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Introduction: For rhythm control of acute atrial flutter (AAFL) 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 AAFL, 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 intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA.
We conducted a scoping review (Medline and EMBASE, 2000–2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters.
Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters.
This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.
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.
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.
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.
Clinical decision support (CDS) has been implemented in many clinical settings in order to improve decision-making. Their potential to improve diagnostic accuracy and reduce unnecessary testing is well documented; however, their effectiveness in impacting physician practice in real world implementations has been limited by poor physician adherence. The objective of this systematic review and meta-regression was to establish the effectiveness of CDS tools on adherence and identify which characteristics of CDS tools increase physician use of and adherence. Methods: A systematic review and meta-analysis was conducted. MEDLINE, EMBASE, PsychINFO, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception to June 2017. Included studies examined CDS in a hospital setting, reported on physician adherence to or use of CDS, utilized a comparative study design, and reported primary data. All tool type was classified based on the Cochrane Effective Practice and Organization of Care (EPOC) classifications. Studies were stratified based on study design (RCT vs. observational). Meta-regression was completed to assess the different effect of characteristics of the tool (e.g. whether the tool was mandatory or voluntary, EPOC classifications). Results: A total of 3,359 candidate articles were identified. Seventy-two met inclusion criteria, of which 46 reported outcomes appropriate for meta-regression (5 RCTs and 41 observational studies). Overall, a trend of increased CDS use was found (pooled RCT OR: 1.36 [95% CI: 0.97-1.89]; pooled observational OR: 2.12 [95% CI: 1.75-2.56]).When type of tool is considered, clinical practice guidelines were superior compared to other interventions (p=.150). Reminders (p=.473) and educational interventions (p=.489) were less successful than other interventions. Multi-modal tools were not more successful that single interventions (p=.810). Lastly, voluntary tools may be supperior to than mandatory tools (p=.148). None of these results are statistically significant. Conclusion: CDS tools accompanied by a planned intervention increases physician utilization and adherence to the tool. Meta-regression found that clinical practice guidelines had the biggest impact on physician adherence although not statistically significant. Further research is required to understand the most effective intervention to maximize physician utilization of CDS tools.
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.
Saturn's moon Enceladus has vents emerging from a sub-surface ocean, offering unique probes into the liquid environment. These vents drain into the larger neutral torus in orbit around Saturn. We present a methanol (CH3OH) detection observed with IRAM 30-m from 2008 along the line-of-sight through Saturn's E-ring. Additionally, we also present supporting observations from the Herschel public archive of water (ortho-H2O; 1669.9 GHz) from 2012 at a similar elongation and line-of-sight. The CH3OH 5(1,1)-4(1,1) transition was detected at 5.9σ confidence. The line has 0.43 km s−1 width and is offset by +8.1 km s−1 in the moon's reference frame. Radiative transfer models allow for gas cloud dimensions from 1750 km up to the telescope beam diameter ~73 000 km. Taking into account the CH3OH lifetime against solar photodissociation and the redshifted line velocity, there are two possible explanations for the CH3OH emission: methanol is primarily a secondary product of chemical interactions within the neutral torus that: (1) spreads outward throughout the E-ring or (2) originates from a compact, confined gas cloud lagging Enceladus by several km s−1. We find either scenario to be consistent with significant redshifted H2O emission (4σ) measured from the Herschel public archive. The measured CH3OH:H2O abundance (>0.5%) significantly exceeds the observed abundance in the direct vicinity of the vents (~0.01%), suggesting CH3OH is likely chemically processed within the gas cloud with methane (CH4) as its parent species.
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.
By examining Herschel images in the HerMES & H-ATLAS surveys at the position of Planck Catalog of Compact Source sources we are able to determine the nature of the Planck sources. Most are simply nearby, known, dusty galaxies, while others are foreground galactic ‘cirrus’ dust. About 11% of sources, though, appear to be groups or clumps of fainter Herschel objects. Followup of a number of these indicates that they are galaxy clusters or protoclusters at z ~1-3 that contain a number of galaxies undergoing contemporaneous massive starbursts. These sources present challenges for current galaxy & cluster formation/evolution models.
This study builds on existing research on the prevalence and consequences of mental illness discrimination by investigating and quantifying the relationships between experienced discrimination and costs of healthcare and leisure activities/social participation among secondary mental health service users in England.
We use data from the Mental Illness-Related Investigations on Discrimination (MIRIAD) study (n = 202) and a subsample of the Viewpoint study (n = 190). We examine experiences of discrimination due to mental illness in the domains of personal relationships, community activities, and health care, and how such experienced discrimination relates to patterns of service use and engagement in leisure activities.
Our findings show that the cost of health services used for individuals who reported previous experiences of discrimination in a healthcare setting was almost twice as high as for those who did not report any discrimination during the last 12 months (Relative Risk: 1.73; 95% Confidence Interval (CI): 1.39, 2.17) and this was maintained after controlling for symptoms and functioning. Experienced discrimination in healthcare (Relative Risk: 0.83; 95% CI: 0.81, 0.84) or in relationships (Relative Risk: 0.89; 95% CI: 0.87, 0.91), however, was associated with lower participation in, and hence lower costs of, leisure activities. Individuals who reported any discrimination in a healthcare setting had, on average, £434 higher costs associated with health service use while reported discrimination in the community was associated with increased leisure costs of £32.
These findings make an important initial step towards understanding the magnitude of the costs of mental health-related discrimination.
Obesity is characterized by chronic low-grade inflammation that may lead to emotional distress and behavioural symptoms. This study assessed the relationship between adiposity, low-grade inflammation, eating behaviour and emotional status in obese women awaiting gastric surgery and investigated the effects of surgery-induced weight loss on this relationship.
A total of 101 women with severe or morbid obesity awaiting gastric surgery were recruited. Assessments were performed before and at 1 year post-surgery and included the measurement of neuroticism and extraversion using the revised Neuroticism–Extraversion–Openness personality inventory (NEO-PI-R) and eating behaviour using the Three-Factor Eating Questionnaire (TFEQ). Blood samples were collected for the measurement of serum inflammatory markers [interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP)] and adipokines (leptin, adiponectin).
At baseline, body mass index (BMI) was positively correlated with inflammatory markers and adipokines. Regression analyses adjusting for age and diabetes revealed that baseline concentrations of IL-6 and hsCRP were associated with the depression and anxiety facets of neuroticism, with higher inflammation predicting higher anxiety and depression. This association remained significant after adjusting for BMI. Gastric surgery induced significant weight loss, which correlated with reduced inflammation. After controlling for BMI variations, decreases in inflammatory markers, notably hsCRP, were associated with reduced anxiety and TFEQ-cognitive restraint scores.
These findings indicate strong associations between adiposity, inflammation and affectivity in obese subjects and show that surgery-induced weight loss is associated concomitantly with reduced inflammation and adipokines and with significant improvement in emotional status and eating behaviour. Inflammatory status appears to represent an important mediator of emotional distress and psychological characteristics of obese individuals.
Phenotypical Down syndrome includes pharyngeal and maxillary hypoplasia and, frequently, constricted maxillary arch with nasal obstruction.
This clinical trial assessed the effects of rapid maxillary expansion on ENT disorders in 24 children with Down syndrome randomly allocated to receive either rapid maxillary expansion or not. Each group received ENT and speech therapy assessments before expansion and after the device had been removed.
In the rapid maxillary expansion group, the yearly ENT infection rate was reduced when assessed after device removal (p < 0.01). The parents of rapid maxillary expansion children reported a reduction in respiratory obstruction symptoms. Audiological assessment revealed improvements in the rapid maxillary expansion group (p < 0.01). Cephalometry showed increased maxillary width in the rapid maxillary expansion group.
Rapid maxillary expansion resulted in a reduction in hearing loss, yearly rate of ENT infections and parentally assessed symptoms of upper airway obstruction, compared with no treatment. These findings are probably related to expanded oronasal space, due to rapid maxillary expansion.