Background-We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could noninvasively evaluate prelesion atherogenic phenotype. Methods and Results-Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultrahigh frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (PϽ0.01 versus nontargeted agent) at all ages for DKO mice. P-selectin and VCAM-1 signal in DKO mice were greater by 3-fold at 10 weeks, 4-to 6-fold at 20 weeks, and 9-to 10-fold at 40 weeks compared to wild-type mice. En face microscopy demonstrated preferential attachment of targeted microbubbles to regions of lesion formation. Conclusions-Noninvasive

Background In many countries emergency departments (EDs) are facing an increase in demand for services, long-waits and severe crowding. One response to mitigate overcrowding has been to provide primary care services alongside or within hospital EDs for patients with non-urgent problems. It is not known, however, how this impacts the quality of patient care, the utilisation of hospital resources, or if it is cost-effective. Objectives To assess the effects of locating primary care professionals in the hospital ED to provide care for patients with non-urgent health problems, compared with care provided by regular Emergency Physicians (EPs), Search methods We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialized register; Cochrane Central Register of Controlled Trials (The Cochrane library, 2011, Issue 4), MEDLINE (1950 to March 21 2012); EMBASE (1980 to April 28 2011); CINAHL (1980 to April 28 2011); PsychINFO (1967 to April 28 2011); Sociological Abstracts (1952 to April 28 2011); ASSIA (1987 to April 28 2011); SSSCI (1945 to April 28 2011); HMIC (1979 to April 28 2011), sources of unpublished literature, reference lists of included papers and relevant systematic reviews. We contacted experts in the field for any published or unpublished studies, and hand searched ED conference abstracts from the last three years. Selection criteria Randomised controlled trials, non-randomised studies, controlled before and after studies and interrupted time series studies that evaluated the effectiveness of introducing primary care professionals to hospital EDs to attend to non-urgent patients, as compared to the care provided by regular EPs. Data collection and analysis Two reviewers independently extracted data and assessed the risk of bias for each included study. We contacted authors of included studies to obtain additional data. Dichotomous outcomes are presented as risk ratios (RR) with 95% confidence intervals (CIs) and continuous outcomes are presented as mean differences (MD) with 95% CIs. Pooling was not possible due to heterogeneity. Main results Three non randomised controlled studies involving a total of 11 203 patients, 16 General Practioners (GPs), and 52 EPs, were included. These studies evaluated the effects of introducing GPs to provide care to patients with non-urgent problems in the ED, as compared to EPs for outcomes such as resource use. The quality of evidence for all outcomes in this review was low, primarily due to the non-randomised design of included studies. The outcomes investigated were similar across studies; however there was high heterogeneity (I2>86%). Differences across studies included the triage system used, the level of expertise and experience of the medical practitioners and type of hospital (urban teaching, suburban community hospital). Two of the included studies report that GPs used significantly fewer healthcare resources than EPs, with fewer blood tests (RR 0.22; 95%CI: 0.14 to 0.33; N=4641; RR 0.35; 95%CI 0.29 to 0.42; N=4684), x-rays (R...

Primary care professionals providing non-urgent care in hospital emergency departments.

T he coronavirus disease 2019 (COVID-19) pandemic is the largest public health crisis in over a century. 1 As of Jan. 15, 2021, COVID-19 has resulted in over 113 million infections and almost 2.5 million deaths globally. 2 The global crude mortality rate among patients diagnosed with COVID-19 is about 3%, but some countries have reported rates that are up to 3 times higher. 2,3 Factors explaining these variations include population differences in demographics, health status and socioeconomics, as well as system factors such as the availability of testing, pandemic preparedness and response, with others yet to be uncovered. 4,5 There is an urgent need for high-quality, populationlevel data to understand modifiable risks for disease severity

Background The etiology for flank pain sometimes experienced during administration of ultrasound contrast agents is unknown. We investigated whether microbubble ultrasound contrast agents are retained within the renal microcirculation which could lead to either flow disturbance or local release of vasoactive and pain mediators downstream from complement activation. Methods Retention of lipid-shelled microbubbles in the renal microcirculation of mice was assessed by confocal fluorescent microscopy and contrast-enhanced ultrasound (CEU) imaging with dose-escalating intravenous injection. Studies were performed with size-segregated microbubbles to investigate physical entrapment, after glycocalyx degradation, and in wild-type and C3-deficient mice to investigate complement-mediated retention. Urinary bradykinin was measured before and after microbubbles. Renal CEU in human subjects (n=13) was performed 7–10 min after completion of lipid microbubble administration. Results In both mice and humans, microbubble retention was detected in the renal cortex by persistent CEU signal enhancement. Microbubble retention in mice was linearly related to dose and occurred almost exclusively in cortical glomerular microvessels. Microbubble retention did not affect microsphere-derived renal blood flow. Microbubble retention was not influenced by glycocalyx degradation nor by microbubble size, thereby excluding lodging, but was reduced by 90% (p<0.01) in C3-deficient mice. Urinary bradykinin increased by 65% five minutes after microbubble injection. Conclusion Lipid-shelled microbubbles are retained in the renal cortex due to complement-mediated interactions with glomerular microvascular endothelium. Microbubble retention does not adversely affect renal perfusion but does generate complement-related intermediates that are known to mediate nociception and could be responsible for flank pain.