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- ArticleTran MH, Nguyen HH, Nguyen QT, Tran TDM, Truong-Nguyen KH, Pham HT.Cureus. 2024 Aug;16(8):e67256.BACKGROUND: Step-based dosing of anticoagulants has been widely implemented for the treatment of coronavirus disease 2019 (COVID-19), but no studies have comprehensively evaluated the effectiveness and safety of this approach. We aimed to investigate whether step-based dosing of anticoagulants was associated with clinical outcomes in patients with COVID-19 compared with standard prophylactic dosing.
METHOD: We conducted a retrospective cohort study on adults hospitalized with moderate-to-severe COVID-19. The exposure was step-based dosing of anticoagulants, including prophylactic anticoagulants (PrA), prophylactic-switching-to-therapeutic anticoagulants (Pr-to-ThA), therapeutic anticoagulants (ThA), and therapeutic-switching-to-prophylactic anticoagulants (Th-to-PrA). The primary effectiveness outcome was a composite of all-cause mortality, admission to an intensive care unit (ICU admission), stroke, and venous thromboembolism (VTE). The primary safety outcome was a composite of major and minor/clinically relevant non-major (CRNM) bleeding.
RESULTS: Among 1,081 records for analysis (mean age 59.9, 49.9% being female), during a median follow-up of 15 days, the primary effectiveness outcome occurred in 333 patients (33.5% in the PrA group, 24.6% in the Pr-to-ThA group, 23.7% in the Th-to-PrA group, and 38.0% in the ThA group). Compared with the PrA group, patients receiving Pr-to-ThA had a lower risk of the primary effectiveness outcome (adjusted odds ratio (OR) 0.64, 95% CI: 0.45 to 0.90, Dunnett-adjusted p = 0.01), while those in the Th-to-PrA and ThA were more likely to experience the primary safety outcome (Th-to-PrA, aOR = 3.00, 95% CI: 1.53 to 5.89; ThA, aOR = 3.05, 95% CI: 1.61 to 5.79).
CONCLUSION: In adults hospitalized with moderate-to-severe COVID-19, compared with standard PrA, the step-based dose-increasing therapy was associated with a lower composite risk of all-cause mortality, ICU admission, stroke, or VTE without evidence of a higher risk of bleeding. ThA dosing was associated with an increase in the bleeding risk, primarily minor and CRNM bleeding. - ArticleKrejsa CM, Holly RD, Heipel M, Bannink KM, Johnson R, Roque R, Heffernan J, Hill J, Chin L, Wagener F, Shiota F, Henderson K, Sivakumar PV, Ren HP, Barahmand-Pour F, Foster D, Clegg C, Kindsvogel W, Ponce R, Hughes SD, Waggie K.PLoS One. 2013;8(6):e67256.Rituximab, a monoclonal antibody targeting CD20 on B cells, is currently used to treat many subtypes of B cell lymphomas. However, treatment is not curative and response rates are variable. Recombinant interleukin-21 (rIL-21) is a cytokine that enhances immune effector function and affects both primary and transformed B cell differentiation. We hypothesized that the combination of rIL-21 plus rituximab would be a more efficacious treatment for B cell malignancies than rituximab alone. We cultured human and cynomolgus monkey NK cells with rIL-21 and found that their activity was increased and proteins associated with antibody dependent cytotoxicity were up-regulated. Studies in cynomolgus monkeys modeled the effects of rIL-21 on rituximab activity against CD20 B cells. In these studies, rIL-21 activated innate immune effectors, increased ADCC and mobilized B cells into peripheral blood. When rIL-21 was combined with rituximab, deeper and more durable B cell depletion was observed. In another series of experiments, IL-21 was shown to have direct antiproliferative activity against a subset of human lymphoma cell lines, and combination of murine IL-21 with rituximab yielded significant survival benefits over either agent alone in xenogeneic mouse tumor models of disseminated lymphoma. Therefore, our results do suggest that the therapeutic efficacy of rituximab may be improved when used in combination with rIL-21.
- ArticleYang X, Li Z, Lei L, Shi X, Zhang D, Zhou F, Li W, Xu T, Liu X, Wang S, Yuan Q, Yang J, Wang X, Zhong Y, Yu L.J Med Internet Res. 2025 Jan 07;27:e67256.BACKGROUND: Oral microenvironmental disorders are associated with an increased risk of heart failure with preserved ejection fraction (HFpEF). Hyperspectral imaging (HSI) technology enables the detection of substances that are visually indistinguishable to the human eye, providing a noninvasive approach with extensive applications in medical diagnostics.
OBJECTIVE: The objective of this study is to develop and validate a digital, noninvasive oral diagnostic model for patients with HFpEF using HSI combined with various machine learning algorithms.
METHODS: Between April 2023 and August 2023, a total of 140 patients were recruited from Renmin Hospital of Wuhan University to serve as the training and internal testing groups for this study. Subsequently, from August 2024 to September 2024, an additional 35 patients were enrolled from Three Gorges University and Yichang Central People's Hospital to constitute the external testing group. After preprocessing to ensure image quality, spectral and textural features were extracted from the images. We extracted 25 spectral bands from each patient image and obtained 8 corresponding texture features to evaluate the performance of 28 machine learning algorithms for their ability to distinguish control participants from participants with HFpEF. The model demonstrating the optimal performance in both internal and external testing groups was selected to construct the HFpEF diagnostic model. Hyperspectral bands significant for identifying participants with HFpEF were identified for further interpretative analysis. The Shapley Additive Explanations (SHAP) model was used to provide analytical insights into feature importance.
RESULTS: Participants were divided into a training group (n=105), internal testing group (n=35), and external testing group (n=35), with consistent baseline characteristics across groups. Among the 28 algorithms tested, the random forest algorithm demonstrated superior performance with an area under the receiver operating characteristic curve (AUC) of 0.884 and an accuracy of 82.9% in the internal testing group, as well as an AUC of 0.812 and an accuracy of 85.7% in the external testing group. For model interpretation, we used the top 25 features identified by the random forest algorithm. The SHAP analysis revealed discernible distinctions between control participants and participants with HFpEF, thereby validating the diagnostic model's capacity to accurately identify participants with HFpEF.
CONCLUSIONS: This noninvasive and efficient model facilitates the identification of individuals with HFpEF, thereby promoting early detection, diagnosis, and treatment. Our research presents a clinically advanced diagnostic framework for HFpEF, validated using independent data sets and demonstrating significant potential to enhance patient care.
TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300078855; https://www.chictr.org.cn/showproj.html?proj=207133. - ArticleRodrigues ET, Nascimento SF, Pires CL, Godinho LP, Churro C, Moreno MJ, Pardal MA.Environ Sci Pollut Res Int. 2021 Dec;28(47):67256-67266.Contributing to the human health risk assessment, the present study aims to evaluate the ability of paralytic shellfish toxins (PSTs) to cross the human intestinal epithelium by using the Caco-2 permeability assay. A crude extract prepared from the PST producer dinoflagellate Gymnodinium catenatum strain, GCAT1_L2_16, and the PST analogue gonyautoxin-5 (GTX-5) prepared from a certified reference material (CRM) were tested. In the conditions of the assay, none of the compounds altered Caco-2 viability, or the integrity of cell monolayers. The GTX-5 apparent permeability coefficients are 0.9×10-7 and 0.6×10-7 cm s-1 for the crude extract and CRM, respectively, thus, <10-6 cm s-1, which indicates that humans absorb this PST analogue poorly. The present study also reveals that, during a 90-min exposure, GTX-5 is not metabolised to a high extent by Caco-2 or retained in the Caco-2 cytoplasm. Since it is known that GTX-5 can be found in the spleen, liver or kidney of the victims, as well as in the urine samples of patients who consumed contaminated seafood, further research is needed to clarify the transport mechanisms involved, permeation time and dose-dependence, and the possible role of intestinal microflora.
- BookBernadette Mazurek Melnyk, Ellen Fineout-Overholt.Summary: "The go-to guide to evidence-based practice in nursing for more than a decade, Evidence-Based Practice in Nursing & Healthcare: A Guide to Best Practice, 5th Edition, presents the latest perspectives on research-backed nursing practice in an engaging, user-friendly approach that has made this the bestselling resource of its kind. AJN award-winning authors Bernadette Melnyk and Ellen Fineout-Overholt combine straightforward, conversational storytelling, inspiring quotes, and engaging case studies to make evidence-based practice accessible for students at any level of familiarity. With real-world examples and meaningful strategies in every chapter, this revised and reimagined 5th Edition gives students the confidence to meet today's clinical challenges and ensure the most effective patient outcomes for years to come. New to this edition: NEW! Reimagined coverage and a new chapter on applying implementation science to clinical practice settings familiarize students with the latest evidence and emerging implementation and evaluation tools.. UPDATED! Content throughout empowers you to more effectively teach evidence-based practice principles in academic and clinical settings. UPDATED! Making EPB Real case studies reinforce clinical application through real-world examples"-- Provided by publisher.
Contents:
Unit 1. Steps 0, 1, and 2 : getting started: Chapter 1. Making the case for evidence-based practice and cultivating a spirit of inquiry / Bernadette Mazurek Melnyk and Ellen Fineout-Overholt
Chapter 2. Asking compelling clinical questions / Ellen Fineout-Overholt and Shelly J. Johnson
Chapter 3. Finding relevant evidence to answer clinical questions / Tami A. Hartzell, Ellen Fineout-Overholt, and Cyndi B. Kelley
Unit 1 making EBP real, a success story: Improving outcomes in intensive care through adherence to evidence-based sedation protocol.
Unit 2. Step 3 : critically appraising evidence: Chapter 4. Critically appraising knowledge for clinical decision making / Ellen Fineout-Overholt
Chaper 5. Clinician expertise and patient-valued preferences as context for critical appraisal for evidence-based decision making / Ellen Fineout-Overholt, Gina M. Nickels-Nelson, and Lisa English Long
Chapter 6. Critically appraising quantitative evidence for clinical decision making / Dónal P. O'Mathúna, Ellen Fineout-Overholt, Debra B. Graham, and Amanda Canada
Chapter 7. Critically appraising qualitative and mixed methods evidence for clinical decision making / Mikki Meadows-Oliver and Chaluza Kapaale
Chapter 8. Advancing optimal care with robust clinical practice guidelines / Doris Grinspun, Bernadette Mazurek Melnyk, Ellen Fineout-Overholt, Shanoja Naik, and Katherine Wallace
Unit 2 making EBP real, a success story: Diabetic foot care in Hispanic females with type II diabetes : an evidence-based quality improvement initiative.
Unit 3. Steps 4 and 5 : moving from evidence to sustainable practice change: Chapter 9. Key strategies for implementing evidence in real-world clinical settings / Lynn Gallagher-Ford, Kevin P. Browne, Amanda Shrout, and Bernadette Mazurek Melnyk
Chapter 10. The role of quality improvement and evidence-based quality improvement in practice change / Ellen Fineout-Overholt, Tracy L. Brewer, Deana Hays, and Dana Tschannen
Chapter 11. Implementing the evidence-based practice competencies in clinical and academic settings to enhance healthcare quality, safety, and patient outcomes / Bernadette Mazurek Melnyk, Lynn Gallagher-Ford, and Cindy Zellefrow
Chapter 12. Leadership strategies for creating and sustaining evidence-based practice organizations / Lynn Gallagher-Ford, Penelope F. Gorsuch, Bernadette Mazurek Melnyk, and Jacalyn S. Buck
Unit 3 making EBP real, a success story: Improving outcomes for depressed adolescents with the brief cognitive behavioral skills building COPE intervention delivered in 30-minute out-patient visits.
Unit 4. Creating and sustaining a culture and environment for evidence-based practice: Chapter 13. Innovation and evidence : a partnership in advancing best practice and high quality care / Kathy Malloch and Timothy Porter-O'Grady
Chapter 14. Models to guide implementation and sustainability of evidence-based practice / Sandra L. Dearholt [and 13 others]
Chapter 15. Implementation science to clinical practice settings : accelerating the uptake of evidence into practice for best outcomes / Sharon Tucker and Molly McNett
Chapter 16. Evidence-based practice mentors : the key to sustaining evidence-based practice in clinical and educational settings / Ellen Fineout-Overholt and Bernadette Mazurek Melnyk
Chapter 17. Creating a vision and motivating a change to evidence-based practice in individuals, teams, and organizations / Bernadette Mazurek Melnyk and Ellen Fineout-Overholt
Chapter 18. Teaching evidence-based practice in academic settings / Ellen Fineout-Overholt, Alice E. Dupler, and Heather Carter-Templeton
Chapter 19. Teaching evidence-based practice in clinical settings / Ellen Fineout-Overholt, Marcella Upshaw, and Kathleen M. Williamson
Unit 4 making EBP real, a success story: Skilled nursing facility readmissions : an evidence-based telemedicine innovation project.
Unit 5. Step 6 : disseminating evidence and evidence-based practice implementation outcomes: Chapter 20. Using evidence to influence health and organizational policy / Todd E. Tussing, John C. Welch, and Jacqueline M. Loversidge
Chapter 21. Disseminating evidence through presentations, publications, health policy briefs, and the media / Cecily L. Betz, Kathryn A. Smith, Bernadette Mazurek Melnyk, and Philip J. Saken
Unit 5. Making EBP real, a success story: Taking a moment : evaluating preceptions of burnout and wellbeing in bone marrow transplant nurses using a mindfulmess smartphone app.
Unit 6. Generating external evidence and writing successful grant proposals: Chapter 22. Generating evidence through quantitative and qualitative research / Bernadette Mazurek Melnyk, Dianne Morrison-Beedy, and Denise Cote-Arsenault
23. Writing a successful grant proposal to fund research and evidence-based practice implementation projects / Bernadette Mazurek Melnyk and Ellen Fineout-Overholt
Chapter 24. Ethical considerations for evidence implementation and evidence generation / Dónal P. O'Mathúna, Joanne Cleary-Holdforth, and Ellen Fineout-Overholt
Unit 6 making EBP real, a success story: COPE/Healthy lifestyles TEEN : a school-based RCT.
Appendix A. Question template for asking PICOT questions
Appendix B. PICOT questions to systematic search strategy : development and use worksheet example
Appendix C. General appraisal overview for all studies
Appendix D. Evaluation table template and synthesis table examples for critical appraisal
Appendix E. ARCC model timeline for an EBP in educational settings
Appendix F. Sample instruments to evaluate EBP in educational settings
Appendix G. Title short versions of instruments to evaluate EBP in clinical settings
Appendix H. Instruments to assess the EBP competencies and EBP mentorship in any setting.
Glossary
Index.