A Multisite Electronic Health Record Integrated Remote Monitoring Intervention for Hypertension Improvement: Protocol for a Randomized Pragmatic Comparative Effectiveness Trial.

BACKGROUND: Hypertension is a major contributor to various adverse health outcomes. Although previous studies have shown the benefits of home blood pressure (BP) monitoring over office-based measurements, there is limited evidence comparing the effectiveness of whether a BP monitor integrated into the electronic health record is superior to a nonintegrated BP monitor. OBJECTIVE: In this paper, we describe the protocol for a pragmatic multisite implementation of a quality improvement initiative directly comparing integrated to nonintegrated BP monitors for hypertension improvement. METHODS: We will conduct a randomized, comparative effectiveness trial at 3 large academic health centers across California. The 3 sites will enroll a total of 660 participants (approximately n=220 per site), with 330 in the integrated BP monitor arm and 330 in the nonintegrated BP control arm. The primary outcome of this study will be the absolute difference in systolic BP in mm Hg from enrollment to 6 months. Secondary outcome measures include binary measures of hypertension (controlled vs uncontrolled), hypertension-related health complications, hospitalizations, and death. The list of possible participants will be generated from a central data warehouse. Randomization will occur after enrollment in the study. Participants will use their assigned BP monitor and join site-specific hypertension interventions. Cross-site learning will occur at regular all-site meetings facilitated by the University of California, Los Angeles Value-Based Care Research Consortium. A pre- and poststudy questionnaire will be conducted to further evaluate participants' perspectives regarding their BP monitor. Linear mixed effects models will be used to compare the primary outcome measure between study arms. Mixed effects logistic regression models will be used to compare secondary outcome measures between study arms. RESULTS: The study will start enrolling participants in the second quarter of 2023 and will be completed by the first half of 2024. Results will be published by the end of 2024. CONCLUSIONS: This pragmatic trial will contribute to the growing field of chronic care management using remote monitoring by answering whether a hypertension intervention coupled with an electronic health record integrated home BP monitor improves patients' hypertension better than a hypertension intervention with a nonintegrated BP monitor. The outcomes of this study may help health system decision makers determine whether to invest in integrated BP monitors for vulnerable patient populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT05390502; clinicaltrials.gov/study/NCT05390502. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45915.

A Variable Selection Algorithm for Creating Replicable Factor Structures.

Exploratory and confirmatory factor analyses are commonly employed to identify and explore underlying factor structures. Unfortunately, when variable selection is involved, results often fluctuate across studies making it difficult to determine the "best" and most replicable factor structure. This study proposes a new factor analysis variable selection algorithm called the Replicable Factor Analytic Solutions (RFAS) that incorporates sound statistical and psychometric practices when selecting the final factor structure, while simultaneously examining the observed variables and factor structures replicability. This article outlines the algorithm development and rationale for each decision in the algorithm's development. An example using simulated and empirical data is also provided to display the algorithm results and delineate the utility of these results for future analysts.

Retrospective identification of infection in the emergency department: A significant challenge in sepsis clinical trials.

BACKGROUND: This study examined three methods for retrospectively identifying infection in emergency department (ED) patients: modified objective definitions of infection (MODI) from the CDC/NHSN, physician adjudication determination of infection, and ED treating physician behavior. METHODS: This study used a subset of data from a prospective sepsis trial. We used Fleiss's Kappa to compare agreement between two physicians retrospectively adjudicating infection based on the patient's medical record, modified infection definition from the CDC/NHSN, and ED treating physician behavior. RESULTS: Overall, there was similar agreement between physician adjudication of infection and MODI criteria (Kappa=0.59) compared to having two physicians independently identify infection through retrospective chart review (Kappa=0.58). ED treating physician behavior was a poorer proxy for infection when compared to the MODI criteria (0.41) and physician adjudication (Kappa = 0.50). CONCLUSIONS: Retrospective identification of infection poses a significant challenge in sepsis clinical trials. Using modified definitions of infection provides a standardized, less time consuming, and equally effective means of identifying infection compared to having multiple physicians adjudicate a patient's chart.

Assessment of a Cellular Host Response Test as a Sepsis Diagnostic for Those With Suspected Infection in the Emergency Department.

OBJECTIVES: Sepsis is a common cause of morbidity and mortality. A reliable, rapid, and early indicator can help improve efficiency of care and outcomes. To assess the IntelliSep test, a novel in vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes, as a rapid diagnostic for sepsis and a measure of severity of illness, as defined by Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation-II scores and the need for hospitalization. DESIGN SETTING SUBJECTS: Adult patients presenting to two emergency departments in Baton Rouge, LA, with signs of infection (two of four systemic inflammatory response syndrome criteria, with at least one being aberration of temperature or WBC count) or suspicion of infection (a clinician order for culture of a body fluid), were prospectively enrolled. Sepsis status, per Sepsis-3 criteria, was determined through a 3-tiered retrospective and blinded adjudication process consisting of objective review, site-level clinician review, and final determination by independent physician adjudicators. MEASUREMENTS AND MAIN RESULTS: Of 266 patients in the final analysis, those with sepsis had higher IntelliSep Index (median = 6.9; interquartile range, 6.1-7.6) than those adjudicated as not septic (median = 4.7; interquartile range, 3.7-5.9; p < 0.001), with an area under the receiver operating characteristic curve of 0.89 and 0.83 when compared with unanimous and forced adjudication standards, respectively. Patients with higher IntelliSep Index had higher Sequential Organ Failure Assessment (3 [interquartile range, 1-5] vs 1 [interquartile range, 0-2]; p < 0.001) and Acute Physiology and Chronic Health Evaluation-II (7 [interquartile range, 3.5-11.5] vs 5 [interquartile range, 2-9]; p < 0.05) and were more likely to be admitted to the hospital (83.6% vs 48.3%; p < 0.001) compared with those with lower IntelliSep Index. CONCLUSIONS: In patients presenting to the emergency department with signs or suspicion of infection, the IntelliSep Index is a promising tool for the rapid diagnosis and risk stratification for sepsis.

Effectiveness of a Patient Education Class to Enhance Knowledge about Lung Cancer Screening: a Quality Improvement Evaluation.

Best practices to facilitate high-quality shared decision-making for lung cancer screening (LCS) are not well established. In our LCS program, patients are first referred to attend a free group education class on LCS, taught by designated clinician specialists, before a personal shared decision-making visit is scheduled. We conducted an evaluation on  the effectiveness of this class to enhance patient knowledge and shared decision-making about LCS. For quality improvement purposes, participants were asked to complete one-page surveys immediately before and after class to assess knowledge and decision-making capacity regarding LCS. To evaluate knowledge gained, we tabulated the distributions of correct, incorrect, unsure, and missing responses to eight true-false statements included on both pre- and post-class surveys and assessed pre-post differences in the number of correct responses. To evaluate decision-making capacity, we tabulated the distributions of post-class responses to items on decision uncertainty. From June 2017 to August 2018, 680 participants completed both pre- and post-class surveys. Participants had generally poor baseline knowledge about LCS. The proportion who responded correctly to each knowledge-related statement increased pre- to post-class, with a mean difference of 0.9 (paired t test, p < 0.0001) in the total number of correct responses between surveys. About 70% reported having all the information needed to make a screening decision. Our results suggest that a well-designed group education class is an effective system-level approach for initially educating and equipping patients with appropriate knowledge to make informed decisions about LCS.

Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage Capacities.

Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single-cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation. Multiple cell fates, including renewed stem cells and committed differentiating progenitors, are specified during this early window of activation. We further show that Sox2 is essential for cells to transition from the activated to neuronal progenitor states. Our study highlights strategies for stem cell-mediated regeneration that may be conserved in other adult stem cell niches.

A conceptual framework: the early and late phases of skeletal muscle dysfunction in the acute respiratory distress syndrome.

Patients with acute respiratory distress syndrome (ARDS) often develop severe diaphragmatic and limb skeletal muscle dysfunction. Impaired muscle function in ARDS is associated with increased mortality, increased duration of mechanical ventilation, and functional disability in survivors. In this review, we propose that muscle dysfunction in ARDS can be categorized into an early and a late phase. These early and late phases are based on the timing in relationship to lung injury and the underlying mechanisms. The early phase occurs temporally with the onset of lung injury, is driven by inflammation and disuse, and is marked predominantly by muscle atrophy from increased protein degradation. The ubiquitin-proteasome, autophagy, and calpain-caspase pathways have all been implicated in early-phase muscle dysfunction. Late-phase muscle weakness persists in many patients despite resolution of lung injury and cessation of ongoing acute inflammation-driven muscle atrophy. The clinical characteristics and mechanisms underlying late-phase muscle dysfunction do not involve the massive protein degradation and atrophy of the early phase and may reflect a failure of the musculoskeletal system to regain homeostatic balance. Owing to these underlying mechanistic differences, therapeutic interventions for treating muscle dysfunction in ARDS may differ during the early and late phases. Here, we review clinical and translational investigations of muscle dysfunction in ARDS, placing them in the conceptual framework of the early and late phases. We hypothesize that this conceptual model will aid in the design of future mechanistic and clinical investigations of the skeletal muscle system in ARDS and other critical illnesses.

Implementation science in cancer prevention and control: a decade of grant funding by the National Cancer Institute and future directions.

BACKGROUND: The National Cancer Institute (NCI) has supported implementation science for over a decade. We explore the application of implementation science across the cancer control continuum, including prevention, screening, treatment, and survivorship. METHODS: We reviewed funding trends of implementation science grants funded by the NCI between 2000 and 2012. We assessed study characteristics including cancer topic, position on the T2-T4 translational continuum, intended use of frameworks, study design, settings, methods, and replication and cost considerations. RESULTS: We identified 67 NCI grant awards having an implementation science focus. R01 was the most common mechanism, and the total number of all awards increased from four in 2003 to 15 in 2012. Prevention grants were most frequent (49.3%) and cancer treatment least common (4.5%). Diffusion of Innovations and Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) were the most widely reported frameworks, but it is unclear how implementation science models informed planned study measures. Most grants (69%) included mixed methods, and half reported replication and cost considerations (49.3%). CONCLUSIONS: Implementation science in cancer research is active and diverse but could be enhanced by greater focus on measures development, assessment of how conceptual frameworks and their constructs lead to improved dissemination and implementation outcomes, and harmonization of measures that are valid, reliable, and practical across multiple settings.

Implementation science in cancer prevention and control: a framework for research and programs in low- and middle-income countries.

Implementation science is a set of tools, principles, and methodologies that can be used to bring scientific evidence into action, improve health care quality and delivery, and improve public health. As the burden of cancer increases in low- and middle-income countries, it is important to plan cancer control programs that are both evidence based and delivered in ways that are feasible, cost-effective, contextually appropriate, and sustainable. This review presents a framework for using implementation science for cancer control planning and implementation and discusses potential areas of focus for research and programs in low- and middle-income countries interested in integrating research into practice and policy.

How pragmatic is it? Lessons learned using PRECIS and RE-AIM for determining pragmatic characteristics of research.

BACKGROUND: The need for high-quality evidence that is applicable in real-world, routine settings continues to increase. Pragmatic trials are designed to evaluate the effectiveness of interventions in real-world settings, whereas explanatory trials aim to test whether an intervention works under optimal situations. There is a continuum between explanatory and pragmatic trials. Most trials have aspects of both, making it challenging to label and categorize a trial and to evaluate its potential for translation into practice. METHODS: We summarize our experience applying the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) combined with external validity items based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to three studies to provide a more robust and comprehensive assessment of trial characteristics related to translation of research. We summarize lessons learned using domains from the combined frameworks for use in study planning, evaluating specific studies, and reviewing the literature and make recommendations for future use. RESULTS: A variety of coders can be trained to use the PRECIS and RE-AIM domains. These domains can also be used for diverse purposes, content areas, and study types, but are not without challenges. Both PRECIS and RE-AIM domains required modification in two of the three studies to evaluate and rate domains specific to study type. Lessons learned involved: dedicating enough time for training activities related to the domains; use of reviewers with a range of familiarity with specific study protocols; how to best adapt ratings that reflect complex study designs; and differences of opinion regarding the value of creating a composite score for these criteria. CONCLUSIONS: Combining both frameworks can specifically help identify where and how a study is and is not pragmatic. Using both PRECIS and RE-AIM allows for standard reporting of key study characteristics related to pragmatism and translation. Such measures should be used more consistently to help plan more pragmatic studies, evaluate progress, increase transparency of reporting, and integrate literature to facilitate translation of research into practice and policy.

Implementation science approaches for integrating eHealth research into practice and policy.

PURPOSE: To summarize key issues in the eHealth field from an implementation science perspective and to highlight illustrative processes, examples and key directions to help more rapidly integrate research, policy and practice. METHODS: We present background on implementation science models and emerging principles; discuss implications for eHealth research; provide examples of practical designs, measures and exemplar studies that address key implementation science issues; and make recommendations for ways to more rapidly develop and test eHealth interventions as well as future research, policy and practice. RESULTS: The pace of eHealth research has generally not kept up with technological advances, and many of our designs, methods and funding mechanisms are incapable of providing the types of rapid and relevant information needed. Although there has been substantial eHealth research conducted with positive short-term results, several key implementation and dissemination issues such as representativeness, cost, unintended consequences, impact on health inequities, and sustainability have not been addressed or reported. Examples of studies in several of these areas are summarized to demonstrate this is possible. CONCLUSIONS: eHealth research that is intended to translate into policy and practice should be more contextual, report more on setting factors, employ more responsive and pragmatic designs and report results more transparently on issues important to potential adopting patients, clinicians and organizational decision makers. We outline an alternative development and assessment model, summarize implementation science findings that can help focus attention, and call for different types of more rapid and relevant research and funding mechanisms.

A systematic review of eHealth cancer prevention and control interventions: new technology, same methods and designs?

There has been a recent surge of eHealth programs in cancer and other content areas, but few reviews have focused on the methodologies and designs employed in these studies. We conducted a systematic review of studies on eHealth interventions on cancer prevention and control published between 2001 and 2010 applying the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) criteria and external validity components from the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. We identified 113 studies that focused on cancer prevention and control of eHealth interventions. Most studies fell midway along the explanatory/pragmatic trial continuum, but few reported on various practical feasibility criteria for translation. Despite vast interest in cancer eHealth and the applied nature of this field, few studies considered key external validity issues. There is a need for use of alternative pragmatic study designs and transparent reporting of external validity components to produce more rapid and generalizable results.

Research to reality (R2R) mentorship program: building partnership, capacity, and evidence.

Despite a wealth of intervention research in cancer control, full integration of evidence-based interventions into practice often fails, at least in part because of inadequate collaboration between practitioners and researchers. The National Cancer Institute piloted a mentorship program designed for practitioners to improve their ability to navigate evidence-based decision making within a context of inadequate resources, political barriers, and organizational constraints. The National Cancer Institute simultaneously sought to provide opportunities for practitioners and researchers to share and learn from each other. We identified four key successes and challenges related to translation as experienced by mentees: (a) establishing and maintaining partnerships, (b) data collection and analysis, (c) navigating context, and (d) program adaptation and evaluation. Mentorship programs have the potential to facilitate increased and more successful integration of evidence-based interventions into practice by promoting and building the capacity for collaborative decision making and generating in-depth understanding of the translation barriers and successes as well as strategies to address the complex contextual issues relative to implementation.

Suppression of glioma progression by Egln3.

Grade IV astrocytoma or glioblastoma has a poor clinical outcome that can be linked to hypoxia, invasiveness and active vascular remodeling. It has recently been suggested that hypoxia-inducible factors, Hifs, increase glioma growth and aggressiveness [1], [2], [3]. Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3), a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma models. Through intracranial tumorigenesis and in vitro assays, we demonstrate for the first time that Egln3 was sufficient to decrease the kinetics of tumor progression and increase survival. We also find that Klf5, a transcription factor important to vascular remodeling, was regulated by hypoxia in glioma. An analysis of the tumor vasculature revealed that elevated Egln3 normalized glioma capillary architecture, consistent with a role for Egln3 in eliciting decreases in the production of Hif-regulated, angiogenic factors. We also find that the hydroxylase-deficient mutant, Egln3(H196A) partially maintained tumor suppressive activity. These results highlight a bifurcation of Egln3 signaling and suggest that Egln3 has a non-hydroxylase-dependent function in glioma. We conclude that Egln3 is a critical determinant of glioma formation and tumor vascular functionality.

Evolution of Cancer Control P.L.A.N.E.T.: moving research into practice.

Evidence-based interventions (EBIs) are not broadly implemented, despite widespread availability of programs, policies, and guidelines. Systematic processes for integrating EBIs with community preference remain challenging for cancer control and prevention, as well as other areas. The Cancer Control P.L.A.N.E.T. (P.L.A.N.E.T) Web portal provides a platform to access data, EBIs, and resources to foster local partnerships and assist public health researchers and practitioners design, implement, and evaluate evidence-based cancer control programs. This article summarizes the evolution of P.L.A.N.E.T. and describes effective and innovative Web 2.0 strategies to increase Web visits, create more interactive platforms for researchers and practitioners to integrate evidence-based resources, community preferences, and the complex context in which programs and policies are implemented. Lessons learned could benefit public health settings and reach low-income, high-risk communities. Researchers, community practitioners, and government partnerships should continue to develop and test innovative ways to address pressing issues in cancer control, health disparities, and health delivery.

Do aspirin and statins prevent severe sepsis?

PURPOSE OF REVIEW: Sepsis is an inflammatory condition associated with significant morbidity and mortality. Given the lack of specific therapies for the condition, prevention has garnered significant interest and increased importance. The article reviews the current literature regarding the use of aspirin and statins for the prevention of sepsis. RECENT FINDINGS: Aspirin and statins have been integral in the prevention of atherosclerotic disease. Additionally, statins have proven beneficial in the prevention of nonatherosclerotic conditions secondary to their pleiotropic effects. In animal models, this pleiotropism modulates many inflammatory pathways of sepsis. The platelet also plays an integral role in this inflammatory cascade of sepsis. Scientific data indicates that antiplatelet therapy, including aspirin, may attenuate these undesirable effects of platelets. Finally, observational studies have shown that patients taking statins have a decreased incidence of sepsis and septic shock, and aspirin may potentiate these benefits. SUMMARY: Sepsis is a deadly and costly condition with no available, specific treatment options. The statins and aspirin are well tolerated and widely used for prevention of cardiovascular disease. Because of their effects on the immune system and inflammatory pathways, they may present viable medical options for the prevention of sepsis.

Factors influencing prostate cancer screening decisions among African American men.

PURPOSE: Due to controversy regarding prostate cancer screening, it is imperative that African American men make informed decisions. Little is known about the role of cultural factors in decision-making for prostate cancer screening among African American men. The purposes of this study were: 1) to investigate components involved with decision-making for prostate cancer screening among African American men; and 2) to identify cultural factors that may influence screening decisions. METHODS: Six focus group sessions were conducted consisting of African American men between the ages of 40 and 70. RESULTS: Eight themes emerged from the discussions about prostate cancer screening. These themes were: 1) men's knowledge of prostate cancer and clinical services; 2) prostate cancer as a threat to manhood; 3) screening as a threat to manhood; 4) self-awareness of health and well-being; 5) value of screening; 6) convenience of prostate specific antigen (PSA) screening; 7) misunderstanding of screening controversy; 8) distrust of the medical community; and 9) shared decision-making. CONCLUSION: This study identifies cultural factors involved with decision-making for prostate cancer screening among African American men.