Endometrial Cancer Molecular Characterization: The Key to Identifying High-Risk Patients and Defining Guidelines for Clinical Decision-Making?
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SUBMITTER: Baiden-Amissah REM
PROVIDER: S-EPMC8391655 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Infertility is a complex condition affecting millions of couples worldwide. The current definition of infertility, based on clinical criteria, fails to account for the molecular and cellular changes that may occur during the development of infertility. Recent advancements in sequencing technology and single-cell analysis offer new opportunities to gain a deeper understanding of these changes. The endometrium has a potential role in infertility and has been extensively studied to identify gene expression profiles associated with (impaired) endometrial receptivity. However, limited overlap among studies hampers the identification of relevant downstream pathways that could play a role in the development of endometrial-related infertility. To address these challenges, we propose sequencing the endometrial transcriptome of healthy and infertile women at the single-cell level to consistently identify molecular signatures. Establishing consensus on physiological patterns in endometrial samples can aid in identifying deviations in infertile patients. A similar strategy has been used with great success in cancer research. However, large collaborative initiatives, international uniform protocols of sample collection and processing are crucial to ensure reliability and reproducibility. Overall, the proposed approach holds promise for an objective and accurate classification of endometrial-based infertility and has the potential to improve diagnosis and treatment outcomes.
| S-EPMC10833067 | biostudies-literature
Project description:BackgroundWhile shared decision making (SDM) and adherence to clinical practice guidelines (CPGs) are important, some believe they are incompatible. This study explored the mutual influence between physicians' intention to engage in SDM and their intention to follow CPGs.MethodsEmbedded within a clustered randomized trial to assess the impact of training physicians in SDM about using antibiotics to treat acute respiratory tract infections, this study evaluated physicians' intentions to both engage in SDM and follow CPGs. A self-administered questionnaire based on the theory of planned behavior evaluated both behavioral intentions and their respective determinants (attitude, subjective norm and perceived behavioral control) at study entry and exit. We used path analysis to explore the relationships between the intentions. We conducted statistical analyses using the maximum likelihood method and the variance-covariance matrix. Goodness of fit indices encompassed the chi-square statistic, the comparative fit index and the root mean square error of approximation.ResultsWe analyzed 244 responses at entry and 236 at exit. In the control group, at entry we observed that physicians' intention to engage in SDM (r?=?0, t?=?0.03) did not affect their intention to follow CPGs; however, their intention to follow CPGs (r?=?-0.31 t?=?-2.82) did negatively influence their intention to engage in SDM. At exit, neither behavioral intention influenced the other. In the experimental group, at entry neither behavioral intention influenced the other; at exit, the intention to engage in SDM still did not influence the intention to use CPGs, although the intention to follow CPGs (r?=?-0.15 t?=?-2.02) slightly negatively influenced the intention to engage in SDM, but this was not clinically significant.ConclusionPhysicians' intention to engage in SDM does not affect their intention to adopt CPGs even after SDM training. Physicians' intention to adopt CPGs had no clinically significant influence on intention to engage in SDM.Trial registrationClinicalTrials.gov NCT01116076.
| S-EPMC3634782 | biostudies-literature
Project description:ImportanceShared decision-making (SDM) is a key component of the provision of ethical care, but prior reviews have indicated that clinical practice guidelines seldom promote or facilitate SDM. It is currently unknown whether these findings extend to contemporary cardiovascular guidelines.ObjectiveTo identify and characterize integration of SDM in contemporary cardiovascular guideline recommendations using a systematic classification system.Design, setting, and participantsThis cross-sectional study assessed the latest guidelines or subsequent updates that included pharmacotherapy recommendations and were published between January 2012 and December 2022 by the American College of Cardiology (ACC), Canadian Cardiovascular Society (CCS), and European Society of Cardiology (ESC). Data were analyzed from February 21 to July 21, 2023.Main outcomes and measuresAll pharmacotherapy recommendations were identified within each guideline. Recommendations that incorporated SDM were rated according to a systematic rating framework to evaluate the quality of SDM incorporation based on directness (range, 1-3; assessing whether SDM was incorporated directly and impartially into the recommendation's text, with 1 indicating direct and impartial incorporation of SDM into the recommendation's text) and facilitation (range, A-D; assessing whether decision aids or quantified benefits and harms were provided, with A indicating that a decision aid quantifying benefits and harms was provided). The proportion of recommendations incorporating SDM was also analyzed according to guideline society and category (eg, general cardiology, heart failure).ResultsAnalyses included 65 guideline documents, and 33 documents (51%) incorporated SDM either in a general statement or within specific recommendations. Of 7499 recommendations, 2655 (35%) recommendations addressed pharmacotherapy, and of these, 170 (6%) incorporated SDM. By category, general cardiology guidelines contained the highest proportion of pharmacotherapy recommendations incorporating SDM (86 of 865 recommendations [10%]), whereas heart failure and myocardial disease contained the least (9 of 315 recommendations [3%]). The proportion of pharmacotherapy recommendations incorporating SDM was comparable across societies (ACC: 75 of 978 recommendations [8%]; CCS: 29 of 333 recommendations [9%]; ESC: 67 of 1344 recommendations [5%]), with no trend for change over time. Only 5 of 170 SDM recommendations (3%) were classified as grade 1A (impartial recommendations for SDM supported by a decision aid), whereas 114 of 170 recommendations (67%) were grade 3D (SDM mentioned only in supporting text and without any tools or information to facilitate SDM).Conclusions and relevanceIn this cross-sectional study across guidelines published by 3 major cardiovascular societies over the last decade, 51% of guidelines mentioned the importance of SDM, yet only 6% of recommendations incorporated SDM in any form, and fewer adequately facilitated SDM.
| S-EPMC10485733 | biostudies-literature
Project description:ObjectivesTo (1) provide an up-to-date overview of shared decision making (SDM)-models, (2) give insight in the prominence of components present in SDM-models, (3) describe who is identified as responsible within the components (patient, healthcare professional, both, none), (4) show the occurrence of SDM-components over time, and (5) present an SDM-map to identify SDM-components seen as key, per healthcare setting.DesignSystematic review.Eligibility criteriaPeer-reviewed articles in English presenting a new or adapted model of SDM.Information sourcesAcademic Search Premier, Cochrane, Embase, Emcare, PsycINFO, PubMed, and Web of Science were systematically searched for articles published up to and including September 2, 2019.ResultsForty articles were included, each describing a unique SDM-model. Twelve models were generic, the others were specific to a healthcare setting. Fourteen were based on empirical data, 26 primarily on analytical thinking. Fifty-three different elements were identified and clustered into 24 components. Overall, Describe treatment options was the most prominent component across models. Components present in >50% of models were: Make the decision (75%), Patient preferences (65%), Tailor information (65%), Deliberate (58%), Create choice awareness (55%), and Learn about the patient (53%). In the majority of the models (27/40), both healthcare professional and patient were identified as actors. Over time, Describe treatment options and Make the decision are the two components which are present in most models in any time period. Create choice awareness stood out for being present in a markedly larger proportion of models over time.ConclusionsThis review provides an up-to-date overview of SDM-models, showing that SDM-models quite consistently share some components but that a unified view on what SDM is, is still lacking. Clarity about what SDM constitutes is essential though for implementation, assessment, and research purposes. A map is offered to identify SDM-components seen as key.Trial registrationPROSPERO registration CRD42015019740.
| S-EPMC6937101 | biostudies-literature
Project description:Substandard drugs are a major public health issue worldwide. Key person such as the Qualified Person in China and Europe is responsible for rejecting substandard drugs during the manufacturing stage. This study applies the Hunt-Vitell ethical decision-making model to study their rejection intentions on substandard drugs. Using the experimental vignette methodology, two scenarios were developed to represent different levels of deviation from regulations in pharmaceutical manufacturing. Responses from 204 Chinese key persons show a decline in deontology, ethical judgment, and rejection intention, and an increase in teleology in the minor deviation scenario, in comparison with the major deviation scenario. The results from the two scenarios show that the Hunt-Vitell ethical decision-making model is well fitted to explain substandard drug rejection intentions. Organizational and occupational commitments have a significant positive impact on deontological evaluation. Whereas, occupational commitments have a significant negative impact on teleological evaluation. This study suggests that strengthening occupational commitment can significantly affect key person's rejection intentions of substandard drugs.
| S-EPMC7081989 | biostudies-literature
Project description:IntroductionWe aimed to systematically evaluate quality of shared decision-making (SDM) in colorectal cancer (CRC) screening clinical practice guidelines (CPGs) and consensus statements (CSs).MethodsSearch for CRC screening guidances was from 2010 to November 2021 in EMBASE, Web of Science, MEDLINE, Scopus and CDSR, and the World Wide Web. Three independent reviewers and an arbitrator rated the quality of each guidance using a SDM quality assessment tool (maximum score: 31). Reviewer agreement was 0.88.ResultsSDM appeared in 41/83 (49.4%) CPGs and 9/19 (47.4%) CSs. None met all the quality criteria, and 51.0% (52/102) failed to meet any quality items. Overall compliance was low (mean 1.63, IQR 0-2). Quality was better in guidances published after 2015 (mean 1, IQR 0-3 vs. mean 0.5, IQR 0-1.5; p = 0.048) and when the term SDM was specifically reported (mean 4.5, IQR 2.5-4.5 vs. mean 0.5, IQR 0-1.5; p < 0.001). CPGs underpinned by systematic reviews showed better SDM quality than consensus (mean 1, IQR 0-3 vs. mean 0, IQR 0-2, p = 0.040).ConclusionSDM quality was suboptimal and mentioned in less than half of the guidances, and recommendations were scarce. Guideline developers should incorporate evidence-based SDM recommendations in guidances to underpin the translation of evidence into practice.
| S-EPMC9786598 | biostudies-literature
Project description:Importance: Early mobilization, out-of-bed activity, is a component of acute stroke unit care; however, stroke patient heterogeneity requires complex decision-making. Clinically credible and applicable CPGs are needed to support and optimize the delivery of care. In this study, we are specifically exploring the role of clinical practice guidelines to support individual patient-level decision-making by stroke clinicians about early mobilization post-stroke. Methods: Our study uses a novel, two-pronged approach. (1) A review of CPGs containing recommendations for early mobilization practices published after 2015 was appraised using purposely selected items from the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence (AGREE-REX) tool relevant to decision-making for clinicians. (2) A cross-sectional study involving semi-structured interviews with Australian expert stroke clinicians representing content experts and CPG target users. Every CPG was independently assessed against the AGREE-REX standard by two reviewers. Expert stroke clinicians, invited via email, were recruited between June 2019 to March 2020.The main outcomes from the review was the proportion of criteria addressed for each AGREE-REX item by individual and all CPG(s). The main cross-sectional outcomes were the distributions of stroke clinicians' responses about the utility of CPGs, specific areas of uncertainty in early mobilization decision-making, and suggested parameters for inclusion in future early mobilization CPGs. Results: In 18 identified CPGs, many did not adequately address the "Evidence" and "Applicability to Patients" AGREE-REX items. Out of 30 expert stroke clinicians (11 physicians [37%], 11 physiotherapists [37%], 8 nurses [26%]; median [IQR] years of experience, 14 [10-25]), 47% found current CPGs "too broad or vague," while 40% rely on individual clinical judgement and interpretation of the evidence to select an evidence-based choice of action. The areas of uncertainty in decision-making revealed four key suggestions: (1) more granular descriptions of patient and stroke characteristics for appropriate tailoring of decisions, (2) clear statements about when clinical flexibility is appropriate, (3) detailed description of the intervention dose, and (4) physical assessment criteria including safety parameters. Conclusions: The lack of specificity, clinical applicability, and adaptability of current CPGs to effectively respond to the heterogeneous clinical stroke context has provided a clear direction for improvement.
| S-EPMC7901923 | biostudies-literature
Project description:OBJECTIVES:It is unclear how guidelines panelists discuss and consider factors (criteria) that are formally and not formally included in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. To describe the use of decision criteria, we explored how panelists adhered to GRADE criteria and sought to identify any emerging non-GRADE criteria when the panelists used the Evidence to Decision (EtD) framework as part of GRADE application. STUDY DESIGN AND SETTING:We used conventional and summative qualitative analyses to identify themes emerging from face-to-face, panel meeting discussions. Forty-eight members from 12 countries participated in the development of five guidelines for the management of venous thromboembolism by the American Society of Hematology. RESULTS:Ten themes corresponded to the GRADE approach and represented all panel discussions. Over half (53%) of the total panel discussions concerned the use of research evidence. When evidence was considered sufficient and clear, the decision-making process proved rapid. CONCLUSION:The GRADE EtD framework provides structure to guidelines panel meetings, and ensures that the panelists consider all established formal GRADE criteria as they decide on the recommendation text, strength, and direction (for or against an intervention). This is the first study assessing the use of GRADE's EtD framework during real-time guidelines development using panel discussions. Given the widespread use of GRADE, this study provides important information for practice recommendations generated when guidelines panels explicitly follow, in a transparent and systematic manner, the structured GRADE EtD framework. By recognizing the extent to which panels discuss and consider GRADE and other (non-GRADE) criteria for producing guideline recommendations, we are one step closer to understanding the decision-making process in panels that use a structured framework such as the GRADE EtD framework.
| S-EPMC7275375 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:The determinants of guideline panels' recommendations remain uncertain. The objective of this study was to investigate factors considered by members of 8 panels convened by the American Society of Hematology (ASH) to develop guidelines using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. STUDY DESIGN AND SETTING:Web-based survey of the participants in the ASH guidelines panels. ANALYSIS:two-level hierarchical, random-effect, multivariable regression analysis to explore the relation between GRADE and non-GRADE factors and strength of recommendations (SOR). RESULTS:In the primary analysis, certainty in evidence [OR = 1.83; (95CI% 1.45-2.31)], balance of benefits and harms [OR = 1.49 (95CI% 1.30-1.69)] and variability in patients' values and preferences [OR = 1.47 (95CI% 1.15-1.88)] proved the strongest predictors of SOR. In a secondary analysis, certainty of evidence was associated with a strong recommendation [OR = 3.60 (95% CI 2.16-6.00)] when panel members recommended "for" interventions but not when they made recommendations "against" interventions [OR = 0.98 (95%CI: 0.57-1.8)] consistent with "yes" bias. Agreement between individual members and the group in rating SOR varied (kappa ranged from -0.01 to 0.64). CONCLUSION:GRADE's conceptual framework proved, in general, to be highly associated with SOR. Failure of certainty of evidence to be associated with SOR against an intervention, suggest the need for improvements in the process.
| S-EPMC7268742 | biostudies-literature
Project description:Two major glycosaminoglycan types, heparan sulfate (HS) and chondroitin sulfate (CS), control many aspects of development and physiology in a type-specific manner. HS and CS are attached to core proteins via a common linker tetrasaccharide, but differ in their polymer backbones. How core proteins are specifically modified with HS or CS has been an enduring mystery. By reconstituting glycosaminoglycan biosynthesis in vitro, we establish that the CS-initiating N-acetylgalactosaminyltransferase CSGALNACT2 modifies all glycopeptide substrates equally, whereas the HS-initiating N-acetylglucosaminyltransferase EXTL3 is selective. Structure-function analysis reveals that acidic residues in the glycopeptide substrate and a basic exosite in EXTL3 are critical for specifying HS biosynthesis. Linker phosphorylation by the xylose kinase FAM20B accelerates linker synthesis and initiation of both HS and CS, but has no effect on the subsequent polymerisation of the backbone. Our results demonstrate that modification with CS occurs by default and must be overridden by EXTL3 to produce HS.
| S-EPMC10570366 | biostudies-literature