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Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.
Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.
Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.
Introduction: Point of care ultrasonography (PoCUS) is an established tool in the initial management of hypotensive patients in the emergency department (ED). It has been shown rule out certain shock etiologies, and improve diagnostic certainty, however evidence on benefit in the management of hypotensive patients is limited. We report the findings from our international multicenter RCT assessing the impact of a PoCUS protocol on diagnostic accuracy, as well as other key outcomes including mortality, which are reported elsewhere. Methods: Recruitment occurred at 4 North American and 3 Southern African sites. Screening at triage identified patients (SBP<100 mmHg or shock index >1) who were randomized to either PoCUS or control groups. Scans were performed by PoCUS-trained physicians. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. Final chart review was blinded to initial impressions and PoCUS findings. Categorical data was analyzed using Fishers two-tailed test. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. The perceived shock category changed more frequently in the PoCUS group 20/127 (15.7%) vs. control 7/125 (5.6%); RR 2.81 (95% CI 1.23 to 6.42; p=0.0134). There was no significant difference in change of diagnostic impression between groups PoCUS 39/123 (31.7%) vs control 34/124 (27.4%); RR 1.16 (95% CI 0.786 to 1.70; p=0.4879). There was no significant difference in the rate of correct category of shock between PoCUS (118/127; 93%) and control (113/122; 93%); RR 1.00 (95% CI 0.936 to 1.08; p=1.00), or for correct diagnosis; PoCUS 90/127 (70%) vs control 86/122 (70%); RR 0.987 (95% CI 0.671 to 1.45; p=1.00). Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We found that the use of PoCUS did change physicians’ perceived shock category. PoCUS did not improve diagnostic accuracy for category of shock or diagnosis.
Introduction: Point of care ultrasound (PoCUS) is an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). While PoCUS protocols have been shown to improve early diagnostic accuracy, there is little published evidence for any mortality benefit. We report the findings from our international multicenter randomized controlled trial, assessing the impact of a PoCUS protocol on survival and key clinical outcomes. Methods: Recruitment occurred at 7 centres in North America (4) and South Africa (3). Scans were performed by PoCUS-trained physicians. Screening at triage identified patients (SBP<100 or shock index>1), randomized to PoCUS or control (standard care and no PoCUS) groups. Demographics, clinical details and study findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. The primary outcome measure was 30-day/discharge mortality. Secondary outcome measures included diagnostic accuracy, changes in vital signs, acid-base status, and length of stay. Categorical data was analyzed using Fishers test, and continuous data by Student T test and multi-level log-regression testing. (GraphPad/SPSS) Final chart review was blinded to initial impressions and PoCUS findings. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no difference between groups for the primary outcome of mortality; PoCUS 32/129 (24.8%; 95% CI 14.3-35.3%) vs. Control 32/129 (24.8%; 95% CI 14.3-35.3%); RR 1.00 (95% CI 0.869 to 1.15; p=1.00). There were no differences in the secondary outcomes; ICU and total length of stay. Our sample size has a power of 0.80 (α:0.05) for a moderate effect size. Other secondary outcomes are reported separately. Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We did not find any mortality or length of stay benefits with the use of a PoCUS protocol, though a larger study is required to confirm these findings. While PoCUS may have diagnostic benefits, these may not translate into a survival benefit effect.
Introduction: Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for emergency department (ED) patients with undifferentiated non-traumatic hypotension. While PoCUS has been shown to improve early diagnosis, there is a minimal evidence for any outcome benefit. We completed an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key resuscitation markers in this group. We report diagnostic impact and mortality elsewhere. Methods: The SHoC-ED1 study compared the addition of PoCUS to standard care within the first hour in the treatment of adult patients presenting with undifferentiated hypotension (SBP<100 mmHg or a Shock Index >1.0) with a control group that did not receive PoCUS. Scans were performed by PoCUS-trained physicians. 4 North American, and 3 South African sites participated in the study. Resuscitation outcomes analyzed included volume of fluid administered in the ED, changes in shock index (SI), modified early warning score (MEWS), venous acid-base balance, and lactate, at one and four hours. Comparisons utilized a T-test as well as stratified binomial log-regression to assess for any significant improvement in resuscitation amount the outcomes. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no significant difference in mean total volume of fluid received between the control (1658 ml; 95%CI 1365-1950) and PoCUS groups (1609 ml; 1385-1832; p=0.79). Significant improvements were seen in SI, MEWS, lactate and bicarbonate with resuscitation in both the PoCUS and control groups, however there was no difference between groups. Conclusion: SHOC-ED1 is the first RCT to compare PoCUS to standard of care in hypotensive ED patients. No significant difference in fluid used, or markers of resuscitation was found when comparing the use of a PoCUS protocol to that of standard of care in the resuscitation of patients with undifferentiated hypotension.
Salmonella enterica causes an estimated 1 million domestically acquired foodborne illnesses annually. Salmonella enterica serovar Enteritidis (SE) is among the top three serovars of reported cases of Salmonella. We examined trends in SE foodborne outbreaks from 1973 to 2009 using Joinpoint and Poisson regression. The annual number of SE outbreaks increased sharply in the 1970s and 1980s but declined significantly after 1990. Over the study period, SE outbreaks were most frequently attributed to foods containing eggs. The average rate of SE outbreaks attributed to egg-containing foods reported by states began to decline significantly after 1990, and the proportion of SE outbreaks attributed to egg-containing foods began declining after 1997. Our results suggest that interventions initiated in the 1990s to decrease SE contamination of shell eggs may have been integral to preventing SE outbreaks.
After a little more than forty years of work related to the interplanetary plasma and the heliosphere the IAU's Commission 49 was formally discontinued in 2015. The commission started its work when the first spacecraft were launched to measure the solar wind in–situ away from Earth orbit, both inward and outward from 1 AU. It now hands over its activities to a new commission during an era of space research when Voyager 1 measures in–situ the parameters of the local interstellar medium at the edge of the heliosphere. The commission will be succeeded by C.E3 with a similar area of responsibility but with more focused specific tasks that the community intends to address during the coming several years. This report includes a short description of the motivation for this commission and of the historical context. It then describes work from 2012 to 2015 during the present solar cycle 24 that has been the weakest in the space era so far. It gave rise to a large number of studies on solar energetic particles and cosmic rays. Other studies addressed e.g. the variation of the solar wind structure and energetic particle fluxes on long time scales, the detection of dust in the solar wind and the Voyager measurements at the edge of the heliosphere. The research is based on measurements from spacecraft that are at present operational and motivated by the upcoming Solar Probe + and Solar Orbiter missions to explore the vicinity of the Sun. We also report here the progress on new and planned radio instruments and their importance for heliospheric studies. Contributors to this report are Carine Briand, Yoichiro Hanaoka, Eduard Kontar, David Lario, Ingrid Mann, John D. Richardson.
Electroencephalography and magnetoencephalography (MEG) studies have identified alterations in gamma-band (30–80 Hz) cortical activity in schizophrenia and mood disorders, consistent with neural models of disturbed glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic evidence suggests specific deficits in GABA-A receptor function in schizoaffective bipolar disorder (SABP), a clinical syndrome with features of both bipolar disorder and schizophrenia. This study investigated gamma oscillations in this under-researched disorder.
MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex-matched healthy controls.
Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t35 = −2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses.
Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco-magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected.
A foodborne outbreak with 49 cases (22 culture positive for Campylobacter sp.) following a wedding party in the East of England was investigated. A retrospective cohort study identified an association between consumption of chicken liver pâté and infection with Campylobacter jejuni/coli. There was a statistically significant association between dose (amount of chicken liver pâté eaten) and the risk of disease [‘tasted’: odds ratio (OR) 1·5, 95% confidence interval (CI) 0·04–∞; ‘partly eaten’: OR 8·4, 95% CI 1·4–87·5; ‘most or all eaten’: OR 36·1, 95% CI 3·3–2119). The local authority found evidence that the preparation of chicken livers breached Food Standards Agency's guidelines. This epidemiological investigation established a clear dose–response relationship between consumption of chicken liver pâté and the risk of infection with Campylobacter. The continuing need to raise public awareness of the risk to human health posed by undercooked chicken liver is evident.
We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.
Electrochromic (EC) devices are able to vary their throughput of visible light and solar energy by the application of a voltage. They are of much interest for “smart” windows in buildings and are able to create energy efficiency, occupant well being, and security. This paper gives a survey over oxide-based EC device technology and also presents some recent advances regarding EC thin films of mixed metal oxides, nanoparticle-containing electrolytes to join these films, and metal-based transparent electrical conductors needed to apply the voltage.
The irradiation behavior of high-density uranium silicides has been a matter of interest to the nuclear industry for use in high power or low enrichment applications. Transmission electron microscopy studies have found that heavy ion bombardment renders U3Si and U3Si2 amorphous at temperatures below about 250 C , and that U3Si becomes mechanically unstable suffering rapid growth by plastic flow [2,3]. In this present work, crystallographic changes preceding amorphization by fission fragment damage have been studied by high-resolution neutron diffraction as a function of damage produced by uranium fission at room temperature. Initially, both silicides had tetragonal crystal structures. Crystallographic and amorphous phases were studied simultaneously by combining conventional Rietveld refinement of the crystallographic phases with Fourier filtering analysis of the non-crystalline scattering component .