Making Science Computable Using Evidence-Based Medicine on Fast Healthcare Interoperability Resources: Standards Development Project.

Background: Evidence-based medicine (EBM) has the potential to improve health outcomes, but EBM has not been widely integrated into the systems used for research or clinical decision-making. There has not been a scalable and reusable computer-readable standard for distributing research results and synthesized evidence among creators, implementers, and the ultimate users of that evidence. Evidence that is more rapidly updated, synthesized, disseminated, and implemented would improve both the delivery of EBM and evidence-based health care policy.

Longitudinal clinical decision support for assessing decisions over time: State-of-the-art and future directions.

Objective: Patients and clinicians rarely experience healthcare decisions as snapshots in time, but clinical decision support (CDS) systems often represent decisions as snapshots. This scoping review systematically maps challenges and facilitators to longitudinal CDS that are applied at two or more timepoints for the same decision made by the same patient or clinician.

Methods: We searched Embase, PubMed, and Medline databases for articles describing development, validation, or implementation of patient- or clinician-facing longitudinal CDS.

Striking a match between FHIR-based patient data and FHIR-based eligibility criteria.

Inputs And Outputs: The Strike-a-Match Function, written in JavaScript version ES6+, accepts the input of two datasets (one dataset defining eligibility criteria for research studies or clinical decision support, and one dataset defining characteristics for an individual patient). It returns an output signaling whether the patient characteristics are a match for the eligibility criteria.

Purpose: Ultimately, such a system will play a "matchmaker" role in facilitating point-of-care recognition of patient-specific clinical decision support.

Representation of evidence-based clinical practice guideline recommendations on FHIR.

Background: Various formalisms have been developed to represent clinical practice guideline recommendations in a computer-interpretable way. However, none of the existing formalisms leverage the structured and computable information that emerge from the evidence-based guideline development process. Thus, we here propose a FHIR-based format that uses computer-interpretable representations of the knowledge artifacts that emerge during the process of evidence-based guideline development to directly serve as the basis of evidence-based recommendations.

Reflections on defining a standard for computable expression of scientific knowledge: What teach us Yoda can.

Science advances at a slow pace but can be accelerated with a standard for computable expression of scientific knowledge, more precisely a technical standard for electronic data exchange of machine-interpretable data expressing scientific knowledge. Efforts to achieve this vision include Evidence-Based Medicine on Fast Healthcare Interoperability Resources (EBMonFHIR), COVID-19 Knowledge Accelerator (COKA), Computable Publishing LLC, Scientific Knowledge Accelerator Foundation, and the Fast Evidence Interoperability Resources (FEvIR) Platform. The vision for communicating scientific research results to be instantly found, viewed, sent, received, and incorporated into thousands of system is a Just-in-time Evidence Dissemination and Integration (JEDI) vision.

A Framework for the Development of Living Practice Guidelines in Health Care.

Background: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence.

Objective: To develop a framework that characterizes the processes of development of living practice guidelines in health care.

Design: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines.

Clinical Quality Measures: A Challenge for-and to-Family Physicians.

Introduction: Improving design, selection and implementation of appropriate clinical quality measures can reduce harms and costs of health care and improve the quality and experience of care delivery. These measures have not been evaluated for appropriateness for use in performance measurement in a systematic, reproducible, and widely accepted manner.

Methods: We defined 10 criteria for evaluation of measure appropriateness in 4 domains: Patient-centeredness of outcomes, specification of population measured and measure detail, reliable evidence that benefits likely outweigh harms, and independence from significant confounders.

Categorizing metadata to help mobilize computable biomedical knowledge.

Introduction: Computable biomedical knowledge artifacts (CBKs) are digital objects conveying biomedical knowledge in machine-interpretable structures. As more CBKs are produced and their complexity increases, the value obtained from sharing CBKs grows. Mobilizing CBKs and sharing them widely can only be achieved if the CBKs are findable, accessible, interoperable, reusable, and trustable (FAIR+T).

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19.

Processes for evidence summarization for patient decision aids: A Delphi consensus study.

Background: Patient decision aids (PDAs) should provide evidence-based information so patients can make informed decisions. Yet, PDA developers do not have an agreed-upon process to select, synthesize and present evidence in PDAs.

Objective: To reach the consensus on an evidence summarization process for PDAs.

Making science computable: Developing code systems for statistics, study design, and risk of bias.

The COVID-19 crisis led a group of scientific and informatics experts to accelerate development of an infrastructure for electronic data exchange for the identification, processing, and reporting of scientific findings. The Fast Healthcare Interoperability Resources (FHIR®) standard which is overcoming the interoperability problems in health information exchange was extended to evidence-based medicine (EBM) knowledge with the EBMonFHIR project. A 13-step Code System Development Protocol was created in September 2020 to support global development of terminologies for exchange of scientific evidence.

The effects of prenatal and postnatal exposure to electromagnetic field on rat ovarian tissue.

Exposure to an electromagnetic field (EMF) can have adverse effects on many organs and tissues, including the reproductive system. This study aimed to investigate the effects of EMF exposure during prenatal and postnatal periods on ovarian development in rat offspring. In this study, rat pups born from eight pregnant rats were used.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

Objectives: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields.

Study Design And Setting: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group.

Results: A request for developing recommendations within 2 week is the usual trigger for an urgent response.

Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances.

Objectives: Alteplase is commonly recommended for acute ischaemic stroke within 4.5 hours after stroke onset. The Third European Cooperative Acute Stroke Study (ECASS III) is the only trial reporting statistically significant efficacy for clinical outcomes for alteplase use 3-4.

Consistency of Recommendations for Evaluation and Management of Hypertension.

Importance: Hypertension is very common, but guideline recommendations for hypertension have been controversial, are of increasing interest, and have profound implications.

Objective: To systematically assess the consistency of recommendations regarding hypertension management across clinical practice guidelines (CPGs).

Design, Setting, And Participants: This cross-sectional study of hypertension management recommendations included CPGs that had been published as of April 2018.

GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions.

Objectives: Clear communication of systematic review findings will help readers and decision makers. We built on previous work to develop an approach that improves the clarity of statements to convey findings and that draws on Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Study Design And Setting: We conducted workshops including 80 attendants and a survey of 110 producers and users of systematic reviews.

Defining certainty of net benefit: a GRADE concept paper.

Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology is used to assess and report certainty of evidence and strength of recommendations. This GRADE concept article is not GRADE guidance but introduces certainty of net benefit, defined as the certainty that the balance between desirable and undesirable health effects is favourable. Determining certainty of net benefit requires considering certainty of effect estimates, the expected importance of outcomes and variability in importance, and the interaction of these concepts.

Modified Delphi survey for the evidence summarisation of patient decision aids: Study protocol.

Introduction: Information included in a patient decision aid (PDA) can significantly influence patients' decisions and is, therefore, expected to be evidence-based and rigorously selected and summarised. PDA developers have not yet agreed on a standardised process for the selection and summarisation of the supporting evidence. We intend to generate consensus on a process (and related steps and criteria) for selecting and summarising evidence for PDAs using a modified Delphi survey.

Molecular Determinants of Substrate Specificity in Human Insulin-Degrading Enzyme.

Insulin-degrading enzyme (IDE) is a 110 kDa chambered zinc metalloendopeptidase that degrades insulin, amyloid β, and other intermediate-sized aggregation prone peptides that adopt β-structures. Structural studies of IDE in complex with multiple physiological substrates have suggested a role for hydrophobic and aromatic residues of the IDE active site in substrate binding and catalysis. Here, we examine functional requirements for conserved hydrophobic and aromatic IDE active site residues that are positioned within 4.

Observations and Reflections on Visualization Literacy in Elementary School.

In this article, we share our reflections on visualization literacy and how it might be better developed in early education. We base this on lessons we learned while studying how teachers instruct, and how students acquire basic visualization principles and skills in elementary school. We use these findings to propose directions for future research on visualization literacy.

Functional requirement for human pitrilysin metallopeptidase 1 arginine 183, mutated in amyloidogenic neuropathy.

Here we report the enzymologic characterization of recombinant human pitrilysin metallopeptidase 1 (Pitrm1) and derivative mutants including the arginine-to-glutamine substitution mutant Pitrm1 R183Q, which has been implicated in inherited amyloidogenic neuropathy. Recombinant Pitrm1 R183Q was readily expressed in and purified from Escherichia coli, but was less active than the recombinant wild-type enzyme against recombinant amyloid beta-peptide (Aβ 1-40). A novel fluorogenic substrate derived from the reported Aβ 1-40 core peptide cleavage sequence, Mca-KLVFFAEDK-(Dnp)-OH, was synthesized and applied to real-time kinetic study of Pitrm1 and derivative mutants including Pitrm1 R183Q.

The GRADE Working Group clarifies the construct of certainty of evidence.

Objective: To clarify the grading of recommendations assessment, development and evaluation (GRADE) definition of certainty of evidence and suggest possible approaches to rating certainty of the evidence for systematic reviews, health technology assessments, and guidelines.

Study Design And Setting: This work was carried out by a project group within the GRADE Working Group, through brainstorming and iterative refinement of ideas, using input from workshops, presentations, and discussions at GRADE Working Group meetings to produce this document, which constitutes official GRADE guidance.

Results: Certainty of evidence is best considered as the certainty that a true effect lies on one side of a specified threshold or within a chosen range.