Randomized Controlled Trials of Electronic Health Record Interventions: Design, Conduct, and Reporting Considerations.

Electronic health record (EHR) systems can be configured to deliver novel EHR interventions that influence clinical decision making and to support efficient randomized controlled trials (RCTs) designed to evaluate the effectiveness, safety, and costs of those interventions. In designing RCTs of EHR interventions, one should carefully consider the unit of randomization (for example, patient, encounter, clinician, or clinical unit), balancing concerns about contamination of an intervention across randomization units within clusters (for example, patients within clinical units) against the superior control of measured and unmeasured confounders that comes with randomizing a larger number of units. One should also consider whether the key computational assessment components of the EHR intervention, such as a predictive algorithm used to target a subgroup for decision support, should occur before randomization (so that only 1 subgroup is randomized) or after randomization (including all subgroups). When these components are applied after randomization, one must consider expected heterogeneity in the effect of the differential decision support across subgroups, which has implications for overall impact potential, analytic approach, and sample size planning. Trials of EHR interventions should be reviewed by an institutional review board, but may not require patient-level informed consent when the interventions being tested can be considered minimal risk or quality improvement, and when clinical decision making is supported, rather than controlled, by an EHR intervention. Data and safety monitoring for RCTs of EHR interventions should be conducted to guide institutional pragmatic decision making about implementation and ensure that continuing randomization remains justified. Reporting should follow the CONSORT (Consolidated Standards of Reporting Trials) Statement, with extensions for pragmatic trials and cluster RCTs when applicable, and should include detailed materials to enhance reproducibility.

Assessing contributions of value-added medical student roles.

Value-added student roles-defined as student activities that simultaneously teach physicianship and improve the healthcare system-have rapidly gained popularity in recent years. Though many agree that value-added medical student roles can contribute both to student learning and to patient outcomes, impact evaluation of these roles can pose a challenge. In this Personal View, we describe our quality improvement project at UC San Francisco aimed at reducing unnecessary physical therapist (PT) referrals. While our primary outcome measure remained unchanged, the project helped to galvanize safe mobilization efforts in the hospital and led to the establishment of a UCSF Health Safe Mobilization Committee, leading to broader and potentially more impactful institutional systems changes. How do we interpret success, and how do we appraise the potential impact students can have in a complex health system? While we agree with the importance of process-focused metrics that assess student participation in an interprofessional, data-driven quality improvement effort, we also see a role for an expanded assessment of student contributions to capture systems improvements that may occur downstream of student activities.

Imprinting on Clinical Rotations: Multisite Survey of High- and Low-Value Medical Student Behaviors and Relationship with Healthcare Intensity.

BACKGROUND: Physician behaviors are important to high-value care, and the learning environment medical students encounter on clinical clerkships may imprint their developing practice patterns. OBJECTIVES: To explore potential imprinting on clinical rotations by (a) describing high- and low-value behaviors among medical students and (b) examining relationships with regional healthcare intensity (HCI). DESIGN: Multisite cross-sectional survey PARTICIPANTS: Third- and fourth-year students at nine US medical schools MAIN MEASURES: Survey items measured high-value (n = 10) and low-value (n = 9) student behaviors. Regional HCI was measured using Dartmouth Atlas End-of-Life Chronic Illness Care data (ratio of physician visits per decedent compared with the US average, hospital care intensity index, ratio of medical specialty to primary care physician visits per decedent). Associations between regional HCI and student behaviors were examined using unadjusted and adjusted (controlling for age, sex, and year in school) logistic regression analyses, using median item ratings to summarize reported engagement in high- and low-value behaviors. KEY RESULTS: Of 2623 students invited, 1304 (50%) responded. Many reported trying to determine healthcare costs (1085/1234, 88%), but only 45% (571/1257) reported including cost details in case presentations. Students acknowledged suggesting tests solely to anticipate what their supervisor would want (1143/1220, 94%), show off their ability to generate a broad differential diagnosis (1072/1218, 88%), satisfy curiosity (958/1217, 79%), protect the team from liability (938/1215, 77%), and build clinical experience (533/1217, 44%). Students in higher intensity regions reported significantly more low-value behaviors: each one-unit increase in the ratio of physician visits per decedent increased the odds of reporting low-value behaviors by 20% (OR 1.20, 95% CI 1.04-1.38; P = 0.01). CONCLUSIONS: Third- and fourth-year medical students report engaging in both high- and low-value behaviors, which are related to regional HCI. This underscores the importance of the clinical learning environment and suggests imprinting is already underway during medical school.

Effect of cost exposure on medical students' preferred mammography screening strategies: A randomized comparison.

Introduction: Many high value care educational interventions have focused on shaping clinical decision-making for individual patients. Few have investigated how trainees integrate cost information into recommendations within a public health context. Methods: Third-year medical students at the University of California San Francisco participated in a small group on benefits and harms of breast cancer screening. We randomly assigned half of small groups to view estimated total costs of different screening strategies. Students selected a screening strategy for coverage by a publicly funded program and one they would recommend to a hypothetical patient. We used the chi-square test for independence and chi-square test for trend to compare proportions. Results: A total of 267 third-year medical students participated. Exposure to costs was associated with selection of significantly less intensive screening strategies for coverage by a publicly funded program (p < 0.05). We found no significant differences in perspectives that involved recommendations for individual patients. Discussion: Students weigh cost considerations more heavily when making decisions about populations, rather than individual hypothetical patients. We suggest that it may be easier for students to relate cost considerations to populations. Initial curricular activities can be framed from this perspective with subsequent activities focusing on individual patient care.

Occupational Therapy Using Zones of Regulation™ Concepts: A Feasibility Study.

There is a lack of peer-reviewed research on occupational therapy using Zones of Regulation™ concepts for autistic youth. The purpose of this article is to describe the feasibility of a newly-developed occupational therapy intervention using Zones of Regulation™ concepts (OT-ZOR) for autistic youth. Specifically, we aimed to evaluate: (a) participant recruitment, retention, and attendance; (b) intervention fidelity, safety, and assessment completion; (c) intervention acceptability; and (d) preliminary participant outcomes. A single-arm feasibility study was completed with outcome measures before and after 10 weeks of OT-ZOR. Fourteen autistic youth ages 6 to 13 completed the study. Youth attended 94% of OT-ZOR sessions. Providers achieved 97% fidelity to the intervention. Occupational therapists and caregivers expressed overall satisfaction with the OT-ZOR intervention. Youth demonstrated significant decreases in irritability, hyperactivity, emotional reactivity, and dysphoria. OT-ZOR is feasible to implement, acceptable to providers and caregivers, and may improve self-regulation in autistic youth.

Occupational Therapy Using Zones of Regulation Concepts: A Feasibility StudyThe research team developed an intervention that combines occupational therapy best practices for autistic youth with concepts from a widely used curriculum for teaching self-regulation skills, the Zones of Regulation™. This article describes the feasibility of implementing this new intervention, named occupational therapy using Zones of Regulation (OT-ZOR). The current feasibility study provided 10 weeks of OT-ZOR to autistic youth ages 6 to 13 and collected data about feasibility of implementing the intervention, acceptability of the intervention to caregivers and providers, and preliminary participant outcomes. OT-ZOR was feasible to implement, as indicated by high rates of retention, attendance, and fidelity to the intervention. OT-ZOR was acceptable to the occupational therapists who provided it, and the caregivers of autistic youth who participated. Youth demonstrated improvements in self-regulation. Overall, we concluded OT-ZOR was feasible to implement, acceptable to providers and caregivers, and may improve self-regulation in autistic youth.

Development and applicability of a risk assessment tool for hospital-acquired mobility impairment in ambulatory older adults.

BACKGROUND: Mobility loss is common in hospitalized older adults, and resources to prevent mobility impairment are finite. Our goal was to use routinely collected data to develop a risk assessment tool that identifies individuals at risk of losing the ability to walk during hospitalization on the first hospital day. Second, we determined if the tool could inform the use of mobility-preserving interventions. METHODS: We included patients admitted to a general medical service, aged ≥65 years, who walked occasionally or frequently on admission (Braden Scale Activity subset > = 3). Patients were considered to have a new mobility impairment if, at discharge, their ability to walk was severely limited or nonexistent or they were confined to bed (Braden Scale Activity subset <3). We used predictors available on the first hospital day to develop (2017-18 cohort) and validate (2019 cohort) a risk assessment tool. We determined the association between predicted risk and therapy use in the validation cohort to highlight the model's clinical utility. RESULTS: 5542 patients were included (median age 76 years, 48% women); 7.6% were discharged unable to walk. The model included 5 predictors: age, medication administrations, Glasgow Coma Scale verbal score, serum albumin, and urinary catheter presence. In the validation cohort, the model discriminated well (c-statistic 0.75) and was strongly associated with hospital-acquired mobility impairment (lowest decile 1%, highest decile 25%). In the validation cohort, therapy consultation ordering increased linearly with predicted risk; however, observed mobility impairment increased exponentially. CONCLUSION: The tool assesses the risk of mobility impairment in all ambulatory hospitalized older adults on the first hospital day. Further, it identifies at-risk older adults who may benefit from mobility interventions.

Disaster mobile health technology: lessons from Haiti.

INTRODUCTION: Mobile health (mHealth) technology can play a critical role in improving disaster victim tracking, triage, patient care, facility management, and theater-wide decision-making. PROBLEM: To date, no disaster mHealth application provides responders with adequate capabilities to function in an austere environment. METHODS: The Operational Medicine Institute (OMI) conducted a qualitative trial of a modified version of the off-the-shelf application iChart at the Fond Parisien Disaster Rescue Camp during the large-scale response to the January 12, 2010 earthquake in Haiti. RESULTS: The iChart mHealth system created a patient log of 617 unique entries used by on-the-ground medical providers and field hospital administrators to facilitate provider triage, improve provider handoffs, and track vulnerable populations such as unaccompanied minors, pregnant women, traumatic orthopedic injuries and specified infectious diseases. CONCLUSION: The trial demonstrated that even a non-disaster specific application with significant programmatic limitations was an improvement over existing patient tracking and facility management systems. A unified electronic medical record and patient tracking system would add significant value to first responder capabilities in the disaster response setting.

Use and diagnostic value of liver enzyme tests in the emergency department and subsequent heart failure diagnosis: a retrospective cohort study.

OBJECTIVES: To determine (1) if liver function tests (LFTs) are ordered in the emergency department (ED) in patients with suspected acute decompensated heart failure (ADHF) and (2) if the pattern of LFT abnormalities are meaningfully associated with a discharge diagnosis of ADHF among patients for whom these tests were ordered. SETTING: We conducted a single-centre retrospective cohort study of patients with suspected ADHF who were seen in an academic tertiary ED using electronic medical records. PARTICIPANTS: All ED patients admitted with suspected ADHF from January 2017 to May 2018, defined as any patient who had a brain natriuretic peptide (BNP) ordered. PRIMARY OUTCOME: The primary outcome was ADHF diagnosis at discharge. RESULTS: In 5323 ED patients with suspected ADHF, 60% (n=3184) had LFTs ordered; 34.6% were abnormal. Men comprised 56% of patients with abnormal LFTs and the average age was 67 years. The odds of a final diagnosis of ADHF in the univariate analysis was 59% higher in patients with abnormal LFTs (OR=1.59, (95% CI 1.35 to 1.87) p<0.001) and remained significant though attenuated after adjusting for BNP, race and ethnicity and age (ORadj=1.31 (95% CI 1.09 to 1.57), p=0.004). Likelihood ratios for abnormal and normal LFTs were 1.2 (95% CI 1.21 to 1.28) and 0.76 (95% CI 0.68 to 0.84), respectively. CONCLUSIONS: A significant proportion (40%) of patients with suspected ADHF was missing LFTs in their ED workup. Among patients with LFTs, abnormal LFTs are associated with discharge diagnosis of ADHF after accounting for potential confounders, but their diagnostic value was relatively low. Future prospective studies are warranted to explore the role of LFTs in the workup of ADHF.

Oral tetrahydrobiopterin improves the beneficial effect of adenoviral-mediated eNOS gene transfer after induction of hindlimb ischemia.

We tested the hypothesis that oral supplementation with the endothelial nitric oxide synthase (eNOS) cofactor tetrahydrobiopterin (BH(4)) improved the therapeutic efficacy of eNOS gene transfer in the ischemic rat hindlimb. BH(4) or vehicle were begun 1 week before induction of hindlimb ischemia, whereas recombinant adenovirus containing bovine eNOS cDNA (AdeNOS) or vehicle [phosphate-buffered saline (PBS)] was infused intra-arterially into the ischemic hindlimb 10 days after induction of ischemia. Rats receiving co-treatment with dietary BH(4) and eNOS gene transfer (the [eNOS, +BH(4)] group) had greater eNOS expression, phospho-eNOS expression (Ser(1177)), Ca(2+)-dependent NOS activity, and nitrite + nitrate concentrations in the ischemic gastrocnemius than did rats receiving AdeNOS alone. The [eNOS, +BH(4)] group demonstrated less nitrotyrosine and a higher ratio of reduced:oxidized glutathione (GSH:GSSG) in the ischemic gastrocnemius muscle than did rats receiving AdeNOS alone. The [eNOS, +BH(4)] group had greater flow recovery and a higher capillary:myocyte ratio in the ischemic hindlimb than did rats receiving AdeNOS alone. Finally, the [eNOS,+BH(4)] group had less necrosis of hindlimb muscles than rats given AdeNOS alone. We conclude that adjunctive dietary therapy with BH(4) increases the beneficial effects of eNOS gene transfer within the ischemic gastrocnemius muscle, as evidenced by increased nitric oxide (NO) production, diminished oxidative stress, enhanced flow recovery, and reduced necrosis.

Endothelial nitric oxide synthase affects both early and late collateral arterial adaptation and blood flow recovery after induction of hind limb ischemia in mice.

OBJECTIVE: The goals of this study were to determine if endothelial nitric oxide synthase (eNOS) affects both early and late collateral arterial adaptation and blood flow recovery after severe limb ischemia in a mouse model and to determine if eNOS-derived NO is necessary for recruitment of chemokine (C-X-C motif) receptor 4 (CXCR4)(+) vascular endothelial growth factor receptor-1 (VEGFR1)(+) hemangiocytes to the site of ischemia. METHODS: Two studies were completed. In the first, hind limb ischemia was induced by unilateral femoral artery excision in three groups: C57Bl6 (wild-type), eNOS(-/-), and C57Bl/6 mice treated with N(G)-nitro-L-arginine methyl ester (L-NAME) from 1 day before excision through day 3 after excision (early L-NAME group). These groups were studied on day 3 after induction of ischemia. In the second study, hind limb ischemia was induced in C57Bl/6 mice (wild-type) and C57Bl/6 mice treated with L-NAME from days 3 through 28 after induction of ischemia. These groups were studied day 28 after ischemia induction. Dependent variables included hind limb perfusion, collateral artery diameter, and the number and location of hemangiocytes within the ischemic hind limb. RESULTS: In the first study, toe gangrene developed in the eNOS(-/-) and early L-NAME treatment groups by day 2. These groups demonstrated less blood flow recovery and smaller collateral artery diameter than the wild-type group. Hemangiocytes were present within the adventitia of collateral arteries in the wild-type group but were only sparsely present, in a random pattern, in the eNOS(-/-) and early L-NAME treatment groups. In the second study, the late L-NAME group showed less blood flow recovery and smaller collateral artery diameter on day 28 of ischemia than the wild-type group. Hemangiocytes were present in a pericapillary distribution in the wild-type group, but were present only sparsely in the late L-NAME treatment group. CONCLUSION: Early (day 3) and late (day 28) adaptive responses to hind limb ischemia both require eNOS-derived NO. NO is necessary for normal hemangiocyte recruitment to the ischemic tissue.

Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse.

BACKGROUND: Most current animal models of hindlimb ischemia use acute arterial occlusion that does not accurately reflect the pathogenesis of gradual arterial occlusion in humans. We, therefore, developed the first mouse model of gradual arterial occlusion and tested the hypothesis that the mechanisms regulating blood flow recovery are critically dependent on the rate of arterial occlusion. METHODS: Gradual arterial occlusion was induced by placing ameroid constrictors on the proximal and distal left femoral artery, and ligating the femoral arterial branches (n = 36). Acute arterial occlusion was accomplished by excising the left femoral artery (n = 36). The blood flow recovery was studied by laser Doppler imaging. Differential gene expression between these two models was assessed by quantitative real-time polymerase chain reactions (PCR). Inflammatory and progenitor cells recruitment were determined by immunohistochemistry. RESULTS: We found that hypoxia-related genes increased significantly in the calf, but not in the thigh, after gradual and acute femoral arterial occlusion (P < .05). Shear-stress dependent genes and inflammatory genes were upregulated immediately in the thigh only after acute femoral arterial occlusion (P < .05). These differences in gene expression were consistent with increased SDF-1alpha expression, recruitment of macrophages and hemangiocytes, and higher blood flow recovery after acute arterial occlusion than after gradual arterial occlusion (P < .05). CONCLUSION: This is the first study to show the mechanisms that regulate blood flow recovery are critically dependent on the rate of arterial occlusion. This novel model of gradual arterial occlusion may more closely resemble the human diseases, and may provide more accurate mechanistic insights for creating novel molecular therapies.

Value-Added Activities in Medical Education: A Multisite Survey of First- and Second-Year Medical Students' Perceptions and Factors Influencing Their Potential Engagement.

PURPOSE: To describe attitudes of first- and second-year U.S. medical students toward value-added medical education, assess their self-reported desire to participate in value-added activities, and identify potentially modifiable factors influencing their engagement. METHOD: The authors conducted a cross-sectional survey of first- and second-year students at nine U.S. medical schools in 2017. Survey items measured students' attitudes toward value-added medical education (n = 7), desire to participate in value-added activities (n = 20), and factors influencing potential engagement (n = 18). RESULTS: Of 2,670 students invited to participate, 1,372 (51%) responded. Seventy-six percent (1,043/1,368) moderately or strongly agreed they should make meaningful contributions to patient care. Students' desire to participate was highest for patient care activities approximating those traditionally performed by physicians, followed by systems improvement activities and lowest for activities not typically performed by physicians. Factors increasing desire to participate included opportunities to interact with practicing physicians (1,182/1,244; 95%), patients (1,177/1,246; 95%), and residents or fellows (1,166/1,246; 94%). Factors decreasing desire to participate included making changes to the health care system (365/1,227; 30%), interacting with patients via phone or electronic communication (410/1,243; 33%), and lack of curricular time (634/1,233; 51%). CONCLUSIONS: First- and second-year medical students agree they should add value to patient care, but their desire to participate in value-added activities varies depending on the nature of the tasks. Medical schools may be able to increase students' desire to participate by enabling face-to-face interactions with patients, embedding students in health care teams, and providing dedicated curricular time.

Hospitalists, value and the future.

Health systems face increasing pressure to optimise value: providing the best quality care for the lowest possible cost. In the US, changes in modern healthcare, along with early efforts to contain costs, fuelled the growth of a new cadre of inpatient clinicians known as hospitalists. This commentary briefly reviews the history of the hospitalist movement through the lens of healthcare value, examines the evidence for value improvement in the care and training provided by hospitalists, and concludes by exploring both the lessons learned and remaining challenges facing hospitalists. We believe that openness to challenging the status quo was a critical enabler of the US hospitalist's impact on both the healthcare workforce and the American care delivery model. This spirit of re-engineering has far-reaching implications, both in the USA and abroad.

Tissue distribution of surfactant proteins A and D in the mouse.

Surfactant proteins A and D, collagen-like lectins (collectins), were first isolated from the lung. In the lung, SP-A and SP-D have roles in surfactant homeostasis and innate immunity. In this study we show that SP-A and SP-D mRNA can be detected in a significant number of non-pulmonary tissues but the proteins have a more limited distribution. SP-D protein was detected in lung, uterus, ovary, and lacrimal gland, whereas SP-A protein was detected only in the lung. The results suggest that SP-D participates in mucosal immunity throughout the body.