Long-Term Sustainability and Acceptance of Antimicrobial Stewardship in Intensive Care: A Retrospective Cohort Study.

OBJECTIVES: To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. DESIGN: A retrospective cohort study. SETTING: An urban, academic medical institution. PATIENTS: Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". CONCLUSIONS: An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Using Acoustic Perturbations to Dynamically Tune Shear Thickening in Colloidal Suspensions.

Colloidal suspensions in industrial processes often exhibit shear thickening that is difficult to control actively. Here, we use piezoelectric transducers to apply acoustic perturbations to dynamically tune the suspension viscosity in the shear-thickening regime. We attribute the mechanism of dethickening to the disruption of shear-induced force chains via perturbations that are large relative to the particle roughness scale. The ease with which this technique can be adapted to various flow geometries makes it a powerful tool for actively controlling suspension flow properties and investigating system dynamics.

Separation of 300 and 100 nm Particles in Fabry-Perot Acoustofluidic Resonators.

Separation of particles on the order of 100 nm with acoustophoresis has been challenging to date because of the competing natures of the acoustic radiation force and acoustic streaming on the particles. In this work, we present a surface acoustic wave (SAW)-based device that integrates a Fabry-Perot type acoustic resonator into a microfluidic channel to separate submicrometer particles. This configuration enhances the overall acoustic radiation force on the particles and thereby offers controlled manipulation of particles as small as 300 nm. Additionally, SAW-based excitation generates high-frequency acoustic waves in the system relative to bulk acoustic wave (BAW)-based actuation, which suppresses Rayleigh streaming effects on the submicrometer particles. We demonstrate a continuous-flow acoustophoretic separation of 300 and 100 nm particles in our device with a separation efficiency of 86.3%. We also present an analytical stochastic method to model the transport of submicrometer particles in the device and predict the migration trajectories as a function of acoustic and velocity potential field strengths. Our model incorporates particle diffusion, which is important for small particles, and successfully predicts the size-dependent separation modality of our system. This device can be used for several applications in microfluidics that require sorting of the submicrometer particles, and the analytical method can also be extended to predict the particle transport in other systems.

Droplet superpropulsion in an energetically constrained insect.

Food consumption and waste elimination are vital functions for living systems. Although how feeding impacts animal form and function has been studied for more than a century since Darwin, how its obligate partner, excretion, controls and constrains animal behavior, size, and energetics remains largely unexplored. Here we study millimeter-scale sharpshooter insects (Cicadellidae) that feed exclusively on a plant's xylem sap, a nutrient-deficit source (95% water). To eliminate their high-volume excreta, these insects exploit droplet superpropulsion, a phenomenon in which an elastic projectile can achieve higher velocity than the underlying actuator through temporal tuning. We combine coupled-oscillator models, computational fluid dynamics, and biophysical experiments to show that these insects temporally tune the frequency of their anal stylus to the Rayleigh frequency of their surface tension-dominated elastic drops as a single-shot resonance mechanism. Our model predicts that for these tiny insects, the superpropulsion of droplets is energetically cheaper than forming jets, enabling them to survive on an extreme energy-constrained xylem-sap diet. The principles and limits of superpropulsion outlined here can inform designs of energy-efficient self-cleaning structures and soft engines to generate ballistic motions.

A virtual care program for outpatients diagnosed with COVID-19: a feasibility study.

BACKGROUND: In patients who are discharged home to self-isolate while coronavirus disease 2019 (COVID-19) test results are pending, there is no formal method for physician assessments or counselling to occur if the result returns positive. Our aim was to develop and test the feasibility of a virtual care program for self-isolating outpatients diagnosed with COVID-19. METHODS: In preparation for this gap in health care, the COVID-19 Expansion to Outpatients (COVIDEO) program was developed at the Sunnybrook Health Sciences Centre, Toronto, Ontario, to provide ongoing care for outpatients diagnosed with COVID-19. As part of a feasibility study, we describe our experiences with the first 50 patients managed using this program from its inception (Mar. 1, 2020) until Mar. 27, 2020. RESULTS: All 50 people who tested positive for COVID-19 at the Sunnybrook Health Sciences Centre and were discharged home to self-isolation during the study period were assessed through the COVIDEO program. Thirty-two patients (64%) were assessed via the Ontario Telemedicine Network virtual care platform, and the remainder by telephone. The median time from viral swab collection to first COVIDEO program assessment was 2 (interquartile range [IQR] 1-2) days. Among the 26 patients for whom further follow-up care through the COVIDEO program was discontinued by the end of March 2020, the median duration of virtual care was 12.5 (IQR 8.75-16) days. During the study period, 6 patients required transfer to hospital for assessment, of whom 4 required admission. INTERPRETATION: We have shown that a virtual care program can be used in the management of outpatients diagnosed with COVID-19. Further studies evaluating its sustainability and impact on health outcomes are underway.

A Retrospective Forensic Review of Unexpected Infectious Deaths.

BACKGROUND: There exists a knowledge gap in identifying the spectrum of infectious pathogens and syndromes that lead to fulminant decline and death. The aim of this study was to better characterize patient-, pathogen-, and disease-related factors in the phenomenon of unexpected infectious deaths. METHODS: We conducted a population-based, retrospective cohort study of all community-based, unexpected infectious deaths in Ontario, Canada between January 2016 and December 2017. Patient-related information, infection-related information, and circumstances around the death were extracted for each case to facilitate descriptive analyses. RESULTS: Of the 7506 unexpected deaths over the study period, 418 (6%) were due to infectious diseases. Bacterial pneumonia (43%) was the most common infectious syndrome, followed by disseminated infection with no clear focus (12%), peritonitis (10%), myocarditis (6%), and pyelonephritis (5%). A pathogen was identified in 210 cases (50%), with the most common being Staphylococcus aureus (n = 35), Streptococcus pneumoniae (n = 30), Streptococcus pyogenes (n = 25), Klebsiella spp. (n = 23), and Escherichia coli (n = 19). Prodromal symptoms were present in 68% of persons before death, with a median (interquartile range) duration of only 1.0 (0.0-4.0) days; just 30% of those who died had had recent healthcare contact before their death. CONCLUSION: Infectious diseases have the capacity to cause fulminant decline and death. The most common cause of unexpected infectious death is bacterial pneumonia, with a predominance of gram-positive bacteria. Given the rapidity of these deaths, preventing a majority of them would require upstream strategies to reduce infection susceptibility and transmission.

Differences in spirometry interpretation algorithms: influence on decision making among primary-care physicians.

BACKGROUND: Spirometry is recommended for the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in international guidelines and may be useful for distinguishing asthma from COPD. Numerous spirometry interpretation algorithms (SIAs) are described in the literature, but no studies highlight how different SIAs may influence the interpretation of the same spirometric data. AIMS: We examined how two different SIAs may influence decision making among primary-care physicians. METHODS: Data for this initiative were gathered from 113 primary-care physicians attending accredited workshops in Canada between 2011 and 2013. Physicians were asked to interpret nine spirograms presented twice in random sequence using two different SIAs and touch pad technology for anonymous data recording. RESULTS: We observed differences in the interpretation of spirograms using two different SIAs. When the pre-bronchodilator FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio was >0.70, algorithm 1 led to a 'normal' interpretation (78% of physicians), whereas algorithm 2 prompted a bronchodilator challenge revealing changes in FEV1 that were consistent with asthma, an interpretation selected by 94% of physicians. When the FEV1/FVC ratio was <0.70 after bronchodilator challenge but FEV1 increased >12% and 200 ml, 76% suspected asthma and 10% suspected COPD using algorithm 1, whereas 74% suspected asthma versus COPD using algorithm 2 across five separate cases. The absence of a post-bronchodilator FEV1/FVC decision node in algorithm 1 did not permit consideration of possible COPD. CONCLUSIONS: This study suggests that differences in SIAs may influence decision making and lead clinicians to interpret the same spirometry data differently.

Glucose transporter expression in an avian nectarivore: the ruby-throated hummingbird (Archilochus colubris).

Glucose transporter (GLUT) proteins play a key role in the transport of monosaccharides across cellular membranes, and thus, blood sugar regulation and tissue metabolism. Patterns of GLUT expression, including the insulin-responsive GLUT4, have been well characterized in mammals. However, relatively little is known about patterns of GLUT expression in birds with existing data limited to the granivorous or herbivorous chicken, duck and sparrow. The smallest avian taxa, hummingbirds, exhibit some of the highest fasted and fed blood glucose levels and display an unusual ability to switch rapidly and completely between endogenous fat and exogenous sugar to fuel energetically expensive hovering flight. Despite this, nothing is known about the GLUT transporters that enable observed rapid rates of carbohydrate flux. We examined GLUT (GLUT1, 2, 3, & 4) expression in pectoralis, leg muscle, heart, liver, kidney, intestine and brain from both zebra finches (Taeniopygia guttata) and ruby-throated hummingbirds (Archilochus colubris). mRNA expression of all four transporters was probed using reverse-transcription PCR (RT-PCR). In addition, GLUT1 and 4 protein expression were assayed by western blot and immunostaining. Patterns of RNA and protein expression of GLUT1-3 in both species agree closely with published reports from other birds and mammals. As in other birds, and unlike in mammals, we did not detect GLUT4. A lack of GLUT4 correlates with hyperglycemia and an uncoupling of exercise intensity and relative oxidation of carbohydrates in hummingbirds. The function of GLUTs present in hummingbird muscle tissue (e.g. GLUT1 and 3) remain undescribed. Thus, further work is necessary to determine if high capillary density, and thus surface area across which cellular-mediated transport of sugars into active tissues (e.g. muscle) occurs, rather than taxon-specific differences in GLUT density or kinetics, can account for observed rapid rates of sugar flux into these tissues.