Developing as health professionals through community volunteering: exploring the value of a partnership between medical students and primary schools online compared to in-person.

INTRODUCTION: Imperial College Teddy Bear Hospital (ICSM-TBH) is a student-led volunteering group, which uses interactive, play-based teaching to educate school pupils aged 5-7 years about healthy lifestyles and healthcare. During the COVID-19 pandemic, volunteering sessions shifted online. The aim of this study was to compare the value of online and in-person ICSM-TBH volunteering for volunteers and school pupils. METHODS: Undergraduate university students at Imperial College London (medicine can be taken as a first degree in the UK) who volunteered with ICSM-TBH between 2019 and 22 were invited to complete an anonymous online questionnaire evaluating their experiences of volunteering online and in-person through Likert-scale questions. Those who completed the questionnaire were also invited to an interview. Teachers who hosted online ICSM-TBH sessions were also invited to an in-person interview, exploring their view of their pupils' experiences with these sessions. Questionnaire results were analysed through descriptive statistics. Interviews were analysed through inductive thematic analysis. RESULTS: Thirty-two university students completed the questionnaire. Of these, 9 experienced both in-person and online volunteering, all of whom preferred in-person volunteering. For those who only volunteered in-person, 92% reported that ICSM-TBH sessions were a positive experience, compared to 100% who volunteered online; 92% in person volunteers agreed or strongly agreed that ICSM-TBH volunteering in person improved their mood, compared to 89% online; and 100% agreed or strongly agreed that ICSM-TBH volunteering in person helped them feel part of a community, compared to 84% online. A total of 12 volunteers and 4 teachers were interviewed, from whom five themes emerged: interaction and engagement (interaction and engagement between pupils and volunteers was more readily achieved in-person); personal and professional development (both online and in-person sessions enabled volunteers to gain valuable skills); community and social (greater sense of community was established in-person); emotional wellbeing and enjoyment (both modalities were enjoyed by volunteers and pupils); and workload (online sessions were more convenient for volunteers but with risk of screen fatigue). CONCLUSION: Overall, both in-person and online volunteering were of substantial benefit to volunteers and school pupils. However, most teachers and volunteers preferred in-person volunteering.

Conversion of Aryl Azides to Aminopyridines.

A longstanding challenge in fundamental functional group interconversion has been the direct transformation of benzene into pyridine via nitrogen insertion and carbon deletion. Herein, we report a protocol for the transformation of aryl azides, easily accessible from their corresponding anilines, to 2-aminopyridines using blue light and oxygen. Mechanistic studies corroborate that the arene to pyridine conversion is achieved by nitrogen insertion into the benzene ring followed by oxidative carbon extrusion.

Using Participatory Design to Engage Physicians in the Development of a Provider-Level Performance Dashboard and Feedback System.

PROBLEM DEFINITION: Performance feedback, in which clinicians are given data on select metrics, is widely used in the context of quality improvement. However, there is a lack of practical guidance describing the process of developing performance feedback systems. INITIAL APPROACH: This study took place at the University of California, San Francisco (UCSF) with hospitalist physicians. Participatory design methodology was used to develop a performance dashboard and feedback system. Twenty hospitalist physicians participated in a series of six design sessions and two surveys. Each design session and survey systematically addressed key components of the feedback system, including design, metric selection, data delivery, and incentives. The Capability Opportunity Motivation and Behavior (COM-B) model was then used to identify behavior change interventions to facilitate engagement with the dashboard during a pilot implementation. KEY INSIGHTS, LESSONS LEARNED: In regard to performance improvement, physicians preferred collaboration over competition and internal motivation over external incentives. Physicians preferred that the dashboard be used as a tool to aid in clinical practice improvement and not punitively by leadership. Metrics that were clinical or patient-centered were perceived as more meaningful and more likely to motivate behavior change. NEXT STEPS: The performance dashboard has been introduced to the entire hospitalist group, and evaluation of implementation continues by monitoring engagement and physician attitudes. This will be followed by targeted feedback interventions to attempt to improve performance.

Effectiveness of an Analytics-Based Intervention for Reducing Sleep Interruption in Hospitalized Patients: A Randomized Clinical Trial.

IMPORTANCE: Sleep has major consequences for physical and emotional well-being. Hospitalized patients experience frequent iatrogenic sleep interruptions and there is evidence that such interruptions can be safely reduced. OBJECTIVE: To determine whether a clinical decision support tool, powered by real-time patient data and a trained prediction algorithm, can help physicians identify clinically stable patients and safely discontinue their overnight vital sign checks. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, with inpatient encounters randomized 1:1 to intervention vs usual care, was conducted from March 11 to November 24, 2019. Participants included physicians serving on the primary team of 1699 patients on the general medical service (not in the intensive care unit) of a tertiary care academic medical center. INTERVENTIONS: A clinical decision support notification informed the physician if the patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model that used real-time patient data as input. The notification provided the physician an opportunity to discontinue measure of nighttime vital signs, dismiss the notification for 1 hour, or dismiss the notification for that day. MAIN OUTCOMES AND MEASURES: The primary outcome was delirium, as determined by bedside nurse assessment of Nursing Delirium Screening Scale scores, a standardized delirium screening tool (delirium diagnosed with score ≥2). Secondary outcomes included mean nighttime vital sign checks. Potential harms included intensive care unit transfers and code blue alarms. All analyses were conducted on the basis of intention-to-treat. RESULTS: A total of 1930 inpatient encounters in 1699 patients (intervention encounters: 566 of 966 [59%] men; mean [SD] age, 53 [15] years) were randomized. In the intervention vs control arm, there was a significant decrease in the mean (SD) number of nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86]; P < .001) with no increase in intensive care unit transfers (49 [5%] vs 47 [5%]; P = .92) or code blue alarms (2 [0.2%] vs 9 [0.9%]; P = .07). The incidence of delirium was not significantly reduced (108 [11%] vs 123 [13%]; P = .32). CONCLUSIONS AND RELEVANCE: While this randomized clinical trial found no difference between groups in the primary outcome, delirium incidence, the secondary findings indicate that a real-time prediction algorithm embedded within a clinical decision support tool in the electronic health record can help physicians identify clinically stable patients who can forgo routine vital sign checks, safely giving them greater opportunity to sleep. Other aspects of hospital care that depend on clinical stability, such as level of care or cardiac monitoring, may be amenable to a similar intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04046458.

Enantioselective Cyclobutenylation of Olefins Using N-Sulfonyl-1,2,3-Triazoles as Vicinal Dicarbene Equivalents.

Cyclobutenes are highly useful synthetic intermediates as well as important motifs in bioactive small molecules. Herein, we report a regio-, chemo-, and enantioselective synthesis of cyclobutenes from olefins using N-sulfonyl-1,2,3-triazoles as vicinal dicarbene equivalents or alkyne [2 + 2] cycloaddition surrogates. Terminal and cis-olefins can be transformed into enantioenriched cyclopropanes via rhodium catalysis. Then, in one pot, treatment of these intermediates with tosyl hydrazide and base effects diazo formation followed by rhodium-catalyzed ring expansion to yield enantioenriched cyclobutenes. These cyclobutenes can be transformed into highly substituted, enantioenriched cyclobutanes, including structures relevant to natural product scaffolds.

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.

Targeted Stat2 deletion in conventional dendritic cells impairs CTL responses but does not affect antibody production.

STAT2 is a central component of the ISGF3 transcriptional complex downstream of type I interferon (IFN-I) signaling. The significance of in vivo IFN-I/STAT1 signals in cDCs is well-established in the generation of antitumor cytotoxic T cell (CTL) responses. However, the role of STAT2 has remained elusive. Here, we report a clinical correlation between cDC markers and STAT2 associated with better survival in human metastatic melanoma. In a murine tumor transplantation model, targeted Stat2 deletion in CD11c+cDCs enhanced tumor growth unaffected by IFNß therapy. Furthermore, STAT2 was essential for both, the activation of CD8a+cDCs and CD11b+cDCs and antigen cross-presentation in vivo for the generation of robust T cell killing response. In contrast, STAT2 in CD11c+cDCs was dispensable for stimulating an antigen-specific humoral response, which was impaired in global Stat2 deficient mice. Thus, our studies indicate that STAT2 in cDCs is critical in host IFN-I signals by sculpting CTL responses against tumors.

STAT2 dependent Type I Interferon response promotes dysbiosis and luminal expansion of the enteric pathogen Salmonella Typhimurium.

The mechanisms by which the gut luminal environment is disturbed by the immune system to foster pathogenic bacterial growth and survival remain incompletely understood. Here, we show that STAT2 dependent type I IFN signaling contributes to the inflammatory environment by disrupting hypoxia enabling the pathogenic S. Typhimurium to outgrow the microbiota. Stat2-/- mice infected with S. Typhimurium exhibited impaired type I IFN induced transcriptional responses in cecal tissue and reduced bacterial burden in the intestinal lumen compared to infected wild-type mice. Although inflammatory pathology was similar between wild-type and Stat2-/- mice, we observed decreased hypoxia in the gut tissue of Stat2-/- mice. Neutrophil numbers were similar in wild-type and Stat2-/- mice, yet Stat2-/- mice showed reduced levels of myeloperoxidase activity. In vitro, the neutrophils from Stat2-/- mice produced lower levels of superoxide anion upon stimulation with the bacterial ligand N-formylmethionyl-leucyl-phenylalanine (fMLP) in the presence of IFNα compared to neutrophils from wild-type mice, indicating that the neutrophils were less functional in Stat2-/- mice. Cytochrome bd-II oxidase-mediated respiration enhances S. Typhimurium fitness in wild-type mice, while in Stat2-/- deficiency, this respiratory pathway did not provide a fitness advantage. Furthermore, luminal expansion of S. Typhimurium in wild-type mice was blunted in Stat2-/- mice. Compared to wild-type mice which exhibited a significant perturbation in Bacteroidetes abundance, Stat2-/- mice exhibited significantly less perturbation and higher levels of Bacteroidetes upon S. Typhimurium infection. Our results highlight STAT2 dependent type I IFN mediated inflammation in the gut as a novel mechanism promoting luminal expansion of S. Typhimurium.

Reducing Unnecessary Treatment of Asymptomatic Elevated Blood Pressure with Intravenous Medications on the General Internal Medicine Wards: A Quality Improvement Initiative.

BACKGROUND: Asymptomatic elevated blood pressure (BP) is common in the hospital. There is no evidence supporting the use of intravenous (IV) antihypertensives in this setting. OBJECTIVE: To determine the prevalence and effects of treating asymptomatic elevated BP with IV antihypertensives and to investigate the efficacy of a quality improvement (QI) initiative aimed at reducing utilization of these medications. DESIGN: Retrospective cohort study. SETTING: Urban academic hospital. PATIENTS: Patients admitted to the general medicine service, including the intensive care unit (ICU), with ≥1 episode of asymptomatic elevated BP (>160/90 mm Hg) during hospitalization. INTERVENTION: A two-tiered, QI initiative. MEASUREMENTS: The primary outcome was the monthly proportion of patients with asymptomatic elevated BP treated with IV labetalol or hydralazine. We also analyzed median BP and rates of balancing outcomes (ICU transfers, rapid responses, cardiopulmonary arrests). RESULTS: We identified 2,306 patients with ≥1 episode of asymptomatic elevated BP during the 10-month preintervention period, of which 251 (11%) received IV antihypertensives. In the four-month postintervention period, 70 of 934 (7%) were treated. The odds of being treated were 38% lower in the postintervention period after adjustment for baseline characteristics, including length of stay and illness severity (OR = 0.62; 95% CI 0.47-0.83; P = .001). Median SBP was similar between pre- and postintervention (167 vs 168 mm Hg; P = .78), as were the adjusted proportions of balancing outcomes. CONCLUSIONS: Hospitalized patients with asymptomatic elevated BP are commonly treated with IV antihypertensives, despite the lack of evidence. A QI initiative was successful at reducing utilization of these medications.

Next-generation audit and feedback for inpatient quality improvement using electronic health record data: a cluster randomised controlled trial.

BACKGROUND: Audit and feedback improves clinical care by highlighting the gap between current and ideal practice. We combined best practices of audit and feedback with continuously generated electronic health record data to improve performance on quality metrics in an inpatient setting. METHODS: We conducted a cluster randomised control trial comparing intensive audit and feedback with usual audit and feedback from February 2016 to June 2016. The study subjects were internal medicine teams on the teaching service at an urban tertiary care hospital. Teams in the intensive feedback arm received access to a daily-updated team-based data dashboard as well as weekly inperson review of performance data ('STAT rounds'). The usual feedback arm received ongoing twice-monthly emails with graphical depictions of team performance on selected quality metrics. The primary outcome was performance on a composite discharge metric (Discharge Mix Index, 'DMI'). A washout period occurred at the end of the trial (from May through June 2016) during which STAT rounds were removed from the intensive feedback arm. RESULTS: A total of 40 medicine teams participated in the trial. During the intervention period, the primary outcome of completion of the DMI was achieved on 79.3% (426/537) of patients in the intervention group compared with 63.2% (326/516) in the control group (P<0.0001). During the washout period, there was no significant difference in performance between the intensive and usual feedback groups. CONCLUSION: Intensive audit and feedback using timely data and STAT rounds significantly increased performance on a composite discharge metric compared with usual feedback. With the cessation of STAT rounds, performance between the intensive and usual feedback groups did not differ significantly, highlighting the importance of feedback delivery on effecting change. CLINICAL TRIAL: The trial was registered with ClinicalTrials.gov (NCT02593253).

Expanded Helicenes: A General Synthetic Strategy and Remarkable Supramolecular and Solid-State Behavior.

A divergent synthetic strategy allowed access to several members of a new class of helicenes, the "expanded helicenes", which are composed of alternating linearly and angularly fused rings. The strategy is based on a three-fold, partially intermolecular [2+2+n] (n = 1 or 2) cycloaddition with substrates containing three diyne units. Investigation of aggregation behavior, both in solution and in the solid state, revealed that one of these compounds forms an unusual homochiral, π-stacked dimer via an equilibrium that is slow on the NMR time scale. The versatility of the method was harnessed to access a selenophene-annulated expanded helicene that, in contrast to its benzannulated analogue, exhibits long-range π-stacking in the solid state. The new helicenes possess low racemization barriers, as demonstrated by dynamic 1H NMR spectroscopy.

Imaging latex-carbon nanotube composites by subsurface electrostatic force microscopy.

Electrostatic modes of atomic force microscopy have shown to be non-destructive and relatively simple methods for imaging conductors embedded in insulating polymers. Here we use electrostatic force microscopy to image the dispersion of carbon nanotubes in a latex-based conductive composite, which brings forth features not observed in previously studied systems employing linear polymer films. A fixed-potential model of the probe-nanotube electrostatics is presented which in principle gives access to the conductive nanoparticle's depth and radius, and the polymer film dielectric constant. Comparing this model to the data results in nanotube depths that appear to be slightly above the film-air interface. This result suggests that water-mediated charge build-up at the film-air interface may be the source of electrostatic phase contrast in ambient conditions.

Comparison of quantity of left ventricular scarring and remodeling by magnetic resonance imaging in patients with versus without diabetes mellitus and with coronary artery disease.

Diabetic patients with coronary artery disease (CAD) are more likely to develop heart failure (HF) than nondiabetic patients, but the mechanism responsible is unclear. Evidence suggests that infarct size and accompanying remodeling may not explain this difference. We used cardiac magnetic resonance (CMR) imaging to compare degree of left ventricular (LV) myocardial scar and remodeling in diabetic and nondiabetic patients with CAD. We evaluated 85 patients (39 diabetic, 46 nondiabetic) who underwent coronary angiography showing obstructive CAD and CMR imaging within 6 months of each other. Myocardial scar was measured by late gadolinium enhancement on CMR imaging and was graded according to spatial and transmural extents on a semiquantitative scale. More diabetic than nondiabetic patients had HF (69% vs 43%, p <0.03); however, groups did not differ in total scar burden (0.94 ± 0.60 vs 1.17 ± 0.74, p = NS), spatial extent of scar, or extent of transmural scar. Diabetes remained an independent predictor of HF after adjustment for CAD and other variables. LV ejection fraction (36 ± 12% vs 37 ± 14%, p = NS) and end-diastolic volume (215 ± 56 vs 217 ± 76 ml, p = NS) were similar for diabetic and nondiabetic patients, respectively. In conclusion, although diabetic patients with CAD had a higher prevalence of HF than nondiabetic patients, there was no difference in myocardial scar, LV volume, or LV ejection fraction. These findings support the theory that mechanisms other than extent of myocardial injury and negative remodeling play a significant role in the development of HF in diabetic patients with CAD.