Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.

Mechanical circulatory support for cardiogenic shock: a network meta-analysis of randomized controlled trials and propensity score-matched studies.

PURPOSE: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. METHODS: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. RESULTS: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66). CONCLUSION: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.

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.

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.

Blood Pressure Targets for Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

BACKGROUND: With ideal mean arterial pressure (MAP) targets in resuscitated out-of-hospital cardiac arrest (OHCA) patients unknown, we performed a meta-analysis of randomised controlled trials (RCTs) to compare the effects of higher versus lower MAP targets. METHODS: We searched four databases until 1 May 2023 for RCTs reporting the effects of higher MAP targets (>70 mmHg) in resuscitated OHCA patients and conducted random-effects meta-analyses. The primary outcome was mortality while secondary outcomes were neurological evaluations, arrhythmias, acute kidney injury, and durations of mechanical ventilation and ICU stay. We conducted inverse-variance weighted strata-level meta-regression against a proportion of non-survivors to assess differences between reported MAPs. We also conducted a trial sequential analysis of RCTs. RESULTS: Four RCTs were included. Higher MAP was not associated with reduced mortality (OR: 1.09, 95%-CI: 0.84 to 1.42, p = 0.51), or improved neurological outcomes (OR: 0.99, 95%-CI: 0.77 to 1.27, p = 0.92). Such findings were consistent despite additional sensitivity analyses. Our robust variance strata-level meta-regression revealed no significant associations between mean MAP and the proportion of non-survivors (B: 0.029, 95%-CI: -0.023 to 0.081, p = 0.162), and trial sequential analysis revealed no meaningful survival benefit for higher MAPs. CONCLUSIONS: A higher MAP target was not significantly associated with improved mortality and neurological outcomes in resuscitated OHCA patients.

Measurement Properties of the 15-Item Singapore Caregiver Quality of Life Scale (SCQOLS-15) in Family Caregivers of Patients with Heart Diseases.

PURPOSE: To evaluate the measurement properties of the 15-item Singapore Caregiver Quality of Life Scale (SCQOLS-15) in family caregivers of patients with heart diseases. METHODS: The SCQOLS-15 survey was self-administered by family caregivers of patients with chronic heart diseases, at baseline and 1 week later. The criterion validity of SCQOLS-15 and its domain scores was assessed by calculating the Spearman correlation coefficient (ρ) with the Brief Assessment Scale for Caregivers (BASC), Caregiver Reaction Assessment (CRA), and their sub-scores. Known-group validity was assessed using the New York Heart Association (NYHA) functional class. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). RESULTS: Of the 327 caregivers included, 65% were adult children and 28% were spouses. The distribution of NYHA classes of the patients was I: 27%, II: 40%, III: 24%, and IV: 9%. There was a positive correlation between the SCQOLS-15 and BASC total scores (ρ = 0.7). SCQOLS-15 domain scores were also correlated with BASC and CRA sub-scores as per a priori hypotheses, with absolute values of ρ ranging from 0.4 to 0.6. The mean values of SCQOLS-15 total and all domain scores were lower among caregivers of patients with NYHA class III/IV compared to those of class I/II patients (each P < 0.05). Among 146 caregivers who completed the follow-up and self-rated a stable quality-of-life, ICCs for test-retest reliability of SCQOLS-15 total and all domain scores were ≥ 0.8. CONCLUSION: The SCQOLS-15 is a valid and reliable instrument for measuring the quality of life in caregivers of heart disease patients.

Determinants of health-related quality of life after out-of-hospital cardiac arrest (OHCA): A systematic review.

OBJECTIVE: With a growing number of out-of-hospital cardiac arrest (OHCA) survivors globally, the focus of OHCA management has now broadened to survivorship. An outcome central to survivorship is health-related quality of life (HRQoL). This systematic review aimed to synthesise evidence related to the determinants of HRQoL of OHCA survivors. METHODS: We systematically searched MEDLINE, Embase, and Scopus from inception to 15 August 2022 to identify studies investigating the association of at least one determinant and HRQoL in adult OHCA survivors. All articles were independently reviewed by two investigators. We abstracted data pertaining to determinants and classified them using a well-established HRQoL theoretical framework - the Wilson and Cleary (revised) model. RESULTS: 31 articles assessing a total of 35 determinants were included. Determinants were classified into the five domains in the HRQoL model. 26 studies assessed determinants related to individual characteristics (n = 3), 12 studied biological function (n = 7), nine studied symptoms (n = 3), 16 studied functioning (n = 5), and 35 studied characteristics of the environment (n = 17). In studies that included multivariable analyses, most reported that individual characteristics (older age, female sex), symptoms (anxiety, depression), and functioning (impaired neurocognitive function) were significantly associated with poorer HRQoL. CONCLUSIONS: Individual characteristics, symptoms, and functioning played significant roles in explaining the variability in HRQoL. Significant non-modifiable determinants such as age and sex could be used to identify populations at risk of poorer HRQoL, while significant modifiable determinants such as psychological health and neurocognitive functioning could serve as targets for post-discharge screening and rehabilitation plans. PROSPERO registration number: CRD42022359303.

Did lockdown influence bystanders' willingness to perform cardiopulmonary resuscitation? A worldwide registry-based perspective.

AIM: Bystander cardiopulmonary resuscitation (CPR) significantly increases the survival rate after out-of-hospital cardiac arrest. Using population-based registries, we investigated the impact of lockdown due to Covid-19 on the provision of bystander CPR, taking background changes over time into consideration. METHODS: Using a registry network, we invited all registries capable of delivering data from 1. January 2017 to 31. December 2020 to participate in this study. We used negative binominal regression for the analysis of the overall results. We also calculated the rates for bystander CPR. For every participating registry, we analysed the incidence per 100000 inhabitants of bystander CPR and EMS-treated patients using Poisson regression, including time trends. RESULTS: Twenty-six established OHCA registries reported 742 923 cardiac arrest patients over a four-year period covering 1.3 billion person-years. We found large variations in the reported incidence between and within continents. There was an increase in the incidence of bystander CPR of almost 5% per year. The lockdown in March/April 2020 did not impact this trend. The increase in the rate of bystander CPR was also seen when analysing data on a continental level. We found large variations in incidence of bystander CPR before and after lockdown when analysing data on a registry level. CONCLUSION: There was a steady increase in bystander CPR from 2017 to 2020, not associated with an increase in the number of ambulance-treated cardiac arrest patients. We did not find an association between lockdown and bystanders' willingness to start CPR before ambulance arrival, but we found inconsistent patterns of changes between registries.

The Effect of Building-Level Socioeconomic Status on Bystander Cardiopulmonary Resuscitation: A Retrospective Cohort Study.

OBJECTIVE: Understanding the social determinants of bystander cardiopulmonary resuscitation (CPR) receipt can inform the design of public health interventions to increase bystander CPR. The association of socioeconomic status with bystander CPR is generally poorly understood. We evaluated the relationship between socioeconomic status and bystander CPR in cases of out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study based on the Singapore cohort of the Pan-Asian Resuscitation Outcomes Study registry between 2010 and 2018. We categorized patients into low, medium, and high Singapore Housing Index (SHI) levels-a building-level index of socioeconomic status. The primary outcome was receipt of bystander CPR. The secondary outcomes were prehospital return of spontaneous circulation and survival to discharge. RESULTS: A total of 12,730 OHCA cases were included, the median age was 71 years, and 58.9% were male. The bystander CPR rate was 56.7%. Compared to patients in the low SHI category, those in the medium and high SHI categories were more likely to receive bystander CPR (medium SHI: adjusted odds ratio [aOR] 1.48, 95% CI 1.30-1.69; high SHI: aOR 1.93, 95% CI 1.67-2.24). High SHI patients had higher survival compared to low SHI patients on unadjusted analysis (OR 1.79, 95% CI 1.08-2.96), but not adjusted analysis (adjusted for age, sex, race, witness status, arrest time, past medical history of cancer, and first arrest rhythm). When comparing high with low SHI, females had larger increases in bystander CPR rates than males. CONCLUSIONS: Lower building-level socioeconomic status was independently associated with lower rate of bystander CPR, and females were more susceptible to the effect of low socioeconomic status on lower rate of bystander CPR.

Prior Cancer Is Associated with Lower Atherosclerotic Cardiovascular Disease Risk at First Acute Myocardial Infarction.

Background: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. Methods: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). Results: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66−2.07). Conclusions: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality.

Effects of Carotid Artery Stiffness on Cerebral Small-Vessel Disease and Cognition.

Background Carotid artery stiffness is associated with cognitive impairment and dementia, but the underlying mechanisms remain unknown. We examined the associations of carotid artery stiffness with cerebral small-vessel disease markers, cognition, and dementia subtypes in a memory clinic cohort. Methods and Results A total of 272 participants underwent carotid ultrasonography, 3 Tesla brain magnetic resonance imaging, and neuropsychological assessment. Carotid ultrasonography was used to assess ß-index, pressure-strain elastic modulus, and pulse-wave velocity-ß. Brain magnetic resonance images were graded for cerebral small-vessel disease markers, including white matter hyperintensities, lacunes, and cerebral microbleeds. Participants were classified as having no cognitive impairment, cognitive impairment and no dementia, or dementia subtyped as Alzheimer disease and vascular dementia. Cognition was assessed using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network harmonization battery. After adjusting for age, sex, cardiovascular risk factors, and diseases, multivariable models showed that ß-index (ß=0.69; P=0.002), elastic modulus (ß=0.78; P<0.001), and pulse-wave velocity-ß (ß=0.80; P<0.001) were associated with white matter hyperintensities, and elastic modulus (odds ratio [OR], 1.39 [95% CI, 1.04-1.85]) and pulse-wave velocity-ß (OR, 1.47 [95% CI, 1.10-1.98]) were independently associated with lacunes. Similarly, ß-index (OR, 2.04 [95% CI, 1.14-4.13]), elastic modulus (OR, 2.22 [95% CI, 1.25-4.42]), and pulse-wave velocity-ß (OR, 2.50 [95% CI, 1.36-5.18]) were independently associated with vascular dementia. Carotid stiffness measures were independently associated with worse performance in global cognition, visuomotor speed, visuospatial function, and executive function. These associations became largely nonsignificant after further adjusting for cerebral small-vessel disease markers. Conclusions In memory clinic patients, carotid artery stiffness was associated with white matter hyperintensities and lacunes, impairment in global and domain-specific cognition, and causative subtypes of dementia, particularly vascular. The effects of carotid stiffness on cognition were not independent of, and were partially mediated by, cerebral small-vessel disease.

Impact of COVID-19 on barriers to dispatcher-assisted cardiopulmonary resuscitation in adult out-of-hospital cardiac arrests in Singapore.

OBJECTIVE: Fewer out-of-hospital cardiac arrest (OHCA) patients received bystander cardiopulmonary resuscitation during the COVID-19 pandemic in Singapore. We investigated the impact of COVID-19 on barriers to dispatcher-assisted cardiopulmonary resuscitation (DA-CPR). METHODS: We reviewed audio recordings of all calls to our national ambulance service call centre during the pandemic (January-June 2020) and pre-pandemic (January-June 2019) periods. Our primary outcome was the presence of barriers to DA-CPR. Multivariable logistic regression was used to assess the effect of COVID-19 on the likelihood of barriers to and performance of DA-CPR, adjusting for patient and event characteristics. RESULTS: There were 1241 and 1118 OHCA who were eligible for DA-CPR during the pandemic (median age 74 years, 61.6 % males) and pre-pandemic (median age 73 years, 61.1 % males) periods, respectively. Compared to pre-pandemic, there were more residential and witnessed OHCA during the pandemic (87 % vs 84.9 % and 54 % vs 38.1 %, respectively); rates of DA-CPR were unchanged (57.3 % vs 61.1 %). COVID-19 increased the likelihood of barriers to DA-CPR (aOR 1.47, 95 % CI: 1.25-1.74) but not performance of DA-CPR (aOR 0.86, 95 % CI: 0.73 - 1.02). Barriers such as 'patient status changed' and 'caller not with patient' increased during COVID-19 pandemic. 'Afraid to do CPR' markedly decreased during the pandemic; fear of COVID-19 transmission made up 0.5 % of the barriers. CONCLUSION: Barriers to DA-CPR were encountered more frequently during the COVID-19 pandemic but did not affect callers' willingness to perform DA-CPR. Distancing measures led to more residential arrests with increases in certain barriers, highlighting opportunities for public education and intervention.

Microaxial Left Ventricular Assist Device in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

Microaxial left ventricular assist devices (LVAD) are increasingly used to support patients with cardiogenic shock; however, outcome results are limited to single-center studies, registry data and select reviews. We conducted a systematic review and meta-analysis, searching three databases for relevant studies reporting on microaxial LVAD use in adults with cardiogenic shock. We conducted a random-effects meta-analysis (DerSimonian and Laird) based on short-term mortality (primary outcome), long-term mortality and device complications (secondary outcomes). We assessed the risk of bias and certainty of evidence using the Joanna Briggs Institute and the GRADE approaches, respectively. A total of 63 observational studies (3896 patients), 6 propensity-score matched (PSM) studies and 2 randomized controlled trials (RCTs) were included (384 patients). The pooled short-term mortality from observational studies was 46.5% (95%-CI: 42.7-50.3%); this was 48.9% (95%-CI: 43.8-54.1%) amongst PSM studies and RCTs. The pooled mortality at 90 days, 6 months and 1 year was 41.8%, 51.1% and 54.3%, respectively. Hemolysis and access-site bleeding were the most common complications, each with a pooled incidence of around 20%. The reported mortality rate of microaxial LVADs was not significantly lower than extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pumps (IABP). Current evidence does not suggest any mortality benefit when compared to ECMO or IABP.

Management of Out-of-Hospital Cardiac Arrest during COVID-19: A Tale of Two Cities.

Variations in the impact of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) have been reported. We aimed to, using population-based registries, compare community response, Emergency Medical Services (EMS) interventions and outcomes of adult, EMS-treated, non-traumatic OHCA in Singapore and metropolitan Atlanta, before and during the pandemic. Associations of OHCA characteristics, pre-hospital interventions and pandemic with survival to hospital discharge were analyzed using logistic regression. There were 2084 cases during the pandemic (17 weeks from the first confirmed COVID-19 case) and 1900 in the pre-pandemic period (corresponding weeks in 2019). Compared to Atlanta, OHCAs in Singapore were older, received more bystander interventions (cardiopulmonary resuscitation (CPR): 65.0% vs. 41.4%; automated external defibrillator application: 28.6% vs. 10.1%), yet had lower survival (5.6% vs. 8.1%). Compared to the pre-pandemic period, OHCAs in Singapore and Atlanta occurred more at home (adjusted odds ratio (aOR) 2.05 and 2.03, respectively) and were transported less to hospitals (aOR 0.59 and 0.36, respectively) during the pandemic. Singapore reported more witnessed OHCAs (aOR 1.96) yet less bystander CPR (aOR 0.81) during pandemic, but not Atlanta (p < 0.05). The impact of COVID-19 on OHCA outcomes did not differ between cities. Changes in OHCA characteristics and management during the pandemic, and differences between Singapore and Atlanta were likely the result of systemic and sociocultural factors.

Clustering of Environmental Parameters and the Risk of Acute Myocardial Infarction.

The association between days with similar environmental parameters and cardiovascular events is unknown. We investigate the association between clusters of environmental parameters and acute myocardial infarction (AMI) risk in Singapore. Using k-means clustering and conditional Poisson models, we grouped calendar days from 2010 to 2015 based on rainfall, temperature, wind speed and the Pollutant Standards Index (PSI) and compared the incidence rate ratios (IRR) of AMI across the clusters using a time-stratified case-crossover design. Three distinct clusters were formed with Cluster 1 having high wind speed, Cluster 2 high rainfall, and Cluster 3 high temperature and PSI. Compared to Cluster 1, Cluster 3 had a higher AMI incidence with IRR 1.04 (95% confidence interval 1.01-1.07), but no significant difference was found between Cluster 1 and Cluster 2. Subgroup analyses showed that increased AMI incidence was significant only among those with age ≥65, male, non-smokers, non-ST elevation AMI (NSTEMI), history of hyperlipidemia and no history of ischemic heart disease, diabetes or hypertension. In conclusion, we found that AMI incidence, especially NSTEMI, is likely to be higher on days with high temperature and PSI. These findings have public health implications for AMI prevention and emergency health services delivery during the seasonal Southeast Asian transboundary haze.

Immunoassay-Compatible Inactivation of SARS-CoV-2 in Plasma Samples for Enhanced Handling Safety.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inactivation is an important step toward enhanced biosafety in testing facilities and affords a reduction in the biocontainment level necessary for handling virus-positive biological specimens. Virus inactivation methods commonly employ heat, detergents, or combinations thereof. In this work, we address the dearth of information on the efficacy of SARS-CoV-2 inactivation procedures in plasma and their downstream impact on immunoassays. We evaluated the effects of heat (56 °C for 30 min), detergent (1-5% Triton X-100), and solvent-detergent (SD) combinations [0.3-1% tri-n-butyl phosphate (TNBP) and 1-2% Triton X-100] on 19 immunoassays across different assay formats. Treatments are deemed immunoassay-compatible when the average and range of percentage recovery (treated concentration relative to untreated concentration) lie between 90-110 and 80-120%, respectively. We show that SD treatment (0.3% TNBP/1% Triton-X100) is compatible with more than half of the downstream immunoassays tested and is effective in reducing SARS-CoV-2 infectivity in plasma to below detectable levels in plaque assays. This facile method offers enhanced safety for laboratory workers handling biological specimens in clinical and research settings.

Association of High-Volume Centers With Survival Outcomes Among Patients With Nontraumatic Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

Importance: Although high volume of cases of out-of-hospital cardiac arrest (OHCA) is a key feature of cardiac arrest centers, which have proven survival benefit, the role of center volume as an independent variable associated with improved outcomes is unclear. Objective: To assess the association of high-volume centers with survival and neurological outcomes in nontraumatic OHCA. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to October 11, 2021, for studies including adult patients with nontraumatic OHCA who were treated at high-volume vs non-high-volume centers. Study Selection: Randomized clinical trials, nonrandomized studies of interventions, prospective cohort studies, and retrospective cohort studies were selected that met the following criteria: (1) adult patients with OHCA of nontraumatic etiology, (2) comparison of high-volume with low-volume centers, (3) report of a volume-outcome association, and (4) report of outcomes of interest. At least 2 authors independently reviewed each article, blinded to each other's decision. Data Extraction and Synthesis: Data abstraction and quality assessment were independently conducted by 2 authors. Meta-analyses were performed for adjusted odds ratios (aORs) and crude ORs using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Survival and good neurological outcomes according to the Cerebral Performance Categories Scale at hospital discharge or 30 days. Results: A total of 16 studies involving 82 769 patients were included. Five studies defined high volume as 40 or more cases of OHCA per year; 3 studies defined high volume as greater than 100 cases of OHCA per year. All other studies differed in definitions. Survival to discharge or 30 days improved with treatment at high-volume centers, regardless of whether aORs (1.28 [95% CI, 1.00-1.64]) or crude ORs (1.43 [95% CI, 1.09-1.87]) were pooled. There was no association between center volume and good neurological outcomes at 30 days or hospital discharge in patients with OHCA (aOR, 0.96 [95% CI, 0.77-1.20]). Conclusions and Relevance: In this meta-analysis and systematic review, care at high-volume centers was associated with improved survival outcomes, even after adjustment for potential confounders, but was not associated with improved neurological outcomes for patients with nontraumatic OHCA. More studies evaluating the relative importance of center volume compared with other variables (eg, the availability of treatment modalities) associated with survival outcomes in patients with OHCA are required.

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.

Investigating 5-Level EQ-5D (EQ-5D-5L) Values Based on Preferences of Patients With Heart Disease.

OBJECTIVES: Several studies have shown that patients with heart disease value hypothetical health states differently from the general population. We aimed to investigate the health preferences of patients with heart disease and develop a value set for the 5-level EQ-5D (EQ-5D-5L) based on these patient preferences. METHODS: Patients with confirmed heart disease were recruited from 2 hospitals in Singapore. A total of 86 EQ-5D-5L health states (10 per patient) were valued using a composite time trade-off method according to the international valuation protocol for EQ-5D-5L; 20-parameter linear models and 8-parameter cross-attribute level effects models with and without an N45 term (indicating whether any health state dimension at level 4 or 5 existed) were estimated. Each model included patient-specific random intercepts. Model performance was evaluated for out-of-sample and in-sample predictive accuracy in terms of root mean square error. The discriminative ability of the utility values was assessed using heart disease-related functional classes. RESULTS: A total of 576 patients were included in the analysis. The preferred model, with the lowest out-of-sample root mean square error, was a 20-parameter linear model including N45. Predicted utility values ranged from -0.727 for the worst state to 1 for full health; the value for the second-best state was 0.981. Utility values demonstrated good discriminative ability in differentiating among patients of varied functional classes. CONCLUSIONS: An EQ-5D-5L value set representing the preferences of patients with heart disease was developed. The value set could be used for patient-centric economic evaluation and health-related quality of life assessment for patients with heart disease.

Gender disparities among adult recipients of layperson bystander cardiopulmonary resuscitation by location of cardiac arrest in Pan-Asian communities: A registry-based study.

BACKGROUND: Bystander cardiopulmonary resuscitation (BCPR) is a critical component of the 'chain of survival' in reducing mortality among out-of-hospital cardiac arrest (OHCA) victims. Inconsistent findings on gender disparities among adult recipients of layperson BCPR have been reported in the literature. We aimed to fill this knowledge gap by investigating the extent of gender disparities in a cross-national setting within Pan-Asian communities. METHODS: We utilised data collected from the Pan-Asian Resuscitation Outcomes Study (PAROS), an international, multicentre, prospective study conducted between 2009 and 2018. We included all OHCA cases with non-traumatic arrest aetiology transported by emergency medical services and excluded study sites that did not consistently collect information about the location of cardiac arrest. Logistic regression was used to analyse the association between gender and BCPR, stratified by location. FINDINGS: We analysed a cohort of 56,192 OHCA cases with an overall BCPR rate of 36.2% (20,329/56,192). At public locations, the BCPR rate was 31.2% (631/2022) for female and 36.4% (3235/8892) for male OHCA victims; while at home, the rate was 38.3% (6838/17,842) for females and 35.1% (9625/27,436) for males. Controlling for site differences and several factors in multivariable logistic regression, we found females less likely to receive BCPR than males in public locations (odds ratio [OR]=0.89, 95% confidence interval [CI]: 0.70-0.99), but more likely to receive BCPR at home (OR=1.16, 95% CI: 1.11-1.21). INTERPRETATION: In Pan-Asian communities, gender differences exist in adult recipients of BCPR and differ between home and public locations. Future studies should account for additional information on bystanders and societal factors to identify targets for interventions. FUNDING: The study was supported by grants from the National Medical Research Council (NMRC/CSA/0049/2013) and Laerdal Foundation (20040).