NCI Cancer Research Data Commons: Resources to Share Key Cancer Data.

Since 2014, the NCI has launched a series of data commons as part of the Cancer Research Data Commons (CRDC) ecosystem housing genomic, proteomic, imaging, and clinical data to support cancer research and promote data sharing of NCI-funded studies. This review describes each data commons (Genomic Data Commons, Proteomic Data Commons, Integrated Canine Data Commons, Cancer Data Service, Imaging Data Commons, and Clinical and Translational Data Commons), including their unique and shared features, accomplishments, and challenges. Also discussed is how the CRDC data commons implement Findable, Accessible, Interoperable, Reusable (FAIR) principles and promote data sharing in support of the new NIH Data Management and Sharing Policy. See related articles by Brady et al., p. 1384, Pot et al., p. 1396, and Kim et al., p. 1404.

Massive hemoptysis with end stage renal disease (ESRD): An initial symptom of rare disease.

Microscopic polyangiitis is a rare autoimmune vasculitis, that could present with renal-pulmonary symptoms, posing diagnostic challenges in patients with preexisting kidney disease. Timely diagnosis is crucial to improve patient outcomes.

Provider-to-provider telehealth for sepsis patients in a cohort of rural emergency departments.

BACKGROUND: Telehealth has been proposed as one strategy to improve the quality of time-sensitive sepsis care in rural emergency departments (EDs). The purpose of this study was to measure the association between telehealth-supplemented ED (tele-ED) care, health care costs, and clinical outcomes among patients with sepsis in rural EDs. METHODS: Cohort study using Medicare fee-for-service claims data for beneficiaries treated for sepsis in rural EDs between February 1, 2017, and September 30, 2019. Our primary hospital-level analysis used multivariable generalized estimating equations to measure the association between treatment in a tele-ED-capable hospital and 30-day total costs of care. In our supporting secondary analysis, we conducted a propensity-matched analysis of patients who used tele-ED with matched controls from non-tele-ED-capable hospitals. Our primary outcome was total health care payments among index hospitalized patients between the index ED visit and 30 days after hospital discharge, and our secondary outcomes included hospital mortality, hospital length of stay, 90-day mortality, 28-day hospital-free days, and 30-day inpatient readmissions. RESULTS: In our primary analysis, sepsis patients in tele-ED-capable hospitals had 6.7% higher (95% confidence interval [CI] 2.1%-11.5%) total health care costs compared to those in non-tele-ED-capable hospitals. In our propensity-matched patient-level analysis, total health care costs were 23% higher (95% CI 16.5%-30.4%) in tele-ED cases than matched non-tele-ED controls. Clinical outcomes were similar. CONCLUSIONS: Tele-ED capability in a mature rural tele-ED network was not associated with decreased health care costs or improved clinical outcomes. Future work is needed to reduce rural-urban sepsis care disparities and formalize systems of regionalized care.

An enigmatic presentation of Escherichia coli endocarditis: Emphasizing the role of brain magnetic resonance imaging.

Key Clinical Message: Infective endocarditis should be considered in any febrile individual with acute onset neurological symptoms. If suspicion is high, a negative brain computed tomography does not virtually exclude embolism, and magnetic resonance imaging is warranted. Abstract: A diagnosis of infective endocarditis (IE) is often delayed, particularly in those infected with unusual organisms. Hereby, we report a case of a female patient presented with dysarthria, confusion, and altered mental status after being treated for Escherichia coli bacteremia. Computed tomography of the brain was unrevealing; however, scattered embolic phenomena were visualized on magnetic resonance imaging (MRI). The case underscores the importance of clinical awareness, particularly in the setting of unusual microorganisms, and the role of brain MRI in the diagnosis of IE.

How medical learners and educators decide what counts as mistreatment: A qualitative study.

INTRODUCTION: The mistreatment or abuse (maltreatment) of medical learners by their peers and supervisors has been documented globally for decades, and there is significant research about the prevalence, sequelae and strategies for intervention. However, there is evidence that learners experience maltreatment as being less clear cut than do researchers, educators and administrators. This definitional ambiguity creates problems for understanding and addressing this issue. The objective of this study was to understand how medical learners and educators make sense of less-than-ideal interactions in the clinical learning environment, and to describe which factors influenced their perception that the encounter constituted maltreatment. METHODS: Using constructivist grounded theory, we interviewed 16 medical students, 15 residents or fellows, and 18 educators associated with a single medical school (n = 49). Data collection began with the most junior learners, iterating with analysis as we progressed through the project. Constant comparative analysis was used to gather and compare stories of 'definitely', 'maybe' and 'definitely not' maltreatment across a variety of axes including experience level, clinical setting and type of interaction. RESULTS: Our data show that learners and educators have difficulty classifying their experiences of negative interpersonal interaction, except in the most severe and concrete cases. While there was tremendous variation in the way they categorised similar experiences, there was consistency in the elements drawn upon to make sense of those experiences. Participants interpreted negative interpersonal interactions on an individual basis by considering factors related to the interaction, initiator and recipient. CONCLUSIONS: Only the most negative behaviour is consistently understood as maltreatment; a complex process of individual sense-making is required to determine the acceptability of each interaction. The differences between how individuals judge these interactions highlight an opportunity for administrative, research and faculty development intervention.

Outcomes Associated With Rural Emergency Department Provider-to-Provider Telehealth for Sepsis Care: A Multicenter Cohort Study.

STUDY OBJECTIVE: To test the hypothesis that provider-to-provider tele-emergency department care is associated with more 28-day hospital-free days and improved Surviving Sepsis Campaign (SSC) guideline adherence in rural emergency departments (EDs). METHODS: Multicenter (n=23), propensity-matched, cohort study using medical records of patients with sepsis from rural hospitals in an established, on-demand, rural video tele-ED network in the upper Midwest between August 2016 and June 2019. The primary outcome was 28-day hospital-free days, with secondary outcomes of 28-day inhospital mortality and SSC guideline adherence. RESULTS: A total of 1,191 patients were included in the analysis, with tele-ED used for 326 (27%). Tele-ED cases were more likely to be transferred to another hospital (88% versus 8%, difference 79%, 95% confidence interval [CI] 75% to 83%). After matching and regression adjustment, tele-ED cases did not have more 28-day hospital-free days (difference 0.07 days more for tele-ED, 95% CI -0.04 to 0.17) or 28-day inhospital mortality (adjusted odds ratio [aOR] 0.51, 95% CI 0.16 to 1.60). Adherence with both the SSC 3-hour bundle (aOR 0.59, 95% CI 0.28 to 1.22) and complete bundle (aOR 0.45, 95% CI 0.02 to 11.60) were similar. An a priori-defined subgroup of patients treated by advanced practice providers suggested that the mortality was lower in the cohort with tele-ED use (aOR 0.11, 95% CI 0.02 to 0.73) despite no significant difference in complete SSC bundle adherence (aOR 2.88, 95% CI 0.52 to 15.86). CONCLUSION: Rural emergency department patients treated with provider-to-provider tele-ED care in a mature network appear to have similar clinical outcomes to those treated without.

Currencies of recognition: What rewards and recognition do Canadian distributed medical education preceptors value?

Background: Medical schools spend considerable time, effort, and money on recognition initiatives for rural and distributed medical education (DME) faculty. Previous literature has focused on intrinsic motivation to teach and there is little in the literature to guide institutional recognition efforts or to predict which items or types of recognition will be most appreciated. Methods: To better understand how rural and DME faculty in Canada value different forms of recognition, we asked faculty members from all Canadian medical schools to complete a bilingual, national online survey evaluating their perceptions of currently offered rewards and recognition. The survey received a robust response in both English and French, across nine Canadian provinces and one territory. Results: Our results indicated that there were three distinct ways that preceptors looked at recognition; these perspectives were consistent across geographic and demographic variables. These "clusters" or "currencies of recognition" included: i) Formal institutional recognition, ii) connections, growth and development, and iii) tokens of gratitude. Financial recognition was also found to be important but separate from the three clusters. Some preceptors did value support of intrinsic motivation most important, and for others extrinsic motivators, or a mix of both was most valued. Conclusions: Study results will help medical schools make effective choices in efforts to find impactful ways to recognize rural and DME faculty.

Rewards and recognition for Canadian distributed medical education preceptors: a qualitative analysis.

Background: Recognition of Distributed Medical Education (DME) preceptors by medical schools ensures that important community-based training opportunities remain available to learners. Yet the literature seldom explores what rewards are meaningful to this population of teachers. The goal of our national project was to provide guidance to medical schools about the financial remuneration and non-financial rewards that are most valued by DME preceptors. Methods: In this qualitative study, we invited DME faculty members from all Canadian medical schools to participate in semi-structured interviews. Participants with a range of medical specialties, stages of career, and geographic locations were interviewed via Zoom videoconferencing. The sessions in English and French were audio-recorded and transcribed. We used line-by-line inductive coding and thematic analysis to examine participant talk about meaningful preceptor recognition. Results: Fourteen participants from multiple provinces were interviewed. Results indicated that the DME faculty are a diverse group of people with diverse needs. Most of the interviewees appreciated the rewards and recognition provided by their medical schools but felt that there are areas for improvement. Recognition is not necessarily monetary and should be tailored to the needs and the values of the recipient. Other themes included: benefits and challenges of being a preceptor, current institutional structures and supports, and the impact of the pandemic on preceptors. Conclusions: The interviews highlighted the importance placed by preceptors on personal rewards and a wide variety of forms of recognition. Based on the findings, we suggest specific steps that medical schools can take to support, engage, and recognize DME faculty.

Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model.

Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. Great interest exists in discovering early cancer biomarkers to improve outcomes. Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/).

An economic and health outcome evaluation of telehealth in rural sepsis care: a comparative effectiveness study.

Aim: Sepsis is a top contributor to in-hospital mortality and, healthcare expenditures and telehealth have been shown to improve short-term sepsis care in rural hospitals. This study will evaluate the effect of provider-to-provider video telehealth in rural emergency departments (EDs) on healthcare costs and long-term outcomes for sepsis patients. Materials & methods: We will use Medicare administrative claims to compare total healthcare expenditures, mortality, length-of-stay, readmissions, and category-specific costs between telehealth-subscribing and control hospitals. Results: The results of this work will demonstrate the extent to which telehealth use is associated with total healthcare expenditures for sepsis care. Conclusion: These findings will be important to inform future policy initiatives to improve sepsis care in rural EDs. Clinical Trial Registration: NCT05072145 (ClinicalTrials.gov).

Sepsis is a severe condition that results from infection. In addition to costly care, sepsis is a leading cause of death and disability. When comparing outcomes, those treated for sepsis in lower volume emergency departments fare worse and rural emergency departments often have lower patient volumes. While telehealth has been shown to improve sepsis care, the effect of telehealth on costs and long-term outcomes for patients is unclear. This study will use Medicare claims data to compare outcomes for people with sepsis in rural emergency departments who had video telehealth used with those who did not have video telehealth used, with the goal of measuring how telehealth affects healthcare costs, hospital readmissions and deaths after hospital discharge.

Energizing scholarly activity in a regional medical campus.

Medical education is increasingly delivered at distributed sites away from Academic Health Sciences Centres. The Council of Ontario Faculties of Medicine recommends schools develop resources and metrics to foster regional campus scholarly activity. Opportunities for distributed program trainees must support learning core skills in research and critical appraisal to comply with medical school accreditation standards and to develop their interests and skills in scholarly work for their future medical careers. We describe a scholarly activity program that is a template for distributed campuses or regional teaching sites seeking to increase learner and faculty engagement and research productivity.

La formation médicale décentralisée se déroule de plus en plus souvent loin des centres universitaires de sciences de la santé. Le Conseil des facultés de médecine de l'Ontario recommande aux facultés de se doter de ressources et de indicateurs pour encourager les activités d'érudition sur les campus régionaux. Les possibilités offertes aux stagiaires des programmes décentralisés doivent favoriser l'apprentissage des habiletés de base en recherche et en lecture critique pour se conformer aux normes d'agrément des facultés de médecine et développer des intérêts et des habiletés en érudition qui leur seront utiles dans leur carrière médicale. Nous décrivons un programme d'activités d'érudition qui peut servir de modèle pour les milieux de formation décentralisés ou les sites d'enseignement régionaux souhaitant stimuler la productivité scientifique et l'implication des apprenants et du corps professoral dans la recherche.

Intrathecal amyloid-beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease.

AIMS: An obstacle to developing new treatment strategies for Alzheimer's disease (AD) has been the inadequate translation of findings in current AD transgenic rodent models to the prediction of clinical outcomes. By contrast, nonhuman primates (NHPs) share a close neurobiology with humans in virtually all aspects relevant to developing a translational AD model. The present investigation used African green monkeys (AGMs) to refine an inducible NHP model of AD based on the administration of amyloid-beta oligomers (AßOs), a key upstream initiator of AD pathology. METHODS: AßOs or vehicle were repeatedly delivered over 4 weeks to age-matched young adult AGMs by intracerebroventricular (ICV) or intrathecal (IT) injections. Induction of AD-like pathology was assessed in subregions of the medial temporal lobe (MTL) by quantitative immunohistochemistry (IHC) using the AT8 antibody to detect hyperphosphorylated tau. Hippocampal volume was measured by magnetic resonance imaging (MRI) scans prior to, and after, intrathecal injections. RESULTS: IT administration of AßOs in young adult AGMs revealed an elevation of tau phosphorylation in the MTL cortical memory circuit compared with controls. The largest increases were detected in the entorhinal cortex that persisted for at least 12 weeks after dosing. MRI scans showed a reduction in hippocampal volume following AßO injections. CONCLUSIONS: Repeated IT delivery of AßOs in young adult AGMs led to an accelerated AD-like neuropathology in MTL, similar to human AD, supporting the value of this translational model to de-risk the clinical trial of diagnostic and therapeutic strategies.

Thioether-Based Polymeric Micelles with Fine-Tuned Oxidation Sensitivities for Chemotherapeutic Drug Delivery.

Oxidation-sensitive drug delivery systems (DDSs) have attracted attention due to the potential to improve efficacy and safety of chemotherapeutics. These systems are designed to release the payload in response to oxidative stress conditions, which are associated with many types of cancer. Despite extensive research on the development of oxidation-sensitive DDS, the lack of selectivity toward cancer cells over healthy cells remains a challenge. Here, we report the design and characterization of polymeric micelles containing thioether groups with varying oxidation sensitivities within the micellar core, which become hydrophilic upon thioether oxidation, leading to destabilization of the micellar structure. We first used the thioether model compounds, 3-methylthiopropylamide (TPAM), thiomorpholine amide (TMAM), and 4-(methylthio)benzylamide (TPhAM) to investigate the effect of the chemical structures of the thioethers on the oxidation by hydrogen peroxide (H2O2). TPAM shows the fastest oxidation, followed by TMAM and TPhAM, showing that the oxidation reaction of thioethers can be modulated by changing the substituent groups bound to the sulfur atom. We next prepared micelles containing these different thioether groups within the core (TP, TM, and TPh micelles). The micelles containing the thioether groups with a higher oxidation sensitivity were destabilized by H2O2 at a lower concentration. Micelle destabilization was also tested in human liver cancer (HepG2) cells and human umbilical vein endothelial cells (HUVECs). The TP micelles having the highest oxidation sensitivity were destabilized in both HepG2 cells and HUVECs, while the TPh micelles, which showed the lowest reactivity toward H2O2, were stable in these cell lines. The TM micelles possessing a moderate oxidation sensitivity were destabilized in HepG2 cells but were stable in HUVECs. Furthermore, the micelles were loaded with doxorubicin (Dox) to evaluate their potential in drug delivery applications. Among the micelles, the TM micelles loaded with Dox showed the enhanced relative toxicity in HepG2 cells over HUVECs. Therefore, our approach to fine-tune the oxidation sensitivity of the micelles has potential for improving therapeutic efficacy and safety of drugs in cancer treatment.

COVID-19 biomarkers and their overlap with comorbidities in a disease biomarker data model.

In response to the COVID-19 outbreak, scientists and medical researchers are capturing a wide range of host responses, symptoms and lingering postrecovery problems within the human population. These variable clinical manifestations suggest differences in influential factors, such as innate and adaptive host immunity, existing or underlying health conditions, comorbidities, genetics and other factors-compounding the complexity of COVID-19 pathobiology and potential biomarkers associated with the disease, as they become available. The heterogeneous data pose challenges for efficient extrapolation of information into clinical applications. We have curated 145 COVID-19 biomarkers by developing a novel cross-cutting disease biomarker data model that allows integration and evaluation of biomarkers in patients with comorbidities. Most biomarkers are related to the immune (SAA, TNF-∝ and IP-10) or coagulation (D-dimer, antithrombin and VWF) cascades, suggesting complex vascular pathobiology of the disease. Furthermore, we observe commonality with established cancer biomarkers (ACE2, IL-6, IL-4 and IL-2) as well as biomarkers for metabolic syndrome and diabetes (CRP, NLR and LDL). We explore these trends as we put forth a COVID-19 biomarker resource (https://data.oncomx.org/covid19) that will help researchers and diagnosticians alike.

TELEmedicine as an intervention for sepsis in emergency departments: a multicenter, comparative effectiveness study (TELEvISED Study).

Sepsis is a life-threatening infection that affects over 1.7 million Americans annually. Low-volume rural hospitals have worse sepsis outcomes, and emergency department (ED)-based telemedicine (tele-ED) has been one promising strategy for improving rural sepsis care. The objective of this study is to evaluate the impact of tele-ED consultation on sepsis care and outcomes in rural ED patients. The TELEvISED study is a multicenter (n = 25) retrospective propensity-matched comparative effectiveness study of tele-ED care for rural sepsis patients in a mature tele-ED network. Telemedicine-exposed patients will be matched with non telemedicine patients using a propensity score to predict tele-ED use. The primary outcome is 28-day hospital free days, and secondary outcomes include adherence with guidelines, mortality and organ failure. ClinicalTrials.gov: NCT04441944.

Paediatric tele-emergency care: A study of two delivery models.

INTRODUCTION: Tele-emergency models have been utilized for decades, with growing evidence of their effectiveness. Due to the variety of tele-emergency department (tele-ED) models used in practice, however, it is challenging to build standardized metrics for ongoing evaluation. This study describes two tele-ED programs, one specialized and one general, that provide care to paediatric populations. Through an examination of model structures and patient populations, we gain insight into how evaluative measures should reflect tele-ED model design and purpose. METHODS: Qualitative descriptions of the two tele-ED models are presented. We show a retrospective cohort analysis describing paediatric patients' key characteristics, reasons for visit, and disposition status by case/control status. Case/control patient encounter data were collected October 2015 through December 2017, from 15 spoke hospitals within each tele-ED program. RESULTS: The two tele-ED models serve distinct paediatric populations, and measures of tele-ED utilization and disposition reflect those differences. In the specialized University of California (UC) Davis Health program, tele-ED was utilized in 36% of paediatric critical care encounters and 78% of those were transferred. In the Avera eCARE program, tele-ED was activated in 1.7% of paediatric encounters and 50.6% of those were transferred. When Avera eCARE paediatric encounters were stratified by severity, measures of tele-ED use and disposition status among high-severity encounters were more similar to UC Davis Health. DISCUSSION: This study describes how design choices of tele-ED models have implications for evaluative measures. Measures of tele-ED model success need to reflect model purpose, populations served, and for whom tele-ED service use is appropriate.

Tele-emergency behavioural health in rural and underserved areas.

INTRODUCTION: Challenges accessing behavioural health services in rural and underserved areas are compounded by severe shortages of behavioural health specialists, and difficulties placing patients. Tele-emergency (tele-ED) behavioural health is a promising solution for enhancing access to specialists and assisting in patient placement. This paper describes two tele-ED behavioural health models in the Midwest delivering mental- and substance use disorder services to rural and underserved adult populations. METHODS: We performed an in-depth examination of two tele-ED behavioural health programmes and their consultation processes. We provide a retrospective case-control analysis of patient characteristics, patient diagnoses, and disposition status for each model. Data were collected from 19 spoke hospitals across the two programmes between November 2015 and December 2017. RESULTS: Tele-ED was activated in 15% of the Avera Health sample and 58% of the Union Hospital sample. This is primarily a reflection of the sample selection process in each model and how each programme is operationalised. Suicide and/or poisoning by drugs were the most frequent diagnoses followed by mood disorders. Rate of transfer to another inpatient facility was much higher for tele-ED cases than controls in both models. DISCUSSION: This paper describes how two distinct tele-ED behavioural health models operating in unique contexts address challenges in access and placement for patients in rural and underserved areas presenting to EDs with behavioural health conditions. The notable difference in disposition rates between cases and controls is indicative of the impact each model is having on care practices and processes.