Modelling clinical narrative as computable knowledge: The NICE computable implementation guidance project.

Introduction: Translating narrative clinical guidelines to computable knowledge is a long-standing challenge that has seen a diverse range of approaches. The UK National Institute for Health and Care Excellence (NICE) Content Advisory Board (CAB) aims ultimately to (1) guide clinical decision support and other software developers to increase traceability, fidelity and consistency in supporting clinical use of NICE recommendations, (2) guide local practice audit and intervention to reduce unwarranted variation, (3) provide feedback to NICE on how future recommendations should be developed. Objectives: The first phase of work was to explore a range of technical approaches to transition NICE toward the production of natively digital content. Methods: Following an initial 'collaborathon' in November 2022, the NICE Computable Implementation Guidance project (NCIG) was established. We held a series of workstream calls approximately fortnightly, focusing on (1) user stories and trigger events, (2) information model and definitions, (3) horizon-scanning and output format. A second collaborathon was held in March 2023 to consolidate progress across the workstreams and agree residual actions to complete. Results: While we initially focussed on technical implementation standards, we decided that an intermediate logical model was a more achievable first step in the journey from narrative to fully computable representation. NCIG adopted the WHO Digital Adaptation Kit (DAK) as a technology-agnostic method to model user scenarios, personae, processes and workflow, core data elements and decision-support logic. Further work will address indicators, such as prescribing compliance, and implementation in document templates for primary care patient record systems. Conclusions: The project has shown that the WHO DAK, with some modification, is a promising approach to build technology-neutral logical specifications of NICE recommendations. Implementation of concurrent computable modelling by multidisciplinary teams during guideline development poses methodological and cultural questions that are complex but tractable given suitable will and leadership.

Which computable biomedical knowledge objects will be regulated? Results of a UK workshop discussing the regulation of knowledge libraries and software as a medical device.

Introduction: To understand when knowledge objects in a computable biomedical knowledge library are likely to be subject to regulation as a medical device in the United Kingdom. Methods: A briefing paper was circulated to a multi-disciplinary group of 25 including regulators, lawyers and others with insights into device regulation. A 1-day workshop was convened to discuss questions relating to our aim. A discussion paper was drafted by lead authors and circulated to other authors for their comments and contributions. Results: This article reports on those deliberations and describes how UK device regulators are likely to treat the different kinds of knowledge objects that may be stored in computable biomedical knowledge libraries. While our focus is the likely approach of UK regulators, our analogies and analysis will also be relevant to the approaches taken by regulators elsewhere. We include a table examining the implications for each of the four knowledge levels described by Boxwala in 2011 and propose an additional level. Conclusions: If a knowledge object is described as directly executable for a medical purpose to provide decision support, it will generally be in scope of UK regulation as "software as a medical device." However, if the knowledge object consists of an algorithm, a ruleset, pseudocode or some other representation that is not directly executable and whose developers make no claim that it can be used for a medical purpose, it is not likely to be subject to regulation. We expect similar reasoning to be applied by regulators in other countries.

Artificial intelligence and clinical decision support: clinicians' perspectives on trust, trustworthiness, and liability.

Artificial intelligence (AI) could revolutionise health care, potentially improving clinician decision making and patient safety, and reducing the impact of workforce shortages. However, policymakers and regulators have concerns over whether AI and clinical decision support systems (CDSSs) are trusted by stakeholders, and indeed whether they are worthy of trust. Yet, what is meant by trust and trustworthiness is often implicit, and it may not be clear who or what is being trusted. We address these lacunae, focusing largely on the perspective(s) of clinicians on trust and trustworthiness in AI and CDSSs. Empirical studies suggest that clinicians' concerns about their use include the accuracy of advice given and potential legal liability if harm to a patient occurs. Onora O'Neill's conceptualisation of trust and trustworthiness provides the framework for our analysis, generating a productive understanding of clinicians' reported trust issues. Through unpacking these concepts, we gain greater clarity over the meaning ascribed to them by stakeholders; delimit the extent to which stakeholders are talking at cross purposes; and promote the continued utility of trust and trustworthiness as useful concepts in current debates around the use of AI and CDSSs.

Enantioselective Catalysis by the Umpolung of Conjugate Acceptors Involving N-Heterocyclic Carbene or Organophosphine 1,4-Addition.

ConspectusConjugate acceptors are one of the most common electrophilic functional groups in organic synthesis. While useful in a diverse range of transformations, their applications are largely dominated by the reactions from which their name is derived (i.e., as an acceptor of nucleophiles in the conjugate position). In 2014, we commenced studies focused on their ability to undergo polarity inversion through the conjugate addition of Lewis base catalysts. The first step in this process provides an enolate, from which the well-developed Rauhut-Currier (RC) and Morita-Baylis-Hillman (MBH) reactions can occur; however, tautomerization to provide a species in which the ß-carbon of the conjugate acceptor can now act as a donor is also possible. When we commenced studies on this topic, reaction designs with this type of species, particularly when accessed using N-heterocyclic carbenes (NHCs), had been reported on only a handful of occasions. Despite a lack of development, conceptually it was felt that reactions taking advantage of polarity switching by Lewis base conjugate addition have a number of desirable features. Perhaps the most significant is the potential to reimagine a ubiquitous functional group as an entirely new synthon, namely, a donor to electrophiles from the conjugate position.Our work has focused on catalysis with both simple conjugate acceptors and also those embedded within more complicated substrates; the latter has allowed a series of cycloisomerizations and annulation reactions to be achieved. In most cases, the reactions have been possible using enantioenriched chiral NHCs or organophosphines as the Lewis base catalysts thereby delivering enantioselective approaches to novel cyclic molecules. While related chemistry can be accessed with either family of catalyst, in all cases reactions have been designed to take advantage of one or the other. In addition, a fine balance exists between reactions that exploit the initially formed enolate and those that involve the polarity-inverted ß-anion. In our studies, this balance is addressed through substrate design, although catalyst control may also be possible. We consider the chemistry discussed in this Account to be in its infancy. Significant challenges remain to be addressed before our broad aim of discovering a universal approach to the polarity inversion of all conjugate acceptors can be achieved. These challenges broadly relate to chemoselectivity with substrates bearing multiple electrophilic functionalities, reliance upon the use of conjugate acceptors, and catalyst efficiency. To address these challenges, advances in catalyst design and catalyst cooperativity are likely required.

Quantification of acceleration as activity counts in ActiGraph wearable.

Digital clinical measures based on data collected by wearable devices have seen rapid growth in both clinical trials and healthcare. The widely-used measures based on wearables are epoch-based physical activity counts using accelerometer data. Even though activity counts have been the backbone of thousands of clinical and epidemiological studies, there are large variations of the algorithms that compute counts and their associated parameters-many of which have often been kept proprietary by device providers. This lack of transparency has hindered comparability between studies using different devices and limited their broader clinical applicability. ActiGraph devices have been the most-used wearable accelerometer devices for over two decades. Recognizing the importance of data transparency, interpretability and interoperability to both research and clinical use, we here describe the detailed counts algorithms of five generations of ActiGraph devices going back to the first AM7164 model, and publish the current counts algorithm in ActiGraph's ActiLife and CentrePoint software as a standalone Python package for research use. We believe that this material will provide a useful resource for the research community, accelerate digital health science and facilitate clinical applications of wearable accelerometry.

Insights from developing and evaluating the NHS blood choices transfusion app to support junior and middle-grade doctor decision making against guidelines.

OBJECTIVES: To: 1. Develop a CE-marked smartphone App to support doctors' concordance with transfusion guidelines in non-bleeding adult patients, emphasising informed consent and anaemia management. 2. Test App accuracy and potential to improve user decisions. BACKGROUND: Studies have shown inappropriate use of blood components and that most junior doctors own smartphones with medical apps. METHODS: A multidisciplinary team developed App screens and logic through an iterative process based on national guidelines. Thirty medical or surgical transfusion scenarios were developed based on national guidelines and each sent to Consultant Haematologist experts in Transfusion Medicine. To obtain a clinical consensus and exclude ambiguous scenarios, their independent decisions and associated certainty were compared. The consensus clinical decision was then compared with guidance from the App. To explore potential App impact on simulated user decisions, 26 junior doctors responded to five transfusion scenarios before and after access to the App. RESULTS: The Blood Choices App agreed with 91% (95% CI: 72%-99%) of expert decisions with a sensitivity of 100% (69% to 100%) and specificity of 85% (55%-98%). Excluding one malfunction scenario, the App had the potential to increase correct decisions by junior doctors from 83% (73%-90%) pre-App use to 96% (88%-99%) post (p-value 0.013), with 90% (67%-99%) saying they would use it in practice. CONCLUSIONS: Transfusion guidelines can be converted into an App with potential to improve guideline concordance. However, evaluating such Apps is essential to understand their limitations, detect malfunctions and prevent harm.

Enantioselective Synthesis of Pyrrolidines by a Phosphine-Catalyzed γ-Umpolung/ß-Umpolung Cascade.

Herein, we report an enantioselective catalytic annulation of electron-poor allenes with aminocrotonates. The reaction proceeds by the umpolung γ-amination of the allenoate and ß-umpolung intramolecular conjugate addition. The reaction provides ready access to pyrrolidines using a homochiral phosphepine catalyst, which allows most products to form in good yields (55-85%) with ≥95:5 er and ≥4:1 dr. An assisted tandem-catalytic variant is also viable, and mechanistic studies supporting the proposed reaction pathway are reported.

An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.

BACKGROUND: The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage. FINDINGS: The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage. CONCLUSION: The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.

Redox Isomerization/(3+2) Allenoate Annulation by Auto-Tandem Phosphine Catalysis.

A phosphine-catalyzed approach to pyrrolines has been developed that involves two mechanistically unlinked catalytic processes. The first involves the redox isomerization of amino crotonates to provide access to aliphatic tosyl imines, which then engage in a (3+2) annulation with various allenoates. The reaction shows generality, with 24 examples established, along with a low yielding and moderately enantioselective variant. Mechanistic studies indicate that the viability of the process is linked to the selection of catalysts with similar propensity to add to the two coupling partners.

Objectively Measured Physical Activity in Patients with COPD: Recommendations from an International Task Force on Physical Activity.

Physical activity (PA) is of key importance for health among healthy persons and individuals with chronic obstructive pulmonary disease (COPD). PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper, therefore, describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure on how to monitor PA using objective assessments, and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should further clarify the relationship between PA and clinical outcomes, test the impact of treatment interventions on PA in individuals with COPD, and successfully propose a PA endpoint for regulatory qualification in the future.

Correction: Online Guide for Electronic Health Evaluation Approaches: Systematic Scoping Review and Concept Mapping Study.

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Online Guide for Electronic Health Evaluation Approaches: Systematic Scoping Review and Concept Mapping Study.

BACKGROUND: Despite the increase in use and high expectations of digital health solutions, scientific evidence about the effectiveness of electronic health (eHealth) and other aspects such as usability and accuracy is lagging behind. eHealth solutions are complex interventions, which require a wide array of evaluation approaches that are capable of answering the many different questions that arise during the consecutive study phases of eHealth development and implementation. However, evaluators seem to struggle in choosing suitable evaluation approaches in relation to a specific study phase. OBJECTIVE: The objective of this project was to provide a structured overview of the existing eHealth evaluation approaches, with the aim of assisting eHealth evaluators in selecting a suitable approach for evaluating their eHealth solution at a specific evaluation study phase. METHODS: Three consecutive steps were followed. Step 1 was a systematic scoping review, summarizing existing eHealth evaluation approaches. Step 2 was a concept mapping study asking eHealth researchers about approaches for evaluating eHealth. In step 3, the results of step 1 and 2 were used to develop an "eHealth evaluation cycle" and subsequently compose the online "eHealth methodology guide." RESULTS: The scoping review yielded 57 articles describing 50 unique evaluation approaches. The concept mapping study questioned 43 eHealth researchers, resulting in 48 unique approaches. After removing duplicates, 75 unique evaluation approaches remained. Thereafter, an "eHealth evaluation cycle" was developed, consisting of six evaluation study phases: conceptual and planning, design, development and usability, pilot (feasibility), effectiveness (impact), uptake (implementation), and all phases. Finally, the "eHealth methodology guide" was composed by assigning the 75 evaluation approaches to the specific study phases of the "eHealth evaluation cycle." CONCLUSIONS: Seventy-five unique evaluation approaches were found in the literature and suggested by eHealth researchers, which served as content for the online "eHealth methodology guide." By assisting evaluators in selecting a suitable evaluation approach in relation to a specific study phase of the "eHealth evaluation cycle," the guide aims to enhance the quality, safety, and successful long-term implementation of novel eHealth solutions.

Digital tools for the recruitment and retention of participants in randomised controlled trials: a systematic map.

BACKGROUND: Recruiting and retaining participants in randomised controlled trials (RCTs) is challenging. Digital tools, such as social media, data mining, email or text-messaging, could improve recruitment or retention, but an overview of this research area is lacking. We aimed to systematically map the characteristics of digital recruitment and retention tools for RCTs, and the features of the comparative studies that have evaluated the effectiveness of these tools during the past 10 years. METHODS: We searched Medline, Embase, other databases, the Internet, and relevant web sites in July 2018 to identify comparative studies of digital tools for recruiting and/or retaining participants in health RCTs. Two reviewers independently screened references against protocol-specified eligibility criteria. Included studies were coded by one reviewer with 20% checked by a second reviewer, using pre-defined keywords to describe characteristics of the studies, populations and digital tools evaluated. RESULTS: We identified 9163 potentially relevant references, of which 104 articles reporting 105 comparative studies were included in the systematic map. The number of published studies on digital tools has doubled in the past decade, but most studies evaluated digital tools for recruitment rather than retention. The key health areas investigated were health promotion, cancers, circulatory system diseases and mental health. Few studies focussed on minority or under-served populations, and most studies were observational. The most frequently-studied digital tools were social media, Internet sites, email and tv/radio for recruitment; and email and text-messaging for retention. One quarter of the studies measured efficiency (cost per recruited or retained participant) but few studies have evaluated people's attitudes towards the use of digital tools. CONCLUSIONS: This systematic map highlights a number of evidence gaps and may help stakeholders to identify and prioritise further research needs. In particular, there is a need for rigorous research on the efficiency of the digital tools and their impact on RCT participants and investigators, perhaps as studies-within-a-trial (SWAT) research. There is also a need for research into how digital tools may improve participant retention in RCTs which is currently underrepresented relative to recruitment research. REGISTRATION: Not registered; based on a pre-specified protocol, peer-reviewed by the project's Advisory Board.

What do senior physicians think about AI and clinical decision support systems: Quantitative and qualitative analysis of data from specialty societies.

AIMS: The aim was to help physicians engage with NHS and other policymakers about the use, procurement and regulation of artificial intelligence, algorithms and clinical decision support systems (CDSS) in the NHS by identifying the professional benefits of and concerns about these systems. METHODS: We piloted a three-page survey instrument with closed and open-ended questions on SurveyMonkey, then circulated it to specialty societies via email. Both quantitative and qualitative methods were used to analyse responses. RESULTS: The results include the current usage of CDSS; identified benefits; concerns about quality; concerns about regulation, professional practice, ethics and liability, as well as actions being taken by the specialty societies to address these; and aspects of CDSS quality that need to be tested. CONCLUSION: While results confirm many expected benefits and concerns about CDSS, they raise new professional concerns and suggest further actions to explore with partners on behalf of the physician community.

Using digital tools in the recruitment and retention in randomised controlled trials: survey of UK Clinical Trial Units and a qualitative study.

BACKGROUND: Recruitment and retention of participants in randomised controlled trials (RCTs) is a key determinant of success but is challenging. Trialists and UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) are increasingly exploring the use of digital tools to identify, recruit and retain participants. The aim of this UK National Institute for Health Research (NIHR) study was to identify what digital tools are currently used by CTUs and understand the performance characteristics required to be judged useful. METHODS: A scoping of searches (and a survey with NIHR funding staff), a survey with all 52 UKCRC CTUs and 16 qualitative interviews were conducted with five stakeholder groups including trialists within CTUs, funders and research participants. A purposive sampling approach was used to conduct the qualitative interviews during March-June 2018. Qualitative data were analysed using a content analysis and inductive approach. RESULTS: Responses from 24 (46%) CTUs identified that database-screening tools were the most widely used digital tool for recruitment, with the majority being considered effective. The reason (and to whom) these tools were considered effective was in identifying potential participants (for both Site staff and CTU staff) and reaching recruitment target (for CTU staff/CI). Fewer retention tools were used, with short message service (SMS) or email reminders to participants being the most reported. The qualitative interviews revealed five themes across all groups: 'security and transparency'; 'inclusivity and engagement'; 'human interaction'; 'obstacles and risks'; and 'potential benefits'. There was a high level of stakeholder acceptance of the use of digital tools to support trials, despite the lack of evidence to support them over more traditional techniques. Certain differences and similarities between stakeholder groups demonstrated the complexity and challenges of using digital tools for recruiting and retaining research participants. CONCLUSIONS: Our studies identified a range of digital tools in use in recruitment and retention of RCTs, despite the lack of high-quality evidence to support their use. Understanding the type of digital tools in use to support recruitment and retention will help to inform funders and the wider research community about their value and relevance for future RCTs. Consideration of further focused digital tool reviews and primary research will help to reduce gaps in the evidence base.

Modeling of Deformable Objects for Robotic Manipulation: A Tutorial and Review.

Manipulation of deformable objects has given rise to an important set of open problems in the field of robotics. Application areas include robotic surgery, household robotics, manufacturing, logistics, and agriculture, to name a few. Related research problems span modeling and estimation of an object's shape, estimation of an object's material properties, such as elasticity and plasticity, object tracking and state estimation during manipulation, and manipulation planning and control. In this survey article, we start by providing a tutorial on foundational aspects of models of shape and shape dynamics. We then use this as the basis for a review of existing work on learning and estimation of these models and on motion planning and control to achieve desired deformations. We also discuss potential future lines of work.

Preserving the Open Access Benefits Pioneered by the Journal of Medical Internet Research and Discouraging Fraudulent Journals.

The Journal of Medical Internet Research (JMIR) was an early pioneer of open access online publishing, and two decades later, some readers and authors may have forgotten the challenges of previous scientific publishing models. This commentary summarizes the many advantages of open access publishing for each of the main stakeholders in scientific publishing and reminds us that, like every innovation, there are disadvantages that we need to guard against, such as the problem of fraudulent journals. This paper then reviews the potential impact of some current initiatives, such as Plan S and JMIRx, concluding with some suggestions to help new open-access publishers ensure that the advantages of open access publishing outweigh the challenges.