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Introduction: Prognostication is a significant challenge early in the post-cardiac arrest period. Common prognostic factors for neurological survival are unreliable (high false positive rates) until 72 hours post-cardiac arrest. It is not known whether there are a combination of factors that can be utilized earlier in the post-cardiac arrest period to accurately predict patient outcome. Our objective was to predict neurological outcome utilizing a novel combination of patient factors early in the post-cardiac arrest period. Methods: We conducted a retrospective cohort study using data from our local cardiac arrest registry. We included adult patients who obtained a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). We excluded patients who did not survive for at least 24 hours post-ROSC and those who had a do not resuscitate (DNR) order within 2 hours of ROSC. We performed an ordinal regression analysis using the proportional odds model to predict neurological outcome (modified rankin score (mRS)). We included a good neurological outcome (mRS 0-2), poor neurological outcome (mRS 3-5), and dead (mRS 6) as an ordinal outcome. We included a number of patient demographics, intra- and post-cardiac arrest factors as covariates in our model. The predictive performance of our model was analyzed using receiver operating characteristic (ROC) curves for discrimination and Brier statistic for calibration. Results: We included 3448 patients in our analysis. We found that an initial shockable rhythm (odds ratio (OR) 4.1; 95% confidence interval (CI) 3.6, 5.4), the absence of pupillary reflexes (OR 3.5; 95% CI 2.4,4.8) and maximum motor score on the Glasgow Coma Scale (GCS) (OR 1.5; 95% CI 1.4,1.6) had the greatest association with improved neurologic outcome. Longer duration of resuscitation was associate with worse outcomes (OR 0.84, 95% CI 0.82,0.87). The overall performance of our model was excellent with an area under the ROC curve of 0.89 and a Brier statistic of 0.13. Conclusion: Our model predicted good neurological outcome with a high rate of accuracy, however external validation of the model is required. This model may be useful in providing initial risk stratification of patients in clinical practice and future research on post-cardiac arrest care.
Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes
Antidepressant use has risen x3-5 in Western countries since the early 1990s, outstripping changes in depression incidence or prevalence. This represents a major public health challenge.
Nationally-collected antidepressant data were used to assess the impact of "Doing Well", (DW) a novel depression care programme operating in Renfrewshire, Scotland. "Doing Well" implemented a model of “stepped collaborative care”, practitioner education and significant service redesign. Prescribing was compared for three groups: "DW" (76,000 population; clinical and educational intervention), "DW neighbours” (101,000 population; educational interventions only), and Scotland (no specific intervention).
A national rise in antidepressant prescriptions was stabilised for the "DW" group (graph). Antidepressant cost/item fell by 42% and 40% in both “DW” and “DW neighbours” groups but rose by 8% nationally.
Access to clinical interventions are required to reduce antidepressant prescriptions, but cost savings may be made with educational interventions alone.
The placenta develops alongside the embryo and fetus and is responsible for fetal gas exchange and nutrition. The placenta also has important immune and endocrine functions and thus undertakes to fulfill the roles played by various somatic organs in the post-natal situation (Figure 5.1). The placental membrane, the chorion, prevents the fetal and maternal blood from mixing, while allowing transport of molecules. The human placenta is haemochorial, which means that maternal blood contacts the chorionic placental membrane (fetal epitheliem).
Organisations and associated management practices are generally considered responsible for promoting employees' enjoyment of work. Our study, on the other hand, seeks to examine the capacity of individual workers to regulate their own experience of fun. We interviewed eight ‘remarkable’ workers who claimed to always (or nearly always) have fun at work. We utilised a critical realist approach in the analysis that enabled the consideration of both structure and agency in the experience of workplace fun. A key research finding was that participants possessed a strong sense of control over their own happiness at work, demonstrated in four ways: (1) a priority placed on fun, (2) a sense of responsibility for fun, (3) a positive orientation to the world and (4) a sense of mastery and challenge in work tasks. Research findings may inspire both individual workers and organisations to adopt an agentic outlook in the workplace, implementing strategies that enhance employee control.
Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate neurodevelopmental disorders that are both characterized by difficulties in social cognition and social functioning. Due to methodological confounds, the degree of similarity in social cognitive impairments across these two disorders is currently unknown. This study therefore conducted a comprehensive comparison of social cognitive ability in ASD and SCZ to aid efforts to develop optimized treatment programs.
In total, 101 individuals with ASD, 92 individuals with SCZ or schizoaffective disorder, and 101 typically developing (TD) controls, all with measured intelligence in the normal range and a mean age of 25.47 years, completed a large battery of psychometrically validated social cognitive assessments spanning the domains of emotion recognition, social perception, mental state attribution, and attributional style.
Both ASD and SCZ performed worse than TD controls, and very few differences were evident between the two clinical groups, with effect sizes (Cohen's d) ranging from 0.01 to 0.34. For those effects that did reach statistical significance, such as greater hostility in the SCZ group, controlling for symptom severity rendered them non-significant, suggesting that clinical distinctions may underlie these social cognitive differences. Additionally, the strength of the relationship between neurocognitive and social cognitive performance was of similar, moderate size for ASD and SCZ.
Findings largely suggest comparable levels of social cognitive impairment in ASD and SCZ, which may support the use of existing social cognitive interventions across disorders. However, future work is needed to determine whether the mechanisms underlying these shared impairments are also similar or if these common behavioral profiles may emerge via different pathways.
Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.
Introduction: Despite significant advances in resuscitation efforts, there are some patients who remain in ventricular fibrillation (VF) after multiple shocks during out-of-hospital cardiac arrest (OHCA). Double sequential external defibrillation (DSED) has been proposed as a treatment option for patients in shock refractory VF. We sought to compare DSED to standard therapy with regards to VF termination and return of spontaneous circulation (ROSC) for patients presenting in shock refractory VF. Methods: We performed a retrospective review of all treated adult OHCA who presented in VF and received a minimum of three successive shocks over a two year period beginning on Jan 1, 2015 in four Canadian EMS agencies. Using ambulance call reports and defibrillator files, we compared VF termination (defined as the absence of VF at the rhythm check following defibrillation and 2 minutes of CPR) and VF termination into a perfusing rhythm with ROSC between patients who received standard therapy (CPR, defibrillation, epinephrine and antiarrhythmics) and those who received DSED (after on-line medical consultation) for shock refractory VF. Cases of traumatic cardiac arrest and those who presented in VF but terminated VF prior to 3 successive shocks were excluded. Results: Among 197 patients who met the study criteria for shock refractory VF, 161 (81.7%) patients received standard therapy and 36 (18.3%) received DSED. For the primary outcome, VF termination was significantly higher for DSED compared to standard therapy (63.9% vs 18.0%; Δ45.9%; 95% CI: 28.3 to 60.5). For the secondary outcome of VF termination into ROSC, DSED was associated with significantly higher ROSC compared to standard care (33.3% vs 13%; Δ20.3%; 95% CI:13.0 to 33.3). The median (IQR) number of failed standard shocks prior to DSED was 8 (6, 10). When DSED terminated VF, it did so with a single DSED shock in 69.6% of cases. Conclusion: Our observational findings suggest improved VF termination and ROSC are associated with DSED compared to standard therapy for shock refractory VF. An appropriately powered randomized controlled trial is required to assess the impact of DSED on patient-important outcomes.
Introduction: 9-1-1 telecommunicators receive minimal education on agonal breathing, often resulting in unrecognized out-of-hospital cardiac arrest (OHCA). We successfully piloted an educational intervention that significantly improved telecommunicators’ OHCA recognition and bystander CPR rates in Ottawa. We sought to better understand the operations of Canadian 9-1-1 communications centers (CC) in preparation for a multi-centre study of this intervention. Methods: We conducted a National survey of all Canadian CCs. Survey domains included information on organizational structure, dispatch system used, education curriculum, and performance monitoring. It was peer-reviewed, translated in French, pilot-tested, and distributed electronically using a modified Dillman method. We designated respondents in each CC before distribution and used targeted follow-up and small incentives to increase response rate. Respondents also described functioning of neighboring CCs if known. Results: We received information from 51/51 provincial and 1/25 territorial CCs, representing 99.7% of the Canadian population. CCs largely utilize the Medical Dispatch Priority System (MPDS) platform (93%), many are Province/Ministry regulated (50%) and most require a High School diploma as minimum entry level education (78%). Telecommunicators receive initial in-class training (median 1.3 months, IQR 0.3-1.9; range 0.1-2.2), often followed by a preceptorship (84.4%) (median 1.0 months, IQR 0.7-1.7; range 0.4-6.0). Educational curriculum includes information on agonal breathing in 41% of CC, without audio examples in 34%. Among responding CCs, over 39,000 suspected OHCA 9-1-1 calls are received annually. Few CCs maintain local performance statistics on OHCA recognition (25%), bystander CPR rates (25%) or survival rates (50%). Most (97%) expressed interest in future research collaborations. Conclusion: Most Canadian telecommunicators receive no or minimal education in recognizing agonal breathing. Further training and improved OHCA monitoring may assist recognition and enhance outcomes.
Early life experiences can affect social behaviour in later life, but opportunities for socio-behavioural development are often overlooked in current husbandry practices. This experiment investigated the effects of rearing piglets in two-stage group lactation (GL) system from 7 or 14 days of age on piglet aggression at weaning. Three lactation housing treatments were applied to a total of 198 piglets from 30 litters of multiparous sows. All dams farrowed in standard farrowing crates (FCs). Group lactation litters were transferred with their dam at 7 (GL7) or 14 days (GL14) postpartum to GL pens (one pen of five sows at 8.4 m2/sow and one pen of seven sows at 8.1 m2/sow, per GL treatment). Farrowing crate litters remained with their dam in a single litter until weaning. At weaning, 10 to 14 piglets from two unfamiliar litters from the same housing treatment were mixed into pens (n=5 pens/treatment) and their behaviour was continuously recorded for 3.5 h. For each pen, the frequency of aggressive bouts (reciprocal and non-reciprocal aggression lasting <5 s), the frequency and duration of fights (reciprocal aggression lasting ⩾5 s) and bullying events (non-reciprocal aggression lasting ⩾5 s) were recorded, along with whether interactions involved familiar or unfamiliar piglets. Aggressive bouts delivered by FC piglets were approximately 1.5 and 3.0 times more frequent than that delivered by GL7 and GL14 piglets, respectively (40.5, 16.7 and 9.9 bouts/pig, respectively; P<0.05). Fighting was more frequent (1.6, 0.3 and 0.4 fights/pig, respectively; P<0.001) and fights were longer (83, 15 and 32 s fight/pig, respectively; P<0.001) between FC piglets than between GL7 or GL14 piglets. Bullying did not differ between housing treatments (P>0.05). GL7 and GL14 piglets engaged in a similar number of fights with unfamiliar as familiar piglets, but FC piglets had almost three times as many fights with unfamiliar than with familiar piglets (P<0.05). This experiment confirms the benefits of GL housing for pig social development. Further investigation is required to determine whether mixing before 14 days postpartum has implications for other indicators of animal welfare and productivity in a two-stage GL housing system.
Loose farrowing pens have been considered as alternatives to crates to enhance sow welfare. A major concern with pen systems is often higher piglet pre-weaning mortality, especially due to crushing by the sow. An optimal management of light and mat surface temperature may promote greater piglet use of the creep, which has been associated with reduced piglet crushing. A total of 108 sows and their piglets were studied in sow welfare and piglet protection pens on a commercial piggery, across two replicates. Sows were randomly assigned to pens arranged within two creep treatments (bright creep: 300 lx v. dark creep: 4 lx), considering mat temperature as a covariate. Twelve sows and their litters in each treatment (24 in total) had their behaviour continuously recorded for 72-h postpartum (pp), and four focal piglets per litter were weighed on the first and third days pp. In situ behaviour observations were performed daily (from 0800 to 1700 h) on all sows and their litters, every 15 min over 72-h pp to record piglet time spent in the creep, latency to enter the creep for the first time, latency for the litter to remain in the creep for at least 10 min, and piglet and sow use of pen areas immediately in front of (A2) and farthest from the creep (A3). Piglets with access to bright creeps spent on average 7.2% more time (P<0.01) in the creeps than piglets in pens with Dark creeps. In addition, for each degree increase in mat temperature, piglets spent on average 2.1% more time (P<0.01) in the creep. Piglets in pens with bright creeps spent less time in A2 (P=0.04) and the least time in A3 (P=0.01). Light or mat temperature did not affect sow use of pen areas or piglet weight gain. Piglets with bright creeps tended (P=0.06) to take longer to enter the creep for the first time after birth, but the latency for 30.0% of the litter to remain clustered for 10 min tended (P=0.08) to be shorter in bright compared to dark creeps. Overall, piglet use of the creep increased with warm mat temperatures and brightness, which should be further investigated as potential strategies to promote piglet safety and reduce crushing in pen farrowing systems.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
Internal gravity wave energy contributes significantly to the energy budget of the oceans, affecting mixing and the thermohaline circulation. Hence it is important to determine the internal wave energy flux
is the pressure perturbation field and
is the velocity perturbation field. However, the pressure perturbation field is not directly accessible in laboratory or field observations. Previously, a Green’s function based method was developed to calculate the instantaneous energy flux field from a measured density perturbation field
, given a constant buoyancy frequency
. Here we present methods for computing the instantaneous energy flux
for an internal wave field with vertically varying background
, as in the oceans where
typically decreases by two orders of magnitude from the pycnocline to the deep ocean. Analytic methods are presented for computing
from a density perturbation field for
varying linearly with
. To generalize this approach to arbitrary
, we present a computational method for obtaining
. The results for
for the different cases agree well with results from direct numerical simulations of the Navier–Stokes equations. Our computational method can be applied to any density perturbation data using the MATLAB graphical user interface ‘EnergyFlux’.
In their focal article, Chernyak-Hai and Rabenu (2018) argue that social exchange theory (SET) needs an update, and in this they are aligned with Cropanzano, Anthony, Daniels, and Hall's (2017) recent critical review of SET. Drawing on Chernyak-Hai and Rabenu's research, we explore two issues in more depth: first, that work relationships are becoming more complex than can be represented by simple dyadic reciprocity; and second, that the context of work is changing rapidly, with implications for workplace relationships. In exploring the ideas put forward by Chernyak-Hai and Rabenu, we draw on Cropanzano et al.’s two-dimensional model of social exchange, with the first dimension being desirable (positive) resources contrasted with undesirable (negative) ones, and the additional dimension being active (exhibit) behavior versus passive (withdraw) behavior. The first valence-oriented dimension fits clearly with the four foci of Chernyak-Hai and Rabenu's research, which cover both positive constructs, namely leader–member exchange (LMX), perceived organizational support and loyalty, and organizational citizenship behaviors (OCB), as well as negative constructs of perceived organizational politics and counterproductive work behaviors (CWB). The second, behavioral dimension proposed by Cropanzano et al. adds useful theoretical specificity that may address Chernyak-Hai and Rabenu's contention that SET needs updating to account for changes in how employees work and how organizations function.
Analysis of historical records of eclipses of the Sun and Moon between 720 BC and AD 1600 gives a measure of the time difference, TT − UT = ΔT. The first derivative in time along a smooth curve fitted to the values of Δ T measures the changes in the length of the day (lod). The average rate of change of the lod is found to be significantly less than that expected on the basis of tidal friction. Fluctuations on a time-scale of centuries to millennia are mainly attributed to the effects of post-glacial uplift and core-mantle coupling.
The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.
Introduction: A two-year Stroke Ambulance (SA) pilot project was implemented at the University of Alberta Hospital (UAH) in February, 2017, the first in the world to utilize this specialized technology in a rural setting. The primary objective is to evaluate clinical and economic implications of timely SA assessment and treatment of hyperacute stroke patients who present to non-stroke centres in rural Alberta and might otherwise have received delayed treatment, or not at all, due to prolonged transfer times. Methods: A steering committee and seven working groups were established, with representation from Alberta Health Services (AHS) programs impacted, to ensure comprehensive project development and implementation. The SA portable CT scanner, point of care laboratory, and videoconference system facilitate diagnosis of stroke in the field. The multidisciplinary team includes a stroke fellow, advanced & primary care paramedics, registered nurse, CT technologist, and telestroke physician. When not dispatched, the team provides stroke expertise and patient care in the emergency department (ED) and diagnostic imaging. The service model includes suspected stroke patients presenting to non-stroke centres within a 250 Km radius of Edmonton (Phase I); patients presenting to Edmonton Zone (EZ) hospitals without CT capability and/or tPA protocols (Phase 2); and expedited transport from EZ hospitals to the UAH for urgent endovascular therapy (EVT) (Phase 3). A health economic analysis will compare stroke ambulance care with standard care. Results: The SA has responded to 54 dispatches, 13 patients thrombolyzed and 3 patients receiving EVT. Median rendezvous to CT time was 10 minutes, median rendezvous to tPA time was 21 minutes, and mean time from symptom onset to tPA was 180 minutes. There were no complications. After SA imaging and assessment, 18 patients were repatriated back to their local community hospital, avoiding unnecessary admission to tertiary care. Conclusion: Our preliminary experience demonstrates that the SA offers a novel approach to performing timely evaluation and treatment of suspected stroke from non-stroke centres and may serve as an excellent triage mechanism, reducing avoidable admissions to overcapacity tertiary care EDs. The SA team provides added value to the ED with stroke expertise and patient care. A comprehensive health economic analysis will determine cost-effectiveness and whether spread is feasible.