chen YJ, Feldman J, Beatrici E, Filipas DK, Moore CM, Trinh QD, Kibel AS, Lipsitz SR, and Cole AP
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- Humans, Male, Aged, Aged, 80 and over, SEER Program, United States, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms diagnosis, Magnetic Resonance Imaging statistics & numerical data, Magnetic Resonance Imaging methods
- Abstract
Background: The rise in advanced prostate cancer has coincided with increased use of Magnetic Resonance Imaging (MRI), leading to the hypothesis that this increase in surveillance registries is an artifact of more sensitive imaging tools. We assessed the association between regional variation in prostate MRI and advanced prostate cancer diagnoses., Methods: We utilized SEER-Medicare data (2004-2015), including men > 65 diagnosed with localized prostate cancer. The predictor variable was the utilization of prostate MRI in each hospital referral region (HRR, representing regional healthcare markets). We compared the proportion of disease recorded as locally advanced or of regional risk group (cT3, cT4, and cN1) which would plausibly have been detected by prostate MRI. We conducted adjusted multivariable analysis and performed correlation analysis with Spearman rank coefficient at the level of the HRR. Sensitivity analysis for years 2011 to 2015 was conducted., Results: Of 98,921 men diagnosed, 4.01% had locally advanced or regional disease. The median prostate MRI utilization rate was 4.58% (IQR [3.03%, 8.12%]). Adjusted multivariable analysis revealed no statistically significant correlation between MRI utilization and proportion of advanced prostate cancer (aOR = 1.01, 95% CI, [0.99,1.03]) in each region. The correlation between MRI usage and advanced diagnosis was not significant (Spearman Ρ = 0.09, P = 0.4). Sensitivity analysis conducted between 2011 and 2015 showed similar results (aOR = 1.008, 95% CI, [0.989, 1.027]; Spearman Ρ = 0.16, P = 0.1)., Conclusions: During our study period, HRR-level utilization of MRI was not associated with higher incidences of advanced prostate cancer. This suggests the rising advanced prostate cancer diagnoses observed in this period are unlikely an artifact of greater sensitivity of modern imaging tests, but potentially due to other factors such as changes in screening or risk factors. With increased utilization and evolving techniques in recent years, the association between MRI and advanced prostate cancer detection warrants continued monitoring., Competing Interests: Declaration of competing interest QDT reports personal fees from Astellas, Bayer, Janssen, and Pfizer, outside the submitted work. QDT reports research funding from the American Cancer Society, the Defense Health Agency, and Pfizer Global Medical Grants. APC reports research funding from the American Cancer Society and Pfizer Global Medical Grants., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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3. ssVERDICT: Self-supervised VERDICT-MRI for enhanced prostate tumor characterization.
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Sen S, Singh S, Pye H, Moore CM, Whitaker HC, Punwani S, Atkinson D, Panagiotaki E, and Slator PJ
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- Male, Humans, Prostate diagnostic imaging, Diffusion Magnetic Resonance Imaging, Algorithms, Supervised Machine Learning, Image Interpretation, Computer-Assisted methods, Deep Learning, Magnetic Resonance Imaging methods, Image Processing, Computer-Assisted methods, Computer Simulation, Least-Squares Analysis, Middle Aged, Prostatic Neoplasms diagnostic imaging, Neural Networks, Computer
- Abstract
Purpose: Demonstrating and assessing self-supervised machine-learning fitting of the VERDICT (vascular, extracellular and restricted diffusion for cytometry in tumors) model for prostate cancer., Methods: We derive a self-supervised neural network for fitting VERDICT (ssVERDICT) that estimates parameter maps without training data. We compare the performance of ssVERDICT to two established baseline methods for fitting diffusion MRI models: conventional nonlinear least squares and supervised deep learning. We do this quantitatively on simulated data by comparing the Pearson's correlation coefficient, mean-squared error, bias, and variance with respect to the simulated ground truth. We also calculate in vivo parameter maps on a cohort of 20 prostate cancer patients and compare the methods' performance in discriminating benign from cancerous tissue via Wilcoxon's signed-rank test., Results: In simulations, ssVERDICT outperforms the baseline methods (nonlinear least squares and supervised deep learning) in estimating all the parameters from the VERDICT prostate model in terms of Pearson's correlation coefficient, bias, and mean-squared error. In vivo, ssVERDICT shows stronger lesion conspicuity across all parameter maps, and improves discrimination between benign and cancerous tissue over the baseline methods., Conclusion: ssVERDICT significantly outperforms state-of-the-art methods for VERDICT model fitting and shows, for the first time, fitting of a detailed multicompartment biophysical diffusion MRI model with machine learning without the requirement of explicit training labels., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)
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- 2024
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4. PI-QUAL version 2: an update of a standardised scoring system for the assessment of image quality of prostate MRI.
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de Rooij M, Allen C, Twilt JJ, Thijssen LCP, Asbach P, Barrett T, Brembilla G, Emberton M, Gupta RT, Haider MA, Kasivisvanathan V, Løgager V, Moore CM, Padhani AR, Panebianco V, Puech P, Purysko AS, Renard-Penna R, Richenberg J, Salomon G, Sanguedolce F, Schoots IG, Thöny HC, Turkbey B, Villeirs G, Walz J, Barentsz J, and Giganti F
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- Male, Humans, Multiparametric Magnetic Resonance Imaging methods, Prostatic Neoplasms diagnostic imaging, Contrast Media, Magnetic Resonance Imaging methods, Magnetic Resonance Imaging standards
- Abstract
Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. CLINICAL RELEVANCE STATEMENT: High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium. KEY POINTS: High-quality images are essential for prostate cancer diagnosis and management using MRI. PI-QUAL v2 simplifies image assessment and expands its applicability to prostate MRI without contrast medium. PI-QUAL v2 focuses on critical technical and qualitative image parameters and emphasises T2-WI and DWI., (© 2024. The Author(s).)
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- 2024
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5. Real-World Safety of Prostate Cancer Focal Therapy: MAUDE Database Analysis.
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Qian Z, Xiao B, Dagnino F, Feldman J, Song J, Zurl H, Stelzl D, Korn S, Reis L, Moore CM, Trinh QD, and Cole AP
- Abstract
Objective: The aim of this study was to assess the real-world safety profile of medical devices used in focal prostate cancer treatment utilizing the Manufacturer and User Facility Device Experience (MAUDE) database. Methods: The MAUDE database was searched for reports on high-intensity focused ultrasound (HIFU), cryoablation, laser ablation, and irreversible electroporation (IRE) devices used in prostate cancer treatment from 1993 to 2023. Adverse events were identified and categorized. Results: We identified 175 reports for HIFU, 1362 for cryoablation, 615 for laser ablation, and 135 for IRE devices, with 28, 284, 126, and 2 respective reports, directly related to prostate cancer treatment. The aggregated data revealed the majority of complications were minor, with 82.5% ( n = 363 out of 440 total complications) classified as Clavien-Dindo grade 1 or 2. Common minor complications included erectile dysfunction and urinary retention. Severe complications such as rectal fistulas were noted in HIFU and IRE treatments, along with singular mortality due to pulmonary embolism in cryoablation. Conclusions: Our analyses from MAUDE reveal that devices used in focal therapy for prostate cancer are predominantly associated with minor complications, underscoring their overall real-world safety profile. However, the occurrence of severe adverse events emphasizes the critical importance of rigorous patient selection and meticulous procedural planning. These findings provide valuable insights into the safety profile of focal therapy devices and contribute to the growing body of evidence on their use in prostate cancer treatment.
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- 2024
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6. The RECONCILE study protocol: Exploiting image-based risk stratification in early prostate cancer to discriminate progressors from non-progressors (RECONCILE).
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Marsden T, Attard G, Punwani S, Giganti F, Freeman A, Haider A, Wingate A, Williams N, Syer T, Pashayan N, Moore CM, Emberton M, and Orczyk C
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- Humans, Male, Prospective Studies, Longitudinal Studies, Neoplasm Grading, Risk Assessment methods, Middle Aged, Prostate pathology, Prostate diagnostic imaging, Biomarkers, Tumor, Prostate-Specific Antigen blood, Aged, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology, Prostatic Neoplasms diagnosis, Magnetic Resonance Imaging methods, Disease Progression
- Abstract
Introduction: RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes., Methods: RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%., Results: Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis., Conclusion: We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Mark Emberton serves as a consultant/educator/trainer to Sonacare Inc., Exact Imaging, Angiodynamics Inc and Profound Medical. Acknowledgements - Mark Emberton receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. Caroline M Moore receives funding from the Prostate Cancer UK, Movember, the Medical Research Council, Cancer Research UK and the NIHR. She receives fees for HIFU proctoring from SonaCare. She has received speaker fees from Astellas, and Jannsen. She carries out research into photodyanamic therapy supported by Spectracure. Shonit Punwani receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Marsden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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7. VISION: An Individual Patient Data Meta-analysis of Randomised Trials Comparing Magnetic Resonance Imaging Targeted Biopsy with Standard Transrectal Ultrasound Guided Biopsy in the Detection of Prostate Cancer.
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Kasivisvanathan V, Wai-Shun Chan V, Clement KD, Levis B, Ng A, Asif A, Haider MA, Emberton M, Pond GR, Agarwal R, Scandrett K, Takwoingi Y, Klotz L, and Moore CM
- Abstract
Background and Objective: The PRECISION and PRECISE trials compared magnetic resonance imaging targeted biopsy (MRI ± TB) with the standard transrectal ultrasound (TRUS) guided biopsy for the detection of clinically significant prostate cancer (csPCa). PRECISION demonstrated superiority of MRI ± TB over TRUS guided biopsy, while PRECISE demonstrated noninferiority. The VISION study is a planned individual patient data meta-analysis (IPDMA) comparing MRI ± TB with TRUS guided biopsy for csPCa diagnosis., Methods: MEDLINE, EMBASE, Web of Science, Cochrane Central of Registered Trials, and ClinicalTrials.gov were searched on the November 12, 2023 for randomised controlled trials of biopsy-naïve patients with a clinical suspicion of prostate cancer undergoing MRI or standard TRUS. Studies were included if its participants with suspicious MRI underwent targeted biopsy alone and those with nonsuspicious lesion avoided biopsy. The primary outcome is the proportion of men diagnosed with csPCa (Gleason ≥3 + 4)., Key Findings and Limitations: Two studies, PRECISION and PRECISE (953 patients), were included in the IPDMA. In the MRI ± TB arm, 32.2% of patients avoided biopsy due to nonsuspicious MRI. MRI ± TB detected 8.7 percentage points (36.3% vs 27.6%; 95% confidence interval [CI] 2.8-14.6, p = 0.004) more csPCa than TRUS biopsy and 12.3 percentage points (9.6% vs 21.9%; 95% CI 7.8-16.9, p < 0.001) less clinically insignificant prostate cancer (cisPCa; Gleason 3 + 3). The overall risk of bias for the included studies were found to be low after assessment using the QUADAS-2, QUADAS-C, and ROB 2.0 tools., Conclusions and Clinical Implications: The MRI ± TB pathway is superior to TRUS biopsy in detecting csPCa and avoiding the diagnosis of cisPCa. MRI should be included in the standard of care pathway for prostate cancer diagnosis., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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8. Footprints in the scan: reducing the carbon footprint of diagnostic tools in urology.
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Woernle A, Moore CM, Allen C, and Giganti F
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- Humans, Urology methods, Radiology Department, Hospital organization & administration, Diagnostic Techniques, Urological trends, Climate Change, Carbon Footprint statistics & numerical data
- Abstract
Purpose of Review: There is an ever-growing focus on climate change and its impact on our society. With healthcare contributing a sizeable proportion of carbon emissions, the sector has a duty to address its environmental impact. We highlight the recent progress, current challenges, and future prospects for reducing the carbon footprint in diagnostic urology, specifically for imaging, without compromising patient care., Recent Findings: The review is separated into four key areas of recent research: the design of a green radiology department, considering both infrastructural as well as behavioural changes that promote sustainability; individual scanners, where we provide an update on recent technological advancements and changes in behaviour that may enhance sustainable use; responsible resource allocation, where it is important to derive the maximal benefit for patients through the smallest use of resources; the recent research regarding single versus reusable urologic endoscopes as a case example., Summary: We offer an overview of the present sustainability landscape in diagnostic urology with the aim of encouraging additional research in areas where existing practices may be challenged. To protect the environment, attention is drawn to both more simple steps that can be taken as well as some more complex and expensive ones., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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9. PRECISE Version 2: Updated Recommendations for Reporting Prostate Magnetic Resonance Imaging in Patients on Active Surveillance for Prostate Cancer.
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Englman C, Maffei D, Allen C, Kirkham A, Albertsen P, Kasivisvanathan V, Baroni RH, Briganti A, De Visschere P, Dickinson L, Gómez Rivas J, Haider MA, Kesch C, Loeb S, Macura KJ, Margolis D, Mitra AM, Padhani AR, Panebianco V, Pinto PA, Ploussard G, Puech P, Purysko AS, Radtke JP, Rannikko A, Rastinehad A, Renard-Penna R, Sanguedolce F, Schimmöller L, Schoots IG, Shariat SF, Schieda N, Tempany CM, Turkbey B, Valerio M, Villers A, Walz J, Barrett T, Giganti F, and Moore CM
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- Humans, Male, Prostate diagnostic imaging, Prostate pathology, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology, Magnetic Resonance Imaging standards, Watchful Waiting standards, Consensus
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Background and Objective: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty., Methods: A panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology. Panellists scored 193 statements using a 1-9 agreement scale, where 9 means full agreement. A summary of agreement, uncertainty, or disagreement (derived from the group median score) and consensus (determined using the Interpercentile Range Adjusted for Symmetry method) was calculated for each statement and presented for discussion before individual rescoring., Key Findings and Limitations: Participants agreed that MRI scans must meet a minimum image quality standard (median 9) or be given a score of 'X' for insufficient quality. The current scan should be compared with both baseline and previous scans (median 9), with the PRECISE score being the maximum from any lesion (median 8). PRECISE 3 (stable MRI) was subdivided into 3-V (visible) and 3-NonV (nonvisible) disease (median 9). Prostate Imaging Reporting and Data System/Likert ≥3 lesions should be measured on T2-weighted imaging, using other sequences to aid in the identification (median 8), and whenever possible, reported pictorially (diagrams, screenshots, or contours; median 9). There was no consensus on how to measure tumour size. More research is needed to determine a significant size increase (median 9). PRECISE 5 was clarified as progression to stage ≥T3a (median 9)., Conclusions and Clinical Implications: The updated PRECISE recommendations reflect expert consensus opinion on minimal standards and reporting criteria for prostate MRI in AS., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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10. Has Active Surveillance for Prostate Cancer Become Safer? Lessons Learned from a Global Clinical Registry.
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Bangma C, Doan P, Zhu L, Remmers S, Nieboer D, Helleman J, Roobol MJ, Sugimoto M, Chung BH, Lee LS, Frydenberg M, Klotz L, Peacock M, Perry A, Bjartell A, Rannikko A, Van Hemelrijck M, Dasgupta P, Moore C, Trock BJ, Pavlovich C, Steyerberg E, Carroll P, Koo KC, Hayen A, and Thompson J
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Background and Objective: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men around the world with low-risk prostate cancer (or in selected cases intermediate-risk disease). Here, we report on the safety and acceptability of AS, and treatment outcomes for low- and intermediate-risk tumours over time in 14 623 men with follow-up of over 6 yr., Methods: Clinical data from 26 999 men on AS from 25 cohorts in 15 countries have been collected in an international database from 2000 onwards., Key Findings and Limitations: Across our predefined four time periods of 4 yr each (covering the period 2000-2016), there was no significant change in overall survival (OS). However, metastasis-free survival (MFS) rates have improved since the second period and were excellent (>99%). Treatment-free survival rates for earlier periods showed a slightly more rapid shift to radical treatment. Over time, there was a constant proportion of 5% of men for whom anxiety was registered as the reason for treatment alteration. There was, however, also a subset of 10-15% in whom treatment was changed, for which no apparent reason was available. In a subset of men (10-15%), tumour progression was the trigger for treatment. In men who opted for radical treatment, surgery was the most common treatment modality. In those men who underwent radical treatment, 90% were free from biochemical recurrence at 5 yr after treatment., Conclusions and Clinical Implications: Our study confirms that AS was a safe management option over the full duration in this large multicentre cohort with long-term follow-up, given the 84.1% OS and 99.4% MFS at 10 yr. The probability of treatment at 10 yr was 20% in men with initial low-risk tumours and 31% in men with intermediate-risk tumours. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours., Patient Summary: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men with prostate cancer around the world. In this report, we show the long-term safety of following AS for men with low- and intermediate-risk prostate cancer. Our study confirms AS as a safe management option for low- and intermediate-risk prostate cancer. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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11. Social Capital as a Framework to Address Organizational Climate Change Policy.
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Becker J, McDermott-Levy R, Moore C, and Mitsdarffer ML
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- Humans, Pennsylvania, Aged, Organizational Policy, Male, Female, Surveys and Questionnaires, Geriatric Nursing, Aged, 80 and over, Middle Aged, Health Policy, Climate Change, Social Capital
- Abstract
Purpose: To examine state Area Agencies on Aging (AAAs) in Pennsylvania for services they provide to older adults regarding extreme events and how readiness can be captured through social networks and policies at the local, state, and federal levels., Method: Using an online survey, 79% of AAA directors answered questions describing perceptions and actions related to social capital and its influence on policy., Results: AAAs acknowledged weather/temperature changes impact the need to prepare for common scenarios of extreme weather, temperature, and flooding. AAAs reported major social connections with county government and one state agency, with limited connections with federal agencies., Conclusion: Multiple opportunities exist for AAAs to consider climate change in expansion efforts, specifically regarding health care. Geriatric nurses can play a key role in expansion, advocacy, and policy development for AAAs that serve older adults in the context of climate change. [ Journal of Gerontological Nursing, 50 (6), 11-15.].
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- 2024
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12. Picture Perfect: The Status of Image Quality in Prostate MRI.
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Woernle A, Englman C, Dickinson L, Kirkham A, Punwani S, Haider A, Freeman A, Kasivisivanathan V, Emberton M, Hines J, Moore CM, Allen C, and Giganti F
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- Humans, Male, Artificial Intelligence, Image Interpretation, Computer-Assisted methods, Image Processing, Computer-Assisted methods, Quality Improvement, Reproducibility of Results, Prostatic Neoplasms diagnostic imaging, Magnetic Resonance Imaging methods, Prostate diagnostic imaging, Prostate pathology
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Magnetic resonance imaging is the gold standard imaging modality for the diagnosis of prostate cancer (PCa). Image quality is a fundamental prerequisite for the ability to detect clinically significant disease. In this critical review, we separate the issue of image quality into quality improvement and quality assessment. Beginning with the evolution of technical recommendations for scan acquisition, we investigate the role of patient preparation, scanner factors, and more advanced sequences, including those featuring Artificial Intelligence (AI), in determining image quality. As means of quality appraisal, the published literature on scoring systems (including the Prostate Imaging Quality score), is evaluated. Finally, the application of AI and teaching courses as ways to facilitate quality assessment are discussed, encouraging the implementation of future image quality initiatives along the PCa diagnostic and monitoring pathway. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)
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- 2024
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13. Urinary and Sexual Impact of Robotic Radical Prostatectomy: Reporting of Patient-reported Outcome Measures in the First Year after Radical Prostatectomy in a Contemporary Multicentre Cohort in the United Kingdom.
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Bridge J, Labban M, Cole AP, Adebusoye B, Smith SC, Protopapa E, McCartan N, Brew-Graves C, Trinh QD, Hamer K, Mallett S, van der Meulen J, and Moore CM
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Background and Objective: Radical prostatectomy (RP) is an established treatment for localised prostate cancer that can have a significant impact on urinary and sexual function, with recovery over time. Our aim was to describe functional recovery in the first year after RP, reporting descriptive outcomes alongside validated patient-reported outcome measure scores (Expanded Prostate Cancer Index Composite, EPIC-26)., Methods: Men undergoing RP between September 2015 and November 2019 completed EPIC-26 at baseline and 1, 3, 6, and 12 mo., Key Findings and Limitations: Overall, 2030 men consented to participation, underwent RP, and completed EPIC-26. At baseline, 97% were pad-free (1928/1996; 95% confidence interval [CI] 96-97%) and 77% were leak-free and pad-free (1529/1996; 95% CI 75-78), with a median EPIC-26 incontinence domain score of 100 (interquartile range [IQR] 86-100). At 12 mo, 65% were pad-free (904/1388; 95% CI 63-68%) and 42% were leak-free and pad-free (583/1388; 95% CI 39-45%), with a median EPIC-26 score of 76 (IQR 61-100). While one in three men reported wearing a pad at 12 mo, fewer than one in ten men needed more than 1 pad/d. At baseline, 1.9% reported a "moderate or big problem" with urine leakage, which increased to 9.7% at 12 mo. At baseline, the median sexual domain score among 1880 men was 74 (IQR 43-92) and 52% had erections sufficient for intercourse without medication (975/1880; 95% CI 50-54%). Among these 975 men, 630 responded at 12 mo, of whom 17% reported sufficient erections for intercourse (105/630; 95% CI 14-20%), without medication in 6% (37/630; 95% CI 4-8%) and needing medication in 11% (68/630; 95% CI 9-13%); the median EPIC-26 domain score was 26 (IQR 13-57)., Conclusions and Clinical Implications: Reporting of functional outcomes after RP in terms of easily understood concepts such as pad-free and leak-free status, and erections with and with medication, alongside the classical report using EPIC-26 domain scores, increases the understanding of RP recovery patterns over the first year., Patient Summary: At 12 months after surgery for prostate cancer, one in ten men reported a moderate or big problem with urine leakage and one in five men reported sufficient erections., (© 2024 The Authors.)
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- 2024
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14. International Variations in Surgical Quality of Care in Men With Prostate Cancer: Results From the TrueNTH Global Registry.
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Sibert NT, Garin O, Ferrer M, Connor SE, Graham ID, Litwin MS, Millar J, Moore CM, Nguyen AV, Paich K, and Kowalski C
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- Humans, Male, Aged, Middle Aged, Surveys and Questionnaires, Quality of Life, Prostatic Neoplasms surgery, Prostatectomy adverse effects, Registries statistics & numerical data, Urinary Incontinence epidemiology, Quality of Health Care standards, Quality of Health Care statistics & numerical data
- Abstract
Purpose: Functional problems such as incontinence and sexual dysfunction after radical prostatectomy (RP) are important outcomes to evaluate surgical quality in prostate cancer (PC) care. Differences in survival after RP between countries are known, but differences in functional outcomes after RP between providers from different countries are not well described., Methods: Data from a multinational database of patients with PC (nonmetastatic, treated by RP) who answered the EPIC-26 questionnaire at baseline (before RP, T0) and 1 year after RP (T1) were used, linking survey data to clinical information. Casemix-adjusted incontinence and sexual function scores (T1) were calculated for each country and provider on the basis of regression models and then compared using minimally important differences (MIDs)., Results: A total of 21,922 patients treated by 151 providers from 10 countries were included. For the EPIC-26 incontinence domain, the median adjusted T1 score of countries was 76, with one country performing more than one MID (for incontinence: 6) worse than the median. Eighteen percent of the variance ( R
2 ) of incontinence scores was explained by the country of the providers. The median adjusted T1 score of sexual function was 33 with no country performing perceivably worse than the median (more than one MID worse), and 34% ( R2 ) of the variance of the providers' scores could be explained by country., Conclusion: To our knowledge, this is the first comparison of functional outcomes 1 year after surgical treatment of patients with PC between different countries. Country is a relevant predictor for providers' incontinence and sexual function scores. Although the results are limited because of small samples from some countries, they should be used to enhance cross-country initiatives on quality improvement in PC care.- Published
- 2024
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15. The Lancet Commission on prostate cancer: planning for the surge in cases.
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James ND, Tannock I, N'Dow J, Feng F, Gillessen S, Ali SA, Trujillo B, Al-Lazikani B, Attard G, Bray F, Compérat E, Eeles R, Fatiregun O, Grist E, Halabi S, Haran Á, Herchenhorn D, Hofman MS, Jalloh M, Loeb S, MacNair A, Mahal B, Mendes L, Moghul M, Moore C, Morgans A, Morris M, Murphy D, Murthy V, Nguyen PL, Padhani A, Parker C, Rush H, Sculpher M, Soule H, Sydes MR, Tilki D, Tunariu N, Villanti P, and Xie LP
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- Humans, Male, Prostatic Neoplasms epidemiology, Prostatic Neoplasms therapy
- Abstract
Competing Interests: Declaration of interests NDJ reports advisory board and personal fees from AstraZeneca, Bayer, Clovis, Janssen, Merck, Merck Sharp & Dohme, Novartis, Sanofi, Astellas, and AAA Accelerator Solutions. FF reports personal fees from Janssen, Astellas, Serimmune, Foundation Medicine, Exact Sciences, Bristol-Myers Squibb, Varian Medical Systems, Novartis, Roivant, Myovant, Bayer, BlueStar Genomics, Artera, Tempus, Genentech, PFS Genomics, and Amgen, and holds stock options in Serimmune, BlueStar Genomics, and Artera. SG reports fees from Tolremo, Ipsen, Silvio Grasso Consulting, WebMD–Medscape, the American Society of Clinical Oncology, European Society for Medical Oncology, Peer Voice, SAKK, the German-speaking European School of Oncology, Radiotelevisione Svizzera Italiana, the Swiss Academy of Multidisciplinary Oncology, Meister ConCept, AdMeTech Foundation, EPG Health, Intellisphere, and Schweizerische Gessellschaft für Medizineische Onkologie. SG also reports travel support from AstraZeneca, Bayer, Intellisphere, and Gilead, paid advisory board participation for Merck Sharp & Dohme, Telixpharma, Bristol-Myers Squibb, AAA International, Orion, Bayer, Novartis, Modra Pharmaceuticals, AstraZeneca, Myriad Genetic, Daiichi Sankyo, Boehringer Ingelheim, Innomedica, Macrogenics, and Pfizer, and holds a patent (WO2009138392). BA-L reports fees from the Cancer Prevention and Research Institute of Texas, the Commonwealth Foundation, the Lyda Hill Foundation, Cancer Research UK, the Wellcome Trust, the Bob Champion Trust, AstraZeneca, Astex Pharmaceuticals, the New York Genome Center, and Existentia, travel support from Cancer Research UK, Astex, the STAT summit, the American Society of Hematology, and the American Association for Cancer Research, and participation in a Cancer Research UK data strategy board. GA reports fees from Janssen, Novartis, Astellas, the Institute of Cancer Research, Veracyte, Artera, Pfizer, AstraZeneca, Astellas, Novartis, Arvinas, Bayer, Sanofi, Propella, and Orion, holds a patent related to blood-based methylation markers (GB1915469.9), and has received equipment from Agilent. EC reports fees from Janssen. RE reports book royalties plus support and fees from the UK National Institute for Health and Care Research, AstraZeneca, Bayer, Ipsen, the Active Surveillance Movember Committee, the American Society of Clinical Oncology, University of Chicago, Dana Farber Cancer Institute, the Spanish National Cancer Research Center, Our Future Health, Jnetics UK, the Institute of Cancer Research, and Convergence Science Centre. RE also reports a pending Cancer Research UK patent, a stock ISA, receipt of gifts from patients (within limits allowed), and other financial interests in private medical practice. SH reports participation on data safety monitoring boards and advisory boards. DH reports fees from Techtrials, Astellas, Adium, Ipsen, Janssen, Bayer, Merck Sharp & Dohme, and Pfizer. MSH reports fees or grant funding from the Prostate Cancer Foundation, the Prostate Cancer Theranostics and Imaging Centre of Excellence, the Australian National Health and Medical Research Council, Movember, the US Department of Defense, Medical Research Future Fund, Bayer, the Peter MacCallum Foundation, Isotopia, the Australian Nuclear Science and Technology Organisation, Merck Sharpe & Dohme, Novartis, AstraZeneca, and Astellas. MSH also reports unrenumerated leadership or fiduciary role in Australian Friends of Sheba. MMog reports fees from NHS England, the UK National Institute for Health and Care Research, and Bayer. CM reports fees from UK National Institute for Health and Care Research, the UK Medical Research Council, Prostate Cancer UK, Cancer Rsearch UK, Sonacare, Ipsen, Bayer, and Astellas. AMo reports fees from Bayer, Myovant, Pfizer, Astellas, AstraZeneca, AAA, Bayer, Exelixis, Janssen, Lantheus, Myovant, Merck, Novartis, Sanofi, and Telix, participation in data Safety monitoring boards and advisory boards for Gilead, and a leadership or fiduciary role in ZERO Prostate Cancer. MMor reports fees from the National Cancer Institute Comprehensive Cancer Center, Lantheus, AstraZeneca, Amgen, Daiichi, Convergent, Pfizer, Clarity, Blue Earth Diagnostics, POINT Diagnostics, Z-Alpha, Ambrx, Flare, Fusion, Curium, Transtherabio, Doximity, BMS, and Celgene, reports a US patent application (18/448 609) for a method of treating prostate cancer, and holds stock options in Doximity. DM reports fees from Novartis, Janssen, Bayer, Astellas, Ipsen, and AstraZeneca. PLN reports fees from Bayer, Astellas, Boston Scientific, AIQ, Astellas, Novartis, Janssen, Blue Earth, Nanocan, and Theranano, and holds stock options in Stratagen Bio, Nanocan, and Reversal Therapeutics. CP reports fees from Artera, which has a financial relationship with University College London (his employer) as part of a data licensing agreement. All other authors declare no competing interests.
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- 2024
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16. Eosinophils in Oral Disease: A Narrative Review.
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Al-Azzawi HMA, Paolini R, Cirillo N, O'Reilly LA, Mormile I, Moore C, Yap T, and Celentano A
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- Humans, Animals, Eosinophilia immunology, Eosinophilia metabolism, Eosinophilia pathology, Cytokines metabolism, Eosinophils immunology, Eosinophils metabolism, Mouth Diseases immunology, Mouth Diseases pathology
- Abstract
The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research.
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- 2024
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17. Applying Machine Learning for Enhanced MicroRNA Analysis: A Companion Risk Tool for Oral Squamous Cell Carcinoma in Standard Care Incisional Biopsy.
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Pruthi N, Yap T, Moore C, Cirillo N, and McCullough MJ
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- Humans, Biopsy, Female, Male, Algorithms, Gene Expression Regulation, Neoplastic, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck pathology, Squamous Cell Carcinoma of Head and Neck diagnosis, Machine Learning, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Mouth Neoplasms diagnosis, MicroRNAs genetics, MicroRNAs metabolism, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell diagnosis
- Abstract
Machine learning analyses within the realm of oral cancer outcomes are relatively underexplored compared to other cancer types. This study aimed to assess the performance of machine learning algorithms in identifying oral cancer patients, utilizing microRNA expression data. In this study, we implemented this approach using a panel of oral cancer-associated microRNAs sourced from standard incisional biopsy specimens to identify cases of oral squamous cell carcinomas (OSCC). For the model development process, we used a dataset comprising 30 OSCC and 30 histologically normal epithelium (HNE) cases. We initially trained a logistic regression prediction model using 70 percent of the dataset, while reserving the remaining 30 percent for testing. Subsequently, the model underwent hyperparameter tuning resulting in enhanced performance metrics. The hyperparameter-tuned model exhibited high accuracy (0.894) and ROC AUC (0.898) in predicting OSCC. Testing the model on cases of potentially malignant disorders (OPMDs) revealed that leukoplakia with mild dysplasia was predicted as having a high risk of progressing to OSCC, emphasizing machine learning's advantage over histopathology in detecting early molecular changes. These findings underscore the necessity for further refinement, incorporating a broader set of variables to enhance the model's predictive capabilities in assessing the risk of oral potentially malignant disorders.
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- 2024
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18. Reply to Jorge Abreu-Gomez, Masoom Haider, and Sangeet Ghai's Letter to the Editor re: Francesco Giganti, Louise Dickinson, Clement Orczyk, et al. Prostate Imaging after Focal Ablation (PI-FAB): A Proposal for a Scoring System for Multiparametric MRI of the Prostate After Focal Therapy. Eur Urol Oncol. 2023;6:629-634.
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Giganti F, Dickinson L, Allen C, and Moore CM
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- Male, Humans, Prostate diagnostic imaging, Prostate surgery, Prostatectomy, Diagnostic Imaging, Multiparametric Magnetic Resonance Imaging, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms surgery
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- 2024
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19. When Is It Too Early To Start Prostate Cancer Screening? Reflections on the PROBASE Study Using Magnetic Resonance Imaging for Men Aged 45 Yr with Elevated Prostate-specific Antigen.
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Moore CM and Albertsen P
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- Humans, Male, Magnetic Resonance Imaging, Middle Aged, Early Detection of Cancer methods, Prostate-Specific Antigen, Prostatic Neoplasms pathology
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- 2024
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20. Inflammatory Lymphedema Masquerading as Bilateral Cellulitis: A Military Dilemma.
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Moore CE
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Bilateral lower extremity inflammatory lymphedema (BLEIL) is a novel condition characterized by confluent erythema and painful edema prominent to the dorsum of the feet and ankles bilaterally following prolonged standing and marching, occurring most often in military recruits. Prolonged standing during the initial week of basic training is thought to cause venous congestion and subsequent inflammatory vasculitis. This condition may be misdiagnosed as bilateral cellulitis, prompting the initiation of unnecessary antibiotic therapy. Increased education and recognition of this new clinical entity would lead to the initiation of appropriate therapy and earlier symptom resolution and, thus, an earlier return to military training. Herein, we describe a small case series of Marine Corps recruit members undergoing their first week of basic training (i.e., "processing week") who developed bilateral lower extremity edema, erythema, and pain localized to the dorsum of the feet and the medial and lateral aspects of the ankles consistent with the diagnosis of BLEIL but were initially diagnosed with bilateral lower extremity cellulitis and received intravenous antimicrobial therapy. With prompt initiation of venous decongestive therapy with leg elevation, both patients had rapid symptom resolution and returned to basic training without any future episodes of symptoms. These cases add to the paucity of data on this clinical entity, illustrate the symptoms and demographics of BLEIL, and describe the importance of recognition and initiation of appropriate therapy., Competing Interests: The views expressed in this case report are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. I am a military service member or employee of the US Government. This work was prepared as part of my official duties. Title 17, USC, §105 provides that copyright protection under this title is not available for any work of the US Government. Title 17, USC, §101 defines US Government work as work prepared by a military service member or employee of the US Government as part of that person's official duties., (Copyright © 2024, Moore et al.)
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- 2024
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21. Prostate MRI and image quality: The urologist's perspective.
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Khan A, Moore CM, and Minhaj Siddiqui M
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- Male, Humans, Urologists, Image-Guided Biopsy methods, Magnetic Resonance Imaging methods, Prostate diagnostic imaging, Prostate pathology, Prostatic Neoplasms pathology
- Abstract
The development of different imaging modalities of the prostate has significantly improved tumor detection, patient risk stratification, and quality of care.Among these, multiparametric magnetic resonance imaging (mp-MRI) has emerged as the most sensitive tool.It is useful in the diagnosis, localization, risk stratification, and staging of clinically significant prostate cancer, PCa. As a result, mp-MRI of the prostate is recommended as the initial diagnostic test for men with suspected PCa. A multidisciplinary approach is crucial in the diagnosis and management of prostate cancer and mp-MRI plays a fundamental role in this scenario.While many aspects of image quality certainly fall within the purview of radiology, it is important to recognize that urologists must also be attentive to imaging quality when utilizing mp-MRI to facilitate PCa management. We present our viewpoint as urologists on how image quality impacts the management of men diagnosed with PCa andattempt to identify the factors that impact mp-MRI image quality, consequences of poor image quality, and finally suggestions for improvements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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22. Active Surveillance for Prostate Cancer: Expanding the Role of MR Imaging and the Use of PRECISE Criteria.
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Englman C, Barrett T, Moore CM, and Giganti F
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- Male, Humans, Watchful Waiting, Prostate diagnostic imaging, Prostate pathology, Magnetic Resonance Imaging methods, Image-Guided Biopsy, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology, Multiparametric Magnetic Resonance Imaging
- Abstract
Multiparametric magnetic resonance (MR) imaging has had an expanding role in active surveillance (AS) for prostate cancer. It can improve the accuracy of prostate biopsies, assist in patient selection, and help monitor cancer progression. The PRECISE recommendations standardize reporting of serial MR imaging scans during AS. We summarize the evidence on MR imaging-led AS and provide a clinical primer to help report using the PRECISE criteria. Some limitations to both serial imaging and the PRECISE recommendations must be considered as we move toward a more individualized risk-stratified approach to AS., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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23. Racial differences in patient-reported outcomes among men treated with radical prostatectomy for prostate cancer.
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Koelker M, Labban M, Frego N, Ye J, Lipsitz SR, Hubbell HT, Edelen M, Steele G, Salinas K, Meyer CP, Makanjuola J, Moore CM, Cole AP, Kibel AS, and Trinh QD
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- Male, Humans, Retrospective Studies, Race Factors, White People, Black or African American, Prostatectomy adverse effects, Patient Reported Outcome Measures, Quality of Life, Prostatic Neoplasms therapy
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Background: Real-world data on racial differences in the side effects of radical prostatectomy on quality of life (QoL) are lacking. We aimed to evaluate differences in patient-reported outcome measure (PROM) among non-Hispanic Black (NHB) and non-Hispanic White (NHW) men using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) questionnaire to measure health-related QoL after radical prostatectomy., Methods: We retrospectively assessed prospectively collected PROMs using EPIC-CP scores at a tertiary care center between 2015 and 2021 for men with prostate cancer undergoing radical prostatectomy. The primary endpoint was the overall QoL score for NHB and NHW men, with a total score of 60 and higher scores indicating worse QoL. An imputed mixed linear regression model was used to examine the effect of covariates on the change in overall QoL score following surgery. A pairwise comparison was used to estimate the mean QoL scores before surgery as well as up to 24 months after surgery., Results: Our cohort consisted of 2229 men who answered at least one EPIC-CP questionnaire before or after surgery, of which 110 (4.94%) were NHB and 2119 (95.07%) were NHW men. The QoL scores differed for NHB and NHW at baseline (2.34, 95% confidence interval [CI] 0.36-4.31, p = 0.02), 3 months (4.36, 95% CI 2.29-6.42, p < 0.01), 6 months (3.26, 95% CI 1.10-5.43, p < 0.01), and 12 months after surgery (2.48, 95% CI 0.19-4.77, p = 0.03) with NHB having worse scores. There was no difference in QoL between NHB and NHW men 24 months after surgery., Conclusions: A significant difference in QoL between NHB and NHW men was reported before surgery, 3, 6, and 12 months after surgery, with NHB having worse QoL scores. However, there was no long-term difference in reported QoL. Our findings inform strategies that can be implemented to mitigate racial differences in short-term outcomes., (© 2023 Wiley Periodicals LLC.)
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- 2024
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24. The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial.
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Light A, Kanthabalan A, Otieno M, Pavlou M, Omar R, Adeleke S, Giganti F, Brew-Graves C, Williams NR, Emara A, Haroon A, Latifoltojar A, Sidhu H, Freeman A, Orczyk C, Nikapota A, Dudderidge T, Hindley RG, Virdi J, Arya M, Payne H, Mitra AV, Bomanji J, Winkler M, Horan G, Moore CM, Emberton M, Punwani S, Ahmed HU, and Shah TT
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- Humans, Male, Biopsy methods, Image-Guided Biopsy methods, Magnetic Resonance Imaging methods, Neoplasm Recurrence, Local diagnostic imaging, Prospective Studies, Multiparametric Magnetic Resonance Imaging, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms radiotherapy
- Abstract
Background: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear., Objective: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation., Design, Setting, and Participants: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here., Intervention: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious., Outcome Measurements and Statistical Analysis: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease., Results and Limitations: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation., Conclusions: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease., Patient Summary: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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25. Evaluating the impact of engaging older adults and service providers as research partners in the co-design of a community mobility-promoting program: a mixed methods developmental evaluation study.
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MacNeil M, Abelson J, Moore C, Lindsay S, Adams J, Alshaikhahmed A, Jain K, Petrie P, and Ganann R
- Abstract
Background: Increasingly researchers are partnering with citizens and communities in research; less is known about research impacts of this engagement. EMBOLDEN is an evidence-informed, mobility-promoting intervention for older adults co-designed by a 26-person Strategic Guiding Council (SGC) of health/social service providers and older adult citizens. This study evaluated research partners' perceptions of engagement strategies, the engagement context, strengths, areas for improvement, as well as the impacts of the guiding council on older-adult identified priority areas., Methods: This study was guided by developmental evaluation, working in partnership with four older adult SGC members who helped to set evaluation priorities, decide methods, and adapt patient-centred evaluation tools. Data sources included a questionnaire, focus groups and document analysis of meeting notes from 16 SGC meetings that took place between December 2019 and February 2022. A thematic approach to analysis guided the coding of focus group transcripts and SGC meeting notes. Convergent mixed methods guided the integration and presentation of qualitative and quantitative data sources in a joint display of evaluation results., Results: Of 26 SGC members, nine completed the evaluation squestionnaire, and five participated in focus groups. Around two thirds of the SGC commonly attended each meeting. EMBOLDEN's SGC was structured to include a diverse group (across gender, ethnicity and discipline) of older adults and service providers, which was perceived as a strength. Engagement processes were perceived as inclusive and well-facilitated, which stimulated discussion at meetings. Advantages and disadvantages of engaging with the SGC virtually, as compared to in-person (as was the case for the first 3 SGC meetings) were also discussed. Impacts of the SGC were identified across preparatory, execution phase and translational stages of research. Impacts of SGC involvement on members were also described., Conclusion: Older adult research partners played an important role designing, implementing, and evaluating co-design approaches in this study. Older adults and service providers can make important contributions to the design, delivery and sharing results of health research through their lived expertise and connections to community. This project contributes to the growing field of citizen and community engagement in research by offering a participatory approach to engagement evaluation that considers diversity, satisfaction, and impact., (© 2023. The Author(s).)
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- 2023
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26. Self-Perception of HIV Risk and Interest in Pre-Exposure Prophylaxis in a General Obstetrics and Gynecology Clinic Population.
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Bunda BA, Raniele RA, Lapayowker SA, Moore CM, Wood ME, McDermott VM, and Naresh A
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- Humans, Risk Factors, Self Concept, Health Knowledge, Attitudes, Practice, HIV Infections drug therapy, Pre-Exposure Prophylaxis, Gynecology, Anti-HIV Agents therapeutic use
- Abstract
Background: Pre-exposure prophylaxis (PrEP) for HIV is underutilized, particularly among attendees of obstetrics and gynecology (Ob/Gyn) clinics. Lack of self-perception of HIV risk is a barrier to PrEP utilization, and a lack of understanding of community risk factors for HIV may contribute to that lack of self-perception of risk. Methods: Attendees of general Ob/Gyn clinics in New Orleans completed a survey assessing HIV knowledge, self-perception of HIV risk, and interest in PrEP. They reviewed a brief written educational intervention on demographic and behavioral risk factors for HIV and availability of PrEP. HIV knowledge, self-perception of HIV risk, and interest in PrEP were reassessed after the intervention. Results: One-hundred seventy individuals completed the survey. Eighty-five participants (50%) expressed initial interest in PrEP. Self-perception of risk of HIV acquisition was associated with interest in PrEP. Ten of 11 (90.9%) respondents who had high self-perceived risk of HIV were interested in PrEP, compared with 75 of 159 (47.2%) of those who had low self-perceived risk ( p = 0.01). The association remained significant in a multivariate analysis. After the intervention, the number of those who perceived themselves to be at risk of HIV increased from 11 to 25 individuals ( p < 0.01) and 20 of these (80%) were interested in PrEP. Knowledge of HIV risk factors increased ( p < 0.01). The intervention did not significantly alter interest in PrEP. Conclusions: Self-perception of HIV risk was associated with interest in PrEP. A brief written educational intervention increased knowledge of HIV risk factors and increased self-perception of risk of HIV. The intervention did not translate to increased interest in PrEP.
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- 2023
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27. Prostate Imaging after Focal Ablation (PI-FAB): A Proposal for a Scoring System for Multiparametric MRI of the Prostate After Focal Therapy.
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Giganti F, Dickinson L, Orczyk C, Haider A, Freeman A, Emberton M, Allen C, and Moore CM
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- Male, Humans, Prostate diagnostic imaging, Prostate surgery, Prostate pathology, Magnetic Resonance Imaging methods, Diffusion Magnetic Resonance Imaging methods, Multiparametric Magnetic Resonance Imaging, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms surgery, Prostatic Neoplasms pathology
- Abstract
At present there is no standardised system for scoring the appearance of the prostate on multiparametric magnetic resonance imaging (MRI) after focal ablation for localised prostate cancer. We propose a novel scoring system, the Prostate Imaging after Focal Ablation (PI-FAB) score, to fill this gap. PI-FAB involves a 3-point scale for rating MRI sequences in sequential order: (1) dynamic contrast-enhanced sequences; (2) diffusion-weighted imaging, split into assessment of the high-b-value sequence first and then the apparent diffusion coefficient map; and (3) T2-weighted imaging. It is essential that the pretreatment scan is also available to help with this assessment. We designed PI-FAB using our experience of reading postablation scans over the past 15 years and include details for four representative patients initially treated with high-intensity focus ultrasound at our institution to demonstrate the scoring system. We propose PI-FAB as a standardised method for evaluating prostate MRI scans after treatment with focal ablation. The next step is to evaluate its performance across multiple experienced readers of MRI after focal therapy in a clinical data set. PATIENT SUMMARY: We propose a scoring system called PI-FAB for assessing the appearance of magnetic resonance imaging scans of the prostate after focal treatment for localised prostate cancer. This will help clinicians in deciding on further follow-up., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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28. The PRECISE Recommendations for Prostate MRI in Patients on Active Surveillance for Prostate Cancer: A Critical Review.
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Sanmugalingam N, Sushentsev N, Lee KL, Caglic I, Englman C, Moore CM, Giganti F, and Barrett T
- Abstract
The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations were published in 2016 to standardize the reporting of MRI examinations performed to assess for disease progression in patients on active surveillance for prostate cancer. Although a limited number of studies have reported outcomes from use of PRECISE in clinical practice, the available studies have demonstrated PRECISE to have high pooled NPV but low pooled PPV for predicting progression. Our experience in using PRECISE in clinical practice at two teaching hospitals has highlighted issues with its application and areas requiring clarification. This Clinical Perspective critically appraises PRECISE on the basis of this experience, focusing on the system's key advantages and disadvantages and exploring potential changes to improve the system's utility. These changes include consideration of image quality when applying PRECISE scoring, incorporation of quantitative thresholds for disease progression, adoption of a PRECISE 3F sub-category for progression not qualifying as substantial, and comparisons with both the baseline and most recent prior examinations. Items requiring clarification include derivation of a patient-level score in patients with multiple lesions, intended application of PRECISE score 5 (i.e., if requiring development of disease that is no longer organ-confined), and categorization of new lesions in patients with prior MRI-invisible disease.
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- 2023
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29. Prostate MR image quality of apparent diffusion coefficient maps versus fractional intracellular volume maps from VERDICT MRI using the PI-QUAL score and a dedicated Likert scale for artefacts.
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Singh S, Giganti F, Dickinson L, Rogers H, Kanber B, Clemente J, Pye H, Heavey S, Stopka-Farooqui U, Johnston EW, Moore CM, Freeman A, Whitaker HC, Alexander DC, Panagiotaki E, and Punwani S
- Subjects
- Male, Humans, Artifacts, Prospective Studies, Diffusion Magnetic Resonance Imaging methods, Magnetic Resonance Imaging methods, Retrospective Studies, Prostate pathology, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology
- Abstract
Purpose: This study aimed to assess the image quality of apparent diffusion coefficient (ADC) maps derived from conventional diffusion-weighted MRI and fractional intracellular volume maps (FIC) from VERDICT MRI (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours) in patients from the INNOVATE trial. The inter-reader agreement was also assessed., Methods: Two readers analysed both ADC and FIC maps from 57 patients enrolled in the INNOVATE prospective trial. Image quality was assessed using the Prostate Imaging Quality (PI-QUAL) score and a subjective image quality Likert score (Likert-IQ). The image quality of FIC and ADC were compared using a Wilcoxon Signed Ranks test. The inter-reader agreement was assessed with Cohen's kappa., Results: There was no statistically significant difference between the PI-QUAL score for FIC datasets compared to ADC datasets for either reader (p = 0.240 and p = 0.614). Using the Likert-IQ score, FIC image quality was higher compared to ADC (p = 0.021) as assessed by reader-1 but not for reader-2 (p = 0.663). The inter-reader agreement was 'fair' for PI-QUAL scoring of datasets with FIC maps at 0.27 (95% confidence interval; 0.08-0.46) and ADC datasets at 0.39 (95% confidence interval 0.22-0.57). For Likert scoring, the inter-reader agreement was also 'fair' for FIC maps at 0.38 (95% confidence interval; 0.10-0.65) and substantial for ADC maps at 0.62 (95% confidence interval; 0.39-0.86)., Conclusion: Image quality was comparable for FIC and ADC. The inter-reader agreement was similar when using PIQUAL for both FIC and ADC datasets but higher for ADC maps compared to FIC maps using the image quality Likert score., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)
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- 2023
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30. External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.
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Light A, Peters M, Reddy D, Kanthabalan A, Otieno M, Pavlou M, Omar R, Adeleke S, Giganti F, Brew-Graves C, Williams NR, Emara A, Haroon A, Latifoltojar A, Sidhu H, Freeman A, Orczyk C, Nikapota A, Dudderidge T, Hindley RG, Virdi J, Arya M, Payne H, Mitra AV, Bomanji J, Winkler M, Horan G, Moore C, Emberton M, Punwani S, Ahmed HU, and Shah TT
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- Humans, Male, Biopsy, Brachytherapy, Neoplasm Recurrence, Local, Prospective Studies, Treatment Outcome, Multicenter Studies as Topic, Clinical Trials as Topic, Prostatic Neoplasms surgery, Prostatic Neoplasms radiotherapy, Salvage Therapy adverse effects
- Abstract
Objectives: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset., Patients and Methods: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments., Results: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range., Conclusion: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)
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- 2023
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31. The Role of Vitamins in Oral Potentially Malignant Disorders and Oral Cancer: A Systematic Review.
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See JKL, Liu X, Canfora F, Moore C, McCullough M, Yap T, Paolini R, and Celentano A
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Background: Micronutrients are vital for general and oral health, and their potential anti-cancer properties are documented. We explore beneficial vitamins for oral potentially malignant disorders (OPMDs) and oral cancer (OC), assessing the therapeutic impacts of essential vitamin supplementation., Methods: We systematically review evidence on vitamin supplementation's therapeutic effects for OPMDs and OC. Relevant studies were identified through comprehensive searches of MEDLINE, Evidence-Based Medicine, and Web of Science until 16 May 2023. All studies underwent risk of bias using criteria modified from the Office of Health Assessment and Translation (OHAT) tool., Results: We analysed 80 papers. Vitamin K, studied in vitro, shows promising therapeutic potential. Vitamin C, investigated in vivo (animals and humans), demonstrated mixed animal results and generally positive human trial effects. Vitamin A's efficacy varied, with positive monotherapy or adjunct effects. Vitamins B and D showed therapeutic benefits. Oral cancer research was extensive, with a focus on oral lichen planus and oral leukoplakia among the 11 OPMDs. All bias levels were reported in 'selective reporting' and 'performance', except for "definitely high" in the 'selection', 'detection', and 'attrition/exclusion' domains., Conclusions: Evidence of vitamin interventions for OPMDs and OC ranges from mixed to promising. Standardizing the study design and outcomes would enhance future research.
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- 2023
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32. Diagnosing Extrapulmonary Sarcoidosis and the Implications of Diagnosis on Military Service.
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Moore CE and Marshall L
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Sarcoidosis is a systemic inflammatory disease that can cause granulomatous infiltration of almost all organs and tissues which allows for a wide variety of presentations that may overlap with other disease processes. Renal sarcoidosis is a much rarer site of extrapulmonary involvement and may present as hypercalcemia, tubular or glomerular dysfunction, and/or granulomatous interstitial nephritis. Prompt diagnosis of sarcoidosis is crucial for initiating appropriate treatment and avoiding organ dysfunction. Herein, we describe a case of an armed forces service member who developed extrapulmonary sarcoidosis and renal sarcoidosis with acute complications refractory to glucocorticoids requiring adalimumab. The case highlights and emphasizes a rare manifestation of extrapulmonary sarcoidosis, the importance of avoiding premature closure of the differential diagnosis to avoid diagnostic delay and treatment imitation, and the unique clinical reasoning that occurs in active-duty personnel where diagnoses and subsequent treatments can have career implications and affect the ability of the service member to maintain the ability to deploy worldwide., Competing Interests: The views expressed in this Case Report are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. I am a military service member or employee of the U.S. Government. This work was prepared as part of my official duties. Title 17, U.S.C., §105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C., §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties., (Copyright © 2023, Moore et al.)
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- 2023
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33. Global Variation in Magnetic Resonance Imaging Quality of the Prostate.
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Giganti F, Ng A, Asif A, Chan VW, Rossiter M, Nathan A, Khetrapal P, Dickinson L, Punwani S, Brew-Graves C, Freeman A, Emberton M, Moore CM, Allen C, and Kasivisvanathan V
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- Humans, Male, Diffusion Magnetic Resonance Imaging, Pelvis, Prospective Studies, Magnetic Resonance Imaging, Prostate diagnostic imaging
- Abstract
Background High variability in prostate MRI quality might reduce accuracy in prostate cancer detection. Purpose To prospectively evaluate the quality of MRI scanners taking part in the quality control phase of the global PRIME (Prostate Imaging Using MRI ± Contrast Enhancement) trial using the Prostate Imaging Quality (PI-QUAL) standardized scoring system, give recommendations on how to improve the MRI protocols, and establish whether MRI quality could be improved by these recommendations. Materials and Methods In the prospective clinical trial (PRIME), for each scanner, centers performing prostate MRI submitted five consecutive studies and the MRI protocols (phase I). Submitted data were evaluated in consensus by two expert genitourinary radiologists using the PI-QUAL scoring system that evaluates MRI diagnostic quality using five points (1 and 2 = nondiagnostic; 3 = sufficient; 4 = adequate, 5 = optimal) between September 2021 and August 2022. Feedback was provided for scanners not achieving a PI-QUAL 5 score, and centers were invited to resubmit new imaging data using the modified protocol (phase II). Descriptive comparison of outcomes was made between the MRI scanners, feedback provided, and overall PI-QUAL scores. Results In phase I, 41 centers from 18 countries submitted a total of 355 multiparametric MRI studies from 71 scanners, with nine (13%) scanners achieving a PI-QUAL score of 3, 39 (55%) achieving a score of 4, and 23 (32%) achieving a score of 5. Of the 48 ( n = 71 [68%]) scanners that received feedback to improve, the dynamic contrast-enhanced sequences were those that least adhered to the Prostate Imaging Reporting and Data System, version 2.1, criteria (44 of 48 [92%]), followed by diffusion-weighted imaging (20 of 48 [42%]) and T2-weighted imaging (19 of 48 [40%]). In phase II, 36 centers from 17 countries resubmitted revised studies, resulting in a total of 62 ( n = 64 [97%]) scanners with a final PI-QUAL score of 5. Conclusion Substantial variation in global prostate MRI acquisition parameters as a measure of quality was observed, particularly with DCE sequences. Basic evaluation and modifications to MRI protocols using PI-QUAL can lead to substantial improvements in quality. Clinical trial registration no. NCT04571840 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almansour and Chernyak in this issue.
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- 2023
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34. Mercury in Neotropical birds: a synthesis and prospectus on 13 years of exposure data.
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Sayers CJ 2nd, Evers DC, Ruiz-Gutierrez V, Adams E, Vega CM, Pisconte JN, Tejeda V, Regan K, Lane OP, Ash AA, Cal R, Reneau S, Martínez W, Welch G, Hartwell K, Teul M, Tzul D, Arendt WJ, Tórrez MA, Watsa M, Erkenswick G, Moore CE, Gerson J, Sánchez V, Purizaca RP, Yurek H, Burton MEH, Shrum PL, Tabares-Segovia S, Vargas K, Fogarty FF, Charette MR, Martínez AE, Bernhardt ES, Taylor RJ, Tear TH, and Fernandez LE
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- Animals, Environmental Monitoring, Ecosystem, Environmental Pollution, Gold, Birds, Mercury analysis
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Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (n = 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics., (© 2023. The Author(s).)
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- 2023
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35. Longitudinal Integrated Ambulatory, Didactic, and Evidenced-Based Medicine Curriculum in Internal Medicine.
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Moore CE and McBee E
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Introduction: The Accreditation Council for Graduate Medical Education (ACGME) endorses evolving scholarly education regarding evidence-based medicine (EBM) and its clinical application in Internal Medicine (IM). The IM residents at Navy Medical Readiness and Training Center San Diego (NMRTC-SD) communicated the need for both increased ambulatory didactic sessions as well as a formal EBM curriculum. Prior to the academic year of 2021-2022, no formal ambulatory or EBM curriculum existed. In July 2021, an integrated EBM-ambulatory curriculum was implemented., Methods: A pre-curriculum needs assessment was performed and thereafter an eight-session integrated ambulatory-EBM curriculum was implemented in the 2021-2022 academic year. Faculty members facilitated small group discussions focused on a particular didactic topic and EBM principle and integrated the learning of both into one session. After each session, residents completed a feedback form. At the end of the year, a post-curriculum needs assessment was collected., Key Results: Thirty-four residents of all post-graduate years (PGY) levels participated from July 2021 to June 2022. Primary outcomes were satisfaction with the didactic portion of the curriculum, perception of receipt of adequate training in EBM principles, and perception of level of competency in practicing EBM principles. Overall, participants reported a substantial increase in satisfaction with didactic teaching and a large increase in the perceived competency in practicing EBM principles., Conclusion: This integrated didactic-EBM curriculum represents an effective method of incorporating didactic topics in IM with the teaching and application of EBM principles, which improved resident satisfaction with the curricula and self-perception of competency in critically appraising medical literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Moore et al.)
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- 2023
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36. Magnetic Resonance Imaging Follow-up of Targeted Biopsy-negative Prostate Lesions.
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Stavrinides V, Eksi E, Finn R, Texeira-Mendes L, Rana S, Trahearn N, Grey A, Giganti F, Huet E, Fiard G, Freeman A, Haider A, Allen C, Kirkham A, Cole AP, Collins T, Pendse D, Dickinson L, Punwani S, Pashayan N, Emberton M, Moore CM, and Orczyk C
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- Male, Humans, Aged, Prostate-Specific Antigen, Follow-Up Studies, Biopsy methods, Magnetic Resonance Imaging methods, Inflammation, Prostate diagnostic imaging, Prostate pathology, Prostatic Neoplasms pathology
- Abstract
Background: The optimal radiological follow-up of prostate lesions negative on magnetic resonance imaging (MRI)-targeted biopsy (MRI-TB) is yet to be optimised., Objective: To present medium-term radiological and clinical follow-up of biopsy-negative lesions., Design, Setting, and Participants: The records for men who underwent multiparametric MRI at the UCLH one-stop clinic for suspected prostate cancer between September 2017 and March 2020 were reviewed (n = 1199). Patients with Likert 4 or 5 lesions were considered (n = 495), and those with a subsequent negative MRI-TB comprised the final study population (n = 91)., Outcome Measurements and Statistical Analysis: Baseline and follow-up MRI and biopsy data (including prostate-specific antigen [PSA], prostate volume, radiological scores, and presence of any noncancerous pathology) were extracted from reports. The last follow-up date was the date of the last test or review in clinic., Results and Limitations: Median follow-up was 1.8 yr (656 d, interquartile range [IQR] 359-1008). At baseline, the median age was 65.4 yr (IQR 60.7-70.0), median PSA was 7.1 ng/ml (IQR 4.7-10.0), median prostate volume was 54 ml (IQR 39.5-75.0), and median PSA density (PSAD) was 0.13 ng/ml
2 (IQR 0.09-0.18). Eighty-six men (95%) had Likert 4 lesions, while the remaining five (5%) had Likert 5 lesions. Only 21 men (23%) had a single lesion; most had at least two. Atrophy was the most prevalent pathology on MRI-TB, present in 64 men (74%), and followed by acute inflammation in 42 (46%), prostatic intraepithelial neoplasia in 33 (36%), chronic inflammation in 18 (20%), atypia in 13 (14%), and granulomatous inflammation in three (3%). Fifty-eight men had a second MRI study (median 376 d, IQR 361-412). At the second MRI, median PSAD decreased to 0.11 ng/ml2 (IQR 0.08-0.18). A Likert 4 or 5 score persisted only in five men (9%); 40 men (69%) were scored Likert 3, while the remaining 13 (22%) were scored Likert 2 (no lesion). Of 45 men with a Likert ≥3 score, most only had one lesion at the second MRI (28 men; 62%). Of six men with repeat MRI-TB during the study period, two were subsequently diagnosed with prostate cancer and both had persistent Likert 4 scores (at baseline and at least one follow-up MRI)., Conclusions: Most biopsy-negative MRI lesions in the prostate resolve over time, but any persistent lesions should be closely monitored., Patient Summary: Lesions in the prostate detected via magnetic resonance imaging (MRI) scans that are negative for cancer on biopsy usually resolve. Repeat MRI can indicate persistent lesions that might need a second biopsy., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2023
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37. Comparison of β-1-3-D-Glucan and Candida Mannan Biomarker Assays with Serological Tests for the Diagnosis of Candidemia.
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Eades CP, Bakri ARBA, Lau JCY, Moore CB, Novak-Frazer L, Richardson MD, and Rautemaa-Richardson R
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Invasive candidiasis, including bloodstream infection (candidemia), encompasses the most severe forms of Candida infection. Several species-specific and non-specific serological assays are commercially available to aid in diagnosis. This study compared the performance of five such biomarker assays. Serum samples from 14 patients with proven or probable invasive candidiasis, and from 10 control patients, were included in the analysis. A total of 50 serum samples were tested using C. albicans germ tube antibody (CAGTA) assay (Vircell), C. albicans IgM, C. albicans IgG and Candida mannan assays (Dynamiker Biotechnology). Among these samples, the β-1-3-D-glucan (BDG) assay (Fungitell), a laboratory standard for the diagnosis of invasive candidiasis, was positive in 20 (40%), intermediate in five (10%) and negative in 25 (50%). In cases of proven or probable candidemia, the sensitivity and specificity of the BDG assay was 86% and 80%, respectively; the Candida mannan assay, 14% and 86%; the CAGTA test, 57% and 60%; the C. albicans IgM assay, 71% and 60%; and C. albicans IgG assay 29% and 90%. In 4/8 (50%) cases with multiple serum samples, C. albicans IgM was positive sooner than BDG. Thus, when used as a rule-out test for invasive candidiasis, our data suggest that the C. albicans IgM assay may assist antifungal stewardship (over serum BDG).
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- 2023
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38. Production and properties of adhesin-free gingipain proteinase RgpA.
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Mahmud ASM, Seers CA, Huq NL, Zhang L, Butler CA, Moore C, Cross KJ, and Reynolds EC
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- Gingipain Cysteine Endopeptidases, Adhesins, Bacterial chemistry, Catalytic Domain, Porphyromonas gingivalis metabolism, Hemagglutinins chemistry, Cysteine Endopeptidases metabolism, Peptide Hydrolases
- Abstract
The Arg-specific gingipains of Porphyromonas gingivalis RgpA and RgpB have 97% identical sequences in their catalytic domains yet their propeptides are only 76% identical. RgpA isolates as a proteinase-adhesin complex (HRgpA) which hinders direct kinetic comparison of RgpA
cat as a monomer with monomeric RgpB. We tested modifications of rgpA identifying a variant that enabled us to isolate histidine-tagged monomeric RgpA (rRgpAH). Kinetic comparisons between rRgpAH and RgpB used benzoyl-L-Arg-4-nitroanilide with and without cysteine and glycylglycine acceptor molecules. With no glycylglycine, values of Km , Vmax , kcat and kcat /Km for each enzyme were similar, but with glycylglycine Km decreased, Vmax increased and kcat increased ~ twofold for RgpB but ~ sixfold for rRgpAH. The kcat /Km for rRgpAH was unchanged whereas that of RgpB more than halved. Recombinant RgpA propeptide inhibited rRgpAH and RgpB with Ki 13 nM and 15 nM Ki respectively slightly more effectively than RgpB propeptide which inhibited rRgpAH and RgpB with Ki 22 nM and 29 nM respectively (p < 0.0001); a result that may be attributable to the divergent propeptide sequences. Overall, the data for rRgpAH reflected observations previously made by others using HRgpA, indicating rRgpAH fidelity and confirming the first production and isolation of functional affinity tagged RgpA., (© 2023. The Author(s).)- Published
- 2023
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39. Acquisition and annotation in high resolution in vivo digital biopsy by confocal microscopy for diagnosis in oral precancer and cancer.
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Yap T, Tan I, Ramani RS, Bhatia N, Demetrio de Souza Franca P, Angel C, Moore C, Reiner T, Bussau L, and McCullough MJ
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Introduction: Scanned fibre endomicroscopes are full point-scanning confocal microscopes with submicron lateral resolution with an optical slice thickness thin enough to isolate individual cell layers, allow active positioning of the optical slice in the z-axis and collection of megapixel images. Here we present descriptive findings and a brief atlas of an acquisition and annotation protocol high resolution in vivo capture of oral mucosal pathology including oral squamous cell carcinoma and dysplasia using a fluorescence scanned fibre endomicroscope with 3 topical fluorescent imaging agents: fluorescein, acriflavine and PARPi-FL., Methods: Digital biopsy was successfully performed via an acquisition protocol in seventy-one patients presenting for investigation of oral mucosal abnormalities using a miniaturized, handheld scanned fibre endoscope. Multiple imaging agents were utilized and multiple time points sampled. Fifty-nine patients had a matched histopathology correlating in location with imaging. The images were annotated back to macrographic location using a purpose-built software, MouthMap™., Results: Acquisition and annotation of cellular level resolved images was demonstrated with all 3 topical agents. Descriptive observations between clinically or histologically normal oral mucosa showed regular intranuclear distance, a regular nuclear profile and fluorescent homogeneity. This was dependent on the intraoral location and type of epithelium being observed. Key features of malignancy were a loss of intranuclear distance, disordered nuclear clustering and irregular nuclear fluorescence intensity and size. Perinuclear fluorescent granules were seen in the absence of irregular nuclear features in lichenoid inflammation., Discussion: High resolution oral biopsy allows for painless and rapid capture of multiple mucosal sites, resulting in more data points to increase diagnostic precision. High resolution digital micrographs can be easily compared serially across multiple time points utilizing an annotation software. In the present study we have demonstrated realization of a high-resolution digital biopsy protocol of the oral mucosa for utility in the diagnosis of oral cancer and precancer.., Competing Interests: LB is an employee and shareholder of Optiscan Imaging. TR is a shareholder of Summit Biomedical Imaging, LLC. S.K., S.P. and co-inventor on filed U.S. patent WO2016164771 that covers methods of use for PARPi-FL. TR is also a co-inventor on U.S. patent WO2012074840, covering the composition of matter for PARPi-FL. TR is a paid consultant for Theragnostics, Inc. This arrangement has been reviewed and approved by Memorial Sloan Kettering Cancer Center in accordance with its conflict of interest policies. TY was awarded a Dean’s Innovation Grant by the University of Melbourne to commission the MouthMap™ project software in collaboration with MoleMap. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from The Australian Government awarded through the Medical Research Future Fund to Optiscan Imaging and the University of Melbourne Dental School in collaborative clinical research to improve screening and early diagnosis of oral cancer. This project was funded in 2020 through the BioMedTech Horizons Program and administered by MTPConnect. TY is the lead researcher in this collaboration. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2023 Yap, Tan, Ramani, Bhatia, Demetrio de Souza Franca, Angel, Moore, Reiner, Bussau and McCullough.)
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- 2023
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40. Protecting Children's Health: Asthma and Climate Change.
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McDermott-Levy R, Pennea E, and Moore C
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- Child, Humans, Climate Change, Child Health, Asthma
- Abstract
Abstract: Children are particularly vulnerable to the impacts of climate change. Their lungs are developing, making children with asthma especially susceptible to temperature extremes, variations in precipitation, poor air quality, and changes in pollen and flora. Structural and social determinants of health, such as racism and poverty, that disproportionately affect children of color are linked to higher rates of asthma and negative effects of climate change. These factors lead to increased absences from school and social activities, loss of work for caregivers, and increased health care costs, thus negatively affecting children, their families, and the greater community. Nurses must support caregivers and children to link climate change to asthma care, be involved in health education; climate change mitigation and adaptation strategies and policies; and develop the evidence to address climate change and asthma strategies. We address the impacts of climate change on children with asthma and nursing adaptation responses., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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41. Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience.
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Habashy D, Reddy D, Peters M, Shah TT, van Son M, van Rossum PSN, Tanaka MB, Cullen E, Engle R, McCracken S, Greene D, Hindley RG, Emara A, Nigam R, Orczyk C, Shergill I, Persad R, Virdi J, Moore CM, Arya M, Winkler M, Emberton M, Ahmed HU, and Dudderidge T
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- Aged, Humans, Male, Androgen Antagonists, Prostate pathology, Prostate-Specific Antigen, Treatment Outcome, Prostatic Neoplasms pathology, Prostatic Neoplasms surgery, Ablation Techniques
- Abstract
Purpose: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality., Materials and Methods: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis., Results: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively ( P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen., Conclusions: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.
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- 2023
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42. A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?
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Patki S, Aquilina J, Thorne R, Aristidou I, Rodrigues FB, Warren H, Bex A, Kasivisvanathan V, Moore C, Gurusamy K, Emberton M, Best LMJ, and Tran MGB
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Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear., Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status., Evidence Acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers., Evidence Synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants., Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results., Patient Summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups., (© 2023 The Author(s).)
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- 2023
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43. Invited Perspective: Decentralized CyanoHAB Monitoring Is Needed to Understand Public Health Risks.
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Moore C
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- Public Health, Harmful Algal Bloom
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- 2023
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44. Effectiveness of system navigation programs linking primary care with community-based health and social services: a systematic review.
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Teggart K, Neil-Sztramko SE, Nadarajah A, Wang A, Moore C, Carter N, Adams J, Jain K, Petrie P, Alshaikhahmed A, Yugendranag S, and Ganann R
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- Adult, Humans, Social Work, Social Support, Patient-Centered Care, Quality of Life, Community Health Services
- Abstract
Background: Fragmented delivery of health and social services can impact access to high-quality, person-centred care. The goal of system navigation is to reduce barriers to healthcare access and improve the quality of care. However, the effectiveness of system navigation remains largely unknown. This systematic review aims to identify the effectiveness of system navigation programs linking primary care with community-based health and social services to improve patient, caregiver, and health system outcomes., Methods: Building on a previous scoping review, PsychInfo, EMBASE, CINAHL, MEDLINE, and Cochrane Clinical Trials Registry were searched for intervention studies published between January 2013 and August 2020. Eligible studies included system navigation or social prescription programs for adults, based in primary care settings. Two independent reviewers completed study selection, critical appraisal, and data extraction., Results: Twenty-one studies were included; studies had generally low to moderate risk of bias. System navigation models were lay person-led (n = 10), health professional-led (n = 4), team-based (n = 6), or self-navigation with lay support as needed (n = 1). Evidence from three studies (low risk of bias) suggests that team-based system navigation may result in slightly more appropriate health service utilization compared to baseline or usual care. Evidence from four studies (moderate risk of bias) suggests that either lay person-led or health professional-led system navigation models may improve patient experiences with quality of care compared to usual care. It is unclear whether system navigation models may improve patient-related outcomes (e.g., health-related quality of life, health behaviours). The evidence is very uncertain about the effect of system navigation programs on caregiver, cost-related, or social care outcomes., Conclusions: There is variation in findings across system navigation models linking primary care with community-based health and social services. Team-based system navigation may result in slight improvements in health service utilization. Further research is needed to determine the effects on caregiver and cost-related outcomes., (© 2023. The Author(s).)
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- 2023
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45. A semi-automated software program to assess the impact of second reads in prostate MRI for equivocal lesions: results from a UK tertiary referral centre.
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Woernle A, Dickinson L, Lelie S, Pendse D, Heffernan Ho D, Ramachandran N, Kirkham A, Von Stempel C, Punwani S, Wah So C, Withington J, Grey A, Collins T, Maffei D, Haider A, Freeman A, Emberton M, Piper JW, Moore CM, Hines J, Orczyk C, Allen C, and Giganti F
- Subjects
- Male, Humans, Tertiary Care Centers, Reading, Magnetic Resonance Imaging methods, Software, United Kingdom, Image-Guided Biopsy methods, Prostate pathology, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology
- Abstract
Purpose: To investigate the utility of a prostate magnetic resonance imaging (MRI) second read using a semi-automated software program in the one-stop clinic, where patients undergo multiparametric MRI, review and biopsy planning in one visit. We looked at concordance between readers for patients with equivocal scans and the possibility for biopsy deferral in this group., Methods: We present data from 664 consecutive patients. Scans were reported by seven different expert genitourinary radiologists using dedicated software (MIM®) and a Likert scale. All scans were rescored by another expert genitourinary radiologist using a customised workflow for second reads that includes annotated biopsy contours for accurate visual targeting. The number of scans in which a biopsy could have been deferred using biopsy results and prostate specific antigen density was assessed. Gleason score ≥ 3 + 4 was considered clinically significant disease. Concordance between first and second reads for equivocal scans (Likert 3) was evaluated., Results: A total of 209/664 (31%) patients scored Likert 3 on first read, 128 of which (61%) were concordant after second read. 103/209 (49%) of patients with Likert 3 scans were biopsied, with clinically significant disease in 31 (30%) cases. Considering Likert 3 scans that were both downgraded and biopsied using the workflow-generated biopsy contours, 25/103 (24%) biopsies could have been deferred., Conclusions: Implementing a semi-automated workflow for accurate lesion contouring and targeting biopsies is helpful during the one-stop clinic. We observed a reduction of indeterminate scans after second reading and almost a quarter of biopsies could have been deferred, reducing the potential biopsy-related side effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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46. Contemporary patterns of local ablative therapies for prostate cancer at United States cancer centers: results from a national registry.
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Koelker M, Labban M, Frego N, Meyer CP, Salomon G, Lipsitz SR, Withington J, Moore CM, Tempany CM, Tuncali K, George A, Kibel AS, Trinh QD, and Cole AP
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- Male, Humans, Aged, United States, Retrospective Studies, Medicare, Registries, Prostatic Neoplasms surgery, Prostatic Neoplasms pathology, Laser Therapy
- Abstract
Purpose: To describe the national-level patterns of care for local ablative therapy among men with PCa and identify patient- and hospital-level factors associated with the receipt of these techniques., Methods: We retrospectively interrogated the National Cancer Database (NCDB) for men with clinically localized PCa between 2010 and 2017. The main outcome was receipt of local tumor ablation with either cryo- or laser-ablation, and "other method of local tumor destruction including high-intensity focused ultrasound (HIFU)". Patient level, hospital level, and demographic variables were collected. Mixed effect logistic regression models were fitted to identify separately patient- and hospital-level predictors of receipt of local ablative therapy., Results: Overall, 11,278 patients received ablative therapy, of whom 78.8% had cryotherapy, 15.6% had laser, and 5.7% had another method including HIFU. At the patient level, men with intermediate-risk PCa were more likely to be treated with local ablative therapy (OR 1.05; 95% CI 1.00-1.11; p = 0.05), as were men with Charlson Comorbidity Index > 1 (OR 1.36; 95% CI 1.29-1.43; p < 0.01), men between 71 and 80 years (OR 3.70; 95% CI 3.43-3.99; p < 0.01), men with Medicare insurance (OR 1.38; 95% 1.31-1.46; p < 0.01), and an income < $47,999 (OR 1.16; 95% CI 1.06-1.21; p < 0.01). At the hospital-level, local ablative therapy was less likely to be performed in academic/research facilities (OR 0.45; 95% CI 0.32-0.64; p < 0.01)., Conclusions: Local ablative therapy for PCa treatment is more commonly offered among older and comorbid patients. Future studies should investigate the uptake of these technologies in non-hospital-based settings and in light of recent changes in insurance coverage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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47. Comparing biparametric to multiparametric MRI in the diagnosis of clinically significant prostate cancer in biopsy-naive men (PRIME): a prospective, international, multicentre, non-inferiority within-patient, diagnostic yield trial protocol.
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Asif A, Nathan A, Ng A, Khetrapal P, Chan VW, Giganti F, Allen C, Freeman A, Punwani S, Lorgelly P, Clarke CS, Brew-Graves C, Muirhead N, Emberton M, Agarwal R, Takwoingi Y, Deeks JJ, Moore CM, and Kasivisvanathan V
- Subjects
- Male, Humans, Prospective Studies, Magnetic Resonance Imaging methods, Biopsy, Multicenter Studies as Topic, Multiparametric Magnetic Resonance Imaging methods, Prostatic Neoplasms diagnosis
- Abstract
Introduction: Prostate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach., Methods: Prostate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision., Ethics and Dissemination: Ethical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial., Trial Registration Number: NCT04571840., Competing Interests: Competing interests: AN is an academic clinical fellow funded by the National Institute for Health and Care Research. PK is an academic clinical fellow funded by the National Institute for Health and Care Research and The Urology Foundation. FG is a recipient of the 2020 Young Investigator Award (20YOUN15) funded by the Prostate Cancer Foundation / CRIS Cancer Foundation. SP is supported by the National Institute of Health and Care Research (NIHR), UCLH and UCL Biomedical Research Centre. ME receives research support from the National Institute of Health and Care Research (NIHR), UCLH and UCL Biomedical Research Centre. YT is funded by a UK NIHR Postdoctoral Fellowship and supported by the NIHR Birmingham Biomedical Research Centre. CMM is an NIHR Research Professor, and receives grants from MRC, CRUK, Movember, and Prostate Cancer UK. VK is funded by Prostate Cancer UK and The John Black Charitable Foundation. He receives speaker fees from the European Association of Urology, Singapore Urology Association, The Clinical Comms Group and Got IT consulting SL. All authors declare that there are no conflicts of interest. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, NIHR, or the Department of Health and Social Care., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
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- 2023
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48. Development and Delivery of a Hands-On Short Course in Adeno-Associated Virus Manufacturing to Support Growing Workforce Needs in Gene Therapy.
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Overton L, Boi C, Shastry S, Smith-Moore C, Balchunas J, Sambandan D, and Gilleskie G
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- Humans, Commerce, Genetic Vectors genetics, Dependovirus genetics, Genetic Therapy
- Abstract
The manufacturing of gene therapy products is a rapidly growing industry bolstered by the tremendous potential of these therapies to provide lifesaving treatment for rare and complex genetic diseases. The industry's steep rise has resulted in a high demand for skilled staff required to manufacture gene therapy products of the expected high quality. To address this skill shortage, more opportunities for education and training in all aspects of gene therapy manufacturing are needed. The Biomanufacturing Training and Education Center (BTEC) at the North Carolina State University (NC State) has developed and delivered (and continues to deliver) a 4-day, hands-on course titled Hands-on cGMP Biomanufacturing of Vectors for Gene Therapy. The course, which consists of 60% hands-on laboratory activities and 40% lectures, aims to provide a comprehensive understanding of the gene therapy production process, from vial thaw through the final formulation step, and analytical testing. This article discusses the design of the course, the backgrounds of the nearly 80 students who have participated in the seven offerings held since March 2019, and feedback from the course participants.
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- 2023
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49. Corrigendum to "Magnetic Resonance Imaging and targeted biopsies compared to transperineal mapping biopsies prior to salvage focal therapy/ablation in localised and metastatic recurrent prostate cancer after radiotherapy. Primary Outcomes from the FORECAST Trial" [Eur Urol 2022;81(6):598-605].
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Shah TT, Kanthabalan A, Otieno M, Pavlou M, Omar R, Adeleke S, Giganti F, Brew-Graves C, Williams NR, Grierson J, Miah H, Emara A, Haroon A, Latifoltojar A, Sidhu H, Clemente J, Freeman A, Orczyk C, Nikapota A, Dudderidge T, Hindley RG, Virdi J, Arya M, Payne H, Mitra A, Bomanji J, Winkler M, Horan G, Moore CM, Emberton M, Punwani S, and Ahmed HU
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- 2023
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50. Best Current Practice and Research Priorities in Active Surveillance for Prostate Cancer-A Report of a Movember International Consensus Meeting.
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Moore CM, King LE, Withington J, Amin MB, Andrews M, Briers E, Chen RC, Chinegwundoh FI, Cooperberg MR, Crowe J, Finelli A, Fitch MI, Frydenberg M, Giganti F, Haider MA, Freeman J, Gallo J, Gibbs S, Henry A, James N, Kinsella N, Lam TBL, Lichty M, Loeb S, Mahal BA, Mastris K, Mitra AV, Merriel SWD, van der Kwast T, Van Hemelrijck M, Palmer NR, Paterson CC, Roobol MJ, Segal P, Schraidt JA, Short CE, Siddiqui MM, Tempany CMC, Villers A, Wolinsky H, and MacLennan S
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- Male, Humans, Consensus, Watchful Waiting methods, Research, Prostate-Specific Antigen, Prostatic Neoplasms diagnosis, Prostatic Neoplasms therapy, Prostatic Neoplasms pathology
- Abstract
Background: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support., Objective: To explore the current best practice and determine the most important research priorities in AS for prostate cancer., Design, Setting, and Participants: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed., Outcome Measurements and Statistical Analysis: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members., Results and Limitations: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons., Conclusions: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer., Patient Summary: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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