Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background and Purpose: Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. Methods: Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). Results: From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients. Conclusion: Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.

Efficacy, safety and patient satisfaction of two-stage versus single-stage computed tomography guided localization and resection of pulmonary nodules.

Background: Low-dose computed tomography (CT) has been increasingly utilized for lung cancer screening. Localization of solitary pulmonary nodules (SPN) is crucial for resection. Two-stage localization method involves dye injection by radiologists prior to the operation. The significant interval between localization and resection is associated with a higher risk of marker failure, psychological distress and procedural complications. Single-stage localization and resection procedure under general anesthesia poses unique challenges. The aim of the study is to compare the safety, efficacy and patient satisfaction between the two methods. Methods: This is a retrospective study comparing outcomes between two-stage and single-stage pre-operative localization of SPN. The primary study outcome was total operating time. Secondary outcomes included successful lesion localization, complication rate, 30-day readmission, mortality, patient satisfaction, and pain level. Results: A total of 26 and 56 patients were included for the single and two-stage group respectively. Total operative time was significantly longer in the single-stage arm (mean: 188 min) than that of the two-stage arm (mean: 172 min, P<0.001) due to the additional time needed for intra-operative localization. Mean satisfaction score was significantly higher in the single-stage group than that of the two-stage group (92 vs. 52.69, P=0.004). Pain level assessed by numerical rating scales was better in the single-stage arm compared to the two-stage arm (mean: 8.8 vs. 4.85, P=0.007). Conclusions: Single-stage localization and resection resulted in a minor increase in total operative time, higher patient satisfaction and less pain with comparable safety and efficacy to conventional two-stage approach.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

BACKGROUND: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone. METHODS: We performed a retrospective cohort study of 120 531 patients with AMI and AIS from the national stroke and AMI registries in Singapore. Patients were categorized into AMI only, AIS only, synchronous CCI (same-day), and metachronous CCI (within 1 week). The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The mortality risks were compared using Cox regression. Multivariable models were adjusted for baseline demographics, clinical variables, and treatment for AMI or AIS. RESULTS: Of 127 919 patients identified, 120 531 (94.2%) were included; 74 219 (61.6%) patients had AMI only, 44 721 (37.1%) had AIS only, 625 (0.5%) had synchronous CCI, and 966 (0.8%) had metachronous CCI. The mean age was 67.7 (SD, 14.0) years. Synchronous and metachronous CCI had a higher risk of 30-day mortality (synchronous: adjusted HR [aHR], 2.41 [95% CI, 1.77-3.28]; metachronous: aHR, 2.80 [95% CI, 2.11-3.73]) than AMI only and AIS only (synchronous: aHR, 2.90 [95% CI, 1.87-4.51]; metachronous: aHR, 4.36 [95% CI, 3.03-6.27]). The risk of cardiovascular mortality was higher in synchronous and metachronous CCI than AMI (synchronous: aHR, 3.03 [95% CI, 2.15-4.28]; metachronous: aHR, 3.41 [95% CI, 2.50-4.65]) or AIS only (synchronous: aHR, 2.58 [95% CI, 1.52-4.36]; metachronous: aHR, 4.52 [95% CI, 2.95-6.92]). In synchronous CCI, AMI was less likely to be managed with PCI and secondary prevention medications (P<0.001) compared with AMI only. CONCLUSIONS: Synchronous CCI occurred in 1 in 200 cases of AIS and AMI. Synchronous and metachronous CCI had higher mortality than AMI or AIS alone.

Persistent Peril: Recurrent Deep Vein Thrombosis and Pulmonary Embolism in a Patient With Protein S Deficiency Despite Optimal Anticoagulation Therapies.

The clotting system has evolved as an adaptive mechanism to prevent blood loss during vascular damage. However, the intricate nature of the clotting cascade and the complexities of human life can sometimes lead to the unnatural activation of this delicate cascade. This can result in blood clot formation within the cardiovascular system, contributing to a wide range of pathological conditions. Abnormal intravascular coagulation most commonly occurs in the deep veins of the lower extremities, and can emboli to other organs, hence, it is termed "venous thromboembolism" (VTE). In this report, we introduce a challenging case of VTE that poses a dilemma for current medical management. The patient with possible protein S deficiency underwent various guideline-directed medical treatments, yet experienced recurrent VTE episodes, including deep vein thrombosis (DVT) and pulmonary embolism (PE), leading to hospital readmissions. This case report sheds light on our challenges in effectively treating VTE.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

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.

Improved interpretable machine learning emergency department triage tool addressing class imbalance.

Objective: The Score for Emergency Risk Prediction (SERP) is a novel mortality risk prediction score which leverages machine learning in supporting triage decisions. In its derivation study, SERP-2d, SERP-7d and SERP-30d demonstrated good predictive performance for 2-day, 7-day and 30-day mortality. However, the dataset used had significant class imbalance. This study aimed to determine if addressing class imbalance can improve SERP's performance, ultimately improving triage accuracy. Methods: The Singapore General Hospital (SGH) emergency department (ED) dataset was used, which contains 1,833,908 ED records between 2008 and 2020. Records between 2008 and 2017 were randomly split into a training set (80%) and validation set (20%). The 2019 and 2020 records were used as test sets. To address class imbalance, we used random oversampling and random undersampling in the AutoScore-Imbalance framework to develop SERP+-2d, SERP+-7d, and SERP+-30d scores. The performance of SERP+, SERP, and the commonly used triage risk scores was compared. Results: The developed SERP+ scores had five to six variables. The AUC of SERP+ scores (0.874 to 0.905) was higher than that of the corresponding SERP scores (0.859 to 0.894) on both test sets. This superior performance was statistically significant for SERP+-7d (2019: Z = -5.843, p < 0.001, 2020: Z = -4.548, p < 0.001) and SERP+-30d (2019: Z = -3.063, p = 0.002, 2020: Z = -3.256, p = 0.001). SERP+ outperformed SERP marginally on sensitivity, specificity, balanced accuracy, and positive predictive value measures. Negative predictive value was the same for SERP+ and SERP. Additionally, SERP+ showed better performance compared to the commonly used triage risk scores. Conclusions: Accounting for class imbalance during training improved score performance for SERP+. Better stratification of even a small number of patients can be meaningful in the context of the ED triage. Our findings reiterate the potential of machine learning-based scores like SERP+ in supporting accurate, data-driven triage decisions at the ED.

Socioeconomic disadvantage and long-term survival duration in out-of-hospital cardiac arrest patients: A population-based cohort study.

Background: Socioeconomic status (SES) is a well-established determinant of cardiovascular health. However, the relationship between SES and clinical outcomes in long-term out-of-hospital cardiac arrest (OHCA) is less well-understood. The Singapore Housing Index (SHI) is a validated building-level SES indicator. We investigated whether SES as measured by SHI is associated with long-term OHCA survival in Singapore. Methods: We conducted an open cohort study with linked data from the Singapore Pan-Asian Resuscitation Outcomes Study (PAROS), and the Singapore Registry of Births and Deaths (SRBD) from 2010 to 2020. We fitted generalized structural equation models, calculating hazard ratios (HRs) using a Weibull model. We constructed Kaplan-Meier survival curves and calculated the predicted marginal probability for each SHI category. Results: We included 659 cases. In both univariable and multivariable analyses, SHI did not have a significant association with survival. Indirect pathways of SHI mediated through covariates such as Emergency Medical Services (EMS) response time (HR of low-medium, high-medium and high SHI when compared to low SHI: 0.98 (0.88-1.10), 1.01 (0.93-1.11), 1.02 (0.93-1.12) respectively), and age of arrest (HR of low-medium, high-medium and high SHI when compared to low SHI: 1.02 (0.75-1.38), 1.08 (0.84-1.38), 1.18 (0.91-1.54) respectively) had no significant association with OHCA survival. There was no clear trend in the predicted marginal probability of survival among the different SHI categories. Conclusions: We did not find a significant association between SES and OHCA survival outcomes in residential areas in Singapore. Among other reasons, this could be due to affordable healthcare across different socioeconomic classes.

Towards advancing Out-of-Hospital cardiac arrest (OHCA) registries globally: Considerations from the global OHCA registry (GOHCAR) collaborative.

A growing number out-of-hospital cardiac arrest (OHCA) registries have been developed across the globe. A few of these are national, while others cover larger geographical regions. These registries have common objectives; continuous quality improvement, epidemiological research and providing infrastructure for clinical trials. OHCA registries make performance comparison across Emergency Medical Services systems possible for benchmarking, hypothesis generation and further research. Changes in OHCA incidence and outcomes provide insights about the effects of secular trends or health services interventions. These registries, therefore, have become a mainstay of OHCA management and research. However, developing and maintaining these registries is challenging. Coordination of different service providers to support data collection, sustainable resourcing, data quality and data security are the key challenges faced by these registries. Despite all these challenges, noteworthy progress has been made and further standardization and co-ordination across registries can result in great international benefit. In this paper we present a 'why' and 'how to' model for setting up OHCA registries, and suggestions for better international co-ordination through a Global OHCA Registries Collaborative (GOHCAR). We draw together the knowledge of a cohort of international researchers, with experience and expertise in OHCA registry development, management, and data synthesis.

Prehospital stroke care in Singapore.

ABSTRACT: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore.

SEPN1-related myopathy depends on the oxidoreductase ERO1A and is druggable with the chemical chaperone TUDCA.

Selenoprotein N (SEPN1) is a protein of the endoplasmic reticulum (ER) whose inherited defects originate SEPN1-related myopathy (SEPN1-RM). Here, we identify an interaction between SEPN1 and the ER-stress-induced oxidoreductase ERO1A. SEPN1 and ERO1A, both enriched in mitochondria-associated membranes (MAMs), are involved in the redox regulation of proteins. ERO1A depletion in SEPN1 knockout cells restores ER redox, re-equilibrates short-range MAMs, and rescues mitochondrial bioenergetics. ERO1A knockout in a mouse background of SEPN1 loss blunts ER stress and improves multiple MAM functions, including Ca2+ levels and bioenergetics, thus reversing diaphragmatic weakness. The treatment of SEPN1 knockout mice with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) mirrors the results of ERO1A loss. Importantly, muscle biopsies from patients with SEPN1-RM exhibit ERO1A overexpression, and TUDCA-treated SEPN1-RM patient-derived primary myoblasts show improvement in bioenergetics. These findings point to ERO1A as a biomarker and a viable target for intervention and to TUDCA as a pharmacological treatment for SEPN1-RM.

The discovery of novel and potent indazole NLRP3 inhibitors enabled by DNA-encoded library screening.

NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1ß and IL-18 as well as to gasdermin d-mediated pyroptotic cell death. Herein, we describe the discovery of a novel indazole series of high affinity, reversible inhibitors of NLRP3 activation through screening of DNA-encoded libraries and the potent lead compound 3 (BAL-0028, IC50 = 25 nM) that was identified directly from the screen. SPR studies showed that compound 3 binds tightly (KD range 104-123 nM) to the NACHT domain of NLRP3. A CADD analysis of the interaction of compound 3 with the NLRP3 NACHT domain proposes a binding site that is distinct from those of ADP and MCC950 and includes specific site interactions. We anticipate that compound 3 (BAL-0028) and other members of this novel indazole class of neutral inhibitors will demonstrate significantly different physical, biochemical, and biological properties compared to NLRP3 inhibitors previously identified.

Trends in hemorrhagic stroke incidence and mortality in a National Stroke Registry of a multi-ethnic Asian population.

INTRODUCTION: High-quality epidemiological data on hemorrhagic stroke (HS) and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), remains limited in Asian ethnicities. We investigated the trends in HS incidence and 30-day mortality from 2005 to 2019 in a multi-ethnic Asian population from a national registry. PATIENTS AND METHODS: Data on all stroke cases from the Singapore Stroke Registry from 2005 to 2019 were collected. Cases were defined using centrally adjudicated review of diagnosis codes. Death outcomes were obtained by linkage with the national death registry. Incidence (per 100,000 people) and 30-day mortality (per 100 people) were measured as crude and age-standardized rates. Trends were analyzed using linear regression. RESULTS: We analyzed 19,017 cases of HS (83.9% ICH; 16.1% SAH). From 2005 to 2019, age-standardized incidence rates (ASIR) for HS remained stable from 34.4 to 34.5. However, age-standardized mortality rates (ASMR) decreased significantly from 29.5 to 21.4 (p < 0.001). For ICH, ASIR remained stable while ASMR decreased from 30.4 to 21.3 (p < 0.001); for SAH, ASIR increased from 2.7 to 6.0 (p = 0.006) while ASMR remained stable. In subgroup analyses, HS incidence increased significantly in persons <65 years (from 18.1 to 19.6) and Malays (from 39.5 to 49.7). DISCUSSION: From 2005 to 2019, ASIR of HS remained stable while ASMR decreased. Decreasing ASMR reflects improvements in the overall management of HS, consistent with global trends. CONCLUSION: Population health efforts to address modifiable risk factors for HS in specific demographic subgroups may be warranted to reduce incidence and mortality of HS.

Association between Conversion to Shockable Rhythms and Survival with Favorable Neurological Outcomes for Out-of-Hospital Cardiac Arrests.

BACKGROUND: The initial cardiac rhythm in out-of-hospital cardiac arrest (OHCA) portends different prognoses and affects treatment decisions. Initial shockable rhythms are associated with good survival and neurological outcomes but there is conflicting evidence for those who initially present with non-shockable rhythms. The aim of this study is to evaluate if OHCA with conversion from non-shockable (i.e., asystole and pulseless electrical activity) rhythms to shockable rhythms compared to OHCA remaining in non-shockable rhythms is associated with better survival and neurological outcomes. METHOD: OHCA cases from the Pan-Asian Resuscitation Outcomes Study registry in 13 countries between January 2009 and February 2018 were retrospectively analyzed. Cases with missing initial rhythms, age <18 years, presumed non-medical cause of arrest, and not conveyed by emergency medical services were excluded. Multivariable logistic regression analysis was performed to evaluate the relationship between initial and subsequent shockable rhythm, survival to discharge, and survival with favorable neurological outcomes (cerebral performance category 1 or 2). RESULTS: Of the 116,387 cases included. 11,153 (9.6%) had initial shockable rhythms and 9,765 (8.4%) subsequently converted to shockable rhythms. Japan had the lowest proportion of OHCA patients with initial shockable rhythms (7.3%). For OHCA with initial shockable rhythm, the adjusted odds ratios (aOR) for survival and good neurological outcomes were 8.11 (95% confidence interval [CI] 7.62-8.63) and 15.4 (95%CI 14.1-16.8) respectively. For OHCA that converted from initial non-shockable to shockable rhythms, the aORs for survival and good neurological outcomes were 1.23 (95%CI 1.10-1.37) and 1.61 (95%CI 1.35-1.91) respectively. The aORs for survival and good neurological outcomes were 1.48 (95%CI 1.22-1.79) and 1.92 (95%CI 1.3 - 2.84) respectively for initial asystole, while the aOR for survival in initial pulseless electrical activity patients was 0.83 (95%CI 0.71-0.98). Prehospital adrenaline administration had the highest aOR (2.05, 95%CI 1.93-2.18) for conversion to shockable rhythm. CONCLUSION: In this ambidirectional cohort study, conversion from non-shockable to shockable rhythm was associated with improved survival and neurologic outcomes compared to rhythms that continued to be non-shockable. Continued advanced resuscitation may be beneficial for OHCA with subsequent conversion to shockable rhythms.

Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.

AIM: For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks. METHODS: We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models. RESULTS: Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score. CONCLUSION: Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.

Incidence and Long-Term Outcomes of Acute Myocardial Infarction Among Survivors of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Despite the increasing long-term survival after out-of-hospital cardiac arrest (OHCA), the risk of subsequent acute myocardial infarction (AMI) remains poorly understood. We aimed to determine the incidence, predictors, and long-term outcomes of AMI among survivors of OHCA. METHODS AND RESULTS: We assembled a retrospective cohort of 882 patients with OHCA who survived to 30 days or discharge from the hospital between 2010 and 2019. Survivors of OHCA had an increased risk of subsequent AMI, defined as AMI occurring 30 days after index OHCA or following discharge from the hospital after OHCA, compared with the general population when matched for age and sex (standardized incidence ratio, 4.64 [95% CI, 3.52-6.01]). Age-specific risks of subsequent AMI for men (standardized incidence ratio, 3.29 [95% CI, 2.39-4.42]) and women (standardized incidence ratio, 6.15 [95% CI, 3.27-10.52]) were significantly increased. A total of 7.2%, 8.3%, and 14.3% of survivors of OHCA had a subsequent AMI at 3 years, 5 years, and end of follow-up, respectively. Age at OHCA (hazard ratio [HR], 1.04 [95% CI, 1.02-1.06]) and past medical history of prior AMI, defined as any AMI preceding or during the index OHCA event (HR, 1.84 [95% CI, 1.05-3.22]), were associated with subsequent AMI, while an initial shockable rhythm was not (HR, 1.00 [95% CI, 0.52-1.94]). Survivors of OHCA with subsequent AMI had a higher risk of death (HR, 1.58 [95% CI, 1.12-2.22]) than those without. CONCLUSIONS: Survivors of OHCA are at an increased risk of subsequent AMI compared with the general population. Prior AMI, but not an initial shockable rhythm, increases this risk, while subsequent AMI predicts death. Preventive measures for AMI including cardiovascular risk factor control and revascularization may thus improve outcomes in selected patients with cardiac pathogenesis.

Association between the extension of smoke-free legislation and incident acute myocardial infarctions in Singapore from 2010 to 2019: an interrupted time-series analysis.

BACKGROUND: We examined the association between smoke-free laws implemented in the outdoors and the common areas of residential apartment blocks and reported acute myocardial infarctions (AMI) in Singapore. METHODS: We used an interrupted time-series design and seasonal autoregressive integrated moving average models to examine the effect of the smoke-free law extensions in 2013 (common areas of residential blocks, covered pedestrian linkways, overhead bridges and within 5 m of bus stops), 2016 (parks) and 2017 (educational institutions, buses and taxis) on the monthly incidence rate of AMIs per 1 000 000 population. RESULTS: We included 133 868 AMI reports from January 2010 to December 2019. Post-2013, there was a decrease in the AMI incidence trend (ß=-0.6 per month, 95%CI -1.0 to -0.29) and 2097 (95% CI 2094 to 2100) more AMIs may have occurred without the extension. There was a significant step-decline in male AMIs and a non-significant step-increase in female AMIs post-2013. Those 65 years and older experienced a greater decline to the postlegislation 2013 trend (ß=-5.9, 95% CI -8.7 to -3.1) compared with those younger (ß=-0.4, 95% CI -0.6 to -0.2), while an estimated 19 591 (15 711 to 23472) additional AMI cases in those 65 years and above may have occurred without the extension. We found a step-increase in monthly AMI incidence post-2016 (ß=14.2, 95%CI 3.3 to 25.0). CONCLUSION: The 2013 smoke-free law extension to residential estates and other outdoor areas were associated with a decline in AMIs and those above the age of 65 years and men appeared to be major beneficiaries. Additional epidemiological evidence is required to support the expanded smoke-free legislation to parks, educational institutions, buses and taxis.

Temporal trends in out-of-hospital cardiac arrest with an initial non-shockable rhythm in Singapore.

Aim: Out-of-hospital cardiac arrest (OHCA) with an initial non-shockable rhythm is the predominant form of OHCA in adults. We evaluated its 10-year trends in epidemiology and management in Singapore. Methods: Using the national OHCA registry we studied the trends of 20,844 Emergency Medical Services-attended adult OHCA from April 2010 to December 2019. Survival to hospital discharge was the primary outcome. Trends and outcomes were analyzed using linear and logistic regression, respectively. Results: Incidence rates of adult OHCAs increased during the study period, driven by non-shockable OHCA. Compared to shockable OHCA, non-shockable OHCAs were significantly older, had more co-morbidities, unwitnessed and residential arrests, longer no-flow time, and received less bystander cardiopulmonary resuscitation (CPR) and in-hospital interventions (p < 0.001). Amongst non-shockable OHCA, age, co-morbidities, residential arrests, no-flow time, time to patient, bystander CPR and epinephrine administration increased during the study period, while presumed cardiac etiology decreased (p < 0.05). Unlike shockable OHCA, survival for non-shockable OHCA did not improve (p < 0.001 for trend difference). The likelihood of survival for non-shockable OHCA significantly increased with witnessed arrest (adjusted odds ratio (aOR) 2.02) and bystander CPR (aOR 3.25), but decreased with presumed cardiac etiology (aOR 0.65), epinephrine administration (aOR 0.66), time to patient (aOR 0.93) and age (aOR 0.98). Significant two-way interactions were observed for no-flow time and residential arrest with bystander CPR (aOR 0.96 and 0.40 respectively). Conclusion: The incidence of non-shockable OHCA increased between 2010 and 2019. Despite increased interventions, survival did not improve for non-shockable OHCA, in contrast to the improved survival for shockable OHCA.

Risk of wound infection with use of sterile versus clean gloves in wound repair at the Emergency Department: A systematic review and meta-analysis.

STUDY OBJECTIVE: Sterile gloves are widely used during wound repair procedures in Emergency Departments (ED) worldwide. It is unclear whether sterile gloves protect against postoperative wound infections. We conducted a systematic review and meta-analysis to determine if sterile gloves offer significant protection against wound infections compared to clean gloves for wound repair in the ED. METHODS: Ovid MEDLINE, Ovid Embase, Cochrane Library and Web Of Science were searched for randomised controlled trials (RCTs) or non-randomized studies of intervention (NRSIs) from their dates of inception to January 2023. RCTs or NRSIs comparing sterile (control) vs. clean/no (intervention) glove use for wound repair procedures in the ED and reporting postoperative wound infections were included. Two investigators independently extracted data and assessed risk-of-bias of each report on a standardised form. Wound infection incidence was pooled using a random effects model. Subgroup analysis was performed to explore heterogeneity. RESULTS: 7 studies were included in the review, with 6 included in the meta-analysis. Of 3227 patients, 115/1608 (7.2%) patients in the intervention group and 135/1619 (8.3%) patients in the control group had postoperative wound infections. Overall RR was 0.86 (95% CI,0.67-1.10, I2=3.6%), and of high evidence certainty (GRADE). Absence of a protective effect was invariant in sensitivity analyses, leave-one-out analysis and subgroup analyses. CONCLUSION: No evidence of additional protection against wound infections with the use of sterile gloves for wound repair in the ED compared to clean gloves was found. However, the review was limited by nonreporting of antibiotic history and time between wound repair and follow-up amongst included studies. Considering the ergonomics, potential cost-savings and environmental impact, clean gloves are a viable alternative to sterile gloves, without compromising wound infection risk in this setting.

Performance of the ROX index in predicting high flow nasal cannula failure in COVID-19 patients: a systematic review and meta-analysis.

COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666-0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2-6 h and 6-12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12-24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.