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Introduction: We previously derived (N = 559) and validated (N = 1,100) the 10-item Ottawa Heart Failure Risk Scale (OHFRS), to assist with disposition decisions for patients with acute heart failure (AHF) in the emergency department (ED). In the current study we sought to use a larger dataset to develop a more concise and more accurate risk scale. Methods: We analyzed data from the prior two studies and from a new cohort. For all 3 groups we conducted prospective cohort studies that enrolled patients who required treatment for AHF at 8 tertiary care hospital EDs. Patients were followed for 30 days. The primary outcome was short-term serious outcome (SSO), defined as death within 30 days, intubation or non-invasive ventilation (NIV) after admission, myocardial infarction, or relapse resulting in hospital admission within 14 days. The fully pre-specified logistic regression model with 13 predictors (where age, pCO2, and SaO2 were modeled using spline functions) was fitted to 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions, and estimated a sample size of 2,000 patients. Results: The 1,986 patients had mean age 77.3 years, male 54.1%, EMS arrival 41.2%, IV NTG 3.3%, ED NIV 5.4%, admission on initial visit 49.5%. Overall there were 236 (11.9%) SSOs including 61 deaths (3.1%), meaning that current admission practice sensitivity for SSO was only 59.7%. The final HEARTRISK6 scale is comprised of 6 variables (points) (C-statistic 0.68): Valvular heart disease (2) Antiarrhythmic medication (2) ED non-invasive ventilation (3) Creatinine 80–150 (1); ≥150 (3) Troponin ≥3x URL (2) Walk test failed (1). The probability of SSO ranged from 4.8% for a total score of 0 to 62.4% for a score of 10, showing good calibration. Choosing a HEARTRISK6 total point admission threshold of ≥3 would yield sensitivity of 70.8% (95%CI 64.5-76.5) for SSO with a slight decrease in admissions to 47.9%. Choosing a threshold of ≥2 would yield a sensitivity of 84.3% (95%CI 79.0-88.7) but require 66.6% admissions. Conclusion: Using a large prospectively collected dataset, we created a more concise and more sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of the HEARTRISK6 scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: For rhythm control of acute atrial fibrillation (AAF) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAF, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an apriori-specified modified intention-to-treat (MITT) basis excluding patients who never received the study infusion (e.g. spontaneous conversion). Data were analyzed using chi-squared tests and logistic regression. Our target sample size was 374 evaluable patients. Results: Of 395 randomized patients, 18 were excluded from the MITT analysis; none were lost to follow-up. The Drug-Shock (N = 198) and Shock Only (N = 180) groups (total = 378) were similar for all characteristics including mean age (60.0 vs 59.5 yrs), duration of AAF (10.1 vs 10.8 hrs), previous AF (67.2% vs 68.3%), median CHADS2 score (0 vs 0), and mean initial heart rate (119.9 vs 118.0 bpm). More patients converted to normal sinus rhythm in the Drug-Shock group (97.0% vs 92.2%; absolute difference 4.8%, 95% CI 0.2-9.9; P = 0.04). The multivariable analyses confirmed the Drug-Shock strategy superiority (P = 0.04). There were no statistically significant differences for time to conversion (91.4 vs 85.4 minutes), total ED length of stay (7.1 vs 7.7 hours), disposition home (97.0% vs 96.1%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion was more common in the Drug-Shock group (8.1% vs 0.6%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAF patients to go home in sinus rhythm. A strategy of initial cardioversion with procainamide was superior to a strategy of immediate ECV.
Clostridium difficile infections (CDIs) affect patients in hospitals and in the community, but the relative importance of transmission in each setting is unknown. We developed a mathematical model of C. difficile transmission in a hospital and surrounding community that included infants, adults and transmission from animal reservoirs. We assessed the role of these transmission routes in maintaining disease and evaluated the recommended classification system for hospital- and community-acquired CDIs. The reproduction number in the hospital was <1 (range: 0.16–0.46) for all scenarios. Outside the hospital, the reproduction number was >1 for nearly all scenarios without transmission from animal reservoirs (range: 1.0–1.34). However, the reproduction number for the human population was <1 if a minority (>3.5–26.0%) of human exposures originated from animal reservoirs. Symptomatic adults accounted for <10% transmission in the community. Under conservative assumptions, infants accounted for 17% of community transmission. An estimated 33–40% of community-acquired cases were reported but 28–39% of these reported cases were misclassified as hospital-acquired by recommended definitions. Transmission could be plausibly sustained by asymptomatically colonised adults and infants in the community or exposure to animal reservoirs, but not hospital transmission alone. Under-reporting of community-onset cases and systematic misclassification underplays the role of community transmission.
Air-breathing evolved in fishes during the Silurian, prior to the conquest of terrestrial environments, as the first air-breathing groups were still aquatic forms. Among fossil fishes and stem-tetrapods, the air-breathing behaviour was described based on anatomical structures and organs, such as spiracles, skeletal buccal pump components, cranial ribs, well-developed pleural ribs, integumentary dermal skeleton, choanae and calcified lungs. However, due to the rarity of soft tissue preservation in the fossil record, the presence of lungs is mostly described among fossil coelacanths, which present a pulmonary complex covered by ossified lung plates throughout its length. Here, we describe the main differences among fossil coelacanth lungs, review some of the accessory air-breathing structures in fossil fishes and stem-tetrapods and discuss the air-breathing evolution that enabled the rise and development of early vertebrates on the terrestrial environment.
For patients with bifascicular block and syncope of unknown origin, different American Heart Association guidelines give Class 2A recommendations for two treatments: the implantable loop recorder (ILR) and empiric pacemaker insertion (PM). Equipoise reflected in guidelines may contribute to uncertainty in management and inefficient resource use. The objective of this analysis is to determine the cost-effectiveness of ILR compared to PM in the management of older adults (age>50 years) with bifascicular block and syncope over two years, from the perspective of a Canadian publicly funded health care system, in the Syncope: Pacing or Recording In ThE Later Years (SPRITELY) trial.
Resource utilization data was collected throughout the trial, and unit costs were assigned (2017 Canadian dollars). Utility was measured at baseline and annually with the EQ-5D-3L. Quality adjusted life years (QALYs) were calculated as area-under-the-curve, and adjusted for baseline imbalances in utility. Confidence intervals for the incremental cost effectiveness ratio were generated with non-parametric bootstrapping.
Mean cost in participants randomized to PM was CAD 9,759 (USD 7,400), compared to CAD 13,453 (USD 10,200) in participants randomized to ILR. The ILR strategy resulted in 0.020 QALYs more than the PM strategy. The incremental cost effectiveness ratio was CAD 186,553 (95% CI: −831,950–1,191,816) (USD 141,900, 95% CI: −632,740–906,440) per additional QALY. In 1,000 bootstrapped replicates, the cost of the ILR strategy was always greater than that of the PM strategy. At the threshold of CAD 50,000 (USD 38,000) per additional QALY, the probability that the ILR strategy is the cost effective option is 0.504.
ILR costs were greater than PM costs, with little difference in QALY outcomes over two-years. Findings are generalizable to patients similar to SPRITELY participants, from the perspective of the Canadian health care system. However, practice pattern variation and payment systems inhibit generalizability to other countries. Future analysis will explore cost and QALY outcomes in countries that participated in the SPRITELY trial.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
The earliest tetrapodomorph fishes appear in Chinese deposits of Early Devonian age, and by the Middle Devonian they were widespread globally. Evidence for the earliest digitated tetrapods comes from largely uncontested Middle Devonian trackways and Late Devonian body fossils. The East Gondwana Provence (Australasia, Antarctica) fills vital gaps in the phylogenetic and biogeographic history of the tetrapods, with the Gondwanan clade Canowindididae exhibiting a high degree of endemism within the early part of the stem tetrapod radiation. New anatomical details of Koharalepis, from the Middle Devonian Aztec Siltstone of Antarctica, are elucidated from synchrotron scan data. These include the position of the orbit, the condition of the hyomandibular, the shape of the palate and arrangement of the vomerine fangs. Biogeographical and phylogenetic models of stem tetrapod origins and radiations are discussed.
Forage maize (Zea mays L.) is often grown year after year on the same land on many intensive dairy farms in north-west Europe. This results in agronomical problems such as weed resistance and decline of soil quality, which may be solved by ley-arable farming. In the current study, forage maize was grown at different nitrogen (N) fertilization levels for 3 years on permanent arable land and on temporary arable land after ploughing out different types of grass–clover swards. Swards differed in management (grazing or cutting) and age (temporary or permanent). Maize yield and soil residual mineral N content were measured after the maize harvest. There was no effect on maize yield of the management of ploughed-out grass–clover swards but a clear effect of the age of grass–clover swards. The N fertilizer replacement value (NFRV) of all ploughed grass–clover swards was >170 kg N/ha in the first year after ploughing. In the third year after ploughing, NFRV of the permanent sward still exceeded 200 kg N/ha, whereas that of the temporary swards decreased to 30 kg N/ha on average. Soil residual nitrate (NO3−) remained below the local, legal threshold of 90 kg NO3− N/ha except for the ploughed-out permanent sward in the third year after ploughing (166 kg NO3− N/ha). The current study highlights the potential of forage maize – ley rotations in saving fertilizer N. This is beneficial both for the environment and for the profitability of dairy production in north-western Europe.
Introduction: Out of hospital cardiac arrest (OHCA) continues to carry a very high mortality rate, with approximately 10% surviving to hospital discharge. In 2015, the American Heart Association release updated guidelines dictating best practices in post-return of spontaneous circulation (ROSC) care, advocating for more liberal utilization of emergent coronary angiography. We sought to determine if the post-ROSC care at our centre during our study period adhered to the previously published (2010) guidelines. Methods: We performed a retrospective analysis (Sept. 2011 - June 2015) of the Resuscitation Outcomes Consortium (ROC) database, which contains pre-hospital, hospital and outcomes data on adult, EMS-treated, non-traumatic OHCA. Patients under 18 years, with missing age data or with obvious non-cardiac causes of arrest were excluded. Key variables included rates of post-ROSC emergent angiography, survival to hospital discharge and survival to hospital discharge with favourable neurologic outcome (modified Rankin score 2). Results: During the study period, there were a total of 997 OHCA; 86 met exclusion criteria. Of the 911 remaining patients, 557 (61.1%) were transported to a local ED. Of those transported to the ED, 262 (47.0%) achieved sustained ROSC, defined as survival to ED discharge. Of those who achieved sustained ROSC, median age was 65 years (IQR=21.75), 66.8% were male. ECG interpretation data was available on 214 patients, of whom 56 had definite STEMI, and 135 had definite absence of STEMI. 37/56 (66.1%) definite STEMI patients received coronary angiography within 24 hours of presentation, as per AHA guidelines. 58/262 (22.1%) post-ROSC patients overall received coronary angiography within 24 hours of presentation to the ED. Of those 58 patients who received emergent angiography, 38 (65.5%) underwent percutaneous coronary intervention (PCI). No patients received fibrinolysis. Of post-ROSC patients who received emergent coronary angiography, 40/58 (69.0%) survived to hospital discharge and 37/58 (63.8%) survived with good neurologic outcome. In comparison, 55/204 (27.0%) who did not receive emergent angiography survived to hospital discharge and 18.8% survived with good neurologic outcome. Conclusion: Only 22.1% of patients with OHCA, and only 66.1% with ECG-proven STEMI underwent emergent coronary angiography post-ROSC. Further investigation into causes for delay or the withholding of emergent angiography is necessary.
Introduction: Out of hospital cardiac arrest (OHCA) continues to carry a very high mortality rate, with approximately 10% surviving to hospital discharge. We sought to determine if outcomes from out of hospital cardiac arrest (OHCA) at our centre were consistent with recently published North American outcomes data from the Resuscitation Outcomes Consortium (ROC). Methods: We performed a retrospective analysis (Sept 2011 June 2015) of the Resuscitation Outcomes Consortium (ROC) database, which contains pre-hospital, in-hospital and outcomes data on adult, EMS-treated, non-traumatic OHCA. Patients under 18 years, with missing age data or with obvious non-cardiac causes of arrest were excluded. Results: During the study period, there were a total of 997 OHCA; 86 met exclusion criteria. Of the 911 remaining patients, 557 (61.1%) were transported to a local ED. 92 (35.1%) were receiving ongoing CPR at the time of their presentation to the ED. Of those transported to the ED, 262 (47.0%) achieved sustained ROSC, defined as survival to ED discharge. A total of 95 patients survived to hospital discharge (36.3% of patients who achieved sustained ROSC, 17.1% of those who were transported to the ED, and 10.4% of the all OHCA). Of those who survived to hospital discharge who had neurologic outcome data, 90.5% had a modified Rankin score of 2. Initial presenting rhythm with EMS was ventricular fibrillation or pulseless ventricular tachycardia in 233 patients. Of these, 212 (91.0%) were transported to the ED, 134 (57.5%) achieved sustained ROSC, and 71 (30.5%) survived to hospital discharge. 54/60 (90.0%) of those with a documented neurologic exam had a favourable neurologic outcome. Initial presenting rhythm with EMS was PEA or asystole in 636 patients. Of these, 320 (50.3%) were transported to the ED, 115 (18.1%) achieved sustained ROSC, and 17 (2.7%) survived to hospital discharge. 9/10 (90%) of those with a documented neurologic exam had a favourable neurologic outcome. 358 of the arrests were witnessed. Of these, 274 (76.5%) were transported to the ED, 150 (41.9%) achieved sustained ROSC, and 51 (15.9%) survived to hospital discharge. 47/53 (88.7%) of those with a documented neurologic exam had a favourable neurologic outcome. Conclusion: Outcomes from out of hospital cardiac arrest in London, Ontario are comparable to other sites across North America.
Objectives: Health technology reassessment (HTR) is a policy process to manage health technologies throughout their lifecycle and ensure their ongoing optimal use. However, within an ever-evolving field, HTR is only one of many concepts associated with the optimization of health technologies. There is limited understanding of how other concepts and processes might differ and/or be interrelated. This study aims to describe the concepts underlying the various technology optimization processes and to reconcile their relationships within the HTR process.
Methods: A synthesis of the literature on approaches to HTR was completed. An inductive synthesis approach was completed to catalogue common concepts and themes. Expert stakeholders were consulted to develop a schematic to diagrammatically depict the relationships among concepts and frame them within the HTR process.
Results: A practical schematic was developed. Common concepts and themes were organized under six major domains that address the following discussion questions: (i) what is the value of the existing technology?; (ii) what is the current utilization gap?; (iii) what are the available tools and resources?; (iv) what are the levers for change?; (v) what is the desired outcome?; and (vi) who are the foundational actors?
Conclusions: Using these six questions to frame the issues faced by HTR will advance the common understanding of HTR, as well as improve implementation of HTR initiatives. These questions will clearly identify the process required to move forward within a complex healthcare system.
A large number of hydrodynamic pulsation models are converged in the first overtone, and their mean properties compared with observations of RRc stars in six globular clusters. The two observed quantities, period and Fourier parameter ϕ31, lead, via the models, to inferred values for mean mass, luminosity and temperature of the RRc sample in each cluster. We find a narrow range in intracluster RRc luminosity and temperature, but a wider range in mass. At the same time, the intercluster spread is wide in all three parameters. A full discussion of our techniques and results will be given elsewhere (Simon and Clement, in preparation).
The SPICA mid- and far-infrared telescope will address fundamental issues in our understanding of star formation and ISM physics in galaxies. A particular hallmark of SPICA is the outstanding sensitivity enabled by the cold telescope, optimised detectors, and wide instantaneous bandwidth throughout the mid- and far-infrared. The spectroscopic, imaging, and polarimetric observations that SPICA will be able to collect will help in clarifying the complex physical mechanisms which underlie the baryon cycle of galaxies. In particular, (i) the access to a large suite of atomic and ionic fine-structure lines for large samples of galaxies will shed light on the origin of the observed spread in star-formation rates within and between galaxies, (ii) observations of HD rotational lines (out to ~10 Mpc) and fine structure lines such as [C ii] 158 μm (out to ~100 Mpc) will clarify the main reservoirs of interstellar matter in galaxies, including phases where CO does not emit, (iii) far-infrared spectroscopy of dust and ice features will address uncertainties in the mass and composition of dust in galaxies, and the contributions of supernovae to the interstellar dust budget will be quantified by photometry and monitoring of supernova remnants in nearby galaxies, (iv) observations of far-infrared cooling lines such as [O i] 63 μm from star-forming molecular clouds in our Galaxy will evaluate the importance of shocks to dissipate turbulent energy. The paper concludes with requirements for the telescope and instruments, and recommendations for the observing strategy.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.
Our current knowledge of star formation and accretion luminosity at high redshift (z > 3–4), as well as the possible connections between them, relies mostly on observations in the rest-frame ultraviolet, which are strongly affected by dust obscuration. Due to the lack of sensitivity of past and current infrared instrumentation, so far it has not been possible to get a glimpse into the early phases of the dust-obscured Universe. Among the next generation of infrared observatories, SPICA, observing in the 12–350 µm range, will be the only facility that can enable us to trace the evolution of the obscured star-formation rate and black-hole accretion rate densities over cosmic time, from the peak of their activity back to the reionisation epoch (i.e., 3 < z ≲ 6–7), where its predecessors had severe limitations. Here, we discuss the potential of photometric surveys performed with the SPICA mid-infrared instrument, enabled by the very low level of impact of dust obscuration in a band centred at 34 µm. These unique unbiased photometric surveys that SPICA will perform will fully characterise the evolution of AGNs and star-forming galaxies after reionisation.