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ObjectivesThe aim of the study was to validate the use of the ABCD2 score for the prediction of stroke after transient ischemic attack (TIA) in patients presenting to the emergency department (ED). The ABCD2 scoring is based on 5 factors as follows: age of at least 60 years; blood pressure of at least 140/90 mm Hg; clinical features such as unilateral weakness and speech impairment alone; duration of at least 60 minutes or 10 to 59 minutes; and diabetes.MethodsThe authors conducted a retrospective observational study of all patients presented to the ED for TIA, as diagnosed by the attending emergency physicians, for a 2-year period. Sensitivity, specificity, and negative predictive value (NPV) were calculated for risk of stroke at 2, 7, 30, and 90 days after presentation.ResultsFrom January 1, 2005, to December 31, 2006, there were 470 patients diagnosed with TIA at the ED. Mean age was 61.0 years (SD, 13.2), with 63.3% males. Age of at least 60 years, unilateral weakness, and duration of at least 60 minutes were found to be significant predictors of stroke at 2 days. An admission rule based on an ABCD2 score of at least 4 showed sensitivity of 86.4% and NPV of 91.7% for stroke at 7 days. Admission based on a score of at least 3 showed sensitivity of 96.6% and NPV of 96.1%. Admission rate was 69.1% and. 83.6%, respectively.ConclusionThe ABCD2 rule showed good sensitivity and NPV for stroke at 7 days. However, NPV was not 100%, and there would still be patients being discharged from the ED and returning with a stroke if this cutoff was implemented in our setting. © 2010 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Context: Only 1% to 8% of adults with out-of-hospital cardiac arrest survive to hospital discharge.Objective: To compare resuscitation outcomes before and after an urban emergency medical services (EMS) system switched from manual cardiopulmonary resuscitation (CPR) to load-distributing band (LDB) CPR.Design, Setting, and Patients: A phased, observational cohort evaluation with intention-to-treat analysis of 783 adults with out-of-hospital, nontraumatic cardiac arrest. A total of 499 patients were included in the manual CPR phase (January 1, 2001, to March 31, 2003) and 284 patients in the LDB-CPR phase (December 20, 2003, to March 31, 2005); of these patients, the LDB device was applied in 210 patients.Intervention: Urban EMS system change from manual CPR to LDB-CPR.Main Outcome Measures: Return of spontaneous circulation (ROSC), with secondary outcome measures of survival to hospital admission and hospital discharge, and neurological outcome at discharge.Results: Patients in the manual CPR and LDB-CPR phases were comparable except for a faster response time interval (mean difference, 26 seconds) and more EMS-witnessed arrests (18.7% vs 12.6%) with LDB. Rates for ROSC and survival were increased with LDB-CPR compared with manual CPR (for ROSC, 34.5%; 95% confidence interval [CI], 29.2%-40.3% vs 20.2%; 95% CI, 16.9%-24.0%; adjusted odds ratio [OR], 1.94; 95% CI, 1.38-2.72; for survival to hospital admission, 20.9%; 95% CI, 16.6%-26.1% vs 11.1%; 95% CI, 8.6%-14.2%; adjusted OR, 1.88; 95% CI, 1.23-2.86; and for survival to hospital discharge, 9.7%; 95% CI, 6.7%-13.8% vs 2.9%; 95% CI, 1.7%-4.8%; adjusted OR, 2.27; 95% CI, 1.11-4.77). In secondary analysis of the 210 patients in whom the LDB device was applied, 38 patients (18.1%) survived to hospital admission (95% CI, 13.4%-23.9%) and 12 patients (5.7%) survived to hospital discharge (95% CI, 3.0%-9.3%). Among patients in the manual CPR and LDB-CPR groups who survived to hospital discharge, there was no significant difference between groups in Cerebral Performance Category (P = .36) or Overall Performance Category (P = .40). The number needed to treat for the adjusted outcome survival to discharge was 15 (95% CI, 9-33).Conclusion: Compared with resuscitation using manual CPR, a resuscitation strategy using LDB-CPR on EMS ambulances is associated with improved survival to hospital discharge in adults with out-of-hospital nontraumatic cardiac arrest. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes. We performed a retrospective analysis of adult asthma patients (aged ≥18 years) treated in the primary and specialist care settings in Singapore between 2015 to 2019. Medication adherence was measured using the medication possession ratio (MPR), and categorised into good adherence (MPR 0.75-1.2), poor adherence (MPR 0.75) or medication oversupply (MPR > 1.2). All statistical analyses were performed using R Studio. 8023 patients, mean age 57 years, were evaluated between 2015 and 2019. Most patients were receiving primary care (70.4%) and on GINA step 1-3 therapies (78.2%). ICS-long-acting beta-2 agonist (ICS-LABA) users increased over the years especially in the primary care, from 33% to 52%. Correspondingly, inpatient admission and ED visit rates decreased over the years. Between 2015 and 2019, the proportion of patients with poor adherence decreased from 12.8% to 10.5% (for ICS) and from 30.0% to 26.8% (for ICS-LABA) respectively. Factors associated with poor adherence included minority ethnic groups (Odds ratio of MPR 0.75-1.2: 0.73-0.93; compared to Chinese), presence of COPD (OR 0.75, 95% CI 0.59-0.96) and GINA step 4 treatment ladder (OR 0.71, 95% CI 0.61-0.85). Factors associated with good adherence were male gender (OR 1.14, 95% CI 1.01-1.28), single site of care (OR 1.22 for primary care and OR 1.76 for specialist care), GINA step 2 treatment ladder (OR 1.28, 95% CI 1.08-1.50). Good adherence was also associated with less frequent inpatient admission (OR 0.91, 95% CI 0.84-0.98), greater SABA overdispensing (OR 1.66, 95% CI 1.47-1.87) and oral corticosteroids use (OR 1.10, 95% CI 1.05-1.14). Inhaled corticosteroid (ICS) adherence has improved generally, however, poor adherence was observed for patients receiving asthma care in both primary and specialist care, and those from the minority ethnicities., (© 2024. The Author(s).)

The widespread use of Chat Generative Pre-trained Transformer (known as ChatGPT) and other emerging technology that is powered by generative artificial intelligence (GenAI) has drawn attention to the potential ethical issues they can cause, especially in high-stakes applications such as health care, but ethical discussions have not yet been translated into operationalisable solutions. Furthermore, ongoing ethical discussions often neglect other types of GenAI that have been used to synthesise data (eg, images) for research and practical purposes, which resolve some ethical issues and expose others. We did a scoping review of the ethical discussions on GenAI in health care to comprehensively analyse gaps in the research. To reduce the gaps, we have developed a checklist for comprehensive assessment and evaluation of ethical discussions in GenAI research. The checklist can be integrated into peer review and publication systems to enhance GenAI research and might be useful for ethics-related disclosures for GenAI-powered products and health-care applications of such products and beyond., Competing Interests: Declaration of interests NL reports funding from the Duke–NUS Signature Research Programme funded by the Ministry of Health, Singapore. JS reports funding from the Wellcome Trust and roles as a Bioethics Committee consultant for Bayer and as an advisory panel member for the Hevolution Foundation. DSWT reports funding from National Medical Research Council, Singapore, Duke–NUS Medical School, and Agency for Science, Technology, and Research; patents on deep learning systems for diabetic retinopathy, glaucoma, and age-related macular degeneration (co-inventor; 2017), a computer-implemented method for training an image classifier using weakly annotated training data (2019), and automatically extracting measurements from an image of a display of a measurement device (2020); has a leadership role (unpaid) as Chair of the AI and Digital Innovation Standing Committee and the Asia–Pacific Academy of Ophthalmology; and serves on the executive committees of the American Academy of Ophthalmology AI Committee, STARD-AI Steering Committee, Imperial College London, DECIDE-AI, and QUANDAS-AI. EJT reports funding from the National Institutes of Health (NIH) Grant and consulting fees as an adviser to Tempus Labs, Pheno.AI, and Abridge. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to investigate the physiological load on bystanders during cardiopulmonary resuscitation (CPR) and the quality of chest compressions in hot and humid environments., Methods: This prospective experimental study compared the physical load and quality of chest compressions among healthy volunteers who performed 10 min chest compression in a climate chamber under normal conditions (for Tokyo) (Wet Bulb Globe Temperature [WBGT] 21 °C) and hot and humid conditions (WBGT 31 °C). The primary outcome was the depth of chest compressions over a 10-minute period. Secondary outcomes included the volunteer's heart rate (HR), core body temperature (BT), Borg scale for assessing fatigue, and blood lactate levels. Data were analyzed using two-way repeated measures analysis of variance (ANOVA) and paired t-tests., Results: Out of 31 participants, 29 participants (mean [SD] age: 21[0.7], male: 21 [70.5 %]) were included in the analysis. For WBGT 21 °C and 31 °C, the mean chest compression depth at 10 min was not statistically difference (the depth of chest compression: 52.2 mm and 51.5 mm (p = 0.52)). At 10 min, heart rate and core temperature were 126 vs. 143 bpm, and 37.4℃ vs. 37.5℃ for WBGT 21℃ vs. WBGT 31℃ (mean differences: 17 bpm [95 % CI: 7.7-26.3], 0.1℃ [95 % CI: -0.1-0.3]). At the end, Borg scale was 16 vs. 18 and lactate levels were 3.9 vs. 5.1 mmol/L (mean differences: 2 [95 % CI: 1-3], 1.2 mmol/L [95 % CI: 0.1-2.3])., Conclusion: there was no significant difference in the depth of chest compression of paramedic students under the conditions between WBGT 31℃ and WBGT 21℃. For secondary outcomes, the lactate and fatigue of bystanders increased under WBGT 31℃ compared to WBGT 21℃. Further research is needed on CPR in hot and humid environments., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Haruka Takahashi has received a research grant from Japan Foundation for Emergency Medicine and ZOLL Foundation. Yohei Okada has received a research grant from the ZOLL Foundation and an overseas scholarship from the FUKUDA foundation for medical technology and the International medical research foundation. Hiroyuki Yokota is an advisor to Aioi Nissay Dowa Insurance Co., Ltd. This organization has no role in conducting this research. Marcus Eng Hock Ong reports grants from the Laerdal Foundation, Laerdal Medical, and Ramsey Social Justice Foundation for funding of the Pan-Asian Resuscitation Outcomes Study an advisory relationship with Global Healthcare SG, a commercial entity that manufactures cooling devices; and funding from Laerdal Medical on an observation program to their Community CPR Training Centre Research Program in Norway. Marcus Eng Hock Ong is a Scientific Advisor to TIIM Healthcare SG and Global Healthcare SG. Marcus Eng Hock Ong is a member of the editorial board of Resuscitation. These organizations have no role in conducting this research. All other authors reported no competing interests]., (© 2024 The Authors.)

This scoping review collates evidence for sex biases in the receipt of bystander cardiopulmonary resuscitation (BCPR) among patients with out-of-hospital cardiac arrest patients globally. The MEDLINE, PsycINFO, CENTRAL, and Embase databases were screened for relevant literature, dated from inception to March 9, 2022. Studies evaluating the association between BCPR and sex/gender in patients with out-of-hospital cardiac arrest, except for pediatric populations and cardiac arrest cases with traumatic cause, were included. The review included 80 articles on BCPR in men and women globally; 58 of these studies evaluated sex differences in BCPR outcomes. Fifty-nine percent of the relevant studies (34/58) indicated that women are less likely recipients of BCPR, 36% (21/58) observed no significant sex differences, and 5% (3/58) reported that women are more likely to receive BCPR. In other studies, women were found to be less likely to receive BCPR in public but equally or more likely to receive BCPR in residential settings. The general reluctance to perform BCPR on women in the Western countries was attributed to perceived frailty of women, chest exposure, pregnancy, gender stereotypes, oversexualization of women's bodies, and belief that women are unlikely to experience a cardiac arrest. Most studies worldwide indicated that women were less likely to receive BCPR than men. Further research from non-Western countries is needed to understand the impact of cultural and socioeconomic settings on such biases and design customized interventions accordingly.

The escalating integration of machine learning in high-stakes fields such as healthcare raises substantial concerns about model fairness. We propose an interpretable framework, fairness-aware interpretable modeling (FAIM), to improve model fairness without compromising performance, featuring an interactive interface to identify a "fairer" model from a set of high-performing models and promoting the integration of data-driven evidence and clinical expertise to enhance contextualized fairness. We demonstrate FAIM's value in reducing intersectional biases arising from race and sex by predicting hospital admission with two real-world databases, the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) and the database collected from Singapore General Hospital Emergency Department (SGH-ED). For both datasets, FAIM models not only exhibit satisfactory discriminatory performance but also significantly mitigate biases as measured by well-established fairness metrics, outperforming commonly used bias mitigation methods. Our approach demonstrates the feasibility of improving fairness without sacrificing performance and provides a modeling mode that invites domain experts to engage, fostering a multidisciplinary effort toward tailored AI fairness., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

The prediction of patient attendance in emergency departments (ED) is crucial for effective healthcare planning and resource allocation. This paper proposes an early warning system that can detect emerging trends in ED attendance, offering timely alerts for proactive operational planning. Over 13 years of historical ED attendance data (from January 2010 till December 2022) with 1,700,887 data points were used to develop and validate: (1) a Seasonal Autoregressive Integrated Moving Average with eXogenous factors (SARIMAX) forecasting model; (2) an Exponentially Weighted Moving Average (EWMA) surge prediction model, and (3) a trend persistence prediction model. Drift detection was achieved with the EWMA control chart, and the slopes of a kernel-regressed ED attendance curve were used to train various machine learning (ML) models to predict trend persistence. The EWMA control chart effectively detected significant COVID-19 events in Singapore. The surge prediction model generated preemptive signals on changes in the trends of ED attendance over the COVID-19 pandemic period from January 2020 until December 2022. The persistence of novel trends was further estimated using the trend persistence model, with a mean absolute error of 7.54 (95% CI: 6.77-8.79) days. This study advanced emergency healthcare management by introducing a proactive surge detection framework, which is vital for bolstering the preparedness and agility of emergency departments amid unforeseen health crises.

Background: Historically in Singapore, all out-of-hospital cardiac arrests (OHCA) were transported to hospital for pronouncement of death. A 'Termination of Resuscitation' (TOR) protocol, implemented from 2019 onwards, enables emergency responders to pronounce death at-scene in Singapore. This study aims to evaluate the cost-effectiveness of the TOR protocol for OHCA management., Methods: Adopting a healthcare provider's perspective, a Markov model was developed to evaluate three competing options: No TOR, Observed TOR reflecting existing practice, and Full TOR if TOR is exercised fully. The model had a cycle duration of 30 days after the initial state of having a cardiac arrest, and was evaluated over a 10-year time horizon. Probabilistic sensitivity analysis was performed to account for uncertainties. The costs per quality adjusted life years (QALY) was calculated., Results: A total of 3,695 OHCA cases eligible for the TOR protocol were analysed; mean age of 73.0 ± 15.5 years. For every 10,000 hypothetical patients, Observed TOR and Full TOR had more deaths by approximately 19 and 31 patients, respectively, compared to No TOR. Full TOR had the least costs and QALYs at $19,633,369 (95% Uncertainty Interval (UI) 19,469,973 to 19,796,764) and 0 QALYs. If TOR is exercised for every eligible case, it could expect to save approximately $400,440 per QALY loss compared to No TOR, and $821,151 per QALY loss compared to Observed TOR., Conclusion: The application of the TOR protocol for the management of OHCA was found to be cost-effective within acceptable willingness-to-pay thresholds, providing some justification for sustainable adoption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The Utstein Out-of-Hospital Cardiac Arrest Resuscitation Registry Template, introduced in 1991 and updated in 2004 and 2015, standardizes data collection to enable research, evaluation, and comparisons of systems of care. The impetus for the current update stemmed from significant advances in the field and insights from registry development and regional comparisons. This 2024 update involved representatives of the International Liaison Committee on Resuscitation and used a modified Delphi process. Every 2015 Utstein data element was reviewed for relevance, priority (core or supplemental), and improvement. New variables were proposed and refined. All changes were voted on for inclusion. The 2015 domains-system, dispatch, patient, process, and outcomes-were retained. Further clarity is provided for the definitions of out-of-hospital cardiac arrest attended resuscitation and attempted resuscitation. Changes reflect advancements in dispatch, early response systems, and resuscitation care, as well as the importance of prehospital outcomes. Time intervals such as emergency medical service response time now emphasize precise reporting of the times used. New flowcharts aid the reporting of system effectiveness for patients with an attempted resuscitation and system efficacy for the Utstein comparator group. Recognizing the varying capacities of emergency systems globally, the writing group provided a minimal dataset for settings with developing emergency medical systems. Supplementary variables are considered useful for research purposes. These revisions aim to elevate data collection and reporting transparency by registries and researchers and to advance international comparisons and collaborations. The overarching objective remains the improvement of outcomes for patients with out-of-hospital cardiac arrest.

We assessed the feasibility of concurrent monitoring of cerebral hemodynamics in adult, comatose out-of-hospital cardiac arrest (OHCA) patients admitted to the National University Heart Centre Singapore from October 2021 to August 2023. Patients underwent continuous near-infrared spectroscopy (NIRS) monitoring in the first 72 h after return of spontaneous circulation (ROSC) and 30-min transcranial Doppler ultrasound (TCD) monitoring at least once. With constant mechanical ventilatory settings and continuous electrocardiographic, pulse oximeter and end-tidal carbon dioxide monitoring, blood pressure was manipulated via vasopressors and cerebral autoregulation assessed by measuring changes in regional cerebral oxygenation (NIRS) and cerebral blood flow velocities (TCD) in response to changes in mean arterial pressure. The primary outcome was neurological recovery at hospital discharge. Amongst the first 16 patients (median age 61, 94% males), we observed four unique patterns: preserved cerebral autoregulation, loss of cerebral autoregulation, cardio-cerebral asynchrony and cerebral circulatory arrest. Patients with preserved cerebral autoregulation had lower levels of neuro-injury biomarkers (neurofilaments light and heavy) and the majority (86%) were discharged with good neurological recovery. Multi-modal assessment of cerebral hemodynamics after OHCA is feasible and derived patterns correlated with neurological outcomes. The between- and within-patient heterogeneity in cerebral hemodynamics calls for more research on individualized treatment strategies.

Background: NULL-PLEASE is a simple and accurate clinical scoring system developed in a Western cohort of patients with out-of-hospital cardiac arrest (OHCA). The need for blood test results limits its use in early stages of care. We adapted and validated the NULL-EASE score (without laboratory tests) in an independent, multiethnic Asian cohort of patients with out-of-hospital cardiac arrest., Methods and Results: Using the Singapore OHCA registry, we included consecutive adult patients with out-of-hospital cardiac arrest who survived to hospital admission between April 2010 to December 2020. In-hospital mortality was the primary outcome. Logistic regression analyses were performed with STATA MP v18. Of 3274 patients (median age 64, interquartile range 54-75; 67.9% male) included in the study, 2476 (75.6%) had in-hospital mortality. NULL-EASE score was significantly lower in survivors compared with nonsurvivors (median [inter quartile range] 3 [1-4] versus 6 [4-7]; P <0.001) and strongly predictive of mortality (area under receiver operating characteristic, 0.81 [95% CI, 0.79-0.83]). Patients with a score of ≥3 had higher odds of mortality (adjusted odds ratio, 8.11 [95% CI, 6.57-10.00]) when compared with those with lower scores, after adjusting for sex, residential arrest, diabetes, respiratory disease, and stroke. A cutoff value of ≥3 predicted mortality with 92.2% sensitivity, 84.1% positive predictive value, 46.1% specificity, and 65.5% negative predictive value. NULL-EASE score performed better in younger compared with older patients (area under receiver operating characteristic, 0.82 versus 0.77, P =0.008)., Conclusions: The NULL-EASE score has good discriminative performance (sensitivity and accuracy) in our multiethnic Asian cohort, but the cutoff of ≥3 falls short of the desired level of specificity for therapeutic decision-making.

The Utstein Out-of-Hospital Cardiac Arrest Resuscitation Registry Template, introduced in 1991 and updated in 2004 and 2015, standardizes data collection to enable research, evaluation, and comparisons of systems of care. The impetus for the current update stemmed from significant advances in the field and insights from registry development and regional comparisons. This 2024 update involved representatives of the International Liaison Committee on Resuscitation and used a modified Delphi process. Every 2015 Utstein data element was reviewed for relevance, priority (core or supplemental), and improvement. New variables were proposed and refined. All changes were voted on for inclusion. The 2015 domains-system, dispatch, patient, process, and outcomes-were retained. Further clarity is provided for the definitions of out-of-hospital cardiac arrest attended resuscitation and attempted resuscitation. Changes reflect advancements in dispatch, early response systems, and resuscitation care, as well as the importance of prehospital outcomes. Time intervals such as emergency medical service response time now emphasize precise reporting of the times used. New flowcharts aid the reporting of system effectiveness for patients with an attempted resuscitation and system efficacy for the Utstein comparator group. Recognizing the varying capacities of emergency systems globally, the writing group provided a minimal dataset for settings with developing emergency medical systems. Supplementary variables are considered useful for research purposes. These revisions aim to elevate data collection and reporting transparency by registries and researchers and to advance international comparisons and collaborations. The overarching objective remains the improvement of outcomes for patients with out-of-hospital cardiac arrest., (Copyright © 2024 European Resuscitation Council, American Heart Association Inc., International Liaison Committee on Resuscitation. Published by Elsevier B.V. All rights reserved.)

Objectives: The objective of this systematic review was to offer a comprehensive overview and explore the associated outcomes from imaging referral guidelines on various key stakeholders, such as patients and radiologists., Materials and Methods: An electronic database search was conducted in Medline, Embase and Web of Science to retrieve citations published between 2013 and 2023. The search was constructed using medical subject headings and keywords. Only full-text articles and reviews written in English were included. The quality of the included papers was assessed using the mixed methods appraisal tool. A narrative synthesis was undertaken for the selected articles., Results: The search yielded 4384 records. Following the abstract, full-text screening, and removal of duplication, 31 studies of varying levels of quality were included in the final analysis. Imaging referral guidelines from the American College of Radiology were most commonly used. Clinical decision support systems were the most evaluated mode of intervention, either integrated or standalone. Interventions showed reduced patient radiation doses and waiting times for imaging. There was a general reduction in radiology workload and utilisation of diagnostic imaging. Low-value imaging utilisation decreased with an increase in the appropriateness of imaging referrals and ratings and cost savings. Clinical effectiveness was maintained during the intervention period without notable adverse consequences., Conclusion: Using evidence-based imaging referral guidelines improves the quality of healthcare and outcomes while reducing healthcare costs. Imaging referral guidelines are one essential component of improving the value of radiology in the healthcare system., Clinical Relevance Statement: There is a need for broader dissemination of imaging referral guidelines to healthcare providers globally in tandem with the harmonisation of the application of these guidelines to improve the overall value of radiology within the healthcare system., Key Points: The application of imaging referral guidelines has an impact and effect on patients, radiologists, and health policymakers. The adoption of imaging referral guidelines in clinical practice can impact healthcare costs and improve healthcare quality and outcomes. Implementing imaging referral guidelines contributes to the attainment of value-based radiology., (© 2024. The Author(s).)

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., Competing Interests: MEH Ong reports an advisory relationship with Global Healthcare SG, a commercial entity that manufactures cooling devices. MEH Ong has a licensing agreement and a patent filed (Application no: 13/047,348) with ZOLL Medical Corporation for a study titled "Method of predicting acute cardiopulmonary events and survivability of a patient". All other authors have no conflict of interests to declare., (Copyright: © 2024 Ning et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention., Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P <0.05 was considered statistically significant., Results: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P =0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P =0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P =0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours., Conclusions: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723., Competing Interests: L.T. is on the Astra Zeneca international advisory board of management of adverse events with the new antibody drug conjugate T-DXd in Asian patients with metastatic breast cancer, Roche Singapore immunotherapy in early stage NSCLC patient journey advisory board. L.T. has received a Philips speaker honorarium in kind and a Siemens Healthineers speaker honorarium. Y.K.K. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, and Novartis (via institution); consulting fees from Abbott Vascular, Medtronic, Novartis, and Peijia Medical; and speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Amgen, Novartis, Astra Zeneca, Microport, Terumo, and Omnicare. Y.K.K. is also cofounder and owns equity in Trisail, for which OrbusNeich is an investor. D.J.H. has received consultant fees from Faraday Pharmaceuticals Inc and Boehringer Ingelheim International GmbH, honoraria from Servier, and research funding from Astra Zeneca and Merck Sharp & Dohme Corp. C.Y.C. has received speaker fees from Novartis and consultancy fees from Boston Scientific and Philips. The other authors report no conflicts.

Background: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase., Methods: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms., Results: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development., Conclusion: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yap Seng Chong reports a relationship with Abbott Nutrition that includes: funding grants and speaking and lecture fees. Keith M Godfrey reports a relationship with Abbott Nutrition that includes: funding grants and speaking and lecture fees. Yap Seng Chong reports a relationship with Nestle that includes: funding grants and speaking and lecture fees. Keith M Godfrey reports a relationship with Nestle that includes: funding grants and speaking and lecture fees. Yap Seng Chong reports a relationship with Danone that includes: funding grants and speaking and lecture fees. Keith M Godfrey reports a relationship with Danone that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hereditary cancer syndromes constitute approximately 10% of all cancers. Cascade testing involves testing of at-risk relatives to determine if they carry the familial pathogenic variant. Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. We searched major databases using keywords and subject heading of "cascade testing". Interventions proposed in each study were classified according to the Effective Practice and Organization of Care (EPOC) taxonomy. Quality of intervention description was assessed using the TIDieR checklist, and evaluation of implementation outcomes was performed using Proctor's Implementation Outcomes Framework. Improvements in rates of genetic testing uptake was seen in interventions across the different EPOC taxonomy strategies. The average TIDieR score was 7.3 out of 12. Items least reported include modifications (18.5%), plans to assess fidelity/adherence (7.4%) and actual assessment of fidelity/adherence (7.4%). An average of 2.9 out of 8 aspects of implementation outcomes were examined. The most poorly reported outcomes were cost, fidelity and sustainability, with only 3.7% of studies reporting them. Most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream. Therefore, further adoption of standardized guidelines in reporting of interventions and formal assessment of implementation outcomes may help promote translation of these interventions into routine practice., (© 2024. The Author(s).)

Background: Prehospital identification of futile resuscitation efforts (defined as a predicted probability of survival lower than 1%) for out-of-hospital cardiac arrest (OHCA) may reduce unnecessary transport. Reliable prediction variables for OHCA 'termination of resuscitation' (TOR) rules are needed to guide treatment decisions. The Universal TOR rule uses only three variables (Absence of Prehospital ROSC, Event not witnessed by EMS and no shock delivered on the scene) has been externally validated and is used by many EMS systems. Deep learning, an artificial intelligence (AI) platform is an attractive model to guide the development of TOR rule for OHCA. The purpose of this study was to assess the feasibility of developing an AI-TOR rule for neurologically favorable outcomes using general purpose AI and compare its performance to the Universal TOR rule., Methods: We identified OHCA cases of presumed cardiac etiology who were 18 years of age or older from 2016 to 2019 in the All-Japan Utstein Registry. We divided the dataset into 2 parts, the first half (2016-2017) was used as a training dataset for rule development and second half (2018-2019) for validation. The AI software (Prediction One®) created the model using the training dataset with internal cross-validation. It also evaluated the prediction accuracy and displayed the ranking of influencing variables. We performed validation using the second half cases and calculated the prediction model AUC. The top four of the 11 variables identified in the model were then selected as prognostic factors to be used in an AI-TOR rule, and sensitivity, specificity, positive predictive value, and negative predictive value were calculated from validation cohort. This was then compared to the performance of the Universal TOR rule using same dataset., Results: There were 504,561 OHCA cases, 18 years of age or older, 302,799 cases were presumed cardiac origin. Of these, 149,425 cases were used for the training dataset and 153,374 cases for the validation dataset. The model developed by AI using 11 variables had an AUC of 0.969, and its AUC for the validation dataset was 0.965. The top four influencing variables for neurologically favorable outcome were Prehospital ROSC, witnessed by EMS, Age (68 years old and younger) and nonasystole. The AUC calculated using the 4 variables for the AI-TOR rule was 0.953, and its AUC for the validation dataset was 0.952 (95%CI 0.949 -0.954). Of 80,198 patients in the validation cohort that satisfied all four criteria for the AI-TOR rule, 58 (0.07%) had a neurologically favorable one-month survival. The specificity of AI-TOR rule was 0.990, and the PPV was 0.999 for predicting lack of neurologically favorable survival, both the specificity and PPV were higher than that achieved with the universal TOR (0.959, 0.998)., Conclusions: The accuracy of prediction models using AI software to determine outcomes in OHCA was excellent and the AI-TOR rule's variables from prediction model performed better than the Universal TOR rule. External validation of our findings as well as further research into the utility of using AI platforms for TOR prediction in clinical practice is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)