Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Intracranial Artery Calcium Burden Predicts Recurrent Cerebrovascular Events in Transient Ischaemic Attack Patients.

BACKGROUND: Patients with initial transient ischaemic attack (TIA) subsequently have a higher risk of recurrent TIA or acute ischemic stroke (AIS). The role of scoring intracranial arterial calcification (IAC) in predicting the prevalence of stroke remains unclear. We aim to evaluate if radiological CT calcium score measuring IAC burden could predict future ischemic events in a cohort of TIA patients. METHODS: We studied consecutive patients from July 2014 to December 2015 who presented with first episode of TIA. All patients had noncontrasted CT or CT-angiogram of the brain on admission. CT calcium score (cm3) was quantified by measuring calcium deposition in the bilateral internal carotid arteries, middle cerebral arteries, and vertebrobasilar system. Patients were followed up for 2 years and ischemic events for either recurrent TIA or AIS were recorded. We compared patients in terms of clinical profile at presentation and CT calcium score using appropriate univariate and multivariable analyses. RESULTS: Of 156 TIA patients studied, 22% (n = 35) had recurrent TIA or AIS within 2 years of follow-up. On univariate analyses, recurrent TIA/AIS was associated with gender (OR 0.61; 95%CI 0.40-0.95; P = .038), hypertension (mean difference 2.49; 95%CI 1.08-5.75; P = .030) and higher CT calcium score (mean difference 0.84 95%CI 0.16-1.52 P = .016). On multivariable logistic regression, a higher CT calcium score was significantly associated with recurrent TIA/AIS (adjusted OR 1.25 95%CI 1.01-1.55 P = .042). CONCLUSIONS: In TIA patients, higher IAC burden by measurement of a quantitative CT calcium score may be associated with recurrent ischemic events.

Association between Bilateral Infarcts Pattern and Detection of Occult Atrial Fibrillation in Embolic Stroke of Undetermined Source (ESUS) Patients with Insertable Cardiac Monitor (ICM).

BACKGROUND AND AIMS: Increasingly, insertable cardiac monitors (ICM) have been used to detect Atrial Fibrillation (AF) in patients with cryptogenic stroke or embolic strokes of undetermined source (ESUS). We aim to examine the characteristics of these patients who were subsequently found to have AF. METHODS: We studied 83 consecutive patients who were comprehensively evaluated using neuroimaging and vessel imaging (computed tomography angiography, magnetic resonance angiography, or transcranial and extracranial Doppler sonography) to have met the previously established ESUS criteria. All 83 patients had ICM implanted between 2015 and 2017. All patients were followed up for at least 1 year, with a median follow-up period of 1.5 ± .5 years. We compared the baseline clinical, laboratory, echocardiographic, neuro-imaging profiles, and clinical outcomes in terms of functional recovery, recurrent stroke, and mortality in patients with and without detected AF. RESULTS: AF detection rate in this ESUS cohort was 12% over the study period. Patients with detected AF were associated with bilateral infarcts pattern at presentation (30% versus 5.5%, P = .035). Infarcts involving multiple vascular territories was not significantly associated with the detection of AF. There were no significant differences in the other clinical characteristics and outcomes between the AF group compared to the group without detected AF. Echocardiographic parameters including left ventricular ejection fraction and left atrial diameter were also not shown to be significantly different. CONCLUSION: Our study found that a neuroimaging profile of bilateral infarcts was associated with AF detection using insertable cardiac monitor in ESUS patients. Larger prospective studies are needed to validate our findings.

Effect of Pretreatment Blood Pressure on Outcomes in Thrombolysed Acute Ischemic Stroke Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Blood pressure (BP) is an important determinant of functional outcome in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA). Current guidelines recommend a BP target of 185/110 mmHg before IV-tPA bolus and maintaining it at less than 180/105 mmHg for the first 24 hours. However, the effect of blood pressure on various outcome measures after systemic thrombolysis remains unclear. METHODS: Following a systematic search of Medline and EMBASE, all observational studies reporting effect of pretreatment BP on 90-day functional outcome as measured by the modified Rankin Scale (mRS) and/ or incidence of symptomatic intracranial hemorrhage (sICH) in AIS patients receiving thrombolytic therapy were included. RESULTS: Of 2181 studies screened, 26 studies, involving 38,937 subjects, met inclusion criteria. Higher prethrombolysis systolic BP was significantly-associated with poorer 90-day functional outcome (Mean difference 3.87 mmHg; 95% confidence interval [CI] 1.18-6.56) and increased incidence of sICH (Mean difference 5.31; 95% CI 2.22-8.40). When studies were stratified by different cut-offs for functional outcome (mRS 0-1 versus 0-2) and definitions of sICH used (Randomized controlled trials or SITS-MOST), there was no significant difference in mean difference between the subgroups. CONCLUSIONS: Our data showed that higher prethrombolysis SBP was associated with poorer outcomes in thrombolysed acute ischemic stroke patients. This may suggest that more aggressive lowering of BP below the current recommendations prior to thrombolysis could be beneficial. The effect of early BP trends after tPA infusion could not be evaluated due to limited available data. Ongoing randomized clinical trials, like ENCHANTED, may provide further insights into the current guidelines and optimal BP levels.

Improvement in Door-to-Needle Time in Patients with Acute Ischemic Stroke via a Simple Stroke Activation Protocol.

BACKGROUND: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT. METHODS: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases. RESULTS: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months. CONCLUSIONS: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies.

Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value. METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more. RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001). CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.

Effects of sex on clinical outcomes of hypertrophic cardiomyopathy in Singapore.

Introduction: Despite the growing recognition that sex can affect the presentation and outcomes in hypertrophic cardiomyopathy (HCM), this relationship is understudied in Asians. Therefore, we aimed to explore sex differences in Asian patients with HCM. Method: A total of 295 consecutive patients diagnosed with HCM were recruited from a tertiary cardiology centre from 2010 to 2017 over a mean of 3.9±2.7 years. We evaluated the effects of sex on the outcomes of HCM in Asian patients. Results: HCM patients were more commonly men (72%). Women were older and had more comorbidities, including hypertension and atrial fibrillation. On transthoracic echocardiography, the indexed left ventricular end-systolic and end-diastolic volumes were similar, but more women had more-than-moderate mitral regurgitation and had a smaller left ventricular outflow tract (LVOT). Women more commonly had findings of obstructive physiology with significant LVOT obstruction, defined as >30 mmHg at rest. The use of implantable cardioverter defibrillators was similar across sexes. On multivariable analysis, women were found to be more likely to develop progressive heart failure requiring admission (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.05-4.71, P=0.021) but had a lower rate of all-cause mortality (HR 0.36, 95% CI 0.19-0.70, P=0.003). Conclusion: Women diagnosed with HCM were older, had more comorbidities and were more likely to develop heart failure while men had a higher risk of all-cause mortality.

Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing.

INTRODUCTION: The gold standard for COVID-19 diagnosis is currently a real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. This is most commonly performed on respiratory secretions obtained via a nasopharyngeal swab. Due to supply chain limitations and high demand worldwide because of the COVID-19 pandemic, access to commercial nasopharyngeal swabs has not been assured. 3D printing methods have been used to meet the shortfall. For longer-term considerations, 3D printing may not compare well with injection molding as a production method due to the challenging scalability and greater production costs of 3D printing. METHODS: To secure sufficient nasopharyngeal swab availability for our national healthcare system, we designed a novel injection molded nasopharyngeal swab (the IM2 swab). We performed a clinical diagnostic study comparing the IM2 swab to the Copan FLOQSwab. Forty patients with a known diagnosis of COVID-19 and 10 healthy controls were recruited. Paired nasopharyngeal swabs were obtained from the same nostril of each participant and tested for SARS-CoV-2 by RT-PCR. RESULTS: When compared to the Copan FLOQswab, results from the IM2 swab displayed excellent overall agreement and positive percent agreement of 96.0% and 94.9%, respectively. There was no significant difference in mean RT-PCR cycle threshold values for the ORF1ab (28.05 vs. 28.03, p = 0.97) and E-gene (29.72 vs. 29.37, p = 0.64) targets, respectively. We did not observe any significant adverse events and there was no significant difference in patient-reported pain. CONCLUSION: In summary, the IM2 nasopharyngeal swab is a clinically safe, highly accurate option to commercial nasopharyngeal swabs.

Left ventricular systolic dysfunction is associated with poor functional outcomes after endovascular thrombectomy.

BACKGROUND: Endovascular thrombectomy (ET) has transformed acute ischemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD, as measured by LV ejection fraction (LVEF), and clinical outcomes in patients with anterior cerebral circulation LVO who underwent ET. METHODS: This multicenter retrospective cohort study examined anterior circulation LVO AIS patients from six international stroke centers. LVSD was measured by assessment of the echocardiographic LVEF using Simpson's biplane method of discs according to international guidelines. LVSD was defined as LVEF <50%. The primary outcome was defined as a good functional outcome using a modified Rankin Scale (mRS) of 0-2 at 3 months. RESULTS: We included 440 AIS patients with LVO who underwent ET. On multivariate analyses, pre-existing diabetes mellitus (OR 2.05, 95% CI 1.24 to 3.39;p=0.005), unsuccessful reperfusion (Treatment in Cerebral Infarction (TICI) grade 0-2a) status (OR 4.21, 95% CI 2.04 to 8.66; p<0.001) and LVSD (OR 2.08, 95% CI 1.18 to 3.68; p=0.011) were independent predictors of poor functional outcomes at 3 months. On ordinal (shift) analyses, LVSD was associated with an unfavorable shift in the mRS outcomes (OR 2.32, 95% CI 1.52 to 3.53; p<0.001) after adjusting for age and ischemic heart disease. CONCLUSION: Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to consider cardiac factors for ET, the degree of monitoring and prognostication post-procedure.

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance. Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design, Setting, and Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers. Main Outcomes and Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs. Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values. Conclusions and Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.

A new non-invasive index for prognosis evaluation in patients with aortic stenosis.

The global left ventricular (LV) contractility index, dσ*/dtmax measures the maximal rate of change in pressure-normalized LV wall stress. We aim to describe the trend of dσ*/dtmax in differing severity of aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) and the association of dσ*/dtmax with clinical outcomes in moderate AS and severe AS. We retrospectively studied a total of 1738 patients with AS (550 mild AS, 738 moderate AS, 450 severe AS) and preserved LVEF ≥ 50% diagnosed from 1st January 2001 to 31st December 2015. dσ*/dtmax worsened with increasing severity of AS despite preserved LVEF (mild AS: 3.69 ± 1.28 s-1, moderate AS: 3.17 ± 1.09 s-1, severe AS: 2.58 ± 0.83 s-1, p < 0.001). Low dσ*/dtmax < 2.8 s-1 was independently associated with a higher composite outcome of aortic valve replacement, congestive cardiac failure admissions and all-cause mortality (adjusted hazard ratio 1.48, 95% CI: 1.25-1.77, p < 0.001). In conclusion, dσ*/dtmax declined with worsening AS despite preserved LVEF. Low dσ*/dtmax < 2.8 s-1 was independently associated with adverse clinical outcomes in moderate AS and severe AS with preserved LVEF.

Effectiveness of near-peer simulation for managing the acutely deteriorating patient among residents of an internal medicine junior residency programme.

INTRODUCTION: Near-peer teaching is gaining popularity as a teaching modality, as it improves the learner's understanding, is targeted at an appropriate level and promotes familiarisation. This study was initiated to evaluate the effectiveness of incorporating near-peer instruction into simulation-based training within a junior residency programme. METHODS: 42 first-year residents from an internal medicine junior residency programme were recruited. Participants underwent a simulation-based training programme conducted over five weeks. Each week involved either an emergency or acute clinical scenario. A structured questionnaire was administered prior to and after the course to compare participants' perceived knowledge, experience and confidence in managing the clinical scenarios. RESULTS: In our study, 83% of participants agreed/strongly agreed that the scenarios were realistic. There were improvements in perceived knowledge, experience and confidence after the course. The greatest improvement was seen for experience (post-simulation: median 7.00 [interquartile range (IQR) 6.00‒8.00] vs. pre-simulation: median 5.00 [IQR 3.00-6.25]). 65% of participants were keen to help with future training. CONCLUSION: Near-peer simulation training was found to be a viable and valuable method of instruction for first-year residents for increasing experience, instilling confidence and improving perceived knowledge. Integration of such programmes within medical education curricula shows good promise of continuity, with many first-year residents inspired to organise subsequent sessions.

Significant aortic stenosis associated with poorer functional outcomes in patients with acute ischaemic stroke undergoing endovascular therapy.

BACKGROUND AND AIM: Bi-directional feedback mechanisms exist between the heart and brain, which have been implicated in heart failure. We postulate that aortic stenosis may alter cerebral haemodynamics and influence functional outcomes after endovascular thrombectomy for acute ischaemic stroke. We compared clinical characteristics, echocardiographic profile and outcomes in patients with or without aortic stenosis that underwent endovascular thrombectomy for large vessel occlusion acute ischaemic stroke. METHODS: Consecutive acute ischaemic stroke patients with anterior and posterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery and basilar artery) who underwent endovascular thrombectomy were studied. Patients were divided into those with significant aortic stenosis (aortic valve area <1.5 cm2) and without. Univariate and multivariate analyses were employed to compare and determine predictors of functional outcomes measured by modified Rankin scale at three months. RESULTS: We identified 26 (8.5%) patients with significant aortic stenosis. These patients were older (median age 76 (interquartile range 68-84) vs. 67 (interquartile range 56-75) years, p = 0.001), but similar in terms of medical comorbidities and echocardiographic profile. Rates of successful recanalisation (73.1% vs. 78.0%), symptomatic intracranial haemorrhage (7.7% and 7.9%) and mortality (11.5% vs. 12.6%) were similar. Significant aortic stenosis was independently associated with poorer functional outcome (modified Rankin scale >2) at three months (adjusted odds ratio 2.7, 95% confidence interval 1.1-7.5, p = 0.048), after adjusting for age, door-to-puncture times, stroke severity and rates of successful recanalisation. CONCLUSION: In acute ischaemic stroke patients managed with endovascular thrombectomy, significant aortic stenosis is associated with poor functional outcome despite comparable recanalisation rates. Larger cohort studies are needed to explore this relationship further.

Comparison of Clinical and Echocardiographic Features of Asymptomatic Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valves.

The clinical and imaging differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with medically managed asymptomatic moderate-to-severe aortic stenosis (AS) have not been studied previously. We aim to characterize these differences and their clinical outcomes in this study. A retrospective observational study was conducted on 836 consecutive cases of isolated asymptomatic moderate-to-severe AS, with median follow-up of 3.4 years. Clinical and echocardiographic characteristics were compared between BAV and TAV patients. Subgroup analysis stratified by AS severity were performed. Survival analysis of all-cause mortality was performed using Kaplan-Meier curves and Cox proportional hazards model. Compared to BAV patients, TAV patients were older (76 ± 11 vs 55 ± 16 years, p <0.001) and had more co-morbidities including hypertension (78% vs 56%; p <0.001), diabetes (41% vs 24%; p <0.001), and chronic kidney disease (20% vs 3%; p = 0.001). TAV patients had less severe aortic valve disease than BAV patients, with a higher aortic valve area index (0.71 ± 0.20 cm2/m2 vs 0.61 ± 0.18 cm2/m2, p <0.001) and less aortic dilation (sinotubular junction: 23.7 ± 4.0 mm vs 26.9 ± 4.8 mm, p <0.001; mid-ascending aorta: 31.4 ± 4.7 mm vs 36.3 ± 6.3 mm, p <0.001). TAV patients were more likely to have eccentric left ventricular hypertrophy and less likely to have a normal geometry (p = 0.003). Competing risk analysis identified increased age (hazard ratio 1.03, 95% confidence interval 1.02 to 1.05, p <0.001) and LVEF (hazard ratio 0.98, 95% confidence interval 0.97 to 0.99, p <0.001) as independent risk factors of all-cause mortality. Valve morphology was not a significant independent risk factor for aortic valve replacement or mortality. In conclusion, asymptomatic TAV patients had more cardiovascular risk factors, less severe aortic valve disease, less sinotubular and mid-ascending aortic dilation, more severe LV remodeling.

Left ventricular vortex formation time in elite athletes: novel predictor of myocardial performance.

BACKGROUND: Efficient transportation of blood through the left ventricle (LV) during diastole depends on vortex formation. Vortex formation time (VFT) can be measured by echocardiography as a dimensionless index. As elite athletes have supranormal diastolic LV function, we aim to assess resting and post-exercise VFT in these athletes and hypothesised that VFT may predict myocardial performance immediately post-exercise. METHOD: Subjects were world class speedskaters training for the Winter Olympic Games. Echocardiographic measurements were obtained before and immediately after 3000 m of racing. VFT was computed as 4×(1-ß)/π×α³×left ventricle ejection fraction where ß is the fraction of diastolic stroke volume contributed by atrial contraction, α is the biplane end diastolic volume (EDV)1/3 divided by mitral annular diameter during early diastole. RESULTS: Baseline VFT was 2.6±0.7 (n=24, age 22±3 years, 67% males). Post-exercise, heart rates increased (64±10 vs 89±12 beats/min, p<0.01); however, VFT was unchanged (2.9±1.0, p>0.05). VFT at rest correlated modestly with post-exertion early diastolic mitral in-flow velocity (E; r=0.59, p=0.01), tissue Doppler-derived early mitral annular velocity (E'; septal and lateral, both r=0.59, p=0.01) and systolic annular velocity (S'; septal: r=0.46, p=0.02 and lateral: r=0.48, p=0.02) but not late diastolic mitral in-flow velocity (A; r=0.06, p>0.05) or annular velocity (A'; septal: r=0.34, p=NS and lateral: r=0.35, p>0.05). CONCLUSION: There was no significant difference between VFT at rest and immediately post-exercise. However, VFT at rest correlated with immediate post-exercise augmented systolic and early diastolic tissue Doppler indicators of myocardial performance in elite athletes.

Left ventricular vortex formation time in elite athletes.

Vortex formation time (VFT) is a continuous measure of the left ventricular (LV) filling that integrates all phases of diastole. This has been previously studied in patients with heart failure. This study examined the differences in VFT between healthy controls and elite athletes. We compared echocardiographic indices between elite male athletes (n = 41) and age-, weight- and sex-matched sedentary volunteers (n = 22). VFT was obtained using the validated formula: 4 × (1 - ß)/π × α3 × LVEF, where ß is the fraction of total transmitral diastolic stroke volume contributed by atrial contraction (assessed by time velocity integral of the mitral E- and A-waves) and α is the biplane end-diastolic volume (EDV)1/3 divided by mitral annular diameter during early diastole. Diastolic function was measured by the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e') (E/e' ratio) and the ratio of E to mitral peak velocity of late filling (A) (E/A ratio). The heart rate was lower (63 ± 10 vs. 74 ± 6 beats per minute, p < 0.001) and the LV end diastolic diameter was larger in athletes as compared to controls (56 ± 3 vs. 50 ± 4 mm, p < 0.001). The VFT was lower in the sedentary group compared to athletes (3.1 ± 0.4 vs. 4.0 ± 0.8, p < 0.001). Similarly, E/e' was higher in sedentary controls compared to athletes (7.5 ± 1.8 vs 4.2 ± 1.0, p < 0.001). Furthermore, there was a modest correlation between VFT and E/A (r = 0.47, p < 0.001) as well as E/e' (r = - 0.33, p = 0.012). In conclusion, the VFT was elevated among elite athletes compared to healthy sedentary controls.

Perceptions of a night float system for intern doctors in an internal medicine program: an Asian perspective.

Long duty hours have been associated with significant medical errors, adverse events, and physician "burn-out". An innovative night float (NF) system has been implemented in our internal medicine program to reduce the negative effects of long duty hours associated with conventional full-call systems. However, concerns remain if this would result in inadequate training for interns. We developed a structured questionnaire to assess junior doctors' perceptions of the NF system compared to full calls, in areas of patient safety, medical training, and well-being. Ninety-seven (71%) of the 137 doctors polled responded. Ninety-one (94%) felt the NF system was superior to the full call system. A strong majority felt NF was beneficial for patient safety compared to full call (94% vs. 2%, p<0.001). The NF system was also perceived to reduce medical errors (94% vs. 2%, p<0.001) and reduce physician "burn-out" (95% vs. 5%, p<0.001). Beyond being a practical solution to duty-hour limitations, there was a significant perceived benefit of the NF system compared to the full call in terms of overall satisfaction, patient safety, reducing medical errors and physician "burn-out".

Acute Health Impacts of the Southeast Asian Transboundary Haze Problem-A Review.

Air pollution has emerged as one of the world's largest environmental health threats, with various studies demonstrating associations between exposure to air pollution and respiratory and cardiovascular diseases. Regional air quality in Southeast Asia has been seasonally affected by the transboundary haze problem, which has often been the result of forest fires from "slash-and-burn" farming methods. In light of growing public health concerns, recent studies have begun to examine the health effects of this seasonal haze problem in Southeast Asia. This review paper aims to synthesize current research efforts on the impact of the Southeast Asian transboundary haze on acute aspects of public health. Existing studies conducted in countries affected by transboundary haze indicate consistent links between haze exposure and acute psychological, respiratory, cardiovascular, and neurological morbidity and mortality. Future prospective and longitudinal studies are warranted to quantify the long-term health effects of recurrent, but intermittent, exposure to high levels of seasonal haze. The mechanism, toxicology and pathophysiology by which these toxic particles contribute to disease and mortality should be further investigated. Epidemiological studies on the disease burden and socioeconomic cost of haze exposure would also be useful to guide policy-making and international strategy in minimizing the impact of seasonal haze in Southeast Asia.

Psychosomatic symptoms during South East Asian haze crisis are related to changes in cerebral hemodynamics.

OBJECTIVES: Forest fires in South Asia lead to widespread haze, where many healthy individuals develop psychosomatic symptoms. We investigated the effects of haze exposure on cerebral hemodynamics and new symptoms. We hypothesised that vasoactive substances present in the haze, would lead to vasodilation of cerebral vasculature, thereby altering cerebral hemodynamics, which in turn may account for new psychosomatic symptoms. METHODS: Seventy-four healthy volunteers were recruited, and serial transcranial Doppler (TCD) ultrasonography was performed to record blood flow parameters of bilateral middle cerebral arteries (MCA). The first TCD was performed in an air-conditioned environment. It was repeated outdoors after the participants spent 30-minutes in the haze environment. The prevailing level of pollutant standards index (PSI) was recorded. Appropriate statistical analyses were performed to compare cerebral hemodynamics at baseline and after haze exposure in all participants. Subgroup analyses were then employed to compare the findings between symptomatic and asymptomatic participants. RESULTS: Study participants' median age was 30 years (IQR 26-34), and new psychosomatic symptoms were reported by 35 (47.3%). There was a modest but significant decrease in pulsatility index (PI) and resistivity index (RI) in the left MCA after haze exposure (PI: p = 0.026; RI: p = 0.021). When compared to baseline parameters, haze exposure resulted in significantly lower mean PI (p = 0.001) and RI (p = 0.001) in symptomatic patients, but this difference was not present in asymptomatic patients (PI: p = 0.919; RI: p = 0.970). CONCLUSION: Haze causes significant alterations in cerebral hemodynamics in susceptible individuals, probably responsible for various psychosomatic symptoms. The prognostic implications and health effects of haze require evaluation in a larger study.