Interdepartmental program to improve outcomes for acute heart failure patients seen in the emergency department.

INTRODUCTION: Acute heart failure patients often have an uncertain or delayed follow-up after discharge from the ED. Our goal was to introduce rapid-access specialty clinics to ensure acute heart failure patients were seen within 7 days, in an effort to reduce admissions and improve follow-up care. METHODS: This prospective cohort study was conducted at two campuses of a large tertiary care hospital. We enrolled acute heart failure patients who presented to the ED with shortness of breath and were later discharged. Following a 12-month before period, we introduced rapid-access acute heart failure clinics staffed by cardiology and internal medicine. We allowed for a 3-month implementation period and then observed outcomes over the subsequent 12-month after period. The primary outcome was hospital admission within 30 days. Secondary outcomes included mortality and actual access to specialty care. RESULTS: Patients in the before (N = 355) and after periods (N = 374) were similar for age and most characteristics. Segmented autoregression analysis demonstrated there was a pre-existing trend to fewer admissions. Attendance at a specialty clinic increased from 17.8 to 42.1% (P < 0.01) and the median days to the clinic decreased from 13 to 6 days (P < 0.01). 30-days mortality did not change. CONCLUSION: Implementation of rapid-access clinics for acute heart failure patients discharged from the ED did not lead to an overall decrease in hospital admissions. It did, however, lead to increased access to specialist care, reduced follow-up times, without an increase in return ED visits or mortality. Widespread use of this rapid-access approach to a specialist can improve care for acute heart failure patients discharged home from the ED.

RéSUMé: INTRODUCTION: Les patients atteints d'insuffisance cardiaque aiguë ont souvent un suivi incertain ou retardé après leur sortie de l'urgence. Notre objectif était de mettre en place des cliniques spécialisées à accès rapide pour veiller à ce que les patients de d'insuffisance cardiaque aiguë soient vus dans les sept jours, afin de réduire les admissions et d'améliorer les soins de suivi. MéTHODES: Cette étude de cohorte prospective a été menée sur deux campus d'un grand hôpital de soins tertiaires. Nous avons recruté des patients atteints de d'insuffisance cardiaque aiguë qui se sont présentés aux urgences avec un essoufflement et qui ont ensuite été renvoyés chez eux. Après une période antérieure de 12 mois, nous avons mis en place des cliniques de d'insuffisance cardiaque aiguë à accès rapide dotées de personnel en cardiologie et en médecine interne. Nous avons prévu une période de mise en œuvre de 3 mois et avons ensuite observé les résultats au cours des 12 mois suivants. Le résultat principal était l'admission à l'hôpital dans les 30 jours. Les résultats secondaires comprenaient la mortalité et l'accès réel aux soins spécialisés. RéSULTATS: Les patients des périodes avant (N = 355) et après (N = 374) étaient similaires pour l'âge et la plupart des caractéristiques. Une analyse d'autorégression segmentée a démontré qu'il y avait une tendance préexistante à moins d'admissions. La fréquentation d'une clinique spécialisée est passée de 17,8 % à 42,1 % (P < 0,01) et les jours médians à la clinique ont diminué de 13 à 6 jours (P < 0,01). La mortalité à 30 jours n'a pas changé. CONCLUSION: La mise en place de cliniques à accès rapide pour les patients d'insuffisance cardiaque aiguë sortant de l'urgence n'a pas entraîné une diminution globale des admissions à l'hôpital Elle a toutefois permis d'améliorer l'accès aux soins spécialisés et de réduire les délais de suivi, sans pour autant augmenter les visites de retour aux urgences ou la mortalité. L'utilisation généralisée de cette approche d'accès rapide à un spécialiste peut améliorer les soins pour les patients atteints de d'insuffisance cardiaque aiguë renvoyés chez eux par les services d'urgence.

Pseudotypes of vesicular stomatitis virus with CD4 formed by clustering of membrane microdomains during budding.

Many plasma membrane components are organized into detergent-resistant membrane microdomains referred to as lipid rafts. However, there is much less information about the organization of membrane components into microdomains outside of lipid rafts. Furthermore, there are few approaches to determine whether different membrane components are colocalized in microdomains as small as lipid rafts. We have previously described a new method of determining the extent of organization of proteins into membrane microdomains by analyzing the distribution of pairwise distances between immunogold particles in immunoelectron micrographs. We used this method to analyze the microdomains involved in the incorporation of the T-cell antigen CD4 into the envelope of vesicular stomatitis virus (VSV). In cells infected with a recombinant virus that expresses CD4 from the viral genome, both CD4 and the VSV envelope glycoprotein (G protein) were found in detergent-soluble (nonraft) membrane fractions. However, analysis of the distribution of CD4 and G protein in plasma membranes by immunoelectron microscopy showed that both were organized into membrane microdomains of similar sizes, approximately 100 to 150 nm. In regions of plasma membrane outside of virus budding sites, CD4 and G protein were present in separate membrane microdomains, as shown by double-label immunoelectron microscopy data. However, virus budding occurred from membrane microdomains that contained both G protein and CD4, and extended to approximately 300 nm, indicating that VSV pseudotype formation with CD4 occurs by clustering of G protein- and CD4-containing microdomains.

A novel method for analysis of membrane microdomains: vesicular stomatitis virus glycoprotein microdomains change in size during infection, and those outside of budding sites resemble sites of virus budding.

Membrane proteins, including viral envelope glycoproteins, may be organized into areas of locally high concentration, commonly referred to as membrane microdomains. Some viruses bud from detergent-resistant microdomains referred to as lipid rafts. However, vesicular stomatitis virus (VSV) serves as a prototype for viruses that bud from areas of plasma membrane that are not detergent resistant. We developed a new analytical method for immunoelectron microscopy data to determine whether the VSV envelope glycoprotein (G protein) is organized into plasma membrane microdomains. This method was used to quantify the distribution of the G protein in microdomains in areas of plasma membrane that did not contain budding sites. These microdomains were compared to budding virus envelopes to address the question of whether G protein-containing microdomains were formed only at the sites of budding. At early times postinfection, most of the G protein was organized into membrane microdomains outside of virus budding sites that were approximately 100-150 nm, with smaller amounts distributed into larger microdomains. In contrast to early times postinfection, the increased level of G protein in the host plasma membrane at later times postinfection led to distribution of G protein among membrane microdomains of a wider variety of sizes, rather than a higher G protein concentration in the 100- to 150-nm microdomains. VSV budding occurred in G protein-containing microdomains with a range of sizes, some of which were smaller than the virus envelope. These microdomains extended in size to a maximum of 300-400 nm from the tip of the budding virion. The data support a model for virus assembly in which G protein organizes into membrane microdomains that resemble virus envelopes prior to formation of budding sites, and these microdomains serve as the sites of assembly of internal virion components.

Organization of the vesicular stomatitis virus glycoprotein into membrane microdomains occurs independently of intracellular viral components.

The glycoprotein (G protein) of vesicular stomatitis virus (VSV) is primarily organized in plasma membranes of infected cells into membrane microdomains with diameters of 100 to 150 nm, with smaller amounts organized into microdomains of larger sizes. This organization has been observed in areas of the infected-cell plasma membrane that are outside of virus budding sites as well as in the envelopes of budding virions. These observations raise the question of whether the intracellular virion components play a role in organizing the G protein into membrane microdomains. Immunogold-labeling electron microscopy was used to analyze the distribution of the G protein in arbitrarily chosen areas of plasma membranes of transfected cells that expressed the G protein in the absence of other viral components. Similar to the results with virus-infected cells, the G protein was organized predominantly into membrane microdomains with diameters of approximately 100 to 150 nm. These results indicate that internal virion components are not required to concentrate the G protein into membrane microdomains with a density similar to that of virus envelopes. To determine if interactions between the G protein cytoplasmic domain and internal virion components were required to create a virus budding site, cells infected with recombinant VSVs encoding truncation mutations of the G protein cytoplasmic domain were analyzed by immunogold-labeling electron microscopy. Deletion of the cytoplasmic domain of the G protein did not alter its partitioning into the 100- to 150-nm microdomains, nor did it affect the incorporation of the G protein into virus envelopes. These data support a model for virus assembly in which the G protein has the inherent property of partitioning into membrane microdomains that then serve as the sites of assembly of internal virion components.