BACKGROUND: Surgical handover is associated with a significant risk of care failures. Existing research displays methodological deficiencies and little consensus on the outcomes that should be used to evaluate interventions in this area. This paper reports a protocol to develop a core outcome set (COS) to support standardisation, comparability, and evidence synthesis in future studies of surgical handover between doctors.
METHODS: This study adheres to the Core Outcome Measures in Effectiveness Trials (COMET) initiative guidance for COS development, including the COS-Standards for Development (COS-STAD) and Reporting (COS-STAR) recommendations. It has been registered prospectively on the COMET database and will be led by an international steering group that includes surgical healthcare professionals, researchers, and patient and public partners. An initial list of reported outcomes was generated through a systematic review of interventions to improve surgical handover (PROSPERO: CRD42022363198). Findings of a qualitative evidence synthesis of patient and public perspectives on handover will augment this list, followed by a real-time Delphi survey involving all stakeholder groups. Each Delphi participant will then be invited to take part in at least one online consensus meeting to finalise the COS.
BACKGROUND: This study was approved by the Royal College of Surgeons in Ireland (RCSI) Research Ethics Committee (202309015, 7th November 2023). Results will be presented at surgical scientific meetings and submitted to a peer-reviewed journal. A plain English summary will be disseminated through national websites and social media. The authors aim to integrate the COS into the handover curriculum of the Irish national surgical training body and ensure it is shared internationally with other postgraduate surgical training programmes. Collaborators will be encouraged to share the findings with relevant national health service functions and national bodies.
CONCLUSIONS: This study will represent the first published COS for interventions to improve surgical handover, the first use of a real-time Delphi survey in a surgical context, and will support the generation of better-quality evidence to inform best practice.
BACKGROUND: Core Outcome Measures in Effectiveness Trials (COMET) initiative 2675.  http://www.comet-initiative.org/Studies/Details/2675 .

Estimation of model accuracy plays a crucial role in protein structure prediction, aiming to evaluate the quality of predicted protein structure models accurately and objectively. This process is not only key to screening candidate models that are close to the real structure, but also provides guidance for further optimization of protein structures. With the significant advancements made by AlphaFold2 in monomer structure, the problem of single-domain protein structure prediction has been widely solved. Correspondingly, the importance of assessing the quality of single-domain protein models decreased, and the research focus has shifted to estimation of model accuracy of protein complexes. In this review, our goal is to provide a comprehensive overview of the reference and statistical metrics, as well as representative methods, and the current challenges within four distinct facets (Topology Global Score, Interface Total Score, Interface Residue-Wise Score, and Tertiary Residue-Wise Score) in the field of complex EMA.

Consensus methods are crucial in developing clinical guidelines. Different methods, such as the Delphi and nominal group techniques, are commonly used, but there is a lack of detailed instructions on how to implement them effectively. The survey aims to explore the opinions and attitudes of the chair, panel and working group on the critical elements of the consensus methods during guideline development.
We used a cross-sectional design to conduct this study and sent a structured questionnaire to stakeholders, including the chair, panel members, and working group participants, through the popular mobile phone application WeChat.We selected participants using a combination of purposive and snowball sampling. The questionnaire gathered information on demographics, experiences, opinions, and concerns regarding consensus methods and guideline development.
The sample comprised 290 participants representing 31 provinces or municipalities. Among them, the most significant number of respondents (n = 107, 36.9%) were from Beijing. Most participants, specifically 211 (72.76%), held senior professional titles, while 186 (64.14%) adhered to ongoing guidelines. The Delphi method was the most commonly used consensus method (n = 132, 42.31%), but the respondents had only a preliminary understanding of it (n = 147, 47.12%). The consensus process also revealed the insufficiency of involving pharmacoeconomists, patients, and nurses.
Consensus methods have to be standardised and used consistently in the guideline development process. The findings of this study offer insights into diverse roles and more effective ways to apply the consensus process during guideline development.

The Analytic Hierarchy Process (AHP) is a method that allows complex decisions to be made from impartiality, making it suitable for reaching a consensus among experts seeking to solve a problem. This method has been successfully applied in other investigations, and its use has been extended to several disciplines. This technical paper presents the lessons learned from a study that relied on the AHP method to determine priority aspects for sustainable neighborhoods. The research is developed in three replicable phases. In each of them, aspects that are recommended to be considered are detailed, for example, in the formulation of the hierarchical structure, selection of experts, expert survey design, and information processing for the determination of weights and levels of importance.•The utilization of software to apply the AHP method can help researchers to optimize time and resources.•Social networks proved to be more effective than conventional methods for identifying and contacting experts.•Subjective sustainability issues can be prioritized by expert consensus.

BACKGROUND: A core outcome set defines the minimum outcomes that should be included in clinical trials, audit or practice. The aim being to increase the quality and relevance of research by ensuring consistency in the measurement and reporting of outcomes. Core outcome sets have been developed for a variety of disease states and treatments. However, there is no established set of core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy. This should be developed using a patient-centred approach to ensure the outcomes measured are relevant to patients and clinical practice.
METHODS: This is a mixed methods study of four phases to develop a core outcome set for refractory childhood epilepsy treated with ketogenic diet therapy. In phase 1, a systematic scoping review of the literature will establish which outcomes are measured in trials of refractory epilepsy treated with ketogenic diet therapy. In phase 2, qualitative interviews with parents and carers will aim to identify the outcomes of importance to these stakeholders. Phase 3 will see a comprehensive list of outcomes collated from the first two phases, grouped into domains according to an outcome taxonomy. Phase 4 will invite parents, health care professionals and researchers to participate in a two-round Delphi study to rate the importance of the presented outcomes. Following which, the core outcome set will be ratified at a face to face consensus meeting.
CONCLUSIONS: This study will guide outcome measurement in future studies of childhood epilepsy treated with ketogenic diet therapy and clinical practice through audit and service evaluation.

MTHFR deficiency still deserves an investigation to associate the phenotype to protein structure variations. To this aim, considering the MTHFR wild type protein structure, with a catalytic and a regulatory domain and taking advantage of state-of-the-art computational tools, we explore the properties of 72 missense variations known to be disease associated. By computing the thermodynamic ΔΔG change according to a consensus method that we recently introduced, we find that 61% of the disease-related variations destabilize the protein, are present both in the catalytic and regulatory domain and correspond to known biochemical deficiencies. The propensity of solvent accessible residues to be involved in protein-protein interaction sites indicates that most of the interacting residues are located in the regulatory domain, and that only three of them, located at the interface of the functional protein homodimer, are both disease-related and destabilizing. Finally, we compute the protein architecture with Hidden Markov Models, one from Pfam for the catalytic domain and the second computed in house for the regulatory domain. We show that patterns of disease-associated, physicochemical variation types, both in the catalytic and regulatory domains, are unique for the MTHFR deficiency when mapped into the protein architecture.

Delphi is a scientific method to organize and structure an expert discussion aiming to generate insights on controversial topics with limited information. The technique has seen a rise in publication frequency in various disciplines, especially over the past decades. In April 2021, the term Delphi method yielded 28,200 search hits in Google Scholar for the past five years alone. Given the increasing level of uncertainty caused by rapid technological and social change around the globe, collective expert opinions and assessments are likely to gain even more importance. Therefore, the paper at hand presents technical recommendations derived from a Delphi study that was conducted amid the outbreak of the COVID-19 pandemic in 2020.•The paper comprehensively demonstrates how to prepare, conduct, and analyze a Delphi study. In this regard, it combines several methodological advancements of the recent past (e.g., dissent analyses, scenario analyses) with state-of-the-art impulses from other disciplines like strategic management (e.g., fuzzy clustering), psychology (e.g., sentiment analyses), or clinical trials (e.g., consensus measurement).•By offering insights on the variety of possibilities to exploit Delphi-based data, we aim to support researchers across all disciplines in conducting Delphi studies and potentially expand and improve the method\'s field of application.

BACKGROUND: Clustering is a crucial step in the analysis of single-cell data. Clusters identified in an unsupervised manner are typically annotated to cell types based on differentially expressed genes. In contrast, supervised methods use a reference panel of labelled transcriptomes to guide both clustering and cell type identification. Supervised and unsupervised clustering approaches have their distinct advantages and limitations. Therefore, they can lead to different but often complementary clustering results. Hence, a consensus approach leveraging the merits of both clustering paradigms could result in a more accurate clustering and a more precise cell type annotation.
RESULTS: We present SCCONSENSUS, an [Formula: see text] framework for generating a consensus clustering by (1) integrating results from both unsupervised and supervised approaches and (2) refining the consensus clusters using differentially expressed genes. The value of our approach is demonstrated on several existing single-cell RNA sequencing datasets, including data from sorted PBMC sub-populations.
CONCLUSIONS: SCCONSENSUS combines the merits of unsupervised and supervised approaches to partition cells with better cluster separation and homogeneity, thereby increasing our confidence in detecting distinct cell types. SCCONSENSUS is implemented in [Formula: see text] and is freely available on GitHub at https://github.com/prabhakarlab/scConsensus .

To develop an agreed upon set of outcomes known as a \"core outcome set\" (COS) for noninfectious uveitis of the posterior segment (NIU-PS) clinical trials.
Mixed-methods study design comprising a systematic review and qualitative study followed by a 2-round Delphi exercise and face-to-face consensus meeting.
Key stakeholders including patients diagnosed with NIU-PS, their caregivers, and healthcare professionals involved in decision-making for patients with NIU-PS, including ophthalmologists, nurse practitioners, and policymakers/commissioners.
A long list of outcomes was developed based on the results of (1) a systematic review of clinical trials of NIU-PS and (2) a qualitative study of key stakeholders including focus groups and interviews. The long list was used to generate a 2-round Delphi exercise of stakeholders rating the importance of outcomes on a 9-point Likert scale. The proportion of respondents rating each item was calculated, leading to recommendations of \"include,\" \"exclude,\" or \"for discussion\" that were taken to a face-to-face consensus meeting of key stakeholders at which they agreed on the final COS.
Items recommended for inclusion in the COS for NIU-PS.
A total of 57 outcomes grouped in 11 outcome domains were presented for evaluation in the Delphi exercise, resulting in 9 outcomes directly qualifying for inclusion and 15 outcomes being carried forward to the consensus meeting, of which 7 of 15 were agreed on for inclusion. The final COS contained 16 outcomes organized into 4 outcome domains comprising visual function, health-related quality of life, treatment side effects, and disease control.
This study builds on international work across the clinical trials community and our qualitative research to construct the world\'s first COS for NIU-PS. The COS provides a list of outcomes that represent the priorities of key stakeholders and provides a minimum set of outcomes for use in all future NIU-PS clinical trials. Adoption of this COS can improve the value of future uveitis clinical trials and reduce noninformative research. Some of the outcomes identified do not yet have internationally agreed upon methods for measurement and should be the subject of future international consensus development.

The United Kingdom (UK) is experiencing a general practitioner (GP) workforce retention crisis. Research has focused on investigating why GPs intend to quit, but less is known about the acceptability and effectiveness of policies and strategies to improve GP retention. Using evidence from research and key stakeholder organisations, we generated a set of potential policies and strategies aimed at maximising GP retention and tested their appropriateness for implementation by systematically consulting with GPs.
28 GP Partners and GPs working in national stakeholder organisations from South West England and London were purposively sampled, and asked to take part in a RAND/UCLA Appropriateness Method panel. Panellists were asked to read an evidence briefing summary, and then complete an online survey on two occasions. During each round, participants rated the appropriateness of policies and strategies aimed at improving GP retention using a nine point scale (1 \'extremely inappropriate\' to 9 \'extremely appropriate\'). Fifty-four potential policies and strategies (equating to 100 statements) were tested, focusing on factors influencing job satisfaction (e.g. well-being, workload, incentives and remuneration, flexible working, human resources systems). Ratings were analysed for panel consensus and categorised based on appropriateness (\'appropriate\', \'uncertain\', \'inappropriate\').
12/28 GPs approached agreed to take part, 9/28 completed two rounds of the online survey between February and June 2018. Panellists identified 24/54 policy and strategy areas (41/100 statements) as \'appropriate\'. Examples included providing GP practices \'at risk\' of experiencing GP shortages with a toolkit for managing recruitment and retention, and interventions to facilitate peer support to enhance health and wellbeing, or support portfolio careers. Strategies to limit GP workload, and manage patient demand were also endorsed.
The panel of experienced GPs identified a number of practical ways to improve GP retention through interventions that might enhance job satisfaction and work-life balance. Future research should evaluate the impact of implementing these recommendations.