Making Digital Health Equitable.

Most agree that the current healthcare system is broken. Fortunately, technology is increasing at an exponential rate and provides a solution for the future. Digital Health is an integrator concept that has the potential to take advantage of technological advantages. Digital Health converges health, healthcare, research, and everyday life. It includes technologies, platforms, and systems that engage consumers in all aspects of life. It makes health and healthcare be people-centered and personalized. Digital health requires total interoperability - standards, common data elements, and the integration of data from all sources. It demands data sharing. Digital Health brings together a wide range of stakeholders for similar goals using the same resources. Digital Health uses mobile devices and wearable sensors and uses Artificial Intelligence and Machine Learning to handle the vast amount of data Digital Health engages. Finally, Digital Health has the potential to open the gap between the different social and economic classes that must be addressed.

Goodbye Electronic Health Record?

The Electronic Health Record has failed to meet its intended purpose. We propose a new approach focusing on the use of data for health and health care. The first step is to create a repository of all patient data with data storage independent of data use. All use functionality is external to data storage. We propose the development of a common data model in which data elements have a rich set of attributes including actionable knowledge. Finally, functionality is provided through a series of application program interfaces (API). New APIs will address directly new methods for using data to increase the effectiveness of data application to improve management of the health and care of a patient. Together these components will open a pathway to finally accomplish the goals of a better future health system.

Economic analysis of a single institutional review board data exchange standard in multisite clinical studies.

BACKGROUND: Single Institutional Review Boards (sIRB) are not achieving the benefits envisioned by the National Institutes of Health. The recently published Health Level Seven (HL7®) Fast Healthcare Interoperability Resources (FHIR®) data exchange standard seeks to improve sIRB operational efficiency. METHODS AND RESULTS: We conducted a study to determine whether the use of this standard would be economically attractive for sIRB workflows collectively and for Reviewing and Relying institutions. We examined four sIRB-associated workflows at a single institution: (1) Initial Study Protocol Application, (2) Site Addition for an Approved sIRB study, (3) Continuing Review, and (4) Medical and Non-Medical Event Reporting. Task-level information identified personnel roles and their associated hour requirements for completion. Tasks that would be eliminated by the data exchange standard were identified. Personnel costs were estimated using annual salaries by role. No tasks would be eliminated in the Initial Study Protocol Application or Medical and Non-Medical Event Reporting workflows through use of the proposed data exchange standard. Site Addition workflow hours would be reduced by 2.50 h per site (from 15.50 to 13.00 h) and Continuing Review hours would be reduced by 9.00 h per site per study year (from 36.50 to 27.50 h). Associated costs savings were $251 for the Site Addition workflow (from $1609 to $1358) and $1033 for the Continuing Review workflow (from $4110 to $3076). CONCLUSION: Use of the proposed HL7 FHIR® data exchange standard would be economically attractive for sIRB workflows collectively and for each entity participating in the new workflows.

Recommendations for achieving interoperable and shareable medical data in the USA.

Easy access to large quantities of accurate health data is required to understand medical and scientific information in real-time; evaluate public health measures before, during, and after times of crisis; and prevent medical errors. Introducing a system in the USA that allows for efficient access to such health data and ensures auditability of data facts, while avoiding data silos, will require fundamental changes in current practices. Here, we recommend the implementation of standardized data collection and transmission systems, universal identifiers for individual patients and end users, a reference standard infrastructure to support calibration and integration of laboratory results from equivalent tests, and modernized working practices. Requiring comprehensive and binding standards, rather than incentivizing voluntary and often piecemeal efforts for data exchange, will allow us to achieve the analytical information environment that patients need.

Clinician Burnout Associated With Sex, Clinician Type, Work Culture, and Use of Electronic Health Records.

Importance: Electronic health records (EHRs) are considered a potentially significant contributor to clinician burnout. Objective: To describe the association of EHR usage, sex, and work culture with burnout for 3 types of clinicians at an academic medical institution. Design, Setting, and Participants: This cross-sectional study of 1310 clinicians at a large tertiary care academic medical center analyzed EHR usage metrics for the month of April 2019 with results from a well-being survey from May 2019. Participants included attending physicians, advanced practice providers (APPs), and house staff from various specialties. Data were analyzed between March 2020 and February 2021. Exposures: Clinician demographic characteristics, EHR metadata, and an institution-wide survey. Main Outcomes and Measures: Study metrics included clinician demographic data, burnout score, well-being measures, and EHR usage metadata. Results: Of the 1310 clinicians analyzed, 542 (41.4%) were men (mean [SD] age, 47.3 [11.6] years; 448 [82.7%] White clinicians, 52 [9.6%] Asian clinicians, and 21 [3.9%] Black clinicians) and 768 (58.6%) were women (mean [SD] age, 42.6 [10.3] years; 573 [74.6%] White clinicians, 105 [13.7%] Asian clinicians, and 50 [6.5%] Black clinicians). Women reported more burnout (survey score ≥50: women, 423 [52.0%] vs men, 258 [47.6%]; P = .008) overall. No significant differences in EHR usage were found by sex for multiple metrics of time in the EHR, metrics of volume of clinical encounters, or differences in products of clinical care. Multivariate analysis of burnout revealed that work culture domains were significantly associated with self-reported results for commitment (odds ratio [OR], 0.542; 95% CI, 0.427-0.688; P < .001) and work-life balance (OR, 0.643; 95% CI, 0.559-0.739; P < .001). Clinician sex significantly contributed to burnout, with women having a greater likelihood of burnout compared with men (OR, 1.33; 95% CI, 1.01-1.75; P = .04). An increased number of days spent using the EHR system was associated with less likelihood of burnout (OR, 0.966; 95% CI, 0.937-0.996; P = .03). Overall, EHR metrics accounted for 1.3% of model variance (P = .001) compared with work culture accounting for 17.6% of variance (P < .001). Conclusions and Relevance: In this cross-sectional study, sex-based differences in EHR usage and burnout were found in clinicians. These results also suggest that local work culture factors may contribute more to burnout than metrics of EHR usage.

Adult-onset cyclic neutropenia is a benign neoplasm associated with clonal proliferation of large granular lymphocytes.

Human cyclic neutropenia occurs in children and adults. Adult-onset cyclic neutropenia is an acquired disease characterized by increased numbers of large granular lymphocytes (LGL), in contrast to childhood-onset cyclic neutropenia in which LGL counts are normal. We investigated the clonality of lymphocytes in these two groups of patients by assessing the rearrangement status of the T cell receptor beta chain gene. Patients with adult-onset cyclic neutropenia showed clonal rearrangement of the T beta gene whereas the children did not. Since LGL are known to have multiple regulatory effects on normal hematopoiesis, the finding of a clonal proliferation of this lymphocyte population implicates these cells in the pathogenesis of cyclic neutropenia.

Evaluative Outcomes in Direct Extraction and Use of EHR Data in Clinical Trials.

Use of electronic health record (EHR) data in clinical trials has long been a goal for researchers. However, few demonstrations and fewer evaluative studies have been published. The variability in outcome choice and measurement hinders synthesis of the extant literature. In collaboration with a contemporaneous systematic review of EHR data use in clinical trial data collection, we analyze reported outcomes and recommend a standardized measure set for the evaluation of human safety, data quality, operational efficiency and cost of eSource solutions.

eSource for Standardized Health Information Exchange in Clinical Research: A Systematic Review.

The availability of research and outcomes data is the primary limitation to evidence-based practice. Today, only a fraction of clinical decisions are based upon evidence derived from randomized control trials (RCTs), the gold-standard of knowledge discovery. At the same time, clinical trial complexity has steadily increased as has the effort required at clinical investigational sites. Direct use of electronic health record (EHR) data for clinical trials has the potential to address some of these needs, improving data quality and reducing cost.

eHealth interoperability.

For improving quality and safety of patient's care, for keeping the costs of health services, but also for successfully managing public health communication and cooperation between all stakeholders is inevitable. Such interoperability can be provided at different levels from simple data exchange up to business interoperability. The paper introduces those interoperability levels and international standards specifying and facilitating them. In that context, the expression of business requirements by domain analysis models or story boards as well as by functional models of the core applications enabling interoperability like EHR systems have been tackled. The role of decision support systems and infrastructural services has been considered as well.

Cyclic hematopoiesis. Effects of endotoxin on colony-forming cells and colony-stimulating activity in grey collie dogs.

Cyclic changes in blood neutrophil counts of grey collie dogs with cyclic hematopoiesis can be eliminated by daily endotoxin injections. Studies were performed to determine the mechanism whereby endotoxin alters this disease. Bone marrow granulocyte-macrophage progenitor cells (colony-forming cells [CFUc]) showed cyclic variation in the untreated grey collie, which was eliminated by chronic endotoxin treatment (Salmonella typhosa lipopolysaccharide W, 5 microgram/kg per day). Similar cyclic variation in blood CFUc was eliminated by this treatment. Tritiated thymidine suicide of the marrow colony-forming cells failed to show cyclic changes to explain the marked swing in CFUc numbers in untreated grey collies. The thymidine suicide rates were not significantly changed by chronic endotoxin treatment. Similarly, serum colony-stimulating activity did not show cyclic variation with the cyclic neutrophil counts in untreated grey collies and was not altered by chronic endotoxin treatment. We suggest that endotoxin eliminates neutrophil cycling in cyclic hematopoiesis by a direct effect on the flux of pluripotent stem cells into the committed stem cell compartment and that this occurs independent of changes in serum colony-stimulating activity.

Canine cyclic hematopoiesis is associated with abnormal purine and pyrimidine metabolism.

Canine cyclic hematopoiesis is an autosomal recessive disease characterized by regular 11-13-d cycles of the neutrophil, reticulocyte, and platelet counts caused by a defect in regulation of marrow stem cell proliferation. Treatment with lithium abrogates cycling of the cell counts in these grey collie dogs. Aware of the defective lymphopoiesis associated with adenosine deaminase and purine nucleoside phosphorylase deficiencies, we hypothesized that abnormal purine or pyrimidine metabolism might be present in these dogs. Using high pressure liquid chromatography, we measured erythrocyte purine and pyrimidine nucleotide levels and plasma purine and pyrimidine nucleosides and bases in normal and grey collie dogs before and during lithium treatment. During neutropenic periods in the grey collies, erythrocyte ATP, GTP, and UTP levels were significantly elevated. Normal dogs made neutropenic with cyclophosphamide did not show such elevations. Lithium treatment normalized the levels of erythrocyte ATP, GTP, and UTP in the grey collies and eliminated the differences between normal and grey collie nucleotide levels. Plasma thymine levels were markedly increased during neutropenia in the grey collie but were not increased in cyclophosphamide-treated normal dogs. The finding of abnormal concentrations of purine and pyrimidine metabolites in these dogs suggest that a metabolic derangement in purine or pyrimidine metabolism may be the cause of the defective stem cell proliferation in this disease.

Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor.

Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 micrograms/kg/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from dogs during neutropenia contained an antibody to rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge with the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF.

Toward a national framework for the secondary use of health data: an American Medical Informatics Association White Paper.

Secondary use of health data applies personal health information (PHI) for uses outside of direct health care delivery. It includes such activities as analysis, research, quality and safety measurement, public health, payment, provider certification or accreditation, marketing, and other business applications, including strictly commercial activities. Secondary use of health data can enhance health care experiences for individuals, expand knowledge about disease and appropriate treatments, strengthen understanding about effectiveness and efficiency of health care systems, support public health and security goals, and aid businesses in meeting customers' needs. Yet, complex ethical, political, technical, and social issues surround the secondary use of health data. While not new, these issues play increasingly critical and complex roles given current public and private sector activities not only expanding health data volume, but also improving access to data. Lack of coherent policies and standard "good practices" for secondary use of health data impedes efforts to strengthen the U.S. health care system. The nation requires a framework for the secondary use of health data with a robust infrastructure of policies, standards, and best practices. Such a framework can guide and facilitate widespread collection, storage, aggregation, linkage, and transmission of health data. The framework will provide appropriate protections for legitimate secondary use.

Pragmatic (trial) informatics: a perspective from the NIH Health Care Systems Research Collaboratory.

Pragmatic clinical trials (PCTs) are research investigations embedded in health care settings designed to increase the efficiency of research and its relevance to clinical practice. The Health Care Systems Research Collaboratory, initiated by the National Institutes of Health Common Fund in 2010, is a pioneering cooperative aimed at identifying and overcoming operational challenges to pragmatic research. Drawing from our experience, we present 4 broad categories of informatics-related challenges: (1) using clinical data for research, (2) integrating data from heterogeneous systems, (3) using electronic health records to support intervention delivery or health system change, and (4) assessing and improving data capture to define study populations and outcomes. These challenges impact the validity, reliability, and integrity of PCTs. Achieving the full potential of PCTs and a learning health system will require meaningful partnerships between health system leadership and operations, and federally driven standards and policies to ensure that future electronic health record systems have the flexibility to support research.

The clinical document architecture and the continuity of care record: a critical analysis.

Health care provides many opportunities in which the sharing of data between independent sites is highly desirable. Several standards are required to produce the functional and semantic interoperability necessary to support the exchange of such data: a common reference information model, a common set of data elements, a common terminology, common data structures, and a common transport standard. This paper addresses one component of that set of standards: the ability to create a document that supports the exchange of structured data components. Unfortunately, two different standards development organizations have produced similar standards for that purpose based on different information models: Health Level 7 (HL7)'s Clinical Document Architecture (CDA) and The American Society for Testing and Materials (ASTM International) Continuity of Care Record (CCR). The coexistence of both standards might require mapping from one standard to the other, which could be accompanied by a loss of information and functionality. This paper examines and compares the two standards, emphasizes the strengths and weaknesses of each, and proposes a strategy of harmonization to enhance future progress. While some of the authors are members of HL7 and/or ASTM International, the authors stress that the viewpoints represented in this paper are those of the authors and do not represent the official viewpoints of either HL7 or of ASTM International.

Bronchial and pulmonary carcinogenesis at focal sites in dogs and hamsters.

Models of the sequential process of lung carcinomas have been developed in dogs and hamsters. The bronchial mucosa, or the pulmonary parenchyma, was exposed at selected focal sites to polycyclic aromatic hydrocarbons [most often benzo(a)pyrene or methylcholanthrene]. In hamsters, sustained release implants that contained carcinogen were implanted into the right lower lobe bronchus. In dogs, for orthotopic carcinogenesis the carcinogens were repeatedly injected into the bronchial submucosa or topically applied to the bronchus; sustained release implants were implanted into the pulmonary parenchyma. Heterotopic focal canine bronchial carcinogenesis was accomplished by exposing s.c. bronchial autografts (8-12/dog) to methylcholanthrene. In both species a predictable, reproducible, preneoplastic continuum that leads to bronchial squamous cell carcinoma that metastasizes has been characterized; serial measurements of total cellular DNA showed that ploidy increased in proportion to the stage of preneoplasia. In both species there were adenocarcinomas, including bronchiolar (bronchioloalveolar) carcinomas and other varieties of non-small cell cancers. Different susceptibility to carcinogenesis has been demonstrated among different inbred strains of hamsters; 58% of cancers were adenocarcinomas in one strain. From these models, specimens that are not readily available from humans can be obtained for the study of cellular events during lung carcinogenesis. In parallel with studies in humans, these animal models can be used to evaluate methods of possible chemoprevention and early detection.

Differential susceptibility to bronchial carcinogenesis in syngeneic hamsters.

Previous studies of chemical carcinogenesis in the lung of Syrian golden hamsters have utilized outbred (nonsyngeneic) animals. Using the endobronchial sustained release implant technique, which causes focally originating cancers in outbred hamsters, we studied the course of bronchial carcinogenesis in two varieties of syngeneic Syrian golden hamsters, the LSH and the F1D strains (BIO 15.16 male X BIO 87.20 female). With either 10% benzo(a)pyrene or 10% methylcholanthrene sustained release implants the time course of epithelial transition from normal to neoplastic was the same for F1D hamsters as previously described for outbred hamsters. Using 10% benzo(a)pyrene sustained release implants the incidence of cancers as a function of time was significantly lower (P less than 0.001) in LSH hamsters as compared to outbred and F1D animals. Of 19 tumors transplanted into syngeneic F1D hamsters, 16 have been successfully propagated by serial transplantation. We conclude that (a) F1D hamsters are comparable to outbred animals in the response of their bronchial epithelium to endobronchial benzo(a)pyrene and methylcholanthrene, (b) there are significant differences in susceptibility to bronchial chemical carcinogenesis among hamster strains, thereby giving opportunity to study potential genetic control mechanisms during bronchial carcinogenesis, and (c) F1D hamsters are suitable for studies of lung cancer biology using tumor transplantation methods.

Differential interaction of normal and preneoplastic hamster bronchi with adriamycin.

Advanced bronchogenic carcinoma in humans is notoriously resistant to the cytocidal actions of cancer chemotherapy. The experiments reported here were undertaken as a first step in examining the mechanisms of resistance of carcinogen-altered bronchus to the actions of the commonly used cancerocidal agent Adriamycin. Syrian Golden hamsters were treated with an endobronchial carcinogen in order to produce bronchial neoplasms or with no carcinogen as controls. Hamsters were then given i.v. Adriamycin, and the amounts and metabolism of bronchial Adriamycin were determined. Peak uptake values were found 5 min after Adriamycin administration, and the amounts of Adriamycin in normal and carcinogen-altered bronchi were found to be similar. Whereas no metabolism of Adriamycin was observed in normal bronchi, 40-60% of total Adriamycin fluorescence was found to be due to Adriamycinol and Adriamycin aglycones in bronchi with premalignant changes. In separate experiments, the susceptibility of normal and carcinogen-altered bronchial extracts to drug-induced lipid peroxidation was measured in vitro. A 50% decrease was found in the ability of carcinogen-altered bronchi to act as a substrate for lipid peroxidation mediated by Adriamycin and an approximately 30% decrease for lipid peroxidation induced by t-butyl-hydroperoxide. These results demonstrate two different mechanisms by which bronchogenic carcinomas might become resistant to the chemotherapeutic actions of Adriamycin. These are by the carcinogen induction of metabolism of Adriamycin to less toxic products and by resistance of the bronchi to free radical damage.

Carcinogenesis in heterotopic respiratory epithelium in canine subcutaneous bronchial autografts.

Short bronchial segments obtained by pneumonectomy were implanted, 9-12 per dog, in the subcutaneous tissues of the back of seven dogs. These subcutaneous bronchial autografts (SBA) became vascularized, and they contained viable, histologically normal respiratory epithelium 4 wk after implantation. From 1-3 mo after implantation, 10% methylcholanthrene in steroid suspension medium was instilled into 21 SBAs, and 10% methylcholanthrene in a silicone polymer sustained release implant was placed in 22 SBAs. Ten SBAs were left carcinogen free as controls. SBA contents were examined cytologically at 3-mo intervals. Biopsies were done from 2-32 mo after carcinogen implantation. Progressive preneoplastic changes were noted in all five dogs which received carcinogen. Curetments of five SBAs after 14-mo exposure to methylcholanthrene yielded 10(4)-10(5) cells from each SBA; 40-70% of the cells obtained were at the same stage of atypical squamous metaplasia. At least one SBA in each dog yielded cancer cells by cytological criteria by 19-29 mo after instillation. Biopsy of a grossly abnormal SBA revealed well-differentiated epidermoid carcinoma at 32 mo. The multiple SBA method provides isolated portions of canine respiratory epithelium for the study of chemical carcinogenesis and for the production of sizable preneoplastic cell populations.