Creating a Culturally Safe Online Data Collection Instrument to Measure Vaccine Confidence Among Indigenous Youth: Indigenous Consensus Method.

BACKGROUND:  Participating in surveys can shape the perception of participants related to the study topic. Administering a vaccine hesitancy questionnaire can have negative impacts on participants' vaccine confidence. This is particularly true for online and cross-cultural data collection because culturally safe health education to correct misinformation is typically not provided after the administration of an electronic survey. OBJECTIVE:  To create a culturally safe, online, COVID-19 vaccine confidence survey for Indigenous youth designed to collect authentic, culturally relevant data of their vaccine experiences, with a low risk of contributing to further vaccine confusion among participants. METHODS:  Using the Aboriginal Telehealth Knowledge Circle consensus method, a team of academics, health care providers, policy makers, and community partners reviewed COVID-19 vaccine hesitancy surveys used in public health research, analyzed potential risks, and created a framework for electronic Indigenous vaccine confidence surveys as well as survey items. RESULTS:  The framework for safer online survey items is based on 2 principles, a first do-no-harm approach and applying a strengths-based lens. Relevant survey domains identified in the process include sociodemographic information, participants' connection to their community, preferred sources for health information, vaccination uptake among family members and peers, as well as personal attitudes toward vaccines. A total of 44 survey items were developed, including 5 open-ended items to improve the authenticity of the data and the analysis of the experiences of Indigenous youth. CONCLUSIONS:  Using an Indigenous consensus method, we have developed an online COVID-19 vaccine confidence survey with culturally relevant domains and reduced the risk of amplifying misinformation and negative impacts on vaccine confidence among Indigenous participants. Our approach can be adapted to other online survey development in collaboration with Indigenous communities.

Surgical Handover Core Outcome Measures (SH-CORE): a protocol for the development of a core outcome set for trials in surgical handover.

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. ETHICS AND DISSEMINATION: 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. DISCUSSION: 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. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) initiative 2675.  http://www.comet-initiative.org/Studies/Details/2675 .

Recent advances and challenges in protein complex model accuracy estimation.

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.

Glossary of healthcare pathways: a methodological approach involving a transdisciplinary team in public health.

Introduction: The healthcare pathway is at the heart of public health organization concerns, but communication between the various players can be an obstacle. This work, produced by a French transdisciplinary team, offers a methodological approach based on formalized consensus to elaborate a glossary of healthcare pathways. A two-steps procedure was elaborated, including a double rounded Delphi method to formalize expert consensus, and two groups of experts: a workgroup and a review group. Methods: The workgroup provided a list of words or expressions that, in their opinion, described, evaluated or compared the healthcare pathways for patients, caregivers or regulators. The review group checked this list and added or deleted words or expressions. Then, definitions were added by the workgroup based into account three dimensions: official, academic and from the field. The review group validated the definitions and provided complementary proposals if needed. Results: After pooling the list of words proposed by each of the six members of the working group, 417 words/expressions were ranked. After the two rounds of evaluation, 294 words/expressions were rated "appropriate" and were analyzed by the review group. This group, after two rounds of evaluation, agreed on 263 words/expressions that were transmitted to the working group who defined them. These definitions were rated by the review group. The first round of evaluation established 195 definitions as being appropriated whereas 68 definitions were amended by the review group. Conclusion: This glossary supports transdisciplinary communication, reduces the extent of variations in practice and optimizes decision-making. International debate on all aspects might be strengthened by an improved understanding of the concept of health pathway.

Development of best practice guidelines for clinical and community service providers to prevent suicide in LGBTQA+ young people: A Delphi expert consensus study.

OBJECTIVE: The aim of this study was to develop best practice guidelines for preventing suicide and reducing suicidal thoughts and behaviours in LGBTQA+ young people (lesbian, gay, bisexual, trans, queer/questioning, asexual, and those of other diverse sexualities and genders) within clinical and community service settings in Australia. METHODS: We conducted a Delphi expert consensus study. A systematic literature search and interviews with key informants informed an initial 270-item questionnaire. Two expert panels completed the questionnaire, delivered over two rounds: (1) Australian professionals with expertise in LGBTQA+ mental health/suicide prevention and (2) Australian LGBTQA+ young people aged 14-25 with lived experience of suicidal thoughts and/or behaviours. Items endorsed as 'essential' or 'important' by >80% of both expert panels were included in the guidelines. RESULTS: A total of 115 people participated in the Delphi process; n = 52 professionals completed Round 1, and n = 42 completed Round 2; n = 63 LGBTQA+ young people completed Round 1, and n = 50 completed Round 2. A total of 290 items were included in the guidelines and grouped into: (1) general principles for creating an affirming and inclusive environment for LGBTQA+ young people; (2) assessing suicide risk and working with suicidal LGBTQA+ young people; (3) considerations for specific LGBTQA+ populations; and (4) advocating for LGBTQA+ young people. CONCLUSION: These guidelines are the first of their kind in Australia. They provide practical support to service providers regardless of prior training in LGBTQ+ identities or mental health, with the aim of reducing suicidal thoughts and behaviours, and preventing suicide, in LGBTQA+ young people.

How well did the consensus methods apply in the guideline development of traditional Chinese medicine: a web-based survey in China.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Lessons learned from a study based on the AHP method for the assessment of sustainability in neighborhoods.

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.

Identifying the research priorities for schema therapy: A Delphi consensus study.

Despite the popularity of schema therapy, there exist several important gaps in research on the schema therapy model and its effectiveness. The number of gaps makes it difficult to determine the research areas of the highest strategic priority to advance schema therapy. The objective of this study was to establish consensus among schema therapy clinicians and researchers on the priority areas for future schema therapy research. A panel of experts in schema therapy (43 clinicians and 13 researchers) participated in a Delphi consensus study. The research areas rated were developed by interviewing the founder of schema therapy, Jeffrey Young, conducting a focus group with the executive board of the International Society for Schema Therapy and screening recent reviews on schema therapy for recommendations for future research. The panel rated 81 research areas in terms of priority across three rounds. Nineteen research areas were rated by 75% of the panel as 'Very high priority' or 'High priority'. These priorities reflected four broad themes: (1) schema therapy constructs and measures, (2) the theoretical assumptions underlying schema therapy, (3) schema therapy and theory in relation to different contexts and outcomes and (4) schema therapy effectiveness and mechanisms of change. The findings are important for establishing a clear research agenda for the future of schema therapy.

A consensus building study to define the role of a 'clinical' pharmacy technician in a Primary Care Network environment in England.

OBJECTIVE: To define criteria of the role of a clinical pharmacy technician that can be applied to the Primary Care Network environment in England. METHOD: Consensus building study using Delphi methodology conducted in three stages: Stage 1: topic generation from a literature review; Stage 2: Delphi process via Jisc Online Surveys; Stage 3: analysis and presentation of identified topics. KEY FINDINGS: A consensus-defined list of 61 criteria appropriate for the role description of a clinical pharmacy technician across all healthcare sectors was derived. This was refined to 35 criteria considered most important to the role of a clinical pharmacy technician working in a Primary Care Network environment. A qualitative analysis of expert panel comments identified the importance of defining the level at which a pharmacy technician conducts each element of the role, suggesting they would be working at an 'advanced' level. Due to the advanced nature of this role, day-to-day supervision would be less than that of a pharmacy technician, and usually conducted by a pharmacist. This research supports existing international literature that a clinical pharmacy technician role releases capacity for other healthcare professionals to focus on more complex patient cases. CONCLUSION: This research has provided a defined list of criteria considered appropriate for the role description of a clinical pharmacy technician. The need to evidence levels of pharmacy technician practice against recognised competency frameworks alongside clear role descriptors was noted. This study adds to the limited international research about pharmacy technician roles and supports the International Pharmaceutical Federation Pharmaceutical workforce development goals.

The CORE-KDT study: a mixed methods protocol to establish core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy.

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. DISCUSSION: 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.

Emergency department opioid discharge instructions: a multidisciplinary national Delphi study.

OBJECTIVES: Currently, there are no Canadian guidelines for discharge instruction to be given to patients receiving an opioid prescription in the ED. This likely contributes to inadequate discharge instructions for these potentially dangerous medications. The principal goal of this study was to develop an interdisciplinary Canadian consensus regarding important concepts to be included in written opioid discharge instructions within the ED setting. METHODS: We conducted a modified Delphi study between May and August 2021. The national multidisciplinary panel consisted of 23 healthcare professionals and one patient partner. The survey consisted of 19 initial concepts developed after a review of the literature and a meeting with local experts. The panel added four new concepts after the first survey round. Three rounds of online surveys were distributed in total. Panel consensus was defined a priori as a disagreement index score less than 1, in accordance with the RAND/UCLA Appropriateness Method. RESULTS: We achieved a 100% response rate in round one and a 96% response rate in rounds two and three of our Delphi study. There was group consensus (disagreement index = 0.66, median importance = 9) that all patients receiving opioid prescriptions from the ED should receive written discharge instructions. The interdisciplinary panel arrived at a consensus on 21/23 concepts for ED opioid discharge instructions. The concepts with the highest level of agreement were related to minimizing the use of the prescribed opioid medication and opioid use safety (mixing with drugs/alcohol, storage, and impairment). CONCLUSION: This Delphi study with a national, multidisciplinary panel achieved consensus on 21 concepts that should be included in written discharge instructions to patients receiving an opioid prescription upon discharge from the ED.

RéSUMé: OBJECTIFS: Actuellement, il n'y a pas de lignes directrices canadiennes sur les instructions de sortie à donner aux patients qui reçoivent une ordonnance d'opioïdes aux urgences. Cela contribue probablement à des instructions de sortie inadéquates pour ces médicaments potentiellement dangereux. L'objectif principal de cette étude était d'établir un consensus canadien interdisciplinaire sur les concepts importants à inclure dans les directives écrites de sortie des opioïdes dans le contexte des urgences. MéTHODES: Nous avons mené une étude Delphi modifiée entre mai et août 2021. Le comité national multidisciplinaire était composé de 23 professionnels de la santé et d'un patient partenaire. L'enquête comprenait 19 concepts initiaux développés après un examen de la littérature et une réunion avec des experts locaux. Le panel a ajouté quatre nouveaux concepts après la première ronde d'enquête. Trois séries de sondages en ligne ont été distribuées au total. Le consensus du panel a été défini a priori comme un indice de désaccord inférieur à 1, conformément à la méthode de pertinence RAND/UCLA. RéSULTATS: Nous avons atteint un taux de réponse de 100 % au premier tour et un taux de réponse de 96 % aux deuxième et troisième tours de notre étude Delphi. Il y avait un consensus de groupe (indice de désaccord = 0,66, importance médiane = 9) sur le fait que tous les patients recevant une ordonnance d'opioïdes aux urgences devraient recevoir des instructions écrites à la sortie de l'hôpital. Le groupe interdisciplinaire est parvenu à un consensus sur les concepts 21/23 pour les instructions de sortie d'opioïdes aux urgences. Les concepts ayant fait l'objet du plus haut niveau d'entente étaient liés à la réduction de l'utilisation des médicaments opioïdes prescrits et à la sécurité de l'utilisation des opioïdes (mélange avec les drogues/alcool, stockage et affaiblissement des facultés). CONCLUSION: Cette étude Delphi avec un panel national multidisciplinaire a permis de parvenir à un consensus sur 21 concepts qui devraient être inclus dans les instructions écrites de sortie aux patients recevant une ordonnance d'opioïdes à leur sortie de l'urgence.

Perceived impact of nurse turnover on the organization: A Delphi study on managers of nursing.

AIMS: The study aimed to identify the aspects and items of nurse turnover impact on organizations as perceived by nursing management. BACKGROUND: Turnover rate does not capture the extent to which an organization is affected by turnover. Another indicator is required to assess the control status of turnover impact. METHODS: A Delphi study was conducted in 2021, where 2670 managers of nursing at 712 hospitals were asked to complete the survey three times. Factor analysis was conducted on these items for which a consensus was reached. RESULTS: Overall, 232 managers who responded multiple times, including the third survey, were included in the analysis. Consensus was reached for 36 items affected by turnover and considered important for nursing management. Using exploratory factor analysis, the following six factors were extracted: quality of nursing care, physical and mental health of nursing staff, workload and working conditions of nursing staff, relationships among nursing staff members, sense of responsibility among nursing staff, and cost and benefit of hiring replacement personnel. CONCLUSIONS: Six factors consisting of 36 items were extracted that can be used to assess the impact of nurse turnover. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers can assess the status of the organization more appropriately by understanding the factors that impact nurse turnover in vaious facilitites and look at strategies to overcome the impact on nurse staffing.

A Cognitive Sample Consensus Method for the Stitching of Drone-Based Aerial Images Supported by a Generative Adversarial Network for False Positive Reduction.

When using drone-based aerial images for panoramic image generation, the unstableness of the shooting angle often deteriorates the quality of the resulting image. To prevent these polluting effects from affecting the stitching process, this study proposes deep learning-based outlier rejection schemes that apply the architecture of the generative adversarial network (GAN) to reduce the falsely estimated hypothesis relating to a transform produced by a given baseline method, such as the random sample consensus method (RANSAC). To organize the training dataset, we obtain rigid transforms to resample the images via the operation of RANSAC for the correspondences produced by the scale-invariant feature transform descriptors. In the proposed method, the discriminator of GAN makes a pre-judgment of whether the estimated target hypothesis sample produced by RANSAC is true or false, and it recalls the generator to confirm the authenticity of the discriminator's inference by comparing the differences between the generated samples and the target sample. We have tested the proposed method for drone-based aerial images and some miscellaneous images. The proposed method has been shown to have relatively stable and good performances even in receiver-operated tough conditions.

Identifying priorities, directions and a vision for Indigenous mental health using a collaborative and consensus-based facilitation approach.

BACKGROUND: Mental health disparities between Indigenous and non-Indigenous people in Canada are related to underlying economic, social, and political inequities that are legacies of colonization and the oppression of Indigenous cultures. It also widely acknowledged that mental health services currently available may not be culturally appropriate in supporting the health needs of Indigenous Canadians. A two-day Indigenous mental health forum examined mental health needs and gaps among Indigenous communities across the Regional Municipality of Wood Buffalo (RMWB) on Treaty 8 territory, in northern Alberta, Canada. This paper outlines the insights generated by stakeholder engagement at the forum to identify and prioritize directions for Indigenous mental health and build a vision and strategy for improving mental health services and programs for the region's diverse Indigenous population. METHODS: We applied a modified nominal group technique (NGT) consensus method embedded within Indigenous knowledge to determine key priorities and directions for Indigenous-focused mental health and synthesize information from discussions that occurred at the forum. Following the NGT, a participatory community visioning exercise was conducted with participants to develop a vision, guiding principles, and components of an action plan for an Indigenous mental health strategy for the RMWB. RESULTS: Four key themes for setting priorities and directions for Indigenous mental health emerged from roundtable group discussions: 1) understand the realities of mental health experiences for Indigenous peoples, 2) design a holistic and culturally rooted mental health system, 3) foster cross-sectoral engagement and collaboration on mental health service delivery, and 4) focus on children and youth. The community visioning exercise helped stakeholders to visualize a direction or path forward for addressing existing gaps in the mental health system and opportunities for strengthening Indigenous mental health in the region. CONCLUSIONS: Forum participants described mental health and well-being around holistic concepts of social and emotional well-being. Addressing Indigenous mental health and wellness involves multi-sectoral action in various settings including community and school through programs, policies, and other interventions that promote mental health for all Indigenous peoples, as well as for those at greater risk such as children and youth.

Preparing, conducting, and analyzing Delphi surveys: Cross-disciplinary practices, new directions, and advancements.

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.

Identification of public health priorities, barriers, and solutions for Kuwait using the modified Delphi method for stakeholder consensus.

The rapid modernization and economic developments in Kuwait, have been accompanied by substantial lifestyle changes such as unhealthy diet and physical inactivity. These modifiable behaviours have contributed to increased rates of non-communicable diseases including diabetes and cardiovascular diseases. Delphi Consensus Method was implemented in the current study to draw stakeholders from all sectors together to develop a consensus on the major public health priorities, barriers and solutions. The process involves administration of a series of questions to selected stakeholders through an iterative process that ends when a consensus has been reached among participants. Results of the iteration process identified obesity, diabetes, cardiovascular diseases along with lack of enforcement of laws and regulation as priority health issues. Results also identified lack of national vision for the development of a public health system, lack of multidisciplinary research investigating sources of disease and methods of prevention and improving efficiency with existing resources in implementation and efficiency as the main barriers identified were. Solutions suggested included investing in healthcare prevention, strengthening communication between all involved sectors through intersectoral collaboration, awareness at the primary healthcare setting and use of electronic health records. The results offer an important opportunity for stakeholders in Kuwait to tackle these priority health issues employing the suggested approaches and solution.

scConsensus: combining supervised and unsupervised clustering for cell type identification in single-cell RNA sequencing data.

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 .

Development of a Core Outcome Set for Clinical Trials in Non-infectious Uveitis of the Posterior Segment.

PURPOSE: 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. DESIGN: Mixed-methods study design comprising a systematic review and qualitative study followed by a 2-round Delphi exercise and face-to-face consensus meeting. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURE: Items recommended for inclusion in the COS for NIU-PS. RESULTS: 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. CONCLUSIONS: 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.

A Glance into MTHFR Deficiency at a Molecular Level.

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, non-RAND modified Delphi, RAND/UCLA appropriateness method and a novel group awareness and consensus methodology for consensus measurement: a systematic literature review.

INTRODUCTION: Increasing demand for reliable evidence in patient care and its delivery has necessitated the development of several approaches for generating quality evidence. In particular, the solicitation of expert opinion has been recognised as a reliable data collection method. However, there are variations and limitations in study approaches using expert opinion as a method of data collection, thereby necessitating the development of a standardised, novel consensus method. METHODS: A systematic literature review was conducted to assess the characteristics of all studies utilising a "Delphi" or "Modified Delphi" methods between January 2008 and December 2018. A search framework was developed, and the review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In total, 764 studies met the study inclusion and exclusion criteria and were included in the review. Heterogeneity on core defining characteristics of the constituent study types was observed in this control group. These 764 studies were compared against the four case studies using the Jandhyala method. Four key themes were identified and discussed: Assessment of Forced or Observed consensus, Assessment and reporting of item Awareness and advisor awareness, Minimum expert engagement profile, and Efficiency of Minimum Engagement Profile. CONCLUSIONS: Existing consensus methodologies have undergone significant modifications by successive authors over time, including ones contradicting core principles where an original method had been defined. The Jandhyala method for generating group consensus and awareness is unique in observing consensus and measuring awareness of subject matter across experts. The Jandhyala method also improves upon the traditional Delphi-style methodologies, through the introduction of new insights into awareness of subject matter in the expert group. A wider application of the Jandhyala method is required to corroborate findings from this research.