Exploring the Impact of Surface Functionalization on the Reaction, Magnetophoretic, and Collective Transport Behavior of Nanoscale Zerovalent Iron.

This study provides a systematic analysis of the transport and magnetophoretic behavior of nanoscale zerovalent iron (nZVI) particles, both bare and surface functionalized by poly(ethylene glycol) (PEG) and carboxymethyl cellulose (CMC), after undergoing a chemical reaction. Here, a simple and well-investigated chemical reaction of methyl orange (MO) degradation by nZVI was used as a model reaction system, and the sand column transport and low-gradient magnetophoretic profiles of the nanoparticles were measured before and after the reaction. The results were compared over time and analyzed in the context of extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory to understand the particle interactions involved. The colloidal stability of both bare and functionalized nZVI particles was enhanced after the reaction due to the consumption of metallic Fe content, resulting in a significant drop in their magnetic properties. As a result, they exhibited improved mobility across the sand column and a slower magnetophoretic collection rate compared to the unreacted particles. Here, the colloidal filtration theory (CFT) was employed to analyze the transport behavior of nZVI particles across the packed sand column. It has been observed that the surface properties of the reacted functionalized particles changed, possibly due to the entrapment of degraded products within the polymer adlayer. Moreover, quartz crystal microbalance with dissipation (QCM-D) measurements were performed to reveal the viscoelastic contribution of the adlayer formed by both bare and functionalized nZVI particles after the reaction on influencing their transport behavior across the sand column. Finally, we proposed the implementation of a high-gradient magnetic trap (HGMT) to reduce the transport distance of the colloidally stable CMC-nZVI, both before and after the reaction. This study sheds light on the behavioral changes of iron nanoparticles after the reaction and highlights environmental concerns regarding the presence of reacted nanoparticles.

Low-Gradient Magnetophoresis of Nanospheres and Nanorods through a Single Layer of Paper.

The possible magnetophoretic migration of iron oxide nanoparticles through the cellulosic matrix within a single layer of paper is challenging with its underlying mechanism remained unclear. Even with the recent advancements of theoretical understanding on magnetophoresis, mainly driven by cooperative and hydrodynamics phenomena, the contributions of these two mechanisms on possible penetration of magnetic nanoparticles through cellulosic matrix of paper have yet been proven. Here, by using iron oxide nanoparticles (IONPs), both nanospheres and nanorods, we have investigated the migration kinetics of these nanoparticles through grade 4 Whatman filter paper with a particle retention of 20-25 µm. By performing droplet tracking experiments, the real-time stained area growth of the particle droplet on the filter paper, under the influences of a grade N40 NdFeB magnet, were recorded. Our results show that the spatial and temporal expansion of the IONP stain is biased toward the magnet and such an effect is dependent on (i) particle concentration and (ii) particle shape. The kinetics data were first analyzed by treating it as a radial wicking fluid, and later the IONP distribution within the cellulosic matrix was investigated by optical microscopy. The macroscopic flow front velocities of the stained area ranged from 259 µm/s to 16 040 µm/s. Moreover, the microscopic magnetophoretic velocity of nanorod cluster was also successfully measured as ∼214 µm/s. Findings in this work have indirectly revealed the strong influence of cooperative magnetophoresis and the engineering feasibility of paper-based magnetophoretic technology by taking advantage of magnetoshape anisotropy effect of the particles.

Comparing outcomes of out-of-hospital cardiac arrest patients with initial shockable rhythm in Singapore and Osaka using population-based databases.

BACKGROUND: Previous research indicated outcomes among refractory out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm were different in Singapore and Osaka, Japan, possibly due to the differences in access to extracorporeal cardiopulmonary resuscitation. However, this previous study had a risk of selection bias. To address this concern, this study aimed to evaluate the outcomes between Singapore and Osaka for OHCA patients with initial shockable rhythm using only population-based databases. METHODS: This was a secondary analysis of two OHCA population-based databases in Osaka and Singapore, including adult OHCA patients with initial shockable rhythm. A machine-learning-based prediction model was derived from the Osaka data (n = 3088) and applied to the PAROS-SG data (n = 2905). We calculated the observed-expected ratio (OE ratio) for good neurological outcomes observed in Singapore and the expected derived from the data in Osaka by dividing subgroups with or without prehospital ROSC. RESULTS: The one-month good neurological outcomes in Osaka and Singapore among patients with prehospital ROSC were 70% (791/1,125) and 57% (440/773), and among patients without prehospital ROSC were 10% (196/1963) and 2.8% (60/2,132). After adjusting patient characteristics, the outcome in Singapore was slightly better than expected from Osaka in patients with ROSC (OE ratio, 1.067 [95%CI 1.012 to 1.125]), conversely, it was worse than expected in patients without prehospital ROSC (OE ratio, 0.238 [95%CI 0.173 to 0.294]). CONCLUSION: This study showed the outcomes of OHCA patients without prehospital ROSC in Singapore were worse than expected derived from Osaka data even using population-based databases. (249/250 words).

Outcome assessment for out-of-hospital cardiac arrest patients in Singapore and Japan with initial shockable rhythm.

BACKGROUND: Singapore and Osaka in Japan have comparable population sizes and prehospital management; however, the frequency of ECPR differs greatly for out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm. Given this disparity, we hypothesized that the outcomes among the OHCA patients with initial shockable rhythm in Singapore were different from those in Osaka. The aim of this study was to evaluate the outcomes of OHCA patients with initial shockable rhythm in Singapore compared to the expected outcomes derived from Osaka data using machine learning-based prediction models. METHODS: This was a secondary analysis of two OHCA databases: the Singapore PAROS database (SG-PAROS) and the Osaka-CRITICAL database from Osaka, Japan. This study included adult (18-74 years) OHCA patients with initial shockable rhythm. A machine learning-based prediction model was derived and validated using data from the Osaka-CRITICAL database (derivation data 2012-2017, validation data 2018-2019), and applied to the SG-PAROS database (2010-2016 data), to predict the risk-adjusted probability of favorable neurological outcomes. The observed and expected outcomes were compared using the observed-expected ratio (OE ratio) with 95% confidence intervals (CI). RESULTS: From the SG-PAROS database, 1,789 patients were included in the analysis. For OHCA patients who achieved return of spontaneous circulation (ROSC) on hospital arrival, the observed favorable neurological outcome was at the same level as expected (OE ratio: 0.905 [95%CI: 0.784-1.036]). On the other hand, for those who had continued cardiac arrest on hospital arrival, the outcomes were lower than expected (shockable rhythm on hospital arrival, OE ratio: 0.369 [95%CI: 0.258-0.499], and nonshockable rhythm, OE ratio: 0.137 [95%CI: 0.065-0.235]). CONCLUSION: This observational study found that the outcomes for patients with initial shockable rhythm but who did not obtain ROSC on hospital arrival in Singapore were lower than expected from Osaka. We hypothesize this is mainly due to differences in the use of ECPR.

'But what if you miss something ?': factors that influence medical student consideration of cost in decision making.

CONTEXT: Cost-conscious care is critical for healthcare sustainability but evidence suggests that most doctors do not consider cost in their clinical decision making. A critical step in changing this is understanding the barriers to encouraging behaviours and attitudes related to cost-conscious care. We therefore conducted a qualitative study to address the research question: what factors influence consideration of cost in emergency medicine (ED) clinical decision making? METHODS: This was a qualitative focus group study using patient vignettes to explore attitudes towards cost-conscious clinical decision making. Participants were Year 4 and Year 5 medical students from Singapore, a country with a fee-for-service healthcare system. After a data-driven initial data analysis, and to make sense of a multitude of factors impacting on cost conscious care, we selected Fishbein's integrative model of behavioural prediction to underpin secondary data analysis. RESULTS: Via four focus groups with 21 participants, we identified five main themes relevant to the integrative model of behavioural prediction. These were: attitudes towards considering cost when managing a patient (e.g., "better safe than sorry"); normative beliefs (e.g., doing what others do, perceptions of patient wishes); efficacy beliefs (e.g., no authority to take decisions or challenge); skills and knowledge (e.g., little knowledge of costs), and environmental constraints (e.g., the nature of the healthcare system). DISCUSSION: Medical students do not consider cost in their clinical decision making due to numerous factors, of which lack of knowledge of costs is but one. While some of the factors identified reflect those found in previous studies with residents and fully-trained staff, and in other contexts, theory driven analysis added value in that it facilitated a richer exploration of why students do not consider cost in clinical decision making. Our findings provide insight to inform how best to engage and empower educators and learners in teaching and learning about cost-conscious care.

Headache in the Emergency Department: A Multicenter Observational Study from Singapore.

Background and Objectives: There is scarce data about the epidemiology, clinical features, investigations, diagnosis, treatment, and outcome in patients attending Singapore emergency departments (EDs) with nontraumatic headache. We sought to describe these characteristics of adult patients presenting to the ED with a primary complaint of headache. Materials and Methods: We performed a cross-sectional study on adult patients with nontraumatic headache over 4 consecutive weeks from 18 March 2019 to 14 April 2019 across four EDs in Singapore. Exclusion criteria were history of head trauma within 48 h of presentation, missing records, interhospital transfers, representation with the same headache as a recent previous visit and headache as an associated symptom. Results: During the study period, 579 patients (representing 1.8% of the total ED census) comprising 55.3% males and with a median age of 36 years presented to the four Singapore EDs with a primary complaint of nontraumatic headache. Paracetamol (41.5%), non-steroidal anti-inflammatory drugs (34.4%) and tramadol (31.5%) were the three commonest analgesics used either singly or in combination. Prochlorperazine (22.9%) and metoclopramide (17.4%) were frequent anti-emetic adjuncts. One-third of patients had computed tomography of the brain performed, which found abnormalities among 20.9% of them. ED diagnoses of primary headache conditions were made in 73.6% of patients. Conclusions: Primary headaches constituted most ED headache diagnoses. ED imaging of selected patients yielded a relatively high pick-up rate for significant intracranial abnormalities. Opioid use for symptomatic relief of headaches in the ED was found to be high, underscoring the need for improvement in headache analgesia relief practices in the ED.

Magnetophoresis of Magnetic Pickering Emulsions Under Low Field Gradient: Macroscopic and Microscopic Motion.

Monodispersed iron oxide nanoparticles (IONPs) coated with polystyrenesulfonate (PSS) and cetrimonium bromide (CTAB) have been used to stabilize magnetic Pickering emulsions (MPEs). Magnetophoresis of MPEs under the influence of a low gradient magnetic field (∇B < 100 T/m) was investigated at the macroscopic and microscopic scale. At the macroscopic scale, for the case of pH 7, the MPE achieved a magnetophoretic velocity of 70.9 µm/s under the influence of ∇B at 93.8 T/m. The magnetic separation efficiency of the MPE at 90% was achieved within 30 min for pH 3, 7, and 10. At pH 10, the colloidal stability of the MPE was the lowest compared to that for pH 3 and 7. Thus, MPE at pH 10 required the shortest time for achieving the highest separation efficiency, as the MPE experienced cooperative magnetophoresis at alkaline pH. The creaming rate of the MPE at all conditions was still lower compared to magnetophoresis and was negligible in influencing its separation kinetics profiles. At the microscopic scale, the migration pathways of the MPEs (with diameters between 2.5 and 7.5 µm) undergoing magnetophoresis at ∇B ∼ 13.0 T/m were recorded by an optical microscope. From these experiments, and taking into consideration the MPE size distribution from the dynamic light scattering (DLS) measurement, we determined the averaged microscopic magnetophoretic velocity to be 7.8 ± 5.5 µm/s. By making noncooperative magnetophoresis assumptions (with negligible interactions between the MPEs along their migration pathways), the calculated velocity of individual MPEs was 9.8 µm/s. Such a value was within the percentage error of the experimental result of 7.8 ± 5.5 µm/s. This finding allows for an easy and quick estimation of the magnetophoretic velocity of MPEs at the microscale by using macroscopic separation kinetics data.

The Transport Behavior of a Biflagellated Microswimmer before and after Cargo Loading.

The changes in the transport behavior of a microswimmer before and after cargo loading are crucial to understanding and control of the motion of a biohybrid microbot. In this work, we show the change in swimming behavior of biflagellated microalgae Chlamydomonas reinhardtii picking up a 4.5 µm polystyrene microbead upon collision. The microswimmer changed from linear forward motion into helical motion upon the attachment of the cargo and swam with a decreased swimming velocity. We revealed the helical motion of the microswimmer upon cargo loading due to suppression of flagella by image analysis of magnified time-lapse images of C. reinhardtii with one microbead attached at the anterior end (between the flagella). Furthered suppression on the flagellum imposed by the loading of the second cargo has led to increased oscillation per displacement traveled and decreased swimming velocity. Moreover, the microswimmer with a microbead attached at the posterior end swam with swimming velocity close to free swimming microalgae and did not exhibit helical swimming behavior. The experimental results and analysis showed that the loading location of the cargo has a great influence over the swimming behavior of the microswimmer. Furthermore, the work balance calculation and mathematical analysis based on Lighthill's model are well consistent with our experimental findings.

Sedimentation Kinetics of Magnetic Nanoparticle Clusters: Iron Oxide Nanospheres vs Nanorods.

A detailed study of the sedimentation kinetics of iron oxide nanoparticle (IONP) clusters composed of nanospheres and nanorods is presented. Measurements were performed to determine the absorbance of an IONP suspension undergoing sedimentation over time by using a UV-vis spectrophotometer with simultaneous monitoring of the hydrodynamic diameter of the clusters formed with dynamic light scattering (DLS). Mathematical analysis based on Happel's spherical and cylindrical models was conducted to reveal the relationship between the settling velocity of the IONP clusters and their packing density. For the case of IONP clusters composed of rodlike particles, two distinctive phases of sedimentation were recorded, with the occurrence of rapid sedimentation at the beginning of the process (phase I) followed by a slower settling rate (phase II). In sedimentation phase II, even though the nanorod clusters had a hydrodynamic size of >500 nm, which was much larger than that of the nanosphere clusters (∼200 nm), their settling velocity of 0.0038 mm/min was still slower than that of the nanosphere clusters. Such observations were mainly a result of the packing density differences between the formed clusters; due to the end-to-end particle interactions of nanorods, the nanorod clusters were less tightly packed and more permeable. In addition to the mathematical analysis, quartz crystal microbalance with dissipation (QCM-D) was employed to measure the "softness" of the IONP clusters formed, and this physical property can be further related to their packing density. This study illustrated that for a rapidly aggregating system, such as magnetic IONPs, not only do the particle shape and size uniformity contribute to the physical properties of the particle clusters formed but also the nature of the aggregation, either end-to-end and/or side-to-side, should be carefully considered when designing a colloidally stable IONP suspension.

Artificial Magnetotaxis of Microbot: Magnetophoresis versus Self-Swimming.

An artificial magnetotactic microbot was created by integrating the microalgal cell with magnetic microbead for its potential application as biomotor in microscale environment. Here, we demonstrate the remote magnetotactic control of the microbot under a low gradient magnetic field (<100 T/m). We characterize the kinematic behavior of the microbots carrying magnetic microbeads of two different sizes, with diameter of 2 and 4.5 µm, in the absence and presence of magnetic field. In the absence of magnetic field, we observed the microbot showed a helical motion as a result of the misalignment between the thrust force and the symmetry axis after the attachment. The microbot bound with a larger magnetic microbead moved with higher translational velocity but rotated slower about its axis of rotation. The viscous force was balanced by the thrust force of the microbot, resulting in a randomized swimming behavior of the microbot at its terminal velocity. Meanwhile, under the influence of a low gradient magnetic field, we demonstrated that the directional control of the microbot was based on following principles: (1) magnetophoretic force was insignificant on influencing its perpendicular motion and (2) its parallel motion was dependent on both self-swimming and magnetophoresis, in which this cooperative effect was a function of separation distance from the magnet. As the microbot approached the magnet, the magnetophoretic force suppressed its self-swimming behavior, leading to a positive magnetotaxis of the microbot toward the source of magnetic field. Our experimental results and kinematic analysis revealed the contribution of mass density variation of particle-and-cell system on influencing its dynamical behavior.

Peri-mortem caesarean section after traumatic arrest: Crisis resource management.

Peri-mortem caesarean section (PMCS) is a very rare procedure performed to improve the chances of survival for both mother and fetus following cardiorespiratory arrest. Non-obstetricians including Emergency Physicians (EPs) are often called upon to perform this procedure under challenging and suboptimal circumstances. We reported a case of PMCS performed timely after traumatic cardiorespiratory arrest that resulted in fetal survival. A 25-year-old primigravida female and six-month pregnant presented to the Emergency Department (ED) of an adult tertiary hospital. She experienced traumatic cardiorespiratory arrest for nearly 27 min following a high-speed motor vehicle crash. Upon ED arrival, she was in pulseless electrical activity. She was immediately intubated with continuation of cardiopulmonary resuscitation. She received bilateral tube thoracostomies as well as intravenous (IV) transfusion of blood products, adrenaline and tranexamic acid. Her fundal height was two centimeters above the umbilicus on palpation. The EP performed a PMCS via a midline laparotomy 3-4 min upon ED arrival. The baby was bradycardic and cyanosed with no spontaneous respiration at birth and was resuscitated by a second EP. She was intubated and the EP gained IV access using a cannula introduced into the umbilical vein. Neonatal hypothermia was avoided using cling wrap. The baby was transported to a nearby neonatal intensive unit. She survived and is currently one year old. The mother, however, did not respond to our resuscitation and succumbed to her multiple injuries. We reviewed the limited literature regarding this potentially life-saving emergency procedure and highlighted the challenges facing our resuscitation team.

Variable importance analysis with interpretable machine learning for fair risk prediction.

Machine learning (ML) methods are increasingly used to assess variable importance, but such black box models lack stability when limited in sample sizes, and do not formally indicate non-important factors. The Shapley variable importance cloud (ShapleyVIC) addresses these limitations by assessing variable importance from an ensemble of regression models, which enhances robustness while maintaining interpretability, and estimates uncertainty of overall importance to formally test its significance. In a clinical study, ShapleyVIC reasonably identified important variables when the random forest and XGBoost failed to, and generally reproduced the findings from smaller subsamples (n = 2500 and 500) when statistical power of the logistic regression became attenuated. Moreover, ShapleyVIC reasonably estimated non-significant importance of race to justify its exclusion from the final prediction model, as opposed to the race-dependent model from the conventional stepwise model building. Hence, ShapleyVIC is robust and interpretable for variable importance assessment, with potential contribution to fairer clinical risk prediction.

Increasing neurologically intact survival after out-of-hospital cardiac arrest among elderly: Singapore Experience.

Objectives: With more elderly presenting with Out-of-Hospital Cardiac Arrests (OHCAs) globally, neurologically intact survival (NIS) should be the aim of resuscitation. We aimed to study the trend of OHCA amongst elderly in a large Asian registry to identify if age is independently associated with NIS and factors associated with NIS. Methods: All adult OHCAs aged ≥18 years attended by emergency medical services (EMS) from April 2010 to December 2019 in Singapore was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Cases pronounced dead at scene, non-EMS transported, traumatic OHCAs and OHCAs in ambulances were excluded. Patient characteristics and outcomes were compared across four age categories (18-64, 65-79, 80-89, ≥90). Multivariable logistic regression analysis determined the factors associated with NIS. Results: 19,519 eligible cases were analyzed. OHCA incidence increased with age almost doubling in octogenarians (from 312/100,000 in 2011 to 652/100,000 in 2019) and tripling in those ≥90 years (from 458/100,000 in 2011 to 1271/100,000 in 2019). The proportion of patients with NIS improved over time for the 18-64, 65-79- and 80-89-years age groups, with the greatest improvement in the youngest group. NIS decreased with each increasing year of age and minute of response time. NIS increased in the arrests of presumed cardiac etiology, witnessed and bystander CPR. Conclusions: Survival with good outcomes has increased even amongst the elderly. Regardless of age, NIS is possible with good-quality CPR, highlighting its importance. End-of-life planning is a complex yet necessary decision that requires qualitative exploration with elderly, their families and care providers.

Machine learning prediction of refractory ventricular fibrillation in out-of-hospital cardiac arrest using features available to EMS.

Background: Shock-refractory ventricular fibrillation (VF) or ventricular tachycardia (VT) is a treatment challenge in out-of-hospital cardiac arrest (OHCA). This study aimed to develop and validate machine learning models that could be implemented by emergency medical services (EMS) to predict refractory VF/VT in OHCA patients. Methods: This was a retrospective study examining adult non-traumatic OHCA patients brought into the emergency department by Singapore EMS from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Data from April 2010 to March 2020 were extracted for this study. Refractory VF/VT was defined as VF/VT persisting or recurring after at least one shock. Features were selected based on expert clinical opinion and availability to dispatch prior to arrival at scene. Multivariable logistic regression (MVR), LASSO and random forest (RF) models were investigated. Model performance was evaluated using receiver operator characteristic (ROC) area under curve (AUC) analysis and calibration plots. Results: 20,713 patients were included in this study, of which 860 (4.1%) fulfilled the criteria for refractory VF/VT. All models performed comparably and were moderately well-calibrated. ROC-AUC were 0.732 (95% CI, 0.695 - 0.769) for MVR, 0.738 (95% CI, 0.701 - 0.774) for LASSO, and 0.731 (95% CI, 0.690 - 0.773) for RF. The shared important predictors across all models included male gender and public location. Conclusion: The machine learning models developed have potential clinical utility to improve outcomes in cases of refractory VF/VT OHCA. Prediction of refractory VF/VT prior to arrival at patient's side may allow for increased options for intervention both by EMS and tertiary care centres.

Technology activated community first responders in Singapore: Real-world care delivery & outcome trends.

BACKGROUND: Community first responders (CFRs) strengthen the Chain of Survival for out-of-hospital cardiac arrest (OHCA) care. Considerable efforts have been invested in Singapore's CFR program, during the years 2016-2020, by developing an app-based activation system called myResponder. This paper reports on national CFR response indicators to evaluate the real-world impact of these efforts. METHODS: We matched data from the Singapore Civil Defence Force's CFR registry with the Pan Asian Resuscitation Outcomes Study (PAROS) registry data to calculate performance indicators. These included the number of CFRs receiving and accepting an issued alert per OHCA event. Also calculated were the fraction of OHCA events where CFRs received an issued alert, or accepted the alert, and arrived at the scene either before or after EMS. We also present trends of these indicators and compare the prevalence of these fractions between the CFR-attended and CFR-unattended OHCA events. RESULTS: Of 6577 alerted OHCA events, 42.7% accepted an alert, 50% of these arrived at the scene and 71% of them arrived before EMS. Almost all CFR response indicators improved over time even for the pandemic year (2020). The fraction of OHCA events where >2 CFRs received an alert increased from 62% to 96%; the same figure for accepting an alert did not change much but >2 CFRs arriving at the scene increased from 0% to 7.5%. The fraction of OHCA events with an automated external defibrillator applied and defibrillation performed by CFR increased from 4.2% to 10.3% and 1.6% to 3%, respectively. Statistically significant differences were observed in these indicators when CFR-attended and CFR-unattended OHCA events were compared. CONCLUSION: This real-world study shows that activating CFRs using mobile technology can improve community response to OHCA and are bearing fruit in Singapore at a national level. Some targets for improvement and future research are highlighted in this report.

Does witness type affect the chance of receiving bystander CPR in out-of-hospital cardiac arrest?

OBJECTIVES: The relationship between the bystander witness type and receipt of bystander CPR (BCPR) is not well understood. Herein we compared BCPR administration between family and non-family witnessed out-of-hospital cardiac arrest (OHCA). BACKGROUND: In many communities, interventions in the past decade have contributed to an increased receipt of BCPR, for example in Singapore from 15% to 60%. However, BCPR rates have plateaued despite sustained and ongoing community-based interventions, which may be related to gaps in education or training for various witness types. The purpose of this study was to investigate the association between witness type and BCPR administration. METHODS: Singapore data from 2010-2020 was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) network registry (n = 25,024). All adult, layperson witnessed, non-traumatic OHCAs were included in this study. RESULTS: Of 10,016 eligible OHCA cases, 6,895 were family witnessed and 3,121 were non-family witnessed. After adjustment for potential confounders, BCPR administration was less likely for non-family witnessed OHCA (OR 0.83, 95% CI 0.75, 0.93). After location stratification, non-family witnessed OHCAs were less likely to receive BCPR in residential settings (OR 0.75, 95% CI 0.66, 0.85). In non-residential settings, there was no statistically significant association between witness type and BCPR administration (OR 1.11, 95% CI 0.88, 1.39). Details regarding witness type and bystander CPR were limited. CONCLUSION: This study found differences in BCPR administration between family and non-family witnessed OHCA cases. Elucidation of witness characteristics may be useful to determine populations that would benefit most from CPR education and training.

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra-early stroke (≤6 h). Our meta-analysis updated the evidence on its safety and benefits in acute stroke. METHODS: We searched major electronic databases for randomized trials comparing transdermal GTN versus placebo/control in acute stroke. Primary outcomes were mortality, 90-day modified Rankin Scale (mRS), and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilization, and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, and assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were ICH versus ischemic stroke, minor (NIHSS ≤5) versus major (NIHSS >5) ischemic stroke, ischemic stroke with versus without thrombolysis, prehospital versus non prehospital settings, time from stroke to randomization ≤6 h versus >6 h, and high versus low overall RoB studies. RESULTS: Seven eligible primary trials enrolled 5363 patients. GTN reduced BP (mean difference [MD] = -4.74 mm Hg, 95% confidence interval [CI] = -6.03 to -3.45 mm Hg] and diastolic BP (MD = -2.94 mm Hg, 95% CI = -3.74 to -2.13 mm Hg) 24 h posttreatment but did not affect 4- to 10-day mortality (relative risk [RR] = 1.11, 95% CI = 0.82 to 1.49), 90-day mortality (RR = 0.96, 95% CI = 0.77 to 1.19), and 90-day mRS >2 (RR = 0.98, 95% CI = 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes. CONCLUSIONS: Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra-early stroke (≤6 h).

Pre- and apnoeic high-flow oxygenation for rapid sequence intubation in the emergency department (the Pre-AeRATE trial): A multicentre randomised controlled trial.

INTRODUCTION: Evidence regarding the efficacy of high-flow nasal cannula (HFNC) oxygenation for preoxygenation and apnoeic oxygenation is conflicting. Our objective is to evaluate whether HFNC oxygenation for preoxygenation and apnoeic oxygenation maintains higher oxygen saturation (SpO2) during rapid sequence intubation (RSI) in ED patients compared to usual care. METHODS: This was a multicentre, open-label, randomised controlled trial in adult ED patients requiring RSI. Patients were randomly assigned 1:1 to either intervention (HFNC oxygenation at 60L/min) group or control (non-rebreather mask for preoxygenation and nasal prongs of at least 15L/min oxygen flow for apnoeic oxygenation) group. Primary outcome was lowest SpO2 during the first intubation attempt. Secondary outcomes included incidence of SpO2 falling below 90% and safe apnoea time. RESULTS: One hundred and ninety patients were included, with 97 in the intervention and 93 in the control group. Median lowest SpO2 during the first intubation attempt was 100% in both groups. Incidence of SpO2 falling below 90% was lower in the intervention group (15.5%) compared to the control group (22.6%) (adjusted relative risk=0.68, 95% confidence interval [CI] 0.37-1.25). Post hoc quantile regression analysis showed that the first quartile of lowest SpO2 during the first intubation attempt was greater by 5.46% (95% CI 1.48-9.45%, P=0.007) in the intervention group. CONCLUSION: Use of HFNC for preoxygenation and apnoeic oxygenation, when compared to usual care, did not improve lowest SpO2 during the first intubation attempt but may prolong safe apnoea time.

Validation of the CaRdiac Arrest Survival Score (CRASS) for predicting good neurological outcome after out-of-hospital cardiac arrest in an Asian emergency medical service system.

BACKGROUND: Survival with favorable neurological outcomes is an important indicator of successful resuscitation in out-of-hospital cardiac arrest (OHCA). We sought to validate the CaRdiac Arrest Survival Score (CRASS), derived using data from the German Resuscitation Registry, in predicting the likelihood of good neurological outcomes after OHCA in Singapore. METHODS: We conducted a retrospective population-based validation study among EMS-attended OHCA patients (≥18 years) in Singapore, using data from the prospective Pan-Asian Resuscitation Outcomes Study registry. Good neurological outcome was defined as a cerebral performance category of 1 or 2. To evaluate the CRASS score in light of the difference in patient characteristics, we used the default constant coefficient (0.8) and the adjusted coefficient (0.2) to calculate the probability of good neurological outcomes. RESULTS: Out of 11,404 analyzed patients recruited between April 2010 and December 2018, 260 had good and 11,144 had poor neurological function. The CRASS score demonstrated good discrimination, with an area under the curve of 0.963 (95% confidence interval: 0.952-0.974). Using the default constant coefficient of 0.8, the CRASS score consistently overestimated the predicted probability of a good outcome. Following adjustment of the coefficient to 0.2, the CRASS score showed improved calibration. CONCLUSION: CRASS demonstrated good discrimination and moderate calibration in predicting favorable neurological outcomes in the validation Singapore cohort. Our study established a good foundation for future large-scale, cross-country validations of the CRASS score in diverse sociocultural, geographical, and clinical settings.