Practical Guide to Implementation Science for Surgical Oncologists: Case Study of Breast Cancer Short Stay Program.

BACKGROUND: Long lags exist in adoption and uptake of evidence-based interventions into real-world clinical practice based on oncology clinical trial results. Implementation science (IS) is a distinct field of health services research that aims to understand the barriers related to adoption of evidence-based guidelines and research in clinical practice. METHODS: Use of IS study design, methods, and outcomes can be elusive to surgical oncologists despite the tremendous need for the application of IS to bridge the evidence-to-practice gap. This report describes key components of high-quality IS. RESULTS: Herein, we illustrate how IS can be used in surgical oncology practice. Examples from implementation of the breast cancer Short Stay Program (SSP) in Netherlands is used to illustrate IS methods. Specific funding and training opportunities in implementation science are described in detail. CONCLUSION: Use of IS in surgical oncology can help improve the uptake of evidence based medicine.

Expenditures and Healthcare Utilization of Patients Receiving Care at a Specialized Primary Care Clinic Designed with and for Autistic Adults.

BACKGROUND: We previously found that autistic adults who received care through a primary care embedded specialized clinic, called the Center for Autism Services and Transition (CAST), had higher satisfaction, continuity of care, and preventive care use than national samples of autistic adults. OBJECTIVE: Examine the impact of CAST on healthcare utilization and expenditures. DESIGN: Retrospective study of medical billing data. SAMPLE: CAST patients (N = 490) were propensity score matched to Medicare-enrolled autistic adults (N = 980) and privately insured autistic adults (N = 980) using demographic characteristics. The median age of subjects was 21 years, 79% were male, and the median duration of observation was 2.2 years. MAIN MEASURES: We quantified expenditures and utilization for primary care; emergency department (ED) visits; inpatient hospitalizations; mental health admissions; and outpatient visits. KEY RESULTS: CAST patients had the highest primary care utilization and expenditures. However, CAST patients had significantly lower expenditures than Medicare-enrolled autistic adults for mental health admissions ($1074 vs $1903), outpatient visits ($1671 vs $2979), and total expenditures ($5893 vs $6987), as well as 57% fewer inpatient hospitalizations. Compared to privately insured autistic adults, CAST patients had significantly lower expenditures for mental health admissions ($1074 vs $1362), inpatient hospitalizations ($3851 vs $4513), and outpatient visits ($1671 vs $6070), as well as 16% fewer inpatient hospitalizations, 24% fewer ED visits, and 50% fewer outpatient visits. On average, CAST patients had more ED visits, mental health admissions, and outpatient visits than Medicare-enrolled autistic adults and more mental health admissions than privately insured autistic adults. CONCLUSIONS: Although CAST patients had greater primary care utilization and expenditures, our findings suggest embedding specialized clinics within broader primary care settings could be an alternative to current standards of care and may reduce expenditures and healthcare utilization in other areas, particularly relative to standard care for privately insured autistic adults.

Assessment of Fall-Related Emergency Medical Service Calls and Transports after a Community-Level Fall-Prevention Initiative.

Background: Getting effective fall prevention into the homes of medically and physically vulnerable individuals is a critical public health challenge. Community paramedicine is emerging globally as a new model of care that allows emergency medical service units to evaluate and treat patients in non-emergency contexts for prevention efforts and chronic care management. The promise of community paramedicine as a delivery system for fall prevention that scales to community-level improvements in outcomes is compelling but untested.Objective: To study the impact of a community paramedic program's optimization of a fall prevention system entailing a clinical pathway and learning health system (called Community-FIT) on community-level fall-related emergency medical service utilization rates.Methods: We used an implementation science framework and quality improvement methods to design and optimize a fall prevention model of care that can be embedded within community paramedic operations. The model was implemented and optimized in an emergency medical service agency servicing a Midwestern city in the United States (∼35,000 residents). Primary outcome measures included relative risk reduction in the number of community-level fall-related 9-1-1 calls and fall-related hospital transports. Interrupted time series analysis was used to evaluate relative risk reduction from a 12-month baseline period (September 2016 - August 2017) to a 12-month post-implementation period (September 2018-August 2019).Results: Community paramedic home visits increased from 25 in 2017, to 236 in 2018, to 517 in 2019, indicating a large increase in the number of households that benefited from the efforts. A relative risk reduction of 0.66 (95% [CI] 0.53, 0.76) in the number of fall calls and 0.63 (95% [CI] 0.46, 0.75) in the number of fall-related calls resulting in transports to the hospital were observed.Conclusions: Community-FIT may offer a powerful mechanism for community paramedics to reduce fall-related 9-1-1 calls and transports to hospitals that can be implemented in emergency medical agencies across the country.

A qualitative study of prevalent laboratory information systems and data communication patterns for genetic test reporting.

PURPOSE: The availability of genetic test data within the electronic health record (EHR) is a pillar of the US vision for an interoperable health IT infrastructure and a learning health system. Although EHRs have been highly investigated, evaluation of the information systems used by the genetic labs has received less attention-but is necessary for achieving optimal interoperability. This study aimed to characterize how US genetic testing labs handle their information processing tasks. METHODS: We followed a qualitative research method that included interviewing lab representatives and a panel discussion to characterize the information flow models. RESULTS: Ten labs participated in the study. We identified three generic lab system models and their relevant characteristics: a backbone system with additional specialized systems for interpreting genetic results, a brokering system that handles housekeeping and communication, and a single primary system for results interpretation and report generation. CONCLUSION: Labs have heterogeneous workflows and generally have a low adoption of standards when sending genetic test reports back to EHRs. Core interpretations are often delivered as free text, limiting their computational availability for clinical decision support tools. Increased provision of genetic test data in discrete and standard-based formats by labs will benefit individual and public health.

A qualitative investigation of biomedical informatics interoperability standards for genetic test reporting: benefits, challenges, and motivations from the testing laboratory's perspective.

PURPOSE: Genetic laboratory test reports can often be of limited computational utility to the receiving clinical information systems, such as clinical decision support systems. Many health-care interoperability (HC) standards aim to tackle this problem, but the perceived benefits, challenges, and motivations for implementing HC interoperability standards from the labs' perspective has not been systematically assessed. METHODS: We surveyed genetic testing labs across the United States and conducted a semistructured interview with responding lab representatives. We conducted a thematic analysis of the interview transcripts to identify relevant themes. A panel of experts discussed and validated the identified themes. RESULTS: Nine labs participated in the interview, and 24 relevant themes were identified within five domains. These themes included the challenge of complex and changing genetic knowledge, the motivation of competitive advantage, provided financial incentives, and the benefit of supporting the learning health system. CONCLUSION: Our study identified the labs' perspective on various aspects of implementing HC interoperability standards in producing and communicating genetic test reports. Interviewees frequently reported that increased adoption of HC standards may be motivated by competition and programs incentivizing and regulating the incorporation of interoperability standards for genetic test data, which could benefit quality control, research, and other areas.

Effects of a Specialized Primary Care Facility on Preventive Service Use Among Autistic Adults: a Retrospective Claims Study.

BACKGROUND: While in some studies, the patient-centered medical home has been linked with increased receipt of preventive services among other populations, there is a paucity of literature testing the effectiveness of medical homes in serving the healthcare needs of autistic adults. OBJECTIVE: To compare the receipt of preventive services by patients at a patient-centered medical home specifically designed for autistic adults (called the Center for Autism Services and Transition "CAST") to US national samples of autistic adults with private insurance or Medicare. DESIGN: Retrospective study of medical billing data. SAMPLE: The study sample included CAST patients (N = 490) who were propensity score matched to Medicare-enrolled autistic adults (N = 980) and privately insured autistic adults (N = 980) using demographic characteristics. The median age of subjects was 21 years old, 79% were male, and the median duration of observation was 2.2 years. MAIN MEASURES: The primary outcome measure was the receipt of any preventive service, as defined by the Medicare Learning Network and AAPC (formerly the American Academy of Professional Coders). Secondary outcome measures included receipt of specific preventive service types (i.e., general health and wellness services, screenings, counseling and therapies, vaccinations, and sexual/reproductive health services). KEY RESULTS: CAST patients had significantly greater odds of receiving any preventive service than Medicare-enrolled (OR = 10.3; 95% CI = 7.6-13.9) and privately insured (OR = 3.1; 95% CI = 2.3-4.2) autistic adults. CAST patients were also significantly more likely to receive screenings and vaccinations than either Medicare beneficiaries (screenings OR = 20.3; 95% CI = 14.7-28.0; vaccinations OR = 5.5; 95% CI = 4.3-7.0) or privately insured beneficiaries (screenings OR = 2.0; 95% CI = 1.6-2.5; vaccinations OR = 3.3; 95% CI = 2.6-4.1). CONCLUSIONS: Autistic adults receiving care through CAST were significantly more likely to recieve preventive care services than national samples of autistic adults. Future comparative effectiveness trials are needed to rigorously assess the impact of primary care-based initiatives to improve care for autistic adults.

Extraction of left ventricular ejection fraction information from various types of clinical reports.

Efforts to improve the treatment of congestive heart failure, a common and serious medical condition, include the use of quality measures to assess guideline-concordant care. The goal of this study is to identify left ventricular ejection fraction (LVEF) information from various types of clinical notes, and to then use this information for heart failure quality measurement. We analyzed the annotation differences between a new corpus of clinical notes from the Echocardiography, Radiology, and Text Integrated Utility package and other corpora annotated for natural language processing (NLP) research in the Department of Veterans Affairs. These reports contain varying degrees of structure. To examine whether existing LVEF extraction modules we developed in prior research improve the accuracy of LVEF information extraction from the new corpus, we created two sequence-tagging NLP modules trained with a new data set, with or without predictions from the existing LVEF extraction modules. We also conducted a set of experiments to examine the impact of training data size on information extraction accuracy. We found that less training data is needed when reports are highly structured, and that combining predictions from existing LVEF extraction modules improves information extraction when reports have less structured formats and a rich set of vocabulary.

Direct concurrent comparison of multiple pediatric acute asthma scoring instruments.

OBJECTIVE: Appropriate delivery of Emergency Department (ED) treatment to children with acute asthma requires clinician assessment of acute asthma severity. Various clinical scoring instruments exist to standardize assessment of acute asthma severity in the ED, but their selection remains arbitrary due to few published direct comparisons of their properties. Our objective was to test the feasibility of directly comparing properties of multiple scoring instruments in a pediatric ED. METHODS: Using a novel approach supported by a composite data collection form, clinicians categorized elements of five scoring instruments before and after initial treatment for 48 patients 2-18 years of age with acute asthma seen at the ED of a tertiary care pediatric hospital ED from August to December 2014. Scoring instruments were compared for inter-rater reliability between clinician types and their ability to predict hospitalization. RESULTS: Inter-rater reliability between clinician types was not different between instruments at any point and was lower (weighted kappa range 0.21-0.55) than values reported elsewhere. Predictive ability of most instruments for hospitalization was higher after treatment than before treatment (p < 0.05) and may vary between instruments after treatment (p = 0.054). CONCLUSIONS: We demonstrate the feasibility of comparing multiple clinical scoring instruments simultaneously in ED clinical practice. Scoring instruments had higher predictive ability for hospitalization after treatment than before treatment and may differ in their predictive ability after initial treatment. Definitive conclusions about the best instrument or meaningful comparison between instruments will require a study with a larger sample size.

An Evolving Ecosystem for Natural Language Processing in Department of Veterans Affairs.

In an ideal clinical Natural Language Processing (NLP) ecosystem, researchers and developers would be able to collaborate with others, undertake validation of NLP systems, components, and related resources, and disseminate them. We captured requirements and formative evaluation data from the Veterans Affairs (VA) Clinical NLP Ecosystem stakeholders using semi-structured interviews and meeting discussions. We developed a coding rubric to code interviews. We assessed inter-coder reliability using percent agreement and the kappa statistic. We undertook 15 interviews and held two workshop discussions. The main areas of requirements related to; design and functionality, resources, and information. Stakeholders also confirmed the vision of the second generation of the Ecosystem and recommendations included; adding mechanisms to better understand terms, measuring collaboration to demonstrate value, and datasets/tools to navigate spelling errors with consumer language, among others. Stakeholders also recommended capability to: communicate with developers working on the next version of the VA electronic health record (VistA Evolution), provide a mechanism to automatically monitor download of tools and to automatically provide a summary of the downloads to Ecosystem contributors and funders. After three rounds of coding and discussion, we determined the percent agreement of two coders to be 97.2% and the kappa to be 0.7851. The vision of the VA Clinical NLP Ecosystem met stakeholder needs. Interviews and discussion provided key requirements that inform the design of the VA Clinical NLP Ecosystem.

Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.

Cooperatively assembled signalling complexes, nucleated by adaptor proteins, integrate information from surface receptors to determine cellular outcomes. In T and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP-76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites recruit key components, including a Tec-family tyrosine kinase, Itk. We identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173, which was phosphorylated upon T-cell receptor stimulation in primary murine and Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of phospholipase C-γ1 (PLC-γ1) in both T and mast cells, and for consequent downstream events, including activation of the IL-2 promoter in T cells, and degranulation and IL-6 production in mast cells. In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to its substrate, PLC-γ1.

Chronic multisymptom illness among female Veterans deployed to Iraq and Afghanistan.

BACKGROUND: Chronic multisymptom illness (CMI) may be more prevalent among female Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) deployed Veterans due to deployment-related experiences. OBJECTIVES: To investigate CMI-related diagnoses among female OEF/OIF/OND Veterans. RESEARCH DESIGN: We estimated the prevalence of the International Classification of Disease-9th edition-Clinical Modification coded CMI-related diagnoses of chronic fatigue syndrome, fibromyalgia (FM), and irritable bowel syndrome (IBS) among female OEF/OIF/OND Veterans with Veterans Health Administration (VHA) visits, FY2002-2012 (n=78,435). We described the characteristics of female Veterans with and without CMI-related diagnoses and VHA settings of first CMI-related diagnoses. RESULTS: The prevalence of CMI-related diagnoses among female OEF/OIF/OND Veterans was 6397 (8.2%), over twice as high as the prevalence 95,424 (3.9%) among the totality of female Veterans currently accessing VHA (P<0.01). There were statistically significant differences in age, education, marital status, military component, service branch, and proportions of those with depression and/or post-traumatic stress disorder diagnoses across females with and without CMI-related diagnoses. Diagnoses were mainly from primary care, women's health, and physical medicine and rehabilitation clinics. CONCLUSIONS: CMI-related diagnoses were more prevalent among female OEF/OIF/OND Veterans compared with all female Veterans who currently access VHA. Future studies of the role of mental health diagnoses as confounders or mediators of the association of OEF/OIF/OND deployment and CMI are warranted. These and other factors associated with CMI may provide a basis for enhanced screening to facilitate recognition of these conditions. Further work should evaluate models of care and healthcare utilization related to CMI in female Veterans.

Mechanism and function of Vav1 localisation in TCR signalling.

The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4(+) and CD8(+) T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3(B)) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3(B) domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.

Publishing protocols for partnered research.

Published scientific protocols are advocated as a means of controlling bias in research reporting. Indeed, many journals require a study protocol with manuscript submission. However, publishing protocols of partnered research (PPR) can be challenging in light of the research model's dynamic nature, especially as no current reporting standards exist. Nevertheless, as these protocols become more prevalent, a priori documentation of methods in partnered research studies becomes increasingly important. Using as illustration a suite of studies aimed at improving coordination and communication in the primary care setting, we sought to identify challenges in publishing PPR relative to traditional designs, present alternative solutions to PPR publication, and propose an initial checklist of content to be included in protocols of partnered research. Challenges to publishing PPR include reporting details of research components intended to be co-created with operational partners, changes to sampling and entry strategy, and alignment of scientific and operational goals. Proposed solutions include emulating reporting standards of qualitative research, participatory action research, and adaptive trial designs, as well as embracing technological tools that facilitate publishing adaptive protocols, with version histories that are able to be updated as major protocol changes occur. Finally, we present a proposed checklist of reporting elements for partnered research protocols.

Requirements for eomesodermin and promyelocytic leukemia zinc finger in the development of innate-like CD8+ T cells.

Conventional and nonconventional T cell development occur in the thymus. Nonconventional thymocytes that bear characteristics typically associated with innate immune cells are termed innate-like lymphocytes (ILLs). Mice harboring a tyrosine to phenylalanine mutation in the adaptor protein Src homology 2 domain-containing leukocyte protein of 76 kDa at residue 145 (Y145F mice) develop an expanded population of CD8(+)CD122(+)CD44(+) ILLs, typified by expression of the T-box transcription factor eomesodermin. Y145F mice also have an expanded population of γδ T cells that produce copious amounts of IL-4 via a mechanism that is dependent on the BTB-ZF transcription factor promyelocytic leukemia zinc finger. Using mice with T cell-specific deletion of Eomes, we demonstrate that this transcription factor is required for CD8(+) ILL development in Y145F as well as wild-type mice. Moreover, we show that promyelocytic leukemia zinc finger and IL-4 are also required for the generation of this ILL population. Taken together, these data shed light on the cell-intrinsic and cell-extrinsic factors that drive CD8(+) ILL differentiation.

Patient Dietary Supplements Use: Do Results from Natural Language Processing of Clinical Notes Agree with Survey Data?

There is widespread use of dietary supplements, some prescribed but many taken without a physician's guidance. There are many potential interactions between supplements and both over-the-counter and prescription medications in ways that are unknown to patients. Structured medical records do not adequately document supplement use; however, unstructured clinical notes often contain extra information on supplements. We studied a group of 377 patients from three healthcare facilities and developed a natural language processing (NLP) tool to detect supplement use. Using surveys of these patients, we investigated the correlation between self-reported supplement use and NLP extractions from the clinical notes. Our model achieved an F1 score of 0.914 for detecting all supplements. Individual supplement detection had a variable correlation with survey responses, ranging from an F1 of 0.83 for calcium to an F1 of 0.39 for folic acid. Our study demonstrated good NLP performance while also finding that self-reported supplement use is not always consistent with the documented use in clinical records.

"Giving the patients less work": A thematic analysis of telehealth use and recommendations to improve usability for autistic adults.

LAY ABSTRACT: Real-time telehealth visits, called "virtual visits," are live video chats between patients and healthcare professionals. There are lots of steps involved in setting up a virtual visit, which may be difficult for some autistic adults. We interviewed 7 autistic adults, 12 family members of autistic adults, and 6 clinic staff from one clinic in the United States. Our goal was to understand their experiences with virtual visits and see how we can make virtual visits easier to use. We re-read text from the interviews to organize experiences and advice that was shared into topics. We found that autistic adults (or their family members) had to connect with clinic staff many times by phone or online over several days to set up a virtual visit. Participants said that having more experience with technology and using the online patient portal made virtual visits easier to use. But, having issues with technology before the visit could make autistic adults and family members anxious. Clinic staff said it was hard for them to meet the needs of people who were using virtual visits and those who were being seen in person at the clinic. Participants recommended reducing the number of calls between staff and autistic adults or family members using the online patient portal instead. Participants also recommended reminder messages, instruction videos, and approximate wait-times to help autistic adults and family members know what to expect for the virtual visit. Our results are based on peoples' experiences at one clinic, but could help other clinics make virtual visits easier to use for autistic adults and their family members.

Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses.

The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76 kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T-cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of WT SLP-76 protein in thymocytes. Here, we show that following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR-generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4+ T-cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. Altogether, our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects.

T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool.

SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) nucleates a signaling complex critical for T-cell receptor (TCR) signal propagation. Mutations in the tyrosines of SLP-76 result in graded defects in TCR-induced signals depending on the tyrosine(s) affected. Here we use 2 strains of genomic knock-in mice expressing tyrosine to phenylalanine mutations to examine the role of TCR signals in the differentiation of effector and memory CD8(+) T cells in response to infection in vivo. Our data support a model in which altered TCR signals can determine the rate of memory versus effector cell differentiation independent of initial T-cell expansion. Furthermore, we show that TCR signals sufficient to promote CD8(+) T-cell differentiation are different from those required to elicit inflammatory cytokine production.

Extracurricular Humanism in Medicine Initiative and Medical Student Wellness: Retrospective Study.

BACKGROUND: Humanism in Medicine Initiative (HIMI), an extracurricular program at Ohio State University College of Medicine (OSUCOM) with 27 subgroups, fosters the humanities. Stress and burnout among first- and second-year medical students are prevalent across the United States. Solutions for stress among first- and second-year medical students have been proposed, but no gold standard exists. The relationship of humanism with stress and burnout has yet to be described in the literature. OBJECTIVE: This study investigates the relationship between participation in the HIMI and stress, burnout, and academic success among first- and second-year medical students. METHODS: First- and second-year medical students enrolled at OSUCOM between August 2018 and August 2019 were recruited. Attendance in the HIMI and membership records were used to measure their participation. Curricular examination scores and those on Step 1 of United States Medical Licensing Examination (USMLE) were used to measure academic success. Stress and burnout were measured using the Maslach Burnout Inventory and the Perceived Stress Scale. RESULTS: In total, 412 students were enrolled with 362 (87%) students participating in HIMI. Those with high participation were more often Black, Asian, female, or with a humanities undergraduate major compared to the overall study population. There were significant relationships between Gold Humanism Honors Society (GHHS) induction and participation of first- and second-year medical students in service- (χ21=5.8, P<.05) or leadership-focused (χ21=19.3, P<.001) HIMI groups. Medium levels of participation in the HIMI were associated with significantly higher stress. Performance on the Step 1 USMLE was not significantly associated with participation levels in the HIMI (low=233.7 vs high=238.0; P=.10). CONCLUSIONS: The HIMI is an extracurricular program vastly utilized by first- and second-year medical students at OSUCOM and did not impact Step 1 USMLE scores. Medium participation in the HIMI was associated with higher stress, and service- and leadership-focused HIMI participation was associated with a higher level of induction to the GHHS. This study identifies areas for future studies to understand the relationship of the HIMI with stress and academic success.