A Multicenter, Prospective Study Comparing Subxiphoid and Parasternal Views During Brief Echocardiography: Effect on Image Quality, Acquisition Time, and Visualized Anatomy.

BACKGROUND: Recent literature has suggested echocardiography (echo) may prolong pauses in chest compressions during cardiac arrest. OBJECTVES: We sought to determine the impact of the sonographic approach (subxiphoid [SX] vs. parasternal long [PSL]) on time to image completion, image quality, and visualization of cardiac anatomy during echo, as performed during Advanced Cardiac Life Support. METHODS: This was a multicenter, randomized controlled trial conducted at 29 emergency departments (EDs) assessing the time to image acquisition and image quality between SX and PSL views for echo. Patients were enrolled in the ED and imaged in a simulated cardiac arrest scenario. Clinicians experienced in echo performed both SX and PSL views, first view in random order. Image quality and time to image acquisition were recorded. Echos were evaluated for identification of cardiac landmarks. Data are presented as percentages or medians with interquartile ranges (IQRs). RESULTS: We obtained 6247 echo images, comprising 3124 SX views and 3123 PSL. Overall time to image acquisition was 9.0 s (IQR 6.7-14.1 s). Image acquisition was shorter using PSL (8.8 s, IQR 6.5-13.5 s) compared with SX (9.3 s, IQR 6.7-15.0 s). The image quality was better with the PSL view (3.86 vs. 3.54; p < 0.0001), twice as many SX images scoring in the worst quality category compared with PSL (8.6% vs. 3.7%). Imaging of the pericardium, cardiac chambers, and other anatomic landmarks was superior with PSL imaging. CONCLUSIONS: Echo was performed in < 10 s in > 50% of patients using either imaging technique. Imaging using PSL demonstrated improved image quality and improved identification of cardiac landmarks.

Sonographic Findings of Left Ventricular Dysfunction to Predict Shock Type in Undifferentiated Hypotensive Patients: An Analysis From the Sonography in Hypotension and Cardiac Arrest in the Emergency Department (SHoC-ED) Study.

Introduction Patients that present to the emergency department (ED) with undifferentiated hypotension have a high mortality rate. Hypotension can be divided into four categories: obstructive, hypovolemic, distributive, and cardiogenic. While it is possible to have overlapping or concomitant shock states, being able to differentiate between cardiogenic shock and the other categories is important as it entails a different treatment regime and extra cautions. In this secondary analysis, we investigate if using focused cardiac ultrasonography (FOCUS) to determine left ventricular dysfunction (LVD) can serve as a reliable test for cardiogenic shock. Methods We prospectively collected FOCUS findings performed in 135 ED patients with undifferentiated hypotension as part of an international study. Patients with clearly identified etiologies for hypotension were excluded, along with other specific presumptive diagnoses. LVD was defined as the identification of a generally hypodynamic left ventricle in the setting of shock. FOCUS findings were collected using a standardized protocol and data collection form. All scans were performed by emergency physicians trained in ultrasound. Final shock type was defined as cardiogenic or noncardiogenic by independent specialist blinded chart review. Results In our findings, 135 patients had complete records for assessment of left ventricular function and additional follow-up data and so were included in this secondary analysis. The median age was 56 years and 53% of patients were male. Disease prevalence for cardiogenic shock was 12% and the mortality rate was 24%. The presence of LVD on FOCUS had a sensitivity of 62.50% (95% confidence interval 35.43% to 84.80%), specificity of 94.12% (88.26% to 97.60%), positive likelihood ratio (LR) 10.62 (4.71 to 23.95), negative LR 0.40 (0.21 to 0.75) and accuracy of 90.37% (84.10% to 94.77%) for detecting cardiogenic shock. Conclusion Detecting left ventricular dysfunction on FOCUS may be useful in the early identification of cardiogenic shock in otherwise undifferentiated hypotensive adult patients in the emergency department.

Does Point of Care Ultrasound Improve Resuscitation Markers in Undifferentiated Hypotension? An International Randomized Controlled Trial From The Sonography in Hypotension and Cardiac Arrest in the Emergency Department (SHoC-ED) Series.

Introduction Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for patients with undifferentiated hypotension, yet there is a paucity of evidence for any outcome benefit. We undertook an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key clinical outcomes. Here we report on resuscitation markers.  Methods Adult patients presenting to six emergency departments (ED) in Canada and South Africa with undifferentiated hypotension (systolic blood pressure (SBP) <100mmHg or a Shock Index >1.0) were randomized to receive a PoCUS protocol or standard care (control). Reported physiological markers include shock index (SI), and modified early warning score (MEWS), with biochemical markers including venous bicarbonate and lactate, at baseline and four hours.  Results A total of 273 patients were enrolled, with data collected for 270. Baseline characteristics were similar for each group. Improvements in mean values for each marker during initial treatment were similar between groups: Shock Index; mean reduction in Control 0.39, 95% CI 0.34 to 0.44 vs. PoCUS 0.33, 0.29 to 0.38; MEWS, mean reduction in Control 2.56, 2.22 to 2.89 vs. PoCUS 2.91, 2.49 to 3.32; Bicarbonate, mean reduction in Control 2.71 mmol/L, 2.12 to 3.30 mmol/L vs. PoCUS 2.30 mmol/L, 1.75 to 2.84 mmol/L, and venous lactate, mean reduction in Control 1.39 mmol/L, 0.93 to 1.85 mmol/L vs. PoCUS 1.31 mmol/L, 0.88 to 1.74 mmol/L. Conclusion We found no meaningful difference in physiological and biochemical resuscitation markers with or without the use of a PoCUS protocol in the resuscitation of undifferentiated hypotensive ED patients. We are unable to exclude improvements in individual patients or in specific shock types.

Just the Facts: The Five F's of Focused Echocardiography in Shock.

A 60-year-old female presents to the emergency department (ED) with a 3-day history of fatigue and mild breathlessness. She has a history of lung cancer. Her vitals indicate shock with a heart rate of 140 bpm, a systolic blood pressure (SBP) of 65 mmHg, a respiratory rate of 28, with an oxygen saturation of 90% on 100% a nonrebreather mask, and a normal temperature at 36°C. Her electrocardiograph (ECG) shows sinus tachycardia. She appears mottled and pale.

Does Point-of-care Ultrasonography Change Emergency Department Care Delivered to Hypotensive Patients When Categorized by Shock Type? A Post-Hoc Analysis of an International Randomized Controlled Trial from the SHoC-ED Investigators.

Introduction Our previously reported randomized-controlled-trial of point-of-care ultrasound (PoCUS) for patients with undifferentiated hypotension in the emergency department (ED) showed no survival benefit with PoCUS. Here, we examine the data to see if PoCUS led to changes in the care delivered to patients with cardiogenic and non-cardiogenic shock. Methods A post-hoc analysis was completed on a database of 273 hypotensive ED patients randomized to standard care or PoCUS in six centres in Canada and South Africa. Shock categories recorded one hour after the ED presentation were used to define subcategories of shock. We analyzed initial intravenous fluid volumes, as well as rates of inotrope use and procedures. Results  261 patients could be classified as cardiogenic or non-cardiogenic shock types. Although there were expected differences in the mean fluid volume administered between patients with non-cardiogenic and cardiogenic shock (p-value<0.001), there was no difference between the control and PoCUS groups (mean non-cardiogenic control 1881mL (95% CI 1567-2195mL) vs non-cardiogenic PoCUS 1763mL (1525-2001mL); and cardiogenic control 680mL (28.4-1332mL) vs. cardiogenic PoCUS 744mL (370-1117mL; p= 0.67). Likewise, there were no differences in rates of inotrope administration nor procedures for any of the subcategories of shock between the control group and PoCUS group patients. Conclusion Despite differences in care delivered by subcategory of shock, we did not find any difference in key elements of emergency department care delivered between patients receiving PoCUS and those who did not. This may help explain the previously reported lack of outcome differences between groups.

Does Point-of-Care Ultrasonography Improve Clinical Outcomes in Emergency Department Patients With Undifferentiated Hypotension? An International Randomized Controlled Trial From the SHoC-ED Investigators.

STUDY OBJECTIVE: Point-of-care ultrasonography protocols are commonly used in the initial management of patients with undifferentiated hypotension in the emergency department (ED). There is little published evidence for any mortality benefit. We compare the effect of a point-of-care ultrasonography protocol versus standard care without point-of-care ultrasonography for survival and clinical outcomes. METHODS: This international, multicenter, randomized controlled trial recruited from 6 centers in North America and South Africa and included selected hypotensive patients (systolic blood pressure <100 mm Hg or shock index >1) randomized to early point-of-care ultrasonography plus standard care versus standard care without point-of-care ultrasonography. Diagnoses were recorded at 0 and 60 minutes. The primary outcome measure was survival to 30 days or hospital discharge. Secondary outcome measures included initial treatment and investigations, admissions, and length of stay. RESULTS: Follow-up was completed for 270 of 273 patients. The most common diagnosis in more than half the patients was occult sepsis. We found no important differences between groups for the primary outcome of survival (point-of-care ultrasonography group 104 of 136 patients versus standard care 102 of 134 patients; difference 0.35%; 95% binomial confidence interval [CI] -10.2% to 11.0%), survival in North America (point-of-care ultrasonography group 76 of 89 patients versus standard care 72 of 88 patients; difference 3.6%; CI -8.1% to 15.3%), and survival in South Africa (point-of-care ultrasonography group 28 of 47 patients versus standard care 30 of 46 patients; difference 5.6%; CI -15.2% to 26.0%). There were no important differences in rates of computed tomography (CT) scanning, inotrope or intravenous fluid use, and ICU or total length of stay. CONCLUSION: To our knowledge, this is the first randomized controlled trial to compare point-of-care ultrasonography to standard care without point-of-care ultrasonography in undifferentiated hypotensive ED patients. We did not find any benefits for survival, length of stay, rates of CT scanning, inotrope use, or fluid administration. The addition of a point-of-care ultrasonography protocol to standard care may not translate into a survival benefit in this group.

Functional and Evolutionary Characterization of a Gene Transfer Agent's Multilocus "Genome".

Gene transfer agents (GTAs) are phage-like particles that can package and transfer a random piece of the producing cell's genome, but are unable to transfer all the genes required for their own production. As such, GTAs represent an evolutionary conundrum: are they selfish genetic elements propagating through an unknown mechanism, defective viruses, or viral structures "repurposed" by cells for gene exchange, as their name implies? In Rhodobacter capsulatus, production of the R. capsulatus GTA (RcGTA) particles is associated with a cluster of genes resembling a small prophage. Utilizing transcriptomic, genetic and biochemical approaches, we report that the RcGTA "genome" consists of at least 24 genes distributed across five distinct loci. We demonstrate that, of these additional loci, two are involved in cell recognition and binding and one in the production and maturation of RcGTA particles. The five RcGTA "genome" loci are widespread within Rhodobacterales, but not all loci have the same evolutionary histories. Specifically, two of the loci have been subject to frequent, probably virus-mediated, gene transfer events. We argue that it is unlikely that RcGTA is a selfish genetic element. Instead, our findings are compatible with the scenario that RcGTA is a virus-derived element maintained by the producing organism due to a selective advantage of within-population gene exchange. The modularity of the RcGTA "genome" is presumably a result of selection on the host organism to retain GTA functionality.

An investigation of cancer rates in the Argentia region, Newfoundland and Labrador: an ecological study.

BACKGROUND: The Argentia region of Newfoundland and Labrador, Canada, was home to a US naval base during a 40-year period between the 1940s and the 1990s. Activities on the base resulted in contamination of the soil and groundwater in the region with chemicals such as heavy metals and dioxins, and residents have expressed concern about higher rates of cancer in their community. This study investigated the rate of cancer diagnosis that is disproportionately high in the Argentia region. METHODS: Cases of cancer diagnosed between 1985 and 2011 were obtained for the Argentia region, two comparison communities, and the province of Newfoundland and Labrador. Crude and age-standardized incidence rates of cancer diagnosis were calculated and compared. The crude incidence rate was adjusted for differences in age demographics using census data, and age-standardized incidence rates were compared. RESULTS: Although the Argentia region had a higher crude rate of cancer diagnosis, the age-standardized incidence rate did not differ significantly from the comparison communities or the provincial average. Argentia has an aging population, which may have influenced the perception of increased cancer diagnosis in the community. CONCLUSIONS: We did not detect an increased burden of cancer in the Argentia region.

Solubilization of proteins: the importance of lysis buffer choice.

The efficient extraction of proteins of interest from cells and tissues is not always straightforward. Here we demonstrate the differences in extraction of the focal adhesion protein Kindlin-2 from choriocarcinoma cells using NP-40 and RIPA lysis buffer. Furthermore, we demonstrate the use of a more denaturing urea/thiourea lysis buffer for solubilization, by comparing its effectiveness for solubilization of small heat-shock proteins from smooth muscle with the often utilized RIPA lysis buffer. Overall, the results demonstrate the importance of establishing the optimal lysis buffer for specific protein solubilization within the experimental workflow.

Effect of vaginal self-sampling on cervical cancer screening rates: a community-based study in Newfoundland.

BACKGROUND: Cervical cancer is highly preventable and treatable if detected early through regular screening. Women in the Canadian province of Newfoundland & Labrador have relatively low rates of cervical cancer screening, with rates of around 40 % between 2007 and 2009. Persistent infection with oncogenic human papillomavirus (HPV) is a necessary cause for the development of cervical cancer, and HPV testing, including self-sampling, has been suggested as an alternative method of cervical cancer screening that may alleviate some barriers to screening. Our objective was to determine whether offering self-collected HPV testing screening increased cervical cancer screening rates in rural communities. METHODS: During the 2-year study, three community-based cohorts were assigned to receive either i) a cervical cancer education campaign with the option of HPV testing; ii) an educational campaign alone; iii) or no intervention. Self-collection kits were offered to eligible women at family medicine clinics and community centres, and participants were surveyed to determine their acceptance of the HPV self-collection kit. Paired proportions testing for before-after studies was used to determine differences in screening rates from baseline, and Chi Square analysis of three dimensional 2 × 2 × 2 tables compared the change between communities. RESULTS: Cervical cancer screening increased by 15.2 % (p < 0.001) to 67.4 % in the community where self-collection was available, versus a 2.9 % increase (p = 0.07) in the community that received educational campaigns and 8.5 % in the community with no intervention (p = 0.193). The difference in change in rates was statistically significant between communities A and B (p < 0.001) but not between communities A and C (p = 0.193). The response rate was low, with only 9.5 % (168/1760) of eligible women opting to self-collect for HPV testing. Of the women who completed self-collection, 15.5 % (26) had not had a Pap smear in the last 3 years, and 88.7 % reported that they were somewhat or very satisfied with self-collection. CONCLUSIONS: Offering self-collected HPV testing increased the cervical cancer screening rate in a rural NL community. Women who completed self-collection had generally positive feelings about the experience. Offering HPV self-collection may increase screening compliance, particularly among women who do not present for routine Pap smears.

Protein solubilization: attend to the choice of lysis buffer.

The efficient extraction of proteins of interest from cells and tissues is not always straightforward. In this process, the use of the optimal lysis buffer for protein solubilization should be considered. Here we demonstrate the use of a urea/thiourea lysis buffer, based on O'Farrell's buffer, and compare its effectiveness for solubilization of proteins from smooth muscle with the often utilized RIPA lysis buffer.