Abstract
Objectives
Improving diagnosis-related education in the health professions has great potential to improve the quality and safety of diagnosis in practice. Twelve key diagnostic competencies have been delineated through a previous initiative. The objective of this project was to identify the next steps necessary for these to be incorporated broadly in education and training across the health professions.
Methods
We focused on medicine, nursing, and pharmacy as examples. A literature review was conducted to survey the state of diagnosis education in these fields, and a consensus group was convened to specify next steps, using formal approaches to rank suggestions.
Results
The literature review confirmed initial but insufficient progress towards addressing diagnosis-related education. By consensus, we identified the next steps necessary to advance diagnosis education, and five required elements relevant to every profession: 1) Developing a shared, common language for diagnosis, 2) developing the necessary content, 3) developing assessment tools, 4) promoting faculty development, and 5) spreading awareness of the need to improve education in regard to diagnosis.
Conclusions
The primary stakeholders, representing education, certification, accreditation, and licensure, in each profession must now take action in their own areas to encourage, promote, and enable improved diagnosis, and move these recommendations forward.
Introduction
“Education is the most powerful weapon which you can use to change the world.”―Nelson Mandela
Improving diagnosis education represents a critically important approach to reduce harm related to diagnostic error in practice [1]. In this paper we review the rationale for this hypothesis, the current state of diagnosis in three of the largest health professions (medicine, nursing, and pharmacy), the foundational work already completed in this area, and consensus recommendations from a panel of interprofessional educational and organizational leaders on the next steps that should be taken. Focusing on the next generation of clinicians is important. It will help ensure more widespread adoption of best practices in diagnosis, and would help improve upon the idiosyncratic nature of diagnostic practice today.
Current diagnosis education is inadequate
Achieving competency in diagnosis is a primary focus in many health professions; however, the focus is relatively narrow, aimed primarily at conveying facts to students without ensuring expertise in the diagnostic process itself. A growing number of schools provide content on clinical reasoning, but this is generally introductory in nature, without emphasizing, for example, critical thinking or cognitive bias. Currently, competence in diagnosis is acquired largely through the apprenticeship model. It consists of gaining experience through clinical contact and emulating the practices of clinical supervisors and mentors. Interprofessional (IP) or team based education experiences focused on diagnosis are limited, if available at all.
The likelihood of diagnostic error in primary care (internal medicine, pediatrics, and family medicine) is approximately 10% [2, 3], and the aggregate harm from diagnostic error is unacceptably high. These findings strongly suggest that current educational practices in medical education are inadequate. Studies on the etiology of diagnostic errors point to a number of contributing factors that are rarely covered in formal health professional education, including many aspects of cognitive- and system-related error, shortcomings in clinical reasoning, communication, teamwork, and working effectively in complex health systems. These findings suggest that addressing diagnostic error will require that learners in all health professions become familiar with the process of diagnosis and how it can be optimized. We refer to this broadly as ‘diagnosis education’ [1, 4, 5]. Improving diagnosis education was a top recommendation in the National Academy of Medicine’s (NAM) report on Improving Diagnosis in Health Care [6].
Twelve key competencies to improve diagnosis have been identified
It is important to identify the outcomes that we want to achieve in education to improve diagnosis. This necessary first step to improve diagnosis education has already been taken. Through an interprofessional consensus-based effort sponsored by the Josiah Macy Jr. Foundation and the Society to Improve Diagnosis in Medicine (SIDM), 12 key competencies to improve diagnosis have been identified and endorsed [7, 8]. This set of key competencies acknowledges that acquiring the foundational knowledge that underlies diagnosis in one’s profession is essential. While absolutely necessary, it is not sufficient. Specific competencies are identified in individual, system-related, and team-based domains that are not typically covered in health professions education today. As examples, healthcare professionals should be competent in using decision support resources, should receive education in clinical reasoning and critical thinking, and be able to recognize and address cognitive biases in clinical reasoning [9]. All health professionals should be experienced and comfortable working as part of a dynamic interprofessional diagnostic team that includes an engaged patient along with the health professionals who know the patient and whose perspective and expertise are important for optimal outcomes in each specific clinical context [10]. The team should know the ‘ins and outs’ of the electronic health record and the system in which they work, and appreciate the many human elements that determine the work context and influence the accuracy and timeliness of the diagnostic process [11], [12], [13]. We must educate health professionals to practice within the ecosystem of modern health care, understanding the impact that context has on diagnostic reasoning is fundamental [14, 15].
The process used to identify next steps
The goal of this project was to delineate the specific ‘next steps’ needed to begin the process of ensuring the competencies are taught and assessed across the health professions. A panel of stakeholders was convened to participate in a series of four virtual 2-h meetings. The panel included 5–10 representatives each from the fields of medicine, nursing, and pharmacy. The first meeting provided an overview and environmental scan on diagnosis education for all participants. Then, all participants met twice within their profession group to discuss and reach consensus on next steps to advance diagnosis education across that profession. The summary findings and recommendations from each profession were reviewed and discussed at the final meeting. These were approved unanimously by the individual participants through a subsequent email survey.
In the following sections, we first review the current state of diagnosis education in each profession. Next we discuss shared needs across all the health professions: developing a common language, creating diagnosis-related content and assessment processes, and performing faculty development. Finally, we present the next steps that each of the stakeholders (educators, certifiers, accreditors, and licensing bodies) must take to drive diagnosis education forward.
The current state of diagnosis education in medicine, nursing, and pharmacy
Medicine
Recognizing improving patient safety education as a priority, the Association of American Medical Colleges (AAMC) developed a set of Quality Improvement and Patient Safety Competencies (QIPS) spanning five safety domains [19]. Similarly, the Accreditation Council for Graduate Medical Education (ACGME) implemented Milestones in 2013 that described competence in medical knowledge in developmental terms, based on an original set of six core competencies: medical knowledge, patient care, interpersonal and communication skills, practice-based learning and improvement, professionalism, and system-based practice [16]. In the 2018 revision, Milestones 2.0, the ACGME placed greater emphasis in all medical specialties on clinical reasoning. Crosswalks between the 12 key diagnostic competencies that our interprofessional group has developed and both the QIPS and Milestone 2.0 competency sets (see Supplementary Appendix A) shows partial but incomplete alignment. Schools and programs need a coherent set of standards in designing their curriculum. Hopefully, subsequent updates of the Milestones and QIPS competency sets can be expanded and refined to accommodate the newer competencies that focus more specifically on diagnosis.
Nursing
The case for expanding diagnosis education in schools of nursing has been made [17], [18], [19], [20], along with recommendations to address state-specific regulatory ‘scope of practice’ restrictions on nursing participation in diagnosis [21]. Nursing continues to work with state regulatory boards to amend language in nurse practice acts that recognizes and promotes the role of nurses in diagnosis, based on their educational preparation.
Diagnostic reasoning has been identified as a central concept in nursing practice and clinical decision making since at least 1970 [22]. It has been addressed most often as part of the nursing processes of assessment, diagnosis, planning, intervention, and evaluation.
Due to complex interprofessional and regulatory dynamics, the art and science of nursing diagnosis has both flourished and been criticized. Despite advances in nursing clinical reasoning and growing awareness of nursing’s important contributions to diagnosis, discussion of the nursing role in “medical” diagnosis has triggered “scope of practice” concerns and thus has mostly been avoided. This results in communication, care, and practice gaps, as well as a failure of collaborative opportunities to maximize the expertise and contributions of nurses to improve health outcomes. Even though nursing is responsible for responding to the “medical” diagnoses established by physicians, advanced practice registered nurses (APRN’s) and particularly registered nurses have been effectively excluded from participating in identifying the “medical” diagnoses, a practice that fails to recognize or take advantage of nursing’s knowledge and skills, and the profession’s shared accountability for achieving best health outcomes. Recognizing the need for RNs to directly and purposefully engage with physicians and other health professionals in establishing, refining, and validating diagnoses is overdue, and this point was emphasized in the NAM report [6].
Although many of the major nursing professional organizations have yet to formally endorse the need to improve diagnosis education for entry-level RNs, the American Association of Colleges of Nursing (AACN) integrated the 12 key competencies into the latest revision of their national curricular standards, known as “The Essentials”, that are used for baccalaureate, master’s and Doctor of Nursing Practice (DNP) programs [23].
For APRN’s (Nurse Practitioners, Clinical Nurse Specialists, Nurse-Midwives, and Nurse Anesthetists), engagement in diagnosis is core to practice, and APRN programs are required to include separate courses on physical examination, pathophysiology, and pharmacology as well as diagnosis and management courses. These courses integrate diagnostic reasoning and differential diagnosis within their content. The role of APRN’s in diagnosis is described in the “Consensus Model for Advanced Practice Registered Nursing Regulation: Licensure, Accreditation, Certification and Education” [24]. Endorsed by 50 nursing organizations, including programmatic accreditors, certifying and licensing bodies, the Consensus Model defines an APRN as “ educationally prepared to assume responsibility and accountability for … assessment, diagnosis, and management of patient problems, which includes the use and prescription of pharmacologic and non-pharmacologic interventions.”
Two of the three bodies that accredit both entry- and advanced-level nursing programs currently have language in their standards that require nursing programs to have interprofessional (IP) education experiences. The third nursing accrediting body has language in its standards that requires IP collaboration in curricular and instructional processes for all entry level, post-licensure, and advanced nursing programs. The National Council of State Boards of Nursing is actively piloting new testing methodologies for the national licensing exam (NCLEX) for all entry-level nurses, with new questions that focus on assessing clinical reasoning and clinical judgement. All APRN national certification bodies include test items related to diagnostic reasoning and differential diagnosis based on practice analyses.
Pharmacy
Several publications have made the case for improving diagnosis-related education in schools of pharmacy; and courses on clinical reasoning, physical examination, and other aspects of diagnosis are now appearing (see Supplementary Appendix B) [25], [26], [27].
Pharmacists are integral members of the interprofessional healthcare team and provide a critical and unique perspective in the interprofessional diagnostic process. The Pharmacist’s Patient Care Process, released by the Joint Commission of Pharmacy Practitioners, is endorsed across the profession and is nationally recognized as an expectation for pharmacists in all settings [28]. The Pharmacist’s Patient Care Process encompasses the following foundational elements of managing safe and effective pharmacotherapy: Collect information; assess the information; identify and prioritize patient problems; follow-up; and evaluate [29]. Pharmacists identify and augment diagnoses that are amenable to self-care in the community setting and contribute to diagnosis in the care of patients with acute and chronic conditions in other practice settings. In the context of an interprofessional team, examples of the pharmacist’s diagnostic contributions include identifying medication-related treatment problems and achieving therapeutic goals based on appropriate diagnosis.
For over a decade, pharmacist education has emphasized the role of pharmacists in patient safety. In 2007, the ‘Argus Commission Report’ from the American Association of Colleges of Pharmacy (AACP) stated that “a culture of safety should permeate the practice of pharmacy in all settings” [30]. The Report was endorsed in 2013 by the Center for the Advancement of Pharmacy Education (CAPE), and in 2015 by the Accreditation Council for Pharmacy Education (ACPE). Most recently, in 2019 the AACP’s House of Delegates adopted a new policy “support[ing] education on the pharmacists’ responsibility for contributing to the diagnostic process to help minimize errors, maximize patient safety, and optimize health outcomes” [31].
Curricular standards in pharmacy education are set by the ACPE; these promote patient safety and interprofessional collaboration, but do not explicitly mention diagnosis except in the context of interpreting laboratory data. Pharmacy students, however, are well-versed in the Pharmacists’ Patient Care Process, described above. Pharmacists have a comprehensive understanding of medication adverse effects and interactions, and are skilled in identifying and managing medication-related problems. Patient assessment skills are a required accreditation element for all accredited U.S. pharmacy schools, of which physical examination is a component. It should be noted, however, that current curricular standards do not provide guidance on the depth and breadth of physical examination training required, nor is there a national competency standard for this skill [27, 32].
Students are exposed to differential diagnoses for common conditions in their pharmacotherapy-related courses, but it is primarily learned implicitly. However, as pharmacists are regularly consulted by patients seeking advice for self-care related complaints, students are exposed to differential diagnosis in their courses on therapeutics. Students learn to recognize signs and symptoms of common conditions and to differentiate between conditions that present similarly so that appropriate self-care or medical referral can be determined. Some schools offer elective courses related to diagnosis [33] and in one school, a stand-alone course in differential diagnosis is a curricular requirement [27].
In post-graduate training, pharmacy residency standards established by the American Society of Health-System Pharmacists (ASHP), encompass the Pharmacists’ Patient Care Process framework and expect advanced clinical skills and participation, without specific mention of the diagnostic process [29]. While the movement to the Doctor of Pharmacy (PharmD) degree helped to advance the requirement of physical assessment/examination and diagnosis training, many practicing pharmacists were not taught these skills in their professional education. Thus, there is a need for education and training programs to fill the gap to support practicing pharmacists in this area.
What are the next steps to improve diagnosis education?
Universal needs
The 12 competencies are applicable to all health professions and must be interpreted through the health profession’s specific lens with respect to teaching, learning, assessment, and practice. An important step is for each profession to determine how each of the competencies is relevant to their practice and to each level of the profession’s educational programs.
Five general requirements to advance diagnosis education apply to every profession. These requirements can and should be developed and shared across the professions:
Shared language and definitions: A shared understanding of key definitions and language around diagnosis is important to enable true teamwork and the emergence of shared mental models of diagnosis. Too often, health professionals approach the same diagnostic situation with different language and understanding of roles, thus inhibiting true and free collaboration.
Appropriate curricular content: Educators will need appropriate curricular content to help develop competence in diagnosis. A number of schools and educators have already developed course work in clinical reasoning and related topics (See Supplementary Appendix B). Many of the competencies can be acquired by early learners, who have not yet mastered clinical content, such as how to promote critical thinking, use decision-support resources, or think in teams. Much of this material is especially well-suited for interprofessional learning experiences, and for engaging didactic learning formats, such as using a flipped classroom, or conducting an escape room scenario [34].
Faculty development: Faculty development is necessary to help faculty improve their own diagnostic abilities and practices, especially given the critical role that faculty competence plays in role-modeling superb patient care. There are promising examples ongoing, such as the SIDM #teachDx Faculty Development Academy. Training-the-trainer events can and should be done interprofessionally to promote faculty understanding and appreciation of the contributions made by each member of the diagnostic team. Notably, most of these curricular elements do not rely on the knowledge content specific to any one profession.
Assessment: Student assessment in most professions currently focuses on content knowledge, often relying too heavily on multiple choice questions. There needs to be formal assessment on the processes of diagnosing, including recognizing or dealing with uncertainty and ambiguity; and currently there is too little. Going forward, assessment of competence in diagnosis should focus more on processes for deriving an appropriate, prioritized, and justified differential diagnosis, not just the ‘single best answer’, as well as identifying best ‘next steps’. Competency assessment also should evaluate team-based diagnosis, and tools to enable team assessment must be developed, validated, and refined. Assessing the elements of the 12 key competencies will require new formative and summative tools that take into account the impact of the setting and context of the diagnostic process including isolated, remote, virtual, and chaotic environments [35].
Awareness: Patients and clinicians share the perception that the quality of diagnosis in health care today is high and constantly improving. Without detracting from either of these assumptions, the ubiquity of diagnostic errors is convincing evidence that further improvements are desirable, and the adequacy of current education and training programs for achieving a reduction in diagnostic errors needs concomitant re-evaluation [6]. Leaders in every health profession need to emphasize to their members that these gaps exist and that improving diagnosis education can improve health outcomes.
Profession-specific needs
The interprofessional panel identified two major ‘next steps’ needed to advance diagnosis education:
Each profession needs to state clearly that it has a role in diagnosis and that education in the profession must prepare students for this role. We firmly believe that diagnostic outcomes in practice would be improved if all health professionals were viewed as collaborators in the diagnostic process. In both Nursing and Pharmacy, and many other health professions, the clinician’s role in diagnosis is not clear, and is complicated by the extensive variability in language and state board regulations. These barriers must be addressed and overcome in order to create truly collaborative, non-hierarchical teams. Examples of nurses and pharmacists participating in the diagnostic process are illustrated in Table 1.
The major education-related stakeholders in each profession need to take actions to rapidly improve diagnosis education. Curricula must be designed that incorporate the 12 competencies, or those relevant to a particular profession. Organizations that accredit programs, and state boards and other regulatory agencies that oversee licensure and certification all need to recognize and encourage profession-specific competencies in diagnosis in each health profession. Each of these stakeholders has important roles to play if diagnosis is to advance. Recommended next steps are presented in Table 2.
Examples of nurses and pharmacists participating in the diagnostic process.
Nurse participation in diagnosis |
|
|
Pharmacist participation in diagnosis |
|
|
Role of each stakeholder in advancing diagnosis education
Organization type | What they could do |
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Schools | Inventory current curriculum and courses; Identify gaps relating to the 12 key competencies |
Revise existing curriculum or add new elements to ensure competency in diagnosis. Develop\increase interprofessional experiences focused on diagnostic reasoning | |
Provide formative and summative assessment of competency | |
Provide opportunities for faculty development | |
Oversight organizations (AAMC, AACN, AACP, etc) | Learn about the new curriculum; Endorse it; Work with Schools & Societies on awareness |
Take a leadership role in helping schools implement competency curriculum | |
Include sessions and keynotes on diagnostic error and diagnosis education at annual meetings | |
Sponsor workshops, faculty development, special interest groups | |
Boards (ABIM, NCSBN, PNCB, etc) | Develop examination questions and question types that probe for competency in the 12 new competency areas. Explore alternatives to single-best answer questions to assess competence in diagnosis. |
Clearly state an expectation for test-takers to be competent in the 12 key areas | |
Accreditors (ACGME, CCNE, CNEA, ACEN, ACPE, ASHP, etc) | Endorse the competencies. |
Raise awareness about the need to improve diagnosis education and use the 12 competencies | |
Incorporate expectations about diagnosis education in the accreditation standards, criteria & blueprints | |
Collaborate in developing content, milestone statements, and assessment tools | |
Professional associations, societies, and colleges (ACP, AAN, AODN, ACCP, APhA, JCPP, NCPA, ASCP, etc) | Endorse the need to improve diagnosis education based on the 12 competencies |
Raise awareness amongst Society members. Include talks and sessions at annual meetings on dx error | |
At least one editorial in the association journal on diagnostic error and improving diagnosis education | |
Develop improvement modules for use in practice (eg, ACP Practice Advisor modules) | |
Take the leadership role in improving diagnosis in the medical professions. Accept responsibility for moving diagnosis education forward, and keeping all stakeholders on track and motivated. | |
Education organizations (APDIM, NONPF, CAPE, NLN, etc) | Raise awareness about the need to improve diagnosis education and use the 12 competencies |
Help schools conduct a curriculum inventory on content relevant to improving diagnosis | |
Sponsor surveys of content on diagnosis education | |
Conduct workshops, webinars to showcase programs that have implemented new content | |
Collect tools and resources programs could use to improve diagnosis education | |
Conduct quarterly contests focused on diagnostic excellence (solving case scenarios) | |
Publish newsletters, social media reports on successful implementations | |
Sponsor a special interest group focused on diagnosis education |
Discussion
Education in the health professions is continually evolving, and each year there are numerous calls to improve education in one domain or another. What distinguishes this call to action to improve diagnosis education is the evidence that diagnostic errors in practice account for an estimated 40,000–80,000 deaths per year in the United States [36]. Our recommendations represent a specific, cohesive set of ‘next steps’ that can and should be taken to address this massive problem. Although the recommendations have focused on three professions as a starting point, they apply to all health professions. The educational leadership in each profession needs to similarly assess their current state of educational practice and begin the process of improving educational offerings and assessment to ensure their graduates can contribute most effectively to diagnosis in practice.
Although the case for improving diagnosis education is evident, the pathway to accomplishing this goal is beset by hurdles. One of the biggest hurdles is the need to agree upon and use a common language that is inclusive and recognized by all health professions. The term “diagnosis”, both the noun and the verb, should be used universally without designation or identification with any one health profession. All health care providers must own the diagnostic process and diagnostic outcomes. Common language will enable a shared mental model of each patient’s case, and improve collaboration and communication among healthcare team members.
Known challenges include concerns about liability and the variability in how diagnosis is viewed and prescribed by state licensing entities. Scope-of-practice reform is needed across health professions to enable clinicians to fully participate in team-based diagnosis, as envisioned by the National Academy of Medicine [6].
Given the negative outcomes for patients associated with diagnostic errors in practice, the recommendations in this proposal should be critically reviewed and urgently acted upon by the education leadership in every health profession. Within each profession, all of the education stakeholders – education, accreditation, certification, and licensing bodies – will need to work together towards the common goal. The recommendations are not sequential; the various stakeholders can and should be working in parallel and collaboratively. Appreciable progress should be documented and become evident to all over the next few years.
Consensus Group
Steering Committee
Mark L Graber MD, FACP, Society to Improve Diagnosis in Medicine;
Andrew Olson MD, FACP, FAAP, University of Minnesota School of Medicine;
Eric Holmboe MD, MACP, FRCP; Accreditation Council for Graduate Medical Education;
Joan Stanley PhD, NP, FAAN, FAANP, American Association of Colleges of Nursing;
Jennifer Danielson PharmD, MBA, CDE, University of Washington School of Pharmacy;
Stephen Schoenbaum MD, MPH, Macy Foundation.
Interprofessional Organizations
Christine Arenson MD, National Center for Interprofessional Education and Practice
Gerry Castro PhD, MPH, PMP, Society to Improve Diagnosis in Medicine
Patricia Cuff MS, MPH, Global Forum on Innovation in Health Professions Education
Pharmacy
Greg Boyer PhD, Accreditation Council for Pharmacy Education
Jeannine Conway PharmD BCPS, University of Minnesota School of Pharmacy
Mandy Jones PharmD, University of Kentucky School of Pharmacy
Anne Lin PharmD, American Association of Colleges of Pharmacy
Gina Luchen PharmD, American Society of Health-System Pharmacists
George E. MacKinnon III, PhD MS RPh FASHP, Medical College of Wisconsin
Janet Silvester PharmD, American Society of Health-System Pharmacists
Nursing
Sharon F. Beasley, PhD, RN, CNE, Accreditation Commission for Education in Nursing
Mary Beth Bigley DrPH, APRN, FAAN, National Organization of Nurse Practitioner Faculties
Michelle Buck MSN APRN CNS, National Council of State Boards of Nursing
Adele Forester MSN RN CPNP, Pediatric Nursing Certification Board
Kelly Gleason PhD, RN, Johns Hopkins University
Judith Halstead PhD RN FAAN ANEF, Commission for Nursing Education Accreditation
Gene Harkless DNSc APRN, University of New Hampshire
Lori Martin-Plank PhD FNPBC GNPBC FAAN, American Association of Nurse Practitioners
Donna Meyer MSN RN ANEF FAAN, Organization for Associate Degree Nursing
Susan Ruppert PhD RN, Commission on Collegiate Nursing Education
Sheila Smith PhD RN ANP-BC FAANP, University of Minnesota School of Nursing
Medicine/Pediatrics
Wallace Carter MD, American Board of Emergency Medicine
Laura Edgar EdD CAE, Accreditation Council for Graduate Medical Education
Hilary Haftel MD MHPE FAAP, American Academy of Pediatrics
Lisa Howley PhD MED, Association of American Medical Colleges
Philip Masters MD FACP, American College of Physicians
Warren Newton MD MPH, American Board of Family Medicine
Greg Ogrinc MD MS, American Boards of Medical Specialties
Asher Tulsky MD, American Board of Internal Medicine
David Turner MD, American Board of Pediatrics
Suzanne Woods MD, American Board of Pediatrics
Implementation Scientists
Geoff Curran PhD, Center for Implementation Research, University of Arkansas
Michelle Daniel MD, University of California San Diego School of Medicine
Diagnosis Educators
Eliana Bonafacino MD MS, University of Pittsburgh Medical Center
Denise Conner MD, University of California San Francisco School of Medicine
Benjamin Kinnear MD Med, Cincinatti Children’s Hospital
Val Lang MD MHPE, University of Rochester School of Medicine
Joe Rencic MD, Boston University School of Medicine
Bob Trowbridge MD, Tufts University and Maine Medical Center
Funding source: Josiah Macy Jr. Foundation
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Research funding: The work reflected in this manuscript was funded by an award from the Josiah Macy Jr. Foundation to a President’s Grant to the Society to Improve Diagnosis in Medicine (SIDM). The funding organization played no role in the study design, in the collection, analysis, or interpretation of the data, in the writing of the report, or in the decision to submit the report for publication. Stephen Schoenbaum MD, special assistant to the CEO of the Macy Foundation, participated in this work based on his experience and interest in interprofessional organization; his input in every instance represented his personal contribution, not as a representative of the Macy Foundation.
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Author contributions: The authors listed met all 4 of the ICJME criteria for authorship. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: Not applicable.
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The online version of this article offers supplementary material (https://doi.org/10.1515/dx-2021-0103).
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